Efficacy of Chloroquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Honduras

Torres, Rosa Elena Mejía; Banegas, Engels; Mendoza, Meisy; Díaz, César; Bucheli, Sandra Tamara Mancero; Fontecha, Gustavo; Alam, Tauqeer; Goldman, Ira F.; Udhayakumar, Venkatachalam; Zambrano, Jose Orlinder Nicolas

doi:10.4269/ajtmh.12-0671

Cited by 30 publications

(28 citation statements)

References 22 publications

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“…The primary and nested Pfmdr1 gene amplification (codons 86–184 and 1034–1246) was performed using 50–250 ng of DNA sample in a 25-µL PCR mix containing 0.5 µM of each primer and 1 × Promega Master Mix following previously published protocols [ 42 – 44 ]. The primary and nested PCR amplification for Pfcrt gene (codons 72–76) was performed using 50–250 ng of DNA sample in a 25-µL PCR mix containing a final concentration of 0.25 µM of each primer and 1 × Promega Master Mix as per a previously published protocol [ 45 ].…”

Section: Methodsmentioning

confidence: 99%

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Chebore

Zhou

Westercamp

et al. 2020

Malar J

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Background: Anti-malarial drug resistance remains a major threat to global malaria control efforts. In Africa, Plasmodium falciparum remains susceptible to artemisinin-based combination therapy (ACT), but the emergence of resistant parasites in multiple countries in Southeast Asia and concerns over emergence and/or spread of resistant parasites in Africa warrants continuous monitoring. The World Health Organization recommends that surveillance for molecular markers of resistance be included within therapeutic efficacy studies (TES). The current study assessed molecular markers associated with resistance to Artemether−lumefantrine (AL) and Dihydroartemisinin−piperaquine (DP) from samples collected from children aged 6-59 months enrolled in a TES conducted in Siaya County, western Kenya from 2016 to 2017. Methods: Three hundred and twenty-three samples collected pre-treatment (day-0) and 110 samples collected at the day of recurrent parasitaemia (up to day 42) were tested for the presence of drug resistance markers in the Pfk13 propeller domain, and the Pfmdr1 and Pfcrt genes by Sanger sequencing. Additionally, the Pfpm2 gene copy number was assessed by real-time polymerase chain reaction. Results: No mutations previously associated with artemisinin resistance were detected in the Pfk13 propeller region. However, other non-synonymous mutations in the Pfk13 propeller region were detected. The most common mutation found on day-0 and at day of recurrence in the Pfmdr1 multidrug resistance marker was at codon 184F. Very few mutations were found in the Pfcrt marker (< 5%). Within the DP arm, all recrudescent cases (8 sample pairs) that were tested for Pfpm2 gene copy number had a single gene copy. None of the associations between observed mutations and treatment outcomes were statistically significant. Conclusion: The results indicate absence of Pfk13 mutations associated with parasite resistance to artemisinin in this area and a very high proportion of wild-type parasites for Pfcrt. Although the frequency of Pfmdr1 184F mutations was high in these samples, the association with treatment failure did not reach statistical significance. As the spread of

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Section: Methodsmentioning

confidence: 99%

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Chebore

Zhou

Westercamp

et al. 2020

Malar J

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“…Sixty-eight P. falciparum samples that were collected during a previous study conducted between September 2008 and September 2009 in the city of Puerto Lempira, which is located in the province of Gracias a Dios, Honduras, were available for this retrospective investigation [ 11 ]. In the original study, filter paper blood spots were collected from febrile patients between the ages of six months and 60 years who had uncomplicated P. falciparum mono-infection and had provided written informed consent at the time of enrollment.…”

Section: Methodsmentioning

confidence: 99%

“…These patients participated in a clinical trial to assess the efficacy of chloroquine. Further information on the patients and study has been published previously [ 11 ]. The study was approved by the institutional ethical review committee of the Ethics Committee of the Medical Sciences Faculty of the National Autonomous University of Honduras (UNAH-IRB 00003070).…”

Section: Methodsmentioning

confidence: 99%

Prevalence of pfhrp2 and pfhrp3 gene deletions in Puerto Lempira, Honduras

Abdallah

Okoth

Fontecha

et al. 2015

Malar J

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102

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BackgroundRecent studies have demonstrated the deletion of the histidine-rich protein 2 (PfHRP2) gene (pfhrp2) in field isolates of Plasmodium falciparum, which could result in false negative test results when PfHRP2-based rapid diagnostic tests (RDTs) are used for malaria diagnosis. Although primary diagnosis of malaria in Honduras is determined based on microscopy, RDTs may be useful in remote areas. In this study, it was investigated whether there are deletions of the pfhrp2, pfhrp3 and their respective flanking genes in 68 P. falciparum parasite isolates collected from the city of Puerto Lempira, Honduras. In addition, further investigation considered the possible correlation between parasite population structure and the distribution of these gene deletions by genotyping seven neutral microsatellites.MethodsSixty-eight samples used in this study, which were obtained from a previous chloroquine efficacy study, were utilized in the analysis. All samples were genotyped for pfhrp2, pfhrp3 and flanking genes by PCR. The samples were then genotyped for seven neutral microsatellites in order to determine the parasite population structure in Puerto Lempira at the time of sample collection.ResultsIt was found that all samples were positive for pfhrp2 and its flanking genes on chromosome 8. However, only 50% of the samples were positive for pfhrp3 and its neighboring genes while the rest were either pfhrp3-negative only or had deleted a combination of pfhrp3 and its neighbouring genes on chromosome 13. Population structure analysis predicted that there are at least two distinct parasite population clusters in this sample population. It was also determined that a greater proportion of parasites with pfhrp3-(and flanking gene) deletions belonged to one cluster compared to the other.ConclusionThe findings indicate that the P. falciparum parasite population in the municipality of Puerto Lempira maintains the pfhrp2 gene and that PfHRP2-based RDTs could be considered for use in this region; however continued monitoring of parasite population will be useful to detect any parasites with deletions of pfhrp2.

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“…DNA isolates were sequenced for point mutations in Pfdhfr , Pfdhps , chloroquine resistance transporter ( Pfcrt ), and Pfmdr1 . The methods used are described elsewhere ( 14 , 16 , 21 , 23 , 24 ).…”

Section: Methodsmentioning

confidence: 99%

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

Baldeviano¹,

Okoth²,

Arróspide³

et al. 2015

Emerg. Infect. Dis.

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Efficacy of Chloroquine for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Honduras

Cited by 30 publications

References 22 publications

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

Prevalence of pfhrp2 and pfhrp3 gene deletions in Puerto Lempira, Honduras

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

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