Malaria parasites imported to China from Central and Western Africa bear high frequencies of mutations conferring resistance to sulfadoxine-pyramethamine, constraining treatment options for source and recipient populations

Authors: ZHAO, LUYI - Kunming Medical University; PI, LIANG - Kunming Medical University; QIN, YUCHENG - Shanglin County People’s Hospital; LU, YUXIN - Shanglin County People’s Hospital; ZENG, WEILIN - Kunming Medical University; XIANG, ZHENG - Kunming Medical University; WEI, XIAOSHENG - Shanglin County People’s Hospital; CHEN, XI - Kunming Medical University; LI, CUIYING - Kunming Medical University; ZHANG, YANMEI - Kunming Medical University; WANG, SIQI - Kunming Medical University; SI, YU - Kunming Medical University; YANG, GONGCHAO - University Of Mississippi Medical Center; HUANG, YAMING - Shanglin County People’s Hospital; Rosenthal, Benjamin; YANG, ZHAOQING - Kunming Medical University

Submitted to: International Journal for Parasitology: Drugs and Drug Resistance
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2019
Publication Date: 11/29/2019
Citation: Zhao, L., Pi, L., Qin, Y., Lu, Y., Zeng, W., Xiang, Z., Wei, X., Chen, X., Li, C., Zhang, Y., Wang, S., Si, Y., Yang, G., Huang, Y., Rosenthal, B.M., Yang, Z. 2019. Malaria parasites imported to China from Central and Western Africa bear high frequencies of mutations conferring resistance to sulfadoxine-pyramethamine, constraining treatment options for source and recipient populations. International Journal for Parasitology: Drug and Drug Resistance. 12:1-6. https://doi.org/10.1016/j.ijpddr.2019.11.002.
DOI: https://doi.org/10.1016/j.ijpddr.2019.11.002

Interpretive Summary: The movement of people and livestock can redistribute variants of pathogens and parasites, creating new challenges for management in recipient countries and shedding important light on conditions abroad. Understanding these processes for parasites important to livestock and human health is crucial to assist veterinarians, physicians, public health officials and those entrusted to safeguard domestic agricultural activities. Here, USDA scientists assisted a team seeking to understand the characteristics of malaria imported to China from Central and West Africa as a model to understand the movement of parasitic infections. They discovered that these imported parasites are very different from those that once were endemic to China, and bear a worrying array of mutations that confer resistance to commonly-used drugs to treat pregnant women and infants. These data alert clinicians to the limits of their customary treatment protocols, and provide more general information concerning the speed by which highly-adapted human and livestock parasites can be spread in an increasingly globalized economy. The result will be of interest to epidemiologists, geneticists, parasitologists, microbiologists, and those engaged in international travel and trade.

Technical Abstract: Imported cases of infectious disease provide invaluable information about epidemiological conditions abroad, and should guide treatment decisions at home and abroad. Here, we examined cases of malaria imported from Africa to China for mutations eroding the efficacy of sulfadoxine-pyrimethamine (SP), sometimes used as an intermittent preventive treatment during for pregnant women and infants. A total of 208 blood samples were collected from P. falciparum-infected workers who had returned from West and Central Africa to Guangxi Province. Samples were analyzed for mutations in dhfr and dhps genes by PCR -sequencing. Drug resistance was widespread in this cohort. A triple-mutant dhfr haplotype most prevalent (>70%), with few wild-type alleles present in cases imported from either West or Central Africa. We report for the first time mutation I164L-dhfr and I431V-dhps in Ghana, and for the first time we found A581G to exceed a clinically-relevant threshold that may counter-indicate current clinical practices. For Pfdhps, the double-mutant IAGKAA was high prevalent haplotype in Ghana, Western Africa. The single-mutant ISGKAA was a majority haplotype in Cameroon. Alarmingly, a quintuple mutant (when considering mutations in both genes) suggest the emergence of ‘super resistance’, possibly limiting the efficacy of this drug combination for even intermittent clinical applications. These data are cause for great concern and call for continued surveillance of the efficacy of SP in source and recipient populations, and should be considered when developing treatment policy for imported malaria cases in China and elsewhere.