Epidemic hand, foot and mouth disease caused by human enterovirus 71, Singapore - Research

Emerging Infectious Diseases, Jan, 2003 by Kwai Peng Chan, Kee Tai Goh, Chia Yin Chong, Eng Swee Teo, Gilbert Lau, Ai Ee Ling

Results

Cases

The number of notifications of HFMD cases to the Ministry of the Environment increased in early September 2000 (Figure 1). The incidence peaked at 308 cases per day on October 10 and decreased to 10 cases per day by October 28. Hospital and general practice physicians and preschool-center operators reported a total of 3,790 cases during these 2 months.

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During the epidemic, 311 samples from 175 clinically diagnosed HFMD case-patients were submitted for virus culture. A total of 138 (78.8%) of these patients were [less than or equal to] 4 years of age, with 12 (6.9%) >10 years of age, the oldest being 71 years old (Table 1). The male-to-female ratio was 1.7:1.

At least one virus was isolated from 147 (47.3%) of the samples collected from 104 (59.4%) HFMD patients, including 2 of 3 who died. Almost all (91.5%) of these patients were [greater than or equal to] 5 years of age with the peak incidence at 1 year (Table 1). A 21-year-old woman was the only patient >10 years of age to yield a virus, identified as HEV71, from vesicles on her hands and feet.

HEV71 was the most commonly isolated virus, detected in 76 (73.1%) of 104 case-patients (Table 2). Three of these patients had a second virus isolated concurrently: echovirus (EV) 25, Rhinovirus, and CMV. Other enteroviruses were isolated in 24 (23.1%) of samples from case-patients. Five cases of CAV 16 were identified, as well as four cases each of CAV6, CAV24, and EV18; three cases of CAV10; and one case each of CAV4, CBV3, CBV4, and CBV5. Four patients (3.8%) tested positive for nonenteroviruses; CMV was isolated from their mouth and from throat swabs.

The two patients with fatal HFMD, from whom HEV71 was isolated, were siblings, a 14-month-old girl and her 2-year-old brother. The girl was admitted to the hospital with fever, rashes on the hands and feet, and oral ulcers of 3 days' duration. Progressive hemodynamic instability, oliguria, metabolic acidosis, and hyperkalemia developed; despite intensive care and resuscitative efforts, she died on day 2 after admission. At autopsy, her lungs showed acute pulmonary edema, acute intraalveolar hemorrhage and diffuse alveolar damage associated with interstitial lymphocytic infiltrates, extensive hyaline membrane formation, patchy atelectasis, and focal pneumocyte desquamation and hypertrophy (Figure 2). Samples from her brain tissue showed lymphocytic leptomeningitis with widespread perivascular cuffing by lymphocytes and plasma cells within the cortex and white matter (Figure 3). The pons, in particular, showed evidence of encephalitis, associated with localized perivascular hemorrhage, focal neuronal necrosis, and microglial reaction (Figure 4). Features of myocarditis were observed; the myocardium showed occasional interstitial infiltrates of lymphocytes and plasma cells associated with focal myonecrosis (Figure 5). HEV71 was isolated from samples taken from the brain, tonsils, intestines, stools, and throat and from swabs of the mouth and rectum. Viral cultures of the lung, heart, and spleen were negative.

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This patient had two older brothers. The 2-year-old brother showed an almost identical clinical course. After 3 days of fever, rash on the hands and feet, and oral ulcers, he too deteriorated under intensive care and died about 2 hours after his sister, within 24 hours of hospitalization. Autopsy findings were similar, showing evidence of acute interstitial pneumonitis, pulmonary edema, encephalitis (including focal neuronal necrosis of the pons), and myocarditis. HEV71 was isolated from postmortem specimens of the tonsils and intestines. Viral cultures of the brain, heart, lungs, spleen, and lymph nodes showed negative results.