Effects of Permethrin-Treated Bed Nets on Immunity to Malaria in Western Kenya I. Antibody Responses in Pregnant Women and Cord Blood in an Area of Intense Malaria Transmission

Abstract

Abstract. As part of a community-based group-randomized trial on the impact of permethrin-treated bed nets (ITNs) on malaria in pregnancy in a holoendemic area of western Kenya, we assessed their effects on antibody responses to Plasmodium falciparum pre-erythrocytic antigens (recombinant circumsporozoite protein [CSP] and peptides complimentary to the repeat region of the liver stage antigen-1 [LSA-1]) and blood stage antigen (recombinant C-terminal domain of the merozoite surface protein-1 [MSP-1 19 kD]) in paired maternal/cord plasma samples obtained from 296 deliveries (157 from ITN villages and 139 control villages). Levels of total IgG and IgG subclasses 1−3 to LSA-1 and total IgG and IgG3 to MSP-1 were lower, whereas those of total IgG to CSP were significantly higher in women from ITN villages than those from control villages. In cord plasma, levels of total IgG and IgG2 to LSA-1 and IgG3 to MSP-1 were lower in ITN villages than in control villages, but antibody responses to CSP were similar. Our results suggest that the use of ITNs decreases antibody responses to LSA-1 and MSP-1 antigens in pregnant women with associated reductions in levels of the same antibodies in cord blood. In contrast, ITN use was found to be associated with increased antibody responses to CSP in pregnant women, but had no effect on antibody levels to CSP in cord blood.

Implications of the Western Kenya Permethrin-Treated Bed Net Study for Policy, Program Implementation, and Future Research

“…Relationships among the development of immunity to malaria, age-related development of the human immune system, and intensity and pattern of malaria transmission remain obscure. Although our results indicate no reduction in the ability of the immune system to mount antibody responses to certain antigens, 10,38 and no evidence that a marked exposure reduction in infants, with continued ITN use, results in increased morbidity in one-year old children, 9 it is by no means clear what this implies for long-term reduction in morbidity and mortality. Therefore, monitoring of age-specific morbidity and mortality in populations subjected to effective longterm malaria transmission reduction remains a high priority for research.…”

The Effect of Intermittent Preventive Treatment during Pregnancy on Malarial Antibodies Depends on HIV Status and Is Not Associated with Poor Delivery Outcomes

“…In the present study, women received only 2 SP doses during pregnancy, which might be a critical number of antimalarial doses to allow the development of antibody responses to placental parasites in HIV-negative mothers. Alternatively, levels of antibodies may be reduced by the use of ITNs in such a way that no further reduction can be observed after administration of the IPTp regimen [36].…”

Micro-geographical variation in exposure to Schistosoma mansoni and malaria, and exacerbation of splenomegaly in Kenyan school-aged children

“…It is a dominant IgG sub-class response to malaria antigens and toxins [22,23], but has a short half-life, and it has been hypothesised that the response wanes rapidly in areas of seasonal transmission [24]. Furthermore, IgG3 responses to blood stage antigen have been correlated with the level of exposure to infection during a bednet intervention in western Kenya [25] – a further indication that reducing exposure to malaria infection results in a measurable difference in this antibody isotype response. Finally, the distance over which the decline in IgG3 responses was measured is consistent with observations from other areas concerning the limited flight range of mosquitoes [26], and personal observations have made it clear that during the dry season there is no other surface water in the area that could harbour mosquito larvae.…”