The study site, Kataragama is located within the malarial-endemic zone of Sri Lanka. Although most of the participants have apparently not been exposed to malaria for over a period of 10 years due to low intensity of malaria transmission, the overall prevalence of anti-malarial antibodies were seen to be very high. This might be a result of asymptomatic infections that may prevail in the area and/or prolonged memory of immune cells/factors, which would need to be confirmed following more in-depth studies . Though all study subjects were considered as un-infected, based on blood-smear examination for malaria, use of more sensitive assays, e.g. PCR, could have helped to detect the presence of a sub-microscopic parasitaemia, if present. However, all individuals showed evidence of previous exposure to malaria when screened for anti-malarial antibodies. The anti-malarial antibody levels anti-AMA1 (Pf), MSP2 (Pf), NANP (Pf) and MSP1 (Pv) were significantly higher in people who had had malaria within the last 10 years. This might be due to the fact of boosting up of the immune system of these individuals when compared to people who did not get malaria during past 10 years.
Higher levels of anti-MSP1 (Pf) and anti-AMA1 (Pv) antibodies were observed among the individuals within the age group 45–59 years compared to other age groups of the community. An increase of sero-prevalence could also be observed up to this age. Such age-related trends in anti-P. falciparum antibody levels have been observed by many workers in diverse population groups at high [14, 15] and even at low malaria transmission levels . Total IgE levels of males were significantly higher than in females in the present study. Many population studies have revealed the sexual dimorphism of total IgE levels for reasons that remain unclear [17, 18]. In the present study however, the particular population is an agricultural community; the men folk spend a considerable amount of time in the fields (compared to women, who engage in fewer outdoor activities) exposing themselves to allergens and/or antigens, that induce high levels of IgE, which play an important role in allergy and are especially associated with type I hypersensitivity .
It was interesting to note that the residents in village Akkarawissa had notably higher antibody levels than did the residents of the other seven villages. Akkarawissa is a farming village its residents mainly focusing on “Chena cultivation” where they burn the patches of jungles to cultivate their crops and its people are known to spend considerable amounts of time in the cultivation areas in the middle of the jungles, compared to other villagers. It is also surrounded by foliage that gives refuge to mosquitoes and other insects. Therefore, it is likely that there is higher exposure to malaria among the residents of this particular area although there was no significant difference between the numbers of past malaria attacks as recalled by these residents when compared to others. In-depth epidemiological studies would need to be carried out to prove (or disprove) the likelihood of increase exposure to malaria by these individuals.
Twenty-three SNPs out of 169 SNPs that were tested were found to be in association with the high levels of anti–malarial antibodies (Chi squared test, p < 0.05). Polymorphism rs1801274 in FCGR2A was associated with elevated levels of anti–MSP1 (Pv). A study done in two ethnic groups in Mali has shown the same polymorphism that had an influence on P. falciparum reactive IgG levels, which was related to protection against malaria . A study based in India has revealed that homozygotes for the polymorphisms rs1801274 correlated with susceptibility to severe falciparum malaria . It was suggested by Parren et al. in 1992 that this polymorphism could affect the regulation of the IgG subclass production or turnover in humans . Therefore, rs1801274 appears to be a polymorphism that is of distinct interest in malaria immunology and warrants further investigations.
A case–control study of malaria based on some ethnic groups in Sudan has revealed significant differences in genotype distribution among cases and controls of the polymorphisms rs10775349 and rs22443250 . Both these SNPs were found to correlate with elevated antibodies in the study population: rs10775349 associated with anti–MSP1 for P. vivax and rs22443250 with total IgE levels.
Both rs1800871 and rs1800872 SNPs were significantly associated with elevated antibody levels against the NANP antigen of P. falciparum and were in complete linkage disequilibrium. Several investigators have reported that polymorphisms in rs1800872 IL10 promoter sequence increase the promoter activity with resultant high levels of IL10 production [24, 25].
A study done in a Thai population revealed that the SNP rs1881457, which is located in the same haplotype block in 5q31-33 region with the RAD50 gene and the promoter of IL13 is significantly associated with severe falciparum malaria . The present study shows that this particular SNP is associated with high levels of anti-AMA1 and anti-NANP for P. falciparum; these findings of the two studies regarding rs1881457 are difficult to reconcile.