| Throughout successive infections Plasmodium falciparum expresses conserved antigens, such as MSP-1 19KD. In vitro and animal-model studies have shown anti-parasitic effects of anti-19KD antibody, yet children's development, of immunity is greatly delayed. Utilizing the biweekly prospective follow-up of women and children exposed to high transmission, two hypotheses were investigated: (1) children's antibody responses to the conserved 19KD only develop after repeated infections, and (2) the high within-host P. falciparum diversity results in immunomodulation.; Anti-19KD was strongly correlated with protection. Children could mount anti-19KD antibody responses upon their first parasitemia, and, while present, the children were protected against parasitemia, fever, and anemia. After 1 year-of-life, the children's isotype composition (primarily IgG 1 and 3) was similar to their naturally-immune mothers. This antibody response, however, only remained for <45 days in the absence of parasitemia.; Superinfection and multiple-genotype malaria infections resulted in high within-host diversity, possibly enabling cooperation to delay the acquisition of malaria immunity. The MSP-1 repetitive region was used to characterize the genetically different parasites within each infection: the complexity of infection (COIK1M20). Controlling for transmission, the previous months' COIK1M20 drug treatment, parasite density and age COI K1M20 was negatively correlated with resistance to parasitemia >500/μl. The resistance was not genotype-specific. Parasitemias with the repeat-lacking RO-33 parasite-type, were more resistant to subsequent parasitemia.; The data suggest that, rather than increasing resistance by exposing the host to different antigenic types, a high COIK1M20 slows the acquisition of immunity. This might be due to overall within-host antigenic diversity. Alternatively, the MSP-1 repeats themselves could result in repeat-diversity immunomodulation, as suggested by (1) antibody responses to MSP-1 repeats being associated with susceptibility, (2) repeat-lacking genotype (RO-33) being associated with protection, (3) the diversity of one allele type (K1 alleles) having a greater impact on resistance.; This research elucidated factors contributing to delayed immunity. The immunity via conserved antigenic determinants, such as MSP-1 19KD, could contribute to protection, but responses are short-lived. The parasite might have evolved a diversity-driven immunomodulation mechanism to evade responses to conserved determinants. This suggests that control measures to decrease the COI could result in a more rapid development of anti-parasite immunity. |
