Age-adjusted Plasmodium falciparum antibody levels in school-aged children are a stable marker of microgeographical variations in exposure to Plasmodium infection

Abstract

Background: Amongst school-aged children living in malaria endemic areas, chronic morbidity and exacerbation of morbidity associated with other infections are often not coincident with the presence or levels of Plasmodium parasitaemia, but may result from long-term exposure to the parasite. Studies of hepatosplenomegaly associated with Schistosoma mansoni infection and exposure to Plasmodium infection indicate that differences that occur over 1-2 km in levels of Plasmodium transmission are related to the degree of exacerbation of hepatosplenomegaly and that Plasmodium falciparum schizont antigen (Pfs)-IgG3 levels may be a marker for the differing levels of exposure.

Methods: To investigate the validity of Pfs-IgG3 measurements as a tool to assess these comparative exposure levels on a microgeographical scale, cross-sectional community surveys were conducted over a 10 x 6 km study site in Makueni District, Kenya, during low and high malaria transmission seasons. During both high and low malaria transmission seasons, thick blood smears were examined microscopically and circulating Pfs-IgG3 levels measured from dried blood spot elute. GIS techniques were used to map prevalence of parasitaemia and Pfs-IgG3 levels.

Results: Microgeographical variations in prevalence of parasitaemia were observed during the high but not the low transmission season. Pfs-IgG3 levels were stable between high and low transmission seasons, but increased with age throughout childhood before reaching a plateau in adults. Adjusting Pfs-IgG3 levels of school-aged children for age prior to mapping resulted in spatial patterns that reflected the microgeographical variations observed for high season prevalence of parasitaemia, however, Pfs-IgG3 levels of adults did not. The distances over which age-adjusted Pfs-IgG3 of school-aged children fluctuated were comparable with those distances over which chronic morbidity has previous been shown to vary.

Conclusion: Age-adjusted Pfs-IgG3 levels of school-aged children are stable and when mapped can provide a tool sensitive enough to detect microgeographical variations in malaria exposure, that would be useful for studying the aetiology of morbidities associated with long-term exposure and co-infections.

Figure 1

Malaria prevalence maps for low and high transmission seasons. Maps of malaria prevalence on a household level, as detected from thick blood smears, during (A) a low transmission season (n = 1044) and (B) a high transmission season (n = 973). Also shown is a cluster of households with a higher than expected prevalence of malaria during the high transmission season, detected using the Kulldorff scan technique (RR = 1.542, p = 0.004). Indicated for the cluster are the number of cases and the expected (exp) number of cases.

Figure 2

High transmission season prevalence of parasitaemia with increasing distance from the nearest pond. Prevalence of Plasmodium falciparum parasitaemia is shown for school-aged children (5- to17-yrs, n = 560; clear bars) and adults (>17-yrs, n = 380; striped bars). Significant differences in prevalence were determined by Chi-squared analysis. *Significantly higher prevalence of malaria infection than further from the ponds (p < 0.001).

Figure 3

Age profiles of Pfs-IgG3 levels during low and high transmission seasons. (A) Longitudinal comparisons of mean +/- 2 standard errors low transmission season (circles) and high transmission season (squares) Plasmodium falciparum schizont Ag (Pfs)-IgG3 levels of individuals who participated at both time points (n = 684), stratified by age. Paired t-tests found no significance between low and high malaria transmission season Pfs-IgG3 levels for any age group. (B) Cross-sectional age-related curves of low transmission (circles, solid line; n = 1044) and high transmission (squares, dashed line; n = 973) Pfs-IgG3 levels; bars represent +/- 2 standard errors.

Figure 4

Microgeographical patterns in age adjusted Pfs-IgG3 levels. (A) Map of mean age-adjusted low transmission season Plasmodium falciparum schizont antigen (Pfs)-IgG3 levels (n = 1044), on a household level. Pfs-IgG3 levels were age-adjusted by linear regression which was split at <= 17-yrs and >17-yrs. (B) Age-adjusted Pfs-IgG3 levels with distance of residence from the nearest permanent stream. Shown are the mean levels +/- 2 standard errors. (C) Age-adjusted Pfs-IgG3 levels with distance of residence from the nearest seasonal pond. Shown are the mean levels +/- 2 standard errors.

Figure 5

Microgeographical patterns in age adjusted Pfs-IgG3 levels stratified by age. Shown are the mean +/- 2 standard errors age adjusted low transmission season Plasmodium falciparum schizont antigen (Pfs)-IgG3 levels of school-aged children (5–17 yrs, n = 574) and adults (>17 yrs, n = 435), who live <0.5 km, 0.6–1.5 km and >1.5 km from the nearest water body (either a permanent stream or a seasonal pond). Statistical significance was determined by ANOVA with Hochberg GT2 post-hoc analysis. **Indicates a significantly lower mean age-adjusted Pfs-IgG3 level than those who live within 0.5 km of the nearest water body, p < 0.01, ***p < 0.001.