Brugian filariasis: 10-year follow-up study on the effectiveness of selective chemotherapy with diethylcarbamazine on Che Ju island, Republic of Korea

Bulletin of the World Health Organization, 65 (1): 67-75 (1987) c) World Health Organization 1987 Brugian filariasis: 10-year follow-up study on the effectiveness of selective chemotherapy with diethyl- carbamazine on Che Ju island, Republic of Korea J. S. KIM,' B. U. No,2 & W. Y. LEE 3 The results of a 10-yearfollow-up of Brugia malayi microfilarial (mf) carrier rates in seven villages on Che Ju island and adjacent islets are reported; four villages initially received large-scale selective treatment with diethylcarbamazine (DEC) and three served as untreated controls. Some 90% of the totalpopulation took part in the pre-treatment blood survey and 82% of the detected mf carriers completed a course of treatment with 72 mg DEC per kg body weight over a period of 24 days. In the DEC-treated villages 92,% of the mf carriers were negative one year after the treatment: the mfratefellfrom 18.2% to 3.3%, the median mfdensity (MfD-50) changed from 28.4 to 5.2 mf/20 mm3 blood, and the infectivity rate in Aedes togoi fellfrom 5.5% to nil. Ten years later these parameters had risen only slightly to 4.1%, 5. 7 mf/20 mm3 blood, and 0.3%, respectively. By contrast, in the untreated control villages none of these parameters changed significantly during the same period. Thus, selective DEC treatment of detected mf carriers is an excellent control measure for human filariasis as it is readily acceptable by the inhabitants and is cost-effective. Suit- able intervals between treatments would be 8-10 years in areas where the mf prevalence rate is 10% or over, and 12-15 years where the prevalence is less than 10%. Che Ju, a large dormant volcanic island off the south-west coast of the Korean peninsula, is a well- known endemic area for filariasis due to Brugia malayi and transmitted by Aedes togoi. In this part of the country the transmission season for B. malayi by A. togoi lasts 4-5 months and there is no animal reservoir. The total population of the island was re- ported to be about 365 000 in 1970 and 462 000 in 1980. An extensive study of filariasis in seven villages on Che Ju was made between 1968 and 1970 by Kim et al. (1, 2). It indicated that a large-scale selective chemotherapeutic campaign using diethylcarbama- zine (DEC) to treat all human microfilarial (mf) carriers would be the control measure of choice in the area, since no animal reservoir was found. In this trial the seven villages were divided into four groups and treated as follows: (1) three villages (Taehung, Tosan and Kapa) received selective DEC ' Professor of Epidemiology, School of Public Health, Seoul National University, 28, Yunkeun-Dong, Chongro-Ku, Seoul 110, Republic of Korea. Requests for reprints should be sent to this author. 2 Graduate student of Epidemiology, School of Public Health, Seoul National University, Seoul. 3Associate Professor of Microbiology, School of Medicine, Yonsei University, Seoul. treatment only; (2) one village (Biyang) received selective DEC treatment combined with DDT resid- ual spray; (3) in one village (Hoengan) DDT residual spray was used alone; and (4) two villages (Hayae and Mara) received no intervention and served as con- trols. The location of each village and their pretreat- ment mf rates and densities are shown in Fig. 1. In order to be sure that any effect on the mf rates was really due to the DEC and not to the placebo effect of selective treatment, the mf-positive individ- uals from all seven villages were first treated with placebo tablets' following the primary survey in 1968. They were then examined again one year later, in 1969; the results revealed no changes in either the mf rate or mf density. Selective DEC treatment was then carried out using 12 doses of 6 mg/kg body weight, on alternate days. About 82% of the mf carriers detected in the four treated villages followed the full course of treatment; the remaining mf-posi- tive persons either refused treatment or were absent during the treatment period. " Placebo tablets, with exactly the same appearance as the diethylcarbamazine tablets, were made of dummy materials by a local drug company. 4752 -67- J. S. KIM ET AL. Q Houqm h DECIUN ylil *) tJ|||_d 0g1rol nilf Bivlig mist (31.0%) a60 Hft(13AW * 12 (i) M_. (2.6) * S I Fig. 1. Location of villages on Che Ju island and nearby islets; figures in parentheses indicate the mf rate and those marked with an asterisk are the median micro- filarial densities (mfD-50 per 20 mm3 blood). Follow-up evaluation after one year showed that 92%o of the mf carriers treated with DEC had become mf negative, and there was a striking decrease in mf density among those treated who remained mf posi- tive. The overall reduction in mf rate for the whole population in the four DEC-treated villages ranged from 760o to 91 o; in addition, no infective mos- quitos were found in these villages. In the untreated control villages, on the other hand, the infection rates in the human and mosquito populations showed no change. The effect of DDT residual spray alone eval- uated in 1970 was not significant when compared with the untreated control villages, although there was a suggestion of some supplernientary effect in the village where the DDT spray was combined with the DEC treatment (2). The present paper presents our findings in the same villages on the long-term effect of selective DEC treatment in the control of Brugian filariasis, and our estimate of the length of time needed between treat- ments in order to keep transmission under control. MATERIALS AND METHODS The 10-year follow-up was carried out in 1979 in the same villages where the short-term effectiveness of selective DEC treatment had been assessed be- tween 1968 and 1970; the same methods were used as before (1, 2). Human survey To determine the current population in the study villages family charts were made with the assistance of the village administration office and this served to identify all persons who had been absent from the village for longer than one month. From those who consented a 20 mm3 blood film was taken from the earlobe at night between 22hOO and 3hOO. The slides were stained with Giemsa following the same methods used in the previous surveys and were exam- ined under the microscope to determine the presence and number of microfilariae. Each slide was exam- ined "blind" by two persons separately to increase the sensitivity and specificity of the examination. Mosquito survey Resting Aedes togoi mosquitos were collected at dawn, as soon as the people got out of their beds, from the inside of mosquito nets under which people had slept, and from the walls and ceilings of rooms of houses that had been chosen at random. The mos- quitos were killed with chloroform, then dissected and examined under a dissecting microscope in a drop of saline for the presence of infective larvae. This was the same method as had been used in 1969. All mos- quitos dissected had had a blood-meal. RESULTS Human survey Populations surveyed. Distribution of the popu- lation of the seven villages in 1968 and 1979 and the proportions whose blood was examined on each occasion are shown in Table 1. The population had decreased slightly in most villages over the 10-year period, although the total population of Che Ju island had increased by about 30% during the same period. This was probably because of migration by many of the younger people from the smaller islets and rural villages to the larger towns in search of work. The coverage rate of the survey was much lower (67.2%70) in 1979 than in 1969 (90.1 %). The response to the survey was poorer in females than males, and young adults and old people were the least respons- ive. Among the 1979 population above 10 years of age, 52% of the cohorts examined 10 years previously were successfully followed up (54% for the DEC- treated villages and 44%o for the control villages). 68 SELECTIVE CHEMOTHERAPY FOR BRUGIAN FILARIASIS Table 1. Distribution of the total population in the seven villages and the numbers surveyed in 1968/69 and 1979/ 80, according to the control measures adopted 1968/1969 1979/1980 No. of Total No. Total No. Control measures in 1969 villages population surveyed population surveyed DEC, selective treatment only 3 2219 2062 (92.9)" 1807 1260 (69.7)" DEC treatment and DDT spray 1 263 242 (92.0) 300 180 (60.0) DDT spray only 1 174 155 (89.1) 127 73 (57.5) No DEC treatment or DDT spray 2 640 511 (79.8) 539 350 (64.9) Total 7 3296 2970 (90.1) 2773 1863 (67.2) ' Figures in parentheses are percentages. Table 2. The number of persons treated with DEC in four villages in 1968/69 as a proportion of the number of mf carriers detected and of the total estimated number of mf carriers in the population 1968/1969 Criteria' Total No. Village population examined (1) (2) (3) (4) (5) Taehung 490 460 136 145 119 87.5 82.1 Tosan 621 568 150 164 114 76.0 69.5 Biyang 263 242 75 81 65 86.7 80.2 Kapa 1108 1034 58 62 46 79.3 74.2 Total 2482 2304 419 452 344 82.1 76.2 e The five criteria are: (1): No. of mf positives actually found. (2): No. of mf positives extrapolated to the total population. (3): No. of mf positives, DEC treated. (4): Percentage treated among mf positives detected. (5): Percentage treated among mf positives extrapolated to the total population. Effects of the selective DEC treatment. Table 2 shows, for each of the four villages treated with DEC in 1969, the total population, the number of persons whose blood was examined, the number of mf carriers actually found, the total estimated number of mf carriers in the population, the number of mf carriers treated with DEC, and the number treated expressed as a proportion both of the number of mf carriers detected and of the total estimated number of carriers in the population. It can be seen that 82% of the mf positives were treated, which amounted to 76/o of the total estimated mf carriers in the villages. Table 3 shows the efficacy of DEC in those mf carriers who were treated, by comparing the mf rates and mf densities recorded in 1968/1969, in 1970 and 1979/1980 in (i) mf carriers who were treated, (ii) mf carriers from the same villages who were not treated, and (iii) mf carriers from untreated control villages. The mf density is derived from the regression formula, Table 3. One-year and 10-year follow-up of mf rates and median densities (mfD-50) in mf-positive individuals detected in 1968/69; DEC-treated and untreated groups are shown separately Untreated group DEC-treated group" DEC-treated villages Untreated villages No. No. No. Year re-examined No. mf(+) MfD-50 re-examined No. mf(+) MfD-50 re-examined No. mf(+) MfD-50 1968/69 - 344 (100)b 25.3 - 75 (100) 21.6 - 98 (100) 15.4 1970 239 19 (7.9) 4.2 12 10 (83.3) 23.2 35 31 (88.6) 16.2 1979/80 103 18 (17.5) 4.5 10 7 (70.0) 20.4 25 20 (80.0) 13.7 DEC was given to the treated group in the winter of 1969 (Nov. 1969 to Jan. 1970) and the mf surveys were done in the summer (July and August) of the years concerned. h Figures in parentheses are percentages. 69 J. S. KIM ET AL. Y= a + b logX where Y is the cumulative percentage of mf positives classified by mf count per unit volume (20 mm3) of blood on a probit scale, and X is the mf count per unit volume of blood; it is expressed as the mfD-50 or the median mf count (4). One year after treatment only 8%7e of those treated remained mf positive, and the mfD-50 had dropped from 25 to 4. More strikingly, 10 years after treat- ment the mf-positive rate among those treated had only risen to 17.5% while the mfD-50 still remained as low as 5. On the other hand the untreated groups within the DEC-treated villages and control villages showed 70-80% positive rates after 10 years without any distinct changes in mf density. The effect of the selective DEC treatment on the whole population of the treated villages is analysed in Tables 4 and 5. Table 4 shows the mf rate and mfD-50 in different 10-year age-group cohorts both before and 10 years after treatment in the DEC-treated villages and untreated control villages. In the treated villages the mf rate of 17.5% and the mfD-50 of 24.4 in 1969, before the DEC treatment, dropped to 5.3% and 5.3 respectively in 1979. In the untreated control villages the much less marked decrease in mf rate (19.2% to 16.1%) and in the mfD-50 (15.4 to 11.2) was not statistically significant. In these cohorts at the 10-year follow-up 78% of the mf positives found in the treated villages and 830o of the mf positives in the control villages had been detected as mf positive in the 1968/1969 pre-treatment surveys. Table 4. Number of mf positives and median density (mfD-50) in 1 0-year,age-group cohorts studied before and 10 years after treatment in DEC-treated villages and untreated control villages 1968/69 1979/80 Cohort and age group No. MfD-50 No. MfD-50 (years) examined No. mf(+) (20 mm3) examined No. mf(+) (20 mm3) DEC-treated cohorts: 0-9 197 31(15.7) 10-19 76 12(15.8) 197 9(4.6) 20-29 86 24(27.9) 76 5 (6.6) 30-39 109 17(15.6) 86 3(3.5) 40-49 61 14(23.0) 109 6 (5.5) 50-59 48 5(10.4) 61 6(9.8) 60-69 26 3(11.5) 48 3(6.3) > 70 3 0(0) 26 0 (0) Total 606 106(17.5) 24.4 603 32(5.3) 5.3 P= 0.000" Untreated control cohorts: 0-9 40 3(7.5) 10-19 1 7 5 (29.4) 40 3 (7.5) 20-29 1 1 4(36.4) 1 7 4(23.5) 30-39 40 8 (20.0) 1 1 3 (27.3) 40-49 1 9 7 (36.8) 40 6 (15.0) 50-59 13 0(0) 19 4(21.1) 60-69 9 2 (22.2) 1 3 2 (15.4) > 70 2 0 (0) 9 2 (22.2) Total 151 29(19.2) 15.4 149 24(16.1) 11.2 P=0.48' Figures in parentheses are percentages, i.e., the mf rate. "Difference of mf rates between 1968/69 and 1979/80 in DEC-treated cohorts. Difference of mf rates between 1968/69 and 1979/80 in untreated control cohorts. 70 SELECTIVE CHEMOTHERAPY FOR BRUGIAN FILARIASIS Table 5 gives the total number of persons examined in each village in 1968/ 1969, 1970 and 1979/ 1980, to- gether with the number and percentage prevalence of mf carriers found on each occasion, and the mfD-50. The most striking feature in the DEC-treated villages is the small change in mf rate and density between the one-year and 10-year follow-up results, i.e., the mf rate of 3.3%o in 1970 rose only to 4.1%o in 1979 and the mf density of 5.2 in 1970 rose only to 5.7 in 1979. The mf rate and density in the control villages showed a slight decrease in 1979 but the differences between the three examinations were not statistically signifi- cant. However, we cannot altogether exclude the possibility that a few persons in the treated villages had shared their DEC with relatives living in the control villages, or that some people in the control villages had purchased DEC under a brand name from a local drugstore and taken it themselves, even though they were unaware that the tablets given to them by the investigators were a placebo. Table 6 shows the total populations in the DEC- treated villages and in the control villages in 1979. Using the mf-positive rates recorded in 1968/1969 as a basis, estimates have been made of the numbers of mf positives that would have been present in 1968/ 1969 in populations of the size recorded in 1979. These figures are then compared with the estimated total numbers of mf positives in the population in 1979. The percentage decrease in the number of mf-positive cases between 1968/1969 and 1979 was 81.5% for the DEC-treated villages and 10.2% for the control villages. Table 7 compares the incidence of new infections between 1969 and 1979 in the DEC-treated and con- trol villages with regard to (i) those born after 1970 and (ii) the known mf negatives in 1969. The inci- dence among the newborns in the control villages was 11.7% compared with 2.9% in the DEC-treated villages, while among the known mf negatives the corresponding rates were 4.1% and 1.4%. Mosquito survey Mosquito surveys of Aedes togoi were carried out in 1968/1969, 1970 and 1979, always in the month of August, when the mosquito population reaches its Table 5. Number of mf positives and median densities (mfD-50) recorded in 1968/69 (before treatment), 1970, and 1979/1980 in each of the DEC-treated and untreated villages 1968/69 1970 1979/80 No. No. No. examined No. mf( +) MfD-50 examined No. mf( +) MfD-50 examined No. mf( +) MfD-50 DEC-treated villages: Taehung 460 1 36 (29.6) a 325 14(4.3) 369 26 (7.0) Tosan 568 150 (26.4) 281 18 (6.4) 429 24 (5.6) Kapa 1034 58(5.6) 511 5(1.0) 462 0(0) Biyangb 242 75(31.0) 113 3(2.7) 180 9(5.0) Total 2304 419 (18.2) 28.4 1230 40(3.3) 5.2 1440 59 (4.1) 5.7 P=0.000' P=0.26"d Untreated control villages: Hayae 396 53(13.4) 33 5(15.2) 288 32(11.1) Mara 115 3 (2.6) 74 3 (4.1) 62 1 (1.6) Hoengan b 155 42 (27.1) 88 23 (26.1) 73 20 (27.4) Total 666 98 (14.7) 16.9 195 31(15.9) 16.2 423 53 (12.5) 11.4 P= 0.30' 'Figures in parentheses are percentages, i.e., the mf rate. Villages where DDT spraying was done in 1969, only once. Difference of mf rates between 1968/69 and 1970, 1979/80 in DEC-treated cohorts. Difference of mf rates between 1970 and 1979/80 in DEC-treated cohorts. Difference of mf rates between 1968/69 and 1979/80 in untreated cohorts. J. S. KIM ET AL. Table 6. Comparison of the estimated numbers of mf positives in seven treated and untreated populations in 1968/69 and in 1979 Estimated Estimated number of mf( +) number of mf( +) (applying the (applying the 1979 Population 1969 rate to rate to 1979 Percentage in 1979 1979 population) whole population) reduction DEC-treated villages: Taehung 400 118 28 76.3 Tosan 628 166 35 78.9 Biyang 300 93 15 83.9 Kapa 779 44 0 100.0 Total 2107 421 78 81.5 Untreated control villages: Hayae 464 62 52 16.1 Hoengan 127 34 35 -+ 3.0 Mara 75 2 1 50.0 Total 666 98 88 10.2 peak. The mosquitos were dissected and examined for infective filarial larvae. Only those that had one or more typical infective larvae indistinguishable from those of Brugia were counted as infective. Table 8 shows the numbers of mosquitos examined, and the numbers infective in each year of the study. In the DEC-treated villages the infectivity rate dropped from 5.5% to nil after one year but increased to 0.3% at the 10-year follow-up. In the untreated con- trol villages the infectivity rate at the 10-year follow- up showed little change compared previously. with 10 years Effect ofDDT residual spray Since the vector mosquito, Aedes togoi, was found to be susceptible to DDT (3), DDT was sprayed in all houses on the Hoengan and Biyang islet villages on a single occasion in the summer of 1969. In Hoengan, where DDT spraying was used alone, there was no Table 7. The incidence of new infections between 1969 and 1979 among newborn children (aged 1-9 years in 1979) and among those who were mf negative in 1968/69 (aged over 10 years in 1979) DEC-treated villages Untreated control villages No. No. mf(+) No. No. mf(+) Age group examined in 1979 MfD-50 examined in 1979 MfD-50 1-9 years 313 9(2.9)0 4.4 77 9(11.7) 7.7 >10 years 500 7(1.4) 3.8 122 5(4.1) 8.3 Total 813 16(2.0) 4.3 199 14(7.0) 7.9 P=O,.001 P= 0.05' Figures in parentheses are percentages, i.e., the mf rate. Difference of incidence rates for 1-9-year age group between DEC-treated and untreated villagers. Difference of incidence rates for > 1 0-year age group between DEC-treated and untreated villagers. 72 SELECTIVE CHEMOTHERAPY FOR BRUGIAN FILARIASIS Table 8. Changes in the Aedes togoi infectivity rate in DEC-treated and untreated control villages between 1968 and 1979 1968/1969 1970 1979 No. No. No. No. No. No. examined infective examined infective examined infective DEC-treated villages: Taehung 284 19(6.7)a 96 0(0) 269 1 (0.4) Tosan 126 4(3.2) 64 0 (0) 134 0 (0) Kapa 67 1 (1.5) 64 0)0) 58 0(0) Biyang 228 15(6.6) 30 0(0) 131 1 (0.8) Total 705 39 (5.5) 254 0 (0) 592 2 (0.3) P= 0.000'' Untreated control villages: Hayae 139 5 (3.6) - - 145 3 (2.1) Hoengan b 106 9 (8.5) - - 36 3 (8.3) Total 245 14(5.7) - - 181 6(3.3) P= 0.25" "Figures in parentheses are percentages, i.e., the infectivity rate. h DDT residual spraying was done in 1969 summer, only once. Difference of mosquito infectivity rates between 1968/69 and 1979 in DEC-treated villages. Difference of mosquito infectivity rates between 1968/69 and 1979 in untreated control villages. evidence of any effect on the mf rate or density. However, in Biyang, where the DDT was combined with selective DEC treatment, the insecticide treat- ment may have had some effect because this islet, which had the highest mf rate and density before the intervention, showed the biggest reduction in mf rate of all the DEC-treated villages at the one-year follow- up (Table 5). DISCUSSION Blood surveys of the total population to identify filarial infection, particularly those done at night, are laborious, expensive, and demanding in man- power. Repeated surveys usually increase the refusal rate which, in turn, makes the control programme extremely difficult. DEC is still the drug of choice for the large-scale treatment of lymphatic filariasis despite troublesome side-reactions associated with the death of parasites, and the inconvenience of giving multiple doses; how- ever, it has proved sufficiently effective to eradicate human lymphatic filariasis in some environments, as on Kapa islet. The problem posed by large-scale chemotherapy for human filariasis is how to achieve the maximum control (or even eradication) with the minimum of expense and effort. In this context there has been dis- cussion on whether mass DEC treatment of the whole population without a previous blood-survey, or after only a small sample survey, is more acceptable and more effective than selective treatment of mf-positive individuals following a blood survey of the whole population. The effectiveness of large-scale DEC treatment in filariasis control depends on (a) ecological variables governing the dynamics of filarial transmission, which may vary greatly from one area to another, and (b) the thoroughness with which the chemotherapy campaign is executed. The major ecological variables include the mf rate and median density (mfD-50) in the human population, the presence or absence of animal reservoirs, human behavioural factors and the degree of man-vector contact, the density and be- haviour of the vector population, and the duration of the season of effective transmission. The thoroughness of mass chemotherapy depends on the degree of drug coverage obtained in the whole population. In selective chemotherapy the effect depends on the coverage obtained in the blood survey to detect mf carriers, on the proportion of mf carriers 73 J. S. KIM ET AL. who complete the full course of treatment and con- vert to the mf-negative state, and on timing the treat- ment so that it is completed within the period of one transmission cycle of the parasite. Large-scale selective DEC treatment of human mf carriers on Che Ju island in 1969 produced excellent short- and long-term effects in controlling filariasis. At the one-year follow-up the mf rate of the popu- lation dropped from 18.2% to 3.3% and the mfD-50 from 28.4 to 5.2; the infectivity rate in the vector mosquitos fell from 5.5% to zero. In the 10-year follow-up, only slight increases were observed in these parameters without any further treatment. Reduction in transmission of B. malayi following large-scale selective DEC treatment was evidenced by (a) the decreased mosquito infectivity rate; (b) in the treated villages, the much lower 10-year incidence rates among new susceptibles born after 1970 and among erstwhile mf-negative adults, compared with the control villages; (c) the very small increase in mf density in the treated group between the one-year and 10-year post-treatment follow-ups; (d) the higher conversion rate to the mf-negative state among untreated mf-positive individuals in DEC-treated villages; and (e) the major impact of selective DEC chemotherapy on the overall mf rate and density in the treated villages. The fact that, at the 10-year follow-up, the con- tinuing mf-positive rate among the erstwhile mf positives who had received treatment was higher (though with lower mf density) than among the newly infected mf positives suggests that most of the former group were relapses rather than reinfections. The fact that the 10-year incidence rates among susceptibles in the 1-9-year age group born after the DEC campaign was higher than among the originally negative adults in both the treated and control villages may indicate that some degree of immunity or resistance to filarial infection had developed in the originally negative adult group. The efficacy of DEC in the mf-positive individuals depends to some extent on the mf density. At the one- year follow-up, the persistent mf-positive rate after completion of treatment was 16.50/o for those with a pre-treatment density above 50 mf/20 mm3 blood, whereas it was only 2.1 07o for those with mf densities below this level. However, the addition of a further 30 mg/kg DEC to the standard treatment at 72 mg/ kg over 12 days often succeeded in eliminating all microfilariae, even from the most heavily infected persons. In a temperate area such as Che Ju island where transmission of B. malayi occurs for only 4-5 months each year, and where no animal reservoir exists, we consider that large-scale selective DEC treatment, provided it is carried out thoroughly, is more accept- able and effective, and less costly in terms of man- power utilization and drug consumption, than mass chemotherapy followed by regular population blood surveys with selective treatment every one or two years. The data obtained from the two follow-up studies after selective DEC treatment on Che Ju island pro- vide an estimate of the intervals needed between treat- ments for B. malayi filariasis. In a situation where the pre-treatment mf rate is around 300o and there is no animal reservoir,. 10 years would appear to be a suitable interval provided that the original blood sur- vey covers over 90070 of the population and at least 80%o of the mf-positive individuals are treated with DEC. On the other hand, if the original mf rate is less than 100/o, as on Kapa islet, and the selective treat- ment has been done thoroughly, the time interval required before the next survey and treatment could be longer, perhaps 15 years. Furthermore, these re- peated treatments, if carried out thoroughly, may finally succeed in eradicating human filariasis after two or three repetitions. We consider that in the situation with B. malayi as described here, appropriate intervals for selective chemotherapy may be 12-15 years for areas where the mf rate is lower than 107o and 8-10 years for areas where the mf rate is 1007o or above. These intervals would doubtless have to be reduced in tropical areas with longer seasons of transmission and, more especially, in areas where there is an animal reservoir. ACKNOWLEDGEMENTS The 1979/80 study was supported by a grant from the Director's Initiative Fund of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (ID 790414). We should like to express our sincere appreciation to all personnel of South Che Ju Health Centre whose devoted assistance made the study possible. We are also grateful to Dr B. 0. L. Duke of the WHO Parasitic Diseases Programme for valuable advice in the data analysis and revision of this paper. 74 SELECTIVE CHEMOTHERAPY FOR BRUGIAN FILARIASIS 75 RESUMt BRUGIOSE: ETUDE PROSPECTIVE DE 10 ANS SUR L'EFFICACITE DE LA CHIMIOTHERAPIE SELECTIVE PAR LA DIETHYLCARBAMAZINE DANS L'ILE DE CHE JU, REPUBLIQUE DE CORtE Cette 6tude a e effectu&e dans trois villages cotiers et quatre ilots de l'lle de Che Ju, en Republique de Coree, pendant la periode 1978-1980. Son objectif particulier etait d'evaluer l'efficacite a long terme du traitement selectif par la diethylcarbamazine (DEC) applique a grande echelle et de determiner les intervalles optimaux entre les traitements selectifs pour combattre la transmission filarienne. Ces villages avaient fait auparavant, en 1968-1970, l'objet d'une enquete approfondie. Apres une etude des aspects ecologiques de la filariose, portant notamment sur l'homme, les animaux et les moustiques vecteurs, on a divise les sept villages en quatre groupes en vue d'evaluer les effets de la chimiotherapie par la DEC et des pulverisations de DDT a effet remanent. A ce moment, on a soumis 91% de la population a des examens de sang et 82% des porteurs de microfilaires detectes dans les villages traites par la DEC ont requ le traitement complet, c'est-a-dire une serie de 12 doses de DEC, a raison de 6 mg/kg de poids corporel, un jour sur deux. La chimiotherapie selective par la DEC et les pulverisations de DDT ont eu lieu en 1969. Lors de l'examen effectue au bout d'un an, 92% des porteurs de microfilaires traites 6taient devenus negatifs et chez les sujets qui etaient restes positifs, on a note une reduction frappante de la densite moyenne de microfilaires, alors qu'il n'y avait pas de changement significatif dans le taux ou la densite de microfilaires chez les porteurs non traites dans les villages temoins. Le taux et la densite de microfilaires parmi les populations des villages traites s'etaient deja abaisses de 5,5-31% (moyenne 18,2%) a 0,9-6,4% (moyenne 3,3%) et de 28,4/20 mm3 de sang a 5,2/20 mm3; il n'a e decouvert aucun moustique vecteur (Aedes togoi) hebergeant des larves de filaires infestantes. Au cours de l'examen de suivi effectue au bout de 10 ans dans la meme region et par les memes methodes, on a pratique des examens de sang sur 67,2% de la population; parmi les sujets de plus de 10 ans, 52% des cohortes examinees 10 ans auparavant ont pu etre revues. Les parametres de la transmission des filaires dans les villages traites par la DEC n'ont presente qu'une faible aug- mentation par comparaison avec les resultats observes un an apres le traitement; ainsi, le taux de microfilaires est passe de 3,3% a 4,1%, la densite de microfilaires s'est elev6e de 5,2 a 5,7/20 mm3 et le taux d'infectiosite des moustiques est passe de 0 a 0,3%; dans les villages temoins non traites, aucun de ces parametres n'avait change de maniere significative par rapport aux donn6es obtenues initialement en 1968-1969. En outre, le taux d'incidence sur 10 ans de l'infection filarienne parmi les sujets sensibles nes apres 1970 et ceux qui etaient auparavant negatifs en ce qui concerne les microfilaires etait, dans les villages traites par la DEC, de 2,9% et de 1 ,47o respectivement, alors que pour la meme periode, dans les villages non traites, ils ont e de 10,4% et de 4,1% respectivement. Les resultats de cette etude montrent que la chimio- therapie selective par la DEC est un moyen efficace pour combattre et meme eradiquer la filariose lymphatique humaine a condition que le traitement selectif par la DEC soit repete rigoureusement deux ou trois fois a des inter- valles appropries. Dans des conditions semblables a celles qui sont decrites ici, c'est-a-dire en l'absence de reservoir animal et avec une periode de transmission des filaires de 4 a 5 mois par an, les intervalles appropries entre les traitements selectifs par la DEC devraient etre de 8 a 10 ans dans les zones oui le taux d'infestation est de 10% ou plus et de 12 a 15 ans dans celles oi le taux d'infestation est inferieur a 10%. Il est hors de doute que ces intervalles devront etre raccourcis dans les regions tropicales ou la saison de transmission des filaires est plus longue et surtout dans les regions ou il existe un reservoir animal. REFERENCES 1. KIM, J. S. ET AL. Ecology of filariasis on Che Ju island. Korean journal of parasitology, 11: 33-53 (1973). 2. KIM, J. S. ET AL. Efficacy of mass treatment for control of human filariasis. Koreanjournal ofparasitology, 11: 54-60 (1973). 3. LEE, W. Y. A study on Aedes togoi as vector of filar- iasis in Che Ju island. Korean journal ofparasitology, 7: 153-159 (1969). 4. SASA, M. Epidemiology of human filariasis in Japan. Progress of medical parasitology in Japan, Vol. 111. Tokyo, Meguro Parasitological Museum, 1966, pp. 388-436.