# Plasmodium vivax Malaria Relapse Risk Depends on Transmission Intensity: Evidence From a Longitudinal Study in Northwest Thailand

## TL;DR

A study in Thailand shows that the risk of relapsing Plasmodium vivax malaria decreases as malaria transmission declines, improving the effectiveness of radical cure treatments.

## Contribution

This study provides evidence that declining transmission reduces the hypnozoite reservoir, increasing the apparent efficacy of radical cure for P vivax.

## Key findings

- The annual incidence of P vivax malaria decreased from 0.19 in 2010 to 0.09 in 2014.
- Primaquine failure rate was 75% lower than predicted based on earlier assessments.
- Young children bear the greatest burden of P vivax relapse in the absence of radical cure.

## Abstract

In northwest Thailand, the provision of radical cure to prevent relapses of Plasmodium vivax malaria has decreased P vivax caseloads and decreased transmission. While malaria control measures were increased, we performed a prospective observational rolling cohort study to describe the changing incidence of P vivax malaria and the associated recurrence rates.

Healthy nonpregnant glucose-6-phosphate dehydrogenase–normal volunteers who had symptomatic P vivax infection in the previous 12–24 months, but who had not received radical cure, were recruited. Supervised primaquine was given daily for 14 days (0.5 mg base/kg/day). Participants were followed 4 and 8 weeks later, then every 2 months until they developed symptomatic or asymptomatic P vivax malaria. Consultation for febrile illnesses was encouraged between follow-up visits. Participants who developed P vivax malaria were replaced with matched volunteers to maintain a continuous cohort of 200 participants.

From March 2010 until September 2014, 380 healthy adults and children were enrolled. Ninety-two individuals developed P vivax malaria, 25 within 4 months of enrollment. The annual incidence of P vivax malaria infection decreased from 0.19 in 2010 to 0.09 infections per person-year in 2014. The primaquine failure rate (P vivax malaria within 4 months of treatment) was 75% less than predicted based on earlier assessments that assumed a constant hypnozoite reservoir.

Declining P vivax transmission reduces the hypnozoite reservoir in the population and the hypnozoite burden in an individual. This increases the apparent efficacy of radical cure in preelimination settings.

Without radical cure, young children bear the greatest burden of Plasmodium vivax relapse. Declining malaria transmission reduces the hypnozoite reservoir and thus the average number of relapses. Thus, apparent radical cure efficacy increases as P vivax prevalence declines.