Genetic characterisation of Plasmodium falciparum isolates with deletion of the pfhrp2 and/or pfhrp3 genes in Colombia: the Amazon region, a challenge for malaria diagnosis and control

Citation:
Okoth S. "Genetic characterisation of Plasmodium falciparum isolates with deletion of the pfhrp2 and/or pfhrp3 genes in Colombia: the Amazon region, a challenge for malaria diagnosis and control." PloS one. 2017:1-17.

Abstract:

Most Plasmodium falciparum-detecting rapid diagnostic tests (RDTs) target histidine-rich
protein 2 (PfHRP2). However, P. falciparumisolates with deletion of the pfhrp2 gene and its
homolog gene, pfhrp3, have been detected. We carried out an extensive investigation on
365 P. falciparumdried blood samples collected from seven P. falciparumendemic sites in
Colombia between 2003 and 2012 to genetically characterise and geographically map
pfhrp2- and/or pfhrp3-negative P. falciparumparasites in the country. We found a high proportion
of pfhrp2-negative parasites only in Amazonas (15/39; 38.5%), and these parasites
were also pfhrp3-negative. These parasites were collected between 2008 and 2009 in
Amazonas, while pfhrp3-negative parasites (157/365, 43%) were found in all the sites and
from each of the sample collection years evaluated (2003 to 2012). We also found that all
pfhrp2- and/or pfhrp3-negative parasites were also negative for one or both flanking genes.
Six sub-population clusters were established with 93.3% (14/15) of the pfhrp2-negative
parasites grouped in the same cluster and sharing the same haplotype. This haplotype
corresponded with the genetic lineage BV1, a multidrug resistant strain that caused two outbreaks
reportedin Peru between 2010 and 2013. We found this BV1 lineage in the Colombian
Amazon as early as 2006. Two new clonal lineages were identified in these parasites
from Colombia: the genetic lineages EV1 and F. PfHRP2 sequence analysis revealed high
genetic diversity at the amino acid level, with 17 unique sequences identified among 53
PfHRP2 sequences analysed. The use of PfHRP2-based RDTs is not recommended in
Amazonas because of the high proportionof parasites with pfhrp2 deletion (38.5%), and
implementation of new strategies for malaria diagnosis and control in Amazonas must be
prioritised.Moreover, studies to monitor and genetically characterise pfhrp2-negative P. falciparumparasites in the Americas are warranted, given the extensive human migration
occurring in the region.

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