Journal Article > LetterFull Text
Clin Infect Dis. 20 March 2024; Volume 78 (Issue 3); 800-801.; DOI:10.1093/cid/ciad459
Schomaker M, Kerschberger B, Boulle A
Clin Infect Dis. 20 March 2024; Volume 78 (Issue 3); 800-801.; DOI:10.1093/cid/ciad459
Journal Article > ResearchFull Text
Trop Med Int Health. 1 March 2024; Volume 29 (Issue 3); 192-205.; DOI:10.1111/tmi.13961
Kerschberger B, Vambe D, Schomaker M, Mabhena E, Daka M, et al.
Trop Med Int Health. 1 March 2024; Volume 29 (Issue 3); 192-205.; DOI:10.1111/tmi.13961
OBJECTIVES
Despite declining TB notifications in Southern Africa, TB‐related deaths remain high. We describe patient‐ and population‐level trends in TB‐related deaths in Eswatini over a period of 11 years.
METHODS
Patient‐level (retrospective cohort, from 2009 to 2019) and population‐level (ecological analysis, 2009–2017) predictors and rates of TB‐related deaths were analysed in HIV‐negative and HIV‐coinfected first‐line TB treatment cases and the population of the Shiselweni region. Patient‐level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient‐level and population‐level predictors of deaths.
RESULTS
Of 11,883 TB treatment cases, 1,302 (11.0%) patients died during treatment: 210/2,798 (7.5%) HIV‐negative patients, 984/8,443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV‐status. The treatment case fatality ratio remained above 10% in most years. At patient‐level, fatality risk was higher in PLHIV (aRR 1.74, 1.51–2.02), and for older age and extra‐pulmonary TB irrespective of HIV‐status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18–1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47–1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB‐LAM testing (aRR 0.65, 0.35–0.90). At population‐level, mortality rates decreased 6.4‐fold (−147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2,785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (−826/100,000 vs. HIV‐negative: −23/100,000), the relative population‐level mortality risk remained higher in PLHIV (aRR 4.68, 3.25–6.72) compared to the HIV‐negative population.
CONCLUSIONS
TB‐related mortality rapidly decreased at population‐level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.
Despite declining TB notifications in Southern Africa, TB‐related deaths remain high. We describe patient‐ and population‐level trends in TB‐related deaths in Eswatini over a period of 11 years.
METHODS
Patient‐level (retrospective cohort, from 2009 to 2019) and population‐level (ecological analysis, 2009–2017) predictors and rates of TB‐related deaths were analysed in HIV‐negative and HIV‐coinfected first‐line TB treatment cases and the population of the Shiselweni region. Patient‐level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient‐level and population‐level predictors of deaths.
RESULTS
Of 11,883 TB treatment cases, 1,302 (11.0%) patients died during treatment: 210/2,798 (7.5%) HIV‐negative patients, 984/8,443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV‐status. The treatment case fatality ratio remained above 10% in most years. At patient‐level, fatality risk was higher in PLHIV (aRR 1.74, 1.51–2.02), and for older age and extra‐pulmonary TB irrespective of HIV‐status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18–1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47–1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB‐LAM testing (aRR 0.65, 0.35–0.90). At population‐level, mortality rates decreased 6.4‐fold (−147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2,785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (−826/100,000 vs. HIV‐negative: −23/100,000), the relative population‐level mortality risk remained higher in PLHIV (aRR 4.68, 3.25–6.72) compared to the HIV‐negative population.
CONCLUSIONS
TB‐related mortality rapidly decreased at population‐level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.
Journal Article > LetterSubscription Only
Clin Infect Dis. 5 August 2023; ciad459.; DOI:10.1093/cid/ciad459
Schomaker M, Kerschberger B, Boulle AM
Clin Infect Dis. 5 August 2023; ciad459.; DOI:10.1093/cid/ciad459
Protocol > Research Protocol
Fernandez MAL, Schomaker M, Mason PR, Fesselet JF, Baudot Y, et al.
18 June 2012
BACKGROUND
In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009.
METHODS
We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs.
RESULTS
This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%.
CONCLUSION
This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.
In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009.
METHODS
We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs.
RESULTS
This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%.
CONCLUSION
This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.
Journal Article > ResearchFull Text
PLOS Med. 9 September 2014; Volume 11 (Issue 9); e1001718.; DOI:10.1371/journal.pmed.1001718
Boulle AM, Schomaker M, May MT, Hogg RS, Shepherd B, et al.
PLOS Med. 9 September 2014; Volume 11 (Issue 9); e1001718.; DOI:10.1371/journal.pmed.1001718
BACKGROUND
High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
METHODS AND FINDINGS
Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.
CONCLUSIONS
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.
High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America.
METHODS AND FINDINGS
Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0–3, 3–6, 6–12, 12–24, and 24–48 months on ART for the period 2001–2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37–0.58, and 1.62, 95% CI 1.27–2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage.
CONCLUSIONS
After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts.
Journal Article > ResearchAbstract
J Acquir Immune Defic Syndr. 22 January 2013; Volume 63 (Issue 1); DOI:10.1097/QAI.0b013e318287c1fe
Hoffman CJ, Schomaker M, Fox MP, Mutevedzi, Giddy J, et al.
J Acquir Immune Defic Syndr. 22 January 2013; Volume 63 (Issue 1); DOI:10.1097/QAI.0b013e318287c1fe
In many resource-limited settings monitoring of combination antiretroviral therapy (cART) is based on the current CD4 count, with limited access to HIV RNA tests or laboratory diagnostics. We examined whether the CD4 count slope over 6 months could provide additional prognostic information.
Journal Article > ResearchFull Text
Int J Epidemiol. 24 June 2016; DOI:10.1093/ije/dyw097
Schomaker M, Leroy V, Wolfs T, Technau KG, Renner L, et al.
Int J Epidemiol. 24 June 2016; DOI:10.1093/ije/dyw097
Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
Journal Article > ResearchFull Text
J Int AIDS Soc. 3 March 2020; Volume 23 (Issue 3); DOI:10.1002/jia2.25458
Kerschberger B, Schomaker M, Jobanputra K, Kabore SM, Teck R, et al.
J Int AIDS Soc. 3 March 2020; Volume 23 (Issue 3); DOI:10.1002/jia2.25458
INTRODUCTION:
The Treat-All policy - antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria - increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini.
METHODS:
This is a prospective cohort study of ≥16-year-old HIV-positive patients initiated on first-line ART under Treat-All and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/mm3 treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure.
RESULTS:
Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/mm3 compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 ≤ 100 cells/mm3 . Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine.
CONCLUSIONS:
Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure.
The Treat-All policy - antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria - increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini.
METHODS:
This is a prospective cohort study of ≥16-year-old HIV-positive patients initiated on first-line ART under Treat-All and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/mm3 treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure.
RESULTS:
Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/mm3 compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 ≤ 100 cells/mm3 . Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine.
CONCLUSIONS:
Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure.
Journal Article > ResearchFull Text
BMC Public Health. 18 June 2012; Volume 12 (Issue 1); 442.; DOI:10.1186/1471-2458-12-442
Fernandez MAL, Schomaker M, Mason PR, Fesselet JF, Baudot Y, et al.
BMC Public Health. 18 June 2012; Volume 12 (Issue 1); 442.; DOI:10.1186/1471-2458-12-442
BACKGROUND
In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009.
METHODS
We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs.
RESULTS
This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%.
CONCLUSION
This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.
In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009.
METHODS
We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs.
RESULTS
This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%.
CONCLUSION
This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic.
Journal Article > ResearchAbstract
Epidemiology. 16 October 2015; DOI:10.1097/EDE.0000000000000412
Schomaker M, Davies A, Malateste K, Renner L, Sawry S, et al.
Epidemiology. 16 October 2015; DOI:10.1097/EDE.0000000000000412