We previously reported that HIV+
pregnant women have fewer antibodies to VSAs from the parasite line CS2, which expresses the var2csa
gene, associated with placental malaria (11
). In the present study of clinical isolates, sera from HIV+
women had fewer antibodies to VSAs expressed by IRBCs from both placental and pediatric isolates than HIV−
women. More than 90% of the maternal serum samples collected near the time of delivery had detectable levels of antibodies to placental VSAs, regardless of their parity and HIV infection status, suggesting that antibodies to placenta-associated VSAs result from a single or a very few episodes of malaria in both HIV+
women. Such a restricted repertoire suggests that these antibodies against placental isolates target relatively conserved epitopes and therefore enable a sufficient antibody response against pregnancy-associated malaria. Because the present study used a range of clinical isolates rather than a single laboratory-adapted isolate, we propose that it better reflects the true extent of the effect of HIV on the levels of antibodies to VSAs.
We had access only to isolates from children with severe malaria. Isolates infecting young children and causing severe disease may express VSAs different from those of isolates causing mild disease or infecting older children (5
). We do not know whether the responses to isolates typically causing mild malaria in children are less affected by HIV than those that we tested here.
In previous studies, the levels of antibodies to most merozoite and sporozoite antigens of P. falciparum
did not differ between pregnant women with and without HIV infection, with the exception of antibodies to AMA-1 and the circumsporozoite protein (1
). Nonpregnant adults with AIDS but not those with asymptomatic HIV infection (adults admitted to hospital with trauma) lacked antibodies to the ring-infected erythrocyte surface antigen (16
). Our data, in conjunction with the available published data, suggest that HIV-induced immunosuppression exerts a significant effect on variant-specific immunity. In children, specific deficits in variant-specific immunity have been associated with subsequent clinical disease due to that variant (6
). Our study was cross-sectional and was not designed to correlate immune responses with malaria parasite infection in the participants. Therefore, further studies are required to determine whether a defect in variant-specific immunity has a critical role in the susceptibility of HIV+
persons to malaria parasite infection and disease.
Our observation that HIV+
multigravidae were more likely than primigravidae and secundigravidae to have impaired antibody responses to pediatric isolates was unexpected. The levels of immunosuppression (as measured by CD4 counts) did not differ significantly with gravidity. It is well recognized that the difference in parasite prevalence between HIV+
women is greatest in multigravidae, but this has been attributed to the impact of HIV on the development of pregnancy-specific immunity (15
). In our previous study (11
), the effect of HIV infection on antibodies to pregnancy-associated VSAs was greatest in the first pregnancy, perhaps because the ability to develop new immune responses is more likely to be affected than existing immunity. Observations that HIV infection in nonpregnant adults increases parasite prevalence and clinical disease and worsens the response to antimalarial therapy (9
) may be explained by the effects of HIV infection on the memory response to malaria; multigravidae might have greater deficits in memory response because they have usually had longer durations of HIV infection. By failing to recognize pediatric isolates, HIV+
multigravidae may be more likely to be challenged by these isolates than HIV−
multigravidae. These pediatric isolates do not sequester in the placenta; but they could cause other complications of malaria, such as anemia, and evidence suggests that HIV infection and malaria have synergistic effects on anemia (15
). Further studies are required to determine the importance of this observation.
We did not have any data on the history of malaria exposure, which may have differed between HIV+ and HIV− women or between women of different gravidities. Our sample size was limited both by access to clinical isolates and by technical limitations to the number of samples that we could test against each isolate. A larger study would allow more definitive conclusions to be drawn.
These findings may have important implications for the prevention of malaria in HIV+ individuals. A lack of immunity to variants causing severe disease in children living in the same environment may translate into the susceptibility of expectant mothers to these parasite strains. Malaria prevention in HIV+ pregnant women (and, perhaps, other HIV+ groups) may minimize the burden of malaria caused by an HIV-related lack of variant-specific immunity.