A four-year surveillance program for detection of Plasmodium falciparum chloroquine resistance in Honduras

Fontecha, Gustavo; Sánchez, Ana; Mendoza, Meisy; Banegas, Engels; Mejía-Torres, Rosa E

doi:10.1590/0074-0276140067

Cited by 11 publications

(14 citation statements)

References 13 publications

(18 reference statements)

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“…In countries where the change in policy from chloroquine to ACT was strictly enforced, marked decrease in chloroquine-resistant parasites in the population was recorded. In a recent surveillance study in Honduras, Central America, where CQ is still used for the management of uncomplicated malaria, all the samples tested showed CQ susceptibility in the Pfcrt “CVMNK” genotype in codons 72–76 [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine

2015

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BackgroundIn Nigeria, despite the change in National malaria drug policy to artemisinin combination therapy (ACT) in 2005 due to widespread chloroquine resistance, chloroquine (CQ) is still widely used in the treatment of malaria because it is cheap, affordable and accessible. The use of ACT for the management of uncomplicated malaria is currently being promoted. The employment of genetic markers to track circulating chloroquine-resistant parasites are useful in elucidating likely poor efficacy of chloroquine, especially in settings where it is not recommended for the treatment of uncomplicated falciparum malaria. This study determined the prevalence of pfcrt haplotypes and point mutations in pfmdr1 genes four years after the change in antimalarial treatment policy from CQ to the ACTs in Lagos, a commercial city in South-West, Nigeria.MethodsThis was a cross sectional study on uncomplicated malaria in children less than 12 years that presented with fever and other symptoms suggestive of malaria. Parasite DNA was extracted from 119 patients out of 251 children who were positive for Plasmodium falciparum by microscopy and amplified. The occurrence of haplotypes was investigated in pfcrt gene using probe-based qPCR and single nucleotide polymorphisms in pfmdr1 gene using nested PCR.ResultsOne hundred and nine (109) of the 119 children with P falciparum infection (91.6%) harbourd parasites with the mutant pfcrt haplotype (CVIET). Out of this, 4.2% comprised a mixture of genotypes encoding CVMNK and CVIET, while 4.2% had the wild type (CVMNK). Furthermore, the frequency of point mutations in pfmdr1 was 62.2% and 69.0% for codons Y86 and F184 respectively. There were no mutations at codons 1034, 1042 and 1246 of the Pfmdr1 genes.ConclusionThe high frequency of the CQ-resistant haplotypes (CVIET) and mutations in Pfmdr1 associated with CQ resistance in P. falciparum among these children suggest that CQ-resistant parasites are still in circulation. Continuous use of chloroquine may continue to increase the level of mutations in pfcrt and pfmdr1genes. There is need to strengthen current case management efforts at promoting ACT use as well as urgently restricting access to chloroquine by the National drug regulatory agency, National Agency for Food Drug Administration and Control (NAFDAC).Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2069472010142303

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Section: Discussionmentioning

confidence: 99%

Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine

2015

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“…Blood samples of patients infected with malaria falciparum were collected on Whatman™ filter paper (GE Healthcare Bio-Sciences Corp, NJ, USA) for routine chloroquine resistance surveillance [18, 19]. DNA was extracted through a Chelex-100 based method [20].…”

Section: Methodsmentioning

confidence: 99%

Genetic variability of Plasmodium falciparum histidine-rich proteins 2 and 3 in Central America

Fontecha

Pinto

Escobar

et al. 2019

Malar J

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BackgroundMalaria is an important disease in many tropical countries. Rapid diagnostic tests (RDTs) are valuable tools for diagnosing malaria in remote areas. The majority of RDTs used for the diagnosis of Plasmodium falciparum are based on the detection of the specific histidine-rich proteins (PfHRP2 and PfHRP3). During the last decade, the threat posed by the lack of expression of these antigens and the variability of the proteins on the diagnosis of malaria has been widely discussed. The aim of this study was to evaluate the genetic diversity of pfhrp2 and pfhrp3 of P. falciparum isolates collected in three Central American countries.MethodsDNA samples were amplified and sequenced to assess the diversity of nucleotides and amino acids. A search for known epitopes within the amino acid sequence was carried out, and the sensitivity of the sequences was evaluated according to a predictive model. A phylogenetic analysis was carried out including homologous sequences from different regions of the world. Protein structures were predicted in silico.ResultsFive different patterns for PfHRP2 and one pattern for PfHRP3 were identified. Isolates from Central America show a high level of genetic diversity in pfhrp2; however, the amino acid sequences seem to contain enough motifs to be detected by the RDTs currently available.ConclusionIt is unlikely that the variability of the pfhrp2 and pfhrp3 genes has a significant impact on the ability of the RDTs to detect the PfHRP antigens in Central America.Electronic supplementary materialThe online version of this article (10.1186/s12936-019-2668-3) contains supplementary material, which is available to authorized users.

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“…Pvmdr1 single and double copy calibrators were created by the insertion of pvmdr1 nucleotides 2751-3354 and pvbtubulin nucleotides 860-1056 in the pCR2.1 vector using the TOPO TA-cloning kit (Invitrogen, Carlsbad, CA) at 1:1 and 2:1 proportions, respectively. The sample copy numbers were calculated using a The ~100% pfcrt K76 frequency in Honduras and Liberia was in line with continued CQ efficacy in both countries [234,256]. Surprisingly and for principally unknown reasons P. falciparum in Honduras therefore remain susceptible to CQ despite six decades of use, the worldwide spread of CQ resistance and the sporadic occurrence of CQ resistant P. falciparum in Nicaragua [257].…”

Section: Real-time Pcrmentioning

confidence: 99%

Single nucleotide polymorphisms in Plasmodium falciparum V type H+ pyrophosphatase gene (pfvp2) and their associations with pfcrt and pfmdr1 polymorphisms

Jovel

Ferreira

Veiga

et al. 2014

Infection, Genetics and Evolution

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The VKP haplotype was dominant. Most pfvp2 405I, 582R and 711S SNPs were seen where CQ resistance was not highly prevalent at the time of blood sampling possibly due to greater genetic variation prior to the bottle neck event of spreading CQ resistance. The association between the pfvp2 VKP haplotype and pfcrt 76T, which may indicate that pfvp2 is involved in CQ resistance, should therefore be interpreted with caution.

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A four-year surveillance program for detection of Plasmodium falciparum chloroquine resistance in Honduras

Cited by 11 publications

References 13 publications

Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine

Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine

Genetic variability of Plasmodium falciparum histidine-rich proteins 2 and 3 in Central America

Single nucleotide polymorphisms in Plasmodium falciparum V type H+ pyrophosphatase gene (pfvp2) and their associations with pfcrt and pfmdr1 polymorphisms

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