Updates on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum

Zaw, Myo Thura; Emran, Nor Amalina; Wang, Qisheng

doi:10.1016/j.jmii.2017.06.009

Cited by 18 publications

(11 citation statements)

References 37 publications

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“…Our results are in agreement with previously published reports on the k13 gene from Africa, where a large number of non-artemisinin resistant associated SNPs have been reported. Notably, the K189T mutation, which is widely prevalent in African artemisininsensitive P. falciparum parasites [31] as well as in South East Asian parasites [32] was observed. We found no evidence of the putative I258M and Y268S/C SNPs associated with AP resistance [11,12], suggesting that the use of AP for prophylaxis for travelers to Eritrea remains effective.…”

Section: Discussionmentioning

confidence: 99%

Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodium falciparum isolates from an endemic African country using the Malaria Resistance Surveillance (MaRS) protocol

et al. 2020

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Background: Routine molecular surveillance for imported drug-resistant malaria parasites to the USA and European Union is an important public health activity. The obtained molecular data are used to help keep chemoprophylaxis and treatment guidelines up to date for persons traveling to malaria endemic countries. Recent advances in next-generation sequencing (NGS) technologies provide a new and effective way of tracking malaria drug-resistant parasites. Methods: As part of a technology transfer arrangement between the CDC Malaria Branch and the Istituto Superiore di Sanità (ISS), Rome, Italy, the recently described Malaria Resistance Surveillance (MaRS) protocol was used to genotype 148 Plasmodium falciparum isolates from Eritrea for kelch 13 (k13) and cytochrome b (cytb) genes, molecular markers associated with resistance to artemisinin (ART) and atovaquone/proguanil (AP), respectively. Results: Spanning the full-length k13 gene, seven non-synonymous single nucleotide polymorphisms (SNPs) were found (K189N, K189T, E208K, D281V, E401Q, R622I and T535M), of which none have been associated with artemisinin resistance. No mutations were found in cytochrome b. Conclusion: All patients successfully genotyped carried parasites susceptible to ART and AP treatment. Future studies between CDC Malaria Branch and ISS are planned to expand the MaRS system, including data sharing, in an effort to maintain up to date treatment guidelines for travelers to malaria endemic countries.

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Section: Discussionmentioning

confidence: 99%

Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodium falciparum isolates from an endemic African country using the Malaria Resistance Surveillance (MaRS) protocol

et al. 2020

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“…To date, F446I has mostly been prevalent near the China–Myanmar and Myanmar–India borders. Near the China–Myanmar border, F446I has been associated with delayed parasite clearance (12); however, this is not relevant to treatment outcomes in the Myanmar–India border area (27). In addition, A676D was previously identified in three studies including samples from northern Myanmar (26, 28, 29).…”

Section: Discussionmentioning

confidence: 99%

Investigation and Evaluation of Genetic Diversity of Plasmodium falciparum Kelch 13 Polymorphisms Imported From Southeast Asia and Africa in Southern China

Feng

Kong

et al. 2019

Front. Public Health

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Objectives: In this study, we aimed to analyse the genetic diversity Kelch 13 (K13) propeller allele of the Plasmodium falciparum isolates mainly imported from Southeast Asia and Africa in southern China, including the provinces of Yunnan and Guangxi. Methods: At enrolment, we collected blood samples from patients with confirmed cases of malaria infection between January 2012 and December 2017, for analysis. Individual patient information was obtained via a malaria surveillance system. The malaria infections and P. falciparum K13 mutations were diagnosed by using a nested polymerase chain reaction (PCR) method. Results: The K13 mutations were identified in 283 P. falciparum isolates from 18 counties in Yunnan and 22 counties in Guangxi. Of Forty-six isolates (46/283, 16.3%) that harbored K13 mutant alleles were detected: 26.8% in Yunnan (33/123) and 8.1% in Guangxi (13/160). A total of 18 different K13 mutations were detected. Only the F446I mutation was detected in Yunnan isolates, and F446I was more frequent (20/46, 43.5%) than other alleles. Further, the temporal distribution of the F446I mutation ratio from 2012 to 2015 exhibited no significant difference in Yunnan Province (2012, 2/13, 15.4%; 2013, 7/40, 17.5%; 2014, 7/33, 21.2%; 2015, 4/37, 10.8%, p = 0.121). A578S allele was the main K13 mutation (5/283, 1.8%) from Africa. The K13 mutants were present in 33.3% of indigenous isolates, 27.4% of isolates from Southeast Asia, and 7.9% of isolates from Africa. The analysis of 10 neutral microsatellite loci of 60 isolates showed that at the TAA109 locus, the expected heterozygosity of F446I ( H e = 0.112 ± 0.007) was much lower than that of wild type and other mutation types in Myanmar isolates. With respect to geographic distribution, TAA109 also exhibited a significant difference between isolates from Southeast Asia ( H e = 0.139 ± 0.012) and those from Africa ( H e = 0.603 ± 0.044). Conclusions: The present findings on the geographic diversity of K13 mutant alleles in P. falciparum may provide a basis for routine molecular surveillance and risk assessment, to monitor artemisinin resistance (ART) in China. Our results will be helpful for enriching the artemisinin resistance database in China during the elimination and post-elimination phases.

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“…It is of particular concern that biological resistance has evolved in both mosquito vectors and malaria parasites [2]. While parasite resistance to ACT is currently confined to the Greater Mekong Subregion of South-East Asia [6, 7], mosquito resistance to pyrethroids (the most common group of insecticides used in bed nets) is now widespread across sub-Saharan Africa [8, 9]. There is a compelling need to develop new anti-malaria tools to complement current interventions.…”

Section: Introductionmentioning

confidence: 99%

Modelling the potential of genetic control of malaria mosquitoes at national scale

2019

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Background The persistence of malaria in large parts of sub-Saharan Africa has motivated the development of novel tools to complement existing control programmes, including gene-drive technologies to modify mosquito vector populations. Here, we use a stochastic simulation model to explore the potential of using a driving-Y chromosome to suppress vector populations in a 10 6 km 2 area of West Africa including all of Burkina Faso. Results The consequence of driving-Y introductions is predicted to vary across the landscape, causing elimination of the target species in some regions and suppression in others. We explore how this variation is determined by environmental conditions, mosquito behaviour, and the properties of the gene-drive. Seasonality is particularly important, and we find population elimination is more likely in regions with mild dry seasons whereas suppression is more likely in regions with strong seasonality. Conclusions Despite the spatial heterogeneity, we suggest that repeated introductions of modified mosquitoes over a few years into a small fraction of human settlements may be sufficient to substantially reduce the overall number of mosquitoes across the entire geographic area. Electronic supplementary material The online version of this article (10.1186/s12915-019-0645-5) contains supplementary material, which is available to authorized users.

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Updates on k13 mutant alleles for artemisinin resistance in Plasmodium falciparum

Abstract: According to the updates in the review, it can be concluded artemisinin resistance does not disseminate to India and African countries within short period whereas regular tracking of these mutants is necessary.

Cited by 18 publications

References 37 publications

Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodium falciparum isolates from an endemic African country using the Malaria Resistance Surveillance (MaRS) protocol

Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodium falciparum isolates from an endemic African country using the Malaria Resistance Surveillance (MaRS) protocol

Investigation and Evaluation of Genetic Diversity of Plasmodium falciparum Kelch 13 Polymorphisms Imported From Southeast Asia and Africa in Southern China

Modelling the potential of genetic control of malaria mosquitoes at national scale

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