Peer Reviewed Publications
2018 |
Muhumuza, Simon; Akello, Evelyn; Kyomugisha-Nuwagaba, Charity; Baryamutuma, Rose; Sebuliba, Isaac; Lutalo, Ibrahim M; Kansiime, Edgar; Kisaakye, Linda N; Kiragga, Agnes N; King, Rachel; Bazeyo, William; Lindan, Christina Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study Journal Article PloS One, 12 (12), 2018. @article{Muhumuza2018, title = {Retention in care among HIV-infected pregnant and breastfeeding women on lifelong antiretroviral therapy in Uganda: A retrospective cohort study}, author = {Simon Muhumuza and Evelyn Akello and Charity Kyomugisha-Nuwagaba and Rose Baryamutuma and Isaac Sebuliba and Ibrahim M. Lutalo and Edgar Kansiime and Linda N. Kisaakye and Agnes N. Kiragga and Rachel King and William Bazeyo and Christina Lindan }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Retention-in-care-among-HIV-infected-pregnant-and-breastfeeding-women-on-lifelong-antiretroviral-therapy-in-Uganda-A-retrospective-cohort-study.pdf}, doi = { 10.1371/journal.pone.0187605}, year = {2018}, date = {2018-12-22}, journal = {PloS One}, volume = {12}, number = {12}, abstract = {BACKGROUND: In 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program. METHODS: We conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as "being alive and receiving ART at the last clinic visit". We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables. RESULTS: The median follow-up time was 20.2 months (IQR 4.2-22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002). CONCLUSION: Retention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: In 2013, Uganda updated its prevention of maternal-to-child transmission of HIV program to Option B+, which requires that all HIV-infected pregnant and breastfeeding women be started on lifelong antiretroviral therapy (ART) regardless of CD4 count. We describe retention in care and factors associated with loss to follow-up (LTFU) among women initiated on Option B+ as part of an evaluation of the effectiveness of the national program. METHODS: We conducted a retrospective cohort analysis of data abstracted from records of 2,169 women enrolled on Option B+ between January and March 2013 from a representative sample of 145 health facilities in all 24 districts of the Central region of Uganda. We defined retention as "being alive and receiving ART at the last clinic visit". We used Kaplan-Meier analysis to estimate retention in care and compared differences between women retained in care and those LTFU using the chi-squared test for dichotomized or categorical variables. RESULTS: The median follow-up time was 20.2 months (IQR 4.2-22.5). The proportion of women retained in HIV care at 6, 12 and 18 months post-ART initiation was 74.2%, 66.7% and 62.0%, respectively. Retention at 18 months varied significantly by level of health facility and ranged from 70.0% among those seen at hospitals to 56.6% among those seen at lower level health facilities. LTFU was higher among women aged less than 25 years, 59.3% compared to those aged 25 years and above, 40.7% (p = 0.02); among those attending care at lower level facilities, 44.0% compared to those attending care at hospitals, 34.1% (p = 0.01), and among those who were not tested for CD4 cell count at ART initiation, 69.4% compared to those who were tested, 30.9% (p = 0.002). CONCLUSION: Retention of women who were initiated on Option B+ during the early phases of roll-out was only moderate, and could undermine the effectiveness of the program. Identifying reasons why women drop out and designing targeted interventions for improved retention should be a priority. |
Bahr, Nathan C; Nuwagira, Edwin; Evans, Emily E; Cresswell, Fiona V; Bystrom, Philip V; Byamukama, Adolf; Bridge, Sarah C; Bangdiwala, Ananta S; Meya, David B; Denkinger, Claudia M; Muzoora, Conrad; Boulware, David R Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study. Journal Article Lancent Infectious Diseases, 18 (1), pp. 68-75, 2018. @article{Bahr2018, title = {Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study.}, author = {Nathan C Bahr and Edwin Nuwagira and Emily E Evans and Fiona V Cresswell and Philip V Bystrom and Adolf Byamukama and Sarah C Bridge and Ananta S Bangdiwala and David B Meya and Claudia M Denkinger and Conrad Muzoora and David R Boulware }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Diagnostic-accuracy-of-Xpert-MTBRIF-Ultra-for-tuberculous-meningitis-in-HIV-infected-adults-a-prospective-cohort-study..pdf}, doi = {: 10.1016/S1473-3099(17)30474-7}, year = {2018}, date = {2018-09-14}, journal = {Lancent Infectious Diseases}, volume = {18}, number = {1}, pages = {68-75}, abstract = {BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. FINDINGS: From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). INTERPRETATION: Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. FUNDING: National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda. HIV-infected adults with suspected meningitis (eg, headache, nuchal rigidity, altered mental status) were screened consecutively at Mbarara Regional Referral Hospital. We centrifuged CSF, resuspended the pellet in 2 mL of CSF, and tested 0·5 mL with mycobacteria growth indicator tube culture, 1 mL with Xpert, and cryopreserved 0·5 mL, later tested with Xpert Ultra. We assessed diagnostic performance against uniform clinical case definition or a composite reference standard of any positive CSF tuberculous test. FINDINGS: From Feb 27, 2015, to Nov 7, 2016, we prospectively evaluated 129 HIV-infected adults with suspected meningitis for tuberculosis. 23 participants were classified as probable or definite tuberculous meningitis by uniform case definition, excluding Xpert Ultra results. Xpert Ultra sensitivity was 70% (95% CI 47-87; 16 of 23 cases) for probable or definite tuberculous meningitis compared with 43% (23-66; 10/23) for Xpert and 43% (23-66; 10/23) for culture. With composite standard, we detected tuberculous meningitis in 22 (17%) of 129 participants. Xpert Ultra had 95% sensitivity (95% CI 77-99; 21 of 22 cases) for tuberculous meningitis, which was higher than either Xpert (45% [24-68]; 10/22; p=0·0010) or culture (45% [24-68]; 10/22; p=0·0034). Of 21 participants positive by Xpert Ultra, 13 were positive by culture, Xpert, or both, and eight were only positive by Xpert Ultra. Of those eight, three were categorised as probable tuberculous meningitis, three as possible tuberculous meningitis, and two as not tuberculous meningitis. Testing 6 mL or more of CSF was associated with more frequent detection of tuberculosis than with less than 6 mL (26% vs 7%; p=0·014). INTERPRETATION: Xpert Ultra detected significantly more tuberculous meningitis than did either Xpert or culture. WHO now recommends the use of Xpert Ultra as the initial diagnostic test for suspected tuberculous meningitis. FUNDING: National Institute of Neurologic Diseases and Stroke, Fogarty International Center, National Institute of Allergy and Infectious Disease, UK Medical Research Council/DfID/Wellcome Trust Global Health Trials, Doris Duke Charitable Foundation. |
Freemen, Esther E; Semeere, Aggrey; Osman, Hany; Peterso, Gary; and Milind Rajadhyaksha, Salvador Gonzalez; Martin, Jeffrey N; Anderson, Rox R; Tearney, Guillermo J; Kang, Dongkyun Smartphone Confocal Microscopy for Imaging Cellular Structures In Human Skin in Vivo. Journal Article BIOMEDICAL OPTICS EXPRESS , 9 (4), pp. 1906–1915, 2018. @article{Freemen2018, title = {Smartphone Confocal Microscopy for Imaging Cellular Structures In Human Skin in Vivo. }, author = {Esther E Freemen and Aggrey Semeere and Hany Osman and Gary Peterso and Milind Rajadhyaksha,and Salvador Gonzalez and Jeffrey N Martin and R. Rox Anderson and Guillermo J Tearney and Dongkyun Kang}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Smartphone-Confocal-Microscopy-for-Imaging-Cellular-Structures-In-Human-Skin-in-Vivo.-4.pdf}, doi = {10.1364/BOE.9.001906}, year = {2018}, date = {2018-04-20}, journal = { BIOMEDICAL OPTICS EXPRESS }, volume = {9}, number = {4}, pages = {1906–1915}, abstract = { We report development of a low-cost smartphone confocal microscope and its first demonstration of in vivo human skin imaging. The smartphone confocal microscope uses a slit aperture and diffraction grating to conduct two-dimensional confocal imaging without using any beam scanning devices. Lateral and axial resolutions of the smartphone confocal microscope were measured as 2 and 5 µm, respectively. In vivo confocal images of human skin revealed characteristic cellular structures, including spinous and basal keratinocytes and papillary dermis. Results suggest that the smartphone confocal microscope has a potential to examine cellular details in vivo and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging. © 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement OCIS codes: (170.1790) Confocal microscopy; (170.1870) Dermatology. }, keywords = {}, pubstate = {published}, tppubtype = {article} } We report development of a low-cost smartphone confocal microscope and its first demonstration of in vivo human skin imaging. The smartphone confocal microscope uses a slit aperture and diffraction grating to conduct two-dimensional confocal imaging without using any beam scanning devices. Lateral and axial resolutions of the smartphone confocal microscope were measured as 2 and 5 µm, respectively. In vivo confocal images of human skin revealed characteristic cellular structures, including spinous and basal keratinocytes and papillary dermis. Results suggest that the smartphone confocal microscope has a potential to examine cellular details in vivo and may help disease diagnosis in resource-poor settings, where conducting standard histopathologic analysis is challenging. © 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement OCIS codes: (170.1790) Confocal microscopy; (170.1870) Dermatology. |
Nyakato, Patience; Kiragga, Agnes N; Kambugu, Andrew; Bradley, John; Baisley, Kathy BMJ Open, 8 (4), 2018. @article{Nyakato2018, title = {Correction of estimates of retention in care among a cohort of HIV-positive patients in Uganda in the period before starting ART: a sampling-based approach}, author = {Patience Nyakato and Agnes N Kiragga and Andrew Kambugu and John Bradley and Kathy Baisley}, url = {https://bmjopen.bmj.com/content/8/4/e017487.long}, year = {2018}, date = {2018-04-20}, journal = {BMJ Open}, volume = {8}, number = {4}, abstract = {OBJECTIVE: The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers. DESIGN: Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500). SETTING: Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015. PARTICIPANTS: A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes. OUTCOME MEASURES: The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care. RESULTS: Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%). CONCLUSION: Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVE: The aim of this study was to use a sampling-based approach to obtain estimates of retention in HIV care before initiation of antiretroviral treatment (ART), corrected for outcomes in patients who were lost according to clinic registers. DESIGN: Retrospective cohort study of HIV-positive individuals not yet eligible for ART (CD4 >500). SETTING: Three urban and three rural HIV care clinics in Uganda; information was extracted from the clinic registers for all patients who had registered for pre-ART care between January and August 2015. PARTICIPANTS: A random sample of patients who were lost according to the clinic registers (>3 months late to scheduled visit) was traced to ascertain their outcomes. OUTCOME MEASURES: The proportion of patients lost from care was estimated using a competing risks approach, first based on the information in the clinic records alone and then using inverse probability weights to incorporate the results from tracing. Cox regression was used to determine factors associated with loss from care. RESULTS: Of 1153 patients registered for pre-ART care (68% women, median age 29 years, median CD4 count 645 cells/µL), 307 (27%) were lost according to clinic records. Among these, 195 (63%) were selected for tracing; outcomes were ascertained in 118 (61%). Seven patients (6%) had died, 40 (34%) were in care elsewhere and 71 (60%) were out of care. Loss from care at 9 months was 30.2% (95% CI 27.3% to 33.5%). After incorporating outcomes from tracing, loss from care decreased to 18.5% (95% CI 13.8% to 23.6%). CONCLUSION: Estimates of loss from HIV care may be too high if based on routine clinic data alone. A sampling-based approach is a feasible way of obtaining more accurate estimates of retention, accounting for transfers to other clinics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. |
Cresswell, Fiona V; Bangdiwala, Ananta S; Meya, David B; Bahr, Nathan C; Vidal, Jose E; M. Estée Török, Le Thi Phuong ; Thwaites, Thao Guy E; Boulwar, David R Absence of Cerebrospinal Fluid Pleocytosis in Tuberculous Meningitis is a Common Occurrence in HIV Co-infection and a Predictor of Poor Outcomes Journal Article International Jouranl of Infectious Deseases, 67 , pp. 77-78, 2018. @article{Cresswell2018, title = {Absence of Cerebrospinal Fluid Pleocytosis in Tuberculous Meningitis is a Common Occurrence in HIV Co-infection and a Predictor of Poor Outcomes }, author = {Fiona V Cresswell and Ananta S Bangdiwala and David B Meya and Nathan C Bahr and Jose E Vidal and M. Estée Török, Le Thi Phuong and Thao Guy E Thwaites and David R Boulwar}, url = {https://www.ijidonline.com/article/S1201-9712(18)30015-8/fulltext}, doi = {10.1016/j.ijid.2018.01.014.}, year = {2018}, date = {2018-03-01}, journal = {International Jouranl of Infectious Deseases}, volume = {67}, pages = {77-78}, abstract = {We read with interest the article by Erdem et al. reporting absence of cerebrospinal fluid (CSF) pleocytosis (≤5 cells/l) in 3% (19/507) of HIV-negative tuberculous meningitis (TBM) patients (Erdem et al., 2017). We wish to highlight both the significance and higher incidence of acellular CSF among HIV-infected adults with TBM. In reviewing 85 microbiologically-confirmed, HIV-associated TBM cases in Uganda, 33% (28/85) had acellular CSF. Acellular CSF was also commonly reported among other HIV-infected microbiologically-confirmed TBM cohorts: 26% (5/19) in Zimbabwe, 19% (20/108) in Brazil, and 21% (18/91) in Argentina (Table1)(Cecchini et al., 2007, Croda et al., 2010, Hakim et al., 2000, Vidal et al., 2010). Prevalence of acellular CSF correlated with the severity of immunosuppression in the Argentinian cohort and occurred twice as often in CD4 counts <50 cells/l(33%, 9/28) than with >50 cells/ (15%, 5/31) (Cecchini et al., 2009). In Vietnam, acellular CSF is less common (4%, 20/461) despite advanced immunosuppression (median CD4 39 cells). Variation between cohorts may be attributable to variable time to CSF analysis, M. tuberculosis strain type, or genetic differences in host immune responses between geographically distinct cohorts (Caws et al., 2008). }, keywords = {}, pubstate = {published}, tppubtype = {article} } We read with interest the article by Erdem et al. reporting absence of cerebrospinal fluid (CSF) pleocytosis (≤5 cells/l) in 3% (19/507) of HIV-negative tuberculous meningitis (TBM) patients (Erdem et al., 2017). We wish to highlight both the significance and higher incidence of acellular CSF among HIV-infected adults with TBM. In reviewing 85 microbiologically-confirmed, HIV-associated TBM cases in Uganda, 33% (28/85) had acellular CSF. Acellular CSF was also commonly reported among other HIV-infected microbiologically-confirmed TBM cohorts: 26% (5/19) in Zimbabwe, 19% (20/108) in Brazil, and 21% (18/91) in Argentina (Table1)(Cecchini et al., 2007, Croda et al., 2010, Hakim et al., 2000, Vidal et al., 2010). Prevalence of acellular CSF correlated with the severity of immunosuppression in the Argentinian cohort and occurred twice as often in CD4 counts <50 cells/l(33%, 9/28) than with >50 cells/ (15%, 5/31) (Cecchini et al., 2009). In Vietnam, acellular CSF is less common (4%, 20/461) despite advanced immunosuppression (median CD4 39 cells). Variation between cohorts may be attributable to variable time to CSF analysis, M. tuberculosis strain type, or genetic differences in host immune responses between geographically distinct cohorts (Caws et al., 2008). |
Castelnuovo, Barbara; Mubiru, Frank; Kiragga, Agnes N; Musomba, Rachel; Mbabazi, Olive; Gonza, Paul; Kambugu, Andrew; Ratanshi, Rosalind Parks Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda Journal Article BMJ Open, 8 (2), 2018. @article{Castelnuovo2018, title = {Antiretroviral treatment Long-Term (ALT) cohort: a prospective cohort of 10 years of ART-experienced patients in Uganda}, author = {Barbara Castelnuovo and Frank Mubiru and Agnes N Kiragga and Rachel Musomba and Olive Mbabazi and Paul Gonza and Andrew Kambugu and Rosalind Parks Ratanshi}, url = {https://bmjopen.bmj.com/content/8/2/e015490.long}, year = {2018}, date = {2018-02-21}, journal = {BMJ Open}, volume = {8}, number = {2}, abstract = {Purpose Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years. Participants A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits. Findings to date Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400 copies/mL was 95.8%. Future plans Through collaboration with other institutions, we are planning several substudies, including the evaluation of the risk for cardiovascular diseases, the assessment of bone mineral density, screening for liver cirrhosis using fibroscan technology and investigation of drug–drug interactions between ART and common drugs used for non-communicable diseases. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Purpose Little information is available on patients on antiretroviral treatment (ART) after a long-term period from sub-Saharan Africa, with the longest follow-up and related outcomes being after 10 years on ART. At the Infectious Diseases Institute (IDI) (Kampala, Uganda), we set up a cohort of patients already on ART for 10 years at the time of enrolment, who will be followed up for additional 10 years. Participants A prospective observational cohort of 1000 adult patients previously on ART for 10 years was enrolled between May 2014 and September 2015. Patients were eligible for enrolment if they were in their consecutive 10th year of ART regardless of the combination of drugs for both first- and second-line ART. Data were collected at enrolment and all annual study visits. Follow-up visits are scheduled once a year for 10 years. Biological samples (packed cells, plasma and serum) are stored at enrolment and follow-up visits. Findings to date Out of 1000 patients enrolled, 345 (34.5%) originate from a pre-existing research cohort at IDI, while 655 (65.5%) were enrolled from the routine clinic. Overall, 81% of the patients were on first line at the time of the enrolment in the ART long-term cohort, with the more frequent regimen being zidovudine plus lamivudine plus nevirapine (44% of the cohort), followed by zidovudine plus lamivudine plus efavirenz (22%) and tenofovir plus lamivudine or emtricitabine plus efavirenz (10%). At cohort enrolment, viral suppression was defined as HIV-RNA <400 copies/mL was 95.8%. Future plans Through collaboration with other institutions, we are planning several substudies, including the evaluation of the risk for cardiovascular diseases, the assessment of bone mineral density, screening for liver cirrhosis using fibroscan technology and investigation of drug–drug interactions between ART and common drugs used for non-communicable diseases. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
Nakiyingi, Lydia; Nakanwagi, Prossy; Briggs, Jessica; Agaba, Tifu; Mubiru, Frank; Mugenyi, Mark; Ssengooba, Willy; Joloba, Moses L; Manabe, Yukari C BMC Infectious Diseases , 18 (1), pp. 87, 2018. @article{Nakiyingi2018, title = {Performance of loop-mediated isothermal amplification assay in the diagnosis of pulmonary tuberculosis in a high prevalence TB/HIV rural setting in Uganda}, author = {Lydia Nakiyingi and Prossy Nakanwagi and Jessica Briggs and Tifu Agaba and Frank Mubiru and Mark Mugenyi and Willy Ssengooba and Moses L. Joloba and Yukari C. Manabe}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Performance-of-loop-mediated-isothermal-amplification-assay-in-the-diagnosis-of-pulmonary-tuberculosis-in-a-high-prevalence-TB-or-HIV-rural-setting-in-Uganda.pdf}, doi = { 10.1186/s12879-018-2992-1}, year = {2018}, date = {2018-02-21}, journal = { BMC Infectious Diseases }, volume = {18}, number = {1}, pages = {87}, abstract = {BACKGROUND: Smear microscopy lacks sensitivity especially in HIV co-infection, resulting in undiagnosed tuberculosis (TB) and high mortality. The loop-mediated isothermal amplification (TB-LAMP) assay can be staged with minimal infrastructure, is rapid, low cost and detection can be with the naked eye. We assessed feasibility and performance of Eiken TB-LAMP test at point-of-need in TB diagnosis in a high prevalence TB/HIV rural setting in Uganda. METHODS: From October 2013-February 2014, TB-LAMP testing was performed on sputum specimens from outpatient presumptive TB adults at a district hospital and two low-level health centers in Kiboga District where smear microscopy is the available routine diagnostic option. TB-LAMP was performed by a technician after a week of training in the district hospital. The technician had no prior experience in the technology. Samples from the low-level health centers were transported to the district hospital for TB-LAMP. RESULTS: Of the 233 presumptive TB (126 at hospital); 113 (48.5%) were HIV-infected; 129 (55%) male; median age 40 (IQR 30-53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were 55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. Among HIV-infected participants, TB-LAMP sensitivity and specificity were 52.3% (95 CI 36.7-67.5%) and 97.1% (95 CI 89.9-99.6) respectively; and 24.4% (95% CI 12.9-39.5) and 98.6% (95% CI 95.1-99.8) respectively among smear-negatives. TB-LAMP sensitivity and specificity were 62.2% (95% CI 44.8-77.5) and 97.8% (95% CI 92.1-99.7) in the hospital setting where central testing occurred compared to 50.0% (95% CI 34.9-65.1) and 98.4% (95% CI 91.2-100) respectively in low-level health centers where specimens were transported centrally. CONCLUSIONS: In this high prevalence TB/HIV rural setting, TB-LAMP performs better than conventional smear microscopy in diagnosis of MTB among presumptive TB patients although the sensitivity is lower than that reported by the World Health Organization. TB-LAMP can easily be performed following a short training period and in absence of sophisticated infrastructure and expertise.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Smear microscopy lacks sensitivity especially in HIV co-infection, resulting in undiagnosed tuberculosis (TB) and high mortality. The loop-mediated isothermal amplification (TB-LAMP) assay can be staged with minimal infrastructure, is rapid, low cost and detection can be with the naked eye. We assessed feasibility and performance of Eiken TB-LAMP test at point-of-need in TB diagnosis in a high prevalence TB/HIV rural setting in Uganda. METHODS: From October 2013-February 2014, TB-LAMP testing was performed on sputum specimens from outpatient presumptive TB adults at a district hospital and two low-level health centers in Kiboga District where smear microscopy is the available routine diagnostic option. TB-LAMP was performed by a technician after a week of training in the district hospital. The technician had no prior experience in the technology. Samples from the low-level health centers were transported to the district hospital for TB-LAMP. RESULTS: Of the 233 presumptive TB (126 at hospital); 113 (48.5%) were HIV-infected; 129 (55%) male; median age 40 (IQR 30-53). Compared to MTB culture, overall sensitivity and specificity of TB-LAMP were 55.4% (95 CI 44.1-66.3) and 98.0% (95 CI 94.3-99.6) respectively. Among HIV-infected participants, TB-LAMP sensitivity and specificity were 52.3% (95 CI 36.7-67.5%) and 97.1% (95 CI 89.9-99.6) respectively; and 24.4% (95% CI 12.9-39.5) and 98.6% (95% CI 95.1-99.8) respectively among smear-negatives. TB-LAMP sensitivity and specificity were 62.2% (95% CI 44.8-77.5) and 97.8% (95% CI 92.1-99.7) in the hospital setting where central testing occurred compared to 50.0% (95% CI 34.9-65.1) and 98.4% (95% CI 91.2-100) respectively in low-level health centers where specimens were transported centrally. CONCLUSIONS: In this high prevalence TB/HIV rural setting, TB-LAMP performs better than conventional smear microscopy in diagnosis of MTB among presumptive TB patients although the sensitivity is lower than that reported by the World Health Organization. TB-LAMP can easily be performed following a short training period and in absence of sophisticated infrastructure and expertise. |
Barbara Castelnuovo Frank Mubiru, Shadia Nakalema Adelline Twimukye ; Kiragga, Agnes Describing the retention in care of human immunodeficiency viruspositive young adults who transition from adolescent to adult care Journal Article International Health, 10 (4), pp. 318-320, 2018. @article{Castelnuovo2018b, title = {Describing the retention in care of human immunodeficiency viruspositive young adults who transition from adolescent to adult care}, author = {Barbara Castelnuovo, Frank Mubiru, Shadia Nakalema, Adelline Twimukye and Agnes Kiragga }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Describing-the-retention-in-care-of-human-immunodeficiency-virus-positive-young-adults-who-transition-from-adolescent-to-adult-care.pdf}, doi = {10.1093/inthealth/ihx063.}, year = {2018}, date = {2018-02-01}, journal = {International Health}, volume = {10}, number = {4}, pages = {318-320}, abstract = {Background: There is a high rate of lost to programme (LTP) in human immunodeficiency virus (HIV)-positive young adults transitioning from paediatric/adolescent to adult care. Methods: We describe and identify risk factors for LTP in all patients 18-23 y of age at the Infectious Diseases Institute (Kampala, Uganda) from 2010 to 2014. Results: A total of 260 of 907 young adults (28.6%) became LTP. Among those on antiretroviral treatment, 39.3% became LTP. We found that the only risk factor associated with LTP was being in World Health Organization stage 3 or 4. Conclusion: There is a need for tracing studies to evaluate the true vital status of LTP in this group}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: There is a high rate of lost to programme (LTP) in human immunodeficiency virus (HIV)-positive young adults transitioning from paediatric/adolescent to adult care. Methods: We describe and identify risk factors for LTP in all patients 18-23 y of age at the Infectious Diseases Institute (Kampala, Uganda) from 2010 to 2014. Results: A total of 260 of 907 young adults (28.6%) became LTP. Among those on antiretroviral treatment, 39.3% became LTP. We found that the only risk factor associated with LTP was being in World Health Organization stage 3 or 4. Conclusion: There is a need for tracing studies to evaluate the true vital status of LTP in this group |
IeDEA, COHERE Cohort Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Program Journal Article Clinical Infectious Diseases, 66 (6), pp. 893–903, 2018. @article{IeDEA2018, title = {Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy: Collaborative Study of Treatment Program}, author = {IeDEA, COHERE Cohort }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Global-Trends-in-CD4-Cell-Count-at-the-Start-of-Antiretroviral-Therapy-Collaborative-Study-of-Treatment-Program.pdf}, doi = {10.1093/cid/cix915}, year = {2018}, date = {2018-01-25}, journal = {Clinical Infectious Diseases}, volume = {66}, number = {6}, pages = { 893–903}, abstract = {Background Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). Methods We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts. Results A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58–104/µL) to 287/µL (250–328/µL) in LICs, from 99/µL (71–140/µL) to 234/µL (192–285/µL) in LMICs, from 71/µL (49–104/µL) to 311/µL (255–379/µL) in UMICs, and from 161/µL (143–181/µL) to 327/µL (286–372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Conclusions Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). Methods We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts. Results A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58–104/µL) to 287/µL (250–328/µL) in LICs, from 99/µL (71–140/µL) to 234/µL (192–285/µL) in LMICs, from 71/µL (49–104/µL) to 311/µL (255–379/µL) in UMICs, and from 161/µL (143–181/µL) to 327/µL (286–372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Conclusions Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART. |
Vululi, Sosthene Tsongo; Bugeza, Samuel; Zeridah, Muyinda; Ddungu, Henry; Openy, Akello Betty; Frank, Mubiru; Parkes‑Ratanshi, Rosalind Prevalence of lower limb deep venous thrombosis among adult HIV positive patients attending an outpatient clinic at Mulago Hospital Journal Article AIDS Research and Therapy, 13 (1), 2018. @article{Vululi2018, title = {Prevalence of lower limb deep venous thrombosis among adult HIV positive patients attending an outpatient clinic at Mulago Hospital}, author = {Sosthene Tsongo Vululi and Samuel Bugeza and Muyinda Zeridah and Henry Ddungu and Akello Betty Openy and Mubiru Frank and Rosalind Parkes‑Ratanshi }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Prevalence-of-lower-limb-deep-venous-thrombosis-among-adult-HIV-positive-patients-attending-an-outpatient-clinic-at-Mulago-Hospital.pdf}, doi = {10.1186/s12981-018-0191-1}, year = {2018}, date = {2018-01-25}, journal = {AIDS Research and Therapy}, volume = {13}, number = {1}, abstract = {BACKGROUND: Deep venous thrombosis (DVT) and its major complication pulmonary embolism (PE) are collectively known as venous thromboembolism. In Uganda, the prevalence of DVT among HIV patients has not been previously published. The aim of the study was to determine the prevalence and sonographic features of lower limb deep venous thrombosis among HIV positive patients on anti-retroviral treatment (ART). METHODS: This was a cross sectional study in which HIV positive patients on ART were recruited from an out-patient HIV clinic at Mulago National Referral Hospital. Patients were randomly selected and enrolled until a sample size of 384 was reached. Study participants underwent compression and Doppler ultrasound studies of both lower limb deep veins using Medison Sonoacer7 ultrasound machine. RESUTS: We found a prevalence of DVT of 9.1% (35 of 384 participants) among HIV patients on ART. The prevalence of latent (asymptomatic) DVT was 2.3%. Among 35 patients with DVT, 42.8% had chronic DVT; 31.1% had acute DVT and the rest had latent DVT. Among the risk factors, the odds of occurrence of DVT among patients with prolonged immobility were 4.81 times as high as in those with no prolonged immobility (p = 0.023; OR = 4.81; 95% CI 1.25-18.62). Treatment with second line anti-retroviral therapy (ART) including protease inhibitors (PIs) was associated with higher odds of DVT occurrence compared with first line ART (p = 0.020; OR = 2.38; 95% CI 1.14-4.97). The odds of DVT occurrence in patients with a lower CD4 count (< 200 cells/µl) were 5.36 times as high as in patients with CD4 counts above 500 cells/µl (p = 0.008). About 48.6% patients with DVT had a low risk according to Well's score. CONCLUSION: DVT was shown in nearly 10% of HIV patients attending an out-patient clinic in an urban setting in Uganda. Risk factors included protease inhibitors in their ART regimen, prolonged immobility, and low CD4 count (< 200 cells/µl). Clinicians should have a low threshold for performing lower limb Doppler ultrasound scan examination on infected HIV patients on ART who are symptomatic for DVT. Therefore, clinicians should consider anti-coagulant prophylaxis and lower deep venous ultrasound screening of patients who are on second line ART regimen with low CD4 cell counts and/or with prolonged immobility or hormonal contraception.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Deep venous thrombosis (DVT) and its major complication pulmonary embolism (PE) are collectively known as venous thromboembolism. In Uganda, the prevalence of DVT among HIV patients has not been previously published. The aim of the study was to determine the prevalence and sonographic features of lower limb deep venous thrombosis among HIV positive patients on anti-retroviral treatment (ART). METHODS: This was a cross sectional study in which HIV positive patients on ART were recruited from an out-patient HIV clinic at Mulago National Referral Hospital. Patients were randomly selected and enrolled until a sample size of 384 was reached. Study participants underwent compression and Doppler ultrasound studies of both lower limb deep veins using Medison Sonoacer7 ultrasound machine. RESUTS: We found a prevalence of DVT of 9.1% (35 of 384 participants) among HIV patients on ART. The prevalence of latent (asymptomatic) DVT was 2.3%. Among 35 patients with DVT, 42.8% had chronic DVT; 31.1% had acute DVT and the rest had latent DVT. Among the risk factors, the odds of occurrence of DVT among patients with prolonged immobility were 4.81 times as high as in those with no prolonged immobility (p = 0.023; OR = 4.81; 95% CI 1.25-18.62). Treatment with second line anti-retroviral therapy (ART) including protease inhibitors (PIs) was associated with higher odds of DVT occurrence compared with first line ART (p = 0.020; OR = 2.38; 95% CI 1.14-4.97). The odds of DVT occurrence in patients with a lower CD4 count (< 200 cells/µl) were 5.36 times as high as in patients with CD4 counts above 500 cells/µl (p = 0.008). About 48.6% patients with DVT had a low risk according to Well's score. CONCLUSION: DVT was shown in nearly 10% of HIV patients attending an out-patient clinic in an urban setting in Uganda. Risk factors included protease inhibitors in their ART regimen, prolonged immobility, and low CD4 count (< 200 cells/µl). Clinicians should have a low threshold for performing lower limb Doppler ultrasound scan examination on infected HIV patients on ART who are symptomatic for DVT. Therefore, clinicians should consider anti-coagulant prophylaxis and lower deep venous ultrasound screening of patients who are on second line ART regimen with low CD4 cell counts and/or with prolonged immobility or hormonal contraception. |
Nelson Kalema Christina Lindan, Dave Glidden Samuel Yoo Achilles Katamba Andama Alfred Winceslaus Katagira Patrick Byanyim Emmanuel Musisi Sylvia Kaswabuli Sanyu Ingvar Josephine Zawedde Christina Yoon Irene Ayakaka Lucian Davis Laurence Huang William Worodria D J; Cattamanchi, Adithya Predictors and short-term outcomes of recurrent pulmonary tuberculosis, Uganda: a cohort study Journal Article South African repository journal, 23 (4), pp. 106-112, 2018. @article{Kalema2018, title = {Predictors and short-term outcomes of recurrent pulmonary tuberculosis, Uganda: a cohort study}, author = {Nelson Kalema, Christina Lindan, Dave Glidden, Samuel D. Yoo, Achilles Katamba, Andama Alfred, Winceslaus Katagira, Patrick Byanyim, Emmanuel Musisi, Sylvia Kaswabuli, Sanyu Ingvar, Josephine Zawedde, Christina Yoon, Irene Ayakaka, J. Lucian Davis, Laurence Huang, William Worodria, and Adithya Cattamanchi}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Predictors-and-short-term-outcomes-of-recurrent-pulmonary-tuberculosis-Uganda-a-cohort-study.pdf}, year = {2018}, date = {2018-01-22}, journal = {South African repository journal}, volume = {23}, number = {4}, pages = {106-112}, abstract = {Introduction: Recurrent tuberculosis (TB) occurring >2 years after completing treatment for a prior TB episode is most often due to reinfection with a new strain of M. tuberculosis. Objectives: We determined the prevalence and outcome of late recurrent TB among hospitalized patients in Kampala, Uganda. Methods: We conducted a retrospective analysis of patients admitted to Mulago Hospital who had cough of >2 weeks' duration and completed TB treatment >2 years prior to admission. All patients had mycobacterial culture performed on two sputum specimens and vital status ascertained 2-months post-enrollment. We performed modeling to identify predictors of recurrent TB and of survival. Results: Among 234 patients, 84 (36%) had recurrent TB. Independent predictors included younger age (aOR=0.64, 95% CI=0.42-0.97, p=0.04), chest pain >2 weeks (aOR=3.32, 95% CI=1.38-8.02, p=0.007), severe weight loss ≥5 kilograms (aOR=4.88, 95% CI=1.66-14.29, p=0.004) and presence of ≥1 WHO danger sign of severe illness (aOR=3.55, 95% CI=1.36-9.29, p=0.01). Two-month mortality was 17.8% (95% CI=10.5-29.2%), and was higher among patients not initiated on TB treatment (aHR=16.67, 95% CI=1.18-200, p=0.04), not on ART if HIV-positive (aHR=16.99, 95% CI=1.17-246.47, p=0.04) and with a history of smoking (aHR=1.20, 95% CI=1.03-1.40, p=0.02). Conclusion: The high prevalence of late recurrent TB likely reflects high levels of TB transmission in Kampala. Increased use of empiric TB treatment and early ART treatment initiation if HIV-positive should be considered in patients with a prior history of TB, particularly if young, with weight loss ≥5kgs, chest pain >2 weeks or ≥1 WHO danger sign of severe illness.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction: Recurrent tuberculosis (TB) occurring >2 years after completing treatment for a prior TB episode is most often due to reinfection with a new strain of M. tuberculosis. Objectives: We determined the prevalence and outcome of late recurrent TB among hospitalized patients in Kampala, Uganda. Methods: We conducted a retrospective analysis of patients admitted to Mulago Hospital who had cough of >2 weeks' duration and completed TB treatment >2 years prior to admission. All patients had mycobacterial culture performed on two sputum specimens and vital status ascertained 2-months post-enrollment. We performed modeling to identify predictors of recurrent TB and of survival. Results: Among 234 patients, 84 (36%) had recurrent TB. Independent predictors included younger age (aOR=0.64, 95% CI=0.42-0.97, p=0.04), chest pain >2 weeks (aOR=3.32, 95% CI=1.38-8.02, p=0.007), severe weight loss ≥5 kilograms (aOR=4.88, 95% CI=1.66-14.29, p=0.004) and presence of ≥1 WHO danger sign of severe illness (aOR=3.55, 95% CI=1.36-9.29, p=0.01). Two-month mortality was 17.8% (95% CI=10.5-29.2%), and was higher among patients not initiated on TB treatment (aHR=16.67, 95% CI=1.18-200, p=0.04), not on ART if HIV-positive (aHR=16.99, 95% CI=1.17-246.47, p=0.04) and with a history of smoking (aHR=1.20, 95% CI=1.03-1.40, p=0.02). Conclusion: The high prevalence of late recurrent TB likely reflects high levels of TB transmission in Kampala. Increased use of empiric TB treatment and early ART treatment initiation if HIV-positive should be considered in patients with a prior history of TB, particularly if young, with weight loss ≥5kgs, chest pain >2 weeks or ≥1 WHO danger sign of severe illness. |
Dorman, Susan E; Schumacher, Samuel G; Alland, David; Nabeta, Pamela; Armstrong, Derek T; King, Bonnie; Hall, Sandra L; Chakravorty, Soumitesh; Cirillo, Daniela M; Nestani Tukvadze, ; Bablishvili, Nino; Stevens, Wendy; Scott, Lesley; Rodrigues, Camilla; Kazi, Mubin I; Joloba, Moses; Nakiyingi, Lydia; Nicol, Mark P; Ghebrekristos, Yonas; Anyango, Irene; Murithi, Wilfred; Dietze, Reynaldo; Peres, Renata Lyrio; Skrahina, Alena; Auchynka, Vera; Chopra, Kamal Kishore; Hanif, Mahmud; Liu, Xin; Xing Yuan, ; Boehme, Catharina C; Ellner, Jerrold J; Denkinger, Claudia M Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study Journal Article Lancent, 18 (1), pp. 76-84, 2018. @article{Dorman2018, title = {Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study}, author = {Susan E Dorman and Samuel G Schumacher and David Alland and Pamela Nabeta and Derek T Armstrong and Bonnie King and Sandra L Hall and Soumitesh Chakravorty and Daniela M Cirillo and Nestani Tukvadze, and Nino Bablishvili and Wendy Stevens and Lesley Scott and Camilla Rodrigues and Mubin I Kazi and Moses Joloba and Lydia Nakiyingi and Mark P Nicol and Yonas Ghebrekristos and Irene Anyango and Wilfred Murithi and Reynaldo Dietze and Renata Lyrio Peres and Alena Skrahina and Vera Auchynka and Kamal Kishore Chopra and Mahmud Hanif and Xin Liu and Xing Yuan, and Catharina C Boehme and Jerrold J Ellner and Claudia M Denkinger}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Xpert-MTBRIF-Ultra-for-detection-of-Mycobacterium.pdf}, doi = {10.1016/S1473-3099(17)30691-6 }, year = {2018}, date = {2018-01-21}, journal = {Lancent}, volume = {18}, number = {1}, pages = { 76-84}, abstract = {Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (–2·7%, –3·9 to –1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (–2·7%, –3·9 to –1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases. |
Juliet Otiti-Sengeri Robert Colebunders, Steven Reynolds Musa Muwonge Getrude Nakigozi Valerian Kiggundu Fred Nalugoda Damalie Nakanjako J Elevated inflammatory cytokines in aqueous cytokine profile in HIV-1 infected patients with cataracts in Uganda Journal Article BMC Ophthalmology, 18 (1), 2018. @article{Otiti-Sengeri2018, title = {Elevated inflammatory cytokines in aqueous cytokine profile in HIV-1 infected patients with cataracts in Uganda}, author = {Juliet Otiti-Sengeri, Robert Colebunders, Steven J. Reynolds, Musa Muwonge, Getrude Nakigozi, Valerian Kiggundu, Fred Nalugoda, Damalie Nakanjako}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Elevated-inflammatory-cytokines-in-aqueous-cytokine-profile-in-HIV-1-infected-patients-with-cataracts-in-Uganda.pdf}, year = {2018}, date = {2018-01-19}, journal = {BMC Ophthalmology}, volume = {18}, number = {1}, abstract = {BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts. METHODS: A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher's exact test and the Student's t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines. RESULTS: The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p = 0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher among those with a CD4+ T cell count greater than 200cells/mm3 compared to those with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively). CONCLUSION: Cataracts among HIV-positive adults were associated with higher intraocular inflammation relative to the healthy elderly individuals with cataracts. There is need to explore the potential role of intra-ocular anti-inflammatory agents in the management of cataracts among HIV positive patients.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts. METHODS: A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher's exact test and the Student's t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines. RESULTS: The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p = 0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher among those with a CD4+ T cell count greater than 200cells/mm3 compared to those with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively). CONCLUSION: Cataracts among HIV-positive adults were associated with higher intraocular inflammation relative to the healthy elderly individuals with cataracts. There is need to explore the potential role of intra-ocular anti-inflammatory agents in the management of cataracts among HIV positive patients. |
Charles B. Holmes Constantin T. Yiannoutsos, Batya Elul Elizabeth Bukusi John Ssali Andrew Kambugu Beverly Musick Craig Cohen Carolyn Williams Lameck Diero Nancy Padian Kara Wools-Kaloustian S K Increased prevalence of pregnancy and comparative risk of program attrition among individuals starting HIV treatment in East Africa. Journal Article PloS One, 13 (1), 2018. @article{Holmes2018, title = {Increased prevalence of pregnancy and comparative risk of program attrition among individuals starting HIV treatment in East Africa.}, author = {Charles B. Holmes, Constantin T. Yiannoutsos, Batya Elul, Elizabeth Bukusi, John Ssali, Andrew Kambugu, Beverly S. Musick, Craig Cohen, Carolyn Williams, Lameck Diero, Nancy Padian, Kara K. Wools-Kaloustian}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Increased-prevalence-of-pregnancy-and-comparative-risk-of-program-attrition-among-individuals-starting-HIV-treatment-in-East-Africa.pdf}, doi = {10.1371/journal.pone.0190828}, year = {2018}, date = {2018-01-17}, journal = {PloS One}, volume = {13}, number = {1}, abstract = {BACKGROUND: The World Health Organization now recommends initiating all pregnant women on life-long antiretroviral therapy (ART), yet there is limited information about the characteristics and program outcomes of pregnant women already on ART in Africa. Our hypothesis was that pregnant women comprised an increasing proportion of those starting ART, and that sub-groups of these women were at higher risk for program attrition. METHODS AND FINDINGS: We used the International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to conduct a retrospective cohort study including HIV care and treatment programs in Kenya, Uganda, and Tanzania. The cohort consecutively included HIV-infected individuals 13 years or older starting ART 2004-2014. We examined trends over time in the proportion pregnant, their characteristics and program attrition rates compared to others initiating and already receiving ART. 156,474 HIV-infected individuals (67.0% women) started ART. The proportion of individuals starting ART who were pregnant women rose from 5.3% in 2004 to 12.2% in 2014. Mean CD4 cell counts at ART initiation, weighted for annual program size, increased from 2004 to 2014, led by non-pregnant women (annual increase 20 cells/mm3) and men (17 cells/mm3 annually), with lower rates of change in pregnant women (10 cells/mm3 per year) (p<0.0001). There was no significant difference in the cumulative incidence of program attrition at 6 months among pregnant women starting ART and non-pregnant women. However, healthy pregnant women starting ART (WHO stage 1/2) had a higher rate of attrition rate (9.6%), compared with healthy non-pregnant women (6.5%); in contrast among women with WHO stage 3/4 disease, pregnant women had lower attrition (8.4%) than non-pregnant women (14.4%). Among women who initiated ART when healthy and remained in care for six months, subsequent six-month attrition was slightly higher among pregnant women at ART start (3.5%) compared to those who were not pregnant (2.4%), (absolute difference 1.1%, 95% CI 0.7%-1.5%). CONCLUSIONS: Pregnant women comprise an increasing proportion of those initiating ART in Africa, and pregnant women starting ART while healthy are at higher risk for program attrition than non-pregnant women. As ART programs further expand access to healthier pregnant women, further studies are needed to better understand the drivers of loss among this high risk group of women to optimize retention.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The World Health Organization now recommends initiating all pregnant women on life-long antiretroviral therapy (ART), yet there is limited information about the characteristics and program outcomes of pregnant women already on ART in Africa. Our hypothesis was that pregnant women comprised an increasing proportion of those starting ART, and that sub-groups of these women were at higher risk for program attrition. METHODS AND FINDINGS: We used the International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to conduct a retrospective cohort study including HIV care and treatment programs in Kenya, Uganda, and Tanzania. The cohort consecutively included HIV-infected individuals 13 years or older starting ART 2004-2014. We examined trends over time in the proportion pregnant, their characteristics and program attrition rates compared to others initiating and already receiving ART. 156,474 HIV-infected individuals (67.0% women) started ART. The proportion of individuals starting ART who were pregnant women rose from 5.3% in 2004 to 12.2% in 2014. Mean CD4 cell counts at ART initiation, weighted for annual program size, increased from 2004 to 2014, led by non-pregnant women (annual increase 20 cells/mm3) and men (17 cells/mm3 annually), with lower rates of change in pregnant women (10 cells/mm3 per year) (p<0.0001). There was no significant difference in the cumulative incidence of program attrition at 6 months among pregnant women starting ART and non-pregnant women. However, healthy pregnant women starting ART (WHO stage 1/2) had a higher rate of attrition rate (9.6%), compared with healthy non-pregnant women (6.5%); in contrast among women with WHO stage 3/4 disease, pregnant women had lower attrition (8.4%) than non-pregnant women (14.4%). Among women who initiated ART when healthy and remained in care for six months, subsequent six-month attrition was slightly higher among pregnant women at ART start (3.5%) compared to those who were not pregnant (2.4%), (absolute difference 1.1%, 95% CI 0.7%-1.5%). CONCLUSIONS: Pregnant women comprise an increasing proportion of those initiating ART in Africa, and pregnant women starting ART while healthy are at higher risk for program attrition than non-pregnant women. As ART programs further expand access to healthier pregnant women, further studies are needed to better understand the drivers of loss among this high risk group of women to optimize retention. |
Musomba Rachel Castelnuovo Barbara, Claire Murphy Charlene Komujuni Patience Nyakato Ponsiano Ocama Mohammed Lamorde Philippa Easterbrooka Rosalind Parkes Ratanshi Uptake of hepatitis B-HIV co-infection screening and management in a resource limited settin Journal Article BMC Hepatology, Medicine and Policy, 2018. @article{Rachel2018, title = {Uptake of hepatitis B-HIV co-infection screening and management in a resource limited settin}, author = {Musomba Rachel, Castelnuovo Barbara, Claire Murphy, Charlene Komujuni, Patience Nyakato, Ponsiano Ocama, Mohammed Lamorde, Philippa Easterbrooka, Rosalind Parkes Ratanshi}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Uptake-of-hepatitis-B-HIV-co-infection-screening-and-management-in-a-resource-limited-setting.pdf}, doi = {10.1186/s41124-017-0030-3}, year = {2018}, date = {2018-01-06}, journal = { BMC Hepatology, Medicine and Policy}, abstract = {Background: WHO hepatitis B guidelines recommend testing all new HIV patients, treating them accordingly or providing immunization. At the Infectious Diseases Institute (IDI) following an audit done in 2012, only 46% patients had been screened for hepatitis B with variable management plans therefore new internal guidelines were implemented. This study describes the uptake of hepatitis B screening and management of patients with hepatitis B and HIV con-infection after the implementation. Methods: Data included for all HIV positive patients in care at IDI by October 2015. Data are expressed as median with interquartile range (IQR) and percentages were compared using the chi square test. Statistical analysis was performed using STATA version 13. The IDI laboratory upper limit of normal for alanine aminotransferase (ALT) and aspartate aminotransferase (ASTs) was 40 IU/ml. Results: Number of hepatitis B screening tests increased from 800 by 2012 to 1400 in 2015. By 2015 8042/8604(93.5%) patients had been screened for hepatitis B. Overall hepatitis B positive were 359 (4.6%). 166 (81.4%) hepatitis B positives were switched to a tenofovir (TDF) containing regimen. Conclusion: Our study confirms the importance of screening for hepatitis B and of using ART regimens containing tenofovir in hepatitis B co-infected patients. Whilst our program has made improvements in care still 18.6% of patients with hepatitis B were not on tenofovir regimens, 98.1% had no hepatitis B viral loads done. Clinicians should recognize the potential for hepatitis B in HIV positive patients and the importance of early diagnosis and treatment to ensure optimal management of cases and follow up.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: WHO hepatitis B guidelines recommend testing all new HIV patients, treating them accordingly or providing immunization. At the Infectious Diseases Institute (IDI) following an audit done in 2012, only 46% patients had been screened for hepatitis B with variable management plans therefore new internal guidelines were implemented. This study describes the uptake of hepatitis B screening and management of patients with hepatitis B and HIV con-infection after the implementation. Methods: Data included for all HIV positive patients in care at IDI by October 2015. Data are expressed as median with interquartile range (IQR) and percentages were compared using the chi square test. Statistical analysis was performed using STATA version 13. The IDI laboratory upper limit of normal for alanine aminotransferase (ALT) and aspartate aminotransferase (ASTs) was 40 IU/ml. Results: Number of hepatitis B screening tests increased from 800 by 2012 to 1400 in 2015. By 2015 8042/8604(93.5%) patients had been screened for hepatitis B. Overall hepatitis B positive were 359 (4.6%). 166 (81.4%) hepatitis B positives were switched to a tenofovir (TDF) containing regimen. Conclusion: Our study confirms the importance of screening for hepatitis B and of using ART regimens containing tenofovir in hepatitis B co-infected patients. Whilst our program has made improvements in care still 18.6% of patients with hepatitis B were not on tenofovir regimens, 98.1% had no hepatitis B viral loads done. Clinicians should recognize the potential for hepatitis B in HIV positive patients and the importance of early diagnosis and treatment to ensure optimal management of cases and follow up. |
Mpoza, Edward; Mukaremera, Liliane; Kundura, Didas Atwebembere; Akampurira, Andrew; Luggya, Tonny; Tadeo, Kiiza Kandole; Pastick, Katelyn A; Sarah C. Bridgt, Lillian Tugume ; Kiggundu, Reuben; Musubire, Abdu K; Williams, Darlisha A; Muzoora, Conrad; Nalintya, Elizabeth; Rajasingham, Radha; Rhein, Joshua; Boulware, David R; Meya, David B; Abassi, Mahsa Evaluation of a point-of-care immunoassay test kit ‘StrongStep’ for cryptococcal antigen detection Journal Article PloS One, 13 (1), 2018. @article{Mpoza2018, title = {Evaluation of a point-of-care immunoassay test kit ‘StrongStep’ for cryptococcal antigen detection}, author = {Edward Mpoza and Liliane Mukaremera and Didas Atwebembere Kundura and Andrew Akampurira and Tonny Luggya and Kiiza Kandole Tadeo and Katelyn A. Pastick and Sarah C. Bridgt, Lillian Tugume and Reuben Kiggundu and Abdu K. Musubire and Darlisha A. Williams and Conrad Muzoora and Elizabeth Nalintya and Radha Rajasingham and Joshua Rhein and David R. Boulware and David B. Meya and Mahsa Abassi}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Evaluation-of-a-point-of-care-immunoassay-test-kit-StrongStep-for-cryptococcal-antigen-detection..pdf}, doi = {10.1371/journal.pone.0190652}, year = {2018}, date = {2018-01-05}, journal = {PloS One}, volume = {13}, number = {1}, abstract = {BACKGROUND: HIV-associated cryptococcal meningitis is the leading cause of adult meningitis in Sub-Saharan Africa, accounting for 15%-20% of AIDS-attributable mortality. The development of point-of-care assays has greatly improved the screening and diagnosis of cryptococcal disease. We evaluated a point-of-care immunoassay, StrongStep (Liming Bio, Nanjing, Jiangsu, China) lateral flow assay (LFA), for cryptococcal antigen (CrAg) detection in cerebrospinal fluid (CSF) and plasma. METHODS: We retrospectively tested 143 CSF and 77 plasma samples collected from HIV-seropositive individuals with suspected meningitis from 2012-2016 in Uganda. We prospectively tested 90 plasma samples collected from HIV-seropositive individuals with CD4 cell count <100 cells/μL from 2016-2017 as part of a cryptococcal antigenemia screening program. The StrongStep CrAg was tested against a composite reference standard of positive Immy CrAg LFA (Immy, Norman, OK, USA) or CSF culture with statistical comparison by McNemar's test. RESULTS: StrongStep CrAg had a 98% (54/55) sensitivity and 90% (101/112) specificity in plasma (P = 0.009, versus reference standard). In CSF, the StrongStep CrAg had 100% (101/101) sensitivity and 98% (41/42) specificity (P = 0.99). Adjusting for the cryptococcal antigenemia prevalence of 9% in Uganda and average cryptococcal meningitis prevalence of 37% in Sub-Saharan Africa, the positive predictive value of the StrongStep CrAg was 50% in plasma and 96% in CSF. CONCLUSIONS: We found the StrongStep CrAg LFA to be a sensitive assay, which unfortunately lacked specificity in plasma. In lower prevalence settings, a majority of positive results from blood would be expected to be false positives.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: HIV-associated cryptococcal meningitis is the leading cause of adult meningitis in Sub-Saharan Africa, accounting for 15%-20% of AIDS-attributable mortality. The development of point-of-care assays has greatly improved the screening and diagnosis of cryptococcal disease. We evaluated a point-of-care immunoassay, StrongStep (Liming Bio, Nanjing, Jiangsu, China) lateral flow assay (LFA), for cryptococcal antigen (CrAg) detection in cerebrospinal fluid (CSF) and plasma. METHODS: We retrospectively tested 143 CSF and 77 plasma samples collected from HIV-seropositive individuals with suspected meningitis from 2012-2016 in Uganda. We prospectively tested 90 plasma samples collected from HIV-seropositive individuals with CD4 cell count <100 cells/μL from 2016-2017 as part of a cryptococcal antigenemia screening program. The StrongStep CrAg was tested against a composite reference standard of positive Immy CrAg LFA (Immy, Norman, OK, USA) or CSF culture with statistical comparison by McNemar's test. RESULTS: StrongStep CrAg had a 98% (54/55) sensitivity and 90% (101/112) specificity in plasma (P = 0.009, versus reference standard). In CSF, the StrongStep CrAg had 100% (101/101) sensitivity and 98% (41/42) specificity (P = 0.99). Adjusting for the cryptococcal antigenemia prevalence of 9% in Uganda and average cryptococcal meningitis prevalence of 37% in Sub-Saharan Africa, the positive predictive value of the StrongStep CrAg was 50% in plasma and 96% in CSF. CONCLUSIONS: We found the StrongStep CrAg LFA to be a sensitive assay, which unfortunately lacked specificity in plasma. In lower prevalence settings, a majority of positive results from blood would be expected to be false positives. |
Catriona Waitt Adeniyi Olagunju, Shadia Nakalema Isabella Kyohaire Andrew Owen Mohammed Lamorde Saye Khoo Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs Journal Article Journal of Antimicrobiol Chemotherapy, 73 (4), pp. 1013-1019, 2018. @article{Waitt2018, title = {Plasma and breast milk pharmacokinetics of emtricitabine, tenofovir and lamivudine using dried blood and breast milk spots in nursing African mother–infant pairs}, author = {Catriona Waitt, Adeniyi Olagunju, Shadia Nakalema, Isabella Kyohaire, Andrew Owen, Mohammed Lamorde, Saye Khoo}, year = {2018}, date = {2018-01-04}, journal = {Journal of Antimicrobiol Chemotherapy}, volume = {73}, number = {4}, pages = {1013-1019}, abstract = {Background: Breast milk transfer of first-line ART from mother to infant is not fully understood. Objectives: To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother-infant pairs. Methods: Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5-6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Results: Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4-8 h compared with 2 h for lamivudine and 2-4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82-1.15) for AUC0-12, whereas for AUC12-20 this was 3.04 (2.87-4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3-22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06-3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6-20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0-0.03) and no infant had measurable tenofovir concentrations. Conclusions: Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Breast milk transfer of first-line ART from mother to infant is not fully understood. Objectives: To determine the concentrations of lamivudine, emtricitabine and tenofovir in maternal blood, breast milk and infant blood from breastfeeding mother-infant pairs. Methods: Intensive pharmacokinetic sampling of maternal dried blood spots (DBS), dried breast milk spots (DBMS) and infant DBS from 30 Ugandan and 29 Nigerian mothers receiving first-line ART and their infants was conducted. DBS and DBMS were collected pre-dose and at 5-6 timepoints up to 12 h following observed dosing. Infant DBS were sampled twice during this period. Lamivudine, emtricitabine and tenofovir were quantified using LC-MS/MS, with non-compartmental analysis to calculate key pharmacokinetic parameters. Results: Peak concentrations in breast milk from women taking lamivudine and emtricitabine occurred later than in plasma (4-8 h compared with 2 h for lamivudine and 2-4 h for emtricitabine). Consequently, the milk-to-plasma (M:P) ratio of lamivudine taken once daily was 0.95 (0.82-1.15) for AUC0-12, whereas for AUC12-20 this was 3.04 (2.87-4.16). Lamivudine was detectable in 36% (14/39) of infants [median 17.7 (16.3-22.7) ng/mL]. For 200 mg of emtricitabine once daily, the median M:P ratio was 3.01 (2.06-3.38). Three infants (19%) had measurable emtricitabine [median 18.5 (17.6-20.8) ng/mL]. For 300 mg of tenofovir once daily, the median M:P ratio was 0.015 (0-0.03) and no infant had measurable tenofovir concentrations. Conclusions: Emtricitabine and lamivudine accumulate in breast milk and were detected in breastfeeding infants. In contrast, tenofovir penetrates the breast milk to a small degree, but is undetectable in breastfeeding infants. |
van James G Hakim Jennifer Thompson, Cissy Kityo Anne Hoppe Andrew Kambugu Joep Oosterhout Abbas Lugemwa Abraham Siika Raymond Mwebaze Aggrey Mweemba George Abongomera Margaret Thomason Philippa Easterbrook Peter Mugyenyi Sarah Walker Nicholas Paton J J A I 18 (1), pp. 47-57, 2018. @article{Hakim2018, title = {Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial.}, author = {James G Hakim, Jennifer Thompson, Cissy Kityo, Anne Hoppe, Andrew Kambugu, Joep J van Oosterhout, Abbas Lugemwa, Abraham Siika, Raymond Mwebaze, Aggrey Mweemba, George Abongomera, Margaret J Thomason, Philippa Easterbrook, Peter Mugyenyi, A Sarah Walker, Nicholas I Paton}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Europe-Africa-Research-Network-for-Evaluation-of-Second-line-Therapy-EARNEST-Trial-Team.-Lopinavir-plus-nucleoside-reverse-transcriptase-inhibitors-lopinavir-plus-raltegravir-or-lopi.pdf}, doi = {10.1016/S1473-3099(17)30630-8}, year = {2018}, date = {2018-01-02}, volume = {18}, number = {1}, pages = {47-57}, abstract = {BACKGROUND: Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings. METHODS: We analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787. FINDINGS: Between April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification. INTERPRETATION: Protease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings. FUNDING: European and Developing Countries Clinical Trials Partnership (EDCTP), UK Medical Research Council, Instituto de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, Merck, ViiV Healthcare, WHO.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings. METHODS: We analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787. FINDINGS: Between April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification. INTERPRETATION: Protease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings. FUNDING: European and Developing Countries Clinical Trials Partnership (EDCTP), UK Medical Research Council, Instituto de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, Merck, ViiV Healthcare, WHO. |
Kajumbula H Fujita AW, Mbabazi Najjuka Izale Akampurira Aisu Lamorde Walwema Bahr NC Meya DB Boulware DR Manabe YC. O C C A S M R Antimicrobial Drug Resistance in Blood Culture Isolates at a Tertiary Hospital, Uganda. Journal Article Emerging Infectious Diseases, 24 (1), 2018. @article{H2018, title = {Antimicrobial Drug Resistance in Blood Culture Isolates at a Tertiary Hospital, Uganda.}, author = {Kajumbula H, Fujita AW, Mbabazi O, Najjuka C, Izale C, Akampurira A, Aisu S, Lamorde M, Walwema R, Bahr NC, Meya DB, Boulware DR, Manabe YC.}, url = {https://wwwnc.cdc.gov/eid/article/24/1/17-1112_article}, doi = {10.3201/eid2401.}, year = {2018}, date = {2018-01-01}, journal = {Emerging Infectious Diseases}, volume = {24}, number = {1}, abstract = {We summarize antimicrobial drug resistance (AMR) patterns from blood cultures at a tertiary hospital in Uganda. High rates of resistance to first-line antibiotic drugs were observed among Staphylococcus aureus and gram-negative organisms. Microbiology services with susceptibility testing should be strengthened to support standardized reporting of AMR data in sub-Saharan Africa.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We summarize antimicrobial drug resistance (AMR) patterns from blood cultures at a tertiary hospital in Uganda. High rates of resistance to first-line antibiotic drugs were observed among Staphylococcus aureus and gram-negative organisms. Microbiology services with susceptibility testing should be strengthened to support standardized reporting of AMR data in sub-Saharan Africa. |
2017 |
Byakika-Kibwika, Pauline; Achan, Jane; Lamorde, Mohammed; Karera-Gonahasa, Carine; Kiragga, Agnes N; Mayanja-Kizza, Harriet; Kiwanuka, Noah; Nsobya, Sam; Talisuna, Ambrose O; Merry, Concepta BMC Infectious Diseases, 17 (1), pp. 794, 2017. @article{Byakika-Kibwika2017, title = {Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial}, author = {Pauline Byakika-Kibwika and Jane Achan and Mohammed Lamorde and Carine Karera-Gonahasa and Agnes N. Kiragga and Harriet Mayanja-Kizza and Noah Kiwanuka and Sam Nsobya and Ambrose O. Talisuna and Concepta Merry}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Intravenous-artesunate-plus-Artemisnin-based-Combination-Therapy-ACT-or-intravenous-quinine-plus-ACT-for-treatment-of-severe-malaria-in-Ugandan-children-a-randomized-controlled-clinical.pdf}, doi = {10.1186/s12879-017-2924-5}, year = {2017}, date = {2017-12-28}, journal = {BMC Infectious Diseases}, volume = {17}, number = {1}, pages = {794}, abstract = {Background: Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. Methods: In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. Results: We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1–2) vs 3 (2–3), P<0. 001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms. Conclusion: In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. Trial registration: The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Keywords: Artesunate, Quinine, Artemisinin combination therapy, Severe malaria, Re-infection }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. Methods: In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. Results: We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1–2) vs 3 (2–3), P<0. 001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms. Conclusion: In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. Trial registration: The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Keywords: Artesunate, Quinine, Artemisinin combination therapy, Severe malaria, Re-infection |
Mahsa Abassi Joshua Rhein, David B. Meya David R. Boulwar Cryptococcal Disease in the Era of "Test and Treat": Is There Cause for Concern? Journal Article Open Forum Infectious Diseases, 5 (51), 2017. @article{Mahsa Abassi2017, title = {Cryptococcal Disease in the Era of "Test and Treat": Is There Cause for Concern?}, author = {Mahsa Abassi, Joshua Rhein, David B. Meya, David R. Boulwar }, url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777480/}, doi = {10.1093/ofid/ofx274}, year = {2017}, date = {2017-12-24}, journal = {Open Forum Infectious Diseases}, volume = {5}, number = {51}, abstract = {Treatment of cryptococcosis requires deferred initiation of antiretroviral therapy (ART). Early ART initiation may be detrimental in the context of cryptococcal infection by increasing the risk of immune reconstitution inflammatory syndrome (IRIS). We present 3 cases where early ART initiation in the presence of unrecognized cryptococcal disease had fatal outcomes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Treatment of cryptococcosis requires deferred initiation of antiretroviral therapy (ART). Early ART initiation may be detrimental in the context of cryptococcal infection by increasing the risk of immune reconstitution inflammatory syndrome (IRIS). We present 3 cases where early ART initiation in the presence of unrecognized cryptococcal disease had fatal outcomes. |
Abassi, Mahsa; Nakigozi, Bozena Morawski Gertrude M; Nakasujja, Noeline; Kong, Xiangrong; Ronald, David Meya Kevin Robertson B; Maria, Gray; Sacktor, Wawer Ned J; Boulware, David R Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda Journal Article Journal of NueroVirology, 23 (3), pp. 369-375, 2017, ISBN: 1355-0284. @article{Abassi2017b, title = {Cerebrospinal fluid biomarkers and HIV-associated neurocognitive disorders in HIV-infected individuals in Rakai, Uganda}, author = { Mahsa Abassi and Bozena M. Morawski Gertrude Nakigozi and Noeline Nakasujja and Xiangrong Kong and David B. Meya Kevin Robertson Ronald and Gray Maria and J. Wawer Ned Sacktor and David R. Boulware}, doi = {10.1007/s13365-016-0505-9}, isbn = {1355-0284}, year = {2017}, date = {2017-12-19}, journal = {Journal of NueroVirology}, volume = {23}, number = {3}, pages = {369-375}, abstract = {In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/μL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid β42. Individuals with CD4 351–500 cells/μL (N = 40) had significantly higher CSF levels of interleukin (IL)-1β, amyloid β42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/μL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid β42. Individuals with CD4 351–500 cells/μL (N = 40) had significantly higher CSF levels of interleukin (IL)-1β, amyloid β42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND. |
Flynn, Andrew G; Anguzu, Godwin; Mubiru, Frank; Kiragga, Agnes N; Kamya, Moses; Meya, David B; Boulware, David R; Kambugu, Andrew; Castelnuovo, Barbara C Socioeconomic position and ten-year survival and virologic outcomes in a Ugandan HIV cohort receiving antiretroviral therapy Journal Article PloS One, 2017. @article{Flynn2017, title = {Socioeconomic position and ten-year survival and virologic outcomes in a Ugandan HIV cohort receiving antiretroviral therapy}, author = {Andrew G. Flynn and Godwin Anguzu and Frank Mubiru and Agnes N. Kiragga and Moses Kamya and David B. Meya and David R. Boulware and Andrew Kambugu and Barbara C. Castelnuovo }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Socioeconomic-position-and-ten-year-survival-and-virologic-outcomes-in-a-Ugandan-HIV-cohort-receiving-antiretroviral-therapy.pdf}, doi = {10.1371/journal. pone.0189055}, year = {2017}, date = {2017-12-15}, journal = {PloS One}, abstract = {Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004–2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004–2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART. |
Abdu Kisekka Musubire David B. Meya, Paul Bohjanen Elly Tebasooke Katabira Patrice Barasukana David Boulware Ana-Claire Meyer R R Frontiers in Neurology, 8 (618), 2017. @article{Musubire2017, title = {A Systematic Review of Non-Traumatic Spinal Cord injuries in Sub-Saharan Africa and a Proposed Diagnostic Algorithm for Resource-Limited Settings}, author = {Abdu Kisekka Musubire, David B. Meya, Paul R. Bohjanen, Elly Tebasooke Katabira, Patrice Barasukana, David R. Boulware, Ana-Claire Meyer}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/A-Systematic-Review-of-Non-Traumatic-Spinal-Cord-Injuries-in-Sub-Saharan-Africa-and-a-Proposed-Diagnostic-Algorithm-for-Resource-Limited-Settings.pdf}, doi = {10.3389/fneur.2017.00618.}, year = {2017}, date = {2017-12-08}, journal = {Frontiers in Neurology}, volume = {8}, number = {618}, abstract = {Background: Non-traumatic myelopathy is common in Africa and there are geographic differences in etiology. Clinical management is challenging due to the broad differential diagnosis and the lack of diagnostics. The objective of this systematic review is to determine the most common etiologies of non-traumatic myelopathy in sub-Saharan Africa to inform a regionally appropriate diagnostic algorithm. Methods: We conducted a systemic review searching Medline and Embase databases using the following search terms: “Non traumatic spinal cord injury” or “myelopathy” with limitations to epidemiology or etiologies and Sub-Saharan Africa. We described the frequencies of the different etiologies and proposed a diagnostic algorithm based on the most common diagnoses. Results: We identified 19 studies all performed at tertiary institutions; 15 were retrospective and 13 were published in the era of the HIV epidemic. Compressive bone lesions accounted for more than 48% of the cases; a majority were Pott’s disease and metastatic disease. No diagnosis was identified in up to 30% of cases in most studies; in particular, definitive diagnoses of non-compressive lesions were rare and a majority were clinical diagnoses of transverse myelitis and HIV myelopathy. Age and HIV were major determinants of etiology. Conclusion: Compressive myelopathies represent a majority of non-traumatic myelopathies in sub-Saharan Africa, and most were due to Pott’s disease. Non-compressive myelopathies have not been well defined and need further research in Africa. We recommend a standardized approach to management of non-traumatic myelopathy focused on identifying treatable conditions with tests widely available in low-resource settings. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Non-traumatic myelopathy is common in Africa and there are geographic differences in etiology. Clinical management is challenging due to the broad differential diagnosis and the lack of diagnostics. The objective of this systematic review is to determine the most common etiologies of non-traumatic myelopathy in sub-Saharan Africa to inform a regionally appropriate diagnostic algorithm. Methods: We conducted a systemic review searching Medline and Embase databases using the following search terms: “Non traumatic spinal cord injury” or “myelopathy” with limitations to epidemiology or etiologies and Sub-Saharan Africa. We described the frequencies of the different etiologies and proposed a diagnostic algorithm based on the most common diagnoses. Results: We identified 19 studies all performed at tertiary institutions; 15 were retrospective and 13 were published in the era of the HIV epidemic. Compressive bone lesions accounted for more than 48% of the cases; a majority were Pott’s disease and metastatic disease. No diagnosis was identified in up to 30% of cases in most studies; in particular, definitive diagnoses of non-compressive lesions were rare and a majority were clinical diagnoses of transverse myelitis and HIV myelopathy. Age and HIV were major determinants of etiology. Conclusion: Compressive myelopathies represent a majority of non-traumatic myelopathies in sub-Saharan Africa, and most were due to Pott’s disease. Non-compressive myelopathies have not been well defined and need further research in Africa. We recommend a standardized approach to management of non-traumatic myelopathy focused on identifying treatable conditions with tests widely available in low-resource settings. |
Kibirige, Davis; Kampiire, Leaticia; Atuhe, David; Mwebaze, Raymond; Katagira, Winceslaus; Muttamba, Winters; Nantanda, Rebecca; Worodria, William; Kirenga, Bruce Access to affordable medicines and diagnostic tests for asthma and COPD in sub Saharan Africa: the Ugandan perspective Journal Article BMC Pulmonary Medicine, 17 (1), pp. 179, 2017. @article{Kibirige2017, title = {Access to affordable medicines and diagnostic tests for asthma and COPD in sub Saharan Africa: the Ugandan perspective}, author = {Davis Kibirige and Leaticia Kampiire and David Atuhe and Raymond Mwebaze and Winceslaus Katagira and Winters Muttamba and Rebecca Nantanda and William Worodria and Bruce Kirenga}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Access-to-affordable-medicines-and-diagnostic-tests-for-asthma-and-COPD-in-sub-Saharan-Africa-the-Ugandan-perspectiv.pdf}, doi = { 10.1186/s12890-017-0527-y}, year = {2017}, date = {2017-12-08}, journal = {BMC Pulmonary Medicine}, volume = {17}, number = {1}, pages = {179}, abstract = {Background: Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management. Methods: Data on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days’ wages it would cost the least paid public servant were analysed. Results: The availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days’ wages for inhaled salbutamol to 17.1 days’ wages for formoterol/budesonide inhalers and 27.8 days’ wages for spirometry. Conclusion: Medicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda. Keywords: Access, Medicines, Diagnostic tests, Asthma, COPD, Sub Saharan Africa, Uganda }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management. Methods: Data on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days’ wages it would cost the least paid public servant were analysed. Results: The availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days’ wages for inhaled salbutamol to 17.1 days’ wages for formoterol/budesonide inhalers and 27.8 days’ wages for spirometry. Conclusion: Medicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda. Keywords: Access, Medicines, Diagnostic tests, Asthma, COPD, Sub Saharan Africa, Uganda |
Castelnuovo, Barbara; Mubiru, Frank; Kalule, Ivan; Nakalema, Shadia; Kiragga, Agnes Challenges in Assessing Outcomes among Infants of Pregnant HIV-Positive Women Receiving ART in Uganda Journal Article AIDS Research and Treatment, 2017. @article{Castelnuovo2017, title = {Challenges in Assessing Outcomes among Infants of Pregnant HIV-Positive Women Receiving ART in Uganda}, author = {Barbara Castelnuovo and Frank Mubiru and Ivan Kalule and Shadia Nakalema and Agnes Kiragga}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Challenges-in-Assessing-Outcomes-among-Infants-of-Pregnant-HIV-Positive-Women-Receiving-ART-in-Uganda.pdf}, doi = {10.1155/2017/3202737}, year = {2017}, date = {2017-12-07}, journal = {AIDS Research and Treatment}, abstract = {Since 2012, the WHO recommends lifelong ART with TDF+FTC/3TC+EFV for all HIV-positive pregnant and breastfeeding women (Option B-plus). In this analysis we describe the proportion of early and late transmission in mothers with high retention in Kampala, Uganda. We included 700 pregnant women from January 2012 to August 2014 with a follow-up extended to August 2016; the median age was 31 years (IQR: 26-35), 36.3% in WHO stage 3/4; median CD4 count was 447 cells/μL (IQR: 301-651) and 73.3% were already on ART for a median time of 28 (IQR: 10-57) months; 52% infants were male and median weight was 3.2 Kg (IQR: 2.5-3.5). Five hundred and sixty-five (80.7%) infants had at least one test for HIV; 22 (3.1%) infants died, all with unknown serostatus; 3 tested positive at week 6 and one additional at months 12 and 18. Two of the mothers of the 4 HIV-positive infants were ART-naïve at the time of pregnancy. We report very low documented HIV transmission comparable with those reported in clinical trials settings; however, demonstrating the efficacy of Option B-plus in terms of averted transmission in routine settings is challenging since high proportion of infants do not have documented HIV tests.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Since 2012, the WHO recommends lifelong ART with TDF+FTC/3TC+EFV for all HIV-positive pregnant and breastfeeding women (Option B-plus). In this analysis we describe the proportion of early and late transmission in mothers with high retention in Kampala, Uganda. We included 700 pregnant women from January 2012 to August 2014 with a follow-up extended to August 2016; the median age was 31 years (IQR: 26-35), 36.3% in WHO stage 3/4; median CD4 count was 447 cells/μL (IQR: 301-651) and 73.3% were already on ART for a median time of 28 (IQR: 10-57) months; 52% infants were male and median weight was 3.2 Kg (IQR: 2.5-3.5). Five hundred and sixty-five (80.7%) infants had at least one test for HIV; 22 (3.1%) infants died, all with unknown serostatus; 3 tested positive at week 6 and one additional at months 12 and 18. Two of the mothers of the 4 HIV-positive infants were ART-naïve at the time of pregnancy. We report very low documented HIV transmission comparable with those reported in clinical trials settings; however, demonstrating the efficacy of Option B-plus in terms of averted transmission in routine settings is challenging since high proportion of infants do not have documented HIV tests. |
Kuznik, Andreas; Iliyasu, Garba; Lamorde, Mohammed; Mahmud, Mustapha; Musa, Baba M; Nashabaru, Ibrahim; Obaro, Stephen; Mohammed, Idris; Habi, Abdulrazaq G 2017. @article{Kuznik2017, title = {Cost-effectiveness of expanding childhood routine immunization against Neisseria meningitidis serogroups C, W and Y with a quadrivalent conjugate vaccine in the African meningitis belt}, author = {Andreas Kuznik and Garba Iliyasu and Mohammed Lamorde and Mustapha Mahmud and Baba M. Musa and Ibrahim Nashabaru and Stephen Obaro and Idris Mohammed and Abdulrazaq G. Habi}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Cost-effectiveness-of-expanding-childhood-routine-immunization-against-Neisseria-meningitidis-serogroups-C-W-and-Y-with-a-quadrivalent-conjugate-vaccine-in-the-African-meningitis-belt.pdf}, doi = {10.1371/journal.pone.0188595}, year = {2017}, date = {2017-11-30}, abstract = {Background Neisseria meningitidis constitutes a major public health problem among countries in the African meningitis belt. Following regional vaccination campaigns for serogroup A and subsequent increases in protection against this serogroup, non-A serogroups such as C and W now pose significant epidemic threats, particularly in young children. Objective To evaluate the cost-effectiveness of broadening coverage from conjugate serogroup A to quadrivalent ACWY vaccination. Methods We developed a 40-year Markov state transition model with annual cycles to simulate costs and clinical outcomes in children aged 1 to 10 in the 26 countries of the African meningitis belt. The incidence of CWY meningitis cases among an unvaccinated population was held constant at inter-epidemic rates of 50 per 100,000/year and 150 per 100,000/year. The country-specific cost and probability of access to meningitis care, vaccine efficacy, the mortality risk among treated and untreated meningitis cases, the risk of clinical sequelae and their respective disability weights were based on published sources. Vaccination cost was based on international prices lists, presented in 2014 US$. Results At an incidence rate of 50 per 100,000/year, routine conjugate vaccination is highly costeffective in 14 out of 26 countries with a cost/DALY averted ranging from US$555-US$787. At the higher incidence rate of 150 per 100,000/year, quadrivalent vaccination is cost-effective in all 26 countries with a cost/DALY averted ranging from US$105-US$250. The annual incidence rate at which routine conjugate quadrivalent vaccination is expected to be economically justifiable ranges from 13 per 100,000/year in Nigeria to 142 per 100,000/year in Burundi. Conclusion Routine quadrivalent conjugate vaccination against Neisseria meningitidis is cost-effective at incidence rates well below the epidemic threshold among children living in the African meningitis belt. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Neisseria meningitidis constitutes a major public health problem among countries in the African meningitis belt. Following regional vaccination campaigns for serogroup A and subsequent increases in protection against this serogroup, non-A serogroups such as C and W now pose significant epidemic threats, particularly in young children. Objective To evaluate the cost-effectiveness of broadening coverage from conjugate serogroup A to quadrivalent ACWY vaccination. Methods We developed a 40-year Markov state transition model with annual cycles to simulate costs and clinical outcomes in children aged 1 to 10 in the 26 countries of the African meningitis belt. The incidence of CWY meningitis cases among an unvaccinated population was held constant at inter-epidemic rates of 50 per 100,000/year and 150 per 100,000/year. The country-specific cost and probability of access to meningitis care, vaccine efficacy, the mortality risk among treated and untreated meningitis cases, the risk of clinical sequelae and their respective disability weights were based on published sources. Vaccination cost was based on international prices lists, presented in 2014 US$. Results At an incidence rate of 50 per 100,000/year, routine conjugate vaccination is highly costeffective in 14 out of 26 countries with a cost/DALY averted ranging from US$555-US$787. At the higher incidence rate of 150 per 100,000/year, quadrivalent vaccination is cost-effective in all 26 countries with a cost/DALY averted ranging from US$105-US$250. The annual incidence rate at which routine conjugate quadrivalent vaccination is expected to be economically justifiable ranges from 13 per 100,000/year in Nigeria to 142 per 100,000/year in Burundi. Conclusion Routine quadrivalent conjugate vaccination against Neisseria meningitidis is cost-effective at incidence rates well below the epidemic threshold among children living in the African meningitis belt. |
Kwizera, Richard; Parkes-Ratanshi, Rosalind; Page, Iain D; Sekaggya-Wiltshire, Christine; Musaazi, Joseph; Fehr, Jan; Castelnuovo, Barbara; Kambugu, Andrew; Denning, David W Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis Journal Article BMC Pulmonary MedicineBMC series – open, 2017. @article{Kwizera2017, title = {Elevated Aspergillus-specific antibody levels among HIV infected Ugandans with pulmonary tuberculosis}, author = {Richard Kwizera and Rosalind Parkes-Ratanshi and Iain D. Page and Christine Sekaggya-Wiltshire and Joseph Musaazi and Jan Fehr and Barbara Castelnuovo and Andrew Kambugu and David W. Denning}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Elevated-Aspergillus-specific-antibody-levels-among-HIV-infected-Ugandans-with-pulmonary-tuberculosis.pdf}, doi = {0.1186/s12890-017-0500-9}, year = {2017}, date = {2017-11-21}, journal = {BMC Pulmonary MedicineBMC series – open}, abstract = { Background The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. Recent evidence suggests that Chronic Pulmonary Aspergillosis and Aspergillus sensitisation might be responsible for significant mortality in patients treated for tuberculosis in Uganda. Methods We retrieved and tested paired serum aliquots for 101 HIV-TB co-infected patients at the beginning and week 24 of TB treatment. We tested samples for Aspergillus-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) using ImmunoCAP®; and Aspergillus-specific IgG and total serum IgE using Immulite® immunoassays. We compared antibody levels between baseline and week 24, relating them to selected baseline characteristics. Results 10% of the patients had elevated Aspergillus-specific IgE (Aspergillus sensitization) and Aspergillus-specific IgG antibodies were elevated in 9% of the patients at the end of TB treatment. There was a significant fall in the Aspergillus-specific IgG antibody levels between baseline and week 24 (P = 0.02). Patients with cluster of differentiation 4 (CD4) T-cell count <100 cells/μl and those who were not on anti-retroviral therapy at baseline had more elevated Aspergillus-specific IgG antibodies (P = 0.01, P = 0.03). The ImmunoCAP® Aspergillus-specific IgG antibody titres were higher at week 24 than baseline with more positives at week 24; even though the difference in means was small. However, this difference was statistically significant (P = 0.02). Pulmonary infiltrates were the commonest x-ray abnormality and only 5% of the patients had pulmonary cavities on chest x-ray at week 24. Conclusion These results suggest that Aspergillus infection may complicate active pulmonary TB and further studies including fungal culture and thoracic imaging may now be indicated to measure the prevalence of pulmonary aspergillosis complicating tuberculosis. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background The incidence of tuberculosis (TB) is high among human immunodeficiency virus (HIV) infected Ugandans. Recent evidence suggests that Chronic Pulmonary Aspergillosis and Aspergillus sensitisation might be responsible for significant mortality in patients treated for tuberculosis in Uganda. Methods We retrieved and tested paired serum aliquots for 101 HIV-TB co-infected patients at the beginning and week 24 of TB treatment. We tested samples for Aspergillus-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) using ImmunoCAP®; and Aspergillus-specific IgG and total serum IgE using Immulite® immunoassays. We compared antibody levels between baseline and week 24, relating them to selected baseline characteristics. Results 10% of the patients had elevated Aspergillus-specific IgE (Aspergillus sensitization) and Aspergillus-specific IgG antibodies were elevated in 9% of the patients at the end of TB treatment. There was a significant fall in the Aspergillus-specific IgG antibody levels between baseline and week 24 (P = 0.02). Patients with cluster of differentiation 4 (CD4) T-cell count <100 cells/μl and those who were not on anti-retroviral therapy at baseline had more elevated Aspergillus-specific IgG antibodies (P = 0.01, P = 0.03). The ImmunoCAP® Aspergillus-specific IgG antibody titres were higher at week 24 than baseline with more positives at week 24; even though the difference in means was small. However, this difference was statistically significant (P = 0.02). Pulmonary infiltrates were the commonest x-ray abnormality and only 5% of the patients had pulmonary cavities on chest x-ray at week 24. Conclusion These results suggest that Aspergillus infection may complicate active pulmonary TB and further studies including fungal culture and thoracic imaging may now be indicated to measure the prevalence of pulmonary aspergillosis complicating tuberculosis. |
Epiu, Isabella; Wabule, Agnes; Kambugu, Andrew; Mayanja-Kizza, Harriet; Tindimwebwa, Jossy Verel Bahe; Dubowitz, Gerald Key bottlenecks to the provision of safe obstetric anaesthesia in low- income countries; a cross-sectional survey of 64 hospitals in Uganda. Journal Article BMC Pregnancy and Childbirth, 2017, ISBN: 1471-2393. @article{Epiu2017, title = {Key bottlenecks to the provision of safe obstetric anaesthesia in low- income countries; a cross-sectional survey of 64 hospitals in Uganda. }, author = {Isabella Epiu and Agnes Wabule and Andrew Kambugu and Harriet Mayanja-Kizza and Jossy Verel Bahe Tindimwebwa and Gerald Dubowitz}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Key-bottlenecks-to-the-provision-of-safe-obstetric-anaesthesia-in-low-income-countries-a-cross-sectional-survey-of-64-hospitals-in-Uganda.pdf}, doi = {10.1186/s12884-017-1566-3}, isbn = {1471-2393}, year = {2017}, date = {2017-11-17}, journal = {BMC Pregnancy and Childbirth}, abstract = { Background Despite recent advances in surgery and anaesthesia which significantly improve safety, many health facilities in low-and middle-income countries (LMICs) remain chronically under-resourced with inability to cope effectively with serious obstetric complications (Knight et al., PLoS One 8:e63846, 2013). As a result many of these countries still have unacceptably high maternal and neonatal mortality rates. Recent data at the national referral hospitals in East Africa reported that none of the national referral hospitals met the World Federation of Societies of Anesthesiologists (WFSA) international standards required to provide safe obstetric anaesthesia (Epiu I: Challenges of Anesthesia in Low-and Middle-Income Countries. WFSA; 2014 http://wfsa.newsweaver.com/Newsletter/p8c8ta4ri7a1wsacct9y3u?a=2&p=47730565&t=27996496). In spite of this evidence, factors contributing to maternal mortality related to anaesthesia in LMICs and the magnitude of these issues have not been comprehensively studied. We therefore set out to assess regional referral, district, private for profit and private not-for profit hospitals in Uganda. Methods We conducted a cross-sectional survey at 64 government and private hospitals in Uganda using pre-set questionnaires to the anaesthetists and hospital directors. Access to the minimum requirements for safe obstetric anaesthesia according to WFSA guidelines were also checked using a checklist for operating and recovery rooms. Results Response rate was 100% following personal interviews of anaesthetists, and hospital directors. Only 3 of the 64 (5%) of the hospitals had all requirements available to meet the WFSA International guidelines for safe anaesthesia. Additionally, 54/64 (84%) did not have a trained physician anaesthetist and 5/64 (8%) had no trained providers for anaesthesia at all. Frequent shortages of drugs were reported for regional/neuroaxial anaesthesia, and other essential drugs were often lacking such as antacids and antihypertensives. We noted that many of the anaesthesia machines present were obsolete models without functional safety alarms and/or mechanical ventilators. Continuous ECG was only available in 3/64 (5%) of hospitals. Conclusion We conclude that there is a significant lack of essential equipment for the delivery of safe anaesthesia across this region. This is compounded by the shortage of trained providers and inadequate supervision. It is therefore essential to strengthen anaesthesia services by addressing these specific deficiencies. This will include improved training of associate clinicians, training more physician anaesthetists and providing the basic equipment required to provide safe and effective care. These services are key components of comprehensive emergency obstetric care and anaesthetists are crucial in managing critically ill mothers and ensuring good surgical outcomes. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Despite recent advances in surgery and anaesthesia which significantly improve safety, many health facilities in low-and middle-income countries (LMICs) remain chronically under-resourced with inability to cope effectively with serious obstetric complications (Knight et al., PLoS One 8:e63846, 2013). As a result many of these countries still have unacceptably high maternal and neonatal mortality rates. Recent data at the national referral hospitals in East Africa reported that none of the national referral hospitals met the World Federation of Societies of Anesthesiologists (WFSA) international standards required to provide safe obstetric anaesthesia (Epiu I: Challenges of Anesthesia in Low-and Middle-Income Countries. WFSA; 2014 http://wfsa.newsweaver.com/Newsletter/p8c8ta4ri7a1wsacct9y3u?a=2&p=47730565&t=27996496). In spite of this evidence, factors contributing to maternal mortality related to anaesthesia in LMICs and the magnitude of these issues have not been comprehensively studied. We therefore set out to assess regional referral, district, private for profit and private not-for profit hospitals in Uganda. Methods We conducted a cross-sectional survey at 64 government and private hospitals in Uganda using pre-set questionnaires to the anaesthetists and hospital directors. Access to the minimum requirements for safe obstetric anaesthesia according to WFSA guidelines were also checked using a checklist for operating and recovery rooms. Results Response rate was 100% following personal interviews of anaesthetists, and hospital directors. Only 3 of the 64 (5%) of the hospitals had all requirements available to meet the WFSA International guidelines for safe anaesthesia. Additionally, 54/64 (84%) did not have a trained physician anaesthetist and 5/64 (8%) had no trained providers for anaesthesia at all. Frequent shortages of drugs were reported for regional/neuroaxial anaesthesia, and other essential drugs were often lacking such as antacids and antihypertensives. We noted that many of the anaesthesia machines present were obsolete models without functional safety alarms and/or mechanical ventilators. Continuous ECG was only available in 3/64 (5%) of hospitals. Conclusion We conclude that there is a significant lack of essential equipment for the delivery of safe anaesthesia across this region. This is compounded by the shortage of trained providers and inadequate supervision. It is therefore essential to strengthen anaesthesia services by addressing these specific deficiencies. This will include improved training of associate clinicians, training more physician anaesthetists and providing the basic equipment required to provide safe and effective care. These services are key components of comprehensive emergency obstetric care and anaesthetists are crucial in managing critically ill mothers and ensuring good surgical outcomes. |
Sekaggya-Wiltshirea, Christine; Lamordea, Mohammed; Kiraggaa, Agnes N; Dooleyc, Kelly E; Kamyad, Moses R; Kambugua, Andrew; Fehrb, Jan; Manabec, Yukari C; Castelnuovo, Barbara The utility of pharmacokinetic studies for the evaluation of exposureresponse relationships for standard dose anti-tuberculosis drugs Journal Article Elsevier Tuberculosis, 108 , pp. 77-82, 2017. @article{Sekaggya-Wiltshirea2017, title = {The utility of pharmacokinetic studies for the evaluation of exposureresponse relationships for standard dose anti-tuberculosis drugs }, author = {Christine Sekaggya-Wiltshirea and Mohammed Lamordea and Agnes N. Kiraggaa and Kelly E. Dooleyc and Moses R. Kamyad and Andrew Kambugua and Jan Fehrb and Yukari C. Manabec and Barbara Castelnuovo}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/The-utility-of-pharmacokinetic-studies-for-the-evaluation-of-exposureresponse-relationships-for-standard-dose-anti-tuberculosis-drugs-.pdf}, year = {2017}, date = {2017-11-06}, journal = {Elsevier Tuberculosis}, volume = {108}, pages = {77-82}, abstract = {Tuberculosis (TB) is a major public health problem. Many countries still fall below the minimum World Health Organization (WHO) TB treatment target success rate. There is conflicting evidence about whether concentrations of anti-tuberculosis drugs given at standard doses have an effect on treatment outcomes. The current data correlating anti-TB drug concentrations and treatment outcome is limited. This article summarized the existing literatureand theirutilityinevaluating theassociation betweeneachanti-TBdrug'sconcentrations using current target concentrations and treatment outcomes in patients with pulmonary tuberculosis receiving standard WHOrecommended dosing.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tuberculosis (TB) is a major public health problem. Many countries still fall below the minimum World Health Organization (WHO) TB treatment target success rate. There is conflicting evidence about whether concentrations of anti-tuberculosis drugs given at standard doses have an effect on treatment outcomes. The current data correlating anti-TB drug concentrations and treatment outcome is limited. This article summarized the existing literatureand theirutilityinevaluating theassociation betweeneachanti-TBdrug'sconcentrations using current target concentrations and treatment outcomes in patients with pulmonary tuberculosis receiving standard WHOrecommended dosing. |
Coffie, Patrick A; Egger, Matthias; Vinikoor, Michael J; Zannou, Marcel; Diero, Lameck; Patassi, Akouda; Kuniholm, Mark H; Seydi, Moussa; Bado, Guillaume; Ocama, Ponsiano; Andersson, Monique I; Messou, Eugène; Minga, Albert; Easterbrook, Philippa; Anastos, Kathryn; Dabis, François; Wandeler, Gilles; for the collaboration, IeDEA Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa. Journal Article BMC Infectious Diseases, 17 (1), pp. 706, 2017. @article{Coffie12017, title = {Trends in hepatitis B virus testing practices and management in HIV clinics across sub-Saharan Africa.}, author = {Patrick A. Coffie and Matthias Egger and Michael J. Vinikoor and Marcel Zannou and Lameck Diero and Akouda Patassi and Mark H. Kuniholm and Moussa Seydi and Guillaume Bado and Ponsiano Ocama and Monique I. Andersson and Eugène Messou and Albert Minga and Philippa Easterbrook and Kathryn Anastos and François Dabis and Gilles Wandeler and for the IeDEA collaboration}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Trends-in-hepatitis-B-virus-testing-practices-and-management-in-HIV-clinics-across-sub-Saharan-Africa..pdf}, doi = {https://dx.doi.org/10.1186%2Fs12879-017-2768-z}, year = {2017}, date = {2017-11-01}, journal = {BMC Infectious Diseases}, volume = {17}, number = {1}, pages = {706}, abstract = {Background: Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA. Methods: A medical chart review was conducted in large urban HIV treatment centers in Côte d’Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen. Results: Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4–14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02–4.79) had a confirmed HCV infection. Conclusions: The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Approximately 8% of HIV-infected individuals are co-infected with hepatitis B virus (HBV) in sub-Saharan Africa (SSA). Knowledge of HBV status is important to guide optimal selection of antiretroviral therapy (ART) and monitor/prevent liver-related complications. We describe changes in testing practices and management of HBV infection over a 3-year period in HIV clinics across SSA. Methods: A medical chart review was conducted in large urban HIV treatment centers in Côte d’Ivoire (3 sites), Benin, Burkina Faso, Cameroon, Kenya, Senegal, South Africa, Togo, Uganda and Zambia (1 site each). Of the patients who started ART between 2010 and 2012, 100 per year were randomly selected from each clinic. Demographic, clinical and laboratory information as well as individual treatment histories were collected using a standardized questionnaire. We examined changes over time in the proportion of patients screened for HBV infection (HBV surface antigen [HBsAg]-positivity), identified predictors of HBV testing using logistic regression, and assessed the proportion of patients initiating a tenofovir (TDF)-containing ART regimen. Results: Overall, 3579 charts of patients initiating ART (64.4% female, median age 37 years) were reviewed in 12 clinics. The proportion of patients screened for HBsAg increased from 17.8% in 2010 to 24.4% in 2012 overall, and ranged from 0.7% in Kenya to 96% in South Africa. In multivariable analyses, age and region were associated with HBsAg screening. Among 759 individuals tested, 88 (11.6%; 95% confidence interval [CI] 9.4–14.1) were HBV-infected, of whom 71 (80.7%) received a TDF-containing ART regimen. HBsAg-positive individuals were twice as likely to receive a TDF-containing first-line ART regimen compared to HBsAg-negative patients (80.7% vs. 40.3%, p < 0.001). The proportion of patients on TDF-containing ART increased from 57.9% in 2010 to 90.2% in 2012 in HIV/HBV-co-infected patients (Chi-2 test for trend: p = 0.01). Only 114 (5.0%) patients were screened for anti-HCV antibodies and one of them (0.9%, 95% CI 0.02–4.79) had a confirmed HCV infection. Conclusions: The systematic screening for HBV infection in HIV-positive patients before ART initiation was limited in most African countries and its uptake varied widely across clinics. Overall, the prescription of TDF increased over time, with 90% of HIV/HBV-coinfected patients receiving this drug in 2012. |
Tucker, Joseph D; Meyers, Kathrine; Best, John; Kaplan, Karyn; Pendse, Razia; Fenton, Kevin A; Andrieux-Meyer, Isabelle; Figueroa, Carmen; Goicochea, Pedro; Gore, Charles; Ishizaki, Azumi; Khwairakpam, Giten; Miller, Veronica; Mozalevskis, Antons; Ninburg, Michael; Ocam, Ponsiano; Peeling, Rosanna; Walsh, Nick; Colombo, Massimo G; Easterbrook1, Philippa The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing. Journal Article BMC Infectious Diseases, 17 (1), 2017. @article{Tucker2017, title = {The HepTestContest: a global innovation contest to identify approaches to hepatitis B and C testing. }, author = {Joseph D. Tucker and Kathrine Meyers and John Best and Karyn Kaplan and Razia Pendse and Kevin A. Fenton and Isabelle Andrieux-Meyer and Carmen Figueroa and Pedro Goicochea and Charles Gore and Azumi Ishizaki and Giten Khwairakpam and Veronica Miller and Antons Mozalevskis and Michael Ninburg and Ponsiano Ocam and Rosanna Peeling and Nick Walsh and Massimo G. Colombo and Philippa Easterbrook1}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/The-HepTestContest-a-global-innovation-contest-to-identify-approaches-to-hepatitis-B-and-C-testing.pdf}, doi = {0.1186/s12879-017-2771-4}, year = {2017}, date = {2017-11-01}, journal = {BMC Infectious Diseases}, volume = {17}, number = {1}, abstract = {Background: Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines. Methods: This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to prespecified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines. Results: The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8); decentralization (n = 8); and task shifting (n = 7). Conclusion: The global innovation contest identified a range of local hepatitis testing approaches that can be used to inform the development of testing strategies in different settings and populations. Further implementation and evaluation of different testing approaches is needed. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Innovation contests are a novel approach to elicit good ideas and innovative practices in various areas of public health. There remains limited published literature on approaches to deliver hepatitis testing. The purpose of this innovation contest was to identify examples of different hepatitis B and C approaches to support countries in their scale-up of hepatitis testing and to supplement development of formal recommendations on service delivery in the 2017 World Health Organization hepatitis B and C testing guidelines. Methods: This contest involved four steps: 1) establishment of a multisectoral steering committee to coordinate a call for contest entries; 2) dissemination of the call for entries through diverse media (Facebook, Twitter, YouTube, email listservs, academic journals); 3) independent ranking of submissions by a panel of judges according to prespecified criteria (clarity of testing model, innovation, effectiveness, next steps) using a 1-10 scale; 4) recognition of highly ranked entries through presentation at international conferences, commendation certificate, and inclusion as a case study in the WHO 2017 testing guidelines. Results: The innovation contest received 64 entries from 27 countries and took a total of 4 months to complete. Sixteen entries were directly included in the WHO testing guidelines. The entries covered testing in different populations, including primary care patients (n = 5), people who inject drugs (PWID) (n = 4), pregnant women (n = 4), general populations (n = 4), high-risk groups (n = 3), relatives of people living with hepatitis B and C (n = 2), migrants (n = 2), incarcerated individuals (n = 2), workers (n = 2), and emergency department patients (n = 2). A variety of different testing delivery approaches were employed, including integrated HIV-hepatitis testing (n = 12); integrated testing with harm reduction and addiction services (n = 9); use of electronic medical records to support targeted testing (n = 8); decentralization (n = 8); and task shifting (n = 7). Conclusion: The global innovation contest identified a range of local hepatitis testing approaches that can be used to inform the development of testing strategies in different settings and populations. Further implementation and evaluation of different testing approaches is needed. |
Osingada, Charles Peter; MonicaOkuga, ; RoseChaloNabirye, ; Sewankambo, Nelson Kaulukusi; DamalieNakanjako, Disclosure of Parental HIV Status to Children Experiences of Adults Receiving Antiretroviral Treatment at an Urban Clinic in Kampala, Uganda Journal Article AIDS Research and Treatment, pp. 11, 2017. @article{Osingada2017, title = {Disclosure of Parental HIV Status to Children Experiences of Adults Receiving Antiretroviral Treatment at an Urban Clinic in Kampala, Uganda}, author = {Charles Peter Osingada and MonicaOkuga and RoseChaloNabirye and Nelson Kaulukusi Sewankambo and DamalieNakanjako}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Disclosure-of-Parental-HIV-Status-to-Children-Experiences-of-Adults-Receiving-Antiretroviral-Treatment-at-an-Urban-Clinic-in-Kampala-Uganda.pdf}, doi = {10.1155/2017/3458684}, year = {2017}, date = {2017-10-25}, journal = {AIDS Research and Treatment}, pages = {11}, abstract = {Limited data are available on the experiences of parental HIV disclosure to children in Uganda. We conducted a qualitative study comprising sixteen in-depth interviews and four focus group discussions with parents receiving highly active antiretroviral therapy. Analysis was done using Atlas.ti qualitative research software. Back-and-forth triangulation was done between transcripts of the in-depth interviews and focus group discussions, and themes and subthemes were developed. Barriers to parents' disclosure included perceptions that children are too young to understand what HIV infection means and fears of secondary disclosure by the children. Immediate outcomes of disclosure included children getting scared and crying, although such instances often gave way to more enduring positive experiences for the parents, such as support in adherence to medical care, help in household chores, and a decrease in financial demands from the children. Country-specific interventions are needed to improve the process of parental HIV disclosure to children and this should encompass preparation on how to deal with the immediate psychological challenges associated with the parent's disclosure.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Limited data are available on the experiences of parental HIV disclosure to children in Uganda. We conducted a qualitative study comprising sixteen in-depth interviews and four focus group discussions with parents receiving highly active antiretroviral therapy. Analysis was done using Atlas.ti qualitative research software. Back-and-forth triangulation was done between transcripts of the in-depth interviews and focus group discussions, and themes and subthemes were developed. Barriers to parents' disclosure included perceptions that children are too young to understand what HIV infection means and fears of secondary disclosure by the children. Immediate outcomes of disclosure included children getting scared and crying, although such instances often gave way to more enduring positive experiences for the parents, such as support in adherence to medical care, help in household chores, and a decrease in financial demands from the children. Country-specific interventions are needed to improve the process of parental HIV disclosure to children and this should encompass preparation on how to deal with the immediate psychological challenges associated with the parent's disclosure. |
O’Hara, Geraldine A; McNaughton, Anna L; Maponga, Tongai; Jooste, Pieter; Ocama, Ponsiano; Chilengi, Roma; Mokaya, Jolynne; Liyayi, Mitchell I; Wachira, Tabitha; Gikungi, David M; Burbridge, Lela; O’Donnell, Denise; Akiror, Connie S; Sloan, Derek; Torimiro, Judith; Yindom, Louis Marie; Walton, Robert; Andersson, Monique; Marsh, Kevin; Newton, Robert; Matthew, Philippa C Hepatitis B virus infection as a neglected tropical disease. Journal Article PloS Neglected Tropical Diseases, 11 (10), 2017. @article{O’Hara2017, title = {Hepatitis B virus infection as a neglected tropical disease.}, author = {Geraldine A. O’Hara and Anna L. McNaughton and Tongai Maponga and Pieter Jooste and Ponsiano Ocama and Roma Chilengi and Jolynne Mokaya and Mitchell I. Liyayi and Tabitha Wachira and David M. Gikungi and Lela Burbridge and Denise O’Donnell and Connie S. Akiror and Derek Sloan and Judith Torimiro and Louis Marie Yindom and Robert Walton and Monique Andersson and Kevin Marsh and Robert Newton and Philippa C. Matthew}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Hepatitis-B-virus-infection-as-a-neglected-tropical-disease.-1.pdf}, doi = { 10.1371/journal.pntd.0005842}, year = {2017}, date = {2017-10-05}, journal = {PloS Neglected Tropical Diseases}, volume = {11}, number = {10}, abstract = {The Global Hepatitis Health Sector Strategy is aiming for “elimination of viral hepatitis as a public health threat” by 2030 [1], while enhanced elimination efforts for hepatitis are also promoted under the broader remit of global Sustainable Development Goals (SDGs) [2]. This is an enormous challenge for hepatitis B virus (HBV) given the estimated global burden of 260 million chronic carriers, of whom the majority are unaware of their infection [3] (Fig 1). We here present HBV within the framework for neglected tropical diseases (NTDs) [4] in order to highlight the ways in which HBV meets NTD criteria and to discuss the ways in which the NTD management paradigm could be used to strengthen a unified global approach to HBV elimination [5]. The major burden of morbidity and mortality from HBV is now borne by tropical and subtropical countries [6]. Many African populations epitomize specific vulnerability to HBV [7], so we here focus particular attention on Africa, both through focus on the existing published literature and through presentation of a unique data set of opinion and experience (see S1 Supporting Information). However, the themes we represent are transferable to other low- and middle-income settings and are relevant on the global stage.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Global Hepatitis Health Sector Strategy is aiming for “elimination of viral hepatitis as a public health threat” by 2030 [1], while enhanced elimination efforts for hepatitis are also promoted under the broader remit of global Sustainable Development Goals (SDGs) [2]. This is an enormous challenge for hepatitis B virus (HBV) given the estimated global burden of 260 million chronic carriers, of whom the majority are unaware of their infection [3] (Fig 1). We here present HBV within the framework for neglected tropical diseases (NTDs) [4] in order to highlight the ways in which HBV meets NTD criteria and to discuss the ways in which the NTD management paradigm could be used to strengthen a unified global approach to HBV elimination [5]. The major burden of morbidity and mortality from HBV is now borne by tropical and subtropical countries [6]. Many African populations epitomize specific vulnerability to HBV [7], so we here focus particular attention on Africa, both through focus on the existing published literature and through presentation of a unique data set of opinion and experience (see S1 Supporting Information). However, the themes we represent are transferable to other low- and middle-income settings and are relevant on the global stage. |
Clair, Nicole St E; Pitt, Michael B; Bakeera-Kitaka, Sabrina; McCall, Natalie; Lukolyo, Heather; Linda D. Arnold, Tobey Audcent ; Batra, Maneesh; Chan, Kevin; Jacquet, Gabrielle A; Schutze, Gordon E; Butteris, Sabrina Global Health: Preparation for Working in Resource-Limited Settings Journal Article American Board of Pediatrics, 2017. @article{Clair2017, title = {Global Health: Preparation for Working in Resource-Limited Settings}, author = {Nicole E. St Clair and Michael B. Pitt and Sabrina Bakeera-Kitaka and Natalie McCall and Heather Lukolyo and Linda D. Arnold, Tobey Audcent and Maneesh Batra and Kevin Chan and Gabrielle A. Jacquet and Gordon E. Schutze and Sabrina Butteris }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Global-Health-Preparation-for-Working-in-Resource-Limited-Settings.-1.pdf}, year = {2017}, date = {2017-10-02}, journal = {American Board of Pediatrics}, abstract = {Trainees and clinicians from high-income countries are increasingly engaging in global health (GH) efforts, particularly in resource-limited settings. Concomitantly, there is a growing demand for these individuals to be better prepared for the common challenges and controversies inherent in GH work. This is a state-of-the-art review article in which we outline what is known about the current scope of trainee and clinician involvement in GH experiences, highlight specific considerations and issues pertinent to GH engagement, and summarize preparation recommendations that have emerged from the literature. The article is focused primarily on short-term GH experiences, although much of the content is also pertinent to long-term work. Suggestions are made for the health care community to develop and implement widely endorsed preparation standards for trainees, clinicians, and organizations engaging in GH experiences and partnerships.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Trainees and clinicians from high-income countries are increasingly engaging in global health (GH) efforts, particularly in resource-limited settings. Concomitantly, there is a growing demand for these individuals to be better prepared for the common challenges and controversies inherent in GH work. This is a state-of-the-art review article in which we outline what is known about the current scope of trainee and clinician involvement in GH experiences, highlight specific considerations and issues pertinent to GH engagement, and summarize preparation recommendations that have emerged from the literature. The article is focused primarily on short-term GH experiences, although much of the content is also pertinent to long-term work. Suggestions are made for the health care community to develop and implement widely endorsed preparation standards for trainees, clinicians, and organizations engaging in GH experiences and partnerships. |
Sekaggya-Wiltshire, Christine; Castelnuovo, Barbara; von Braun, Amrei; Musaazi, Joseph; Muller, Daniel; Buzibye, Allan; Gutteck, Ursula; Henning, Lars; Ledergerber, Bruno; Corti, Natascia; Lamorde, Mohammed; Fehr, Jan; Kambugu, Andrew BMJ Open, 7 (9), 2017. @article{Sekaggya-Wiltshire2017, title = {Cohort profile of a study on outcomes related to tuberculosis and antiretroviral drug concentrations in Uganda: design, methods and patient characteristics of the SOUTH study}, author = {Christine Sekaggya-Wiltshire and Barbara Castelnuovo and Amrei von Braun and Joseph Musaazi and Daniel Muller and Allan Buzibye and Ursula Gutteck and Lars Henning and Bruno Ledergerber and Natascia Corti and Mohammed Lamorde and Jan Fehr and Andrew Kambugu }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Cohort-profile-of-a-study-on-outcomes-related-to-tuberculosis-and-antiretroviral-drug-concentrations-in-Uganda-design-methods-and-patient-characteristics-of-the-SOUTH-study.pdf}, doi = {10.1136/bmjopen-2016-014679.}, year = {2017}, date = {2017-09-18}, journal = {BMJ Open}, volume = {7}, number = {9}, abstract = {AbstrAct Purpose Tuberculosis (TB) is a leading cause of death among people living with HIV in sub-Saharan Africa. Several factors influence the efficacy of TB treatment by leading to suboptimal drug concentrations and subsequently affecting treatment outcome. The aim of this cohort is to determine the association between anti-TB drug concentrations and TB treatment outcomes. Participants Patients diagnosed with new pulmonary TB at the integrated TB-HIV outpatient clinic in Kampala, Uganda, were enrolled into the study and started on firstline anti-TB treatment. Findings to date Between April 2013 and April 2015, the cohort enrolled 268 patients coinfected with TB/HIV ; 57.8% are male with a median age of 34 years (IQR 29–40). The median time between the diagnosis of HIV and the diagnosis of TB is 2 months (IQR 0–22.5). The majority of the patients are antiretroviral therapy naive (75.4%). Our population is severely immunosuppressed with a median CD4 cell count at enrolment of 163 cells/µL (IQR 46–298). Ninety-nine per cent of the patients had a diagnosis of pulmonary TB confirmed by sputum microscopy, Xpert/RIF or culture and 203 (75.7%) have completed TB treatment with 5099 aliquots of blood collected for pharmacokinetic analysis. Future plans This cohort provides a large database of well-characterised patients coinfected with TB/HIV which will facilitate the description of the association between serum drug concentrations and TB treatment outcomes as well as provide a research platform for future substudies including evaluation of virological outcomes. trial registration number NCT01782950; Pre-results}, keywords = {}, pubstate = {published}, tppubtype = {article} } AbstrAct Purpose Tuberculosis (TB) is a leading cause of death among people living with HIV in sub-Saharan Africa. Several factors influence the efficacy of TB treatment by leading to suboptimal drug concentrations and subsequently affecting treatment outcome. The aim of this cohort is to determine the association between anti-TB drug concentrations and TB treatment outcomes. Participants Patients diagnosed with new pulmonary TB at the integrated TB-HIV outpatient clinic in Kampala, Uganda, were enrolled into the study and started on firstline anti-TB treatment. Findings to date Between April 2013 and April 2015, the cohort enrolled 268 patients coinfected with TB/HIV ; 57.8% are male with a median age of 34 years (IQR 29–40). The median time between the diagnosis of HIV and the diagnosis of TB is 2 months (IQR 0–22.5). The majority of the patients are antiretroviral therapy naive (75.4%). Our population is severely immunosuppressed with a median CD4 cell count at enrolment of 163 cells/µL (IQR 46–298). Ninety-nine per cent of the patients had a diagnosis of pulmonary TB confirmed by sputum microscopy, Xpert/RIF or culture and 203 (75.7%) have completed TB treatment with 5099 aliquots of blood collected for pharmacokinetic analysis. Future plans This cohort provides a large database of well-characterised patients coinfected with TB/HIV which will facilitate the description of the association between serum drug concentrations and TB treatment outcomes as well as provide a research platform for future substudies including evaluation of virological outcomes. trial registration number NCT01782950; Pre-results |
Surowiec, Izabella; Gouveia-Figueira, Sandra; Orikiiriza, Judy; Lindquis, Elisabeth; Bonde, Mari; Magambo, Jimmy; Muhinda, Charles; Sven Bergström, Johan Normark ; Trygg, Johan The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children. Journal Article BMC Malaria Journal, 16 (1), 2017. @article{Surowiec2017b, title = {The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children. }, author = {Izabella Surowiec and Sandra Gouveia-Figueira and Judy Orikiiriza and Elisabeth Lindquis and Mari Bonde and Jimmy Magambo and Charles Muhinda and Sven Bergström, Johan Normark and Johan Trygg}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/The-oxylipin-and-endocannabidome-responses-in-acute-phase-Plasmodium-falciparum-malaria-in-children-1.pdf}, doi = {10.1186/s12936-017-2001-y}, year = {2017}, date = {2017-09-18}, journal = {BMC Malaria Journal}, volume = {16}, number = {1}, abstract = { Background Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism. Methods Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA®) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis). Results Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls. Conclusions It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed. Keywords OxylipinsEndocannabinoidsMalaria infection Plasmodium falciparum }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initiation and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism. Methods Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncomplicated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatography mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA®) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis). Results Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13-HODE, 9-HODE and 13-oxo-ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5-lipoxygenase (5-LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls. Conclusions It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed. Keywords OxylipinsEndocannabinoidsMalaria infection Plasmodium falciparum |
Surowiec, Izabella; Gouveia‑Figueira, Sandra; Orikiiriza, Judy; Lindquist, Elisabeth; Bonde, Mari; Magambo, Jimmy; Muhinda, Charles; Bergström, Sven; Normark, Johan; Trygg, Johan The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children. Journal Article |Malaria Journal , 16 (1), pp. 358, 2017. @article{Surowiec2017, title = {The oxylipin and endocannabidome responses in acute phase Plasmodium falciparum malaria in children. }, author = {Izabella Surowiec and Sandra Gouveia‑Figueira and Judy Orikiiriza and Elisabeth Lindquist and Mari Bonde and Jimmy Magambo and Charles Muhinda and Sven Bergström and Johan Normark and Johan Trygg}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/The-oxylipin-and-endocannabidome-responses-in-acute-phase-Plasmodium-falciparum-malaria-in-children.pdf}, doi = { 10.1186/s12936-017-2001-y}, year = {2017}, date = {2017-09-08}, journal = {|Malaria Journal }, volume = {16}, number = {1}, pages = {358}, abstract = {Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initia‑ tion and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism. Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncompli‑ cated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatog‑ raphy mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS‑DA®) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis). Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13‑HODE, 9‑HODE and 13‑oxo‑ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5‑lipoxygenase (5‑LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls. Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed. Keywords: Oxylipins, Endocannabinoids, Malaria infection, Plasmodium falciparum }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Oxylipins and endocannabinoids are low molecular weight bioactive lipids that are crucial for initia‑ tion and resolution of inflammation during microbial infections. Metabolic complications in malaria are recognized contributors to severe and fatal malaria, but the impact of malaria infection on the production of small lipid derived signalling molecules is unknown. Knowledge of immunoregulatory patterns of these molecules in malaria is of great value for better understanding of the disease and improvement of treatment regimes, since the action of these classes of molecules is directly connected to the inflammatory response of the organism. Methods: Detection of oxylipins and endocannabinoids from plasma samples from forty children with uncompli‑ cated and severe malaria as well as twenty controls was done after solid phase extraction followed by chromatog‑ raphy mass spectrometry analysis. The stable isotope dilution method was used for compound quantification. Data analysis was done with multivariate (principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS‑DA®) and univariate approaches (receiver operating characteristic (ROC) curves, t tests, correlation analysis). Results: Forty different oxylipin and thirteen endocannabinoid metabolites were detected in the studied samples, with one oxylipin (thromboxane B2, TXB2) in significantly lower levels and four endocannabinoids (OEA, PEA, DEA and EPEA) at significantly higher levels in infected individuals as compared to controls according to t test analysis with Bonferroni correction. Three oxylipins (13‑HODE, 9‑HODE and 13‑oxo‑ODE) were higher in severe compared to uncomplicated malaria cases according to the results from multivariate analysis. Observed changes in oxylipin levels can be connected to activation of cytochrome P450 (CYP) and 5‑lipoxygenase (5‑LOX) metabolic pathways in malaria infected individuals compared to controls, and related to increased levels of all linoleic acid oxylipins in severe patients compared to uncomplicated ones. The endocannabinoids were extremely responsive to malaria infection with majority of this class of molecules found at higher levels in infected individuals compared to controls. Conclusions: It was possible to detect oxylipin and endocannabinoid molecules that can be potential biomarkers for differentiation between malaria infected individuals and controls and between different classes of malaria. Metabolic pathways that could be targeted towards an adjunctive therapy in the treatment of malaria were also pinpointed. Keywords: Oxylipins, Endocannabinoids, Malaria infection, Plasmodium falciparum |
Semeere, Aggrey; Freeman, Esther; Wenger, Megan; Glidden, David; Bwana, Mwebesa; Kanyesigye, Micheal; Asirwa, Fredrick Chite; Rotich, Elyne; Busakhala, Naftali; Oga, Emmanuel; Jedy-Agba, Elima; Kwaghe, Vivian; Iregbu, Kenneth; Adebamowo, Clement; Jaquet, Antoine; Dabis, Francois; Phiri, Sam; Bohlius, Julia; Egger, Matthias; Yiannoutsos, Constantin T; Wools-Kaloustian, Kara; Martin, Jeffrey Updating vital status by tracking in the community among patients with epidemic Kaposi sarcoma who are lost to follow-up in sub-Saharan Africa. Journal Article BMC Cancer, 17 (1), pp. 611, 2017. @article{Semeere2017, title = {Updating vital status by tracking in the community among patients with epidemic Kaposi sarcoma who are lost to follow-up in sub-Saharan Africa.}, author = {Aggrey Semeere and Esther Freeman and Megan Wenger and David Glidden and Mwebesa Bwana and Micheal Kanyesigye and Fredrick Chite Asirwa and Elyne Rotich and Naftali Busakhala and Emmanuel Oga and Elima Jedy-Agba and Vivian Kwaghe and Kenneth Iregbu and Clement Adebamowo and Antoine Jaquet and Francois Dabis and Sam Phiri and Julia Bohlius and Matthias Egger and Constantin T. Yiannoutsos and Kara Wools-Kaloustian and Jeffrey Martin }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Updating-vital-status-by-tracking-in-the-community-among-patients-with-epidemic-Kaposi-sarcoma-who-are-lost-to-follow-up-in-sub-Saharan-Afric.pdf}, doi = {10.1186/s12885-017-3549-1}, year = {2017}, date = {2017-09-02}, journal = {BMC Cancer}, volume = {17}, number = {1}, pages = {611}, abstract = {Background: Throughout most of sub-Saharan Africa (and, indeed, most resource-limited areas), lack of death registries prohibits linkage of cancer diagnoses and precludes the most expeditious approach to determining cancer survival. Instead, estimation of cancer survival often uses clinical records, which have some mortality data but are replete with patients who are lost to follow-up (LTFU), some of which may be caused by undocumented death. The end result is that accurate estimation of cancer survival is rarely performed. A prominent example of a common cancer in Africa for which survival data are needed but for which frequent LTFU has precluded accurate estimation is Kaposi sarcoma (KS). Methods: Using electronic records, we identified all newly diagnosed KS among HIV-infected adults at 33 primary care clinics in Kenya, Uganda, Nigeria, and Malawi from 2009 to 2012. We determined those patients who were apparently LTFU, defined as absent from clinic for ≥90 days at database closure and unknown to be dead or transferred. Using standardized protocols which included manual chart review, telephone calls, and physical tracking in the community, we attempted to update vital status amongst patients who were LTFU. Results: We identified 1222 patients with KS, of whom 440 were LTFU according to electronic records. Manual chart review revealed that 18 (4.1%) were classified as LFTU due to clerical error, leaving 422 as truly LTFU. Of these 422, we updated vital status in 78%; manual chart review was responsible for updating in 5.7%, telephone calls in 26%, and physical tracking in 46%. Among 378 patients who consented at clinic enrollment to be tracked if they became LTFU and who had sufficient geographic contact/locator information, we updated vital status in 88%. Duration of LTFU was not associated with success of tracking, but tracking success was better in Kenya than the other sites. Conclusion: It is feasible to update vital status in a large fraction of patients with HIV-associated KS in sub-Saharan Africa who have become LTFU from clinical care. This finding likely applies to other cancers as well. Updating vital status amongst lost patients paves the way towards accurate determination of cancer survival. Keywords: Loss to follow-up, Tracking, Tracing, Updating vital status, Survival, Mortality, Kaposi sarcoma, HIV/AIDS, Cancer, Resource-limited settings, Sub-Saharan Africa }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Throughout most of sub-Saharan Africa (and, indeed, most resource-limited areas), lack of death registries prohibits linkage of cancer diagnoses and precludes the most expeditious approach to determining cancer survival. Instead, estimation of cancer survival often uses clinical records, which have some mortality data but are replete with patients who are lost to follow-up (LTFU), some of which may be caused by undocumented death. The end result is that accurate estimation of cancer survival is rarely performed. A prominent example of a common cancer in Africa for which survival data are needed but for which frequent LTFU has precluded accurate estimation is Kaposi sarcoma (KS). Methods: Using electronic records, we identified all newly diagnosed KS among HIV-infected adults at 33 primary care clinics in Kenya, Uganda, Nigeria, and Malawi from 2009 to 2012. We determined those patients who were apparently LTFU, defined as absent from clinic for ≥90 days at database closure and unknown to be dead or transferred. Using standardized protocols which included manual chart review, telephone calls, and physical tracking in the community, we attempted to update vital status amongst patients who were LTFU. Results: We identified 1222 patients with KS, of whom 440 were LTFU according to electronic records. Manual chart review revealed that 18 (4.1%) were classified as LFTU due to clerical error, leaving 422 as truly LTFU. Of these 422, we updated vital status in 78%; manual chart review was responsible for updating in 5.7%, telephone calls in 26%, and physical tracking in 46%. Among 378 patients who consented at clinic enrollment to be tracked if they became LTFU and who had sufficient geographic contact/locator information, we updated vital status in 88%. Duration of LTFU was not associated with success of tracking, but tracking success was better in Kenya than the other sites. Conclusion: It is feasible to update vital status in a large fraction of patients with HIV-associated KS in sub-Saharan Africa who have become LTFU from clinical care. This finding likely applies to other cancers as well. Updating vital status amongst lost patients paves the way towards accurate determination of cancer survival. Keywords: Loss to follow-up, Tracking, Tracing, Updating vital status, Survival, Mortality, Kaposi sarcoma, HIV/AIDS, Cancer, Resource-limited settings, Sub-Saharan Africa |
Kwizera, Richard; Akampurira, Andrew; Kandole, Tadeo K; Nielsen, Kirsten; Kambugu, Andrew; Meya, David B; Boulware, David R; Rhein, Joshua; on behalf of the Team, ASTRO-CM Study BMC Microbiology, 17 (1), pp. 182, 2017. @article{Kwizera2017c, title = {Evaluation of trypan blue stain in a haemocytometer for rapid detection of cerebrospinal fluid sterility in HIV patients with cryptococcal meningitis.}, author = {Richard Kwizera and Andrew Akampurira and Tadeo K. Kandole and Kirsten Nielsen and Andrew Kambugu and David B. Meya and David R. Boulware and Joshua Rhein and on behalf of the ASTRO-CM Study Team}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Evaluation-of-trypan-blue-stain-in-a-haemocytometer-for-rapid-detection-of-cerebrospinal-fluid-sterility-in-HIV-patients-with-cryptococcal-meningitis-1.pdf}, year = {2017}, date = {2017-08-22}, journal = {BMC Microbiology}, volume = {17}, number = {1}, pages = {182}, abstract = {Background: Quantitative culture is the most common method to determine the fungal burden and sterility of cerebrospinal fluid (CSF) among persons with cryptococcal meningitis. A major drawback of cultures is a long turnaround-time. Recent evidence demonstrates that live and dead Cryptococcus yeasts can be distinguished using trypan blue staining. We hypothesized that trypan blue staining combined with haemocytometer counting may provide a rapid estimation of quantitative culture count and detection of CSF sterility. To test this, we evaluated 194 CSF specimens from 96 HIV-infected participants with cryptococcal meningitis in Kampala, Uganda. Cryptococcal meningitis was diagnosed by CSF cryptococcal antigen (CRAG). We stained CSF with trypan blue and quantified yeasts using a haemocytometer. We compared the haemocytometer readings versus quantitative Cryptococcus CSF cultures. Results: Haemocytometer counting with trypan blue staining had a sensitivity of 98% (64/65), while CSF cultures had a sensitivity of 95% (62/65) with reference to CSF CRAG for diagnostic CSF specimens. For samples that were positive in both tests, the haemocytometer had higher readings compared to culture. For diagnostic specimens, the median of log10 transformed counts were 5.59 (n = 64, IQR = 5.09 to 6.05) for haemocytometer and 4.98 (n = 62, IQR = 3.75 to 5.79) for culture; while the overall median counts were 5.35 (n = 189, IQR = 4.78–5.84) for haemocytometer and 3.99 (n = 151, IQR = 2.59–5.14) for cultures. The percentage agreement with culture sterility was 2.4% (1/42). Counts among non-sterile follow-up specimens had a median of 5.38 (n = 86, IQR = 4.74 to 6.03) for haemocytometer and 2.89 (n = 89, IQR = 2.11 to 4.38) for culture. At diagnosis, CSF quantitative cultures correlated with haemocytometer counts (R2 = 0.59,P < 0.001). At 7–14 days, quantitative cultures did not correlate with haemocytometer counts (R2 = 0.43, P = 0.4). Conclusion: Despite a positive correlation, the haemocytometer counts with trypan blue staining did not predict the outcome of quantitative cultures in patients receiving antifungal therapy. Keywords: Trypan blue, Cryptococcal meningitis, HIV, Diagnostic techniques and procedures, Point-of-care systems }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Quantitative culture is the most common method to determine the fungal burden and sterility of cerebrospinal fluid (CSF) among persons with cryptococcal meningitis. A major drawback of cultures is a long turnaround-time. Recent evidence demonstrates that live and dead Cryptococcus yeasts can be distinguished using trypan blue staining. We hypothesized that trypan blue staining combined with haemocytometer counting may provide a rapid estimation of quantitative culture count and detection of CSF sterility. To test this, we evaluated 194 CSF specimens from 96 HIV-infected participants with cryptococcal meningitis in Kampala, Uganda. Cryptococcal meningitis was diagnosed by CSF cryptococcal antigen (CRAG). We stained CSF with trypan blue and quantified yeasts using a haemocytometer. We compared the haemocytometer readings versus quantitative Cryptococcus CSF cultures. Results: Haemocytometer counting with trypan blue staining had a sensitivity of 98% (64/65), while CSF cultures had a sensitivity of 95% (62/65) with reference to CSF CRAG for diagnostic CSF specimens. For samples that were positive in both tests, the haemocytometer had higher readings compared to culture. For diagnostic specimens, the median of log10 transformed counts were 5.59 (n = 64, IQR = 5.09 to 6.05) for haemocytometer and 4.98 (n = 62, IQR = 3.75 to 5.79) for culture; while the overall median counts were 5.35 (n = 189, IQR = 4.78–5.84) for haemocytometer and 3.99 (n = 151, IQR = 2.59–5.14) for cultures. The percentage agreement with culture sterility was 2.4% (1/42). Counts among non-sterile follow-up specimens had a median of 5.38 (n = 86, IQR = 4.74 to 6.03) for haemocytometer and 2.89 (n = 89, IQR = 2.11 to 4.38) for culture. At diagnosis, CSF quantitative cultures correlated with haemocytometer counts (R2 = 0.59,P < 0.001). At 7–14 days, quantitative cultures did not correlate with haemocytometer counts (R2 = 0.43, P = 0.4). Conclusion: Despite a positive correlation, the haemocytometer counts with trypan blue staining did not predict the outcome of quantitative cultures in patients receiving antifungal therapy. Keywords: Trypan blue, Cryptococcal meningitis, HIV, Diagnostic techniques and procedures, Point-of-care systems |
Ssempijja, Victor; Nakigozi, Gertrude; Chang, Larry; Gray, Ron; Wawer, Maria; Ndyanabo, Anthony; Kasule, Jingo; Serwadda, David; Castelnuovo, Barbara; van’t Hoog, Anja; Reynolds, Steven James BMC Infectious Diseases, 17 (1), 2017. @article{Ssempijja2017, title = {Rates of switching to second-line antiretroviral therapy and impact of delayed switching on immunologic, virologic, and mortality outcomes among HIV-infected adults with virologic failure in Rakai, Uganda}, author = {Victor Ssempijja and Gertrude Nakigozi and Larry Chang and Ron Gray and Maria Wawer and Anthony Ndyanabo and Jingo Kasule and David Serwadda and Barbara Castelnuovo and Anja van’t Hoog and Steven James Reynolds}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Rates-of-switching-to-second-line-antiretroviral-therapy-and-impact-of-delayed-switching-on-immunologic.pdf}, doi = {10.1186/s12879-017-2680-6}, year = {2017}, date = {2017-08-22}, journal = {BMC Infectious Diseases}, volume = {17}, number = {1}, abstract = {Background: Switch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90′ of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005. Methods: Retrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of ≥50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients. Results: The cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs ≤ 5000 copies/ml, patients with VLs = 5001–10,000 copies/ml had an aHR = 1.81 (95% CI = 0.9–3.6), and patients with VLs > 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9–6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 ≥ 100 cells/ul (aHR = 2.30, 95% CI = 1.5–3.6). Mortality in patients not switched to second-line ART was 11.9%, compared to 1.2% for those who switched (p = 0.009). Patients switched after 12 months of of virologic failure were more likely to experience CD4 decline and/or further VL increases. (Continued on next page) }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Switch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90′ of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005. Methods: Retrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of ≥50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients. Results: The cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs ≤ 5000 copies/ml, patients with VLs = 5001–10,000 copies/ml had an aHR = 1.81 (95% CI = 0.9–3.6), and patients with VLs > 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9–6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 ≥ 100 cells/ul (aHR = 2.30, 95% CI = 1.5–3.6). Mortality in patients not switched to second-line ART was 11.9%, compared to 1.2% for those who switched (p = 0.009). Patients switched after 12 months of of virologic failure were more likely to experience CD4 decline and/or further VL increases. (Continued on next page) |
Shete, Priya B; Ravindran, Resmi; Chang, Emily; Worodria, William; Chaisson, Lelia H; Alfred Andama4, Lucian Davis J; Luciw, Paul A; Huang, Laurence; Khan, Imran H; Cattamanchi, Adithya . Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda. Journal Article PloS One, 12 (8), 2017. @article{Shete2017, title = {. Evaluation of antibody responses to panels of M. tuberculosis antigens as a screening tool for active tuberculosis in Uganda.}, author = {Priya B. Shete and Resmi Ravindran and Emily Chang and William Worodria and Lelia H. Chaisson and Alfred Andama4, J. Lucian Davis and Paul A. Luciw and Laurence Huang and Imran H. Khan and Adithya Cattamanchi}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Evaluation-of-antibody-responses-to-panels-of-M.-tuberculosis-antigens-as-a-screening-tool-for-active-tuberculosis-in-Uganda.pdf}, doi = {10.1371/journal.pone.0180122}, year = {2017}, date = {2017-08-02}, journal = {PloS One}, volume = {12}, number = {8}, abstract = {Background Improved systematic screening of high-risk groups is a key component of the tuberculosis (TB) elimination strategy endorsed by the World Health Organization (WHO). We used a multiplex microbead immunoassay to measure antibody responses to 28 M. tuberculosis (M.tb) antigens, and assessed whether combinations of antibody responses achieve accuracy thresholds required for a TB screening test. Methods A random selection of plasma samples obtained from consecutive HIV-negative adults who were admitted to Mulago Hospital in Kampala, Uganda with cough2 weeks’ but<6 months’ duration were analyzed for serological response to 28 M.tb antigens using an inhouse multiplex microbead immunoassay. We compared the median difference of the antibody response to each antigen between patients with and without culture-confirmed TB, ranked each antigen according to variable importance (VIM), and assessed the sensitivity and specificity of combinations of antibody responses using an advanced classification algorithm, SuperLearner. Results Among the 237 patients included in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and 113 (48%) had TB. Median antibody levels to eight antigens ere significantly different between patients with and without TB. A panel including eight of the top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a specificity of 88.6% (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38, Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be>90%, specificity remained close to 70% with as few as 3 antigens included in the panels. Conclusions Measuring antibody responses to combinations of antigens could facilitate TB screening and should be further evaluated in populations being targeted for systematic screening. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Improved systematic screening of high-risk groups is a key component of the tuberculosis (TB) elimination strategy endorsed by the World Health Organization (WHO). We used a multiplex microbead immunoassay to measure antibody responses to 28 M. tuberculosis (M.tb) antigens, and assessed whether combinations of antibody responses achieve accuracy thresholds required for a TB screening test. Methods A random selection of plasma samples obtained from consecutive HIV-negative adults who were admitted to Mulago Hospital in Kampala, Uganda with cough2 weeks’ but<6 months’ duration were analyzed for serological response to 28 M.tb antigens using an inhouse multiplex microbead immunoassay. We compared the median difference of the antibody response to each antigen between patients with and without culture-confirmed TB, ranked each antigen according to variable importance (VIM), and assessed the sensitivity and specificity of combinations of antibody responses using an advanced classification algorithm, SuperLearner. Results Among the 237 patients included in the analysis, 119 (50%) were female, median age was 32 years (IQR 25, 46), and 113 (48%) had TB. Median antibody levels to eight antigens ere significantly different between patients with and without TB. A panel including eight of the top ranked antigens had a sensitivity of 90.6% (95% CI 89.4, 93.8) and a specificity of 88.6% (95% CI 78.2, 97.6) (Ag85B, Ag85A, Ag85C, Rv0934-P38, Rv3881, BfrB, Rv3873, and Rv2878c). With sensitivity constrained to be>90%, specificity remained close to 70% with as few as 3 antigens included in the panels. Conclusions Measuring antibody responses to combinations of antigens could facilitate TB screening and should be further evaluated in populations being targeted for systematic screening. |
Kwizera, Richard; Akampurira, Andrew; Williams, Darlisha; Meya, David Boulware David R B; on behalf of the Team, ASTRO-CM Study PloS One, 12 (7), 2017. @article{Kwizera2017b, title = {Acridine orange fluorescent microscopy is more sensitive than India ink light microscopy in the rapid detection of cryptococcosis among CrAg positive HIV patients}, author = {Richard Kwizera and Andrew Akampurira and Darlisha Williams and David R. Boulware David B. Meya and on behalf of the ASTRO-CM Study Team}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Acridine-orange-fluorescent-microscopy-is-more-sensitive-than-India-ink-light-microscopy-in-the-rapid-detection-of-cryptococcosis-among-CrAg-positive-HIV-patients.pdf}, doi = {10.1371/journal.pone.0182108}, year = {2017}, date = {2017-07-27}, journal = {PloS One}, volume = {12}, number = {7}, abstract = {Background India ink microscopy on cerebrospinal fluid is still utilized in resource limited settings for the diagnosis of cryptococcal meningitis despite its poor sensitivity. We hypothesized that staining fungal nucleic acids with fluorescent dyes instead of the capsule with India ink might improve sensitivity for the diagnosis of cryptococcal meningitis. Methods We enrolled 96 HIV-infected participants with cryptococcal meningitis who provided 194 CSF specimens at serial time points in Kampala, Uganda. Cryptococcosis was diagnosed by cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) test and only positive samples were included. We stained CSF with India ink and acridine orange. We cultured the same samples on standard fungal media. We compared acridine orange to CrAg, India ink and CSF culture. Results Acridine orange was more sensitive (96%) than India ink (79%) with reference to CSF CrAg. Acridine orange and India ink had a statistically significant difference (P<0.001) with a 25% correlation for detection of Cryptococcus yeasts. India ink had more negative results (22%) than acridine orange (4%). The sensitivity for India ink increased (86%) while that of acridine orange did not change (97%) when compared to CSF culture. However, both India ink and acridine orange had poor predictive values with reference to culture. Conclusion Acridine orange is a better alternative to India ink in the rapid detection of cryptococcosis among CrAg positive HIV patients}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background India ink microscopy on cerebrospinal fluid is still utilized in resource limited settings for the diagnosis of cryptococcal meningitis despite its poor sensitivity. We hypothesized that staining fungal nucleic acids with fluorescent dyes instead of the capsule with India ink might improve sensitivity for the diagnosis of cryptococcal meningitis. Methods We enrolled 96 HIV-infected participants with cryptococcal meningitis who provided 194 CSF specimens at serial time points in Kampala, Uganda. Cryptococcosis was diagnosed by cerebrospinal fluid (CSF) cryptococcal antigen (CrAg) test and only positive samples were included. We stained CSF with India ink and acridine orange. We cultured the same samples on standard fungal media. We compared acridine orange to CrAg, India ink and CSF culture. Results Acridine orange was more sensitive (96%) than India ink (79%) with reference to CSF CrAg. Acridine orange and India ink had a statistically significant difference (P<0.001) with a 25% correlation for detection of Cryptococcus yeasts. India ink had more negative results (22%) than acridine orange (4%). The sensitivity for India ink increased (86%) while that of acridine orange did not change (97%) when compared to CSF culture. However, both India ink and acridine orange had poor predictive values with reference to culture. Conclusion Acridine orange is a better alternative to India ink in the rapid detection of cryptococcosis among CrAg positive HIV patients |
Kranzer, Katharina; Bradley, John; Musaazi, Joseph; Nyathi, Mary; Gunguwo, Hilary; Ndebele, Wedu; Dixon, Mark; Ndhlovu, Mbongeni; Rehman, Andrea; Khan, Palwasha; Vogt, Florian; Apollo, Tsitsi; Ferrand, Rashida Abbas Loss to follow‐up among children and adolescents growing up with HIV infection: age really matters Journal Article Journal of the International AIDS Society, 20 (1), 2017. @article{Kranzer2017, title = {Loss to follow‐up among children and adolescents growing up with HIV infection: age really matters}, author = {Katharina Kranzer and John Bradley and Joseph Musaazi and Mary Nyathi and Hilary Gunguwo and Wedu Ndebele and Mark Dixon and Mbongeni Ndhlovu and Andrea Rehman and Palwasha Khan and Florian Vogt and Tsitsi Apollo and Rashida Abbas Ferrand}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Loss-to-follow‐up-among-children-and-adolescents-growing-up-with-HIV-infection-age-really-matters.pdf}, doi = {10.7448/IAS.20.1.21737}, year = {2017}, date = {2017-07-17}, journal = {Journal of the International AIDS Society}, volume = {20}, number = {1}, abstract = { Introduction: Globally, increasing numbers of HIV‐infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss‐to‐follow‐up (LTFU) from HIV care services among children as they transition from childhood through adolescence. Methods: Individuals aged 5–19 years initiated on ART in a public‐sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age‐bands namely: 5–9 (children), 10–14 (young adolescents) and 15–19 (older adolescents). The effect of age at ART initiation, current age (using a time‐updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression. Results: Of 2273 participants, 1013, 875 and 385 initiated ART aged 5–9, 10–14 and 15–19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age‐band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94–2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05–3.07). In older adolescents, the LTFU rate among those who started ART in that age‐band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age‐groups. Conclusions: Adolescents had higher rates of LTFU compared to other age‐groups, with older adolescents at particularly high risk in all analyses. Age‐updated analyses that examine movement across narrow age‐bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction: Globally, increasing numbers of HIV‐infected children are reaching adolescence due to antiretroviral therapy (ART). We investigated rates of loss‐to‐follow‐up (LTFU) from HIV care services among children as they transition from childhood through adolescence. Methods: Individuals aged 5–19 years initiated on ART in a public‐sector HIV clinic in Bulawayo, Zimbabwe, between 2005 and 2009 were included in a retrospective cohort study. Participants were categorized into narrow age‐bands namely: 5–9 (children), 10–14 (young adolescents) and 15–19 (older adolescents). The effect of age at ART initiation, current age (using a time‐updated Lexis expansion) and transitioning from one age group to the next on LTFU was estimated using Poisson regression. Results: Of 2273 participants, 1013, 875 and 385 initiated ART aged 5–9, 10–14 and 15–19 years, respectively. Unlike those starting ART as children, individuals starting ART as young adolescents had higher LTFU rates after moving to the older adolescent age‐band (Adjusted rate ratio (ARR) 1.54; 95% CI: 0.94–2.55) and similarly, older adolescents had higher LTFU rates after transitioning to being young adults (ARR 1.79; 95% CI: 1.05–3.07). In older adolescents, the LTFU rate among those who started ART in that age‐band was higher compared to the rate among those starting ART at a younger age (ARR = 1.70; 95% CI: 1.05, 2.77). This however did not hold true for other age‐groups. Conclusions: Adolescents had higher rates of LTFU compared to other age‐groups, with older adolescents at particularly high risk in all analyses. Age‐updated analyses that examine movement across narrow age‐bands are paramount in understanding how developmental heterogeneity in children affects HIV outcomes. |
Meyer, Amanda J; Atuheire, Collins; Worodria, William; Kizito, Samuel; Katamba, Achilles; Sanyu, Ingvar; Andama, Alfred; Ayakaka, Irene; Cattamanchi, Adithya; Bwanga, Freddie; Huang, Laurence; Davis, Lucian J Sputum quality and diagnostic performance of GeneXpert MTB/RIF among smear-negative adults with presumed tuberculosis in Uganda. Journal Article 12 (7), 2017. @article{Meyer2017, title = {Sputum quality and diagnostic performance of GeneXpert MTB/RIF among smear-negative adults with presumed tuberculosis in Uganda. }, author = {Amanda J. Meyer and Collins Atuheire and William Worodria and Samuel Kizito and Achilles Katamba and Ingvar Sanyu and Alfred Andama and Irene Ayakaka and Adithya Cattamanchi and Freddie Bwanga and Laurence Huang and J. Lucian Davis}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Sputum-quality-and-diagnostic-performance-of-GeneXpert-MTBRIF-among-smear-negative-adults-with-presumed-tuberculosis-in-Uganda.pdf}, doi = {10.1371/journal.pone.0180572}, year = {2017}, date = {2017-07-07}, volume = {12}, number = {7}, abstract = {Background Introduction of GeneXpert MTB/RIF (Xpert) assay has constituted a major breakthrough for tuberculosis (TB) diagnostics. Several patient factors may influence diagnostic performance of Xpert including sputum quality. Objective We carried out a prospective, observational, cross-sectional study to determine the effect of sputum quality on diagnostic performance of Xpert among presumed TB patients in Uganda. Methods We collected clinical and demographic information and two sputum samples from participants. Staff recorded sputum quality and performed LED fluorescence microscopy and mycobacterial culture on each sample. If both smear examinations were negative, Xpert testing was performed. We calculated diagnostic yield, sensitivity, specificity, and other indicators for Xpert for each stratum of sputum quality in reference to a standard of mycobacterial culture. Results Patients with salivary sputum showed a trend towards a substantially higher proportion of samples that were Xpert-positive (54/286, 19%, 95% CI 15–24) compared with those with all other sputum sample types (221/1496, 15%, 95% CI 13–17). Blood-stained sputum produced the lowest sensitivity (28%; 95% CI 12–49) and salivary sputum the highest (66%; 95% CI 53–77). Specificity didn’t vary meaningfully by sample types. Salivary sputum was significantly more sensitive than mucoid sputum (+13%, 95% CI +1 to +26), while bloodstained sputum was significantly less sensitive (-24%, 95% CI -42 to -5). Conclusions Our findings demonstrate the need to exercise caution in collecting sputum for Xpert and in interpreting results because sputum quality may impact test yield and sensitivity. In particular, it may be wise to pursue additional testing should blood-stained sputum test negative while salivary sputum should be readily accepted for Xpert testing given its higher sensitivity and potentially higher yield than other sample types. These findings challenge conventional recommendations against collecting salivary sputum for TB diagnosis and could inform new standards for sputum quality. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background Introduction of GeneXpert MTB/RIF (Xpert) assay has constituted a major breakthrough for tuberculosis (TB) diagnostics. Several patient factors may influence diagnostic performance of Xpert including sputum quality. Objective We carried out a prospective, observational, cross-sectional study to determine the effect of sputum quality on diagnostic performance of Xpert among presumed TB patients in Uganda. Methods We collected clinical and demographic information and two sputum samples from participants. Staff recorded sputum quality and performed LED fluorescence microscopy and mycobacterial culture on each sample. If both smear examinations were negative, Xpert testing was performed. We calculated diagnostic yield, sensitivity, specificity, and other indicators for Xpert for each stratum of sputum quality in reference to a standard of mycobacterial culture. Results Patients with salivary sputum showed a trend towards a substantially higher proportion of samples that were Xpert-positive (54/286, 19%, 95% CI 15–24) compared with those with all other sputum sample types (221/1496, 15%, 95% CI 13–17). Blood-stained sputum produced the lowest sensitivity (28%; 95% CI 12–49) and salivary sputum the highest (66%; 95% CI 53–77). Specificity didn’t vary meaningfully by sample types. Salivary sputum was significantly more sensitive than mucoid sputum (+13%, 95% CI +1 to +26), while bloodstained sputum was significantly less sensitive (-24%, 95% CI -42 to -5). Conclusions Our findings demonstrate the need to exercise caution in collecting sputum for Xpert and in interpreting results because sputum quality may impact test yield and sensitivity. In particular, it may be wise to pursue additional testing should blood-stained sputum test negative while salivary sputum should be readily accepted for Xpert testing given its higher sensitivity and potentially higher yield than other sample types. These findings challenge conventional recommendations against collecting salivary sputum for TB diagnosis and could inform new standards for sputum quality. |
Kharono, Brenda; Nabisere, Ruth; Persis, Nabyonga Kiddu; Nakakeeto, Jackie; Openy, Abraham; Kitaka, Sabrina Bakeera Knowledge, Attitudes, and Perceived Risks Related to Diabetes Mellitus Among University Students in Uganda: A Cross-Sectional Study. Journal Article East African Research Journal, 1 (2), pp. 105-112, 2017. @article{Kharono2017, title = {Knowledge, Attitudes, and Perceived Risks Related to Diabetes Mellitus Among University Students in Uganda: A Cross-Sectional Study.}, author = {Brenda Kharono and Ruth Nabisere and Nabyonga Kiddu Persis and Jackie Nakakeeto and Abraham Openy and Sabrina Bakeera Kitaka}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Knowledge-Attitudes-and-Perceived-Risks-Related-to-Diabetes-Mellitus-Among-University-Students-in-Uganda-A-CrossSectional-Study.pdf}, year = {2017}, date = {2017-07-01}, journal = {East African Research Journal}, volume = {1}, number = {2}, pages = {105-112}, abstract = {Background—Diabetes mellitus is on the rise in low-income countries, including Uganda, owing to the ‘westernization’ of individual lifestyles. It remains unanswered whether the majority of university students who are rapidly embracing ‘western’ lifestyles have any knowledge of diabetes or perceive themselves to be at risk of acquiring the disease. The aim of the study was to assess the knowledge, attitudes, and perceived risks related to diabetes mellitus among university students in Uganda. Methods—This descriptive cross-sectional study was conducted in 4 universities in Uganda from August to November 2013. The data collection tool included questions on risk factors, symptoms, personal risks, and practices to prevent diabetes mellitus. We interviewed 378 university students using pretested self-administered semi-structured questionnaires. Only students who consented to participate in the study were included. Data were entered into EpiData version 3.1 and analysed using SPSS version 18. Results—Almost all (99%) of the students had knowledge about diabetes mellitus. The majority (83.1%) reported that diabetes mellitus is not completely a genetic/hereditary disease. Only a minority of respondents reported that they should worry about diabetes before 45 years of age. Common symptoms of diabetes reported by the respondents included constant hunger, blurred vision, fatigue, and frequent urination. Conclusions—Our study revealed that the majority of university students in Uganda had good knowledge about the risk factors and symptoms of diabetes mellitus. The majority also perceived themselves to be at risk of diabetes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background—Diabetes mellitus is on the rise in low-income countries, including Uganda, owing to the ‘westernization’ of individual lifestyles. It remains unanswered whether the majority of university students who are rapidly embracing ‘western’ lifestyles have any knowledge of diabetes or perceive themselves to be at risk of acquiring the disease. The aim of the study was to assess the knowledge, attitudes, and perceived risks related to diabetes mellitus among university students in Uganda. Methods—This descriptive cross-sectional study was conducted in 4 universities in Uganda from August to November 2013. The data collection tool included questions on risk factors, symptoms, personal risks, and practices to prevent diabetes mellitus. We interviewed 378 university students using pretested self-administered semi-structured questionnaires. Only students who consented to participate in the study were included. Data were entered into EpiData version 3.1 and analysed using SPSS version 18. Results—Almost all (99%) of the students had knowledge about diabetes mellitus. The majority (83.1%) reported that diabetes mellitus is not completely a genetic/hereditary disease. Only a minority of respondents reported that they should worry about diabetes before 45 years of age. Common symptoms of diabetes reported by the respondents included constant hunger, blurred vision, fatigue, and frequent urination. Conclusions—Our study revealed that the majority of university students in Uganda had good knowledge about the risk factors and symptoms of diabetes mellitus. The majority also perceived themselves to be at risk of diabetes. |
Wandera, Bonnie; Tumwesigye, Nazarius M; Nankabirwa, Joaniter I; Kambugu, Andrew D; Mafigiri4, David K; Kapiga, Saidi; Sethi, Ajay K Hazardous alcohol consumption is not associated with CD4+ T-cell count decline among PLHIV in Kampala Uganda: A prospective cohort study Journal Article PloS One, 12 (6), 2017. @article{Wandera2017, title = {Hazardous alcohol consumption is not associated with CD4+ T-cell count decline among PLHIV in Kampala Uganda: A prospective cohort study}, author = {Bonnie Wandera and Nazarius M. Tumwesigye and Joaniter I. Nankabirwa and Andrew D. Kambugu and David K. Mafigiri4 and Saidi Kapiga and Ajay K. Sethi}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Hazardous-alcohol-consumption-is-not-associated-with-CD4-T-cell-count-decline-among-PLHIV-in-Kampala-Uganda-A-prospective-cohort-study.pdf}, doi = {10.1371/journal.pone.0180015}, year = {2017}, date = {2017-06-30}, journal = {PloS One}, volume = {12}, number = {6}, abstract = {Introduction There is limited data on the effects of alcohol on immunological response among persons living with HIV (PLHIV) in sub-Saharan Africa. We assessed the relationship between hazardous alcohol use and CD4+ T-cell count, among PLHIV in Uganda. Methods PLHIV aged18 years were enrolled in a cohort study at the Infectious diseases clinic Kampala, Uganda. Alcohol consumption was assessed at enrolment (baseline) and 6 monthly thereafter using the alcohol use disorders identification test (AUDIT). The CD4+ Tcell counts, assessed at baseline and over the next 12 months were compared between alcohol use strata, using linear mixed effects regression. Using longitudinal mediation analysis methods, we estimated the effect of alcohol induced ART non-adherence on CD4+ Tcell count. Results Of the 1566 participants enrolled, 863(44.1%) were non-alcohol users (AUDIT score = 0), 433(27.7%) were non-hazardous (AUDIT score 1–7) alcohol users while 270 (17.2%) were hazardous (AUDIT score8) alcohol users. The overall median (IQR) baseline CD4+ T-cell count was 356 (243–516) cells/μl. There were no differences in the median baseline CD4+ T-cell count between hazardous and nonhazardous alcohol users compared to non-alcohol users in both the non-ART (p = 0.43) and ART group (p = 0.77). }, keywords = {}, pubstate = {published}, tppubtype = {article} } Introduction There is limited data on the effects of alcohol on immunological response among persons living with HIV (PLHIV) in sub-Saharan Africa. We assessed the relationship between hazardous alcohol use and CD4+ T-cell count, among PLHIV in Uganda. Methods PLHIV aged18 years were enrolled in a cohort study at the Infectious diseases clinic Kampala, Uganda. Alcohol consumption was assessed at enrolment (baseline) and 6 monthly thereafter using the alcohol use disorders identification test (AUDIT). The CD4+ Tcell counts, assessed at baseline and over the next 12 months were compared between alcohol use strata, using linear mixed effects regression. Using longitudinal mediation analysis methods, we estimated the effect of alcohol induced ART non-adherence on CD4+ Tcell count. Results Of the 1566 participants enrolled, 863(44.1%) were non-alcohol users (AUDIT score = 0), 433(27.7%) were non-hazardous (AUDIT score 1–7) alcohol users while 270 (17.2%) were hazardous (AUDIT score8) alcohol users. The overall median (IQR) baseline CD4+ T-cell count was 356 (243–516) cells/μl. There were no differences in the median baseline CD4+ T-cell count between hazardous and nonhazardous alcohol users compared to non-alcohol users in both the non-ART (p = 0.43) and ART group (p = 0.77). |
Musaazi, J; Kiragga, A N; Castelnuovo, B; Kambugu, A; Bradley, J; Rehman, A M Tuberculosis treatment success among rural and urban Ugandans living with HIV: a retrospective studyy. Journal Article 7 (2), pp. 100-109, 2017. @article{Musaazi2017, title = {Tuberculosis treatment success among rural and urban Ugandans living with HIV: a retrospective studyy.}, author = {J. Musaazi and A. N. Kiragga and B. Castelnuovo and A. Kambugu and J. Bradley and A. M. Rehman }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Tuberculosis-treatment-success-among-rural-and-urban-Ugandans-living-with-HIV-a-retrospective-study..pdf}, doi = {10.5588/pha.16.0115}, year = {2017}, date = {2017-06-21}, volume = {7}, number = {2}, pages = {100-109}, abstract = {Setting: Government health centres and hospitals (six urban and 20 rural) providing tuberculosis (TB) treatment for people living with the human immunodeficiency virus (PLHIV) in central and western Uganda. Objective: To identify and quantify modifiable factors that limit TB treatment success among PLHIV in rural Uganda. Design: A retrospective cross-sectional review of routine Uganda National Tuberculosis and Leprosy Programme clinic registers and patient files of HIV-positive patients who received anti-tuberculosis treatment in 2014. Results: Of 191 rural patients, 66.7% achieved treatment success compared to 81.1% of 213 urban patients. Adjusted analysis revealed higher average treatment success in urban patients than in rural patients (OR 3.95, 95%CI 2.70-5.78, P < 0.01, generalised estimating equation model). Loss to follow-up was higher and follow-up sputum smear results were less frequently recorded in TB clinic registers among rural patients. Patients receiving treatment at higher-level facilities in rural settings had greater odds of treatment success, while patients receiving treatment at facilities where drug stock-outs had occurred had lower odds of treatment success. Conclusion: Lower reported treatment success in rural settings is mainly attributed to clinic-centred factors such as treatment monitoring procedures. We recommend strengthening treatment monitoring and delivery.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Setting: Government health centres and hospitals (six urban and 20 rural) providing tuberculosis (TB) treatment for people living with the human immunodeficiency virus (PLHIV) in central and western Uganda. Objective: To identify and quantify modifiable factors that limit TB treatment success among PLHIV in rural Uganda. Design: A retrospective cross-sectional review of routine Uganda National Tuberculosis and Leprosy Programme clinic registers and patient files of HIV-positive patients who received anti-tuberculosis treatment in 2014. Results: Of 191 rural patients, 66.7% achieved treatment success compared to 81.1% of 213 urban patients. Adjusted analysis revealed higher average treatment success in urban patients than in rural patients (OR 3.95, 95%CI 2.70-5.78, P < 0.01, generalised estimating equation model). Loss to follow-up was higher and follow-up sputum smear results were less frequently recorded in TB clinic registers among rural patients. Patients receiving treatment at higher-level facilities in rural settings had greater odds of treatment success, while patients receiving treatment at facilities where drug stock-outs had occurred had lower odds of treatment success. Conclusion: Lower reported treatment success in rural settings is mainly attributed to clinic-centred factors such as treatment monitoring procedures. We recommend strengthening treatment monitoring and delivery. |
Schutz, Charlotte; Boulware, David R; Huppler-Hullsiek, Katherine; von Hohenberg, Maximilian; Rhein, Joshua; Taseera, Kabanda; Thienemann, Friedrich; Muzoora, Conrad; Meya, David B; Meintjes, Graeme Acute Kidney Injury and Urinary Biomarkers in Human Immunodeficiency Virus–Associated Cryptococcal Meningitis Journal Article Open Forum Infectious Diseases, 11 (2), 2017. @article{Schutz2017, title = {Acute Kidney Injury and Urinary Biomarkers in Human Immunodeficiency Virus–Associated Cryptococcal Meningitis}, author = {Charlotte Schutz and David R. Boulware and Katherine Huppler-Hullsiek and Maximilian von Hohenberg and Joshua Rhein and Kabanda Taseera and Friedrich Thienemann and Conrad Muzoora and David B. Meya and Graeme Meintjes}, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Acute-Kidney-Injury-and-Urinary-Biomarkers-in-Human-Immunodeficiency-Virus–Associated-Cryptococcal-Meningitis-1.pdf}, doi = {10.1093/ofid/ofx127}, year = {2017}, date = {2017-06-20}, journal = {Open Forum Infectious Diseases}, volume = {11}, number = {2}, abstract = {Background. Cryptococcus is the most common etiology of adult meningitis in Africa. Amphotericin B deoxycholate remains paramount to treatment, despite toxicities, including acute kidney injury (AKI). We assessed the ability of the following urine markers to predict AKI in patients who received amphotericin B: urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), tissue inhibitor of metalloproteinases-2 (TIMP-2), and protein. Methods. One hundred and thirty human immunodeficiency virus (HIV)–infected participants with cryptococcal meningitis were enrolled and received amphotericin and fluconazole for 2 weeks. We defined AKI as glomerular filtration rate (GFR) < 60 mL/ min/1.73 m2; measured urine NGAL, CysC, TIMP-2, and protein; and explored AKI incidence, risk factors, and associations with mortality using Cox proportional hazards models. Results. Participants were 48% female with a median age of 35 years, a median CD4 count of 21 cells/μL, and 44% died within 12 months. Incident AKI occurred in 42% and was associated with mortality (adjusted hazard ratio [aHR] = 2.8; P < .001). Development of AKI was associated with female sex (P = .04) and with higher CD4 count (49 vs 14 cells/μL; P < .01). Urine protein level in the highest quartile independently predicted AKI and mortality (aHR = 1.64, P = .04; aHR = 2.13, P = .02, respectively). Urine NGAL levels in the highest quartile independently predicted AKI (aHR = 1.65; P = .04). Conclusions. Acute kidney injury occurred in 42% of patients, and AKI was associated with mortality. Urine biomarkers, specifically urine protein, may be useful for antecedent prediction of amphotericin-associated AKI but need further evaluation. Keywords. acute kidney injury; amphotericin B; biological marker; cystatin C; neutrophil gelatinase-associated lipocalin; protein; tissue inhibitor of metalloproteinase-2. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Background. Cryptococcus is the most common etiology of adult meningitis in Africa. Amphotericin B deoxycholate remains paramount to treatment, despite toxicities, including acute kidney injury (AKI). We assessed the ability of the following urine markers to predict AKI in patients who received amphotericin B: urine neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), tissue inhibitor of metalloproteinases-2 (TIMP-2), and protein. Methods. One hundred and thirty human immunodeficiency virus (HIV)–infected participants with cryptococcal meningitis were enrolled and received amphotericin and fluconazole for 2 weeks. We defined AKI as glomerular filtration rate (GFR) < 60 mL/ min/1.73 m2; measured urine NGAL, CysC, TIMP-2, and protein; and explored AKI incidence, risk factors, and associations with mortality using Cox proportional hazards models. Results. Participants were 48% female with a median age of 35 years, a median CD4 count of 21 cells/μL, and 44% died within 12 months. Incident AKI occurred in 42% and was associated with mortality (adjusted hazard ratio [aHR] = 2.8; P < .001). Development of AKI was associated with female sex (P = .04) and with higher CD4 count (49 vs 14 cells/μL; P < .01). Urine protein level in the highest quartile independently predicted AKI and mortality (aHR = 1.64, P = .04; aHR = 2.13, P = .02, respectively). Urine NGAL levels in the highest quartile independently predicted AKI (aHR = 1.65; P = .04). Conclusions. Acute kidney injury occurred in 42% of patients, and AKI was associated with mortality. Urine biomarkers, specifically urine protein, may be useful for antecedent prediction of amphotericin-associated AKI but need further evaluation. Keywords. acute kidney injury; amphotericin B; biological marker; cystatin C; neutrophil gelatinase-associated lipocalin; protein; tissue inhibitor of metalloproteinase-2. |
Waitta, Catriona; Penchalaa, Sujan Diliiy; Olagunjua, Adeniyi; Amaraa, Alieu; Elsea, Laura; Lamordeb, Mohammed; Khooa, Saye Journal of Chromatograpy B, 1060 , pp. 300-307, 2017. @article{Waitta2017, title = {Development, validation and clinical application of a method for the simultaneous quantification of lamivudine, emtricitabine and tenofovir in dried blood and dried breast milk spots using LC-MS/MS. }, author = {Catriona Waitta and Sujan Diliiy Penchalaa and Adeniyi Olagunjua and Alieu Amaraa and Laura Elsea and Mohammed Lamordeb and Saye Khooa }, url = {https://www.idi-makerere.com/wp-content/uploads/2018/07/Development-validation-and-clinical-application-of-a-method-for-the-simultaneous-quantification-of-lamivudine-emtricitabine-and-tenofovir-in-dried-blood-and-dried-breast-milk-spots-using.pdf}, doi = {10.1016/j.jchromb.2017.06.012}, year = {2017}, date = {2017-06-17}, journal = {Journal of Chromatograpy B}, volume = {1060}, pages = {300-307}, abstract = {Objectives: To present the validation and clinical application of a LC–MS/MS method for the quantification of lamivudine (3TC), emtricitabine (FTC) and tenofovir (TFV) in dried blood spots (DBS) and dried breast milk spots (DBMS). Methods: DBS and DBMS were prepared from 50 and 30μL of drug-spiked whole blood and human breast milk, respectively. Following extraction with acetonitrile and water, chromatographic separation utilised a Synergi polar column with a gradient mobile phase program consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection and quantification was performed using a TSQ Quantum Ultra triple quadrupole mass spectrometer. The analytical method was used to evaluate NRTI drug levels in HIV-positive nursing mothers-infant pairs. Results: The assay was validated over the concentration range of16.6–5000 ng/mL for 3TC, FTC and TFV inDBS and DBMS except for TFV in DBMS where linearity was established from 4.2–1250 ng/mL. Intra and inter-day precision (%CV) ranged from 3.5–8.7 and accuracy was within 15% for all analytes in both matrices. The mean recovery in DBS was>61% and in DBMS>43% for all three analytes. Matrix effect was insignificant. Median AUC0-8 values in maternal DBS and DBMS, respectively, were 4683 (4165–6057) and 6050 (5217–6417) ng h/mL for 3TC, 3312 (2259–4312) and 4853 (4124–6691) ng h/mL for FTC and 1559 (930–1915) and 56 (45–80) ngh/mL for TFV. 3TC and FTC were quantifiable (>16.6 ng/mL) in DBS from 2/6 and 1/6 infants respectively whereas TFV was undetectable in all infants. Conclusions: DBS and DBMS sampling for bioanalysis of 3TC, FTC and TFV is straightforward, robust, accurate and precise, and ideal for use in low-resource settings. }, keywords = {}, pubstate = {published}, tppubtype = {article} } Objectives: To present the validation and clinical application of a LC–MS/MS method for the quantification of lamivudine (3TC), emtricitabine (FTC) and tenofovir (TFV) in dried blood spots (DBS) and dried breast milk spots (DBMS). Methods: DBS and DBMS were prepared from 50 and 30μL of drug-spiked whole blood and human breast milk, respectively. Following extraction with acetonitrile and water, chromatographic separation utilised a Synergi polar column with a gradient mobile phase program consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection and quantification was performed using a TSQ Quantum Ultra triple quadrupole mass spectrometer. The analytical method was used to evaluate NRTI drug levels in HIV-positive nursing mothers-infant pairs. Results: The assay was validated over the concentration range of16.6–5000 ng/mL for 3TC, FTC and TFV inDBS and DBMS except for TFV in DBMS where linearity was established from 4.2–1250 ng/mL. Intra and inter-day precision (%CV) ranged from 3.5–8.7 and accuracy was within 15% for all analytes in both matrices. The mean recovery in DBS was>61% and in DBMS>43% for all three analytes. Matrix effect was insignificant. Median AUC0-8 values in maternal DBS and DBMS, respectively, were 4683 (4165–6057) and 6050 (5217–6417) ng h/mL for 3TC, 3312 (2259–4312) and 4853 (4124–6691) ng h/mL for FTC and 1559 (930–1915) and 56 (45–80) ngh/mL for TFV. 3TC and FTC were quantifiable (>16.6 ng/mL) in DBS from 2/6 and 1/6 infants respectively whereas TFV was undetectable in all infants. Conclusions: DBS and DBMS sampling for bioanalysis of 3TC, FTC and TFV is straightforward, robust, accurate and precise, and ideal for use in low-resource settings. |
