Disease Prevention and Control / Communicable Diseases / Malaria
Malaria and HIV Interactions and Their Implications for Public Health Policy
Report of a WHO Technical Consultation, Geneva, Switzerland, 23–25 June 2004
Malaria and HIV are among the two most important global health problems of our time. Together, they cause more than 4 million deaths a year. Malaria accounts for more than a million deaths each year, of which over 80% occur in tropical Africa, where malaria is the leading cause of mortality in children under five years of age. Aside from young children, pregnant women are among the most affected by the disease. Depending on malaria transmission intensity, the main complications of malaria during pregnancy include maternal death, severe anaemia, and adverse birth outcomes such as low birth weight. Constituting 10% of the overall disease burden, malaria places a substantial strain on health services and costs Africa about US$ 12 billion in lost production each year.
Sub-Saharan Africa is also home to an estimated 25 million adults and children living with HIV/AIDS. In 2003 in Africa, HIV claimed the lives of some 2.2 million people and over 600 000 children were newly infected with the virus. HIV increasingly accounts for a large proportion of mortality among children under five years in heavily affected countries. By 2002, the virus was responsible for almost 10% of all child deaths in the region. By taking its greatest toll on people in the prime of their working and parenting lives, HIV hinders sustainable development in Africa.
Treatment of HIV/AIDS with highly effective combination antiretroviral therapy is now being scaled up in most highburden countries in line with the WHO 3 by 5 initiative, which sets a global target of 3 million people in need of therapy living in resource-limited countries on ART by the end of 2005. Treatment is now an integral component of all HIV/AIDS programmes and will help accelerate and reinvigorate prevention efforts. The new focus on care and treatment provided by 3 by 5 is a further impetus to consider the main preventable and treatable causes of morbidity and mortality in HIV-infected adults and children globally.
Malaria and HIV/AIDS are both diseases of poverty and causes of poverty and they share determinants of vulnerability. Given the wide geographical overlap in occurrence and the resulting co-infection, the interaction between the two diseases clearly has major public health implications. WHO convened a technical consultation in Geneva from 23 to 25 June 2004 with researchers, policy-makers and programme managers to review evidence on interactions between malaria and HIV and the implications of such interactions on prevention and control of both diseases. The technical consultation included presentations of working papers, group and plenary discussions as well as recommendations that form the basis of this report.
The major burden of malaria and HIV occur in sub-Saharan Africa, South-East Asia, Latin America and the Caribbean. However, the prevalence of malaria and HIV as well as the extent of geographical overlap varies widely within each region. Even in countries with a high prevalence of both infections, there may be differences in disease distribution at a local level.
The impact of the interaction of malaria and HIV is most apparent in areas with generalized HIV 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 (i.e. Central African Republic, Malawi, Mozambique, Zambia and Zimbabwe), more than 90% of the population is exposed to malaria, and HIV prevalence in adults is above 10%. In contrast, southern Africa, which has a relatively low burden of malaria is the worst HIV-affected sub-region. 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 occurs in the general population in Belize, El Salvador, Guatemala, Honduras, Guyana, and Brazil. South-East Asian countries such as Myanmar and Thailand have a generalized HIV epidemic but malaria distribution is heterogeneous in this region. Considering that an estimated 1 billion people in South-East Asia are exposed to unstable malaria even small overlaps of malaria and HIV in these settings may have a large public health impact.
In areas with a low malaria and HIV burden, certain population groups such as migrant workers and injecting drug users are at high risk for both diseases, and they facilitate transmission of HIV from high-risk groups to the general population. Transmission of both malaria and HIV can result from improper blood-transfusion practices and unsafe injections.
In HIV-infected individuals, a malaria case definition based on fever alone can result in a febrile illness due to a wide range of ordinary, virulent and opportunistic infections being misdiagnosed and treated as malaria. 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 antimalarial drugs, it has become necessary to consider the widespread introduction of parasitological diagnosis, particularly in areas with a high HIV prevalence. The low specificity of a fever-based malaria case definition could diminish the validity of malaria case fatality data.
Evidence of interactions between malaria and HIV in nonpregnant adults is accumulating. In areas with stable malaria, HIV increases the risk of malaria infection and clinical malaria in adults, especially in those with advanced immunosuppression. In settings with unstable malaria, HIV-infected adults are at increased risk of complicated and severe malaria and death. Reports also suggest that antimalarial treatment failure may be more common in HIV-infected adults with low CD4-cell counts compared to those not infected with HIV. Additional research is needed to investigate the impact of malaria on the natural history of HIV, potential therapeutic implications, and interactions at a cellular and molecular level.
Acute malaria episodes cause a temporary increase in viral replication of HIV and hence plasma viral load. However, there is no evidence that malaria has a substantial effect on clinical progression of HIV, HIV transmission or response to antiretroviral treatment in areas where malaria and HIV overlap.
Few studies have examined the interaction of malaria and HIV in children. In areas of stable malaria, HIV-infected children may be at increased risk of clinical malaria compared to children not infected with HIV. Advanced immunosuppression in HIV- infected children results in more episodes of clinical malaria and higher parasite densities compared with HIV-infected children whose immune status is less compromised. In areas of unstable malaria HIV-infected children may be at increased risk of severe disease and death. However, no conclusions can be made to date without further specific data on co-infection with malaria and HIV.
The effects of interactions between malaria and HIV are particularly deleterious to maternal and infant health. HIV infection impairs the ability of pregnant women to control P. falciparum infection. They are more likely to develop clinical and placental malaria, more often have detectable malaria parasitaemia and have higher malaria parasite densities.
It is estimated that in 2003 in sub-Saharan Africa, at least 440 000 women had malaria infection during pregnancy attributable to HIV. Most women in their first or second pregnancy are at higher risk of severe or complicated malaria than during subsequent pregnancies. HIV alters this typical pattern by shifting the burden from mainly women in their first or second pregnancy to all pregnant women. 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. As a result, a considerable proportion of children born to women with dual malaria and HIV infection have low birth weight and are more likely to die during infancy. Whether infection with malaria increases the risk of mother-to-child transmission of HIV is unclear, as studies examining this relationship have inconsistent findings.
The presence of HIV results in a poorer response to both prophylaxis and treatment of malaria during pregnancy. Furthermore, there is a risk of adverse drug reactions if sulfadoxine- pyrimethamine for the prevention of malaria in pregnant women and cotrimoxazole for opportunistic infection prophylaxis are taken together, as both are sulfacontaining drugs.
Pharmacokinetic interactions of ARVs with antimalarials involve mostly non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) which are included in first- or second-line therapy for HIV. The potential for interaction resulting in excessive toxicity suggests that lumefantrine should be used with caution in patients receiving protease inhibitors (PIs) and halofantrine is contraindicated. The effect in patients receiving NNRTIs is unknown.
Widespread cotrimoxazole use could accelerate the development of resistance in malaria parasites to sulfadoxinepyrimethamine, the first-line drug for the treatment of uncomplicated malaria and the prevention of malaria in pregnant women in many parts of Africa. While more research to investigate pharmacokinetic interactions is required, emphasis should be placed on close monitoring and pharmacovigilance in the treatment of malaria and HIV.
Implications for health systems and service delivery: Providing integrated health services in areas heavily affected by malaria and HIV is crucial for reducing the burden of the two diseases. The introduction of new medicines and diagnostics by malaria and HIV programmes at the same time, offers opportunities for joint planning, training and service delivery.
Consideration of research needs: In light of the epidemiological overlap and global importance of the two diseases, there is an urgent need for more research on a wide range of unanswered questions. Only with sufficient evidence can appropriate public-health policy be devised on integrating the prevention, care, treatment and support activities for malaria and HIV. The consultation has considered the key research issues that should guide further research in this area.
Conclusion: This technical consultation was the first meeting of international experts assessing the impact of interactions between malaria and HIV on the health of people affected by both diseases. The meeting was a major step in identifying implications of such interactions for research, public health policy and health service delivery. The challenge is to combine activities to control malaria and HIV at various levels of the health system, tailor responses to community needs, and optimize the use of scarce resources for integrated service delivery. There are many opportunities for synergism, in particular at a time of growing political and financial commitment to reduce the burden of HIV/AIDS, tuberculosis and malaria.