Plasmodium falciparum Genetic Diversity in Bangladesh Does Not Suggest a Hypoendemic Population Structure

Abstract

Abstract. Despite the recommendation for the use of merozoite surface protein 1 (msp1), merozoite surface protein 2 (msp2), and glutamate-rich protein (glurp) genes as markers in drug efficacy studies by World Health Organization and their limited use in Bangladesh, the circulating Plasmodium falciparum population genetic structure has not yet been assessed in Bangladesh. This study presents a comprehensive report on the circulating P. falciparum population structure based on msp1, msp2, and glurp polymorphic gene markers in Bangladesh. Among the 130 pretreatment (day 0) P. falciparum samples from seven malaria-endemic districts, 14 distinct genotypes were observed for msp1, 20 for msp2, and 13 for glurp. Polyclonal infection was reported in 94.6% (N = 123) of the samples. Multiplicity of infection (MOI) for msp1 was the highest (1.5) among the MOIs of the markers. The heterozygosity for msp1, msp2, and glurp was 0.89, 0.93, and 0.83, respectively. Data according to different malaria-endemic areas are also presented and discussed. Bangladesh is considered as a malaria-hypoendemic country. However, the prevalence of polyclonal infection and the genetic diversity of P. falciparum do not represent hypoendemicity.

Molecular analysis demonstrates high prevalence of chloroquine resistance but no evidence of artemisinin resistance in Plasmodium falciparum in the Chittagong Hill Tracts of Bangladesh

“…Two patients had recurrent P. falciparum parasitaemia after the follow up period of the primary study had ended [ 34 ], 32 and 36 days after the diagnosis of their initial infection. To assess whether the recurrent cases represented recrudescence or re-infection events, genotyping was conducted at the msp1 (K1 of Block-2), msp 2 (3D7 of central domain), and glurp loci following standard protocols [ 39 , 40 ]. Taq polymerase, PCR buffer, dNTPs and restriction enzymes were sourced from New England BioLabs Inc, USA and a Bio-Rad C1000 thermal cycler was used for amplification.…”

Diversity analysis of MSP1 identifies conserved epitope organization in block 2 amidst high sequence variability in Indian Plasmodium falciparum isolates

“…This data and that of others indicate a possible positive association between MOI and endemicity of P. falciparum [ 63 – 66 ]. Nevertheless, this correlation may not be an absolute one as MOI of P. falciparum ranges from 1.00 to 2.70 in few hypoendemic regions of Southeast Asia [ 67 , 68 ]. A very high MOI of 3 ± 2.24 detected in the age group ≤ 18, is suggestive of a weaker immunity of younger people.…”

Population Genetics and Molecular Epidemiology of Eukaryotes

“…We now know that infection with multiple genotypes is common, albeit with a small number of individuals, so that MOI ranges from 1–3. MOI is used as an indicator of the intensity of transmission and diversity (4). While this set of markers clearly has utility and often performs the purpose for which it was designed, it has some significant technical and analytic limitations.…”

“…Instead, a relatively high MOI and high heterozygosity, more typical of hyperendemic regions of Africa, were observed and this is consistent with a much larger population than expected. This indicated to the authors that the current national strategy should now include asymptomatic cases, since they likely contributed to the overall size of the population and persistence (4). …”