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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

ABSTRACT: BACKGROUND:Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART. METHODS AND FINDINGS:Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness. CONCLUSIONS:ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality.

SUBMITTER: Johnson LF

PROVIDER: S-EPMC5726614 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

Johnson Leigh F LF May Margaret T MT Dorrington Rob E RE Cornell Morna M Boulle Andrew A Egger Matthias M Davies Mary-Ann MA

PLoS medicine 20171212 12

<h4>Background</h4>Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART.<h4>M ...[more]

PMID: 29232366

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Project description:BackgroundMpumalanga in South Africa is committed to eliminating malaria by 2018 and efforts are increasing beyond that necessary for malaria control. Differential Equation models may be used to study the incidence and spread of disease with an important benefit being the ability to enact exogenous change on the system to predict impact without committing any real resources. The model is a deterministic non-linear ordinary differential equation representation of the dynamics of the human population. The model is fitted to weekly data of treated cases from 2002 to 2008, and then validated with data from 2009 to 2012. Elimination-focused interventions such as the scale-up of vector control, mass drug administration, a focused mass screen and treat campaign and foreign source reduction are applied to the model to assess their potential impact on transmission.ResultsScaling up vector control by 10% and 20% resulted in substantial predicted decreases in local infections with little impact on imported infections. Mass drug administration is a high impact but short-lived intervention with predicted decreases in local infections of less that one infection per year. However, transmission reverted to pre-intervention levels within three years. Focused mass screen and treat campaigns at border-entry points are predicted to result in a knock-on decrease in local infections through a reduction in the infectious reservoir. This knock-on decrease in local infections was also predicted to be achieved through foreign source reduction. Elimination was only predicted to be possible under the scenario of zero imported infections in Mpumalanga.ConclusionsA constant influx of imported infections show that vector control alone will not be able to eliminate local malaria as it is insufficient to interrupt transmission. Both mass interventions have a large and immediate impact. Yet in countries with a large migrant population, these interventions may fail due to the reintroduction of parasites and their impact may be short-lived. While all strategies (in isolation or combined) contributed to decreasing local infections, none was predicted to decrease local infections to zero. The number of imported infections highlights the importance of reducing imported infections at source, and a regional approach to malaria elimination.

Project description:BackgroundMultidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa.MethodsWe calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa.FindingsThe model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040.InterpretationMDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis.FundingUS Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination.

Project description:BACKGROUND:Measuring and monitoring progress towards Millennium Development Goals (MDG) 4 and 5 required valid and reliable estimates of maternal and child mortality. In South Africa, there are conflicting reports on the estimates of maternal and neonatal mortality, derived from both direct and indirect estimation techniques. This study aimed to systematically review the estimates made of maternal and neonatal mortality in the period from 1990 to 2015 in South Africa and determine trends over this period. METHODS:Nationally-representative studies reporting on maternal and neonatal mortality in South Africa were included for synthesis. Literature search for eligible studies was conducted in five electronic databases: Medline, Africa-Wide Information, Scopus, Web of Science and CINAHL. Searches were restricted to articles written in English and presenting data covering the period between 1990 and 2015. Reference lists of retrieved articles were screened for additional publications, and grey literature was searched for relevant documents for the review. Three independent reviewers were involved in study selection, data extractions and achieving consensus. RESULTS:In total, 969 studies were retrieved and 670 screened for eligibility yielding 25 studies reporting data on maternal mortality and 14 studies on neonatal mortality. Most of the studies had a low risk of bias. Estimates from the institutional reporting differed from the international metrics with wide uncertainty/confidence intervals. Moreover, modelled estimates were widely divergent from estimates obtained through empirical methods. In the last two decades, both maternal and neonatal mortality appear to have increased up to 2009, followed by a decrease, more pronounced in the care of maternal mortality. CONCLUSION:Estimates from both global metrics and institutional reporting, although widely divergent, indicate South Africa has not achieved MDG 4a and 5a goals but made a significant progress in reducing maternal and neonatal mortality. To obtain more accurate estimates, there is a need for applying additional estimation techniques which utilise available multiple data sources to correct for underreporting of these outcomes, perhaps the capture-recapture method. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42016042769.

Project description:ObjectivesTo develop a regional model of COVID-19 dynamics for use in estimating the number of infections, deaths and required acute and intensive care (IC) beds using the South West England (SW) as an example case.DesignOpen-source age-structured variant of a susceptible-exposed-infectious-recovered compartmental mathematical model. Latin hypercube sampling and maximum likelihood estimation were used to calibrate to cumulative cases and cumulative deaths.SettingSW at a time considered early in the pandemic, where National Health Service authorities required evidence to guide localised planning and support decision-making.ParticipantsPublicly available data on patients with COVID-19.Primary and secondary outcome measuresThe expected numbers of infected cases, deaths due to COVID-19 infection, patient occupancy of acute and IC beds and the reproduction ('R') number over time.ResultsSW model projections indicate that, as of 11 May 2020 (when 'lockdown' measures were eased), 5793 (95% credible interval (CrI) 2003 to 12 051) individuals were still infectious (0.10% of the total SW population, 95% CrI 0.04% to 0.22%), and a total of 189 048 (95% CrI 141 580 to 277 955) had been infected with the virus (either asymptomatically or symptomatically), but recovered, which is 3.4% (95% CrI 2.5% to 5.0%) of the SW population. The total number of patients in acute and IC beds in the SW on 11 May 2020 was predicted to be 701 (95% CrI 169 to 1543) and 110 (95% CrI 8 to 464), respectively. The R value in SW was predicted to be 2.6 (95% CrI 2.0 to 3.2) prior to any interventions, with social distancing reducing this to 2.3 (95% CrI 1.8 to 2.9) and lockdown/school closures further reducing the R value to 0.6 (95% CrI 0.5 to 0.7).ConclusionsThe developed model has proved a valuable asset for regional healthcare services. The model will be used further in the SW as the pandemic evolves, and-as open-source software-is portable to healthcare systems in other geographies.

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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

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Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

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