TY - JOUR
T1 - Longitudinal surveillance of drug resistance in Plasmodium falciparum isolates from the China-Myanmar border reveals persistent circulation of multidrug resistant parasites
AU - Bai, Yao
AU - Zhang, Jiaqi
AU - Geng, Jinting
AU - Xu, Shiling
AU - Deng, Shuang
AU - Zeng, Weilin
AU - Wang, Zenglei
AU - Ngassa Mbenda, Huguette Gaelle
AU - Zhang, Jie
AU - Li, Na
AU - Wu, Yanrui
AU - Li, Cuiying
AU - Liu, Huae
AU - Ruan, Yonghua
AU - Cao, Yaming
AU - Yang, Zhaoqing
AU - Cui, Liwang
N1 - Funding Information:
The authors wish to thank the field team for their assistance in sample collection. We are grateful to the local communities and hospitals for their participation in this research. This project was funded by the National Natural Science Foundation of China ( 31260508 to ZY, 81761128017 to YC), and the National Institutes of Health ( U19 AI089672 and R01 AI128940 to LC). YW and CL were supported by grant 2014FB005 and 2017FE468-185 from Yunnan Province . HL was supported by the Ph.D. Starting Fund from Kunming Medical University (# 1 ).
Funding Information:
The authors wish to thank the field team for their assistance in sample collection. We are grateful to the local communities and hospitals for their participation in this research. This project was funded by the National Natural Science Foundation of China (31260508 to ZY, 81761128017 to YC), and the National Institutes of Health (U19 AI089672 and R01 AI128940 to LC). YW and CL were supported by grant 2014FB005 and 2017FE468-185 from Yunnan Province. HL was supported by the Ph.D. Starting Fund from Kunming Medical University (#1).
Publisher Copyright:
© 2018
PY - 2018/8
Y1 - 2018/8
N2 - Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007–2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC50 values to all the drugs tested as compared to the reference 3D7 strain. Parasites were also genotyped in seven genes that were associated with drug resistance including pfcrt, pfmdr1, pfmrp1, pfdhfr, pfdhps, pfnhe1, and PfK13 genes. Despite withdrawal of chloroquine and antifolates from treating P. falciparum, parasites remained highly resistant to these drugs and mutations in pfcrt, pfdhfr, and pfdhps genes were highly prevalent and almost reached fixation in the study parasite population. Except for pyronaridine, quinine and lumefantrine, all other tested drugs exhibited significant temporal variations at least between some years, but only chloroquine and piperaquine had a clear temporal trend of continuous increase of IC50s. For the pfmrp1 gene, several mutations were associated with altered sensitivity to a number of drugs tested including chloroquine, piperaquine, lumefantrine and dihydroartemisinin. The association of PfK13 mutations with resistance to multiple drugs suggests potential evolution of PfK13 mutations amid multidrug resistance genetic background. Furthermore, network analysis of drug resistance genes indicated that certain haplotypes associated multidrug resistance persisted in these years, albeit there were year-to-year fluctuations of the predominant haplotypes.
AB - Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007–2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC50 values to all the drugs tested as compared to the reference 3D7 strain. Parasites were also genotyped in seven genes that were associated with drug resistance including pfcrt, pfmdr1, pfmrp1, pfdhfr, pfdhps, pfnhe1, and PfK13 genes. Despite withdrawal of chloroquine and antifolates from treating P. falciparum, parasites remained highly resistant to these drugs and mutations in pfcrt, pfdhfr, and pfdhps genes were highly prevalent and almost reached fixation in the study parasite population. Except for pyronaridine, quinine and lumefantrine, all other tested drugs exhibited significant temporal variations at least between some years, but only chloroquine and piperaquine had a clear temporal trend of continuous increase of IC50s. For the pfmrp1 gene, several mutations were associated with altered sensitivity to a number of drugs tested including chloroquine, piperaquine, lumefantrine and dihydroartemisinin. The association of PfK13 mutations with resistance to multiple drugs suggests potential evolution of PfK13 mutations amid multidrug resistance genetic background. Furthermore, network analysis of drug resistance genes indicated that certain haplotypes associated multidrug resistance persisted in these years, albeit there were year-to-year fluctuations of the predominant haplotypes.
UR - http://www.scopus.com/inward/record.url?scp=85047315099&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047315099&partnerID=8YFLogxK
U2 - 10.1016/j.ijpddr.2018.05.003
DO - 10.1016/j.ijpddr.2018.05.003
M3 - Article
C2 - 29793059
AN - SCOPUS:85047315099
SN - 2211-3207
VL - 8
SP - 320
EP - 328
JO - International Journal for Parasitology: Drugs and Drug Resistance
JF - International Journal for Parasitology: Drugs and Drug Resistance
IS - 2
ER -
