Pre-existing partner-drug resistance to artemisinin combination therapies facilitates the emergence and spread of artemisinin resistance : a consensus modelling study
Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved..
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 facilitates the early emergence of artemisinin resistance and is a major public health concern. Higher-grade partner-drug resistance has the largest effect, with piperaquine resistance accelerating the early emergence of artemisinin-resistant alleles the most. Continued investment in molecular surveillance of partner-drug resistant genotypes to guide choice of first-line ACT is paramount.
FUNDING: Schmidt Science Fellowship in partnership with the Rhodes Trust; Bill & Melinda Gates Foundation; Wellcome Trust.
Errataetall: | |
---|---|
Medienart: |
E-Artikel |
Erscheinungsjahr: |
2022 |
---|---|
Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
---|---|
Enthalten in: |
The Lancet. Microbe - 3(2022), 9 vom: 28. Sept., Seite e701-e710 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Watson, Oliver J [VerfasserIn] |
---|
Links: |
---|
Themen: |
Antimalarials |
---|
Anmerkungen: |
Date Completed 08.09.2022 Date Revised 08.02.2023 published: Print-Electronic ErratumIn: Lancet Microbe. 2022 Nov 25;:. - PMID 36442493 Citation Status MEDLINE |
---|
doi: |
10.1016/S2666-5247(22)00155-0 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM344505782 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM344505782 | ||
003 | DE-627 | ||
005 | 20231226022927.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2022 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/S2666-5247(22)00155-0 |2 doi | |
028 | 5 | 2 | |a pubmed24n1148.xml |
035 | |a (DE-627)NLM344505782 | ||
035 | |a (NLM)35931099 | ||
035 | |a (PII)S2666-5247(22)00155-0 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Watson, Oliver J |e verfasserin |4 aut | |
245 | 1 | 0 | |a Pre-existing partner-drug resistance to artemisinin combination therapies facilitates the emergence and spread of artemisinin resistance |b a consensus modelling study |
264 | 1 | |c 2022 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 08.09.2022 | ||
500 | |a Date Revised 08.02.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a ErratumIn: Lancet Microbe. 2022 Nov 25;:. - PMID 36442493 | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. | ||
520 | |a 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 | ||
520 | |a 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) | ||
520 | |a 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 | ||
520 | |a INTERPRETATION: Partner-drug resistance in ACTs facilitates the early emergence of artemisinin resistance and is a major public health concern. Higher-grade partner-drug resistance has the largest effect, with piperaquine resistance accelerating the early emergence of artemisinin-resistant alleles the most. Continued investment in molecular surveillance of partner-drug resistant genotypes to guide choice of first-line ACT is paramount | ||
520 | |a FUNDING: Schmidt Science Fellowship in partnership with the Rhodes Trust; Bill & Melinda Gates Foundation; Wellcome Trust | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Antimalarials |2 NLM | |
650 | 7 | |a Artemether, Lumefantrine Drug Combination |2 NLM | |
650 | 7 | |a Artemether |2 NLM | |
650 | 7 | |a C7D6T3H22J |2 NLM | |
700 | 1 | |a Gao, Bo |e verfasserin |4 aut | |
700 | 1 | |a Nguyen, Tran Dang |e verfasserin |4 aut | |
700 | 1 | |a Tran, Thu Nguyen-Anh |e verfasserin |4 aut | |
700 | 1 | |a Penny, Melissa A |e verfasserin |4 aut | |
700 | 1 | |a Smith, David L |e verfasserin |4 aut | |
700 | 1 | |a Okell, Lucy |e verfasserin |4 aut | |
700 | 1 | |a Aguas, Ricardo |e verfasserin |4 aut | |
700 | 1 | |a Boni, Maciej F |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t The Lancet. Microbe |d 2020 |g 3(2022), 9 vom: 28. Sept., Seite e701-e710 |w (DE-627)NLM312200277 |x 2666-5247 |7 nnns |
773 | 1 | 8 | |g volume:3 |g year:2022 |g number:9 |g day:28 |g month:09 |g pages:e701-e710 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/S2666-5247(22)00155-0 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 3 |j 2022 |e 9 |b 28 |c 09 |h e701-e710 |