Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis.
Emergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have be...
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Public Library of Science (PLoS)
2021-03-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008850&type=printable |
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| author | Amber Kunkel Michael White Patrice Piola |
| author_facet | Amber Kunkel Michael White Patrice Piola |
| author_sort | Amber Kunkel |
| collection | DOAJ |
| description | Emergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have been proposed to help limit resistance and accelerate elimination. The objective of this study was to better understand the potential impacts of triple ACTs and chemoprophylaxis, using a mathematical model parameterized using data from Cambodia. We used a simple compartmental model to predict trends in malaria incidence and resistance in Cambodia from 2020-2025 assuming no changes in transmission since 2018. We assessed three scenarios: a status quo scenario with artesunate-mefloquine (ASMQ) as treatment; a triple ACT scenario with dihydroartemisinin-piperaquine (DP) plus mefloquine (MQ) as treatment; and a chemoprophylaxis scenario with ASMQ as treatment plus DP as chemoprophylaxis. We predicted MQ resistance to increase under the status quo scenario. Triple ACT treatment reversed the spread of MQ resistance, but had no impact on overall malaria incidence. Joint MQ-PPQ resistance declined under the status quo scenario for the baseline parameter set and most sensitivity analyses. Compared to the status quo, triple ACT treatment limited spread of MQ resistance but also slowed declines in PPQ resistance in some sensitivity analyses. The chemoprophylaxis scenario decreased malaria incidence, but increased the spread of strains resistant to both MQ and PPQ; both effects began to reverse after the intervention was removed. We conclude that triple ACTs may limit spread of MQ resistance in the Cambodia, but would have limited impact on malaria incidence and might slow declines in PPQ resistance. Chemoprophylaxis could have greater impact on incidence but also carries higher risks of resistance. Aggressive strategies to limit transmission the GMS are needed to achieve elimination goals, but any intervention should be accompanied by monitoring for drug resistance. |
| format | Article |
| id | doaj-art-abdf8f577db4494d8cfcaeb2d415c7b3 |
| institution | OA Journals |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2021-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-abdf8f577db4494d8cfcaeb2d415c7b32025-08-20T02:01:03ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-03-01173e100885010.1371/journal.pcbi.1008850Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis.Amber KunkelMichael WhitePatrice PiolaEmergence of resistance to artemisinin and partner drugs in the Greater Mekong Subregion has made elimination of malaria from this region a global priority; it also complicates its achievement. Novel drug strategies such as triple artemisinin combination therapies (ACTs) and chemoprophylaxis have been proposed to help limit resistance and accelerate elimination. The objective of this study was to better understand the potential impacts of triple ACTs and chemoprophylaxis, using a mathematical model parameterized using data from Cambodia. We used a simple compartmental model to predict trends in malaria incidence and resistance in Cambodia from 2020-2025 assuming no changes in transmission since 2018. We assessed three scenarios: a status quo scenario with artesunate-mefloquine (ASMQ) as treatment; a triple ACT scenario with dihydroartemisinin-piperaquine (DP) plus mefloquine (MQ) as treatment; and a chemoprophylaxis scenario with ASMQ as treatment plus DP as chemoprophylaxis. We predicted MQ resistance to increase under the status quo scenario. Triple ACT treatment reversed the spread of MQ resistance, but had no impact on overall malaria incidence. Joint MQ-PPQ resistance declined under the status quo scenario for the baseline parameter set and most sensitivity analyses. Compared to the status quo, triple ACT treatment limited spread of MQ resistance but also slowed declines in PPQ resistance in some sensitivity analyses. The chemoprophylaxis scenario decreased malaria incidence, but increased the spread of strains resistant to both MQ and PPQ; both effects began to reverse after the intervention was removed. We conclude that triple ACTs may limit spread of MQ resistance in the Cambodia, but would have limited impact on malaria incidence and might slow declines in PPQ resistance. Chemoprophylaxis could have greater impact on incidence but also carries higher risks of resistance. Aggressive strategies to limit transmission the GMS are needed to achieve elimination goals, but any intervention should be accompanied by monitoring for drug resistance.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008850&type=printable |
| spellingShingle | Amber Kunkel Michael White Patrice Piola Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis. PLoS Computational Biology |
| title | Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis. |
| title_full | Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis. |
| title_fullStr | Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis. |
| title_full_unstemmed | Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis. |
| title_short | Novel anti-malarial drug strategies to prevent artemisinin partner drug resistance: A model-based analysis. |
| title_sort | novel anti malarial drug strategies to prevent artemisinin partner drug resistance a model based analysis |
| url | https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1008850&type=printable |
| work_keys_str_mv | AT amberkunkel novelantimalarialdrugstrategiestopreventartemisininpartnerdrugresistanceamodelbasedanalysis AT michaelwhite novelantimalarialdrugstrategiestopreventartemisininpartnerdrugresistanceamodelbasedanalysis AT patricepiola novelantimalarialdrugstrategiestopreventartemisininpartnerdrugresistanceamodelbasedanalysis |