RESEARCH Epidemiologic Clues to SARS Origin in China Rui-Heng Xu,* Jian-Feng He,* Meirion R. Evans,†‡ Guo-Wen Peng,* Hume E Field,§ De-Wen Yu,* Chin-Kei Lee,¶ Hui-Min Luo,* Wei-Sheng Lin,* Peng Lin,* Ling-Hui Li,* Wen-Jia Liang,* Jin-Yan Lin,* and Alan Schnur#1 An epidemic of severe acute respiratory syndrome ipalities (Foshan, Jiangmen, Zhongshan, Guangzhou, (SARS) began in Foshan municipality, Guangdong Shenzhen, Zhaoqing) from November 2002 to mid- Province, China, in November 2002. We studied SARS January 2003. On February 3, 2003, province-wide case reports through April 30, 2003, including data from mandatory case reporting of atypical pneumonia that used case investigations and a case series analysis of index a standard case definition and reporting form was institut- cases. A total of 1,454 clinically confirmed cases (and 55 deaths) occurred; the epidemic peak was in the first week ed. The provincial health department also introduced a of February 2003. Healthcare workers accounted for 24% range of public health control measures, including guide- of cases. Clinical signs and symptoms differed between lines on epidemiologic investigation of cases and contacts children (<18 years) and older persons (>65 years). (February 3) and on hospital admission, clinical manage- Several observations support the hypothesis of a wild ani- ment, and infection control arrangements for patients mal origin for SARS. Cases apparently occurred independ- (February 9). Subsequently, the department issued guide- ently in at least five different municipalities; early lines on community prevention and control, including case-patients were more likely than later patients to report mandatory home quarantine of contacts (March 27); com- living near a produce market (odds ratio undefined; lower menced public service announcements about personal pro- 95% confidence interval 2.39) but not near a farm; and 9 (39%) of 23 early patients, including 6 who lived or worked tection and seeking prompt medical attention (March 27); in Foshan, were food handlers with probable animal con- and introduced free hospital treatment for patients with tact. SARS (April 30). Border control measures were intro- duced at all points of entry into the province during mid- April according to WHO recommendation (6). We n March 12, 2003, the World Health Organization describe the epidemiology of the SARS epidemic in O(WHO) issued a global alert about cases of atypical Guangdong through April 30, 2003, focusing on the pneumonia in Guangdong Province and Hong Kong observed pattern of spread of disease, the signs and symp- Special Administrative Region, China, and in Vietnam (1). toms, and the investigation of early cases. The disease, now known as severe acute respiratory syn- drome (SARS), is caused by coronavirus infection (2,3) Methods and subsequently spread rapidly worldwide. The earliest identified cases of the disease occurred in Guangdong Study Population Province in late 2002 (4). Guangdong Province has a population of 85.2 million, On January 2, 2003, two cases of atypical pneumonia in including 9.9 million in Guangzhou city (7). All public the city of Heyuan, Guangdong Province, were associated health and most hospital services are under the direction of with transmission of infection to several healthcare work- the Health Bureau of Guangdong Provincial People’s ers at the hospital (5). Investigation by the Guangdong Government. The public health function is performed by Provincial Center for Disease Control and Prevention led one provincial Center for Disease Control and several to the identification of clusters of cases in six other munic- municipal centers, together with a network of district and county centers, each responsible for a population of *Guangdong Province Center for Disease Control and Prevention, 500,000–1 million. Nearly all hospitals are operated by Guangzhou, China; †University of Wales College of Medicine, the public sector, but patients are charged for medical Cardiff, United Kingdom; ‡National Public Health Service for Wales, Cardiff, United Kingdom; §Animal Research Institute, Brisbane, Australia; ¶Australian National University, Canberra, 1Drs. Evans, Field, and Lee were consultants for the World Health Australia; and #World Health Organization, Beijing, China Organization; they assisted in its Beijing office. 1030 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 10, No. 6, June 2004 SARS Origin in China treatment. Primary health care in the province is rudimen- and exposure risk factors for community cases (non- tary, and most patients report directly to hospital emer- healthcare workers), including travel history, hospital vis- gency rooms. its, animal contact, and living conditions. Patients not employed as healthcare workers were classified as com- Data Sources munity case-patients. Comparisons were made between We analyzed data from two sources: the Guangdong sur- features of early-onset and late-onset community cases, veillance database and a case investigations database. We and primary (no contact history) and secondary communi- also interviewed staff from the Guangdong Provincial ty cases. Extra information was collected on early patients Centers for Disease Control, and Foshan Municipal Center by means of informal interviews with center staff, which for Disease Control to obtain supplementary information on focused on index patients in each of the seven municipali- early-onset cases. Information on early cases in the neigh- ties initially affected. Data were particularly sought on boring Guangxi Province was obtained from local investi- occupational history and contact networks, and a detailed gators by a visiting WHO team, led by one of the authors case series was compiled. (CKL). Early cases were defined as those with a date of onset from November 1, 2002, to January 31, 2003, and late Data Analysis cases as those with a date of onset from February 1 to April Data were entered into Excel databases (Microsoft, 30, 2003. Population denominators were obtained from the Redmond, WA). Descriptive analyses were carried out Guangdong provincial census for 2000 (7). using EpiInfo version 6 (Centers for Disease Control, Atlanta, GA) and SPSS version 10.0 (SPSS Inc., Chicago, Surveillance Database IL). The surveillance database was used for analysis by age, Guangdong Provincial Center for Disease Control coor- sex, occupation, and clinical signs and symptoms. The case dinated the surveillance database. Early cases were identi- investigation database was used for comparing early- and fied during the course of case investigations or after late-onset cases and cases with or without a contact history. voluntary reporting by clinicians. Such cases were only Incidence rates were calculated for November 2002 to April included in the database if they conformed to the case def- 2003. For comparisons of signs and symptoms by age, inition subsequently adopted for surveillance. Since early younger adults were used as the reference group for both February 2003, hospitals at all levels in the health system children and older persons. Chi-square test or, when appro- were required to report cases of atypical pneumonia (prob- priate, Fisher exact test was used for comparison of propor- able SARS) immediately by telephone to the local center tions, Mann-Whitney test for comparison of continuous for disease control, which then forwarded reports electron- variables, and chi-square test for linear trend for analysis of ically to the provincial center on the same day. The diag- time trends. We report maximum likelihood estimates for nostic criteria for reporting were: 1) having close contact odds ratios (OR) with exact 95% mid-p confidence inter- with a patient or having infected other people, 2) fever vals (CI) and consider p < 0.05 to be significant. (>38°C) and symptoms of respiratory illness, 3) leukocyte count <10.0 x 109/L, 4) radiographic evidence of infiltrates Results consistent with pneumonia or respiratory distress syndrome on chest x-ray, and 5) no response to antimicrobial drug Surveillance Database treatment (within 72 hours). Patients were considered to be A total of 1,454 SARS cases were reported in probable SARS patients if they meet criteria 1–4 or 2–5 but Guangdong Province from November 16, 2002, through were excluded if an alternative diagnosis could fully April 30, 2003, including 55 deaths, a crude case-fatality explain their illness. The dataset contains patient demo- rate of 3.8% for all ages, and 12.7% in people >65 years. graphics, including occupation; dates of onset, admission Two children died: a 4-year-old, previously healthy girl and report; criteria required for the case definition; and with lobar pneumonia of unknown cause and a 10-year-old details of laboratory specimens that were collected. boy with recent acute hepatitis B. The initial phase of the epidemic, November–late Case Investigation Database January, was characterized by sporadic cases followed by a Contact tracing staff at the district center level adminis- sharp rise in late January and a sharp decline in the first half tered a standard questionnaire to all case-patients within 24 of February, and thereafter a gradual decline (Figure 1). The hours of reporting. These data form the basis of the case epidemic peak occurred at the end of the first week of investigation database and comprise patient demographics; February with approximately 55 new cases each day. Cases clinical features on admission to hospital; contact history occurred in 15 municipalities in