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Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study

BACKGROUND: Despite recent intensification of control measures, Plasmodium vivax poses a major challenge for malaria elimination efforts. Liver-stage hypnozoite parasites that cause relapsing infections can be cleared with primaquine; however, poor treatment adherence undermines drug effectiveness....

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Autores principales: Nekkab, Narimane, Lana, Raquel, Lacerda, Marcus, Obadia, Thomas, Siqueira, André, Monteiro, Wuelton, Villela, Daniel, Mueller, Ivo, White, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064585/
https://www.ncbi.nlm.nih.gov/pubmed/33891582
http://dx.doi.org/10.1371/journal.pmed.1003535
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author Nekkab, Narimane
Lana, Raquel
Lacerda, Marcus
Obadia, Thomas
Siqueira, André
Monteiro, Wuelton
Villela, Daniel
Mueller, Ivo
White, Michael
author_facet Nekkab, Narimane
Lana, Raquel
Lacerda, Marcus
Obadia, Thomas
Siqueira, André
Monteiro, Wuelton
Villela, Daniel
Mueller, Ivo
White, Michael
author_sort Nekkab, Narimane
collection PubMed
description BACKGROUND: Despite recent intensification of control measures, Plasmodium vivax poses a major challenge for malaria elimination efforts. Liver-stage hypnozoite parasites that cause relapsing infections can be cleared with primaquine; however, poor treatment adherence undermines drug effectiveness. Tafenoquine, a new single-dose treatment, offers an alternative option for preventing relapses and reducing transmission. In 2018, over 237,000 cases of malaria were reported to the Brazilian health system, of which 91.5% were due to P. vivax. METHODS AND FINDINGS: We evaluated the impact of introducing tafenoquine into case management practices on population-level transmission dynamics using a mathematical model of P. vivax transmission. The model was calibrated to reflect the transmission dynamics of P. vivax endemic settings in Brazil in 2018, informed by nationwide malaria case reporting data. Parameters for treatment pathways with chloroquine, primaquine, and tafenoquine with glucose-6-phosphate dehydrogenase deficiency (G6PDd) testing were informed by clinical trial data and the literature. We assumed 71.3% efficacy for primaquine and tafenoquine, a 66.7% adherence rate to the 7-day primaquine regimen, a mean 5.5% G6PDd prevalence, and 8.1% low metaboliser prevalence. The introduction of tafenoquine is predicted to improve effective hypnozoite clearance among P. vivax cases and reduce population-level transmission over time, with heterogeneous levels of impact across different transmission settings. According to the model, while achieving elimination in only few settings in Brazil, tafenoquine rollout in 2021 is estimated to improve the mean effective radical cure rate from 42% (95% uncertainty interval [UI] 41%–44%) to 62% (95% UI 54%–68%) among clinical cases, leading to a predicted 38% (95% UI 7%–99%) reduction in transmission and over 214,000 cumulative averted cases between 2021 and 2025. Higher impact is predicted in settings with low transmission, low pre-existing primaquine adherence, and a high proportion of cases in working-aged males. High-transmission settings with a high proportion of cases in children would benefit from a safe high-efficacy tafenoquine dose for children. Our methodological limitations include not accounting for the role of imported cases from outside the transmission setting, relying on reported clinical cases as a measurement of community-level transmission, and implementing treatment efficacy as a binary condition. CONCLUSIONS: In our modelling study, we predicted that, provided there is concurrent rollout of G6PDd diagnostics, tafenoquine has the potential to reduce P. vivax transmission by improving effective radical cure through increased adherence and increased protection from new infections. While tafenoquine alone may not be sufficient for P. vivax elimination, its introduction will improve case management, prevent a substantial number of cases, and bring countries closer to achieving malaria elimination goals.
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spelling pubmed-80645852021-05-04 Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study Nekkab, Narimane Lana, Raquel Lacerda, Marcus Obadia, Thomas Siqueira, André Monteiro, Wuelton Villela, Daniel Mueller, Ivo White, Michael PLoS Med Research Article BACKGROUND: Despite recent intensification of control measures, Plasmodium vivax poses a major challenge for malaria elimination efforts. Liver-stage hypnozoite parasites that cause relapsing infections can be cleared with primaquine; however, poor treatment adherence undermines drug effectiveness. Tafenoquine, a new single-dose treatment, offers an alternative option for preventing relapses and reducing transmission. In 2018, over 237,000 cases of malaria were reported to the Brazilian health system, of which 91.5% were due to P. vivax. METHODS AND FINDINGS: We evaluated the impact of introducing tafenoquine into case management practices on population-level transmission dynamics using a mathematical model of P. vivax transmission. The model was calibrated to reflect the transmission dynamics of P. vivax endemic settings in Brazil in 2018, informed by nationwide malaria case reporting data. Parameters for treatment pathways with chloroquine, primaquine, and tafenoquine with glucose-6-phosphate dehydrogenase deficiency (G6PDd) testing were informed by clinical trial data and the literature. We assumed 71.3% efficacy for primaquine and tafenoquine, a 66.7% adherence rate to the 7-day primaquine regimen, a mean 5.5% G6PDd prevalence, and 8.1% low metaboliser prevalence. The introduction of tafenoquine is predicted to improve effective hypnozoite clearance among P. vivax cases and reduce population-level transmission over time, with heterogeneous levels of impact across different transmission settings. According to the model, while achieving elimination in only few settings in Brazil, tafenoquine rollout in 2021 is estimated to improve the mean effective radical cure rate from 42% (95% uncertainty interval [UI] 41%–44%) to 62% (95% UI 54%–68%) among clinical cases, leading to a predicted 38% (95% UI 7%–99%) reduction in transmission and over 214,000 cumulative averted cases between 2021 and 2025. Higher impact is predicted in settings with low transmission, low pre-existing primaquine adherence, and a high proportion of cases in working-aged males. High-transmission settings with a high proportion of cases in children would benefit from a safe high-efficacy tafenoquine dose for children. Our methodological limitations include not accounting for the role of imported cases from outside the transmission setting, relying on reported clinical cases as a measurement of community-level transmission, and implementing treatment efficacy as a binary condition. CONCLUSIONS: In our modelling study, we predicted that, provided there is concurrent rollout of G6PDd diagnostics, tafenoquine has the potential to reduce P. vivax transmission by improving effective radical cure through increased adherence and increased protection from new infections. While tafenoquine alone may not be sufficient for P. vivax elimination, its introduction will improve case management, prevent a substantial number of cases, and bring countries closer to achieving malaria elimination goals. Public Library of Science 2021-04-23 /pmc/articles/PMC8064585/ /pubmed/33891582 http://dx.doi.org/10.1371/journal.pmed.1003535 Text en © 2021 Nekkab et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nekkab, Narimane
Lana, Raquel
Lacerda, Marcus
Obadia, Thomas
Siqueira, André
Monteiro, Wuelton
Villela, Daniel
Mueller, Ivo
White, Michael
Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study
title Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study
title_full Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study
title_fullStr Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study
title_full_unstemmed Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study
title_short Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study
title_sort estimated impact of tafenoquine for plasmodium vivax control and elimination in brazil: a modelling study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064585/
https://www.ncbi.nlm.nih.gov/pubmed/33891582
http://dx.doi.org/10.1371/journal.pmed.1003535
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