@article{Watson:2022:10.1016/S2666-5247(22)00155-0,
author = {Watson, OJ and Gao, B and Nguyen, TD and Tran, TN-A and Penny, MA and Smith, DL and Okell, L and Aguas, R and Boni, MF},
doi = {10.1016/S2666-5247(22)00155-0},
journal = {The Lancet Microbe},
pages = {e701--e710},
title = {Pre-existing partner-drug resistance to artemisinin combination therapies facilitates the emergence and spread of artemisinin resistance: a consensus modelling study},
url = {http://dx.doi.org/10.1016/S2666-5247(22)00155-0},
volume = {3},
year = {2022}
}

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TY  - JOUR
AB  - BACKGROUND: Artemisinin-resistant genotypes of Plasmodium falciparum have now emerged a minimum of six times on three continents despite recommendations that all artemisinins be deployed as artemisinin combination therapies (ACTs). Widespread resistance to the non-artemisinin partner drugs in ACTs has the potential to limit the clinical and resistance benefits provided by combination therapy. We aimed to model and evaluate the long-term effects of high levels of partner-drug resistance on the early emergence of artemisinin-resistant genotypes. METHODS: Using a consensus modelling approach, we used three individual-based mathematical models of Plasmodium falciparum transmission to evaluate the effects of pre-existing partner-drug resistance and ACT deployment on the evolution of artemisinin resistance. Each model simulates 100 000 individuals in a particular transmission setting (malaria prevalence of 1%, 5%, 10%, or 20%) with a daily time step that updates individuals' infection status, treatment status, immunity, genotype-specific parasite densities, and clinical state. We modelled varying access to antimalarial drugs if febrile (coverage of 20%, 40%, or 60%) with one primary ACT used as first-line therapy: dihydroartemisinin-piperaquine (DHA-PPQ), artesunate-amodiaquine (ASAQ), or artemether-lumefantrine (AL). The primary outcome was time until 0·25 580Y allele frequency for artemisinin resistance (the establishment time). FINDINGS: Higher frequencies of pre-existing partner-drug resistant genotypes lead to earlier establishment of artemisinin resistance. Across all models, a 10-fold increase in the frequency of partner-drug resistance genotypes on average corresponded to loss of artemisinin efficacy 2-12 years earlier. Most reductions in time to artemisinin resistance establishment were observed after an increase in frequency of the partner-drug resistance genotype from 0·0 to 0·10. INTERPRETATION: Partner-drug resistance in ACTs facil
AU  - Watson,OJ
AU  - Gao,B
AU  - Nguyen,TD
AU  - Tran,TN-A
AU  - Penny,MA
AU  - Smith,DL
AU  - Okell,L
AU  - Aguas,R
AU  - Boni,MF
DO  - 10.1016/S2666-5247(22)00155-0
EP  - 710
PY  - 2022///
SN  - 2666-5247
SP  - 701
TI  - Pre-existing partner-drug resistance to artemisinin combination therapies facilitates the emergence and spread of artemisinin resistance: a consensus modelling study
T2  - The Lancet Microbe
UR  - http://dx.doi.org/10.1016/S2666-5247(22)00155-0
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35931099
UR  - http://hdl.handle.net/10044/1/101274
VL  - 3
ER  - 

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