Fifty Years of the Korean Society for Parasitology

Academic Meetings

The first activity of the Society was the academic meeting held on 21 November 1959 at the Lecture Room "A" of Seoul National University Hospital [3]. A total of 30 research results were presented there. The first presentation was "A case of Isospora belli infection." Other presentations at the first meeting included histochemical studies on Ascaris suum and Ascaris lumbricoides, morphological studies on subgenus Spirometra tapeworms, excystation of Clonorchis sinensis metacercariae, epidemiological studies of human paragonimiasis in Cheju Island, trials of dithiazanine iodide on C. sinensis, anthelmintic evaluation of bephenium hydroxynaphthoate, a case of spinal paragonimiasis, a case of intestinal myiasis by Sarcophaga species, etc. The academic meeting was held once annually until 1966. In 1967, the Society began to have another periodic meeting in spring. Since 1963, the number of presentations at the Society meetings increased to 60-70 annually. As of 2009, the annual meeting and general assembly have been held yearly without interruption.

Literature

Another product of the Society activities was a literature database on Korean parasites and parasitic diseases published in 1961 [4]. A total of 777 articles, including those written before 1945 by Japanese scholars, such as Professor H. Kobayashi and his colleagues and those published around the Korean War by scientists and medical doctors of the U.S. Army Medical Corps, as well as by some Korean authors, were listed with their bibliographic data. In 1963, the Korean Journal of Parasitology was inaugurated. The journal was regarded by Korean medical scientists as one of the best medical journals published in Korea [5-6]. Bibliometric analysis of the journal articles appeared in a separate article in this supplement.

Organization and activity of parasite control

Members of the Society participated in founding the Korea Association for Parasite Eradication (KAPE), a business partner of the Society, in 1964 [7]. After the foundation of KAPE, there was a policy debate on how to promote the control activities against soil-transmitted helminthiasis. One was an enlightenment movement of people to combat parasitic diseases together with propagation of a new toilet tank device separating urine from feces in farm houses. Another was a parasite control program already undergone by the Japanese Association of Parasite Prevention, a business model of school-based selective mass chemotherapy undertaken twice a year. After the debate, it was decided to adopt the business model of mass chemotherapy. One difference from Japanese model was a legal base for its activity. The Japanese model of the business was purely civilian in which people voluntarily participated in a parasite control movement. To be successful in Korea, however, legal support was considered necessary. The Law of Parasitic Diseases Prevention was thus drafted, was agreed upon in the National Assembly, and was promulgated by the ROK Government in 1966. The Society members also participated in recruiting Japanese assistance for initiating KAPE's activity. Vehicles, drugs, instruments for microscopy and laboratory works, and training program of business and technical personnel were kindly provided by the Overseas Technical Cooperation Agency (OTCA, now JICA) of Japan for 6 years from 1968. Parasite control activity by KAPE actually began in 1969 and continued for 27 years until 1995. Domestically and internationally, the parasite control activity in Korea has been regarded as a success [8].

The progress of activity of the Malaria Eradication Team of the Ministry of Health and Social Affairs, collaborated with the World Health Organization (WHO), was scientifically analyzed and the results were read in academic meetings of the Society. Unstable vivax malaria in many previously endemic areas in Korea was found already regressive in the early 1960s, resulting in "anophelism sine paludism." The Team reported the usefulness of passive case detection in the malaria control program and mapped regressing and persisting endemic foci in Korea. The Team stopped its activity in 1968 [9].

Introducing science and technology

Advanced science and technology of parasitology, new to Korea, were introduced from the USA, Europe, and Japan in order to solve domestic issues. Anti-parasitic drugs and diagnostics were welcomed with particular enthusiasm. Piperazine for ascariasis/enterobiasis and metronidazole for amebiasis were introduced. In the case of bithionol, its clinical efficacy was evaluated soon after its discovery in Japan for treating human paragonimiasis [10,11]. Hetol was once tried for clonorchiasis in 1965 and finally given up because of its nephrotoxicity.

Intradermal test for clonorchiasis and paragonimiasis using veronal-buffered antigen [12] and complement fixation test for paragonimiasis [13] were also introduced [14]. Based on the complement fixation tests of cerebrospinal fluid, patients of cerebral paragonimiasis could be diagnosed [15] and then treated with bithionol [16].

Many different stool examination techniques had been also evaluated. Of them, sensitivity of cellophane thick smear technique (Kato-Katz) was compared with that of the formalin-ether concentration technique [17]. Soon, cellophane thick smear was adopted as KAPE's main method of mass stool examination. Throughout the selective mass chemotherapy program that was undertaken for decades, infected students could be screened out using this simple and inexpensive technique that made mass stool examination possible. Application of Stoll's egg counting technique was extended to C. sinensis and A. lumbricoides in order to estimate burden of the infections. Egg counting was also used in evaluation of the efficacy of anthelmintics.

Importance of epidemiology of parasitic infections

Malaria, trypanosomiasis, leishmaniasis, schistosomiasis, filariasis, and leprosy were recognized by WHO as 6 major tropical diseases that needed worldwide research efforts. In Korea, except for regressing malaria and lymphatic filariasis, parasitic infections of domestic importance, such as soil-transmitted nematode infections, clonorchiasis, paragonimiasis, cysticercosis, etc., were not listed. Therefore, in order to combat domestic parasites, research on these infections had to be done locally without foreign supports. In such a context, concepts of epidemiology and social medicine were emerged as a reasonable approach. Fortunately, in the 1960s, many local surveys were undertaken in different villages, institutions or specific groups of people. Athletes and players who participated in the Olympic Games, for example, were examined for parasitic infections. Local endemic areas of filariasis, clonorchiasis, and paragonimiasis were mapped one by another. In comparing the survey results with those reported long before by Japanese, American or Korean researchers, differences in prevalence were recognized. However, it was difficult to tell whether the situations were improving or worsening, because the degree of infections varied greatly by area. There was therefore a need for comprehensive and realistic evaluation of the nationwide situation.

Korea in the latter half of 1960s began to industrialize; national wealth also began to accumulate. In 1970, for the first time, the ROK Government was able to draft national budget plan based solely on national tax revenue. In accordance with economic improvement, public health issues became more of a widespread concern, and modern medicine found an appreciative welcome. The ROK Government's Ministry of Health and Social Affairs supported civilian organizations acting against tuberculosis, leprosy and parasitic diseases which were assembled by medical professionals and business officers. The first issue that these organizations had met was to arrive at a reasonable estimate the national burden of the diseases. In 1965, the Korean Institute of Tuberculosis reported results of the first national survey of tuberculosis prevalence collected from a national random sample. The members of the Korean Society for Parasitology were impressed by the report and decided to follow the good example.

Surveys

After completing its second-year activity, KAPE reported in 1970 [18] that 10,871,280 fecal samples from elementary, middle and high school students nationwide were examined microscopically. The egg positive rates in the year were; Ascaris lumbricoides 55.2%, hookworm 1.0%, Trichuris trichiura 46.8%, Trichostrongylus orientalis 0.7%, Clonorchis sinensis 0.5%, Paragonimus westermani 0.01%, and Taenia species 0.6%, respectively.

These data showed the weight of social burden of parasitic infections. However, these data, together with those obtained in successive years, were criticized in 2 aspects. One criticism was that these data could not represent a general prevalence, because only students were examined. Prevalence rates of the hookworm, C. sinensis and Taenia species were known to be much higher in adults than those in students. Another criticism was that sensitivity of mass fecal examination was a little lower than those obtained in the research laboratory. The problem of low sensitivity should be excused because the difference was not major, and the KAPE examination was done as a business and most importantly, heavy infection cases, which most needed anthelmintic treatment, did not escape detection. Though excused, in terms of its assessment of national prevalence, the data in KAPE reports were in any case defective. A national survey in random samples from whole Korean population was, therefore, necessary for proper evaluation of the progress of control activity. The Ministry of Health and Social Affairs agreed on the necessity, submitted budget plan for a survey to the National Assembly, and secured the budget. The National Statistical Office provided KAPE with a national random sample comprising of one sample from approximately one thousand people. KAPE staff collected fecal samples and examined them. Members of the Society reviewed survey plans including examination techniques and items of questionnaires, and prepared the reports. The surveys of prevalence of intestinal parasitic infection were conducted in this way every 5 years 7 times, in 1971, 1976 [19], 1981, 1986, 1992, 1997, and 2004. The surveys were a good evaluation system for parasite control although their coverage was limited to intestinal helminths. In retrospect, the 1970s was the most critical period in the change of parasitic infections in Korea. After initiating the national survey, local surveys of small size undertaken by researchers became more specific, focusing on possible hidden endemic areas of clonorchiasis, paragonimiasis, metagonimiasis, and others.

Drug evaluation

Until the end of 1960s, only a few kinds of anthelmintics, such as piperazine, santonin, kainic acid, and bithionol, were available in Korean market. Hexylresorcinol and tetrachlorethylene were also used but rarely. Pyrvinium pamoate for enterobiasis was imported since the mid-1960s. Anthelmintics were one of the most favored medicines at that time; people could purchase them without physician's prescription. In remote villages, fake or true anthelmintic were sold by unlicensed merchants. With economic development, the size of anthelmintic market increased further. New anthelmintics such as pyrantel pamoate and mebendazole were found to be safe and effective for intestinal nematodes, and were introduced in the early 1970s. A copy mebendazole appeared in the market almost exactly after the original was introduced.

Until the late 1970s, no safe and effective drug for clonorchiasis existed. A drug screening system for Clonorchis sinensis was thus established in experimental rabbits, which were orally infected with 500 metacercariae; and candidate chemicals were tested in the model. Dehydroemetine late-releasing tablets, niclofolan, bisbendazole and others were tried both in the model and in infected patients [20]. However, these were found to have either low efficacy or narrow safety margins.

In 1972, praziquantel was found to have anthelmintic activities in Germany. Its efficacy and safety evaluation in human schistosomiasis and intestinal cestode infections had already been done. Bayer, its manufacturer, wanted to extend its spectrum of efficacy to other helminth parasites. The efficacy of praziquantel in treating human clonorchiasis, were examined in Korea and reported in 1981 [21]. This discovery was nationally welcomed. The clinical efficacy of praziquantel was also evaluated for infections of Hymenolepis nana, Taenia solium, Paragonimus westermani [22] and T. solium cysticercosis [23]. No chemotherapeutics had hitherto been available for T. solium cysticercosis. Praziquantel became the first drug which was proved to be effective for neurocysticercosis. The efficacy was examined clinically by using either brain computerized tomography (CT) or biopsy of degenerating worms in subcutaneous nodules. Praziquantel became the first drug to cure hymenolepiasis. Praziquantel was also practically the first drug that treated human paragonimiasis. Bithionol had been used; however, because of its side effects such as drug eruptions, severe diarrhea and other gastrointestinal symptoms, patients could not comply with the recommended dose schedule. In the praziquantel evaluation for paragonimiasis, objective evidences of a cure were very difficult to secure, but the difficulty was overcome by long-term follow-ups of chest radiography, and antibody tests in addition to clinical improvement and egg negative conversion. Praziquantel was effective, and have negligible side effects, and was welcomed by patients, clinicians and parasitologists.

Mass chemotherapeutic control

The first trial of mass chemotherapeutic control of parasitic infections in Korea began in 1964 for human paragonimiasis in Cheju Island [24]. The well designed trial was based on the fact that zoonotic Paragonimus infections on the island was almost nonexistent, because the population of wild carnivora, cats and dogs were reduced to a level of extinction due either to deforestation or to national rat control program using rodenticide in the early 1960s. In this context, it was hypothesized that treating most paragonimiasis patients using bithionol would eliminate infection sources to freshwater snails and crabs, thus would control the human disease. The program was well progressed until the early 1970s when a confounding factor intervened. Streams were polluted with pesticides, insecticides and household and industrial wastes. Intermediate hosts disappeared from endemic foci only to reappear again decades later.

Mass chemotherapeutic control programs of lymphatic filariasis were done in the early 1970s also in Cheju Island, using diethylcarbamazine [25]. After examining night blood smears, microfilaremic cases were treated with the drug. The program was undertaken for 5 years, and collaborated with Japanese workers. In addition to control studies, microfilarial morphology and confirmation of causative pathogen as Brugia malayi, circadian rhythm of microfilariae, vector efficiency of Aedes togoi mosquitos, and mathematical modeling of filarial epidemiology were studied. Korean workers tried to reduce the severity of adverse reactions by reducing the initial dose of diethylcarbamazine. Japanese workers focused on clinical studies and made a cat model of Brugia malayi infection. Mass chemotherapeutic control of lymphatic filariasis was also confounded by improved living standard of local people such as use of bed nets, building new houses and extensive spraying of insecticide in orange farms in the endemic villages. Since 1975, the project of lymphatic filariasis control was transferred to local health centers.

In the case of mass chemotherapeutic control of Ascaris lumbricoides, an experimental epidemiologic study was designed to confirm a theoretical model. The model, proposed by a Japanese parasitologist, Dr. Y. Komiya, theorized the effects of mass chemotherapy in a situation of continuous occurrence of reinfection [26]. In the Korean field study, undertaken for 5 years in Hwa-Seong County, reinfection patterns were evaluated not only by egg positive rates but also by counting worms expelled by quick acting and effective pyrantel pamoate. In the study, it was concluded that a year's interval mass treatment could not lower the infection rates in a population. This conclusion was explained on the basis of life span of adult A. lumbricoides, which was estimated to be 7-8 months in human hosts. Worm populations were replaced every 7-8 months in host population. Therefore, it was found that the shorter the mass chemotherapy intervals were, the lower the resulting infection rates in a population [27]. In the case of 2-months interval mass chemotherapy, A. lumbricoides could not discharge eggs because they were removed before maturation. Reinfection was ceased when 2-months interval mass chemotherapy were repeated for 3 years, probably by depleting already contaminated infective eggs in environment. In the worm burden study, reinfection burdens were found to go parallel with reinfection rates. Korean experiments showed that Ascaris infections can be controlled by mass chemotherapy if repeated in appropriate intervals for a certain period. The worm frequency was found to be distributed in negatively skewed pattern in host population, which was mathematically fitted to the equation of negative binomial distribution rather than Polya Eggenburger distribution [28]. Other factors analyzed included seasonal incidence in Korea, egg discharging pattern in low worm burden cases, familial aggregation pattern of the infection. This study of population dynamics of A. lumbricoides seemed to impress the WHO staffs of tropical medicine. A research team of Epidemiology of Infectious Diseases, Imperial College, London, undertook a similar study in the fishing villages of southern India.

Control of familial enterobiasis had been difficult even though effective chemotherapeutics were available. In a series of experiments and observations, it was concluded that, in chemotherapeutic control of familial enterobiasis, all members should be treated with mebendazole or other anthelmintics simultaneously for 4 times each in 20-day interval. This conclusion was based on new findings of research on the life span of longer than 40 days in female E. vermicularis [29], and the limitation of efficacy of anthelmintics on early developmental stages as obtained in randomized, double-blind study [30].

Experimental studies

In the early 1970s, hookworm infection rates were found to have lowered very quickly in Korea. In order to find factors involved, pesticides and insecticides were examined for their effects on the third stage larvae of hookworm [31]. These chemicals were used extensively when the green revolution began in the early 1970s. Their killing effects on the larvae were proved. It seemed that these chemicals were one of active players in lowering hookworm infection in Korea, together with improved defecation habits, wide use of chemical fertilizer instead of human manure, clothing and shoes worn by most people etc. In short, reinfection of hookworms was quickly reduced during the time when society changed.

Toxocariasis studies were focused on the mode of transmission. Transplacental transmission was reported in experimental animals [32]. Eating raw cattle liver was studied as a human infection source [33], which belatedly attracted attention in the late 2000s.

Over 90% of Entamoeba histolytica infected cases are asymptomatic. To explain the enigmatic low incidence of clinical amebiasis among the infected, host factors such as host immunity, stress, nutrition etc. were studied extensively in the 1970s [34].

Researches on antibody tests for paragonimiasis and clonorchiasis were also undertaken applying succesively immunodiffusion, immunoelectrophoresis [35], counterimmunoelectrophoresis and indirect fluorescent antibody test [36]. As in the complement fixation test, these antibody tests were difficult to undertake. Antibody tests for paragonimiasis, however, were found always diagnostic anyway.

Researches on intestinal trematodes

One line of research was classical one on intestinal trematodes. In addition to pathological studies on experimental Metagonimus yokogawai infection, studies began on fauna of intestinal trematodes in Korea. Starting with new locality descriptions of Echinostoma cinetorchis and Heterophyes nocens, surveys on rat and dog intestinal trematodes were undertaken. During 2 decades from 1980 to the end of 1990s [38], human intestinal infections of Echinostoma hortense, Echinochasmus japonicus, Acanthoparyphium tyosenense, Pygidiopsis summa, Stellantchasmus falcatus, Stictodora fuscata, Stictodora lari, Metagonimus takahashii, Metagonimus miyairi, Plagiorchis muris, Centrocestus armatus, Neodiplostomum seoulense, Gymnophalloides seoi etc. were described. Korea was a new locality to most of them. Life cycle, modes of human infection and fine tegumental structure of each trematode were described.

Of them, 2 trematodes were of particular interest. One was Neodiplostomum seoulense, a diplostomatid trematode of rodent intestine, for which human was a new host; the index human infection case was a snake eater. The trematode's life cycle was elucidated [39]. Another trematode was Gymnophalloides seoi, which was intestinal trematode of a migratory bird, Paleartic oystercatcher [40]. Its metacercarial stage was found in oysters. The intestinal infections with this trematode were found to be limited in seaside villages of southwestern Korea. This series of intestinal trematode research made both Korean and food hygiene specialists worldwide understand how many different parasitic infections could be contracted by eating raw freshwater, brackish water zone fishes and mollusks.

Progress in praziquantel application

After applying praziquantel in treatment of clonorchiasis and other parasitic diseases, 2 researches and a project were done in the 1980s. One was developing a new manufacturing process of praziquantel which was undertaken by a Korean pharmacist. The new process produced the medicine with higher purity and with low incidence of side effects. And it made the drug affordable.

Another research was a study on action mechanism of praziquantel against trematodes. By transmission and scanning electron microscopy, the process of tegumental vacuolizations and damages was observed in C. sinensis, M. yokogawai, and P. westermani after exposure to praziquantel [41].

Clonorchis infected Korean patients purchased and administered praziquantel voluntarily nationwide. Until the 1970s, clonorchiasis was known as a fatal disease. Before praziquantel, treatment of choice was surgical liver massage and draining bile through a tube in order to let liver flukes crawl outside. After marketing, demands for praziquantel were immediate and enormous. From 1983, the ROK Government purchased praziquantel and distributed it to local health centers to treat infected cases in rural villages. The egg positive rate in Korean people, however, remained unchanged even after the use of praziquantel. In the successive national surveys undertaken in 1986, 1992, 1997 [42] and 2004, the estimated numbers of C. sinensis infection were between 5 hundred thousand and one million. In contrast, the data of worm burden estimation by Stoll's egg count showed remarkable reduction of the number of patients in the category of moderate and heavy infections. About 90% of the infected were in category of light infections (EPG below 1,000). The prevalence of clinical clonorchiasis with cholangitis was reduced while asymptomatic light infections persisted.

Clinical studies on tissue invading helminthiases

Enzyme-linked immunosorbent assay (ELISA) was originally developed as a method of protein measurement. This technique was modified to antibody tests for parasitic infections in 1974. Since then, it revolutionized antibody tests worldwide. ELISA was introduced in Korea in 1980 and was applied in antibody test for clonorchiasis [43]. Next, ELISA antibody test for paragonimiasis was developed [44]. By ELISA, pulmonary paragonimiasis could be screened out with ease among treatment-resistant tuberculosis patients. Paragonimiasis was once forgotten disease among specialists of chest medicine in Korea, mainly because of difficulty in diagnosis. After applying ELISA antibody test, 20-200 pulmonary paragonimiasis patients were diagnosed every year during past 2 decades. Antibody test for cerebral paragonimiasis using cerebrospinal fluid was requested by neurologists in Korea and was developed using cerebrospinal fluid of patients as a test sample.

Korean neurologists and neurosurgeons then requested antibody tests for neurocysticercosis because brain CT findings of the disease were highly variable. For example, there was a considerable number of neurocysticercosis patients manifesting only hydrocephalus without multiple low density lesions in brian CT. The antibody test using serum and cerebrospinal fluid were developed, and diagnostic sensitivity and specificity were evaluated [45]. Since 1986, brain imaging combined with antibody tests became routine procedures in diagnosing neurocysticercosis in Korea. Comparative evaluation of 2 diagnostic modalities was reported in 1988 [46]. Because each of positive antibody test and brain images are regarded as major findings in neurocysticercosis, patients with positive findings in the 2 diagnostic modalities could be diagnosed. In Korea, more than 3,000 neurocysticercosis patients were diagnosed by this method during past 2 decades.

Epidemiologic characteristics, and histopathologic findings of human sparganosis [47,48] had been studied in Korea. The disease has showed relatively high incidence in East Asian countries. Because cases of spinal sparganosis had been reported in Korea, and sporadic cases of brain sparganosis were known in the early 1980s, the antibody test by ELISA for sparganosis was developed and evaluated [49]. It was incorporated in multi-antigen screening system together with T. solium metacestode cyst fluid antigen and crude P. westermani antigen in patients with space occupying lesion. Though infrequent, serum and cerebrospinal fluid of unexpected number of patients reacted positively only to sparganum antigen in the multi-antigen screenings. By collaboration with neuroradiologists, the brain CT findings of surgery-confirmed, antibody positive patients were described [50]. As in neurocysticercosis, rarely occurring neurosparganosis could be diagnosed preoperatively by combination of neuroimaging and antibody test. Since the latter half of 1980s, the multi-antigen screening system, composed of 4 antigens including crude C. sinensis antigen with above-listed 3, replaced invasive intradermal tests in Korea.

Biochemical and immunological studies

After the development of antibody tests for tissue invading helminthiasis, nature of diagnostic proteins from the parasites began to be studied. Basic biochemical technologies such as hybridoma and monoclonal antibody, SDS-polyacryamide gel electrophoresis, immunoblotting, and protein separation techniques such as gel filtration, chromatography, affinity chromatography and isoelectric focusing, were introduced in parasite research. Since the latter half of 1980s, proteolytic enzymes of many helminth parasites, especially cysteine proteinase, began to be characterized in Korea [51]. One cyst fluid proteins of T. solium metacestodes was purified and partly characterized. Proteins in crude extracts of P. westermani, and Spirometra mansoni plerocercoids were also analyzed for their antigenic subunit bands.

Since the early 1980s, Korean strains of free living amoeba such as Naegleria species and Acanthamoeba species were isolated and maintained in laboratory animal models. Using the model, immunological studies of various kinds together with pathological studies were undertaken [52]. Not only antibody responses but also cell mediated immunity was observed in this meticulously built models [53].

International and domestic recognition

In the 1980s, international circles of parasitology and tropical medicine began to pay attention to the research products of Korean parasitology. Abstract journals, such as Tropical Diseases Bulletin and Helminthological Abstracts indexed a part of articles published in the Korean J Parasitology. The WHO library in Geneva, Switzerland requested compliment copies of the journal. The textbook Clinical Parasitology (9th edition, 1984) of Beaver PC et al. listed more than 20 Korean articles in its reference, and listed Korean J Parasitology as one of periodicals in the field of parasitology. Most importantly, the U.S. National Library of Medicine began to index contents of the journal in Medline database since 1989.

In 1986, KAPE changed its name to the Korea Association of Health (KAH. later changed again to the Korean Association of Health Promotion, KAHP). The change was decided in a milieu of congratulating a success in parasite control. National activity of parasite control was transferred from KAPE to KAH. Based on the data of the fourth national survey on prevalence of intestinal helminths in 1986, the Expert Committee for Parasite Control of KAH resolved a decision to reduce the size of mass stool examination gradually over 10 years, ending it in 1995, and the resolution was agreed by the Government.

Classical researches of parasitology

Classical studies of parasitology were continued in the 1990s in Korea. The enigma of Taenia saginata infections in pork eating population was elucidated in Taiwan by discovering its metacestodes in the liver of locally reared pigs. The habits of raw eating of pig liver were not limited to Taiwan but widely practiced in Asian population including Korea. At first the discoverer of the new mode of infection considered the tapeworm a strain and then changed to a subspecies name Taenia saginata taiwanensis and finally named it as T. saginata asiatica. In Korea, after a series of meticulous studies on life cycle and morphology, a species name of Taenia asiatica was proposed [54]. This proposal elicited debates worldwide. Molecular parasitologists preferred the subspecies name while classical parasitologists agreed that it should be a separate species. Studies on molecular evidences are ongoing as to the taxonomic position of the tapeworm.

Another classical research was done in the epidemic of reemerging vivax malaria. ROK was free from indigenous vivax malaria for 14 years from 1979 to 1993 when an index case was detected. Immediately, Korean parasitologists proposed a surveillance system. And they depicted the epidemic, and defined it as a border malaria in 1998 [55]. Studies on reemerging malaria were described in a separate article in this supplement.

An occurrence of human infections of trichinellosis was diagnosed in Korea at last [56]. Searches for this important zoonosis had failed to find any infection in Korea until 1997, either in domestic pigs or in human. Eating undercooked badger meat was found to be the infection source in the first human infection. First Korean infections of Capillaria philippinensis [57], C. hepatica [58], and Dirofilaria immitis [59] were reported in the 1990s.

Studies on Pneumocystis carinii were undertaken. Two rat strains of P. carinii were identified in Korea. Their molecular karyotypes were utilized in epidemiologic tracing of the strains. As a mode of transmission, air borne infection was proved to occur in an experimental setting. It was found that most Korean children acquired infections and naturally immunized before 2 years of age [60].

Antibody positive rates of Toxoplasma gondii were examined in different groups in Korea for more than 15 years. The average rate was 5%, which was much lower than those in west Europeans. Two incidents of human foodborne toxoplasmosis outbreaks were described in Korea [61].

Studies on the pathology on C. sinensis infections continued in the 1990s. Carcinogenic effects of the infection were observed in dimethylnitrosamine administered hamsters [62,63]. This study was important in a changed situation of C. sinensis infection. Due to lowered infection burdens, morbidity of cholangitis reduced. However, cases of cholangiocarcinoma continued to be detected and were found to be associated with infection of C. sinensis. High incidence of cholangiocarcinoma was observed in high endemic areas in southern Korea than in low endemic areas.

Pathological changes of biliary tract were studied after praziquantel treatment in C. sinensis infected experimental animals [64]. After parasitological cure, however, dilated intrahepatic biliary ducts did not shrink to normal and periductal fibrosis remained unchanged or minimally reduced. These findings were important clinically because pathologic imaging findings in ultrasound or CT in human patients may not represent the present infection.

Clinical and epidemiological studies on amebic keratitis have been done utilizing molecular markers of Acanthamoeba species [65]. Studies on medically important vectors have been undertaken since the 1990s. Two species of trombiculid mites, Leptotrombidium pallidum and L. scutellare were identified as main vectors of scrub typhus in Korea. And their ecology was described. In vitro culture system of Dermatophagoides farinae and D. pteronyssinus was set up and large amount of the mites are supplied to specialists of allergic diseases.

Cell biology, immunology, and biochemical studies

Availability of cells and protozoa from ATTC and laboratory maintained protozoan parasite such as RH strain Toxoplasma gondii, Trichomonas vaginalis, and free living amoebas stimulated cell biological, immunological and biochemical studies in Korea. Host cell penetration mechanism of T. gondii, energy metabolism, and physiology of T. vaginalis and host cell response, roles of cytokines and chemokines in trichomoniasis model have been studied [66]. Interleukin-8 gene expression was examined in human colon epithelial cell line which was exposed to Entamoeba histolytica [67].

Proteolytic and anti-oxidant enzymes in helminth parasites were also studied. At least 7 serine-, and a cysteine proteases of Spirometra mansoni plerocercoid (sparganum) were purified and partially characterized. Of them, a cysteine protease, characterized as secretory cathepsin S, was found to degrade human immunoglobulin G in a papain-like fashion [68]. Two different cysteine proteases of P. westermani metacercariae were involved in their excystment process [69]. The study result added a role of cysteine proteases in trematode life cycle. Many different trematodes metacercariae and protozoan cysts were found to utilize cysteine proteases in their excystment. The purified enzymes of P. westermani have been utilized in a series of works on their role in mobilizing host eosinophils. Anti-oxidant enzymes, such as glutathione S-transferase were also studied in helminth parasites.

International communications and cooperations

In relation to international academic activity, 2 big changes happened in the latter half of 1980s and early half of 1990s in Korea. In 1989, Koreans were allowed to travel abroad. Before that year, to save foreign exchange, the ROK Government allowed foreign travel after reviewing applications. A few elite Korean parasitologists, who were invited by congress secretariat, could attend international meetings. In 1992, for the first time in the Society history, more than 30 Korean parasitologists attended the XIIIth meeting of International Congress of Tropical Medicine and Malaria (ICTMM) held in Pattaya, Thailand. Thereafter, scores of Korean parasitologists attend ICOPA, ICTMM and other international meetings and communicated with specialists of foreign countries.

Another big change was the declaration of Globalization policy of the ROK Government in 1994. And ROK was accepted as a member country of OECD in 1996. Activity of the Korea International Cooperation Agency (KOICA) was expanded thereafter. As an NGO activity of KOICA programs, KAH and members of the Society participated in the cooperation project with Institute of Parasitic Diseases in Shanghai, Chinese Academy of Preventive Medicine for 5 years. In 1995, the Society members organized a voluntary meeting with Japanese parasitologists under the name of "Forum Cheju" and have had annual meetings.

Since 1995, many Korean universities required their faculties a file of Science Citation Index (SCI) journal articles as a proof of achievements when applied a promotion or tenure. In the same year, grant giving organizations, such as the Korea Science and Engineering Foundation and the Korean Research Foundation, also asked a list SCI articles authored by applicant when an application was submitted. The changed policy stimulated international academic communications of Korean scientists including parasitologists.