An outbreak of hand, foot, and mouth disease in Singapore

Bulletin of the World Health Organization, 60 (6): %5-969 (1982) An outbreak of hand, foot, and mouth disease in Singapore K. T. GOH,' S. DORAISINGHAM,2 J. L. TAN,3 G. N. LIM,4 & S. E. CHEW4 Epidemiological studies were carried out during an extensive outbreak of hand, foot and mouth disease caused by coxsackievirus A 16 in Singapore in 1981. Most of the cases were concentrated in densely populated public housing estates, and the morbidity rate was highest in children under 5 years ofage. The mean secondary attack ratefor children under 12 years ofage was 76.7% compared with an overall rate of31.3%. The incubation period rangedfrom I to 7 days. Factorsfavouring the transmission ofinfection within a household included sharing of household and personal articles with the index case. The disease was mild and self-limiting. Hand, foot, and mouth (HFM) disease is a viral infection caused by an enterovirus, usually cox- sackievirus type A 16 (1-5); coxsackievirus types A5, A10, B2, and B5, and other enteroviruses are less frequent causes of the illness (6, 7). The disease derives its name from the characteristic papular or vesicular lesions involving primarily the skin of the hands and feet, and the buccal mucosa. Epidemics of HFM disease have been reported in several temperate countries since it was first reported in Toronto, Canada in 1957 (1-9). In Singapore, the disease was first recognized in an outbreak in June-July 1970 (10). Another outbreak affecting 104 persons occurred between September 1972 and January 1973 (11). Coxsackievirus A 16 was isolated from the stool of one patient in 1972. In April-May 1976, coxsackie- virus A 16 was isolated from the oral lesions of three patients with HFM disease by the Virus Laboratory, Government Department of Pathology. It is not known whether or not an outbreak occurred at the time. An increase in the number of cases of HFM disease was first noted in a government polyclinic in the Clementi area of Singapore in September 1981. In order to determine the extent of infection in the com- munity, all government outpatient and maternal and child health clinics were alerted and requested to notify any occurrence of the disease. The clinical cri- teria for diagnosis based on the findings in the 1972-73 outbreak were circulated to the doctors. ' Head, Quarantine and Epidemiology Department, Ministry of the Environment, Princess House, Alexandra Road, Singapore. 2 Consultant Virologist, Department of Pathology, Ministry of Health, Singapore. 3 Registrar, Quarantine and Epidemiology Department, Ministry of the Environment, Singapore. 4 Registrar, Primary Health Care Services, Ministry of Health, Singapore. A total of 742 cases were notified during the period September-December 1981. This paper describes the clinical, epidemiological, and virological features of the outbreak. MATERIALS AND METHODS All cases notified by primary health care doctors directly to the Quarantine & Epidemiology Depart- ment during the initial period of the outbreak were investigated. Physical examination was carefully conducted by a medical doctor and the presenting clinical symptoms and signs recorded. Relevant epi- demiological data such as age, sex, ethnic group, home address, date of onset of symptoms, contact history, and source of infection were obtained from either the patient or the parent. Home visiting was carried out to follow up the cases seen at the primary health care clinics, to look for secondary cases in families, and to determine the time interval between the onset of symptoms in the index case and sub- sequent cases. Environmental and social conditions in the home, including the extent of sharing of house- hold articles, were noted. Virological investigations were carried out on 23 patients attending two primary health care clinics where most of the cases were seen. Specimens were collected from oral ulcers and vesicular skin erup- tions, stored in Hanks' virus transport medium con- taining penicillin, gentamicin, and amphotericin B for the suppression of bacterial and fungal growth, and sent to the Virus Laboratory, Government Department of Pathology, for virus isolation. The specimens were inoculated into HeLa (rhinovirus- sensitive) cells, human embryo lung fibroblasts, and 4251 -965 K. T. GOH ET AL. primary cynomolgous monkey kidney cells. In this group of patients, positive specimens were associated with the appearance of cytopathogenic effects only in monkey kidney cells, at about the eighth day post- inoculation. However, isolates obtained towards the end of the outbreak were found to grow with ease in HeLa and human diploid cells as well. Positive iso- lates were identified by virus neutralization tests at the Enterovirus Reference Laboratory, Department of Microbiology, National University of Singapore. RESULTS Epidemiology A total of 270 cases were investigated. These included 83 secondary cases from 63 families detected during the epidemiological investigations. Most of the cases were concentrated in densely populated public housing estates. Almost all the cases (93.3 0/) were in children under 10 years of age, with 64.4% in the age group 1-4 years (Table 1). The ethnic-specific morbidity rate was highest among the Chinese (Table 2), and the male to female ratio was 1.2: 1. The majority of cases (61.2Gb) had no history of contact with a known case of HFM disease. Of those with a contact history, 70.6% contracted the infection from a member of the same household. Public swim- ming pools were not implicated, and there was no reported outbreak in any kindergarten, nursery, or other institution for preschool children. Sixty families with secondary cases were studied in detail to determine the secondary attack rate, incu- bation period of the disease, and environmental Table 1. Age and sex distribution and age-specific morbidity rates of 270 cases of hand, foot, and mouth disease, S,ingapore Morbidity Age Total rate per group Male Female 100 000 (years) No. % population a <1 16 14 30 11.1 105.3 1-4 95 79 174 64.4 5-9 27 21 48 17.8 21.4 10-14 5 3 8 3.0 3.4 15-44 4 6 10 3.7 0.8 Total 147 123 270 100 11.2 a Based on 1980 census population (source: Department of Statistics, Singapore). Table 2. Ethnic distribution and ethnic-specific morbidity rates of 270 cases of hand, foot, and mouth disease, Singapore Cases Rate per Ethnic 100 000 group No. % Population a population Chinese 229 84.8 1 856 237 12.3 Malay 37 13.7 351 508 10.5 Indian 3 1.1 154 632 1.9 Others 1 0.4 51 568 1.9 Total 270 100 2 413 945 11.2 a Based on 1980 census (source: Department of Statistics, Singapore). conditions that facilitated the transmission of infec- tion. All the index cases in these families were children under 12 years of age. Of 256 home contacts, 80 were found to have HFM disease, giving a mean secondary attack rate of 31.30o (range, 9.1-66.60o). Consider- ing only children below 12 years of age, the mean secondary attack rate was much higher, at 76.7% (range, 33.3-100%). The incubation period, calculated as the interval between the date of onset of symptoms in the index case and the onset of rash in subsequent cases in the family ranged from 1 to 7 days, with a median of 4 days. On the basis of a case-control study carried out in the 60 families with secondary cases, it was found that sharing of beds and bedding, towels, handkerchiefs, clothing, feeding bottles and teats, eating utensils, toothbrushes, and toys, and sleeping in the same room as the index case were all significant factors favouring the transmission of infection (Table 3). Clinicalfeatures The main presenting symptoms of the disease were rash (76.5%), pain in the mouth or throat (65.0%), and fever (53.0%). Upper respiratory symptoms occurred in about one-third of the cases, but gastro- intestinal symptoms were infrequent. The skin lesions were found mainly on the hands, feet, and buttock/ perianal regions; the palms and soles were involved in about half of the cases. However, in a number of cases, skin lesions were also found scattered on other parts of the body (Table 4). Most of the mouth lesions had already ulcerated by the time the patients were first examined. Only 13 (5.67o) of the patients had a temperature above 38 °C when seen by the doctor. The patients were treated symptomatically with analgesics, sedatives, and topical application of bland 966 HAND, FOOT, AND MOUTH DISEASE IN SINGAPORE Table 3. Case-control studies on the association of sharing of household and personal articles and bedroom, and transmission of infection in 60 families, during an outbreak of HFM disease in Singapore in 1981 No. who shared No. who did not share with index case with index case p Item value ill well % ill ill well % ill bed, bedding 37 38 49.3 43 138 23.8 < 0.001 towel, handkerchief 50 31 61.7 30 145 17.1 < 0.0000001 feeding bottle, teat 9 0 100.0 71 176 28.7 0.00002b eating utensil 46 39 54.1 34 137 19.9 < 0.0000001 a toothbrush 5 1 83.3 75 175 30.0 0.012296b toy 55 1 3 80.9 25 163 13.3 < 0.000001 a clothing 5 0 100.0 75 176 29.9 0.00272 b bedroom 53 82 39.3 27 94 22.3 <0.01a ax2test. bFisher's exact test. Table 4. Clinical features of 234 cases of hand, foot, and mouth disease, Singapore' Symptom No. % Sign No. % Sign No. % Rash 179 76.5 Enanthem (Mouth lesions) Exanthem (Skin lesions) Pain in the Type Type mouth or throat 152 65.0 Fever 124 53.0 Ulcer 143 61.1 Maculopapules 212 90.6 Refused feeds 104 44.4 Petechial Vesicles 120 51.3maculopapules 96 41 .0 Bullae 18 7.7 Fretfulness 85 36.3 Vesicle 35 15.0 All three lesions 11 4.7 Cough 85 36.3 Anorexia 75 32.1 Site Site Excessive Buccal mucosa 130 55.6 Hand/arm 185 79.1 salivation 63 26.9 Lips 109 46.6 Palm 145 62.0 Insomnia 57 24.4 Palate 105 44.9 Foot/ankle 168 71.8 Itch 50 21.4 Tongue 102 43.6 Sole 105 44.9 Dysphagia 44 18.8 Pharynx/tonsil 63 26.9 Thigh/knee 98 41.9 Coryza 40 17.1 Gums 44 18.8 Buttock/ Malaise 35 15.0 perianal region 143 61.1 Vomiting 20 8.5 Enlarged Diarrhoea 13 5.6 cervical nodes 53 22.6 Abdominal pain 12 5.1 Headache 10 4.3 e 36 cases were excluded because available information was incomplete. lotions or local anaesthetic creams to relieve the pain. Laboratory findings All of them recovered spontaneously. The median Coxsackievirus A 16 was isolated from 12 (52.27o)duration of illness was 6 days. A 9-month old baby of the 23 patients investigated (9 of 20 oral swabs and was admitted to the hospital with febrile fits, but the 3 samples of vesicle fluid). clinical course was uneventful. 967 K. T. GOH ET AL. DISCUSSION Most reported outbreaks of HFM disease have occurred in cities in the temperate zones of southern Africa, North America, Australia, and Europe (1-9). In the United Kingdom, a 2-3 year cyclic pattern in the incidence of the disease has been noted (12). In tropical areas, the disease would probably be reported more frequently if medical and health staff were alerted to the characteristic clinical presentation. The clinical and epidemiological features of this outbreak are generally similar to those of previous outbreaks in Singapore as well as those in the temperate countries. The disease was mild and self- limiting. However, in young children, ulceration of the oral cavity caused rather distressing symptoms and interfered with proper feeding. Except for one child with febrile fits, no complications were reported, although aseptic meningitis (9), meningo- encephalitis (13), myocarditis (14), and paralytic disease resembling poliomyelitis (15) have been reported elsewhere. The virus has also been known to cause spontaneous abortion in pregnant women (16), and four babies born in Toronto 6 months after the epidemic in 1957 were reported to have minor congenital defects (1). Coxsackievirus A 16 was isolated from the oral ulcers, and as about one-third of the cases also had acute upper respiratory symptoms, the virus was probably disseminated by droplets. This may account for the large number of cases occurring in densely populated public housing estates and the fact that more than half of the cases had no history of contact with a known case. Although virus isolation from stools was not attempted, coxsackievirus A 16 was iso- lated from a case in the previous outbreak (11). Therefore, infection may have been transmitted by the oral-faecal route, especially among toddlers at play. The disease had a high infectivity rate among close contacts, and children of the same household were at the greatest risk; parents of these children were also affected. Transmission of infection within a house- hold was facilitated by the sharing of household articles such as toys, toothbrushes, feeding bottles, and teats, which were probably contaminated by droplets, saliva, or excreta. Although the skin vesicles resolved spontaneously, they could be easily injured. Thus, infection may also have been spread by the sharing of towels, handkerchiefs, clothing, or bed- ding contaminated with vesicle fluid. During an outbreak, appropriate health education should be given to prevent secondary transmission of infection. ACKNOWLEDGEMENTS The authors are indebted to Associate Professor L. H. Lee, Department of Microbiology, National University of Singapore for typing the virus isolates, and to Dr A. E. Ling and staff of the Virus Laboratory, Department of Pathology, Ministry of Health for technical assistance. The support given by Dr Y. K. Ng, Director, Outpatient Services, Ministry of Health, Dr T. J. Stanley and the inspectorate staff of the Epidemiology Unit, Ministry of the Environment is also gratefully acknowledged. We thank Mrs K. Indumathy for secretarial assistance. RtSUMIL .tPIDtMIE D'INFECTION CUTANEOMUQUEUSE A VIRUS COXSACKIE (HAND, FOOT AND MOUTH DISEASE) A SINGAPOUR Cette maladie, parfois appel&e syndrome main-pied- bouche, a fait l'objet d'une etude epidemiologique, clinique et virologique lors d'une epidemie qui s'est produite a Singa- pour. Pendant la periode septembre-decembre 1981, un total de 742 cas a et signale par les dispensaires de soins de sante primaires du gouvernement. La plupart des cas etaient concentres dans des ensembles publics d'habitations a popu- lation dense. Le taux de morbidite etait maximal chez les enfants de moins de cinq ans avec un taux de masculinite de 1,2:1. Parmi les trois principaux groupes ethniques de Singa- pour, les taux de morbidite pour 100 000 habitants ont ete de 12,3 parmi les Chinois, de 10,5 parmi les Malais et de 1,9 chez les Indiens. Pour plus de 60%o des cas, il n'y avait pas d'antecedents de contact avec un cas connu. Parmi ceux qui avaient eu un contact, 70,607o ont contracte l'infection d'un membre du meme menage. Le taux moyen d'atteinte secon- daire chez les enfants de moins de 12 ans etait de 76,70o contre un taux global de 31,3% pour la totalite des groupes d'age. La periode moyenne d'incubation etait de quatre 968 HAND, FOOT, AND MOUTH DISEASE IN SINGAPORE 969 jours (intervalle: 1-7 jours). Une etude de cas avec temoins a rev& que le fait de partager avec le cas initial des articles, tels que serviettes, mouchoirs, brosses a dents, couverts et assiettes, jouets, biberons, tetines et vetements, ou de dormir dans la meme piece, representait des facteurs impor- tants favorables a la transmission de l'infection (P < 0,01). Le syndrome morbide etait generalement benin et guerissait de lui-meme. La duree mediane de la maladie etait de six jours. Les principaux signes cliniques ont e des eruptions maculopapuleuses et vesiculeuses (76,5%), des ulcerations buccales (65,0%) et de la fievre (53,0%). Les paumes des mains et les plantes des pieds etaient atteintes dans environ 50% des cas. Le Coxsackievirus A 16 a e isole de 12 (52,2%) des 23 ecouvillonnages d'uIceres buccaux et de liquide des vesicules chez les malades. REFERENCES 1. ROBINSON, C. R. 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