Quantifying Plasmodium vivax radical cure efficacy: a modelling study integrating clinical trial data and transmission dynamics

Ciavarella, C; Drakeley, C; Price, RN; Mueller, I; White, M

Author(s): Ciavarella, C; Drakeley, C; Price, RN; Mueller, I; White, M;
Details: Publication Year 2025-06,Volume 25,Issue #6,Page 668-677
Journal Title: Lancet Infectious Diseases
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
Keywords: Humans; *Malaria, Vivax/drug therapy/transmission/epidemiology; *Antimalarials/therapeutic use/administration & dosage; *Primaquine/therapeutic use/administration & dosage; *Plasmodium vivax/drug effects; *Aminoquinolines/therapeutic use/administration & dosage; Male; Treatment Outcome; Female; Adult; Clinical Trials as Topic; Young Adult; Recurrence; Middle Aged; Adolescent
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: Refer to copyright notice on published article.

Creation Date: 2025-02-07 11:22:06

Last Modified: 2025-05-29 02:28:56