Malaria, an important communicable disease for many years in Korea, prevailed throughout the country until the 1950s. Since then, cases rapidly declined until it was declared eradicated in 1979 (WHO, 1981). Recently malaria has re-emerged in South Korea and become an important public health threat. Several review papers on malaria in Korea have been published (Paik and Tsai, 1963; Kim, 1982; Paik et al., 1988; Lee et al., 1994; Chai, 1999). Most of these review papers focussed on a specific period. Therefore, a historical review is meaningful for more comprehensive understanding of the epidemiology and potential for malaria control/eradication. In particular, the accomplishments of the National Malaria Eradication Service (NMES) activities, most of which were not officially ducumented are reported rather in detail. Only endemic Plasmodium vivax in Korea was dealt in this review, excluding imported cases of P. malariae, P. falciparum and other imported strains of P. vivax. Though there was a strong evidence that P. malariae was endemic in limited areas of Chungchongnam-do in 1929-1930 (Chiba and Aki, 1930; Oh, 1930), it was no longer considered as a health threat.

Malaria was prevalent and a major health threat in Korea during previous centuries. The vivax malaria was first reported in 1913 by Hasegawa. He reported 1,328 cases of Korean civilians and 147 cases of Japanese soldiers at 13 locations throughout the country (Table 1). Analysis of 1,201 cases showed that (1) 74.5% was male and 25.5% female, (2) age composition was 44.9% in < 10 years, 20.9% in 11-20 years, 14.5% in 21-30 years, 8.7% in 31-40 years, 5.1% in 41-50 years, and 5.9% in > 51 years, and (3) seasonal occurrence was 1.9% in January, 2.2% in February, 2.4% in March, 5.3% in April, 7.8% in May, 21.4% in June, 15.1% in July, 16.1% in August, 14.8% in September, 9.0% in October, 2.7% in November, and 1.2% in December. Epidemiological significance was that the highest positive rate was shown in the age group under 10 years old (44.8%), and 19.7% of the total cases occurred during the period of non-transmission season (November-May), indicating that a Korean strain would be the delayed type temperate zone strain. Among the 67,531 patients who visited the Kangnung Provincial Hospital in Kangwon-do in 1917-1925, 3,083 cases (4.6%) were diagnosed as vivax malaria (Table 2). Many of the cases were reported during the non-transmission period when daily temperatures were below 15℃, suggesting the protracted incubation of vivax malaria in Korea (Himeno, 1926). Malaria parasite rates of school children in Kangwon-do were 8.1% in Korean students and 3.8% in Japanese students at Cholwon, and 16.1% in Korean students and 7.3% in Japanese students at Chunchon (Tanabe, 1927). Kodama (1928) reported that malaria was prevalent throughout Kangwon-do, particularly in counties bordering the Taibaek mountains, where rice paddies were limited. Kobayashi (1931) reported 2,322 malaria cases in 1922, 1,366 cases in 1923, 619 cases in 1924 and 635 cases in 1925 in 6 different locations (Table 3). He also mentioned that malaria cases occurred throughout the Korean peninsula with an uneven geographical distribution, and malaria was the major endemic disease in some areas, whereas very rare in many other areas, indicating focal malaria transmissions. It is interesting to note that the highest number of malaria cases were reported in Hamhung, Hamkyongnam-do in 1910 (Hasegawa, 1913) and in 1923-1925 (Nagai, 1925). Among a total of 26,775 patients admitted to Severance Hospital, Seoul, during a 10 year period (1926-1935), 84 patients (0.3%) were diagnosed as malaria (Table 4) (Choi, 1936).

Available information reported on malaria in Korea prior to 1945 indicates that vivax malaria was endemic and prevalent throughout the Korean peninsula, demonstrating an uneven geographical distribution with a higher incidence rate in mountainous areas rather than large rice growing regions.

There were little data reported for the prevalence of malaria in Korea during the second world war (1941-1945), a period following post-indenpendence (1945-1950) and the Korean war (1950-1953). Among 3,983 students of middle schools in Seoul in 1948, 584 students (14.7%) were diagnosed as malaria (Chun, 1959). In 1952, 1,032 malaria cases were reported from April through September (peak in July) in Yangyang-gun (county), Kangwon-do, of which the highest rate was identified in children under 5 years (Kim and Han, 1953). They also conducted a mass blood survey of 208 soldiers and found 4.8% positive rate. The military medical office reported from a military population of 400,000 that there were 8,855 cases (2.2%) and 5,741 cases (1.4%) of malaria in 1953 and 1954, respectively. US troops dispatched to the Korean war were provided chloroquine chemoprophylaxis (weekly) during the transmission season. Nevertheless 1,513 soldiers were reported with vivax malaria from July 1951 through November 1952 (Hanky et al., 1953). Among 1,350 Canadian soldiers that deployed to Korea during the Korean war in 1952, 152 (11.3%) became ill with vivax malaria after returning home country (Hale and Halpenny, 1953).

Judging from such limited data, it is certain that the prevalence of malaria in Korea increased in remarkable degree as a result of the Korean war. Because of poor records and population movement, the geographical distribution is not well understood.

The National Malaria Eradication Service (NMES) was established in April 1959 as a joint project of the Republic of Korea and the UN/WHO Western Pacific Regional Office. The Service was consisted of 28 Korean members and 2-3 WHO consultants (malariologist, parasitologist and/or entomologist), assigned to parasitological laboratory, entomological and epidemiological teams. The results of NMES activities were incompletely reported in published documents (Paik and Tsai, 1963; Whang, 1962, 1963, 1964; Paik et al., 1965; Paik and van der Gugten, 1966; NMES, 1966; Hong, 1967; Chen et al., 1967; Ree and Paik 1967; Hong and Ree, 1968). The followings are the summarized results of NMES activities.

A prolonged incubation period has been observed from many strains of P. vivax, mainly in the temperate zone, such as Dutch, Madagascar, USSR and Korea. The first observation of longterm incubation period of Korean P. vivax was made by Hasegawa (1913). He reported that 6 Japanese soldiers returned from Korea to Osaka, Japan in April 1910 and demonstrated the onset of malaria in June 1910. As there was no malaria in Osaka, they were suspected to be infected in Korea during the transmission season of the previous year. He also observed that out of 1,201 malaria cases 251 (20.9%) occurred from December through April during the non-transmission season. In the 1950s, several workers reported both short and long incubation periods of a Korean strain of P. vivax (Eddleman et al., 1951; Hall and Loomis, 1952; Brunetti, 1954; Brunetti et al., 1954; Tiburskaja et al., 1968). Brunetti et al. (1954) reported that an outbreak of vivax malaria in California, USA, resulted from veterans returning from the Korean war. Nine persons became ill after an incubation period of 10-40 days while 26 persons became ill after an incubation period of 217-316 days. Exoerythrocytic stages of the North Korean strain could still be found in the liver 255 days after the inoculation of sporozoites (Garhnam et al., 1975). They mentioned that the North Korean strain resembled the Dutch and St. Elizabeth strains and lied between P. vivax vivax and P. vivax hibernans because it did not always show a long incubation period. Shute et al. (1976) experimentally studied the effect of numbers of sporozoites inoculated on the length of the incubation period using the North Korean strain of P. vivax. All 6 subjects inoculated with 10-100 sporozoites became ill after a long incubation period (262-628 days). Among 5 persons injected with 1,000 sporozoites, 4 became ill after a long incubation (257-386 days) and one 16 days after inoculation. All 5 subjects inoculated with 100,000 sporozoites became ill after a short incubation period (13-16 days). They concluded that there are two strains (populations) of sporozoites, one governing long incubation and the other short incubation, with the strain of short incubation representing a small proportion of the whole population. Tiburskaja and Vrublevskaja (1977) experimentally infected humans with the North Korean strain of P. vivax through bites of the infected mosquitoes. Among 77 patients, 19 (24.7%) became ill after a short incubation period (14-22 days) and 58 (75.3%) after a long incubation period. Among 58 cases of long incubation period, 1 case (1.3%) became ill after 1 month, 11 (14.3%) after 8 months, 14 (18.2%) after 9 months, 14 (18.2%) after 10 months, 13 (16.9%) after 11 months, 3 (3.9%) after 12 months, and 2 (2.6%) after 13 months.

One indigenous case of P. vivax was reported in Paju-gun, Kyonggi-do in July 1993 (Chai et al., 1994). Since then the number of cases has been rapidly increased annually, as shown in Table 16 (National Institute of Health, 1995, 1996, 1997, 1998, 2000; Lee et al., unpublished). The discharged soldiers who were infected while on army service and a paroxism was presented at home after discharge were put in the "soldier" category.

The majority of the cases were reported in military personnel, particularly at beginning of the outbreak, composed of 90% in 1994, 92.5% in 1995, 86.8% in 1996, 79.1% in 1997, 70.8% in 1998, and 57.8% in 1999. The rate of soldiers has been decreasing year after year, and the number of soldier cases decreased from 2,784 in 1998 to 2,092 in 1999. By sociopolitical factors, it was suggested that the rate in military personnel should have been higher than for civilians since soldiers on sentry duty were severely exposed to mosquito bites throughout the night outdoors in and/or near the DMZ where domestic animals were not available for feeding of zoophilic vector mosquitoes. After 1997, many soldiers serving in and/or near the DMZ were placed on chloroquine prophylaxis through the whole mosquito season with primaquine at end of the season (Kim et al., 1997, 1998; Lee, 1998). Chemo-prophylaxis and other measures such as wear of permethrin-treated uniforms resulted in continuous decrease in the number of cases in military personnel in 1999. Lee (1998) reported that chloroquine (300 mg/week) and primaquine (15 mg/day for 14 days) for chemoprophylaxis were administered to soldiers who served in high risk areas (in and/or near the DMZ). None of properly administered soldiers developed malaria, whereas 11% of inadequately administered soldiers and 89% of untreated soldiers developed malaria. The decrease in reported malaria cases in soldiers in 1999 resulted in an overall decrease to 3,621 (0.9x) from 3,932 in 1998, inspite that the malaria cases of civilians increased to 1,529 (1.3x) in 1999 from 1,148 in 1998.

Predromal symptoms of 87 patients of vivax malaria was observed (Lim et al., 1996). Thrombocytopenia appeared in 72.4% of the patients with 124,000±71,000/µl, anemia in 92% with 12.4±2.2 g/dl of hemoglobins, and splenomegaly in 72%. High fever (≥ 40℃) was shown in most of the patients, with 48 h periodicity in 72.4%, 24 h periodicity in 10% and no periodicity in 17.6%. Kim and Lim (1997) studied symptoms of 26 patients of ROK Army and observed myalgia (88.5%), vomiting (34.6%), diarrhea (3.8%), and oral herpes simplex (3.8%), besides typical malaria symptoms such as fever, chills, headache, etc. Hematologic findings were anemia (92.3%), thrombocytopenia (61.5%), leukopenia (50%), and leukocytosis (19.2%). Song (1965) reported that parasite density in blood of 171 patients in Korea was 3,853/mm³, of which number of gametocytes were 135/mm³ (3.5% of the total). On the other side, Lim et al. (1996) reported that gametocytes were most frequently found (95.7%), and the next was ring form trophozoites. Kim and Lim (1997) also observed that the majority of parasite stage was gametocytes (92.3%) in their blood smears and the next young trophozoites (26.4%). As these gametocyte rates were unusually high, re-observation of the slides for confirmation is required.

Hankey et al. (1953) reported that 355 veterans infected with P. vivax were treated with 1,500 mg of chloroquine (base) in 3 days (3 doses of 300 mg during the first 24 h, a single dose of 300 mg daily for 2 days), and 137 (38.6%) relapsed at least once. The mean duration from the first attack to the second was 68.6 days in average (range 39-247 days). Tiburskaja and Vrublevskaja (1977) observed that out of 74 patients treated with chloroquine after the first attack, 23 (31.1%) relapsed, of which 11 cases relapsed once, 11 cases twice and 1 case 3 times.

Among 272 patients treated with chloroquine 1,500 mg in 3 days plus primaquine 27 mg/day for 14 days, 2 cases relapsed, whereas no one relapsed among 348 patients treated with chloroquine 1,500 mg in 3 days plus primaquine 15 mg/day for 14 days (Alving et al,. 1953). In the course of these studies, only minimal evidence of drug toxicity was observed. One patient treated with chloroquine alone developed mild generalized pruritus which subsided 4 days after the drug was stopped. A similar mild pruritus developed in a patient treated with chloroquine and primaquine. It disappeared after chloroquine was stopped and before the administration of primaquine was completed. There was no evidence of hemolytic anemia in any patient. Approximately 15% of the patients had a mild to moderately severe anemia (hemoglobin concentration of 6.4-12 gm/100 cc) at the time treatment was instituted.

The patients of veterans with vivax malaria acquired in Korea were treated at the time of a late acute attack and followed for more than 4 months thereafter. The effect of a daily dose of 10-30 mg of primaquine for 14 consecutive days on the relapse rate is shown in Table 19. Among a total of 334 patients treated with chloroquine alone, 146 (43.8%) relapsed at least once after treatment. None of the patients treated with 20 or 30 mg of primaquine daily for 14 days relapsed (Jones et al., 1953). A regimen of 20 mg of primaquine daily for 7 days was studied in order to determine whether a shorter period of treatment was equally effective. Thirty-six patients (51.4%) treated with chloroquine alone relapsed, and 2 (2.9%) of 68 patients treated with 20 mg of primaquine daily plus chloroquine 1,500 mg in 3 days relapsed 51 and 68 days after treatment, respectively. A regimen of 15 mg of primaquine daily for 7 days resulted in 1 relapse (3.2%) out of 31 patients 49 days after treatment (Lorenzo et al., 1953). Curative effect of primaquine 15 mg daily for 14 days was tested with 625 veterans of long-term latency, who had been exposed to malaria in Korea in the summer of 1951 and returned to USA before January 1952. None of the 294 men treated with primaqine developed malaria during the 6 months' period following treatment, whereas 58 (17.5%) of 331 men treated with a placebo gave a history of malaria (Coatney et al., 1953).

Anopheles sinensis had been suspected as the vector species of malaria for many years in Korea (Hasegawa, 1913; Kobayashi, 1932; Yokoo, 1944). In 1962, An. sinensis was confirmed for the first time as a malaria vector species; total 5,086 females collected at Kaegun-myon, Yangpyong-gun, Kyonggi-do during the period of 1960-1962 were dissected for salivary gland, and sporozoites were observed from one female, showing a 0.02% sporozoite rate (Ree et al., 1967). In 1967, 4,018 females of An. sinensis were dissected in Chongsong-gun, Kyongsangbuk-do and sporozoites were found in 2 females, showing a 0.05% infection rate (Hong, 1977). He also dissected 89 An. yatsushiroensis and found one positive for oocysts (not sporozoites). In an experimental infection study, sporozoites developed in 2 females out of 9 An. yatsushiroensis (Hong, 1977). These two study results strongly suggest that An. yatsushiroensis is also a vector species of malaria in Korea.

Study results on bionomics and/or behaviour of An. sinensis are available in many references (Yokoo, 1944; Whang, 1962, 1964; Paik et al., 1965; NMES, 1966; Chen et al., 1967; Ree and Paik, 1967; Hong, 1967, 1977; Ree et al., 1981; Lee and Ree, 1991; Ree and Lee, 1993; Shim et al., 1997), summary of which are as follows: (1) broad range of breeding places such as rice paddy, marsh, stream, reservoir, pond, water pool with vegetation, temporary rain pool, etc., (2) highly zoophilic with particular preferences of cows and pigs, (3) feeding activity throughout night with a peak during 1100-0300 hours, (4) rather strong phototaxis, (5) moderate to low daily survival, (6) 2.5-3 days of gonotrophic cycle, (7) mainly outdoor resting habit, (8) seasonal prevalence of May-October, with a large peak in late June-early July and a small peak in late August-early September, (9) population density extremely high, and (10) hibernating mainly outdoors, such as grasses, bushes, dike and others.

Korean vivax malaria had been endemic for longtime with low incidence and prevailed throughout the country including Cheju-do and became epidemic during the Korean war (1950-1953). In 1959-1969, when NMES activities was implemented, malaria endemicity was declining, with very low endemicity in south-west and south, plain areas and high endemic foci in north Kyongsangbuk-do and north and east of Kyonggi-do. NMES activities greatly contributed to accelerating disapperance of malaria endemicity particularly in the focal areas, and resulting in the malaria eradication from the Republic of Korea (South Korea) in 1979.

Since 1993, malaria has re-emerged mainly in north Kyonggi-do and north-west Kangwon-do, located bordering the DMZ. It is postulated that malaria in North Korea had persisted with low endemicity until an epidemic started in 1994, as meteorological and socio-economical factors changed in favor of vectors and parasites, resulting in an outbreak in north Kyonggi-do. This outbreak may have resulted from sporozoite-infected mosquitoes dispersing from North Korea across the DMZ to South Korea.

All historic records tell that vivax malaria in Korea results in unstable malaria, with epidemics occurring when environmental factors such as climatic, socio-ecological, political (wars), entomological and parasitological factors change in favor of vectors and/or parasites. PCD is a feasible and recommendable control measure in cost-effect point of view against the unstable vivax malaria in Korea.