Abstract
BackgroundThe incidence of malaria in Sri Lanka has significantly declined in recent years. Similar trends were seen in Kataragama, a known malaria endemic location within the southern province of the country, over the past five years. This is a descriptive study of anti-malarial antibody levels and selected host genetic mutations in residents of Kataragama, under low malaria transmission conditions.MethodsSera were collected from 1,011 individuals residing in Kataragama and anti-malarial antibodies and total IgE levels were measured by a standardized ELISA technique. Host DNA was extracted and used for genotyping of selected SNPs in known genes associated with malaria. The antibody levels were analysed in relation to the past history of malaria (during past 10 years), age, sex, the location of residence within Kataragama and selected host genetic markers.ResultsA significant increase in antibodies against Plasmodium falciparum antigens AMA1, MSP2, NANP and Plasmodium vivax antigen MSP1 in individuals with past history of malaria were observed when compared to those who did not. A marked increase of anti-MSP1(Pf) and anti-AMA1(Pv) was also evident in individuals between 45–59 years (when compared to other age groups). Allele frequencies for two SNPs in genes that code for IL-13 and TRIM-5 were found to be significantly different between those who have experienced one or more malaria attacks within past 10 years and those who did not. When antibody levels were classified into a low-high binary trait, significant associations were found with four SNPs for anti-AMA1(Pf); two SNPs for anti-MSP1(Pf); eight SNPs for anti-NANP(Pf); three SNPs for anti-AMA1(Pv); seven SNPs for anti-MSP1(Pv); and nine SNPs for total IgE. Eleven of these SNPs with significant associations with anti-malarial antibody levels were found to be non–synonymous.ConclusionsEvidence is suggestive of an age–acquired immunity in this study population in spite of low malaria transmission levels. Several SNPs were in linkage disequilibrium and had a significant association with elevated antibody levels, suggesting that these host genetic mutations might have an individual or collective effect on inducing or/and maintaining high anti–malarial antibody levels.
Highlights
The incidence of malaria in Sri Lanka has significantly declined in recent years
A significant reduction of malaria incidence was observed after the year 2002 due to many reasons, including the modifications introduced to the National Malaria Control Programme to be in line with the New Global Malaria Control Strategy recommended by the World Health Organization
(Pf ) (p = 0.002) and anti-MSP1 (Pv) (p = 0.003) levels were significantly higher in people who have had one or more clinical malaria episodes within the past 10 years, when compared to those who gave no evidence of clinical malaria during past 10 years (Table 3)
Summary
Ethical clearance Ethical clearance for this study was granted by the Ethics Review Committee, Faculty of Medicine, University of Colombo. Serum samples were added in duplicates after washing the incubated plates with PBS/T. The cut-off value of the assay was determined by calculating the arithmetic mean of the absorbance of negative control samples obtained from European individuals who had never been exposed to malaria and adding three standard deviations to that value (mean OD + 3SD). Data analysis Antibody levels were analysed in relation to age, gender and the history of malaria. For the genetic analysis a total of 170 SNPs in 62 genes were genotyped (Additional File 2 SNPs). This included 65 SNPs with known associations with malaria infection/disease severity. Linkage disequilibrium (LD) plots for the 19 genes where the 23 significant SNPs were located were generated using Haploview (V4.2)
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