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Interaction of malaria and HIV in Africa

Is well known at a biological and health systems level, but often ignored.

Malaria and HIV/AIDS are two of the most important infectious diseases worldwide, accounting for almost 9% of the total burden of disease in sub-Saharan Africa (1). There is good evidence of a biological interaction between them, but their combined impact on health systems is even more substantial, especially in Africa. This is often ignored.

Evidence for a biological interaction in people who are co-infected has grown. Until 1998 there was "no convincing evidence for an interaction between malaria and HIV." (2) By 2006 it was estimated that the interaction of malaria and HIV in one Kenyan district alone had caused 980 000 excess malaria episodes and 8 500 excess HIV infections since HIV’s emergence in the 1980s (3). Malaria is more common and severe in adults with HIV, pregnant women, and children (4). HIV viral load is greater in women with placental malaria, and infants born to women with both HIV and placental malaria are of greater risk of premature delivery, low birth weight, or death compared with infants born to women with HIV infection alone. Malaria causes increased HIV viral load in blood and breast milk and reduced CD4 cell count (4). Malaria treatment is less effective in non-pregnant adults with HIV (5).

Nonetheless, research into malaria and HIV continues to be largely separate. A global policy document about co-infection with malaria and HIV was released by the World Health Organization in 2005 (1), but little has been done since, and other potential biological interactions have rarely been properly assessed.

Although the biological interaction between malaria and HIV is becoming increasingly evident, what is the interaction at health systems level? Worldwide, malaria and HIV/AIDS prevention and control programmes are being scaled up because of a welcome increase in support for both diseases. However, operational malaria and HIV/AIDS programmes continue to be planned separately, despite having a substantial impact on one another. One of the impacts is on human resources. In Africa and to a lesser extent in Asia and Latin America, the shortage of experienced healthcare staff means that the same health personnel are expected to deliver the scaled up programmes for both diseases, yet there is seldom joint planning.

The diagnostic strategy needs to be coordinated. Diagnosis of acute febrile illness is made more complex for each disease by the fact that the other is common. Presentations of HIV related bacterial disease and malaria can be very similar in adults and children, yet this is often ignored in expert guidance. Meningitis, non-typhi salmonella, and pneumonia can all be misdiagnosed as malaria. Diagnostic strategies designed by malaria experts commonly insist that all fever is treated as malaria; similarly, strategies designed by HIV specialists fail to mention malaria. This is potentially damaging and a missed opportunity. For example, adults presenting with malaria often have a greater HIV seroprevalence than the general population. Even if malaria is suspected in those patients, it provides a good opportunity to promote HIV testing and counselling (6).

Preventive strategies used for one disease are also often planned without regard for the other, although the impact can be positive or negative depending how it is deployed. Co-trimoxazole, a drug used to treat and prevent opportunistic infections in patients with HIV, reduces the risk of clinical malaria in adults and children infected with HIV by 70% if given alone (7), and up to 95% when combined with antiretroviral drugs and use of bednets treated with insecticide (8). In many operational settings cotrimoxazole has replaced intermittent preventive therapy with sulphadoxine-pyramethamine in pregnant women with HIV despite there being no published data on the efficacy of the drugs in preventing placental malaria.

The risk of interactions between drugs for the two diseases has only recently begun to be tackled, albeit current evidence indicates dangerous interactions between antiretrovirals and some artemisinin based combination treatment for malaria (5). Thus, a high risk of neutropenia was seen in HIV infected children receiving antiretrovirals and amodiaquine-artesunate (9). The relatively high rates of non-malarial causes of fever in people with HIV combined with a reduction in the risk of malaria with cotrimoxazole prophylaxis imply that presumptive treatment for malaria should be avoided in African adults with HIV or children with HIV who take cotrimoxazole prophylaxis until we know more.

These are just some examples of the interactions between malaria and HIV in pregnant and non-pregnant adults and children in Africa at biological, case management, and health systems levels. It is time for the development of a comprehensive operational research and policy strategy to tackle key knowledge gaps regarding malaria and HIV co-infection. In the context of continuing availability of resources this in turn will support the integration of interventions for both diseases, maximising their impact and cost effectiveness. Health systems can then be strengthened rather than overloaded within the typically "vertically" managed worlds of malaria and HIV/AIDS prevention and control.

Cite this as:BMJ 2009;338:b2141

Richard Reithinger, honorary lecturer1, Moses R Kamya, professor2, Christopher JM Whitty, professor3, Grant Dorsey, associate professor4, Sten H Vermund, director of the institute and professor of pediatrics5

1 London School of Hygiene and Tropical Medicine, London, 2 Medical School, Makerere University, Kampala, Uganda, 3 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK, 4 Department of Medicine, University of California San Francisco, California, USA, 5 Institute for Global Health and Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA

Correspondence to: R Reithinger

Competing interests: None declared.

Provenance and peer review: Not commissioned; externally peer reviewed.

References1. World Health Organization. Malaria and HIV interactions and their implications for public health policy. Geneva: WHO, 2005. 2. Chandramohan D, Greenwood BM. Is there an interaction between human immunodeficiency virus and Plasmodium falciparum? Int J Epidemiol 1998;27:296-301.[Abstract/Free Full Text] 3. Abu-Raddad LJ, Patnaik P, Kublin JG. Dual infection with HIV and malaria fuels the spread of both diseases in sub-Saharan Africa. Science 2006;314:1603-6.[Abstract/Free Full Text] 4. Laufer MK, Plowe CV. The interaction between HIV and malaria in Africa. Curr Infect Dis Reports 2007;9:47-54.5. Khoo S, Back D, Winstanley P. The potential for interactions between antimalarial and antiretroviral drugs. AIDS 2005;19:995-1005.6. Bebell LM, Gasasira A, Kiggundu M, Dokomajilar C, Kamya MR, Charlebois ED, et al. HIV-1 infection in patients referred for malaria blood smears at government health clinics in Uganda. J AIDS 2007;46:624-30.7. Mermin J, Lule J, Ekwaru JP, Malamba S, Downing R, Ransom R, et al. Effect of cotrimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Lancet 2004;364:1428-34.8. Mermin J, Ekwaru JP, Liechty CA, Were W, Downing R, Ransom R, et al. Effect of cotrimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study. Lancet 2006;367:1256-61.9. Gasasira AF, Kamya MR, Achan J, Mebrahtu T, Kalyango JN, Ruel T, et al. High risk of neutropenia in HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda. Clin Infect Dis 2008;46:985-91.

Source: BMJ