Rapid dissemination of newly introduced Plasmodium vivax genotypes in South Korea

Abstract

Reemerged Plasmodium vivax malaria in South Korea has not yet been eradicated despite continuous governmental efforts. It has rather become an endemic disease. Our study aimed to determine the genetic diversity in P. vivax merozoite surface protein-1 (PvMSP-1) and circumsporozoite protein (PvCSP) genes over an extended period after its reemergence to its current status. Sequence analysis of PvMSP-1 gene sequences from the 632 P. vivax isolates during 1996-2007 indicates that most isolates recently obtained were different from isolates obtained in the initial reemergence period. There was initially only one subtype (recombinant) present but its subtypes have varied since 2000; six MSP-1 subtypes were recently found. A similar variation was observed by CSP gene analysis; a new CSP subtype was found. Understanding genetic variation patterns of the parasite may help to analyze trends and assess extent of endemic malaria in South Korea.

Figure 1.

High-risk areas for malaria in Republic of Korea in 1999, 2002, 2005, and 2008. A, Spot map of the occurrence of Plasmodium vivax malaria. Active local transmission may occur near the Demilitarized Zone (DNZ). South Korea and North Korea are separated by the yellow national boundary line with the DMZ adjacent to the line. B, Major risk area of P. vivax malaria in South Korea. Results are plotted in yellow, orange, and red, which represent < 10.0, 10.1–99.9, and > 100.0 patients/1,000 population, respectively. The subsets by year (1999, 2000, 2005, and 2008) represent 23 high-risk areas in South Korea that showed epidemiological changes. GH = Ganghwa-gun; DG = Dong-gu; SG = Seo-gu; OG = Ongjin-gun; JG = Jung-gu, Gyeonggi-do Province; GaP = Gapyeong-gun; GY = Goyang-si; GYDY = Goyang-si Deogyang-gu; GYID = Goyang-si Ilsan-Donggu; GYIS = Goyang-si Ilsan-Seogu; GIP = Gimpo-si; DDC = Dongducheon-si; YJ = Yangju-gun; YC = Yeoncheon-gun; UJB = Uijeongbu-si; PC = Pocheon-gun; PJ = Paju-si, Gangwon-do Province; GS = Goseong-gun; YG = Yanggu-gun; IJ = Inje-gun; CW = Cheorwon-gun; CC = Chuncheon-si; HC = Hwacheon-gun.

Figure 2.

Malaria incidence rate and relative risk for the Republic of Korea and the Democratic People's Republic of Korea, 1999–2008.

Figure 3.

Comparison of amino acid sequences of Plasmodium vivax merozoite surface protein-1 (PvMSP-1) from South Korea with those from worldwide strains. Amino acid positions indicated by shaded regions depict non-synonymous substitutions and poly-Q residues in isolates from the Republic of Korea.

Figure 4.

Frequency of Plasmodium vivax merozoite surface protein-1 (PvMSP-1) and P. vivax circumsporozoite protein (PvCSP) strains in the Republic of Korea during the study period. A, Between 1996 and 2000, most isolates differed from recombinant to Sal-1 strains. Black circles indicate subtypes of the Sal-1 strain and white circles indicate subtypes of the Belem strain. • = only S-b subtype; •• = S-a and S-b subtypes; ••• = S-a, S-b, and S-c subtypes; ○ = only B-1 subtype; ○○ = B-1 and B-2 subtypes. B, PvCSP subtypes of isolates from the Republic of Korea that diversified during 1996–2007.

Figure 5.

Plasmodium vivax merozoite surface protein-1 (PvMSP-1) gene distance tree constructed by using the phylogenic tree neighbor-method. PvMSP-1 gene sequences of strains obtained from the Republic of Korea and from GenBank were analyzed. Numbers on branches indicate bootstrap proportions from 1,000 replicates. Scale bar indicates 0.1 amino acids substitutions per site and is proportional to the genetic difference (%).