Clonal Outbreak ofPlasmodium falciparumInfection in Eastern Panama

Abstract

Identifying the source of resurgent parasites is paramount to a strategic, successful intervention for malaria elimination. Although the malaria incidence in Panama is low, a recent outbreak resulted in a 6-fold increase in reported cases. We hypothesized that parasites sampled from this epidemic might be related and exhibit a clonal population structure. We tested the genetic relatedness of parasites, using informative single-nucleotide polymorphisms and drug resistance loci. We found that parasites were clustered into 3 clonal subpopulations and were related to parasites from Colombia. Two clusters of Panamanian parasites shared identical drug resistance haplotypes, and all clusters shared a chloroquine-resistance genotype matching the pfcrt haplotype of Colombian origin. Our findings suggest these resurgent parasite populations are highly clonal and that the high clonality likely resulted from epidemic expansion of imported or vestigial cases. Malaria outbreak investigations that use genetic tools can illuminate potential sources of epidemic malaria and guide strategies to prevent further resurgence in areas where malaria has been eliminated.

Malaria Genomics in the Era of Eradication

“…One strategy is using case investigation or reactive case detection, where cases identified through passive case detection are then followed to determine whether other individuals in the household or neighborhood are also infected. Genomic tools have also been used for outbreak investigation (Obaldia et al 2015) and may assist in identifying parasite types under "prevention of reintroduction" conditions in elimination settings. Genomic strategies not only provide a sensitive means of identifying who is infected, but also provide evidence for the spatial and temporal relationships among infected individuals.…”

Adaptive evolution of malaria parasites in French Guiana: Reversal of chloroquine resistance by acquisition of a mutation in pfcrt

“…This evolving situation underscores the importance of understanding the evolutionary dynamics of antimalarial drug resistance in distinct transmission contexts. In Central or South America, where clonal propagation can occur (3), the population genetic diversity is reduced, with high rates of inbreeding (4). As a consequence, strong drug pressure can ultimately lead to fixation of drug resistance alleles, even if they generate a fitness cost to parasites in the absence of drug pressure.…”

Molecular Investigation into a Malaria Outbreak in Cusco, Peru: Plasmodium falciparum BV1 Lineage is Linked to a Second Outbreak in Recent Times

“…Peru reported 43,468 malaria cases in 2013, 84% of which were attributed to Plasmodium vivax infection while 16% (7,371) were due to Plasmodium falciparum. 1 As Peru and other South American countries progress toward the malaria pre-elimination phase, the utilization of appropriate parasite detection tools will facilitate effective disease surveillance and case management.…”

“…5 The highly clonal dynamic observed in this P. falciparum population is the result of decreased outcrossing and genetic drift primarily resulting from inbreeding and asexual replication. 7 In general, the low P. falciparum genetic diversity found in South America relates to the low transmission intensity in this region. With fewer parasite types, there are limited opportunities for outcrossing during meiosis in the mosquito, which results in highly related or even clonal parasites.…”

“…In addition, although there have been some reports on the use and interpretation of Plasmodium molecular genetics tools for outbreak investigations, 3,7 this methodology should be standardized for routine use to identify not only the Plasmodium species but the source(s) of a malaria outbreak and the prevalence of long-lasting drug-resistant P. falciparum strains. …”