Malaria and HIV: interplay of risk.

Does infection with malaria increase the risk that a mother with HIV will pass the AIDS virus along to her newborn? Recent findings are equivocal, but the possibilities they raise are alarming.

In the 21 November 2003 issue of AIDS, Heena Brahmbhatt, an assistant scientist at the Johns Hopkins Bloomberg School of Public Health, and colleagues described a reanalysis of data collected in the 1990s to examine whether controlling sexually transmitted diseases (STDs) in Ugandan women would lower the rate of HIV infection in these women's newborns. That question remains unanswered, but Brahmbhatt did find a positive relationship between the presence of malaria parasites in the placenta and the risk of HIV infection in the newborn. After adjusting for confounders, a baby born to a woman with placental malaria was almost three times as likely to be infected with HIV as a baby born to a mother without malaria parasites in the placenta.

Ronald Gray, a professor of reproductive epidemiology at the Bloomberg School of Public Health, oversaw the STD trial from which Brahmbhatt distilled her data. He says the hematoxylin--eosin stain used to test the placentas was chosen to meet the original goal of determining the impact of STDs on HIV transmission, but is not a good stain for malaria because it will pick up only high parasite loads. The investigators are reexamining the placentas using stains that are highly specific for malaria. Interim analyses using these improved stains show that placental malaria is significantly associated with mother-to-child HIV transmission, and that the presence of malaria increases the mother's HIV viral load.

However, a study scheduled to appear in the April 2004 issue of Emerging Infectious Diseases by researchers from the U.S. Centers for Disease Control and Prevention and the Kenya Medical Research Institute found fewer HIV-infected babies born to mothers with placental malaria, although the risk of mother-to-child HIV transmission was increased among mothers with high placental parasitemia. A third study out of Belgium's Ghent University and University of Antwerp and Kenya's Coast Provincial General Hospital, published in the 1 December 2003 Journal of Infectious Diseases, found no association between placental malaria and mother-to-child HIV transmission.

Differences among the three studies may reflect a complex balance between the immune response against malaria and the degree of immune suppression by HIV. This balance can tip in the direction of either greater risk of mother-to-child HIV transmission or a protective effect, depending on the degree of immune suppression and the severity of the malarial infection in the placenta, says Robert Newman, a medical officer in the Centers for Disease Control and Prevention Malaria Branch and coauthor of the Emerging Infectious Diseases paper.

Of the Brahmbhatt study, Gray says, "Yes, it was a small sample. Yes, it was secondary data analysis, and there are some limits to the methods. Nevertheless, it's potentially an important observation, because if placental malaria really does enhance mother-to-child HIV transmission, that would give us a very strong rationale for much more intense malaria suppression in pregnancy than is now done."

Several hypotheses could explain why having malaria would facilitate mother-to-child transmission of HIV, Brahmbhatt says. Malaria may damage the placenta, increasing the exchange of maternal and fetal blood. Malaria may also increase the expression of a cell surface receptor called CCR5, which HIV uses to gain entry into cells.

Even if malaria does not affect HIV transmission to newborns, says Newman, it's still associated with premature delivery and low birth weight. "In no way do we think that it does not make sense to prevent malaria in pregnancy," he says. "If I were a program manager ... I would plow ahead with preventing both diseases [among pregnant women]."