Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics
Issued Date
2025-01-01
Resource Type
ISSN
14733099
eISSN
14744457
Scopus ID
2-s2.0-85217249225
Pubmed ID
39818221
Journal Title
The Lancet Infectious Diseases
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Lancet Infectious Diseases (2025)
Suggested Citation
Ciavarella C., Drakeley C., Price R.N., Mueller I., White M. Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics. The Lancet Infectious Diseases (2025). doi:10.1016/S1473-3099(24)00689-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/105332
Title
Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics
Author(s)
Corresponding Author(s)
Other Contributor(s)
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.