Genetically diverse Plasmodium falciparum infections, within-host competition and symptomatic malaria in humans

Paul Sondo,Halidou Tinto,Hermann Sorgho,Innocent Valea,Jean-Bosco Ouedraogo,Karim Derra,Odile Zampa,Thierry Lefevre,Tinga Robert Guiguemde,Seydou Diallo-Nakanabo,Adama Kazienga,Zekiba Tarnagda

doi:10.1038/s41598-018-36493-y

Paul Sondo, Halidou Tinto + Show 10 more

Open Access

https://doi.org/10.1038/s41598-018-36493-y

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Abstract

There is a large genetic diversity of Plasmodium falciparum strains that infect people causing diverse malaria symptoms. This study was carried out to explore the effect of mixed-strain infections and the extent to which some specific P. falciparum variants are associated with particular malaria symptoms. P. falciparum isolates collected during pharmacovigilance study in Nanoro, Burkina Faso were used to determine allelic variation in two polymorphic antigens of the merozoite surface (msp1 and msp2). Overall, parasite density did not increase with additional strains, suggesting the existence of within-host competition. Parasite density was influenced by msp1 allelic families with highest parasitaemia observed in MAD20 allelic family. However, when in mixed infections with allelic family K1, MAD20 could not grow to the same levels as it would alone, suggesting competitive suppression in these mixed infections. Host age was associated with parasite density. Overall, older patients exhibited lower parasite densities than younger patients, but this effect varied with the genetic composition of the isolates for the msp1 gene. There was no effect of msp1 and msp2 allelic family variation on body temperature. Haemoglobin level was influenced by msp2 family with patients harboring the FC27 allele showing lower haemoglobin level than mono-infected individuals by the 3D7 allele. This study provides evidence that P. falciparum genetic diversity influenced the severity of particular malaria symptoms and supports the existence of within-host competition in genetically diverse P. falciparum.

Highlights

Malaria is the commonest parasitic disease worldwide leading to about 445000 deaths annually[1]
This study was carried out using these polymorphic markers to explore: (i) whether some specific family strains of P. falciparum were mostly associated with the occurrence of particular malaria symptoms such as high body temperature, severe anemia, and high parasite densities; (ii) whether within-host competition occurred; and (iii) whether mixed infections were associated to lower or higher disease severity
Parasite density was significantly influenced by the msp[1] allelic family with highest parasitemia observed for MAD20, followed by RO33 and K1 (LRT X26 = 22.73, P = 0.0009, Fig. 1a)

Summary

Introduction

Malaria is the commonest parasitic disease worldwide leading to about 445000 deaths annually[1]. There is great genetic polymorphism within P. falciparum species and people living in endemic area are frequently and simultaneously infected by several Plasmodium strains[3] This genetic diversity of the parasite is one of the main factors responsible for the slow acquisition (several years) of immunity against malaria. This study was carried out using these polymorphic markers to explore: (i) whether some specific family strains of P. falciparum were mostly associated with the occurrence of particular malaria symptoms such as high body temperature, severe anemia, and high parasite densities; (ii) whether within-host competition occurred (when certain genotypes in mixed infections cannot grow to the same levels as it would alone); and (iii) whether mixed infections were associated to lower or higher disease severity

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