Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics
- Author(s)
- Ciavarella, C; Drakeley, C; Price, RN; Mueller, I; White, M;
- Journal Title
- Lancet Infectious Diseases
- Publication Type
- Jan 13 epub
- Abstract
- BACKGROUND: Plasmodium vivax forms dormant liver stages (hypnozoites) that can reactivate weeks to months after primary infection. Radical cure requires a combination of antimalarial drugs to kill both the blood-stage and liver-stage parasites. Hypnozoiticidal efficacy of the liver-stage drugs primaquine and tafenoquine cannot be estimated directly because hypnozoites are undetectable. We aimed to estimate hypnozoiticidal efficacy from clinical trial data, and quantify the community-level impact of implementing case management with radical cure. METHODS: We calibrated a novel P vivax Recurrence Model to publicly available data from prospective clinical trials to estimate the hypnozoiticidal efficacy of different supervised primaquine (3·5 mg/kg or 7 mg/kg over 7 or 14 days) and tafenoquine (5 mg/kg or 7·5 mg/kg single dose) regimens in patients with normal glucose-6-phosphate dehydrogenase (G6PD) activity. We used an existing P vivax Individual-Based Model to quantify the 5-year impact of case management with unsupervised primaquine or tafenoquine regimens across various transmission settings. FINDINGS: We estimated median hypnozoiticidal efficacies of 99·1% (95% credible interval 96·0-100) for primaquine 7 mg/kg over 14 days; 96·3% (90·8-99·7) for primaquine 7 mg/kg over 7 days; 72·3% (68·1-76·3) for primaquine 3·5 mg/kg over 7 or 14 days; 62·4% (49·1-76·3) for tafenoquine 5 mg/kg single dose; and 87·5% (62·1-99·3) for tafenoquine 7·5 mg/kg single dose. 5 years of community-level tafenoquine case management was estimated to reduce P vivax transmission by 74-79% where pre-intervention prevalence as measured by PCR was low (<2%) and by 17-20% where prevalence as measured by PCR was high (around 35%). Similar 5-year reductions were estimated with primaquine case management only when adherence to the primaquine regimen was above 50%. INTERPRETATION: Substantial reductions in prevalence as measured by PCR were predicted with primaquine and tafenoquine regimens if these could be implemented with high coverage and adherence. The benefits of preventing P vivax relapses need to be balanced against the risks of inducing severe haemolysis in patients with G6PD deficiency. FUNDING: Bill & Melinda Gates Foundation and Horizon Europe.
- Publisher
- Elsevier
- Research Division(s)
- Infection and Global Health
- PubMed ID
- 39818221
- Publisher's Version
- https://doi.org/10.1016/s1473-3099(24)00689-3
- Open Access at Publisher's Site
https://doi.org/10.1016/S1473-3099(24)00689-3- Terms of Use/Rights Notice
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Creation Date: 2025-02-07 11:22:06
Last Modified: 2025-02-07 11:24:04