11
Bulletin ofthe World Health Organization, 62 (3): 451-461 (1984) © World Health Organization 1984 Relationship between prevalence and intensity of Opisthorchis viverrini infection, and clinical symptoms and signs in a rural community in north-east Thailand E. S. UPATHAM,1 V. VIYANANT,1 S. KURATHONG, J. ROJBORWONWITAYA, W. Y. BROCKELMAN,' S. ARDSUNGNOEN,l P. LEE,' & S. VAJRASTHIRA4 In a large village in north-east Thailand, the overall prevalence of Opisthorchis viver- rini infection (based on Stoll's quantitative egg count) was 89.5%o in a total population of 1651 individuals. The prevalence was 32% in children under 5 years, 90% in those aged 5-9 years, and averaged 95.6%o in age groups above 10years. The mean faecal egg output (indi- cative of intensity of infection) was highest in the 40-49-year age group and remained rela- tively constant through older ages. In all age groups the prevalence and intensity of infec- tion in both men and women were similar. A history of eating raw freshwater fish occurred more frequently in infected persons than in those uninfected. The following symptoms occurred significantly more frequently in groups with higher intensities of infection: weakness, flatulence or dyspepsia, and abdominalpain in the right upper quadrant. Nevertheless, infectedpersons did not report a reduced ability to work. Anorexia, nausea, vomiting, and diarrhoea were only weakly cor- related with the intensity of infection. A palpable liver occurred more frequently in the infected groups and was correlated with intensity of infection. Icteric conjunctivae were observed in 2.2% of infected persons but not in the uninfected. Some 5-10%o of the popu- lation had symptoms that were attributable to opisthorchiasis.. Although millions of people in north-east Thailand are infected with Opisthorchis viverrini (1-3), the frequency with which signs and symptoms of illness are found in relation to the prevalence and intensity of infection in this population remains unknown. This is because nearly all previous investigations have been epidemiological studies of selected groups of inhabi- tants in an endemic area (1, 4-6) or of hospitalized patients (7), or reviews of clinicopathological ma- terial (8, 9). In the present investigation, a cross-sectional method originally employed for studying schistoso- miasis (10, 11) was applied. With this method, the prevalence and intensity of 0. viverrini infections, as determined by quantitative egg counts, were cor- related with morbidity, as indicated by standard ' Center for Applied Malacology and Entomology, Department of Biology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 4, Thailand, Requests for reprints should be sent to Dr E. S. Upatham. 2 Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand. 3Department of Medicine, Rajvithi Hospital, Bangkok Thailand. 4Department of Helminthology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. medical examinations. Compared with our prelimi- nary study in Nong Ranya (12), the present investi- gation was carried out in a larger village where 1651 (91%) of the 1812 residents living in 337 households had their stools examined and 1176 (65%) had a clinical examination as well. MATERIALS AND METHODS Population studied The district of Chonnabot is situated in Khon Kaen Province in north-east Thailand (Fig. 1). Chonnabot village, located 5 km to the west of the village of Nong Ranya, is a designated municipal area with modern facilities which smaller villages do not have. Besides easy accessibility, the village is close to shallow reser- voirs and streams where the two intermediate hosts of 0. viverrini, Bithynia snails and cyprinoid fish, abound. Chonnabot was also selected because of its large heterogeneous population. At the initiation of the project, a meeting was held in the village to explain the purpose of the survey to the villagers and to enlist their cooperation. 4418 -451-

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Bulletin ofthe World Health Organization, 62 (3): 451-461 (1984) © World Health Organization 1984

Relationship between prevalence and intensity ofOpisthorchis viverrini infection, and clinical symptomsand signs in a rural community in north-east Thailand

E. S. UPATHAM,1 V. VIYANANT,1 S. KURATHONG, J. ROJBORWONWITAYA,W. Y. BROCKELMAN,' S. ARDSUNGNOEN,l P. LEE,' & S. VAJRASTHIRA4

In a large village in north-east Thailand, the overall prevalence of Opisthorchis viver-rini infection (based on Stoll's quantitative egg count) was 89.5%o in a total population of1651 individuals. The prevalence was 32% in children under 5 years, 90% in those aged 5-9years, and averaged 95.6%o in age groups above 10years. The meanfaecal egg output (indi-cative of intensity of infection) was highest in the 40-49-year age group and remained rela-tively constant through older ages. In all age groups the prevalence and intensity of infec-tion in both men and women were similar.

A history of eating raw freshwater fish occurred more frequently in infected personsthan in those uninfected. The following symptoms occurred significantly more frequentlyin groups with higher intensities of infection: weakness, flatulence or dyspepsia, andabdominalpain in the right upper quadrant. Nevertheless, infectedpersons did not report areduced ability to work. Anorexia, nausea, vomiting, and diarrhoea were only weakly cor-related with the intensity of infection. A palpable liver occurred more frequently in theinfected groups and was correlated with intensity of infection. Icteric conjunctivae wereobserved in 2.2% of infected persons but not in the uninfected. Some 5-10%o of the popu-lation had symptoms that were attributable to opisthorchiasis..

Although millions of people in north-east Thailandare infected with Opisthorchis viverrini (1-3), thefrequency with which signs and symptoms of illnessare found in relation to the prevalence and intensity ofinfection in this population remains unknown. This isbecause nearly all previous investigations have beenepidemiological studies of selected groups of inhabi-tants in an endemic area (1, 4-6) or of hospitalizedpatients (7), or reviews of clinicopathological ma-terial (8, 9).

In the present investigation, a cross-sectionalmethod originally employed for studying schistoso-miasis (10, 11) was applied. With this method, theprevalence and intensity of 0. viverrini infections, asdetermined by quantitative egg counts, were cor-related with morbidity, as indicated by standard

' Center for Applied Malacology and Entomology, Departmentof Biology, Faculty of Science, Mahidol University, Rama VI Road,Bangkok 4, Thailand, Requests for reprints should be sent to DrE. S. Upatham.

2 Department of Medicine, Faculty of Medicine, RamathibodiHospital, Bangkok, Thailand.

3Department of Medicine, Rajvithi Hospital, BangkokThailand.

4Department of Helminthology, Faculty of Tropical Medicine,Mahidol University, Bangkok, Thailand.

medical examinations. Compared with our prelimi-nary study in Nong Ranya (12), the present investi-gation was carried out in a larger village where 1651(91%) of the 1812 residents living in 337 householdshad their stools examined and 1176 (65%) had aclinical examination as well.

MATERIALS AND METHODS

Population studied

The district of Chonnabot is situated in Khon KaenProvince in north-east Thailand (Fig. 1). Chonnabotvillage, located 5 km to the west of the village of NongRanya, is a designated municipal area with modernfacilities which smaller villages do not have. Besideseasy accessibility, the village is close to shallow reser-voirs and streams where the two intermediate hosts of0. viverrini, Bithynia snails and cyprinoid fish,abound. Chonnabot was also selected because of itslarge heterogeneous population.At the initiation of the project, a meeting was held

in the village to explain the purpose of the survey tothe villagers and to enlist their cooperation.

4418 -451-

E. S. UPATHAM ET AL.

Stool examination

During the survey period (March-June 1980) fieldworkers collected one stool specimen from each of1651 villagers and took them to a field laboratorywhere they were examined. Stoll's egg counts (13)were performed on all specimens to detect 0. viverrinieggs. Approximately 1 g of each stool was preservedin a vial containing Merthiolate(thiomersal)-iodine-formaldehyde; all vials were then labelled and trans-ferred to the laboratory in Bangkok where they wereexamined for other parasitic ova (14, 15).

RESULTS

The age structure of the 1651 individuals who pro-vided faecal specimens is shown in Fig. 2. The pro-portion of the population less than 20 years old con-stituted about 50070 of the total. The male: femaleratio was 46:54.

AGE (YEARS)

FEMALES - B gL MALES

E~~~~~~~~~~~~~~~~~~~

Fig. 1. Map of the study area.

Medical history and physical examination

A questionnaire concerning a variety of major andminor symptoms possibly attributable to 0. viverriniinfection was prepared in Thai. Altogether 1176 indi-viduals who came to a local wat (monastery) wereinterviewed by one of two paramedical personnelusing this questionnaire.

After the interview, the villagers were examined byone of three physicians. Liver size was measured bothin the midclavicular and midsternal lines while theexaminee was recumbent. Extension of the organbelow the costal margin was determined, midwaybetween inspiration and expiration, with a tapemeasure. Similarly, spleen size was measured both inthe anterior axillary and midaxillary lines. Neither theresults of stool examination nor the findings in thequestionnaire were known to the examiner in ad-vance.

Data processing and analysis

The data were coded and punched on cards andmost of the analysis was carried out by computerusing chi-square tests.

Ii

30 25 20 15 10 5 0 5 10PERCENTAGE

Fig. 2. Age structure of the studyChonnabot village.

15 20 25 30

population of

Opisthorchis viverrini infection0. viverrini eggs were detected in the stools of 1478

individuals or 89.5%7o of those who provided faecalspecimens. The prevalence data, according to age andsex, are shown in Table 1 and in Fig. 3. The prevalencein children under 5 years, including 41 infants, was32%7o; it rose to 90%o in those aged 5-9 years andremained relatively constant through the older agegroups. Males and females showed similar per-centages of infection in all age groups, with a mean of89%o for males and 90'70 for females. Of the 41 infantsexamined, 3 (7%o) were stool-positive.The population was divided according to the

presence and intensity of infection as follows (Fig. 4):10%o were uninfected, 1 Io% had light infections (< 1egg per mg of faeces), 36%o had moderate infections(1-10 eggs per mg of faeces), 33% had heavy infec-tions (> 10-50 eggs per mg of faeces), and 9%7o hadvery heavy infections (> 50 eggs per mg of faeces).The mean egg counts (per mg of faeces) for theexamined population were 18.82 ± 1.17 for males,20.30± 1.16 for females, and 19.55±0.88 for bothcombined. The mean egg counts according to agegroup and sex are shown in Table 1 and Fig. 3. Theintensity of infection in both males and females rosesteadily in early life, peaked in the 40-49-year agegroup and remained relatively constant thereafter. Inmales, there was an unexplained surge in the 20-24-year age group. Overall, there was no consistent

452

OPISTHORCHIS VIVERRINI INFECTION IN THAILAND

Table 1. Distribution0. viverrini

of the population of Chonnabot village according to age group, sex and prevalence of

Egg counts/mg of faeces from infected individuals

Sex Age No. Prevalence Arithmetic mean Geometric mean(years) examined

Males 0-4 84 33.3 2.8±1.2 10.5±1.2

5-9 119 91.6 9.0± 1.4 2.9± 1.5

10-14 111 96.4 13.3±1.6 6.4±1.7

15-19 96 96.9 16.2± 1.7 8.5± 1.9

20-24 37 94.6 26.6±6.4 12.2±6.8

25-29 48 97.9 18.3 ± 3.7 8.3± 4.1

30-39 82 96.3 20.3± 2.8 10.2 ± 3.0

40-49 77 96.1 31.7 ± 6.1 12.8±6.5

50-59 55 98.2 30.0±6.1 11.9±6.7

> 60 56 98.2 27.9 ± 4.7 12.0 ± 5.2

Total 765 89.0 18.9 ±1.2 7.0 ±1.3

Females 0-4 72 30.6 2.9 ±1.7 0.6 ±1.8

5-9 106 87.7 9.6 ± 2.0 2.9 ± 2.1

10-14 114 94.7 8.4± 1.1 3.8± 1.2

15-19 108 96.3 18.7±3.0 8.0±3.1

20-24 78 94.9 21.2 ± 3.3 7.2 ± 3.7

25-29 63 98.4 21.2 ±4.2 9.1 ±4.6

30-39 113 97.3 24.5 ± 3.5 8.9 ± 3.8

40-49 85 97.7 31.6 ± 4.8 11.6 ± 5.3

50-59 75 96.0 28.5±4.8 14.3±5.1

) 60 72 95.9 26.0 ± 3.5 11.8 ± 3.9

Total 886 90.0 20.0 ± 1.2 6.9 ± 1.2

Both sexes 0-4 156 32.1 2.9 ± 1.0 0.5 ± 1.0

5-9 225 39.8 9.3 ±1.2 2.9 ±1.3

10-14 225 95.6 10.8±9.4 4.9 ± 1.1

15-19 204 96.6 17.6±1.8 8.2±1.9

20-24 115 94.8 22.9 ± 3.0 8.5 ± 3.3

25-29 111 98.2 20.5±2.9 8.7±3.1

30-39 195 96.9 22.7 ± 2.3 9.4± 2.5

40-49 162 96.9 31.7±3.8 12.2±4.1

50-59 130 96.9 29.1 ±3.8 13.2±4.0

60 128 96.9 26.9±2.8 11.9±3.1

Total 1651 89.5 19.5±0.7 6.9±0.9

453

454 E. S. UPATHAM ET AL.

.40

M"s

FIEMALES.30

M

IO

O 0-4 5 -9 42 09 9 604

AGE GROPhS YEARS)

Fig. 3. Intensity of Opisthorchis viverrini infection inrelation to age group and sex in the infected populationof Chonnabot village.

40

a- 30~2D 250.

*200 1515I-

INFECTION none liEGGS/MG 0 (I 1-10 )l0-50 )50

Fig. 4. Percentages of uninfected individuals and thosewith different intensities of Opisthorchis viverrini infec-tion in the study population of Chonnabot village.

difference in intensity of infection between males andfemales. However, in most age groups, the mean eggcount in females was slightly higher than that inmales.

Associated intestinal parasitic infectionsOf the 1651 individuals who provided stool speci-

mens for examination, 726 (440Wo) were found to

harbour other intestinal parasites. The numbers ofpersons positive for other parasites were as follows:hookworm (89), Trichuris trichiura (9), Taenia spp.(25), Echinostoma spp. (103), Enterobius ver-micularis (7), Giardia lamblia (76), and small intes-tinal flukesa (417).

Personal histories

Table 2 shows the prevalence of a history of eatingkoi-pla, a popular dish containing raw freshwater fishwith viable metacercariae. In the uninfected group,only 19% recalled eating this dish, while most people(79%o) in the infected group admitted eating koi-pla.The prevalence of such histories increased with theintensity of infection, from 49%o to 9307o in the groupswith light to very heavy infections, respectively. Thecorrelation was highly significant for the samplepopulation as a whole (P < 0.001), and for most agegroups independently.

Table 3 lists the prevalence of symptomsattributed to 0. viverrini. Because their reportedsymptoms were deemed to be relatively unreliable, the108 children less than 5 years old were excluded fromthese analyses. Approximately 9701o and 9907o of thepopulation claimed that they had not been preventedfrom doing their usual daily work in the preceding 24hours and during the preceding 2 weeks, respectively,regardless of the presence or intensity of infection. Incontrast, while 1607o and 2007o of the uninfected popu-lation felt weak during, respectively, the previous 24hours and 2 weeks, these percentages rose to 3607o and42%, respectively, in the very heavily infected group.These changes were statistically very significant(P < 0.025 and P < 0.005, respectively). Likewise,anorexia, flatulence or dyspepsia, and abdominalpain in the right upper quadrant occurred much morefrequently in the infected groups, and there were cor-relations between these symptoms and the presence(and intensity) of infection (significance ranging fromP < 0.025 to P < 0.005 for persons with symptomsduring preceding 24 hours and 2 weeks). Vomitingoccurred in approximatety 2-601o of the infectedpopulation, but not in the uninfected group; how-ever, these results were not statistically significant(P > 0.05). Diarrhoea and nausea also occurred mostfrequently in the heavily infected group, and this wasstatistically significant in cases with symptoms withinthe previous 24 hours or during the last 2 weeks (seeTable 3).

The possibility that these symptoms could be dueto other coexisting intestinal parasitic infections wasalso investigated; Table 4 lists the prevalenceof symptoms in 37 individuals who had neither

a The small intestinal flukes covered in this study includePhaneropsolus bonnei, Prosthodendrium molenkampi, Haplorchisyokogawai, and Haplorchis taichui (16, 17).

OPISTHORCHIS VIVERRINI INFECTION IN THAILAND

Table 2. Number of cases classified by history of eating koi-pla and intensity of 0. viverrini infection. The last columnindicates the probability at which the null hypothesis of independence between frequency of eating koi-pla and inten-sity of infection is rejected with the chi-square test. For the separate age groups the data were pooled into either 2 or3 infection categories before testing, depending on sample sizes.

No. of cases according to theAge group History of intensity of 0. viverrini infection (eggs/mg faeces) TotalP(years) eating

koi-pla 0 < 1 1-10 > 10-50 > 50

0-4 No 63 23 5 1 0 92

Yes 2 2 8 2 0 14 < 0.0001

5-9 No 10 23 29 6 0 68

Yes 4 25 50 37 3 119 < 0.0001

10-14 No 2 12 38 8 0 60

Yes 6 1 2 71 47 7 143 0.0016

15-19 No 3 4 13 3 1 24

Yes 1 5 34 44 5 89 0.00046

20-29 No 5 4 8 1 2 20

Yes 1 8 39 40 13 101 < 0.0001

30-39 No 1 3 11 6 0 21

Yes 1 6 40 46 13 106 0.037

40-49 No 1 5 3 1 2 12

Yes 2 4 35 54 24 119 0.0059

50-59 No 2 0 5 0 1 8

Yes 2 2 23 48 16 910.031

> 60 No 1 0 2 4 1 8

Yes 2 7 22 28 15 74

All ages No 88 74 114 30 7 313

Yes 21 71 322 346 96 856 < 0.0001

0. viverrini nor any other intestinal parasitic infectionand in 586 individuals who had 0. viverrini but noother intestinal parasitic infection. Approximately,97-990o of these people claimed they were not pre-vented from carrying out their usual daily activities inthe previous 24 hours and 2 weeks, regardless of thepresence or the intensity of infection. Weakness,flatulence or dyspepsia, and abdominal pain in theright upper quadrant were found more frequently inthe infected groups, the symptoms occurring in theprevious 24 hours or during the preceding 2 weeks.The chi-square probabilities were not significant

for the results given in Table 4 except in the case ofabdominal pain. Nevertheless, there are correlationsbetween symptoms (weakness, anorexia, flatulenceand abdominal pain) and levels of infection; the smallsample size appears to be the main reason for the lackof statistical significance. The percentage of persons

with weakness increased with increasing infectionover all five grades of infection in the predicteddirection (P for 5 points in predicted order = 1/5! =0.0083). In the case of anorexia, flatulence, andabdominal pain, the proportions of individuals withthese symptoms at the highest intensity of infectionshow virtually no decline when persons infected withother parasites are eliminated. Therefore, we con-clude that these symptoms were not primarily due toother parasitic infections.

Physical examination

Liver enlargement was relatively common in thepopulation (Table 5). At the midsternal line, mild tomoderate hepatomegaly (arbitrarily defined as a pal-pable liver of up to 7 cm) was observed in 2207o of theuninfected group and approximately 290Vo of the

455

E. S. UPATHAM ET AL.

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OPISTHORCHIS VIVERRINI INFECTION IN THAILAND

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E. S. UPATHAM ET AL.

Table 5. Number of cases with liver enlargement at the midsternal line, in relation to intensity of infection by0. viverrini. Chi-square tests were made with the 3-7 cm and 7 cm categories pooled.

A. All persons sampled

No. of cases according to intensity of 0. viverrini (eggs/mg faeces)Liver enlarged(midsternal line) 0 < 1 1-10 > 10-50 > 50 Total

0 79 97 314 259 70 819

1-3 cm 13 13 26 26 8 86

> 3-7 cm 9 32 87 83 22 233

>7 cm 0 0 9 10 3 22

Total 101 142 436 378 103 1160

X2(12) = 21.63; P = 0.042

B. Excluding persons with infections due to other helminth parasites

No. of cases according to intensity of 0. viverrini (eggs/mg faeces)Liver enlarged(midsternal line) 0 < 1 1-10 > 10-50 > 50 Total

0 68 77 200 149 23 517

1-3cm 12 11 14 10 5 52

>3-7cm 7 24 43 45 8 127

>7cm 0 0 4 3 2 9

Total 87 112 261 207 38 705

X2(8) = 21.41; P = 0.0061

infected groups. Meanwhile, a markedly enlargedliver (at this line), arbitrarily defined as a palpableliver of more than 7 cm, was not found in the un-infected group but occurred in 207o of the infectedgroups. Hepatomegaly at the midclavicular line(Table 6) was observed in 2407o of the uninfectedgroup and approximately 31 tVo of the infected groups.The relationship between degree of hepatomegaly andintensity of infection was tested with chi-square in a3 x 5-cell table with three liver enlargement categoriesand five infection levels. The relationship was signifi-cant both for hepatomegaly at the midsternal line(P < 0.05) and midclavicular line (P < 0.005). Posi-tive correlations between hepatomegaly and infectionlevel were present when the population was dividedinto three or more age groups, but these were notsignificant, mostly owing to the small sample sizes.However, hepatomegaly at neither the midsternalnor the midclavicular lines was correlated with age.Spearman rank correlation coefficients between liversize and age were + 0.032 and + 0.003, respectively(P> 0.10), so that age is not a confounding vari-able.

Palpable spleen was recorded in only one of the1166 individuals examined. There was no associationbetween egg concentration and stool consistency.

Icteric conjunctivae were not observed in the un-infected groups, but occurred in 3 persons (0.430%o)with light infections (< 1 egg per mg of faeces) and in20 persons (4.1%o) with heavy infections (> 10-50eggs per mg of faeces). This difference is highly sig-nificant (P < 0.0001).

Percentage ofpopulation affected

A rough approximation of the percentages of thetotal population with symptoms attributable tooplisthorchiasis may be obtained from our data. Wehave done this using the data in Table 4 to avoid theeffects of parasites other than 0. viverrini. First, thebaseline percentages of symptoms in persons notaffected by 0. viverrini must be established. Thesewere calculated from the 126 persons uninfected orlightly infected with 0. viverrini, from the question-naire data. The percentage of these "unaffected"persons showing a given symptom is subtracted from

458

OPISTHORCHIS VIVERRINI INFECTION IN THAILAND

Table 6. Number of cases with liver enlargement at the midclavicular line, in relation to intensity of infection by0. viverrini. Chi-square tests made with the 3-7 cm and > 7 cm categories pooled.

A. All persons sampled

No. of cases according to intensity of 0. viverrini (eggs/mg faeces)Liver enlarged(midclavicular line) 0 < 1 1-10 > 10-50 > 50 Total

0 78 96 322 260 79 835

1-3cm 17 31 51 43 12 154

>3-7 cm 8 15 62 75 12 172

>7cm 0 0 1 0 0 1

Total 103 142 436 378 103 1162

X2(s) = 24.53; P = 0.00 1 9

B. Excluding persons with infections due to other helminth parasites

No. of cases according to intensity of 0. viverrini (eggs/mg faeces)Liver enlarged(midclavicular line) 0 < 1 1-10 > 10-50 > 50 Total

0 66 78 202 146 28 520

1-3 cm 16 23 31 22 5 97

> 3-7 cm 5 11 27 39 5 87

>7cm 0 0 1 0 0 1

Total 87 112 261 207 38 705

x2(8) = 1 9.48; P = 0.012

Table 7. Percentages of total sample population withsymptoms attributable to opisthorchiasis, calculatedfrom the percentages of persons in the moderate, heavy,and very heavy infection categories with symptoms inexcess of the baseline levels. A negative value indicatesan insignificant deficit in the percentage showingsymptoms in relation to the baseline level.

% of population withsymptoms attributable to

opisthorchiasis during previous:Symptoms

24 hours 2 weeks

Inability to work - 0.6 0.4

Weakness 3.9 5.7

Anorexia 0 1 .2

Nausea - 1.1 3.3

Vomiting - 0.1 2.6Flatulence 4.4 6.6

Abdominal pain 2.8 8.0

Diarrhoea 2.1 2.1

Hepatomegaly(midsternal line) > 3 cm 4.3

(midclavicular line) > 3 cm 5.0

the percentages of persons showing the symptom inthe moderate, heavy and very heavy infection gradesto yield the percentages of persons with symptomsattributable to 0. viverrini in these grades. Whenthese differences are multiplied by the proportions ofthe sample population in these grades and summed,we obtain an estimate of the total population withmeasurable symptoms attributable to opisthorchiasisin excess of the baseline levels. Table 7 summarizesthese percentages for symptoms within the 24-hourand 2-week periods reported in the questionnaire, andfor hepatomegaly of more than 3 cm below the costalmargin.

DISCUSSION

Previous studies to evaluate the morbidity of opis-thorchiasis due to 0. viverrini have either beenhampered by other concomitant intestinal parasitosesor failed to include an adequate uninfected controlgroup. In an earlier study, the signs and symptomswere found to occur with equal frequency in theinfected and uninfected groups (5). But as in thisstudy the intensity of infection was not measured,the infected group was likely to contain a large

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E. S. UPATHAM ET AL.

proportion of lightly infected individuals whosechances of showing symptoms were small.The present study of morbidity of opisthorchiasis

in Chonnabot is the first in which (1) an attemptwas made to examine an entire community, (2) theinfected subjects were separated according to theintensity of infection (based on quantitative egg ex-cretion data), (3) an uninfected control group fromthe same community was included, and (4) in order toexclude other associated intestinal parasitoses, aseparate analysis was carried out on persons who werenot infected by other parasites. Furthermore, theparamedical personnel who completed the question-naires and the physicians who examined the subjectshad no prior knowledge of their infection status, andthus observer bias was eliminated.A comparison of the present study with the prelimi-

nary study in Nong Ranya (12) shows that, in both,the populations were Thai of north-eastern origin andboth areas were not endemic for malaria. Unlike thesituation in Nong Ranya, not all the inhabitants inChonnabot were farmers; many were shopkeepers orlabourers. Furthermore, the population in Chon-nabot was slightly more heavily infected than that inNong Ranya (12). Males were more heavily infectedin Nong Ranya, while in Chonnabot the infection inmales and females was similar overall. The age struc-ture and sex distribution of the two populations weresimilar. Hepatomegaly, both at the midsternal andmidclavicular lines, occurred more frequently in theinfected individuals in Chonnabot, which can beexplained by the higher average intensity of infectionthere.The results of the present study confirm that, with

or without any other associated intestinal parasitosis,the symptoms and signs of weakness, flatulence or

dyspepsia, abdominal pain in the right upper quad-rant, icteric conjunctivae, and hepatomegaly (at bothmidsternal and midclavicular lines) occurred signifi-cantly more frequently in the infected groups andwere related to the intensity of infection. The abilityto work and signs of nausea, vomiting, diarrhoea,and splenomegaly were unrelated to the intensity ofopisthorchiasis. When other associated intestinalparasitoses were excluded, flatulence and abdominalpain remained just as prevalent in the highly infectedindividuals but the proportion of persons with weak-ness declined somewhat. We conclude that of all thesymptoms and signs previously attributed to Opis-thorchis viverrini infection, only abdominal pain,flatulence or dyspepsia, weakness or malaise, andhepatomegaly are associated with this infection.The percentages of the population with symptoms

attributable to opisthorchiasis are in the order of5-10% for weakness, flatulence, and abdominalpain, and 5% for hepatomegaly. These proportionsare high enough to indicate that opisthorchiasis is adisease of public health significance in heavily in-fected villages, and is not one that produces medicalcomplications in only rare cases. The percentageshave been corrected for baseline levels of symptoms inuninfected or lightly infected groups, and are likely tobe underestimates owing to limitations in the ques-tionnaire that was used.Our studies in Nong Ranya and Chonnabot reveal a

very high prevalence of opisthorchiasis in these com-munities, living near water-beds and streams wherethe two intermediate hosts of 0. viverrini are com-monly present, and where people are fond of eatingkoi-pla (18). Whether these cases occur in villagesfarther from these sources of infection remains to beinvestigated.

ACKNOWLEDGEMENTS

We thank the District Officer of Chonnabot, Khon Kaen Province, for permission to work in the area and Dr Kenneth S.Warren, Director of Health Sciences Division, the Rockefeller Foundation, for his advice and encouragement. This studywas supported by a grant from the Rockefeller Foundation.

RESUME

RELATION ENTRE LA PREVALENCE ET L'INTENSITE DE L'INFESTATIONPAR OPISTHORCHIS VIVERRINI ET LES SIGNES ET SYMPTOMES CLINIQUES DANS UNE

COLLECTIVITE RURALE DU NORD-EST DE LA THAILANDE

A Chonnabot, gros village de la province de Khon Kaen,dans le nord-est de la Thailande, la prevalence globale de ladistomatose a Opisthorchis viverrini (&valuee par lamethode de denombrement des aeufs de Stoll) s'est reveleegale a 89,5% sur une population totale de 1651 habitants.La pr&valence etait de 32% chez les moins de 5 ans, de 90%

chez les enfants de 5 a 9 ans, s'etablissant en moyenne A95,6%7o dans les groupes d'age au-dela de 10 ans. L'evalua-tion moyenne d'ceufs dans les selles (revelatrice du degred'infestation) etait maximale dans le groupe d'age 40-49 anset relativement constante au-dela. Dans tous les groupesd'age, la prevalence et l'intensite de l'infestation etaient

460

OPISTHORCHIS VIVERRINI INFECTION IN THAILAND 461

comparables chez les hommes et les femmes.Chez les sujets parasites plus frequemment que chez les

autres, l'interrogatoire a montre qu'ils avaient consommeanterieurement du koi pla (un plat a base de poisson d'eaudouce mange cru qui contient des metacercaires viables).Dans les groupes oui l'infestation etait plus massive, on aobserve beaucoup plus souvent les sympt6mes suivants:asthenie, flatulence ou dyspepsie et douleur abdominale auniveau du quadrant superieur droit. Toutefois, les sujetsparasites n'ont pas declare etre moins aptes au travail que les

sujets non infestes. Anorexie, nausees, vomissements etdiarrhee n'etaient que faiblement correles avec le degred'infestation. Un foie palpable, tant au niveau de la lignemediosternale qu'A celui de la ligne medioclaviculaire, etaitplus frequent parmi le groupe parasite et ce signe presentaitune correlation avec le degre d'infestation. Un ictere interes-sant la conjonctive a e observe chez 23 des sujets infestes(2,2%), alors qu'aucun sujet indemne ne presentait ce signe.Environ 5 a 10% des membres de cette population etaientporteurs de sympt6mes attribuables a la distomatose.

REFERENCES

1. SADUN, E. H. Studies on Opisthorchis viverrini inThailand. American journal of hygiene, 62: 81-115(1955).

2. VAJRASTHIRA, S. & HARINASUTA, C. Study of helmin-thic infections in Thiland. I. Incidence, distribution andepidemiology of seven common intestinal helminths.Journal of the Medical Association of Thailand, 40:309-340 (1957).

3. WYKOFF, D. E. ET AL. Opisthorchis viverrini in Thai-land. The life-cycle and comparison with O.felineus.Journal ofparasitology, 51: 207-214 (1965).

4. HARINASUTA, C. & VAJRASTHIRA, S. Opisthorchiasis inThailand. Annals of tropical medicine and parsitology,54: 100-105 (1960).

5. WYKOFF, D. E. ET AL. Clinical manifestations of Opis-thorchis viverrini infections in Thailand. Americanjournal of tropical medicine and hygiene, 15: 914-918(1966).

6. PRAPASARATHORN, T. ET AL. Study on ecology andprevalence of intestinal parasites with special referenceto the intensity of human hookworm infections andopisthorchiasis in a health development area, Bantard,Udorn Province. Journal of the Medical Association ofThailand, 50: 423-445 (1967).

7. HARINASUTA, C. & VAJRASTHIRA, S. Study on opisthor-chiasis in Thailand. 1. The incidence of opisthorchiasisin patients of fifteen hospitals in the northeast. Journalof Medical Association of Thailand, 42: 584-598(1959).

8. PRADATSUNDARASAR, A. Some observations on liverfluke infestation. Siriraj Hospital gazette, 2: 379-384(1950).

9. KOOMPIROCHANA, C. ET AL. Opisthorchiasis: a clinico-pathologic study of 154 autopsy cases. Southeast Asianjournal of tropical medicine andpublic health, 9: 60-64(1978).

10. COOK, J. A. ET AL. A controlled study of morbidity ofschistosomiasis mansoni in St. Lucian children, basedon quantitative egg excretion. American journal oftropical medicine and hygiene, 23: 625-633 (1974).

11. WARREN, K. S. ET AL. Schistosomiasis mansoni inYemeni in California: duration of infection, presenceof disease, and therapeutic management. Americanjournal of tropical medicine and hygiene, 23: 902-909(1974).

12. UPATHAM, E. S. ET AL. Morbidity in relation to inten-sity of infection in opisthorchiasis viverrini: study of acommunity in Khon Kaen, Thailand. American journalof tropical medicine and hygiene, 31: 1156-1163(1982).

13. STOLL, N. R. An effective method of counting hook-worm eggs in faeces. American journal of hygiene, 3:59-70 (1923).

14. SAPERO, J. J. & LAWLESS, D. K. The "MIF" stain-preservation technique for the identification of intes-tinal protozoa. American journal of tropical medicineand hygiene, 2: 613-619 (1953).

15. KHALAJ, G. I. A new concentration technique for thedemonstration of protozoa and helminth eggs in faeces.American journal of tropical medicine and hygiene, 4:23-28 (1955).

16. MANNING, G. S. ET AL. Preliminary report on Pha-neropsolus bonnei Lie kian, 1951, a newly discoveredhuman intestinal fluke from northeastern Thailand.Journal of the Medical Association of Thailand. 53:173-178 (1970).

17. MANNING, G. S. ET AL. A description of newly dis-covered intestinal parasites endemic to northeasternThailand. Journal of the Medical Association ofThailand. 54: 466-474 (1971).

18. HARINASUTA, C. Opisthorchiasis in Thailand: a review.In: Proceedings of the IVth Southeast Asian Seminaron Parsitology and Tropical Medicine. Schistosomiasisand other snail-transmitted helminthiases, Manila,24-27 February 1969. Manila, 1969, pp. 153-264.