An epidemic of cockles-associated hepatitis A in Singapore

Bulletin ofthe WorldHealth Organization, 62 (6): 893 - 897 (1984) © World Health Organization 1984 An epidemic of cockles-associated hepatitis A in Singapore K. T. GOH,' L. CHAN,2 J. L. DING,2 & C. J. OON3 An epidemic of serologically confirmed hepatitis A occurred between May and September 1983 in Singapore. The vehicle of transmission was traced to raw and partially cooked cockles, Anadara granosa, which had been importedfrom places with no sanitary control on the production. Strict controls on imported cockles are warranted. Viral hepatitis is a disease of major public health importance in Singapore (1). A clearer picture of the epidemiology of the disease has emerged following routine investigations of every notified case since June 1976 (2, 3). During the non-epidemic period, the distribution of acute cases caused by hepatitis A virus, hepatitis B virus and hepatitis non-A, non-B virus was found to be 30%, 46% and 24%, respec- tively (4). In May 1983, a sharp increase in the number of notified cases of acute viral hepatitis, which were negative for hepatitis B surface antigen (HBsAg), was noted (Fig. 1). In order to determine the source of infection and mode of transmission so that appropriate preventive and control measures could be taken, an intensive epidemiological study was planned and conducted. MATERIALS AND METHODS All acute cases of viral hepatitis with a compatible history, abnormal liver function tests, and absence of HBsAg in the serum (determined by reverse passive haemagglutination, rPHA) that were reported during the outbreak period were investigated. Relevant epi- demiological data, e.g., concerning contacts with jaundiced persons, travel outside the country, and food establishments patronized up to three months prior to the onset of the illness, were collected. Contact tracing in the homes, neighbourhood and work places of the reported cases was also carried out. As the initial investigations could not establish a X Head, Quarantine and Epidemiology Department, Ministry of the Environment, Princess House, Alexandra Road, Singapore 0315, Singapore. Requests for reprints should be sent to this author. 2 Research Scientist, University Department of Medicine (1), Singapore General Hospital, Singapore. 3Associate Professor, University Department of Medicine (1), Singapore General Hospital, Singapore. common source of exposure, questionnaires for case- control studies were designed to elicit information regarding food preferences and the frequency of con- sumption of a list of food items which are recognized vehicles of transmission of hepatitisA (5, 6). Because of possibly better recollection of the food consumed in those who were ill than in the controls, we first inquired into general food preferences before deter- mining the frequency of consumption. Patients who had no history of contact with a hepatitis case were questioned about the consumption of a variety of locally available shellfish, fish, raw vegetables, ice- cream, iced drinks, and fruits between two weeks and two months prior to the onset of illness. Controls of the same age groups, sex, and race and with no past history of jaundice were chosen from either the same household or in the immediate neighbouring prem- ises. They were asked identical questions covering the previous three months. The test for statistical signifi- cance was by McNemar's method (7). Blood samples obtained from 25 acute cases (negative for HBsAg, by rPHA) during the outbreak period were analysed by enzyme immunoassay for anti-HAV IgM or the IgM-specific antibody to hepatitis A virus (using HAVAB-M), for HBsAg (using AUSZYME II), for anti-HBc or the antibody to hepatitis B core antigen (using CORZYME), and for anti-HBs or the antibody to HBsAg (using AUSAB-EIA). RESULTS A total of 322 cases of acute viral hepatitis were notified during the period between 21 May and 29 September 1983. No additional icteric cases were identified through contact tracing. Of the reported cases, 296 were infected locally and 26 were imported. The indigenous cases comprised 107 cases positive for HBsAg, 161 cases negative for HBsAg when screened 4489 -893- K. T. GOH ET AL. 15 a A 5 2 12 192 2I29 I2 30 7 k 21 23 46 162 2 9 16 2a 30 S X20 V 3 1 1 J JAN I fB |I m OR I I | JUL AIG |I SE Onset of Jaundice Fig. 1. Incidence of acute viral hepatitis and HBsAg-positive cases by week of onset of jaundice in Singapore, January-September 1983. Table 1. Ethnic distribution and specific attack rates of 1612 qases of acute viral hepatitis (HBsAg-negative)b betweLn May and September 1983 No. of Estimated 1982 Rate perEthnic gup cases mid-year 100 000 population Chinese 142 1 896 700 75 Malay 9 362 400 2.5d Indian 10 158 300 6.3 Others 0 54 400 0 Total 161 2 471 800 6.5 Table 2. Age and sex distribution and age-specific attack rates of 161 a cases of acute viral hepatitis (HBsAg-negative)b between May and September 1983 No. of cases Estimated 1982 Age group mid-year Rate per (years) Males Females Both populationc 100 000 0-4 1 0 1 195 400 0.5 5-14 9 5 14 437700 3.2 15-24 47 19 66 569 800 11.6 25-34 45 16 61 504 900 12.1 35-44 5 3 8 293900 2.7 45-54 3 4 7 210500 3.3 t55 3 1 4 259600 1.5 Total 113 48 161 2471 800 6.5 Eight foreigners were excluded. b Determined by reverse passive haemagglutination. Source: Department of Statistics, Singapore. to0 u Week omdu ' Eight foreigners were excluded. b Determined by reverse passive haemagglutination. ' Source: Department of Statistics, Singapore.d P<0.01. 894 COCKLES-ASSOCIATED HEPATITIS A by the rPHA method, and 28 cases that were clinically diagnosed. Of the three major ethnic groups in Singapore, the Chinese had the highest attack rate, which was signi- ficantly higher than that of the Malays (P < 0.01) (Table 1). No significant difference was observed between Chinese and Indians, or between Malays and Indians (P > 0.05). The age-specific attack rate was high in the 15-34-year age group and the male to female ratio was 2.4:1 (Table 2). About three- quarters of the cases required hospitalization. No death was reported. Cases were distributed all over the island with no clustering of cases in any locality either by residential addresses or by places of work. Most of them (65.8%) stayed in high-rise public housing estates provided with modern sanitary facili- ties. No particular food establishment was impli- cated. Both the cases and controls had no travel history during the preceding six months. Thirty-eight matched pairs (cases and controls) were available for study. They comprised the follow- ing by race, age group, and sex: Chinese (34 pairs), Malays (3 pairs), and Indians (I pair); aged 5-14 years (6 pairs), 15-34 years (31 pairs); 35-54 years (1 pair); males (27 pairs) and females (11 pairs). Of these, 23 pairs were from the same household. Results of the case-control studies showed that the consumption of cockles was significantly related to the illness (P < 0.005) (Table 3). The relative risk (8) was 14, and the attributable risk (or proportion of cases attributed Table 3. Distribution of 38 case-control pairs by history of consumption of specified food items Case ate Case did not eat Food item P value' Control Control did Control Control did ate not eat ate not eat Cockles ('See-hum') 19 14 1 4 < 0.005b Oysters 3 7 3 25 NSc Crabs 13 7 8 10 NS Prawns 35 3 0 0 NS Mussels 1 4 4 29 NS Clams 3 8 2 25 NS Cuttlefish 22 2 5 9 NS Fish 37 0 1 0 NS Other seafood 0 2 1 35 NS Ice-cream 13 1 3 21 NS Iced drinks 25 3 2 8 NS Cut fruits/fruit juice 27 1 3 7 NS Frozen fruits 5 0 0 33 NS Raw vegetables 14 1 1 22 NS a By McNemar's test (7). b Relative risk = 14. ' NS= Not statistically significant. Table 4. Laboratory results on 25 cases of acute viral hepatitis, May-June 1983 HBV markers Anti-HAV IgM HBsAg Anti-HBc Anti-HBs Positive Negative Positive Negative Positive Negative Positive Negative Number 23 20O 25 5b 23 13 12 tested a Also negative for HBsAg, anti-HBc and anti-HBs. b Three of these were also positive for anti-HBs. 895 K. T. GOH ET AL. to the consumption of cockles) was 81 %!o (9). No other types of shellfish and food items were incriminated. Twenty-three out of 25 acute cases were serological- ly confirmed to have hepatitis A by the presence of anti-HAV IgM. The other two acute cases were negative for HBsAg, anti-HBs, anti-HBc and anti- HAV IgM (Table 4). DISCUSSION Bivalve molluscs harvested from sewage-polluted areas are well-known health hazards as they are filter- feeders and may concentrate viruses from even mini- mally polluted water (10). The consumption of con- taminated raw or inadequately cooked shellfish has been responsible for both epidemic and endemic transmission of hepatitis A, although most outbreaks described were not serologically confirmed (10-17). In Singapore, a small outbreak of hepatitis A in 1978 and a major outbreak in 1980 were caused by imported cockles and oysters, respectively (3). The 1983 epidemic was associated with the con- sumption of the cockle, Anadara granosa (Linnaeus), which is cultivated along the muddy coastal regions in many countries of south-east Asia without any sanitary control over their production and harvest. The risk of human faecal contamination has been in- creasing as more and more settlements encroach on the estuarine areas where the cockles are grown. No health certificate is required for the import of cockles into Singapore. Live shellfish are brought in by the wholesalers in gunny sacks, without refrigera- tion, and immediately distributed to the markets and food centres. All the live cockles were obtained from one country in the region. About 9.7 tonnes were con- sumed by the population per day. The flesh and the gut are removed from the shell and usually eaten either raw or half-cooked with a chilli sauce and spices. One of the favourite methods of preparing cockles for consumption is to pour boiling water over them till the shells are partially opened. Raw shucked cockles are also commonly used by hawkers and restaurants as additional ingredients in the food. They are lightly fried with noodles or served with curry noodle soup. The temperature attained by such methods of preparation prior to consumption is insufficient to inactivate the virus that might be present in the core of the shellfish (18). Although under laboratory conditions, hepatitis A virus becomes non-infective after one minute at 98 IC (19), cockles commercially processed by one to two minutes of steaming to remove the shells, followed by five minutes of boiling, were responsible for an exten- sive outbreak in the United Kingdom in 1980-81 (17). Cockles are a favourite food item among the ethnic Chinese in Singapore who, unlike the Malays, prefer to consume them raw or half-cooked. This may account for the high attack rate among the Chinese in this epidemic. There are several reasons to explain why other types of bivalve molluscs were not implicated in this epidemic. Firstly oysters, which are another favourite shellfish among the population, are now subject to health controls following an oyster-associated outbreak of hepatitis A in 1980 (3). Live oysters can only be imported into Singapore from countries where there is legislation for licensing of oyster farms and for mandatory testing of the microbiological quality of the oysters and of the water in which the oysters are cultured. The import of chilled shucked oysters from south-east Asian countries is prohibited, and frozen oysters brought in from these countries can only be released for sale if they satisfy the estab- lished bacteriological standards. Secondly, other types of shellfish are prepared in a different manner. They are properly fried with chilli and spices before consumption. Moreover, they are not popular ingredients with the hawkers and restaurants and only small quantities are imported. There are numerous limiting factors in case-control studies. In this epidemic, a large pro- portion of the population might have been infected and some of the matched control subjects could actually have been infected asymptomatically. This would make demonstration of an epidemiological association more difficult. Also, the inclusion of household controls means that both cases and controls are likely to have a similar life style and this could lead to underestimation of any epidemiological association. Despite these practical limitations, the association of cockles consumption and hepatitis A was strong, even though based on relatively few matched pairs. There is no direct virological evidence to prove the epidemiological association between ingestion of cockles and hepatitis A infection, because it is difficult to trace the suspected shellfish retrospect- ively and there is no adequate method to detect the virus in cockles. However, routine monitoring of cockles brought in from the production areas have been shown to be grossly contaminated, and a variety of enteropathogenic organisms including Vibriopara- haemolyticus, enteropathogenic Escherichia coli, salmonellae, shigellae, Clostridium welchii, and Vibrio cholerae have been isolated (20, 22). As soon as the vehicle of transmission was incriminated, the public was advised to refrain from ingesting raw and partially cooked cockles. However, the traditional behavioural pattern was difficult to modify and the ways of preparing cockles remained unchanged. The outbreak did not terminate until four 896 COCKLES-ASSOCIATED HEPATITIS A 897 months later in September. In the developing coun- tries, it is difficult to prevent pollution of estuarine waters where cockles grow best or to relay them in clean water before export. Depuration will make the shellfish too costly as a cheap food. Experiments on sterilization of cockles by microwave ovens were also conducted, but the altered appearance, taste and texture of the sterilized products were not acceptable to the consumers. Therefore, as long as the population in Singapore continues to prepare cockles in the traditional way, epidemics of hepatitis A can be expected from time to time. RESUMt UNE EPIDEMIE D'HEPATITE A ASSOCIEE A DES COQUES A SINGAPOUR Des enquetes 6pid6miologiques ont e men&es pour determiner la source d'infection et le mode de transmission de l'hepatite A lors d'une epidemie qui s'est produite a Singapour. Pendant la periode comprise entre mai et septembre 1983, on a signale un total de 161 cas aigus donnant une reaction negative en ce qui concerne l'antigene de surface de l'hepatite B dans l'epreuve d'hemaggluti- nation passive invers&e. Le taux d'atteinte le plus 6leve s'observait parmi les adultes ag6s de 15 a 34 ans, surtout dans le groupe ethnique des Chinois, le nombre de cas chez les hommes etant presque deux fois et demie plus eleve que chez les femmes. Les resultats des 6tudes cas-t6moins ont montre que la consommation de coques (Anadara granosa) importees, crues ou partiellement cuites, 6tait associ6e a la maladie (P < 0,005), le risque relatif 6tant de 14 et le risque attribuable (a savoir la proportion de cas attribues a la consommation de coques) de 81 %. 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