Bull. Org. mond. Sante' 1959, 21, Bull. Wld Hlth Org. 721-726 Clonorchiasis and Paragonimiasis in the Republic of Korea Report on a Prevalence Survey using Intradermal Tests BRYCE C. WALTON 1 & IL CHYU 2 Until recently, information on the distribution of and prevalence of infection with the liver fluke, Clonorchis sinensis, and the lung fluke, Paragonimus westermani, was based almost entirely on surveys by stool or sputum examination, involving techniques insuf- ficiently sensitive and too costly and time-consuming to allow of really adequate coverage. However, a simple and reliable intradermal test for these infections has now been developed, based on the use ofpurified antigens, and this has been used in a survey of nearly 10 000 persons in the Republic of Korea. The results show that the spread of these infections is much wider than had previously been thought. It is estimated that in South Korea alone some 4.5 million people are infected with clonorchiasis and up to 1.5 million with para- gonimiasis-a public health problem of considerable magnitude. Clonorchis sinensis has long been recognized as in the US Army's 406th Medical General Laboratory being highly endemic in the Naktong, Kum, Nam, (Sadun, Walton et al., 1959; Sadun, Buck & Walton, Sumgin, and Han river valleys and has been con- 1959). This test has proved to be a reliable tool for sidered to be the principal cause of the many cases epidemiological investigations in a preliminary sur- of liver cirrhosis in Korea (Crane et al., 1955). vey in Korea (Sadun, Buck et al., 1959). Because of Paragonimus westermani has been reported to be its simplicity, ease of application, and low cost, this endemic in small scattered areas throughout the method was selected as the most practical means country, and although it is much less widely dis- of testing a large population sample, and was used tributed than the liver fluke, its prevalence and for this survey carried out under the joint auspices serious effects make it a public health problem of of the Ministry of Health and Social Affairs of the serious proportions. Republic of Korea and the WHO Regional Office Previous information on the distribution of pre- for the Western Pacific. valence of infection with these two parasites has been based on surveys by stool or sputum examination. DESCRIPTION OF LOCALITIES AND SELECTION With these techniques, the recovery of P. westermani OF SAMPLES eggs is difficult and often impossible. In addition, The Republic of Korea, with a population of the techniques are expensive and time-consuming. over 21 500 000, is divided into nine provinces. Therefore, such surveys have been too limited in With the exception of the island province of Cheju either geographical coverage or number of persons Do off the southern tip of the peninsula, all pro- examined to provide an adequate basis for evalua- vinces contain some elements of the six extensive tion of the situation in regard to these parasites. river systems which cover the major portion of the Recently, an intradermal test for these infections country. Except for the narrow strip of land to the by the use of purified antigens has been developed east of the high spine of the coastal range, which 1 Captain, Medical Service Corps, US Army; Chief, extends along the entire eastern coast, the country Parasitology Division, Third US Army Medical Laboratory, is characterized by wide, flat-bottomed valleys Fort McPherson, Ga., USA; Consultant, WHO Regional with meandering streams. Office for the Western Pacific. Localities for the skin testing were selected in 2 Chief, Department of Parasitology, National Institute of Health, Seoul, Republic of Korea eight of the nine provinces and included both areas 842 -721- 722 B. C. WALTON & I. CHYU FIG. I IL le 0 LO N rl O m 0 LOCALITIES IN REPUBLIC OF KOREA SURVEYED W UZ _- O CN _1 O CQw + n aa _- M _ r- O cm co FOR CLONORCHIASIS AND PARAGONIMIASIS v- _- _r _ _- _ - ll ls- - 000 0 0 _- f- 0 CD C lit 00 00 1 04 t r1- 0o 0 IL 04 04 t 04 v co q v 10 CD O '-'-( 04 lq (0o 0000co 0co CD (0(0(0(001O0O1O 01 z 0:0 + _ _0010 04 01 0 IL N'-_-_C0_0CV- + 04 z x LO Co (0 C - (0W CD 0 W(0D 4toLO co co4 L 04 co X 00 1004U qt C 00 001 ?) OIL 01 _ - 10 - W 01 01° 0 -0c 4(010 40 cm (01004 c - X CO WM - UM t Ct0eQo 0) to ( 0 z C known to be endemic and areas from which the rc 01 _ Mt- 01- 0 0 ( 1 0 Ministry of Health had no information regarding 0 010 the prevalence of these diseases. The areas chosen U C) L0) 004 00 co010 C ( O L _0 C> W W ( D f010_C 04 (Fig. 1) included localities on small tributaries or 0 01 away from streams, as well as some in major river uJ basins. A total of 7085 persons were tested in this 0. series. In addition, 2686 persons tested in two 04 10)0000- r~- 010C U) provinces during a prior co-operative study by the z ILu o LO_ - (0- O c e 406th Medical General Laboratory and the German 0 Red Cross Hospital are included. These data are 040 co 01041010rOle - were _1 v01(004(0000(00101(D OD 01 t 0o(0 0 completely comparable, since they obtained _CY 0C4Wc 4 c a- o le C4 co C~~~~~~~~~~4co with the same antigens and methods. However, it 0 IL should be pointed out that the earlier study was designed to evaluate the and no attempt 0 IL '- ' co ' 04 CD antigens, z was made to select a representative sample of the 0 10~ ~ ~ ~ ~ 4 population as to sex and age-group. The distribu- 004000Z 1°0000 W 04 L B s t048 CD.WOWF tion by province, sex, and age-group of the total co 10 01 _00 CD t 100 00 Co population tested is presented in Table 1. Although I- t 0 00 IL (0 CD (0011010 an adequate sampling was obtained for both sexes, the number of males tested was consistently greater. ~ 0~ 0- (00 0 Comparable samples were obtained in all provinces, -J |~~~~~~~~~~~~~1 to with the exceptions of Kyonggi Do, where fewer UL O 0 0 0 0 0 0 0 0 I- persons were reached because of transport difficul- 0 0 0 0 0 0 0 0 0 ties, and Kyong Sang Nam Do, where a larger _- population group was tested in the prior antigen O O 0 0 evaluation study. The age distribution was essen- 00 0 tially uniform with the exception of the 0-5-year 0 U group. This group cannot be considered typical, C 01 CM Z since it a small of o C 0 0 C E -a represents very number children E0 =C .C0 0 .~ (L 0 selected from an area highly endemic for clonor- C 0 C C c c _ chiasis in an effort to determine 0 cC U 0 0 0 z possible familial >. 0 .C sC >. >. sC YYUUYYUUUs7 sC relationships of the infection. CLONORCHIASIS AND PARAGONIMIASIS IN KOREA 723 MATERIAL AND METHODS tions with C. sinensis and some double infections might be missed. A few individuals (63) showed The antigens for the intradermal tests were acid- identical-sized wheals from the two antigens. These soluble protein fractions of whole worm prepara- were interpreted as double infections. tions obtained by Melcher fractionation, and the methods were those reported by Sadun, Buck & Clonorchiasis Walton (1959) and Sadun, Walton et al. (1959). As indicated in Table 2 and Fig. 2, positive The antigens were standardized to contain approxi- reactions to C. sinensis antigen were obtained in all mately 10 mg of protein per 100 ml. All individuals provinces, with the highest percentages occurring were given intradermally, on the volar surface of the in Kyong Sang Puk To, where 53% of all males same arm, P. westermani antigen, C. sinensis antigen, and 14 % of all females tested gave positive reactions. and a buffered saline Merthiolate (thiomersal) con- The lowest percentages was found in Cheju Do, trol, sufficient to produce a bleb with an area of where 3 % of males and 1 % of females were positive approximately 20 mm2. The area of the ensuing reactors. Positive reactions were found in children wheals was estimated after 15 minutes by means of a in a highly endemic area as early as two years of transparent sheet on which calibrated rings out- age. Prior stool examinations in the same locality lining areas between 20 mm2 to 700 mm2 had been confirm this, with C. sinensis infections found in traced. In cases where the edges of the wheal were children as young as 18 months.1 With the exception somewhat indistinct, they were carefully outlined of the atypical 0-5-year age-group, males had a by drawing on the skin with a ballpoint pen to consistently higher rate than females (Table 3). In ensure greater ease and accuracy in estimating the general, an increase in the percentages positive size when viewing through the transparent film. occurred vith age up to 41-50 years. Under the testing procedure, three stations were set up for all persons being processed. At the first station essential information-i.e., name, age, sex, TABLE 2 and pertinent history-was entered on a serially PERCENTAGE OF POSITIVE REACTIONS numbered register. At this time, the corresponding TO SKIN TEST ANTIGENS BY PROVINCE register number was written with a ballpoint pen Clonorchis Paragonimus on the wrist of the person to be tested and the Province forearm swabbed with an alcohol sponge.