Across 41 countries in sub-Saharan Africa, the HIV-1 epidemic may have increased the incidence of clinical malaria by 1.3% (95% CI 0.6%–7.9%) and malaria deaths by 4.9% (95% CI 3.1%–17.1%) in 2004. Continentwide impact was limited by the different geographic distributions of the 2 diseases and their different age patterns.
For southern Africa, estimated proportional increases were <28% (95% CI 14%–47%) for malaria incidence and <114% (95% CI 37%–188%) for malaria deaths. An impact of HIV-1 of this magnitude may have contributed to observed increases of malaria in the 1990s in areas of unstable transmission, including Kwa-Zulu Natal (13,14
) and northern Zambia (15
). Outside southern Africa, however, HIV-1 is unlikely to be a major contributor to rises in malaria, and where this appears to be so, a more plausible explanation may be overdiagnosis of fevers as malaria in HIV-1 patients. Such over-diagnosis may occur unintentionally in settings where malaria is diagnosed without parasitologic confirmation because of the increased frequency of acute fevers in HIV-1 patients (10
). Intentional misdiagnosis could also occur, if doctors are reluctant to diagnose illness as HIV-related for fear of social stigma.
These estimates have several limitations. First, the magnitude of effects of HIV-1 on malaria incidence and death risk in individual patients is critical () but uncertain because of diagnostic problems in settings of high malaria transmission and a lack of population-based data from areas of low intensity and unstable transmission.
Second, results are sensitive to age patterns in malaria (), which are not well known. The sharp contrast in estimated impact of HIV-1 between the 5 southern African countries and the remainder of Africa depends on the assumption that malaria declines more slowly with age in South Africa, where all malaria is assumed to be unstable. In practice, the shift from unstable to stable malaria transmission, i.e., from clinical effects in all age groups to a predominance in young children, is more gradual; thus, effects of HIV on malaria in Zimbabwe and Zambia, for example, may be more similar than we estimated. The estimation method developed here could, nevertheless, be applied to more refined age-specific estimates of malaria incidence and death.
Finally, subnational heterogeneity in malaria or HIV, apart from urban/rural differences, was not considered, and this fact may have biased the estimation for countries where either or both diseases are heterogeneously distributed, such as Kenya, Ethiopia, Tanzania, and South Africa (42
). For example, in South Africa, both malaria and HIV-1 are concentrated in Kwa-Zulu Natal, so that their interaction may be greater than our estimate.
The impact of HIV-1 that we have estimated only pertains to malaria cases and deaths and does not include effects on anemia or adverse birth outcomes attributable to concurrent malaria and HIV-1 in pregnant women. In areas of high-intensity transmission, such as in Kenya and Malawi, the latter effects might be more important than malaria cases and deaths per se. Also, our analysis did not cover the effect of HIV-1 on demand for antimalarial drugs. In most of rural Africa, antimalarial drugs are presumptively prescribed to treat any fever without an obvious nonmalarial cause. Recurrent fevers in HIV-1 patients may, therefore, cause considerable overuse of antimalarial drugs, increasing not only costs but also the risk for drug resistance. The HIV-1 epidemic thus underlines the need to improve capacity for laboratory diagnosis of febrile disease in Africa.
To limit the impact of HIV-1 on malaria, HIV-infected persons, in addition to young children and pregnant women, may form a target group for provision of insecticide-treated mosquito nets (2
). In areas of low intensity and unstable transmission, HIV may be a reason for intensifying or resuming indoor residual spraying to control malaria vectors. For HIV-infected persons who are prone to treatment failure with conventional antimalarial drugs (27,32,33,43
), effective combination therapy is of utmost importance.
Highly active antiretroviral combination therapy has great potential to reduce HIV-related malaria (44
). Cotrimoxazole prophylaxis, recommended for adults and children living with HIV in Africa (45
), is also effective in reducing clinical malaria, independent of baseline CD4 (41,46,47
). Combined HIV and malaria interventions might best be delivered at peripheral health centers, including antenatal clinics (2
HIV-1 appears to have increased the impact of malaria disease and death in South Africa compared to the 1980s, although data do not allow a precise quantification of this effect. In areas of high HIV and low-intensity or unstable malaria, continued vigilance and intensified malaria control are indicated. In HIV-infected adults, pregnant women, and children, malaria is among the simplest opportunistic infections to prevent and treat.