Molecular Epidemiology of<i>Plasmodium falciparum</i>Malaria Outbreak, Tumbes, Peru, 2010–2012

BackgroundMalaria burden in Brazil has reached its lowest levels in 35 years and Plasmodium vivax now accounts for 84% of cases countrywide. Targeting residual malaria transmission entrenched in the Amazon is the next major challenge for ongoing elimination efforts. Better strategies are urgently needed to address the vast reservoir of asymptomatic P. vivax carriers in this and other areas approaching malaria elimination.MethodsWe evaluated a reactive case detection (RCD) strategy tailored for P. vivax transmission in farming settlements in the Amazon Basin of Brazil. Over six months, 41 cases detected by passive surveillance triggered four rounds of RCD (0, 30, 60, and 180 days after index case enrollment), using microscopy- and quantitative real-time polymerase chain reaction (qPCR)-based diagnosis, comprising subjects sharing the household (HH) with the index case (n = 163), those living in the 5 nearest HHs within 3 km (n = 878), and individuals from 5 randomly chosen control HHs located > 5 km away from index cases (n = 841). Correlates of infection were identified with mixed-effects logistic regression models. Molecular genotyping was used to infer local parasite transmission networks.Principal findings/ConclusionsSubjects in index and neighbor HHs were significantly more likely to be parasitemic than control HH members, after adjusting for potential confounders, and together harbored > 90% of the P. vivax biomass in study subjects. Clustering patterns were temporally stable. Four rounds of microscopy-based RCD would identify only 49.5% of the infections diagnosed by qPCR, but 76.8% of the total parasite biomass circulating in the proximity of index HHs. However, control HHs accounted for 27.6% of qPCR-positive samples, 92.6% of them from asymptomatic carriers beyond the reach of RCD. Molecular genotyping revealed high P. vivax diversity, consistent with complex transmission networks and multiple sources of infection within clusters, potentially complicating malaria elimination efforts.

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“…falciparum outbreaks in Peru [36] and Panama [37]. To the contrary, we characterized a highly diverse P .…”

Section: Discussionmentioning

confidence: 99%

Reactive Case Detection for Plasmodium vivax Malaria Elimination in Rural Amazonia

et al. 2016

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“…; Baldeviano et al . ). However, the potential for P. falciparum elimination is much less evident in Africa, the continent with most cases of infection and the highest malaria disease burden.…”

Section: Introductionmentioning

confidence: 97%

Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution

Duffy

Ba²,

Assefa

et al. 2017

Molecular Ecology

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To determine whether the major human malaria parasite Plasmodium falciparum exhibits fragmented population structure or local adaptation at the northern limit of its African distribution where the dry Sahel zone meets the Sahara, samples were collected from diverse locations within Mauritania over a range of ~1000 km. Microsatellite genotypes were obtained for 203 clinical infection samples from eight locations, and Illumina paired‐end sequences were obtained to yield high coverage genomewide single nucleotide polymorphism (SNP) data for 65 clinical infection samples from four locations. Most infections contained single parasite genotypes, reflecting low rates of transmission and superinfection locally, in contrast to the situation seen in population samples from countries further south. A minority of infections shared related or identical genotypes locally, indicating some repeated transmission of parasite clones without recombination. This caused some multilocus linkage disequilibrium and local divergence, but aside from the effect of repeated genotypes there was minimal differentiation between locations. Several chromosomal regions had elevated integrated haplotype scores (|iHS|) indicating recent selection, including those containing drug resistance genes. A genomewide FST scan comparison with previous sequence data from an area in West Africa with higher infection endemicity indicates that regional gene flow prevents genetic isolation, but revealed allele frequency differentiation at three drug resistance loci and an erythrocyte invasion ligand gene. Contrast of extended haplotype signatures revealed none to be unique to Mauritania. Discrete foci of infection on the edge of the Sahara are genetically highly connected to the wider continental parasite population, and local elimination would be difficult to achieve without very substantial reduction in malaria throughout the region.

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“…Clonal P. falciparum outbreaks have been reported from Solomon Islands [45], the highlands of Papua New Guinea [46] or Latin America [38, 47, 48], and in some cases were tracked back to regions of ongoing transmission [38, 48]. Genotyping thus confirmed that cases in previously malaria-free regions were caused by a few imported parasites.…”

Section: Assessing Population Structure To Inform and Guide Malaria Cmentioning

confidence: 84%

“…P. falciparum clonal parasite populations, consistent with outbreaks in regions with very low transmission, occurred in several countries [38, 45–48]. In contrast, clonal or near-clonal P. vivax population structure was only reported in a few cases and the findings are difficult to interpret.…”

Section: Genetic Diversity and Population Structure As Surrogate Markmentioning

confidence: 99%

“…Lastly, in regions with previously no malaria reported, genotyping can help to distinguish between local outbreaks caused by imported infections (i.e. clonal population structure), and ongoing, but previously undetected transmission (Figure 1C) [38]. If transmission had been ongoing, diversity is expected to be maintained.…”

Section: Assessing Population Structure To Inform and Guide Malaria Cmentioning

confidence: 99%

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Malaria Epidemiology at the Clone Level

Koepfli

Müeller

2017

Trends in Parasitology

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Genotyping to distinguish between parasite clones is nowadays a standard in many molecular epidemiological studies of malaria. It has become crucial in drug trials and to follow individual clones in epidemiological studies, and to understand how drug resistance emerges and spreads. Here, we will review the applications of the increasingly available genotyping tools and whole genome sequencing data, and argue for a better integration of population genetics findings into malaria control strategies.

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Molecular Epidemiology ofPlasmodium falciparumMalaria Outbreak, Tumbes, Peru, 2010–2012

Abstract: Multidrug-resistant parasites from the Amazon region caused the outbreak in the northern coastal region.

Cited by 55 publications

References 26 publications

Reactive Case Detection for Plasmodium vivax Malaria Elimination in Rural Amazonia

Reactive Case Detection for Plasmodium vivax Malaria Elimination in Rural Amazonia

Population genetic structure and adaptation of malaria parasites on the edge of endemic distribution

Malaria Epidemiology at the Clone Level

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