Malaria and HIV/AIDS share determinants of vulnerability. Given the wide geographical overlap in occurrence and the resulting prevalence of co-infection, the interaction between the two diseases clearly has major public health implications (1). In sub-Saharan Africa, around 300 million cases of malaria occur annually and an estimated 25 million adults and children are living with HIV/AIDS. In 2003 in Africa, HIV/AIDS claimed the lives of an estimated 2.2 million people (2), and malaria 1 million, especially children (3). In South-East Asia, Latin America and the Caribbean there is also significant overlap of these two diseases.
A8.1 Epidemiological overlaps between malaria and HIV/AIDS
The impact of the interaction of malaria and HIV/AIDS is most apparent in areas with generalized HIV/AIDS epidemics and stable malaria. Sub-Saharan Africa carries a high burden of both diseases, thus co-infection is common in many areas. In the most severely affected countries (Central African Republic, Malawi, Mozambique, Zambia and Zimbabwe), more than 90% of the population are exposed to malaria and the prevalence of HIV infection in adults is owep 10% (2). In contrast, southern Africa, which has a relatively low burden of malaria, is the worst affected subregion for HIV infection with prevalence as high as 30%. The frequent malaria epidemics in southern Africa may, however, increase the risk of dual infection.
In Latin America and the Caribbean, some overlap of malaria and HIV/AIDS occurs in the general population in Belize, Brazil, El Salvador, Guatemala, Guyana and Honduras. South-East Asian countries, such as Cambodia, Myanmar and Thailand, have a generalized HIV/AIDS epidemic but malaria distribution is heterogeneous in this region. Significant overlap is likely to occur in a number of Indian cities with urban malaria and increasing HIV transmission. Considering that an estimated one billion people in South-East Asia are exposed to unstable malaria, it is clear that even a small overlap of malaria and HIV/AIDS in these settings may have a large public health impact.
A8.2 Evidence of interactions between malaria and HIV/AIDS
A8.2.1 Impact of HIV/AIDS on malaria during pregnancy
There is substantial evidence of the effects of interactions between malaria and HIV/AIDS in pregnant women. HIV infection impairs the ability of pregnant women to control a P. falciparum infection (4, 5). They are more likely to develop clinical and placental malaria, more often have detectable malaria parasitaemia and have higher malaria parasite densities in peripheral blood (6, 7). Compared to women with either malaria or HIV infection, co-infected pregnant women are at increased risk of anaemia, preterm birth and intrauterine growth retardation (8, 9). As a result, children born to women with dual malaria and HIV infection are at high risk of low birth weight and death during infancy.
The presence of HIV/AIDS may result in a poorer response to treatment with antimalarials and to intermittent preventive treatment for malaria during pregnancy. Furthermore, there is a risk of adverse reactions if SP for the prevention of malaria in pregnant women and cotrimoxazole (a coformulation of trimethoprim and sulfamethoxazole) for prophylaxis against opportunistic infections are taken together, as both are sulfa-containing medicines.
A8.2.2 Impact of HIV/AIDS on malaria in non-pregnant adults
Evidence on interactions between malaria and HIV/AIDS in non-pregnant adults is accumulating. In areas with stable malaria, HIV infection increases the risk of malaria infection and clinical malaria in adults, especially in those with advanced immunosuppression (10-12). In settings with unstable malaria, HIV-infected adults with AIDS are at increased risk of severe malaria and death (13, 14). Antimalarial treatment failure may be more common in HIV-infected adults with low CD4 cell counts than in those not infected with HIV (15, 16).
A8.2.3 Effects of malaria on HIV infection
Acute malaria episodes cause a temporary increase in replication of HIV and hence in plasma viral load (17). However, so far there is no evidence that malaria has a substantial effect on the clinical progression of HIV infection, HIV transmission or response to antiretroviral treatment in areas where malaria and HIV overlap.
A8.2.4 HIV/AIDS and malaria in children
Few studies have examined the interaction of malaria and HIV/AIDS in children (18, 19). However, HIV-infected children with advanced immunosuppression may have more episodes of clinical malaria and higher parasite densities than those whose immune status is less compromised. In areas of unstable malaria, HIV-infected children may be more likely to experience severe disease or coma (20).
A8.2.5 Drug interactions
There are currently no documented clinical or pharmacological interactions between antimalarials and antiretrovirals. However, pharmacokinetic interactions between certain antimalarials and non-nucleoside reverse transcriptase inhibitors and protease inhibitors are theoretically possible and could lead to toxicity. This suggests that patients receiving protease inhibitors (and the non-nucleoside reverse transcriptase inhibitor delavirdine) should avoid halofantrine. Other antimalarials such as artemether-lumefantrine may also have the potential to interact with antiretrovirals.
Medicines used in the management of opportunistic infections in people living with HIV/AIDS may also interact with antimalarials (21). Interactions are possible between cotrimoxazole, which is used for prophylaxis of opportunistic infections, and S P, which is used for intermittent preventive treatment of malaria in pregnant women in some parts of Africa. It is recommended that SP should not be given if co-trimoxazole is being taken daily as this probably provides an equivalent antimalarial effect. While more research is required, emphasis should be placed on close monitoring and pharmacovigilance in the treatment of malaria and HIV/AIDS.
A8.3 Implications for health systems and service delivery
In HIV-infected individuals, the use of a malaria case definition based on fever alone can result in a febrile illness that may be due to a wide range of ordinary, virulent and opportunistic infections being misdiagnosed and treated as malaria (22, 23). This may lead to inappropriate care of HIV-infected adults with severe febrile illnesses due to causes other than malaria. With the use of more costly antimalarials, it has become necessary to give greater emphasis to parasitological diagnosis (24), and this is particularly important in areas of high prevalence of HIV infection.
In areas affected by malaria and HIV/AIDS, integrated health services are crucial for the introduction of new drugs and diagnostic materials, and offer opportunities for joint planning, training and service delivery.
A8.4 Key recommendations
WHO makes the following recommendations (25).
• HIV-infected pregnant women in areas with stable malaria should - depending on the stage of HIV infection - receive either intermittent preventive treatment for malaria with at least three doses of sulfadoxine-pyrimethamine or daily cotrimoxazole prophylaxis for HIV/AIDS opportunistic infections. Malarial illness in HIV-infected pregnant women who are receiving cotrimoxazole prophylaxis should be managed with non-sulfa antimalarials.
• In areas with stable malaria and a high prevalence of HIV infection, use of a fever-based malaria case definition may result in febrile illnesses caused by opportunistic infections being misdiagnosed as malaria, leading to overtreatment of malaria. Confirmatory parasitological testing for malaria should be applied with high priority in patients at risk of HIV/AIDS (in particular in older children and adults). In addition, health providers should offer HIV testing and counselling.
• In countries with generalized HIV/AIDS epidemics, routine monitoring of antimalarial drug efficacy or effectiveness should include assessment of the effect of HIV on antimalarial treatment outcomes.
• Further research should be undertaken to evaluate possible interactions between antimalarials and antiretrovirals, and pharmacovigilance should be introduced to monitor adverse drug reactions for both the new antimalarials and antiretrovirals.
1. Hay S et al. The global distribution and population at risk of malaria: past, present, and future. Lancet Infectious Diseases, 2004, 4:327-336.
2. UNAIDS 2004 report on the global AIDS epidemic. Geneva, Joint United Nations Programme on HIV/AIDS, 2004 (UNAIDS. Report on the global HIV/AIDS epidemic. June 2004).
3. Korenromp EL et al. Measurement of trends in childhood malaria mortality in Africa: an assessment of progress towards targets based on verbal autopsy. Lancet Infectious Diseases, 2003, 3:349-358.
4. Steketee RW et al. Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1. American Journal of Tropical Medicine and Hygiene, 1996, 55:42-49.
5. Ter Kuile F et al. The burden of co-infection with human immunodeficiency virus type 1 and malaria in pregnant women in sub-Saharan Africa. American Journal of Tropical Medicine and Hygiene, 2004, 71:41-54.
6. van Eijk et al. Human immunodeficiency virus seropositivity and malaria as risk factors for third-trimester anemia in asymptomatic pregnant women in western Kenya. American Journal of Tropical Medicine and Hygiene, 2001, 65:623-630.
7. van Eijk AM et al. The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya. AIDS, 2003, 17, 585-594.
8. Bloland PB et al. Maternal HIV infection and infant mortality in Malawi: evidence for increased mortality due to placental malaria infection. AIDS, 1995, 9:721-726.
9. Inion I et al. Placental malaria and perinatal transmission of human immunodeficiency virus type 1. Journal of Infectious Diseases, 2003, 188:1675-1678.
10. Leaver RJ, Haile Z, Watters DA. HIV and cerebral malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1990, 84:201.
11. Niyongabo T et al. Prognostic indicators in adult cerebral malaria: a study in Burundi, an area of high prevalence of HIV infection. Acta Tropica, 1994, 56:299-305.
12. Whitworth J et al. Effect of HIV-1 and increasing immunosuppression on malaria parasitaemia and clinical episodes in adults in rural Uganda: a cohort study. Lancet, 2000, 356:1051-1056.
13. Khasnis AA, Karnad DR. Human immunodeficiency virus type 1 infection in patients with severe falciparum malaria in urban India. Journal of Postgraduate Medicine, 2003, 49:114-117.
14. Grimwade K et al. HIV infection as a cofactor for severe falciparum malaria in adults living in a region of unstable malaria transmission in South Africa. AIDS, 2004, 18:547-554.
15. Colebunders R et al. Incidence of malaria and efficacy of oral quinine in patients recently infected with human immunodeficiency virus in Kinshasa, Zaire. Journal of Infection, 1990, 21:167-173.
16. Birku Y et al. Delayed clearance of Plasmodium falciparum in patients with human immunodeficiency virus co-infection treated with artemisinin. Ethiopian Medical Journal, 2002, 40(Suppl. 1):17-26.
17. James G K et al. Effect of Plasmodium falciparum malaria on concentration of HIV-1-RNA in the blood of adults in rural Malawi: a prospective cohort study. Lancet, 2005, 365:233-240.
18. Nguyen-Dinh et al. Absence of association between Plasmodium falciparum malaria and human immunodeficiency virus infection in children in Kinshasa, Zaire. Bulletin of the World Health Organization, 1987, 65:607-613.
19. Taha T et al. Childhood malaria parasitaemia and human immunodeficiency virus infection in Malawi. Transactions of the Royal Society of Tropical Medicine and Hygiene, 1994, 88:164-165.
20. Grimwade K et al. Childhood malaria in a region of unstable transmission and high human immunodeficiency virus prevalence. Pediatric Infectious Disease Journal, 2003, 22:1057-1063.
21. Lefèvre G et al. Pharmacokinetics and electrocardiographic pharmacodynamics of artemether-lumefantrine (Riamet®®) with concomitant administration of ketoconazole in healthy subjects. British Journal of Clinical Pharmacology, 2002, 54:485-492
22. Francesconi P et al. HIV, malaria parasites, and acute febrile episodes in Ugandan adults: a case-control study. AIDS, 2001, 15:2445-450.
23. French N et al. Increasing rates of malarial fever with deteriorating immune status in HIV-1-infected Ugandan adults. AIDS, 2001, 15:899-906.
24. The role of laboratory diagnosis to support malaria disease management: focus on the use of RDTs in areas of high transmission deploying ACT treatment. Geneva, World Health Organization, in press.
25. Report of a technical consultation: malaria and HIV interactions and their implications for public health policy: Geneva, Switzerland, 23-25 June 2004. Geneva, World Health Organization, 2004.