Determinants of Plasmodium falciparum multiplicity of infection and genetic diversity in Burkina Faso

Abstract

Background Investigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso. Methods Blood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction. Results In the study area, infected people harboured an average of 2.732 (± 0.056) different parasite genotypes. A significant correlation between the monthly MOI and the monthly malaria incidence was observed, suggesting that MOI could be a good predictor of transmission intensity. A strong effect of season on MOI was observed, with infected patients harbouring higher number of parasite genotypes during the rainy season as compared to the dry season. There was a negative relationship between MOI and host age. In addition, MOI decreased with increasing parasite densities, suggesting that there was a within-host competition among co-infecting genetically distinct P. falciparum variants. Each allelic family of the msp1 and msp2 genes was present all year round with no significant monthly fluctuation. Conclusions In high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.

Plasmodium falciparum gametocyte carriage in symptomatic patients shows significant association with genetically diverse infections, anaemia, and asexual stage density

“…Nevertheless, these findings, although highlighting an association with gametocyte carriage do not establish causal relationship, i.e., these allelic families are mostly engaged in sexual differentiation than others. For example, if this was true, the RO33 allelic family should have been the commonest allelic family (mostly transmitted) yet it is the less represented in the study area [ 9 ]. Therefore, further investigations exploring the effect of allelic family variability on gametocytaemia with special attention towards the infectivity of RO33 allelic family for anopheline mosquitoes are needed.…”

“…MOI referred to the number of different parasite genotypes co-existing within a given infection. MOI was calculated separately for msp1 and msp2 and the final MOI value for each clinical isolate represented the maximum MOI value from both msp1 and msp2 loci as previously described in detail [ 5 , 9 ]. A sample was classified as belonging to a given allelic family (K1, MAD20 or RO33 for msp1 and 3D7 or FC27 for msp2 ) on the basis of an occurrence of at least one band after DNA amplification using the family specific primers [ 5 , 9 , 44 ].…”

“…Multi-genotype infections may result from several distinct mono-infected mosquito bites overtime and/or from a single multiple-infected mosquito bite [ 6 , 7 ]. In human infections, highly polymorphic markers such as Merozoite Surface Protein 1 and 2 ( msp1 and msp2 ) are commonly used as polymorphic markers to distinguish parasite genetic variants [ 5 , 8 , 9 ]. Using this approach allows differentiation of distinct parasite genotypes within a particular infection ranging from 1 (monoclonal infection) up to 10 (multiclonal infection) in endemic settings [ 3 , 9 – 12 ].…”

“…Contrasting predictions can be made regarding the relationship between gametocyte production and multiplicity of infection (MOI). First, the existence of within-host competition among distinct genotypes of malaria parasites [ 5 , 9 , 17 ] could result in an increased investment in reproduction and transmission to flee the competition [ 18 , 19 ]. Second, in presence of competitors, parasites could divert resource away from transmission towards replication to maximize their competitive success and hence their within-host survival [ 20 , 21 ].…”

Antimalarials in mosquitoes overcomeAnophelesandPlasmodiumresistance to malaria control strategies

“…In this study we demonstrate the feasibility of incorporating antimalarials into LLINs, IRS and ATSBs to stop parasite transmission by the Anopheles female. Our proof of principle compound ATQ was effective at killing a polyclonal, field-derived parasite isolate from sub-Saharan Africa, showing that an antimalarial-based LLIN or IRS could suppress transmission even in areas of malaria hyperendemicity such as Burkina Faso, where parasite haplotype diversity and complexity of infection are high (30, 31). Crucially, complete transmission-blocking activity was maintained in Bama-R mosquitoes that are highly resistant to insecticides.…”