Severe acute respiratory syndrome in Singapore: clinical features of index patient and initial contacts - SARS - Dispatches

Emerging Infectious Diseases, June, 2003 by Li-Yang Hsu, Cheng-Chuan Lee, Justin A. Green, Brenda Ang, Nicholas I. Paton, Lawrence Lee, Jorge S. Villacian, Poh-Lian Lim, Arul Earnest, Yee-Sin Leo

Severe acute respiratory syndrome (SARS) is an emerging viral infectious disease. One of the largest outbreaks of SARS to date began in Singapore in March 2003. We describe the clinical, laboratory, and radiologic features of the index patient and the patient's initial contacts affected with probable SARS.

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Severe acute respiratory syndrome (SARS), an atypical pneumonia characterized by high rate of transmission to healthcare workers (1), began in Guangdong Province, China, in November 2002. One of the largest SARS outbreaks to date began in Singapore in mid-March 2003 and was traced to a traveler returning from Hong Kong.

According to the World Health Organization, a suspected case of SARS is defined as documented fever (temperature >38[degrees]C), lower respiratory tract symptoms, and contact with a person believed to have had SARS or history of travel to an area of documented transmission. A probable case is a suspected case with chest radiographic findings of pneumonia, acute respiratory distress syndrome (ARDS), or an unexplained respiratory illness resulting in death, with autopsy findings of ARDS without identifiable cause (2). We describe the clinical features of the index patient in Singapore and the patient's initial group of contacts affected with probable SARS.

The Index Case

The index case of SARS in Singapore ocurred in a previously healthy 23-year-old woman of Chinese ethnicity who had stayed on the 9th floor of a hotel during a vacation to Hong Kong, February 20-25, 2003. A physician from southern China who stayed on the same floor of the hotel during this period is believed to have been the source of infection for this index patient and the index patients of outbreaks in Vietnam and Canada.

Fever and headache developed in the patient on February 25 and a dry cough on February 28. She was admitted to Tan Tock Seng Hospital, Singapore, on March 1. On admission she had oral temperature of 37.6[degrees]C and was lethargic. The chest was clear to auscultation. The remainder of her physical examination was normal. The total leukocyte count (2.7 x [10.sup.9]/L), lymphocyte count (0.9 x [10.sup.9]/L), and platelet count (102 x [10.sup.9]/L) were reduced below normal laboratory ranges. Electrolytes and liver biochemistry results were normal. The chest x-ray showed patchy consolidation of both upper and lower lobes of her right lung (Figure 1a). Blood cultures were sterile, and tests for urinary Legionella antigen, particle agglutination test for Mycoplasma pneumoniae antibodies, and complement fixation test for Chlamydia antibodies were negative. Immunofluorescence performed on nasopharyngeal aspirates for viral antigens of influenza virus A and B, parainfluenza virus, respiratory syncytial virus, and adenovirus was negative.

[FIGURE 1 OMITTED]

Intravenous levofloxacin, 500 mg once a day, was administered, but the patient's temperature continued to spike up to 40[degrees]C, and the cough persisted. On day 5 of hospitalization, she became breathless and required supplemental oxygen. Sequential chest x-rays showed progressive, extensive involvement of the right lung, with new infiltrates appearing on the left (Figure 1c). Liver enzymes became elevated, with an ALT of 200 U/L (7-36 U/L) and AST of 208 U/L (15-33 U/L); serum lactate dehydrogenase (LDH) levels rose to 1518 U/L (200-500 U/L). Intravenous vancomycin (1 g twice a day) and oral oseltamivir (75 mg twice a day) were added to the regimen. Nine days after admission, the patient began to improve clinically, the laboratory abnormalities returned towards normal, and the chest x-ray abnormalities stabilized and resolved. The patient has remained well.

Electron microscopy of the specimens obtained by nasopharyngeal aspiration on day 7 of hospitalization showed viral particles of <100 nm with widely spaced, club-shaped surface projections characteristic of coronaviruses.

Clinical Features of Contact Cases

When the index patient was seen in early March, the clinical features and highly infectious nature of SARS were not known. For the first 6 days of hospitalization, the patient was in a general ward, without barrier infection control measures. One of eight physicians who attended her became infected, as did 9 of approximately 30 nursing staff. SARS also developed in 1 of 12 patients in adjacent beds during her hospitalization and 9 of approximately 30 family members and friends who visited her during this time. Nineteen of these 20 patients were admitted to our hospital for treatment and isolation (1 was treated outside Singapore), and we recorded prospectively the clinical features of their illnesses with a standardized data collection form. In addition to demographic data, this form elicited information on occupation, date(s) of exposure to suspected cases, travel history after February 20, dates of onset of various symptoms, results of blood tests, and chest radiographic findings.

The demographic profiles of the index and 19 contact cases are shown (Table 1). An epidemic curve of the index and contact cases is shown in Figure 2. Because most healthcare staff in our hospital are women, a high proportion of the case-patients (75%) were female. The median age of patients was 28 years. All were previously healthy, except one who had diabetes mellitus and end-stage renal failure and one who had a history of childhood asthma. One patient was a smoker. For seven patients who only had one exposure to the index patient, the median incubation period was 4 days (estimated range 2-8 days). For those with multiple exposures (13 patients), median incubation period was either 7 days (range 4-12 days, calculated from day 1 of exposure), or 5 days (range 3-9 days, calculated from midpoint of exposure period). The median period from onset of symptoms to admission was 6 days (range 0-9 days)