Suboptimal Doses of Antimalarials Relative to Increasing Body Weight and the Risk of Plasmodium vivax Recurrence in the Republic of Korea Armed Forces, 2012-2021

Abstract

Background: We aimed to analyze the epidemiology, clinical characteristics, and outcomes of malaria caused by Plasmodium vivax among military members of the Republic of Korea (ROK).

Methods: We reviewed the medical records of patients diagnosed with P. vivax malaria in 16 military hospitals in the ROK between 2012-2021, excluding other types of malaria, as well as imported cases and those treated in civilian hospitals.

Results: In total, 653 patients were treated for P. vivax malaria. Their mean age was 22.0 ± 3.8 years, and their mean body weight was 73.4 ± 10.8 kg. Hospitalization occurred in 92.0% (n = 601) of the cases, with 4.4% (n = 29) recurring. The mean administered dose was 20.7 ± 3.4 mg/kg for the chloroquine (CQ) base and 3.5 ± 1.2 mg/kg for the primaquine (PQ) base. Between 2012-2016 and 2017-2021, the mean patient body weight increased (72.9 ± 11.1 vs. 74.3 ± 10.3 kg, P = 0.044). Correspondingly, the total administered doses of CQ (1,476.0 ± 144.0 vs. 1,515.1 ± 155.1 mg, P = 0.010) and PQ (242.6 ± 79.7 vs. 265.7 ± 92.3 mg, P < 0.001) were increased. However, there was no difference in the weight-based dosage of CQ (20.7 ± 3.6 vs. 20.7 ± 3.2 mg/kg, P = 0.580) or PQ (3.33 ± 1.1 vs. 3.64 ± 1.3 mg/kg, P = 0.256), nor in the percentage of patients who received sub-recommended doses. Among the 27 patients who experienced recurrence and had available initial treatment data, the proportion of those prescribed PQ (24 [88.9%] vs. 623 [99.5%], P = 0.001) and the mean PQ dose (2.75 ± 0.7 vs. 3.50 ± 1.2 mg/kg, P = 0.003) were significantly lower in the recurrence group.

Conclusion: Over time, as the body weight of patients with P. vivax malaria in the ROK military has increased, the administered dosages of CQ and PQ have correspondingly risen. However, these dosages often remain suboptimal when compared to the body weight-based recommendations by the World Health Organization. Of particular concern is the continued administration of antimalarial drugs at suboptimal doses, which may contribute to an elevated risk of recurrence. Further education may therefore be beneficial to ensuring appropriate dosing for more effective malaria treatment.

Keywords: Body Weight; Epidemiology; Malaria; Military Personnel; Plasmodium vivax.

Fig. 1. Time interval distribution between the initial and recurrent diagnosis of Plasmodium vivax malaria. Of the 29 patients with recurrence, the time interval for 27 patients was available. Among these, 23 (85.2%) experienced a recurrence within 2 months. Fourteen (51.9%) experienced a recurrence within 35 days (dotted line). One patient experienced recurrence after nearly 2 years (possibly due to re-infection).