Insecticide-treated bed nets reduce plasma antibody levels and limit the repertoire of antibodies to Plasmodium falciparum variant surface antigens

Abstract

The use of insecticide-treated bed nets (ITN) has been documented to reduce malaria morbidity and mortality in areas with endemic malaria, but concerns have been raised that ITN usage could affect the acquisition of malaria immunity. Several lines of evidence have indicated that antibodies against variant surface antigens (VSA) are important in the development of naturally acquired immunity to Plasmodium falciparum malaria and may thus be good indicators of immune status. We have compared the levels of VSA antibodies in plasma from children who have used ITN for 4 years to levels in plasma from children from a nearby village not using ITN. A total of 97 plasma samples were analyzed using 13 different P. falciparum isolates. We found that the children using ITN had significantly lower VSA antibody levels and recognized a smaller proportion of the VSA expressed by the tested parasite isolates than children not using ITN.

FIG. 1

VSA plasma antibody levels in relation to age among children sleeping under ITN (○) (n = 48) and unprotected children (●) (n = 49). The antibody levels were measured by flow cytometry, and the figure shows the cumulative MFI for 13 parasite isolates. The solid lines show linear regression, and dotted lines represent the 95% confidence interval.

FIG. 2

VSA plasma antibody levels and repertoire in children sleeping under ITN (○) and unprotected children (●). (A) Plasma antibody levels to VSA carried by the parasite isolate L1047. The y axis at left shows the MFI measured by flow cytometry. The y axis at right shows the reactivity in dilutions of a hyperimmune plasma pool (HIP). The reactivity of Danish control plasma + 2 SD (DC) is indicated by the dotted line. The x axis shows the plasma donor age. (B) Percentage of parasite isolates recognized in relation to age, assessed by counting how many of the 13 parasite isolates the donor had plasma VSA antibody reactivity to above the cutoff level (mean reactivity of Danish controls + 2 SD).