Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction

Eugenia Lo, Jennifer Nguyen, Winny Oo, Elizabeth Hemming-Schroeder, Guofa Zhou, Zhaoqing Yang, Liwang Cui, Guiyun Yan

Research output: Contribution to journalArticle

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Abstract

Background: Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to reflect the susceptibility of parasites or the efficiency of antimalarials. The association of genetic polymorphisms and artemisinin resistance has been documented. This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar. Methods: A total of 63 P. falciparum and 130 P. vivax samples collected from two internally-displaced populations and one surrounding village were examined for parasitemia changes. At least four samples were taken from each patient, at the first day of diagnosis up to 3 months following the initial treatment. The amount of parasite gene copy number was estimated using quantitative real-time PCR based on a species-specific region of the 18S rRNA gene. For samples that showed residual or recurred parasitemia after treatment, microsatellites were used to identify the 'post-treatment' parasite genotype and compared such with the 'pre-treatment' genotype. Mutations in genes pfcrt, pfmdr1, pfatp6, pfmrp1 and pfK13 that are potentially associated with ACT resistance were examined to identify if mutation is a factor for residual or persistent parasitemia. Results: Over 30 % of the P. falciprium infections showed delayed clearance of parasitemia after 2-3 days of treatment and 9.5 % showed recurred parasitemia. Mutations in codon 876 of the pfmrp1 corroborated significance association with slow clearance time. However, no association was observed in the variation in pfmdr1 gene copy number as well as mutations of various codonsinpfatp6, pfcrt, and pfK13 with clearance time. For P. vivax, over 95 % of the infections indicated cleared parasitemia at days 2-3 of treatment. Four samples were found to be re-infected with new parasite strains based on microsatellite genotypes after initial treatment. Conclusion: The appearance of P.falciparum infected samples showing delayed clearance or recurred parasitemia after treatment raises concerns on current treatment and ACT drug resistance.

Original languageEnglish (US)
Article number154
JournalBMC Infectious Diseases
Volume16
Issue number1
DOIs
StatePublished - Apr 16 2016

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Myanmar
Parasitemia
Antimalarials
Plasmodium falciparum
Real-Time Polymerase Chain Reaction
China
Parasites
Mutation
Therapeutics
Gene Dosage
Genotype
Microsatellite Repeats
Genetic Polymorphisms
Infection
rRNA Genes
Drug Resistance
Codon
Genes
Malaria

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

Cite this

Lo, Eugenia ; Nguyen, Jennifer ; Oo, Winny ; Hemming-Schroeder, Elizabeth ; Zhou, Guofa ; Yang, Zhaoqing ; Cui, Liwang ; Yan, Guiyun. / Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction. In: BMC Infectious Diseases. 2016 ; Vol. 16, No. 1.
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title = "Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction",
abstract = "Background: Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to reflect the susceptibility of parasites or the efficiency of antimalarials. The association of genetic polymorphisms and artemisinin resistance has been documented. This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar. Methods: A total of 63 P. falciparum and 130 P. vivax samples collected from two internally-displaced populations and one surrounding village were examined for parasitemia changes. At least four samples were taken from each patient, at the first day of diagnosis up to 3 months following the initial treatment. The amount of parasite gene copy number was estimated using quantitative real-time PCR based on a species-specific region of the 18S rRNA gene. For samples that showed residual or recurred parasitemia after treatment, microsatellites were used to identify the 'post-treatment' parasite genotype and compared such with the 'pre-treatment' genotype. Mutations in genes pfcrt, pfmdr1, pfatp6, pfmrp1 and pfK13 that are potentially associated with ACT resistance were examined to identify if mutation is a factor for residual or persistent parasitemia. Results: Over 30 {\%} of the P. falciprium infections showed delayed clearance of parasitemia after 2-3 days of treatment and 9.5 {\%} showed recurred parasitemia. Mutations in codon 876 of the pfmrp1 corroborated significance association with slow clearance time. However, no association was observed in the variation in pfmdr1 gene copy number as well as mutations of various codonsinpfatp6, pfcrt, and pfK13 with clearance time. For P. vivax, over 95 {\%} of the infections indicated cleared parasitemia at days 2-3 of treatment. Four samples were found to be re-infected with new parasite strains based on microsatellite genotypes after initial treatment. Conclusion: The appearance of P.falciparum infected samples showing delayed clearance or recurred parasitemia after treatment raises concerns on current treatment and ACT drug resistance.",
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Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction. / Lo, Eugenia; Nguyen, Jennifer; Oo, Winny; Hemming-Schroeder, Elizabeth; Zhou, Guofa; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun.

In: BMC Infectious Diseases, Vol. 16, No. 1, 154, 16.04.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction

AU - Lo, Eugenia

AU - Nguyen, Jennifer

AU - Oo, Winny

AU - Hemming-Schroeder, Elizabeth

AU - Zhou, Guofa

AU - Yang, Zhaoqing

AU - Cui, Liwang

AU - Yan, Guiyun

PY - 2016/4/16

Y1 - 2016/4/16

N2 - Background: Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to reflect the susceptibility of parasites or the efficiency of antimalarials. The association of genetic polymorphisms and artemisinin resistance has been documented. This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar. Methods: A total of 63 P. falciparum and 130 P. vivax samples collected from two internally-displaced populations and one surrounding village were examined for parasitemia changes. At least four samples were taken from each patient, at the first day of diagnosis up to 3 months following the initial treatment. The amount of parasite gene copy number was estimated using quantitative real-time PCR based on a species-specific region of the 18S rRNA gene. For samples that showed residual or recurred parasitemia after treatment, microsatellites were used to identify the 'post-treatment' parasite genotype and compared such with the 'pre-treatment' genotype. Mutations in genes pfcrt, pfmdr1, pfatp6, pfmrp1 and pfK13 that are potentially associated with ACT resistance were examined to identify if mutation is a factor for residual or persistent parasitemia. Results: Over 30 % of the P. falciprium infections showed delayed clearance of parasitemia after 2-3 days of treatment and 9.5 % showed recurred parasitemia. Mutations in codon 876 of the pfmrp1 corroborated significance association with slow clearance time. However, no association was observed in the variation in pfmdr1 gene copy number as well as mutations of various codonsinpfatp6, pfcrt, and pfK13 with clearance time. For P. vivax, over 95 % of the infections indicated cleared parasitemia at days 2-3 of treatment. Four samples were found to be re-infected with new parasite strains based on microsatellite genotypes after initial treatment. Conclusion: The appearance of P.falciparum infected samples showing delayed clearance or recurred parasitemia after treatment raises concerns on current treatment and ACT drug resistance.

AB - Background: Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to reflect the susceptibility of parasites or the efficiency of antimalarials. The association of genetic polymorphisms and artemisinin resistance has been documented. This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar. Methods: A total of 63 P. falciparum and 130 P. vivax samples collected from two internally-displaced populations and one surrounding village were examined for parasitemia changes. At least four samples were taken from each patient, at the first day of diagnosis up to 3 months following the initial treatment. The amount of parasite gene copy number was estimated using quantitative real-time PCR based on a species-specific region of the 18S rRNA gene. For samples that showed residual or recurred parasitemia after treatment, microsatellites were used to identify the 'post-treatment' parasite genotype and compared such with the 'pre-treatment' genotype. Mutations in genes pfcrt, pfmdr1, pfatp6, pfmrp1 and pfK13 that are potentially associated with ACT resistance were examined to identify if mutation is a factor for residual or persistent parasitemia. Results: Over 30 % of the P. falciprium infections showed delayed clearance of parasitemia after 2-3 days of treatment and 9.5 % showed recurred parasitemia. Mutations in codon 876 of the pfmrp1 corroborated significance association with slow clearance time. However, no association was observed in the variation in pfmdr1 gene copy number as well as mutations of various codonsinpfatp6, pfcrt, and pfK13 with clearance time. For P. vivax, over 95 % of the infections indicated cleared parasitemia at days 2-3 of treatment. Four samples were found to be re-infected with new parasite strains based on microsatellite genotypes after initial treatment. Conclusion: The appearance of P.falciparum infected samples showing delayed clearance or recurred parasitemia after treatment raises concerns on current treatment and ACT drug resistance.

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DO - 10.1186/s12879-016-1482-6

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VL - 16

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

SN - 1471-2334

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