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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.
BMC Infect Dis. 2016 Apr 16; 16:154.BI

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.

Authors+Show Affiliations

Program in Public Health, University of California at Irvine, Irvine, CA, 92697-4050, USA.Program in Public Health, University of California at Irvine, Irvine, CA, 92697-4050, USA.Program in Public Health, University of California at Irvine, Irvine, CA, 92697-4050, USA.Program in Public Health, University of California at Irvine, Irvine, CA, 92697-4050, USA.Program in Public Health, University of California at Irvine, Irvine, CA, 92697-4050, USA.Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.Department of Entomology, Pennsylvania State University, University Park, PA, USA.Program in Public Health, University of California at Irvine, Irvine, CA, 92697-4050, USA. guiyuny@uci.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27084511

Citation

Lo, Eugenia, et al. "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." BMC Infectious Diseases, vol. 16, 2016, p. 154.
Lo E, Nguyen J, Oo W, et al. 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. BMC Infect Dis. 2016;16:154.
Lo, E., Nguyen, J., Oo, W., Hemming-Schroeder, E., Zhou, G., Yang, Z., Cui, L., & Yan, G. (2016). 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. BMC Infectious Diseases, 16, 154. https://doi.org/10.1186/s12879-016-1482-6
Lo E, et al. 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. BMC Infect Dis. 2016 Apr 16;16:154. PubMed PMID: 27084511.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2016/04/16/ PY - 2015/09/09/received PY - 2016/03/25/accepted PY - 2016/4/17/entrez PY - 2016/4/17/pubmed PY - 2016/10/27/medline KW - Artemisinin-combined therapy KW - Malaria KW - Microsatellite KW - P. falciparum KW - P. vivax KW - Parasite clearance KW - Quantitative PCR KW - Resistance genes SP - 154 EP - 154 JF - BMC infectious diseases JO - BMC Infect. Dis. VL - 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. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/27084511/full_citation L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-1482-6 DB - PRIME DP - Unbound Medicine ER -