Quadruple Mutations in Dihydrofolate Reductase of
            <i>Plasmodium falciparum</i>
            Isolates from Car Nicobar Island, India

Ahmed, Anwar; Das, Manoj; Dev, Vas; Saifi, Muheet Alam; Wajihullah,; Sharma, Yagya D.

doi:10.1128/aac.50.4.1546-1549.2006

Cited by 33 publications

(37 citation statements)

References 15 publications

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“…Este escenario en el año 2002 puede haberse modificado, incrementando el número de mutaciones en cada población. Al respecto, la presencia de tres o más mutaciones en un mismo gen se ha asociado a resistencia constitutiva (11) , por lo que es conveniente buscar nuevas posibilidades de otros antimaláricos que en combinación terapéutica pueden ser más eficaces en la contención de la enfermedad.…”

Section: Discussionunclassified

“…La vigilancia molecular tiene como objetivo evaluar el comportamiento génico de las cepas de P. falciparum que, finalmente, se podían traducir en un seguimiento de las resistencias constitutivas, expresadas como un mayor número de mutaciones en los alelos evaluados (10,11) ; así como una vigilancia coordinada con resistencias presentes en otros países con asociación de los genes evaluados, y con ello poder tener mayor cuidado al momento de realizar las recomendaciones sobre los nuevos esquemas terapéuticos. El objetivo del estudio fue identificar la frecuencia de mutaciones genéticas asociados a la resistencia de cloroquina y sulfadoxina-pirimetamina en la frontera del Ecuador, colindante con Perú y Colombia.…”

Section: Introductionunclassified

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Alelos mutantes asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en Plasmodium falciparum de las fronteras Ecuador-Perú y Ecuador-Colombia

Arróspide

Hijar-Guerra

Mora³

et al. 2014

Rev Peru Med Exp Salud Publica

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RESUMENSe evaluó la frecuencia de mutaciones en los genes pfCRT y DHFR/DHPS del Plasmodium falciparum asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en 83 cepas provenientes de los distritos Esmeralda y Machala ubicados en las fronteras entre Ecuador-Perú y Ecuador-Colombia durante el año 2002. Se empleó la reacción en cadena de polimerasa (PCR) convencional y sus variantes. El gen pfCRT presentó más de 90% de muestras mutantes en Esmeralda y Machala. Para el gen DHFR, el 90% de las cepas fueron muestras mutantes en Esmeralda, tres fueron mutaciones dobles y una triple; en Machala se encontró 25% de formas mutantes simples y 75% de formas mixtas (formas silvestres/mutantes). En conclusión, la resistencia a cloroquina se ha fijado en las cepas portadoras de la mutación K76T pfCRT, mientras que la impronta genética a la resistencia a pirimetamina está en evolución, principalmente en el distrito de Esmeralda.Palabras clave: Plasmodium falciparum; Resistencia bacteriana a fármacos; Cloroquina; Sulfadoxina; Pirimetamina (fuente: DeCS BIREME) MUTANT ALLELES ASSOCIATED TO CHLOROQUINE AND SULFADOXINE-PYRIMETHANIME RESISTANCE IN Plasmodium falciparum OF THE ECUADOR-PERU AND ECUADOR-COLOMBIA BORDERS ABSTRACTThe frequency of mutations in pfCRT and DHFR/DHPS genes of Plasmodium falciparum associated with resistance to chloroquine and sulfadoxine-pyrimethamine was evaluated in 83 strains from the districts of Esmeralda and Machala, located on the borders of Ecuador-Peru and Ecuador-Colombia in 2002. Polymerase chain reaction (PCR), conventional and its variants, was used. Mutations in the pfCRT gene were found in more than 90% of the samples from Esmeralda and Machala. For the DHFR gene, 90% of the strains were mutant samples from Esmeralda, 3 were double mutations and 1 was a triple mutation. In Machala, 25% were simple mutant forms and 75% mixed mutant forms (wild forms/mutant). In conclusion, resistance to chloroquine has been fixed in strains carrying K76T pfCRT mutation, whereas genetic imprinting for resistance to pyrimethamine is evolving, particularly in the district of Esmeralda.

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Section: Discussionunclassified

Section: Introductionunclassified

Alelos mutantes asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en Plasmodium falciparum de las fronteras Ecuador-Perú y Ecuador-Colombia

Arróspide

Hijar-Guerra

Mora³

et al. 2014

Rev Peru Med Exp Salud Publica

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“…in contrast, higher levels of sP resistance and treatment failures were recorded from Kenya, tanzania, northeastern part of india, Ethiopia and the sudan, where intense malaria transmission was observed and P. falciparum species dominates over P. vivax (Pearce et al 2003, Ahmad et al 2006, schunk et al 2006. it seems that there is an association between the degree of malaria transmission and number of pfdhfr mutations.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of mutation and phenotypic expression associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum and Plasmodium vivax

Zakai¹,

Khan²,

Asma³

2013

FOLIA PARASIT

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therapeutic efficacy of sulfadoxine-pyrimethamine (sP), which is commonly used to treat falciparum malaria, was assessed in isolates of Plasmodium falciparum (Welch, 1897) and Plasmodium vivax (grassi et Feletti, 1890) of Aligarh, Uttar Pradesh, North india and taif, saudi Arabia during 2011-2012. Both the species showed mutations in dihydrofolate reductase (DHFr) enzyme as they have common biochemical drug targets. Mutation rate for pfdhfr was higher compared to pvdhfr because the drug was mainly given to treat falciparum malaria. since both the species coexist, P. vivax was also exposed to sP due to faulty species diagnosis or medication without specific diagnosis. low level of mutations against sP in P. falciparum of saudi isolates indicates that the sP combination is still effective for the treatment of falciparum malaria. since sP is used as first-line of treatment because of high level of resistance against chloroquine (cQ), it may result in spread of higher level of mutations resulting in drug resistance and treatment failure in near future. therefore, to avoid further higher mutations in the parasite, use of better treatment regimens such as artesunate combination therapy must be introduced against sP combination.

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“…Over 90% of the total malaria incidence is reported from sub-Saharan and tropical Africa; however, each year Southeast Asia, including the Indian subcontinent, reports approximately 2.5 million malaria cases, 75% of which are from India (20). Further, Plasmodium falciparum incidence in India has increased dramatically over the past few years, including the spread of drugresistant strains (1,2,23,46,47).…”

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confidence: 99%

Evidence of Selective Sweeps in Genes Conferring Resistance to Chloroquine and Pyrimethamine in Plasmodium falciparum Isolates in India

Mixson‐Hayden

Jain

McCollum

et al. 2010

Antimicrob Agents Chemother

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Treatment of Plasmodium falciparum is complicated by the emergence and spread of parasite resistance to many of the first-line drugs used to treat malaria. Antimalarial drug resistance has been associated with specific point mutations in several genes, suggesting that these single nucleotide polymorphisms can be useful in tracking the emergence of drug resistance. In India, P. falciparum infection can manifest itself as asymptomatic, mild, or severe malaria, with or without cerebral involvement. We tested whether chloroquine-and antifolate drug-resistant genotypes would be more commonly associated with cases of cerebral malaria than with cases of mild malaria in the province of Jabalpur, India, by genotyping the dhps, dhfr, pfmdr-1, and pfcrt genes using pyrosequencing, direct sequencing, and real-time PCR. Further, we used microsatellites surrounding the genes to determine the origins and spread of the drug-resistant genotypes in this area. Resistance to chloroquine was essentially fixed, with 95% of the isolates harboring the pfcrt K76T mutation. Resistant genotypes of dhfr, dhps, and pfmdr-1 were found in 94%, 17%, and 77% of the isolates, respectively. Drugresistant genotypes were equally likely to be associated with cerebral malaria as with mild malaria. We found evidence of a selective sweep in pfcrt and, to a lesser degree, in dhfr, indicating high levels of resistance to chloroquine and evolving resistance to pyrimethamine. Microsatellites surrounding pfcrt indicate that the resistant genotypes (SVMNT) were most similar to those found in Papua New Guinea.

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Quadruple Mutations in Dihydrofolate Reductase of Plasmodium falciparum Isolates from Car Nicobar Island, India

Cited by 33 publications

References 15 publications

Alelos mutantes asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en Plasmodium falciparum de las fronteras Ecuador-Perú y Ecuador-Colombia

Alelos mutantes asociados a la resistencia a cloroquina y sulfadoxina-pirimetamina en Plasmodium falciparum de las fronteras Ecuador-Perú y Ecuador-Colombia

Prevalence of mutation and phenotypic expression associated with sulfadoxine-pyrimethamine resistance in Plasmodium falciparum and Plasmodium vivax

Evidence of Selective Sweeps in Genes Conferring Resistance to Chloroquine and Pyrimethamine in Plasmodium falciparum Isolates in India

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