Risk of recurrent Plasmodium vivax malaria after chloroquine plus low-dose primaquine in Pakistan: a prospective cohort study

Background Plasmodium vivax remains a major public health challenge in Pakistan. Radical cure is required to eliminate liver stages of the parasite and prevent relapses, however there is limited evidence to inform the optimal primaquine regimen in Pakistan. Clinical outcomes following treatment with the national standard regimen of chloroquine and primaquine were evaluated in a prospective cohort of patients with P. vivax malaria recruited into a biobanking study. Methods Data from a prospective clinical cohort study in Thatta district, Sindh Province, Pakistan, were analysed to evaluate treatment outcomes. Adult patients with microscopy-confirmed P. vivax mono-infection and glucose-6-phosphate dehydrogenase (G6PD) activity ≥70% of the adjusted male median were treated, according to national guidelines, with chloroquine (25 mg/kg over 3 days) plus primaquine (0.25 mg/kg/day for 14 days; total dose 3.5 mg/kg). Treatment was provided with adherence support through phone calls and participants were followed for nine months. The cumulative risk of recurrent P. vivax parasitaemia at 9-months post treatment was estimated using Kaplan–Meier analysis. Safety outcomes included assessment of symptoms on day 14 and changes in haemoglobin concentrations during follow-up. Findings Between August 2023 and April 2024, 80 participants were enrolled, three of whom had P. symptomatic vivax recurrences on days 61, 158 and 189 after treatment. No asymptomatic recurrences were detected. The cumulative incidence of recurrence at 9 months was 3.9% (95% confidence interval 1.3–11.6). Treatment was well tolerated, with no serious adverse events. None of the patients had clinically significant haemolysis and haematological recovery following acute malaria was rapid. Interpretation In G6PD-normal adults with P. vivax malaria in southern Pakistan, there is a low risk of P. vivax recurrence within 9 months following 14-day low-dose primaquine. Funding This work was supported by the Gates Foundation.