Abstract

BackgroundSouth Africa aims to eliminate malaria transmission by 2023. However, despite sustained vector control efforts and case management interventions, the Vhembe District remains a malaria transmission hotspot. To better understand Plasmodium falciparum transmission dynamics in the area, this study characterized the genetic diversity of parasites circulating within the Vhembe District.MethodsA total of 1153 falciparum-positive rapid diagnostic tests (RDTs) were randomly collected from seven clinics within the district, over three consecutive years (2016, 2017 and 2018) during the wet and dry malaria transmission seasons. Using 26 neutral microsatellite markers, differences in genetic diversity were described using a multiparameter scale of multiplicity of infection (MOI), inbreeding metric (Fws), number of unique alleles (A), expected heterozygosity (He), multilocus linkage disequilibrium (LD) and genetic differentiation, and were associated with temporal and geospatial variances.ResultsA total of 747 (65%) samples were successfully genotyped. Moderate to high genetic diversity (mean He = 0.74 ± 0.03) was observed in the parasite population. This was ascribed to high allelic richness (mean A = 12.2 ± 1.2). The majority of samples (99%) had unique multi-locus genotypes, indicating high genetic diversity in the sample set. Complex infections were observed in 66% of samples (mean MOI = 2.13 ± 0.04), with 33% of infections showing high within-host diversity as described by the Fws metric. Low, but significant LD (standardised index of association, ISA = 0.08, P < 0.001) was observed that indicates recombination of distinct clones. Limited impact of temporal (FST range − 0.00005 to 0.0003) and spatial (FST = − 0.028 to 0.023) variation on genetic diversity existed during the sampling timeframe and study sites respectively.ConclusionsConsistent with the Vhembe District’s classification as a ‘high’ transmission setting within South Africa, P. falciparum diversity in the area was moderate to high and complex. This study showed that genetic diversity within the parasite population reflects the continued residual transmission observed in the Vhembe District. This data can be used as a reference point for the assessment of the effectiveness of on-going interventions over time, the identification of imported cases and/or outbreaks, as well as monitoring for the potential spread of anti-malarial drug resistance.

Highlights

  • South Africa aims to eliminate malaria transmission by 2023

  • This study showed that genetic diversity within the parasite population reflects the continued residual transmission observed in the Vhembe District

  • Plasmodium falciparum is the predominant species which accounts for the majority of cases and fatalities in the South Africa [5], with Anopheles funestus and the Anopheles gambiae complex the main vector species associated with transmission, which mainly occurs in the hot and rainy season between September and May [5]

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Summary

Introduction

South Africa aims to eliminate malaria transmission by 2023. despite sustained vector control efforts and case management interventions, the Vhembe District remains a malaria transmission hotspot. Like a number of other regions in the world, southern Africa experienced a resurgence in malaria cases and deaths during the 2017/2018 season [2] This resulted in South Africa reporting more than 30 000 cases, a surge in numbers previously only experienced during the 1999/2000 drug and insecticide resistance outbreak [3,4,5]. The Vhembe District is situated in the north-eastern border region of the country bordered by Mozambique to the southeast, Zimbabwe to the north and Botswana to the northwest (Fig. 1) This region experiences sustained, seasonal malaria transmission and accounts for 60% of the country’s burden [4]. Other causative factors for the persistent residual transmission observed in the Vhembe District, despite sustained vector control strategies and public health interventions, include antimalarial drug resistance, insecticide resistance and vector species variance between An. gambiae and An. funestus [7, 11,12,13,14,15]

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