HIV and malaria can independently cause serious complications during pregnancy, endangering the health and survival of both the pregnant woman and her infant. But when the two diseases occur together, the dangers are compounded, according to two recent studies from Africa.
The first study, conducted in Zimbabwe and published in November’s Journal of Acquired Immune Deficiency Syndromes, found that the symptoms of malaria were about four times more likely to develop in HIV-infected women than in those without HIV. Dual infection was associated with an increased risk of maternal, perinatal, and early infant death compared to either disease alone. A second study from Uganda, published as a letter in this month’s AIDS, found an increased risk of placental malaria in HIV infected women. This in turn was associated with a greater risk of HIV transmission to the infant.
These conclusions are consistent with the findings of a Kenyan study of HIV and malaria coinfection, published earlier this year in AIDS. That study reported that dual infection was associated with low birth weights, preterm deliveries, and slow gestational development. These studies provide more solid evidence that there is a significant interaction between the two diseases — at least in pregnant women.
Though HIV and malaria cause illness and death side by side in most of sub-Saharan Africa, early studies were not able to agree upon whether either epidemic disease had a major impact upon the other (in particular, whether contracting both infections made either disease worse). More recent studies suggest that the effect of dual infection is greater in patients with advanced HIV disease and a suppressed immune function. But given the frequency of co-infection, any potential interaction warranted further exploration since even a small effect could have significant public health consequences.
An increase in the incidence and fatality from malaria in pregnant women and their infants is a particular cause for concern because these pregnant women and infants are already at great risk from the mosquito-borne illness. In areas where malaria transmission is high, the disease kills about one million children each year. Those who survive the repeated infections develop partial immunity to the disease, usually by the age of five.
While immunity doesn’t eradicate the disease from the body, or stop new infections, it usually prevents symptoms. But for reasons that remain unclear, women may lose this acquired immunity to malaria during pregnancy. If she contracts malaria during pregnancy, she may develop a severe case of the disease that could lead to a preterm delivery, low birth weight, growth retardation, or the death of the infant or herself.
The study in Zimbabwe measured the relative effects of HIV, malaria and coinfection on pregnancy in 986 women admitted to a hospital in an endemic area for both HIV and malaria. 8.3% of the women were HIV positive, while 14.7% had symptomatic malaria.
The study found that HIV-infected women were more likely to develop malaria during pregnancy than HIV negative women (odds ratio [OR] = 3.96). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74) and preterm delivery (OR = 4.10), respectively. Both infections were also independently associated with increased risk of low birth weight malaria, very low birth weight and fetal growth restriction.
Infants born to coinfected women were much more likely to die. The risk of death for infants born to women affected by malaria, HIV, or both, was 18.05, 40.24 and 73.90 respectively when compared with infants born to HIV-negative and malaria-free women,
Although most (140 or 96.6%) women with malaria were given treatment, in many cases the drug provided was chloroquine, which due to resistance is often ineffective in southeastern Africa. Overall, 44 women (4.5%) died during the study period. By far the most common cause of death was cerebral malaria, occurring in 24 cases (and accounting for 54.5% of all the deaths).
HIV-infected women were approximately 22 times more likely to die than HIV-uninfected women. There was a similar risk for those with malaria. Women with dual infections had the greatest risk of death compared with those with only HIV infection (OR = 4.2) or malaria infection (OR = 5.05).
“Our results emphasize the importance of controlling malaria when assessing the effect of HIV on all pregnancy outcomes", the authors say. "In our study population, HIV-infected women were more likely to present with malaria during pregnancy, a finding consistent with that of other studies showing higher parasite density and increased frequency of clinical malaria among HIV-infected individuals. It is possible that HIV infection impairs the immune response to P. falciparum. [the parasite that causes malaria].”
The study’s authors also note that “malaria infection in HIV-positive pregnant women might possibly increase the risk of mother to-child transmission of HIV.”
That concern was echoed in the Ugandan study, which assessed the effects of placental malaria on mother-to-child transmission (MTCT) of HIV. The data were collected as part of a prospective randomised trial of STD treatment that had enrolled 746 HIV-positive mother–infant pairs.
Placental malaria was more common in HIV-positive than HIV-negative women. Lab tests were conducted on 668 placentas from women of known HIV status. 62 of the placentas (9.3%) tested positive for malaria. Among HIV-positive mothers, 13.6% (21/155) had placental malaria, compared with 8.0% (41/510) of HIV-negative mothers (p = 0.039) Overall, the rate of MTCT was 20.4% in the study. But the MTCT rate was 40% (6/15) in those with placental malaria and 15.4% (12/78) in those without malaria (p = 0.027). MTCT was significantly associated with maternal viral load and placental malaria infection.
Although the study demonstrates that coinfection with malaria can increase the likelihood of a mother transmitting HIV, the authors also suggest that interventions designed to prevent malaria during pregnancy might also reduce the rate of mother to child HIV transmission. They conclude that “randomised trials of intensive malaria control in HIV-positive women are urgently needed.”
References
Ayisi JG et al. The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya. AIDS. 17: 585–594, 2003.
Brahmbhatta, H et al. The effects of placental malaria on mother-to-child HIV transmission in Rakai, Uganda. AIDS 17: 2540-2541, 2003.
Ticconi C et al. Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe. J Acquir Immune Defic Syndr 34: 289–294. 2003.