Imperial College London
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Professor Jake Baum

Faculty of Natural Sciences, Department of Life Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 5420jake.baum Website

 
 
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Location

 

c/o Baum labSir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Witmer:2021:10.1128/AAC.00898-20,
author = {Witmer, K and Dahalan, F and Delves, M and Yahiya, S and Watson, O and Straschil, U and Chiwcharoen, D and Sorboon, B and Pukrittayakamee, S and Pearson, R and Howick, V and Lawniczak, M and White, N and Dondorp, A and Okell, L and Chotivanich, K and Ruecker, A and Baum, J},
doi = {10.1128/AAC.00898-20},
journal = {Antimicrobial Agents and Chemotherapy},
pages = {1--17},
title = {Transmission of artemisinin-resistant malaria parasites to mosquitoes under antimalarial drug pressure},
url = {http://dx.doi.org/10.1128/AAC.00898-20},
volume = {65},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Resistance to artemisinin-based combination therapy (ACT) in the Plasmodium falciparum parasite is threatening to reverse recent gains in reducing global deaths from malaria. Whilst resistance manifests as delayed parasite clearance in patients the phenotype can only spread geographically via the sexual stages and mosquito transmission. In addition to their asexual killing properties, artemisinin and its derivatives sterilise sexual male gametocytes. Whether resistant parasites overcome this sterilising effect has not, however, been fully tested. Here, we analysed P. falciparum clinical isolates from the Greater Mekong Subregion, each demonstrating delayed clinical clearance and known resistance-associated polymorphisms in Kelch13 (PfK13var). As well as demonstrating reduced asexual sensitivity to drug, certain PfK13var isolates demonstrated a marked reduction in sensitivity to artemisinin in an in vitro male gamete formation assay. Importantly, this same reduction in sensitivity was observed when the most resistant isolate was tested directly in mosquito feeds. These results indicate that, under artemisinin drug pressure, whilst sensitive parasites are blocked, resistant parasites continue transmission. This selective advantage for resistance transmission could favour acquisition of additional host-specificity or polymorphisms affecting partner drug sensitivity in mixed infections. Favoured resistance transmission under ACT coverage could have profound implications for the spread of multidrug resistant malaria beyond Southeast Asia.
AU  - Witmer,K
AU  - Dahalan,F
AU  - Delves,M
AU  - Yahiya,S
AU  - Watson,O
AU  - Straschil,U
AU  - Chiwcharoen,D
AU  - Sorboon,B
AU  - Pukrittayakamee,S
AU  - Pearson,R
AU  - Howick,V
AU  - Lawniczak,M
AU  - White,N
AU  - Dondorp,A
AU  - Okell,L
AU  - Chotivanich,K
AU  - Ruecker,A
AU  - Baum,J
DO  - 10.1128/AAC.00898-20
EP  - 17
PY  - 2021///
SN  - 0066-4804
SP  - 1
TI  - Transmission of artemisinin-resistant malaria parasites to mosquitoes under antimalarial drug pressure
T2  - Antimicrobial Agents and Chemotherapy
UR  - http://dx.doi.org/10.1128/AAC.00898-20
UR  - https://aac.asm.org/content/65/1/e00898-20/
UR  - http://hdl.handle.net/10044/1/84903
VL  - 65
ER  -
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