Lien vers Pubmed [PMID] – 39818221
Lien vers HAL – pasteur-04893546
Lien DOI – 10.1016/s1473-3099(24)00689-3
The Lancet Infectious Diseases, In press, ⟨10.1016/s1473-3099(24)00689-3⟩
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 liverstage 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.
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.