Co-infection of malaria and helminthiases: effect on the genetic diversity of targeted vaccine candidates and anti-malarial resistance markers in Mfou health disctrict

Abstract

Malaria and helminthiasis are major parasitic diseases that impose a significant global burden. Due to their overlapping geographical distributions, co-infection with these parasites is common. Helminth infections have been shown to modulate the immune response in individuals infected with malaria, thereby altering the selection pressure on the genetic structure of Plasmodium falciparum populations. However, the impact of helminth parasites on the genetic diversity of Plasmodium drug resistance markers and vaccine candidates remains poorly understood in regions where both infections are endemic. This study investigated the effect of malaria and helminth co-infection on the genetic diversity of targeted Plasmodium falciparum vaccine candidates (Pfmsp-1 and Pfmsp-2 genes) and the antimalarial multi-drug resistance marker (Pfmdr-1 gene) in the Mfou Health District, Centre Region of Cameroon. A total of 521 participants were enrolled during various cross-sectional studies in Nkassomo, Vian, Lobe and Ndangueng. Malaria diagnostics were confirmed using Rapid Diagnostic Tests (RDT), microscopy, and PCR in blood samples, while the Kato-Katz method was used to confirm helminth infections in stool samples. The Pfmsp-1, Pfmsp-2 and Pfmdr-1 genes were genotyped by nested-PCR in mono- and co-infected individuals to assess the impact of soil-transmitted helminthiasis (STHs). The prevalence of malaria in the study population was 46.64% (243/521) by RDT, 35.70% (186/521) by microscopy, and 17.66% (92/521) by PCR. Helminth infections and co-infections with malaria were found in 10.75% (56/521) and 3.65% (19/521) of the participants respectively. Ascaris lumbricoides and Trichuris trichiura constituted the main helminthiasis in the study communities. Overall, all Pfmsp-1 and Pfmsp-2 allelic families were found in mono- and co-infected individuals. A total of 09 and 09 different alleles were respectively found in mono- and co-infected individuals for the Pfmsp-1 gene, and 12 and 13 alleles for the Pfmsp-2 gene. The overall Multiplicity of infection (MOI) was higher in the co-infected population (MOI = 4.06) compared to the mono-infected population (MOI = 2.83). P. falciparum mono-infected individuals exhibited an overall expected heterozygosity (He) of 1.47, while the coinfected ones with STHs showed an He of 1.09. The Pfmdr-1 gene was highly diverged in coinfected individuals (03 different alleles, MOI = 1.38) compared to mono-infected individuals (02 different allele, MOI = 1.11). These preliminary data highlighted that coinfection by soil transmitted helminthiasis can increase the genetic diversity of P. falciparum vaccine genes and drug resistance makers, affecting the potential efficacy of antimalarial drugs and vaccines. Continuous monitoring of the effects of STHs on the multiplicity of Plasmodium infection could guide towards decision-making in the selection of efficient drugs and vaccines for coinfected individuals with malaria and STHs in co-endemic areas.