Review Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment Elizabeth L Corbett, Barbara Marston, Gavin J Churchyard, Kevin M De Cock Lancet 2006; 367: 926–37 Rapid scale-up of antiretroviral treatment programmes is happening in Africa, driven by international advocacy and London School of Hygiene and policy directives and supported by unprecedented donor funding and technical assistance. This welcome Tropical Medicine, London development offers hope to millions of HIV-infected Africans, among whom tuberculosis is the major cause of WC1E 7HT, UK (E L Corbett PhD, serious illness and death. Little in the way of HIV diagnosis or care was previously offered to patients with Prof G J Churchyard PhD, K M De Cock MD); Biomedical tuberculosis, by either national tuberculosis or AIDS control programmes, with tuberculosis services focused Research and Training exclusively on diagnosis and treatment of rising numbers of patients. Tuberculosis control in Africa has yet to adapt Institute, Harare, Zimbabwe to the new climate of antiretroviral availability. Many barriers exist, from drug interactions to historic differences in (E L Corbett); Centers for the way that tuberculosis and HIV are perceived, but failure to successfully integrate HIV and tuberculosis control Disease Control and Prevention, Nairobi, Kenya will threaten the viability of both programmes. Here, we review tuberculosis epidemiology in Africa and policy (B Marston MD, K M De Cock); implications of HIV/AIDS treatment scale-up. and Aurum Health, Johannesburg, South Africa “Nothing endures but change” greatly affect tuberculosis control, hopefully for the better (G J Churchyard) but possibly for the worse.5 Patients with HIV-related Correspondence to: Heraclites, c535–c475 BC Dr Liz Corbett, Biomedical tuberculosis must make up a substantial proportion of Research and Training Institute, Although we view tuberculosis as one disease, and those reached by antiretroviral treatment. Important National Institute of Health Mycobacterium tuberculosis alone as its cause, four philosophical and practical changes to address HIV and Research, Josiah Tongogara epidemiological patterns can be usefully distinguished. tuberculosis in a coordinated manner will be needed if Avenue, P O Box CY 1753, Causeway, Harare, Zimbabwe So-called traditional tuberculosis in developing countries the increased tuberculosis incidence that has afflicted [email protected] with low rates of HIV infection responds to well- Africa during the past decade is to be reversed. organised control programmes.1 Tuberculosis in the industrialised world is increasingly attributable to 200 immigration, whereas high rates of multidrug resistance threaten control in parts of eastern Europe.2 Finally, HIV- related disease has emerged as the dominant challenge in sub-Saharan Africa (hereafter referred to as Africa),3,4 150 with the size of the epidemic calling for a response beyond the traditional boundaries of tuberculosis control. Increasing access to antiretroviral treatment in Africa, an unimaginable aspiration a few years ago, is now an international priority. The global importance of 100 tuberculosis and its association with the HIV/AIDS US$ pandemic are acknowledged by the Millennium Development Goals, and unprecedented funds are being provided by the Global Fund to Fight AIDS, 50 Tuberculosis, and Malaria, the US President’s Emergency Plan for AIDS Relief, and the World Bank’s multicountry HIV/AIDS programme (figure 1). In this Review, we discuss current understanding of 0 tuberculosis epidemiology and control policies in Africa. Malawi Gabon Kenya The new commitment to antiretroviral treatment will Lesotho Tanzania Namibia Zambia Zimbabwe BotswanaCameroonSwaziland South Africa Cote d´lvoireMozambique Search strategy and selection criteria Central African Republic Country Publications related to tuberculosis or antiretroviral treatment in Africa were identified by systematically searching PubMed and Google Scholar with terms including, but not Figure 1: Average donor support per person with HIV/AIDS for the 15 African restricted to, the following combinations: “tuberculosis Africa”, “tuberculosis HIV”, countries with the highest adult HIV prevalence in 2004 Donations calculated from the US President’s Emergency Plan for AIDS Relief, “tuberculosis antiretroviral”, “mortality/survival tuberculosis”. Further publications were the World Bank multicountry HIV/AIDS programme for Africa, and the Global identified from references cited in relevant articles, reports, and workshop and Fund for AIDS, Tuberculosis, and Malaria (excludes support for malaria). For conference proceedings. The search was restricted to publications in English, but not information about donations, see: restricted by date. http://www.worldbank.org/afr/aids/ map_docs.htm http://www.state.gov/s/gac/ http://www.theglobalfund.org/en/ 926 www.thelancet.com Vol 367 March 18, 2006 Review HIV and epidemiology of tuberculosis in Africa Burden of HIV/AIDS and tuberculosis Population 3 Figure 2 summarises the disproportionate burden of HIV-infected adults HIV and tuberculosis infection and disease in Africa at New tuberculosis cases the start of the new millennium.3 In 2003, an estimated 8·8 million new cases of tuberculosis resulted in HIV-infected new tuberculosis cases 4 1·7 million deaths. 27% of these cases and 31% of HIV/M tuberculosis coinfections these deaths arose in Africa, home to only 11% of the world’s population.4 HIV prevalence in tuberculosis Figure 2: Disproportionate burden of HIV, HIV-related tuberculosis, and M tuberculosis coinfections in Africa, patients is less than 1% in the Western Pacific region for 2000 but 38% in Africa.3 In countries with the highest HIV Every person represents 5% of the global total, with African people shown in red and the rest of the world in blue.3 prevalence, more than 75% of cases of tuberculosis are HIV-associated.4 Southern Africa has the highest prevalence of HIV In Africa, tuberculosis is often the first manifestation infection and had the highest incidence of tuberculosis of HIV infection, and it is the leading cause of death before the HIV/AIDS era. In the six southern African among HIV-infected patients.6–11 In hospital-based countries with adult HIV prevalence of more than 20%, series, 40–65% of HIV-infected African patients with tuberculosis case-notification rates are 461–719 per respiratory disease had tuberculosis.6,8 In primary health 100 000 per year; by comparison, the notification rate in and chest clinic settings, tuberculosis was confirmed in the USA was 5 per 100 000 per year.4 True yearly rates in 43–70% of adults with cough for 3 weeks or longer Africa are likely to be even higher because of under- (chronic cough) in Zimbabwe, Kenya, and Malawi.12,13 diagnosis and under-reporting.4 Patients with tuberculosis now commonly present with atypical symptoms: M tuberculosis was isolated from 9% HIV and infectiousness and transmission of tuberculosis of adults with acute pneumonia in Kenya,14 35% of The critical period with respect to infectiousness is people with cough for less than 3 weeks in Malawi,15 before diagnosis, because most patients become non- 23% of febrile HIV-infected inpatients in Tanzania,16 infectious soon after starting treatment, even if they are and 13% of HIV-infected patients with chronic HIV-infected.22 Both intensity and duration of diarrhoea in Kenya.17 In Cote d’Ivoire, the Democratic infectiousness are highly variable, with some individuals Republic of Congo, and Kenya, 38–47% of autopsies in remaining very infectious for prolonged periods, HIV-positive adults indicated tuberculosis as the cause sometimes with apparently minor symptoms.23–26 HIV- of death,9–11 although tuberculosis had been diagnosed positive individuals with tuberculosis are less infectious during life in only about half of those with autopsy- than HIV-negative patients since they are less often and proven disease. Increased risk for tuberculosis from HIV infection in 80 Africa MAL Comparison of HIV prevalence in general populations ETH ZIM and tuberculosis patients shows that tuberculosis BOT incidence was 8·3 times higher in HIV-positive than 60 KEN SOA LES HIV-negative African people in 2003 (figure 3).4,18 In CAF 2000, similar methods led to an estimated relative rate IVC BUU of 5·9, whereas estimates from individual cohort TAN BFA HAI IVC studies range from less than 5 to more than 20.3 40 COD CAE RWA KEN Tuberculosis incidence increases with worsening MOZ BFA immunosuppression, so that relative rates rise during NIE 19–21 GHA the course of an HIV epidemic. DJI 20 DJI Tuberculosis incidence in African countries with high Measured prevalence of HIV in tuberculosis (%) CNG HIV prevalence CAM Reported tuberculosis case rates rose by 6·4% per year in the WHO African region in the late 1990s,4 but with 0 up to five-fold increases since 1990 in some countries.4 0 10 20 30 40 Incidence might have peaked in some countries Estimated prevalence of HIV in adults (%) (figure 4)18 but at very high rates. The high case rate in Africa contributed to a global rise in tuberculosis Figure 3: Estimated prevalence of HIV in tuberculosis patients Prevalence measured in national surveys (blue dots) and subnational surveys (red dots; data reported to WHO),4 incidence of 1% in 2003, despite stable or declining plotted against prevalence of HIV in adults (data from UNAIDS).18 Country abbreviations available from rates in the rest of the world.4 reference 4. Figure kindly