This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features!
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log in
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
doi: 10.1038/srep20100.

Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border

Affiliations

Distinctive origin of artemisinin-resistant Plasmodium falciparum on the China-Myanmar border

Run Ye et al. Sci Rep. .

Abstract

The artemisinin (ART), discovered in China, has been widely used against malaria in China over the last 30 years. Understanding the emergence and origin of ART resistance in China is therefore of great interest. We analyzed 111 culture-adapted isolates of P. falciparum from China-Myanmar (CM) border for their susceptibility to dihydroartemisinin using the ring stage survival assay (RSA0-3h) and genotyped their K13 genes. Of the isolates, 59 had a wild type of the K13 marker and a median ring survival rate of 0.26% (P95 = 1.005%). Among the remaining isolates harboring single mutations in the K13 marker, 26 survived at >P95(median survival rate = 2.95%). Further, we genotyped the K13 gene of 693 isolates collected from different regions in China and China-Myanmar/Thai-Cambodia/Thai-Myanmar (CM/TC/TM) borders, 308 (44.4%) had K13 mutations and marked differences in the patterns of K13 mutations were observed between the CM and the TC/TM borders. A network diagram showed that majority of the K13 mutant alleles from the CM border clustered together including those harboring the high resistant-associated R539T mutations. The resistant parasites carrying distinct halplotypes suggested the multiple indigenous origins of the resistant alleles, which highlight the importance of surveillance of resistance in all malaria endemic areas where ART has been introduced.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Map showing location of study sites and proportions of isolates with high survival rates and mutations of the K13 gene.
The proportions of isolates with parasite survival rates above P95 are indicated in orange and below P95 in pink in the Nabang-Lazan valley. The proportions of wild type isolates are shown in blue and with mutations in the propeller domain of the K13 gene in red. The map was created in ArcGIS 9.3 software (ESRI Inc., Redlands, CA, USA) (http://www.esri.com/).
Figure 2
Figure 2. Correlation of parasite survival rates in the RSA0−3h and K13 polymorphisms in 111 isolates.
Red circles: survival rates>P95; blue circles: survival rates <P95. One circle represents one isolate. The locations of the K13 mutations are indicated as amino acid positions. Mutations previously reported to be associated with ART resistance are indicated by an asterisk.
Figure 3
Figure 3. Network diagram revealing three geographically distinct origins for the R539T and C580Y mutant alleles.
Based on data from 11 neutral microsatellites and three SNPs (arps10, fd and pph), all 169 isolates were initially classified into two major independent networks, e.g. China-Myanmar(CM) group and Thailand-Cambodia/Thailand-Myanmar(TC/TM) group. Isolates from the CM border, the TC border and the TM border are shown in yellow, dark blue and sky-blue respectively. Dots with red and pink circles represent the isolates with K13 mutant alleles R539T and C580Y respectively. (A) origins of the R539T mutant allele, (B) origins of the C580Y mutant allele.
Figure 4
Figure 4. Haplotypes of the isolates with the R539T mutation from the China-Myanmar border, Thailand-Cambodia border and Thailand-Myanmar border.
The ten SNP markers are located in the six genes (KH3 1–6) that highly differentiated in KH3 subpopulation of Cambodia, where artemisinin-resistant isolates with R539T mutations are found. Haplotypes are defined based on the combination of the SNPs. w: wild type, DNW: no successful amplification.

References

    1. Tu Y. The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nat Med 17, 1217–20 (2011). - PubMed
    1. Miller L. H. & Su X. Artemisinin: discovery from the Chinese herbal garden. Cell 146, 855–8 (2011). - PMC - PubMed
    1. WHO. Guidelines for the treatment of malaria, Second edition. (World Health Organization, Geneva, 2010).
    1. Sinha S., Medhi B. & Sehgal R. Challenges of drug-resistant malaria. Parasite 21, 61 (2014). - PMC - PubMed
    1. Dondorp A. M. et al.. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361, 455–67 (2009). - PMC - PubMed

Publication types

Full text links
Nature Publishing Group full text link Nature Publishing Group Free PMC article
Cite

AltStyle によって変換されたページ (->オリジナル) /