Spontaneous Clearance of Polymerase Chain Reaction–Positive Plasmodium vivax Parasitemia in Northwestern Thailand: An Epidemiological Perspective

Abstract

Background. Asymptomatic, low-density Plasmodium vivax infections pose a significant challenge to malaria elimination because of their subclinical presentation and potential for ongoing transmission. However, the natural history of such untreated infections, including the extent to which they resolve spontaneously, remains poorly understood and has not been systematically studied for P. vivax. Methods. We conducted a longitudinal cohort study from 2018 to 2023 in northwestern Thailand, incorporating 14 rounds of mass blood surveys (MBS) covering approximately 5000 individuals. Blood samples were screened for P. vivax using both microscopy and polymerase chain reaction (PCR). Participants with PCR-positive, submicroscopic parasitemia were followed in subsequent surveys to assess infection dynamics. Turnbull survival analysis estimated time to spontaneous clearance, and Cox proportional hazards models identified demographic factors associated with clearance. Results. Among 210 P. vivax infections detected by microscopy and/or PCR, 154 were detected only by PCR. After excluding individuals lost to follow-up or with coinfections, 101 participants were analyzed. Most infections (72, 69.9%) cleared spontaneously within 3 subsequent MBS. Turnbull survival analysis revealed that the probability of persistent infections declined to 25.0% (95% CI: 4.0–100.0) by day 47 and 7.0% (95% CI: 1.0–38.0) by day 232. Clearance was not significantly associated with age, sex, nationality, occupation, or education. Conclusions. A considerable proportion of submicroscopic P. vivax infections resolved spontaneously without treatment, providing the first field-based evidence of this phenomenon. These findings suggest a role for naturally acquired immunity and highlight implications for surveillance and targeted intervention strategies in malaria elimination contexts.