Elsevier

The Lancet

Volume 384, Issue 9947, 13–19 September 2014, Pages 1005-1070
The Lancet

Articles
Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

https://doi.org/10.1016/S0140-6736(14)60844-8Get rights and content

Summary

Background

The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

Methods

To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010–13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

Findings

Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

Interpretation

Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. Incidence rates for HIV, tuberculosis, and malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

Funding

Bill & Melinda Gates Foundation.

Introduction

The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal 6 (MDG 6). The high priority status of these three diseases in the development community was confirmed through the creation of the Global Fund to Fight AIDS, Tuberculosis and Malaria in 2002. Bilateral initiatives such as the President's Emergency Plan for AIDS Relief and the President's Malaria Initiative also added substantial new resources. From 2000 to 2011, multilaterals, bilaterals, foundations, and non-governmental organisations have invested US$51·6 billion for HIV, $11·3 billion for malaria, and $8·3 billion for tuberculosis (price in 2011 US dollars) in development assistance for health (DAH).1 Substantial benefits of these investments have been documented in several studies.2, 3, 4, 5, 6, 7, 8, 9 In the lead up to the MDG deadline of 2015 and amid the global debate on development goals post-2015, important questions have been raised about the advantages and disadvantages of maintaining focus on these three diseases.5, 10, 11, 12, 13, 14, 15, 16, 17, 18 The rise of the importance of non-communicable diseases in some regions of the developing world19, 20, 21, 22, 23, 24, 25, 26 have led to calls for goals that cover a broader range of diseases.10, 15, 17, 19, 20, 24, 25, 27, 28 At the same time, ambitious goals of zero tuberculosis incidence and deaths and zero HIV incidence and deaths have been formulated by some groups;29, 30, 31, 32, 33, 34 the Secretary-General of the UN had already established a goal of zero malaria deaths by 2015.35 Understanding the distribution and trends of these three diseases and how they have been affected by the MDG era is an important input to this wider debate.12, 36

Because of their prominence, there are major UN efforts on an annual basis to track the epidemiology of these three diseases. UNAIDS now produces country estimates of HIV incidence, prevalence, and death every year.37 Over many years, they have developed a sophisticated modelling approach to track the epidemic—their primary input in generalised epidemics is annual antenatal clinic serosurveillance data and periodic household surveys that include blood testing.38, 39 The annual Global Tuberculosis Report from the World Health Organization (WHO) provides estimates of incidence and deaths from tuberculosis by country. Crucial inputs to the assessment of incidence are case notifications and national expert opinion on the case-detection rate, and separate modelling of cause of death data from vital registration systems and verbal autopsy studies. For the World Malaria Report, WHO uses a complicated strategy to estimate incidence and mortality that varies by region and age group. For child malaria deaths in sub-Saharan Africa, the main inputs are verbal autopsy studies and estimated malaria risk. Estimates are adjusted post-hoc for coverage of insecticide-treated bednets (ITNs). Outside of sub-Saharan Africa and for low-transmission countries in Africa reported case numbers are combined with an assumed case-fatality rate. These three efforts have provided important insights into the geographical distribution and likely trends in the diseases.

Despite these efforts, extraordinary uncertainty exists at the country-level in the burden of all three. The burdens of HIV and malaria are concentrated in sub-Saharan Africa; countries that, other than South Africa, have very poor vital registration and incomplete notification systems. Tuberculosis is concentrated in Asia and southern Africa where a few more countries have better data systems but there are still huge gaps in information. Modelling strategies for tracking the diseases have evolved to be necessarily complex in view of the incomplete and often conflicting nature of the data. For HIV and malaria, UN modelling efforts explicitly use information about intervention delivery and assumed benefits of intervention. The distinction between data for disease outcomes and data for intervention coverage driving the results of these efforts is blurred. In the more complex modelling strategies, the compounded effect of uncertainty about different parameters can be hard to characterise. Efforts to model the three diseases are largely independent of each other—the exception is recent coordinated efforts to understand the intersection of tuberculosis and HIV.40

The Global Burden of Disease 2010 Study provided a comprehensive update on levels and trends of a large number of diseases, injuries, and risk factors for 187 countries from 1990 to 2010.41, 42, 43, 44, 45, 46, 47, 48 The Global Burden of Disease collaboration is now generating annual updates, the first of which is the Global Burden of Disease, Injuries, and Risk Factors Study 2013 (GBD 2013). The GBD 2013 provides an opportunity to examine the evidence on the levels and trends in the three MDG 6 diseases within the comprehensive and coherent framework of the GBD. Compared with GBD 2010, we have given special emphasis in the GBD 2013 to incorporate new data, to more rigorously identify and incorporate further key sources of uncertainty, and to incorporate adjustments for the biases that are present in different data sources. A crucial aspect of the GBD effort is to quantify time trends; comparing trends from 1990 to 2000 and from 2000 to 2013 provides an opportunity to see if there has been accelerated progress since the Millennium Declaration. The GBD 2013 supersedes all previously published GBD results.

Section snippets

Overview

The overall conceptual and analytical framework for the GBD is described elsewhere.41, 42, 43, 44, 45, 46, 47, 48 Major refinements of the analytical approach for different diseases and risk factors are explored in other papers.49, 50, 51 We summarise here the methods used for the analysis of the three diseases, emphasising refinements since the GBD 2010. All refinements in methods have been applied to the full 1990–2013 time series to ensure comparability of results. Metadata for input sources

Results

Figure 7 shows the estimated trend in global numbers of incident cases, people living with HIV (prevalence), and deaths from HIV. Global HIV incidence peaked in 1997 with 2·8 million (95% uncertainty intervals 2·7 to 3·1) new infections and has since decreased at 2·7% (2·0 to 3·1) per year. From 1997 to 2005, incidence decreased at 3·8% (3·0 to 4·6) per year and from 2005 to 2013 at 1·6% (0·6 to 2·4) per year. New infections in children decreased from 340 000 (323 000 to 363 000) in 2000 to

Discussion

HIV, tuberculosis, and malaria remain major health challenges in 2013. The mean age of death differs substantially between them, at 15·3 years for malaria, 38·6 years for HIV, and 52·9 years for tuberculosis in HIV-negative individuals, which means that the burden in terms of years of life lost varies across the diseases. Tuberculosis deaths have decreased globally since 1990, and after 2000 incidence, prevalence, and death have all decreased. HIV incidence peaked in 1997 and mortality peaked

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