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Young A. Kang, MD,‡ Soon Young Seo, ... Environment and Department of Biology, Kyung Hee University, Seoul, Korea; ‡Division of Epidemic Intelligence Service, ... imported malaria is very important, but there is no good way to determine imported vs. ... Case-1 and Case-2 exact match with an Indian isolate, and Case-3.
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Study of the Genetic Discrimination Between Imported and Autochthonous Cases of Malaria in South Korea Kyung Mi Choi, PhD,∗† Yien Kyoung Choi, PhD,∗† Young A. Kang, MD,‡ Soon Young Seo, MS,‡ Hyeong Woo Lee, PhD,§ Shin Hyeong Cho, PhD,∗ Won Ja Lee, PhD,∗ Ho Gun Rhie, PhD,† Ho Sa Lee, PhD,† and Jung Yeon Kim, PhD∗ ∗ Division

of Malaria and Parasitic Diseases, National Institute of Health, Korea CDC, Seoul, Korea; † Institute of Global Environment and Department of Biology, Kyung Hee University, Seoul, Korea; ‡ Division of Epidemic Intelligence Service, National Institute of Health, Korea CDC, Seoul, Korea; § Department of Pathology, University of Florida, Gainesville, FL, USA DOI: 10.1111/j.1708-8305.2010.00473.x

There has been a great increase of Plasmodium vivax incidences in the Republic of Korea and the genetic diversity of the parasite became more complex with the rapid dissemination of newly introduced genotypes. Surveillance of imported malaria is very important, but there is no good way to determine imported vs. internal cases. In this study, we characterized imported vivax cases, analyzed the genetic sequence of three imported vivax malaria cases for the merozoite surface protein-1 (MSP-1) and circumsporozoite protein (CSP) genes, and clearly discriminated an imported vivax case that was misdiagnosed as indigenous by genetic analysis. PCR reaction for the merozoite surface protein1 (MSP-1) and circumsporozoite protein (CSP) genes from three imported vivax cases were amplified and sequenced. The genetic variations were compared with a previously constructed database of South Korean isolates. The imported vivax cases showed various patterns on incubation period before onset. Most cases were from other parts of Asia. The MSP-1 gene sequence analysis of three imported cases showed that the imported cases had completely different sequences from any subtypes from Korean isolates. Case-1 and Case-2 exact match with an Indian isolate, and Case-3 had great similarity with isolates from countries neighboring Indonesia. CSP gene analysis based on the repeat patterns showed similar results that the sequences from the imported cases well matched with the patient’s traveled countries and completely discriminated with indigenous cases. AMA-1 gene analysis also supported these results. We were able to clearly distinguish three imported vivax cases from indigenous by using a genetic database of Korean isolates and were able to suspect its origin by genotyping. This study demonstrated the usefulness of genetic survey on imported malaria cases.

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lasmodium vivax is the most widespread of four Plasmodium species that infect humans. Recently, P vivax resistance to antimalarial drugs has been increasing.1 Migration and tourism to malaria-endemic regions increase the threat of malaria importation.2 Since reemergence in 1993, vivax malaria is endemic in Korea, with seasonal prevalence. Between 1994 and 2008, 621 cases of imported malaria were reported in South Korea. Among imported cases from 2002 to 2008, 36.8% were P vivax.3 An intriguing vivax case (case 2) was reported in July 2008 and initially misdiagnosed as Corresponding Author: Jung Yeon Kim, PhD, Division of Malaria and Parasitic Diseases, National Institute of Health, Korea Center for Disease Control and Prevention, 194 Tongil-Lo, Eunpyung-Gu, Seoul 122-701, Korea. E-mail: [email protected]

autochthonous because the patient lived in the malariaendemic area and had symptoms during malaria season in Korea (Table 1). The epidemiological survey revealed that the patient had traveled in Southeast Asia (mainly India; Table 1), and a 6-month incubation period before onset occurred similarly to Korean malaria. Previously, we demonstrated that the genetic variation of P vivax malaria in Korea has increased in complexity, compared to earlier strains, due to rapid dissemination of newly introduced malaria.4 Thus, it is crucial to survey and control the import of malaria to prevent the spread of new subtypes and minimize genetic diversity in malaria-endemic and malaria-free countries. The ability to discriminate between imported and autochthonous malaria cases has been limited. In this study, however, we were able to discriminate between these cases using genotyping based on the genetic database we systematically analyzed previously.4 © 2010 International Society of Travel Medicine, 1195-1982 Journal of Travel Medicine 2011; Volume 18 (Issue 1): 63–66

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Mi Choi et al.

Table 1

Travel history of imported vivax malaria cases listed in this study

No.

Sex

Age

Travel start

Travel end

Travel period

Case 1 Case 2 Case 3

M M M

47 — 35

January 4, 2007 June 2007 October 1, 2009

January 19, 2007 December 2007 October 6, 2009

2 wk >6 mo