Epidemiological Aspects of Imported Exotic Malaria Cases in the Republic of Korea and Japan, 2015~2017

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Epidemiological Aspects of Imported Exotic Malaria Cases in the Republic of Korea and Japan, 2015~2017

Myeong-Jin Lee, Ph.D.

, Won-Chang Lee, Ph.D.

, Young Hwan Kwon, M.D.

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Received: September 16, 2019, Accepted: September 30, 2019 Correspondence: Young Hwan Kwon, Aeromedical Center, Korean Air

260, Haneul-gil, Gangseo-ru, Seoul, 07505, Korea Tel: 82-00-2656-7150, Fax: 82-00-2656-8858 E-mail: younghkwon@koreanair.com

I. INTRODUCTION

Malaria is a life-threatening disease caused by intraerythrocytic protozoa of the genus Plasmodium that is transmitted to people through the bites of infected female Anopheles mosquitoes. In 2017, there were an estimated 219 million cases and deaths reached 435,000 due to malaria in 90 countries [1]. Malaria is caused by infection with one or more of four species of Plasmodium (i.e., P. vivax, P. falciparum, P. ovale, and P. malariae) that can infect humans, and other Plasmodium species infected animals [2]. Indigenous malaria has been successfully eradicated in North America, Europe, and a few other previously endemic locations. Extensive antimalarial programs, improvement of health care service, and advances in socio-economic development have all contributed to one of the most significant achievements

in public health of the twentieth century [3].

In Korea, no domestic case of malaria has been reported from 1980 to 1992. However, since the infection of a military personnel in the demilitarization (DMZ) area in Gyeonggi and Gangwon province which lies in the north part of Seoul city in the Korean peninsula in 1993, a number of malaria cases has begun to emerge, and P. vivax is the most common type of malaria, prevalent in 97.5% of domestic cases [4].

On the other hand, in Japan, indigenous malaria was

eradicated in 1961 and now only imported malaria cases are

encountered [5,6]. Nevertheless, a new malaria transmission

pattern is increasingly seen in Korea and Japan. The steadily

mounting movement of travelers from developed countries to

the tropics and the affluent immigration to the industrialized

world from countries where malaria has remained are

responsible for the emergence of imported malaria. Recently,

imported malaria has been an increasing problem in Korea and

Japan in the last two decades, representing the main risk for

travelers visiting tropical and sub-tropical countries where

malaria is endemic. Moreover, an increasing number of Koreans

and Japanese have been traveling to malaria-endemic countries

ב׵׸׷׺׼׭׬֨׍؀׷׼ױ׫֨וש״ש׺ױש֨׋ש׻׭׻֨ױ׶֨ד׷׺׭ש֨ש׶׬֨גש׸ש׶



΅ΒΓΝΖ͑͑͢͟΅ΣΖΟΕΤ͑ΚΟ͑ΥΙΖ͑ΔΦΞΦΝΒΥΚΧΖ͑ΚΟΔΚΕΖΟΔΖ͑ΣΒΥΖ͑ΠΗ͑ΖΩΠΥΚΔ͑ΞΒΝΒΣΚΒ ΚΟΗΖΔΥΚΠΟΤ͑ΓΖΥΨΖΖΟ͑ͼΠΣΖΒ͑ΒΟΕ͑ͻΒΡΒΟ͑ͣͦ͢͝͡ίͣͨ͢͡

ͺΥΖΞ ͼΠΣΖΒ ͻΒΡΒΟ

ʹΒΤΖΤ ʹͺ΃ ʹΒΤΖΤ ʹͺ΃

ͿΒΥΚΠΟΨΚΕΖ ͧͣ͢ ͦ͛͛͟͢͡͡ ͦͣ͢ ͥ͟͢͡͡

΀ΧΖΣΤΖΒ͑ΥΣΒΧΖΝΖΣΤ ͧͣ͢ ͣͤͩ͟͡ ͦͣ͢ ͣͪͨ͛͛͟͡

ʹͺ΃ͫ͑ ʹΦΞΦΝΒΥΚΧΖ͑ ΚΟΔΚΕΖΟΔΖ͑ ΣΒΥΖ͑ ΡΖΣ͑ ͑͢͡͡͝͡͡͡ ΡΠΡΦΝΒΥΚΠΟΤ͑ ΒΟΕ͑

ΠΧΖΣΤΖΒ͑ΥΣΖΒΧΖΝΖΣΤ͟

ͺΟΕΚΔΒΥΖΕ͑ Β͑ ΤΚΘΟΚΗΚΔΒΟΥ͑ ΗΣΠΞ͑ ΥΙΖ͑ ΥΠΥΒΝ͑ ΧΒΝΦΖ͑͝ ͛΁＜ͦ͑͟͡͡ ΒΟΕ͑ ͛͛΁

＜͟͢͟͡͡

΅ΒΓΝΖ͑ͣ͟ ʹΠΞΡΒΣΒΥΚΧΖ͑ΠΓΤΖΣΧΒΥΚΠΟ͑ΠΗ͑ΖΡΚΕΖΞΚΔ͑ΒΤΡΖΔΥΤ͑ΠΗ͑ΖΩΠΥΚΔ ΞΒΝΒΣΚΒ͑ΚΟΗΖΔΥΚΠΟΤ͑ΓΖΥΨΖΖΟ͑ͼΠΣΖΒ͑ΒΟΕ͑ͻΒΡΒΟ͑ͣͦ͢͝͡ίͣͨ͢͡

ͺΥΖΞ ͼΠΣΖΒ ͻΒΡΒΟ

ʹΒΤΖΤ ͖ͪͦ͑ʹͺ ʹΒΤΖΤ ͖ͪͦ͑ʹͺ

͸ΖΟΕΖΣ

͑͑;ΒΝΖ ͤ͢͡ ͨͥ͟͢ίͩͧͤ͟ ͧ͑͢͢ ͧͪͦ͟ίͤͦ͟͡

͑͑ͷΖΞΒΝΖ ͑ͤͣ ͤͨ͢͟ίͣͦͪ͟ ͑ͤͧ ͧͪ͢͟ίͤͦ͟͡

͑͑΅ΠΥΒΝ ͧͣ͢ ͦͣ͢

͑͑΁͞ΧΒΝΦΖ

＜͟͢͡͡ ＜͟͢͡͡

;ΒΝΖ͑ΥΠ͑ΗΖΞΒΝΖ͑ΣΒΥΚΠ

͑͑;ΒΝΖ͠ΗΖΞΒΝΖ ͑͑ͥͧ͟͡ ͑͑ͤͣͣ͟

ͲΘΖ͞ΒΕΛΦΤΥΖΕ͑ΘΣΠΦΡΤ

͑͑＜ͪ͢ ͑͑ͣ͑ ͞ ͑ͪ͛͢ ͑ͥ͟͢ίͤ͢͟͢

͑͑ͣ͡ίͤͪ ͑ͧͤ͑ ͤͥ͢͟ίͥͧͥ͟ ͑ͨͧ͛ ͥͣ͟͢ίͦͩ͟͡

͑͑ͥ͡ίͦͪ ͑ͩͥ͛͛ ͥͥͣ͟ίͦͪͧ͟ ͑ͦ͡ ͣͦͥ͟ίͥͥ͟͡

͑͑＞ͧ͡ ͑ͤ͢ ͑ͤͩ͟ίͣͣ͢͟ ͑ͤ͢ ͑ͥ͟͢ίͤ͢͟͢

͑͑΅ΠΥΒΝ ͧͣ͢ ͦͣ͢

͑͑΁͞ΧΒΝΦΖ

＜͟͢͡͡ ＜͟͢͡͡

΃ΖΞΒΣΜΤͫ͑΅ΙΖ͑ΠΥΙΖΣ͑ΗΠΠΥΟΠΥΖΤ͑ΒΣΖ͑ΚΟ͑΅ΒΓΝΖ͑͢͟

for business, vacation, and other reasons [6-9].

In the present descriptive study, we investigated the current epidemiological aspects of EM imported by oversea travelers in Korea and Japan from 2015 to 2017. To assess the trend in relative factors of EM infected travelers visiting malaria-endemic areas.

II. MATERIALS AND METHODS

ՇՄ թ֋ֈ֌ջտււշքչջԶ պշ֊շԶ օռԶ փշւշֈտշԶ տքԶ աօֈջշԶ շքպԶ ՠշֆշք

The raw data on 162 confirmed EM cases (excludes 59 cases notified as “foreigners” by KCDC) in Korea were obtained from the Annual Reports of EM cases in the Disease Statistics System (website) of the Korea Center for Disease Control and Prevention (KCDC), 2015~2017 [8], and the Control index of malaria by the KCDC [9]. Data of the 152 EM cases (excludes 3 cases notified as “other” in 2016) of Japan were obtained from the Surveillance Data of EM cases from 2015 to 2017 of the Infectious Disease Surveillance Center (IDSC), the National Institute of Infectious Disease (NIID) in Japan [10-13].

ՈՄ թ֊շ֊տ։֊տչշւԶշքշւ֏։տ։

To better quantify the impact of EM on health in Korea and Japan, we compiled and analyzed information regarding the CIR per 100,000 populations nationwide and in travelers, and relative risk factors including gender, male-to-female morbidity ratio (MFMR), age distributions, and cases of EM species and imported from possible origins. Statistically significant differences between epidemic aspects and risk factors were determined using the Pearson’s chi-square test and paired t-test, and

estimating 95% confidence intervals (95% CIs). Results were considered statistically significant for a P-value of less than ƕ0.05.

III. RESULTS AND DISCUSSION

Malaria that affected Koreans is mainly in one of two main groups. The first group is Plasmodium vivax malaria, which reemerged in Korea in 1993. The second is imported malaria by oversea travelers and has been increasing in Korea in the last two decades, representing the main risk for travelers visiting malarious countries.

Nevertheless, the present study analyzes all of EM cases reported in Korea and Japan from 2015 to 2017 to assess the trend in epidemiological aspects of EM infected travelers visiting malaria-endemic areas.

As the results of Table 1 show, we observed 162 cases of EM in Korea with a CIR of 0.105 per 100,000 population nationwide and the CIR of the oversea travelers was 0.238 per 100,000 travelers from 2015 to 2017. During the same period in Japan, 152 cases of EM in nationwide with a CIR of 0.041 and in the oversea travelers with a CIR of 0.297 were observed.

When compared, the CIR of EM of nationwide in Korea was much high than in Japan, but a CIR of imported by oversea travelers in Korea was lower than that in Japan (Pƕ0.01).

These significant differences between the two countries can be

explained based on the differences in their epidemics pattern

 ו؁׭׷׶ׯֵגױ׶֨ה׭׭ִ֨׭׼֨ש״ֶ

΅ΒΓΝΖ͑ͥ͟ ʹΠΞΡΒΣΒΥΚΧΖ͑ΠΓΤΖΣΧΒΥΚΠΟ͑ΠΗ͑ΡΠΤΤΚΓΝΖ͑ΠΣΚΘΚΟ͑ΠΗ͑ΚΞΡΠΣΥΖΕ ΖΩΠΥΚΔ͑ΞΒΝΒΣΚΒ͑ΔΒΤΖΤ͑ΚΟ͑ΠΧΖΣΤΖΒΤ͑ΥΣΒΧΖΝΤ͑ΚΟ͑ͼΠΣΖΒΟ͑ΒΟΕ͑ͻΒΡΒΟΖΤΖ͝

ͣͦ͢͡ίͣͨ͢͡

΁ΠΤΤΚΓΝΖ͑ΠΣΚΘΚΟΤ ͼΠΣΖΒ ͻΒΡΒΟ

ʹΒΤΖΤ͑ ʹΠΦΟΥΣΚΖΤ ʹΒΤΖΤ ʹΠΦΟΥΣΚΖΤ

ͲΤΚΒ͑͗͑΀ΔΖΒΟΚΒ ͑ͩ͑͢ ͑͢͡ ͑ͣͩ͑ ͑͑ͪ

;ΚΕΕΝΖ͑ΖΒΤΥ͑͗͑ͲΗΣΚΔΒ ͥͥ͛͛͢ ͑ͣͧ ͦ͑͢͢ ͑ͣͦ

ʹΖΟΥΣΒΝ͑͗͑΄ΠΦΥΙ͑ͲΞΖΣΚΔΒ ͑͑͡ ͑͑͡ ͑͑͢ ͑͑͢

·ΚΤΚΥΖΕ͑ΞΦΝΥΚΡΝΖ͠ΦΟΜΟΠΨΟ ͑͑͡ ͑͑͡ ͑͑ͪ ͑͑ͪ

΅ΠΥΒΝ ͧͣ͢ ͑ͤͦ ͦͣ͢ ͑ͥͥ

΃ΖΞΒΣΜΤͫ͑΅ΙΖ͑ΠΥΙΖΣ͑ΗΠΠΥΟΠΥΖΤ͑ΒΣΖ͑ΚΟ͑΅ΒΓΝΖ͑͢͟

ͷΚΘ͑͑͟͢͟΅ΣΖΟΕΤ͑ΚΟ͑ΥΙΖ͑ΕΚΤΥΣΚΓΦΥΚΠΟ͑ΡΒΥΥΖΣΟ͑ΠΗ͑ΚΞΡΠΣΥΖΕ͑ΖΩΠΥΚΔ͑ΞΒΝΒΣΚΒ ΔΒΤΖΤ͑ΓΪ͑ΒΘΖ͞ΒΕΛΦΤΥΖΕ͑ΘΣΠΦΡΤ͑ΚΟ͑ͼΠΣΖΒ͑ΒΟΕ͑ͻΒΡΒΟ͑ͣͦ͢͝͡ίͣͨ͢͟͡

΅ΒΓΝΖ͑ ͤ͑͟ ʹΠΞΡΒΣΒΥΚΧΖ͑ ΠΓΤΖΣΧΒΥΚΠΟ͑ ΠΗ͑ ΖΩΠΥΚΔ͑ ΞΒΝΒΣΚΒ͑ ΔΒΤΖΤ͑ ΚΟ͑

ΧΒΣΚΠΦΤ͑ΤΡΖΔΚΖΤ͑ΓΖΥΨΖΖΟ͑ͼΠΣΖΒ͑ΒΟΕ͑ͻΒΡΒΟ͑ͣͦ͢͝͡ίͣͨ͢͡

΄ΡΖΔΚΖΤ͑ ͼΠΣΖΒ ͻΒΡΒΟ

ʹΒΤΖΤ͑ ͖ͪͦ͑ʹͺ ʹΒΤΖΤ͑ ͖ͪͦ͑ʹͺ

΁͑͟ΗΒΝΔΚΡΒΣΦΞ ͨ͑͢͡ ͦͩͩ͟ίͨͤͥ͟ ͢͢͡ ͦͩͪ͟ίͨͤͪ͟

΁͑͟ΧΚΧΒΩ ͑ͣͥ͑ ͑ͪͤ͟ίͣͤ͟͡ ͪ͢ ͑ͨͣ͟ίͨͩ͢͟

΁͑͟ΠΧΒΝΖ ͑ͧ͛͢ ͑ͦͤ͟ίͥͦ͢͟ ͧ ͑ͪ͟͡ίͨ͟͢

΁͑͟ΞΒΝΒΣΚΒΖ ͑͑ͥ ͑͟͢͡ίͥͪ͟ ͥ ͑͟͢͡ίͦ͟͢

ΆΟΜΟΠΨΟ ͑͢͢ ͞ ͣͣ ͞

΅ΠΥΒΝ ͧͣ͢ ͦͣ͢

΃ΖΞΒΣΜΤͫ͑΅ΙΖ͑ΠΥΙΖΣ͑ΗΠΠΥΟΠΥΖΤ͑ΒΣΖ͑ΚΟ͑΅ΒΓΝΖ͑͢͟

of EM cases imported by travelers [4-8], while the majority of malaria infections in Japan occur among persons who have traveled to or from areas with ongoing malaria transmission.

The total number of patients with acute malaria in Japan has been around 100Ê150 annually for the past two decades. Of those, about 75% are Japanese and 25% are foreigners [6].

Table 2 lists the epidemiological aspects of EM infectious cases in Korea and Japan between 2015 and 2017, analyzed by gender, MFMR, and age. More cases were males than females in both Korea (80.2% vs. 19.8%, Pƕ0.01) and Japan (76.3% vs. 23.7%, Pƕ0.01). The proportion of infections by sex was similar in both countries. Additionally, we utilized the MFER to estimate and compare the incident cases of EM infections between Korea and Japan. We observed similar MFMRs, 4.06 and 3.22 in Korea and Japan, respectively. The data may represent a difference in activities associated with

exposure in possible origins between men and women [4-8].

The distribution of EM cases in Korea by the age-specific adjusted group was as follows: for the age groups of under 19, 20-39, 40-59, and over 60 years old the percentages were 1.2%, 38.9%, 51.9%, and 8.0% respectively (Pƕ0.01). In Japan, the rates of infection in the respective age groups were 8.6%, 50.0%, 32.9%, and 8.6%, respectively (Pƕ0.01).

However, the distribution by age groups was different between Korea and Japan; over 51.9% of the cases of Korea occurred in the 40-59 years old age group, and in Japan, there was a high incidence in youth age, that 20Ê39 years old group (P ƕ0.05) (Fig. 1).

Table 3 shows comparative observation of the distribution of the plasmodium species of EM cases between Korea and Japan.

From 2015 to 2017 a total of 162 persons were diagnosed with EM in Korean. One hundred seven (66.1%) of the 162 cases were infected with P. falciparum, while 24 cases or 14.8% were diagnosed with P. vivax, 16 cases or 9.9% with P. ovale, 4 cases or 2.5% with P. malariae, and 11 cases or 6.8% with unknown cases, respectively. During the same period in Japan, the percentages of the 152 persons infected with P. falciparum, P.

vivax, P. ovale, P. malariae and unknown cases were 101 cases or 66.4%, 19 cases or 12.5%, 6 cases or 4.0%, 4 cases or 2.6%, and 22 cases or 14.5%, respectively. Notably, the risk rates of P. ovale in Korea were much higher than those of Japan (Pƕ

0.05). These data strongly indicate that the EM incidence is

influenced by their travel areas. Although the number of

Korean and Japanese individuating abroad has increased

steadily, reaching approximately several ten-million per year,

the incidences of various travel-related health problems both

countries remain unknown [4,7-13]. Malaria is one of the

prevalent infectious diseases in tropical or sub-tropical areas and

remains a significant public health problem in the world. In

Korea and Japan, most of the people affected with malaria are

ב׵׸׷׺׼׭׬֨׍؀׷׼ױ׫֨וש״ש׺ױש֨׋ש׻׭׻֨ױ׶֨ד׷׺׭ש֨ש׶׬֨גש׸ש׶

people who travel to or from tropical or subtropical areas where the disease is endemic [1-13].

Table 4 shows, the possible origins for the EM infections in Korea and Japan from 2015 to 2017. A total of 162 cases of EM in Korea were associated with the Middle East & Africa region (144 cases or 88.9% of total cases) and Asian & Oceania region (18 cases or 11.9%), while a total of 152 cases of EM were reported in Japan. Notable, among them, most cases were from the Middle East & Africa region 115 cases or 75.7%, followed by Asia and Oceania 28 cases or 18.4%, Central and South America one case or 0.7%, and visited multiple/unknown 9 cases or 5.9%, respectively. While many Korean and Japanese people travel to Asian countries where malaria risk is limited, the number of those visiting highly malaria-endemic areas like sub-Saharan Africa or Oceania is steadily increasing. Consequently, countermeasures against a possible increase in the number of malaria cases, especially that falciparum malaria cases in the future, should become a priority [1,4,14-16]. Moreover, for example of the United States in 2015, the region of acquisition and diagnosis were known for 1,428 (96.2%) of 1,485 imported EM cases. Among these, 1,210 (84.7%) were acquired in Africa, 123 (8.6%) from Asia, and 66 (4.6%) from Central America and the Caribbean, respectively [17]. Nevertheless, although there were some limitations and problems in the present study due to them being only reports to the KCDC of Korea and IDSC of Japan from 2015 to 2017, some meaningful epide- miologic aspects were revealed. These differences in malaria risk factors reflect the different influences of epidemic patterns and aspects of malaria between the two countries.

In conclusion, many Korean and Japanese travelers are unaware of diseases in the countries they visit and do not adequately protect themselves. Careful attention to avoid contact with mosquitoes is very important to prevent a malaria infection, but challenging. No practical method of immunization is available to date. Various types of chemoprophylaxis agents for malaria have been used for a long time [1,13-17]. To implement effective education measures against imported malaria, evaluation of infection risks based on the incidence rates of malaria per given number of travelers to each area/country is necessary.

ACKNOWLEDGEMENT

We give thanks for Korea Center for Disease Control and Prevention in Korea and National Institute of Infectious Disease in Japan.

REFERENCES

1. World Health Organization (WHO). Malaria. Catalyzed by WHO and RBM Partnership to END Malaria, 19 November 2018.

https://www.who.int/news-room/fact-sheets/detail/malaria/. Accessed on 27 Feb. 2019.

2. Thwing J, Skarbinski J, Newman RD, Baeber AM, Mali S, Robert J.M, Slutsker L, Arguin PM. Malaria Surveillance-United States, 2005. Morbidity and Mortality Weekly Report (MMWR).

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12. Infectious Agents Surveillance Report (IASR). Malaria, Japan, 2006-2017. IASR;39(10):167-175.

13. Infectious Disease Survellance Center (IDSC). Trends in Notifiable of Imported Cases among Select Notifiable Infectious Diseases in Japan. http: www.jnto.go.jp/niid/ja/dengue-imported.html/ Assessed; Jan.

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본 연구는 2015년부터 2017년까지 한국과 일본에서 보고된 해외유입 말라리아(Exotic Malaria) 사례를 분석하여 말라리아 발병 국가를 방문한 여행자들의 위험 요인과 한국과 일본의 발병 유형에 차이점이 있는지를 확인하고자 하였다. 2015년

부터 2017년까지 한국의 질병통제예방센터(KCDC)와 일본의 국립전염병연구소(NIID) 웹사이트에서 얻은 해외유입 말라

리아에 대한 자료를 분석하였다 . 한국 전역에서 162건의 해외유입 말라리아가 발생하여 10만명당 누적 발생률 (CIR)이

0.105이며, 해외여행자 10만명당 CIR은 0.238이었다. 같은 기간 일본 전역에서 152건의 해외유입 말라리아가 발생하여

10만명당 CIR이 0.041, 해외여행자 10만명당 CIR이 0.297이었다. 양국을 비교했을 때 전국적으로 해외유입 말라리아의 CIR은

일본에 비해 훨씬 높았지만(Pƕ0.01), 한국 해외여행자의 CIR은 일본보다 낮았다 (Pƕ0.01). 두 나라 모두 여성보다 남성의 경우 해외유입 말라리아 감염이 더 많았다(한국에서는 4.06배, 일본에서는 3.22배). 한국에서는 40a50세 연령층에서 감염 발생률이 가장 높았고(전체 사례의 51.9%), 일본에서는 20-39세 연령층에서 감염발생률이 가장 높았다(전체 사례의 50.0%) (Pƕ0.01).

중심단어 해외유입 말라리아 , 누적 발생률, 역학 동향, 한국과 일본