Evaluation of the efficacy of chloroquine chemoprophylaxis for vivax malaria among Republic of Korea military personnel

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most prevalent inborn disorder. This X-chromosome-linked recessive disease affects more than 400 million people globally, and is associated with haemolytic anaemia after medication with the anti-latent malaria drug, primaquine. To prevent malaria, the Republic of Korea (ROK) Army administers malaria chemoprophylaxis. Due to the previously low G6PD deficiency prevalence in the ROK, prior to primaquine administration, testing for G6PD deficiency was not mandatory. In this study, to evaluate the risk from malaria chemoprophylaxis in the ROK, G6PD deficiency prevalence was investigated. Methods: Blood specimens from 1632 soldiers entering training camp for the 3 rd Infantry of the ROK Army were collected. CareStart ™ Biosensor for G6PD and haemoglobin (Hb) was used to detect G6PD levels. G6PD variants using the DiaPlexC G6PD Genotyping kit (Asian type) and full-length sequencing were examined. Results: Of 1632 blood specimens tested, none was observed to be G6PD deficient. The median value of all tested samples was 7.582 U/g Hb. An investigation of 170 G6PD DNA variants was analysed and categorized as partially low normal [n = 131, 30-80% (2.27-6.05 U/g Hb) of the median value], high [n = 3, > 150% (> 11.373 U/g Hb) of the median value], or normal [n = 36, 80-150% (6.05-11.373 U/g Hb) of the median value], and none was amplified by the DiaPlexC kit. Five silent mutations (C→T) in 131 partially low normal specimens were found at the 1311th nucleotide position by sequence analysis. Another 8 silent mutations (T93C) were also detected in 131 partially low normal specimens. Thus, it is inferred that these silent mutations could be related to G6PD activity. Conclusions: This G6PD deficiency prevalence study, conducted among participants from the 3rd Infantry of the ROK Army, provided crucial evidence for the safety of malaria chemoprophylaxis. This study showed that the prevalence of G6PD deficiency among 1632 young soldiers was wholly absent. Although G6PD phenotypic mutations were not detected, many silent mutations (C1311T and T93C) were observed. Thus, it is inferred that malaria chemoprophylaxis is relatively safe against G6PD deficiency-mediated haemolytic anaemia. However, given the number of individuals whose G6PD were at the partially low normal range and the frequent detection of G6PD deficiency-related mutations, consistent monitoring of G6PD deficiency is needed.

Section: Introductionmentioning

confidence: 99%

Investigation of glucose-6-phosphate dehydrogenase (G6PD) deficiency prevalence in a Plasmodium vivax-endemic area in the Republic of Korea (ROK)

Lee

Lee³

et al. 2020

“…Although this chemoprophylaxis has contributed to the containment of vivax malaria, the possibility of the emergence of chloroquine-resistant P. vivax strains has been a concern. Indeed, chemoprophylaxis failure has been reported in several cases, despite the attainment of sufficiently high plasma concentrations of hydroxychloroquine [ 6 , 16 ]. Therefore, monitoring for chloroquine-resistant P. vivax is important for the control of malaria in Republic of Korea.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, military personnel and residents living in the demilitarized zone are under high risk of contracting vivax malaria. Military personnel accounted for 25.3 % (1029/4063) of all malaria cases reported from 2008 to 2010 [ 6 ]. This percentage rose to 44.7 % (1811/4063) when military personnel diagnosed with vivax malaria following discharge from the service were counted [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of single nucleotide polymorphisms of pvmdr1 and microsatellite genotype in Plasmodium vivax isolates from Republic of Korea military personnel

Chung

Jeong

Dinzouna-Boutamba

et al. 2015

Self Cite

BackgroundChloroquine has been administered to the soldiers of the Republic of Korea as prophylaxis against vivax malaria. Recent increase in the number of chloroquine-resistant parasites has raised concern over the chemoprophylaxis and treatment of vivax malaria.MethodsTo monitor the development of chloroquine-resistant parasites in the Republic of Korea, analyses of single nucleotide polymorphisms (SNPs) of pvmdr1 and microsatellite markers were performed using samples collected from 55 South Korean soldiers infected with Plasmodium vivax.ResultsFour SNPs, F1076L, T529, E1233, and S1358, were identified. Among these, S1358 was detected for the first time in Korea. The microsatellite-based study revealed higher genetic diversity in samples collected in 2012 than in 2011.ConclusionsTaken together, the results indicate that P. vivax with a newly identified SNP of pvmdr1 has been introduced into the Korean P. vivax population. Therefore, continuous monitoring for chloroquine-resistant parasites is required for controlling vivax malaria in the Republic of Korea.

“…There are some limitations in the present report, e.g., low compliance, which made it difficult to assess the exact effectiveness of the chemoprophylaxis programme established by the MND [ 22 ]. Because civilians are not allowed to reside in many of the malaria high-risk areas near the DMZ (including the CCZ), there are differences between the civilian residential areas and ROK Army installations where soldiers reside.…”

Section: Discussionmentioning

confidence: 99%

Malaria control and chemoprophylaxis policy in the Republic of Korea Armed Forces for the previous 20 years (1997–2016)

Huh

Yoon

et al. 2018

BackgroundVivax malaria reemerged along the Demilitarized Zone (DMZ), Republic of Korea (ROK), in 1993. While it was hypothesized that vivax malaria would spread throughout the peninsula, nearly all cases were due to exposure near the DMZ. To reduce spillover of vivax malaria to the civilian community, the ROK Ministry of National Defense (MND) initiated malaria prevention policies including a large-scale chemoprophylaxis programme in malaria high-risk areas in 1997. The present study investigated the overall changes in the incidence of malaria among ROK soldiers and the mass chemoprophylaxis program from 1997 to 2016.ResultsPeak numbers of vivax malaria were reported in 2000, with most cases reported near the DMZ, before declining to the current levels. To combat the rapid increase in the number of malaria cases and its expansion throughout the ROK, the MND implemented mosquito control and personal protection programmes. The MND also implemented a large-scale vivax malaria chemoprophylaxis programme using hydroxychloroquine (400 mg weekly) in 1997, and primaquine (15 mg × 14 days) as terminal chemoprophylaxis in 2001. Additionally, an improved medical system enabled the rapid detection and treatment of malaria to reduce morbidity and decrease transmission of malaria from humans to mosquitoes. Following the full implementation of these programmes, the incidence of vivax malaria declined in both ROK Armed Forces and civilian populations. Subsequently, several changes in the ROK Armed Forces chemoprophylaxis programme were implemented, including the reduction of the period of hydroxychloroquine prophylaxis by 2 months (2008) and other changes in the chemoprophylaxis policy, e.g., only ROK Armed Forces personnel in moderate risk groups received terminal primaquine chemoprophylaxis (2011), and in 2016, the discontinuation of terminal primaquine chemoprophylaxis in moderate-risk area.ConclusionsThe resurgence of vivax malaria in the ROK Armed Forces personnel near the DMZ was successfully suppressed through the implementation of a mass malaria chemoprophylaxis programme initiated by the MND in 1997, as well as several other factors that may have contributed to the reduction of malaria transmission since 2000. Given the current malaria situation in the ROK and North Korea, it is necessary to reevaluate the ROK Armed Forces and civilian malaria control policies.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2449-4) contains supplementary material, which is available to authorized users.