Epidemiologic Clues to SARS Origin in China

Transcription

1 RESEARCH Epidemiologic Clues to SARS Origin in Chin Rui-Heng Xu,* Jin-Feng He,* Meirion R. Evns, Guo-Wen Peng,* Hume E Field, De-Wen Yu,* Chin-Kei Lee, Hui-Min Luo,* Wei-Sheng Lin,* Peng Lin,* Ling-Hui Li,* Wen-Ji Ling,* Jin-Yn Lin,* nd Aln Schnur# 1 An epidemic of severe cute respirtory syndrome (SARS) begn in Foshn municiplity, Gungdong Province, Chin, in November We studied SARS cse reports through April 30, 2003, including dt from cse investigtions nd cse series nlysis of index cses. A totl of 1,454 cliniclly confirmed cses (nd 55 deths) occurred; the epidemic pek ws in the first week of Februry Helthcre workers ccounted for 24% of cses. Clinicl signs nd symptoms differed between children (<18 yers) nd older persons (>65 yers). Severl observtions support the hypothesis of wild niml origin for SARS. Cses pprently occurred independently in t lest five different municiplities; erly cse-ptients were more likely thn lter ptients to report living ner produce mrket (odds rtio undefined; lower 95% confidence intervl 2.39) but not ner frm; nd 9 (39%) of 23 erly ptients, including 6 who lived or worked in Foshn, were food hndlers with probble niml contct. *Gungdong Province Center for Disese Control nd Prevention, Gungzhou, Chin; University of Wles College of Medicine, Crdiff, United Kingdom; Ntionl Public Helth Service for Wles, Crdiff, United Kingdom; Animl Reserch Institute, Brisbne, Austrli; Austrlin Ntionl University, Cnberr, Austrli; nd #World Helth Orgniztion, Beijing, Chin On Mrch 12, 2003, the World Helth Orgniztion (WHO) issued globl lert bout cses of typicl pneumoni in Gungdong Province nd Hong Kong Specil Administrtive Region, Chin, nd in Vietnm (1). The disese, now known s severe cute respirtory syndrome (SARS), is cused by coronvirus infection (2,3) nd subsequently spred rpidly worldwide. The erliest identified cses of the disese occurred in Gungdong Province in lte 2002 (4). On Jnury 2, 2003, two cses of typicl pneumoni in the city of Heyun, Gungdong Province, were ssocited with trnsmission of infection to severl helthcre workers t the hospitl (5). Investigtion by the Gungdong Provincil Center for Disese Control nd Prevention led to the identifiction of clusters of cses in six other municiplities (Foshn, Jingmen, Zhongshn, Gungzhou, Shenzhen, Zhoqing) from November 2002 to mid- Jnury On Februry 3, 2003, province-wide mndtory cse reporting of typicl pneumoni tht used stndrd cse definition nd reporting form ws instituted. The provincil helth deprtment lso introduced rnge of public helth control mesures, including guidelines on epidemiologic investigtion of cses nd contcts (Februry 3) nd on hospitl dmission, clinicl mngement, nd infection control rrngements for ptients (Februry 9). Subsequently, the deprtment issued guidelines on community prevention nd control, including mndtory home qurntine of contcts (Mrch 27); commenced public service nnouncements bout personl protection nd seeking prompt medicl ttention (Mrch 27); nd introduced free hospitl tretment for ptients with SARS (April 30). Border control mesures were introduced t ll points of entry into the province during mid- April ccording to WHO recommendtion (6). We describe the epidemiology of the SARS epidemic in Gungdong through April 30, 2003, focusing on the observed pttern of spred of disese, the signs nd symptoms, nd the investigtion of erly cses. Methods Study Popultion Gungdong Province hs popultion of 85.2 million, including 9.9 million in Gungzhou city (7). All public helth nd most hospitl services re under the direction of the Helth Bureu of Gungdong Provincil People s Government. The public helth function is performed by one provincil Center for Disese Control nd severl municipl centers, together with network of district nd county centers, ech responsible for popultion of 500,000 1 million. Nerly ll hospitls re operted by the public sector, but ptients re chrged for medicl 1 Drs. Evns, Field, nd Lee were consultnts for the World Helth Orgniztion; they ssisted in its Beijing office Emerging Infectious Diseses Vol. 10, No. 6, June 2004

2 SARS Origin in Chin tretment. Primry helth cre in the province is rudimentry, nd most ptients report directly to hospitl emergency rooms. Dt Sources We nlyzed dt from two sources: the Gungdong surveillnce dtbse nd cse investigtions dtbse. We lso interviewed stff from the Gungdong Provincil Centers for Disese Control, nd Foshn Municipl Center for Disese Control to obtin supplementry informtion on erly-onset cses. Informtion on erly cses in the neighboring Gungxi Province ws obtined from locl investigtors by visiting WHO tem, led by one of the uthors (CKL). Erly cses were defined s those with dte of onset from November 1, 2002, to Jnury 31, 2003, nd lte cses s those with dte of onset from Februry 1 to April 30, Popultion denomintors were obtined from the Gungdong provincil census for 2000 (7). Surveillnce Dtbse Gungdong Provincil Center for Disese Control coordinted the surveillnce dtbse. Erly cses were identified during the course of cse investigtions or fter voluntry reporting by clinicins. Such cses were only included in the dtbse if they conformed to the cse definition subsequently dopted for surveillnce. Since erly Februry 2003, hospitls t ll levels in the helth system were required to report cses of typicl pneumoni (probble SARS) immeditely by telephone to the locl center for disese control, which then forwrded reports electroniclly to the provincil center on the sme dy. The dignostic criteri for reporting were: 1) hving close contct with ptient or hving infected other people, 2) fever (>38 C) nd symptoms of respirtory illness, 3) leukocyte count <10.0 x 10 9 /L, 4) rdiogrphic evidence of infiltrtes consistent with pneumoni or respirtory distress syndrome on chest x-ry, nd 5) no response to ntimicrobil drug tretment (within 72 hours). Ptients were considered to be probble SARS ptients if they meet criteri 1 4 or 2 5 but were excluded if n lterntive dignosis could fully explin their illness. The dtset contins ptient demogrphics, including occuption; dtes of onset, dmission nd report; criteri required for the cse definition; nd detils of lbortory specimens tht were collected. Cse Investigtion Dtbse Contct trcing stff t the district center level dministered stndrd questionnire to ll cse-ptients within 24 hours of reporting. These dt form the bsis of the cse investigtion dtbse nd comprise ptient demogrphics; clinicl fetures on dmission to hospitl; contct history (living with, working with, cring for, or visiting the home of ptient) nd nme, ge, nd ddress detils of contcts; nd exposure risk fctors for community cses (nonhelthcre workers), including trvel history, hospitl visits, niml contct, nd living conditions. Ptients not employed s helthcre workers were clssified s community cse-ptients. Comprisons were mde between fetures of erly-onset nd lte-onset community cses, nd primry (no contct history) nd secondry community cses. Extr informtion ws collected on erly ptients by mens of informl interviews with center stff, which focused on index ptients in ech of the seven municiplities initilly ffected. Dt were prticulrly sought on occuptionl history nd contct networks, nd detiled cse series ws compiled. Dt Anlysis Dt were entered into Excel dtbses (Microsoft, Redmond, WA). Descriptive nlyses were crried out using EpiInfo version 6 (Centers for Disese Control, Atlnt, GA) nd SPSS version 10.0 (SPSS Inc., Chicgo, IL). The surveillnce dtbse ws used for nlysis by ge, sex, occuption, nd clinicl signs nd symptoms. The cse investigtion dtbse ws used for compring erly- nd lte-onset cses nd cses with or without contct history. Incidence rtes were clculted for November 2002 to April For comprisons of signs nd symptoms by ge, younger dults were used s the reference group for both children nd older persons. Chi-squre test or, when pproprite, Fisher exct test ws used for comprison of proportions, Mnn-Whitney test for comprison of continuous vribles, nd chi-squre test for liner trend for nlysis of time trends. We report mximum likelihood estimtes for odds rtios (OR) with exct 95% mid-p confidence intervls (CI) nd consider p < 0.05 to be significnt. Results Surveillnce Dtbse A totl of 1,454 SARS cses were reported in Gungdong Province from November 16, 2002, through April 30, 2003, including 55 deths, crude cse-ftlity rte of 3.8% for ll ges, nd 12.7% in people >65 yers. Two children died: 4-yer-old, previously helthy girl with lobr pneumoni of unknown cuse nd 10-yer-old boy with recent cute heptitis B. The initil phse of the epidemic, November lte Jnury, ws chrcterized by spordic cses followed by shrp rise in lte Jnury nd shrp decline in the first hlf of Februry, nd therefter grdul decline (Figure 1). The epidemic pek occurred t the end of the first week of Februry with pproximtely 55 new cses ech dy. Cses occurred in 15 municiplities in the province but were concentrted in the Perl River delt re (Figure 2A), nd confined lmost exclusively to urbn res, prticulrly the Emerging Infectious Diseses Vol. 10, No. 6, June

3 RESEARCH vriety of nimls were slughtered on the premises), one ws mrket produce buyer for resturnt, nd one ws snke seller in produce mrket (where vriety of live nimls were offered for sle). Six of the food hndlers lived or worked in Shunde (1.7 million popultion), n urbn district of Foshn municiplity, though none could be directly linked to ech other through contct history. Figure 1. Epidemic curve of cses of severe cute respirtory syndrome by dte of onset, November 1, 2002 April 30, 2003, in Gungdong Province, Chin, showing cses in the community nd in helthcre workers. seven municiplities of Foshn, Gungzhou, Heyun, Jingmen, Shenzhen, Zhongshn, nd Zhoqing (locted km from Gungzhou). The highest incidence occurred in Gungzhou city (12.5 cses per 100,000 people) (Figure 2B), nd outbreks pper to hve occurred in different municiplities t vrying stges of the epidemic (Figure 3). Medin ge of ptients ws 35.0 yers (rnge 0 92 yers), nd the highest ge-specific incidence ws in persons yers (3.2 per 100,000 people) (Figure 4); 53.2% of cses were femle. Five deths occurred mong 343 cses in helthcre workers (24% of 1,429 cses for whom occuption is known); 75.1% of helthcre worker cses were in women. The proportion of helthcre worker ptients ws highest in the erly phse of the epidemic (32% with dte of onset in Jnury 2003) nd declined s the epidemic progressed (27% in Februry, 18% in Mrch, nd 17% in April) (Tble 1). Throughout the epidemic, high proportion of community cse-ptients did not report contct history, rnging from 58% in Februry to 74% in April. This proportion ws even higher in children (91% in those <5 yers, 81% in those 5 14 yers) nd in persons >65 yers (82%). Anlysis of occuption sttus, excluding helthcre workers nd cse-ptients with known exposure, shows tht the proportion of cses in students (0% in Jnury 2003 or before; 7% in Februry; 14% in Mrch; 18% in April, p < 0.001) nd housewives (0% in Jnury 2003 or before; 5% in Februry; 14% in Mrch; 15% in April, p < 0.001) incresed s the epidemic progressed (Tble 2). A high proportion (9/23, 39%) of erly cses were food hndlers (this ctegory includes persons who hndle, kill, nd sell food nimls, s well s those who prepre nd serve food), but none were frmers hndling livestock or poultry. Of the nine erly cses in food hndlers, seven were resturnt chefs working in township resturnts (where Cse Investigtion Dtbse Detiled dt from cse investigtion interviews were vilble for 662 (45%) of 1,454 ptients. Medin ge ws 31.0 yers (rnge 0 86 yers), 56% were femle, nd 44% were mle. The signs nd symptoms in dults (18 64 yers) were compred with those in children (<18 yers) nd older persons (>65 yers) (Tbles 3 nd 4). Children were more likely to hve runny nose nd dry cough on physicl exmintion but less likely to hve chills, mlise, hedche, muscle ches, or difficulty brething. Older persons were more likely to report hving sputum nd to hve dry or productive cough on physicl exmintion but less likely to complin of chills, mlise, or sore throt. Nerly Figure 2. Geogrphic distribution of popultion in: (A) urbn districts of Gungzhou city, (B) Gungdong Province nd district-specific incidence of severe cute respirtory syndrome (per 100,000 popultion) Emerging Infectious Diseses Vol. 10, No. 6, June 2004

4 SARS Origin in Chin Figure 3. Timeline of cses of severe cute respirtory syndrome by week of onset, November 1, 2002 April 30, 2003, in the seven predominntly ffected municiplities of Gungdong Province, Chin. ll ptients hd high body temperture (medin 39.0 C, rnge C) lsting in most ptients for 1 to 4 dys (medin 4.0 dys; rnge 1 9 dys). Medin leukocyte count ws 5.8 x 10 9 /L (rnge x 10 9 /L), nd 13.9% of ptients hd leukopeni (<3.5 x 10 9 /L). Older persons hd higher medin leukocyte count thn younger dults (6.6 x 10 9 /L for those >65 yers, 5.6 x 10 9 /L for those yers, p = 0.056), nd fewer hd leukopeni. Comprison of cse ctegories indicte tht community cse-ptients with contct history were more likely to hve visited hospitl in the previous 2 weeks thn ptients without contct history (OR 6.83, 95% CI 2.89 to 16.73) (Tble 5). Ptients without contct history were no more likely to report history of trvel or niml contct. Erly-onset ptients were more likely to live within wlking distnce of produce mrket (n griculturl mrket where live nimls re sold, killed, nd butchered in situ, lso known s wet mrket ) thn lte-onset ptients (OR undefined, lower 95% CI 2.39). Living ner poultry or livestock frm or hving other types of niml contct, including domestic pets or livestock, poultry, or specific wild nimls or birds, ws not ssocited with high risk for SARS. Cse Series of Index Ptients The index ptients in ech of the seven erliest ffected municiplities ll hd dte of onset before Jnury 31, 2003 (Tble 6). In five municiplities (Foshn, Jingmen, Zhongshn, Gungzhou, Shenzhen), outbreks pper to hve occurred independently, but the outbrek in Heyun my be linked to tht in Shenzhen nd the outbrek in Zhoqing to tht in Gungzhou. Index ptients from the eight other municiplities involved in the epidemic hd dte of onset fter Mrch 1, 2003, nd trvel history to n ffected re, so these were excluded from the nlysis. Ptient 1 hd the erliest cse, identified by retrospective cse serching. He lived with his wife nd four children in Foshn city nd becme ill on November 16, He hd not trveled outside Foshn in the 2 weeks before his illness nd hd no contct history, but he hd prepred food including chicken, domestic ct, nd snke. He ws prt of cluster of five ptients, including his wife (42 yers old, onset December 1), 50-yer-old unt who visited him in the hospitl on November 20 (onset November 27), nd the unt s 50-yer-old husbnd (onset November 30) nd 22-yer-old dughter (onset December 4) (online Appendix, Cluster A; vilble from: ncidod/eid/vol10no6/ _pp.htm). None of ptient l s four children were ill. Subsequent clusters in Foshn included food hndler who infected fmily member nd two helthcre workers (online Appendix, Cluster B) nd food hndler who infected severl helthcre workers (online Appendix, Cluster C). Ptient 2 lived in Heyun but worked s resturnt chef in Shenzhen. His work ws minly stir-frying nd did not involve killing nimls. His niml contct history is unknown. He returned to Heyun fter becoming ill, ws dmitted to the locl hospitl nd trnsferred to Gungzhou 2 dys lter. He infected work collegue (41- yer-old mn, onset December 16), six helthcre workers in Heyun (onset December 24 28), nd physicin who Figure 4. Number of ptients with severe cute respirtory syndrome by ge, nd ge-specific incidence (per 10,000 popultion), November 1, 2002 April 30, 2003, Gungdong Province, Chin. Emerging Infectious Diseses Vol. 10, No. 6, June

5 RESEARCH Tble 1. Month of onset of SARS in community cse -ptients nd in helthcre workers, Gungdong, Chin, November 2002 April 2003 Community cse-ptients contct history Month of onset Yes (%) No (%) Helthcre worker (%) Totl b Nov (0) 3 (100) 0 (0) 3 (100) Dec (11) 12 (63) 5 (26) 19 (100) Jn (18) 87 (50) 55 (32) 173 (100) Feb (14) 419 (58) 195 (27) 718 (100) Mr (20) 197 (62) 59 (18) 319 (100) Apr (9) 129 (74) 29 (17) 174 (100) Totl 216 (15) 847 (60) 343 (24) 1,406 (100) SARS, severe cute respirtory syndrome. b Informtion ws not vilble on contct history for 48 cses. ccompnied him in the mbulnce from Heyun to Gungzhou (28-yer-old mn, onset December 25). Ptient 3, from Jingmen, hd no contct history, no history of niml contct, nd no known forwrd trnsmission. Ptient 4 worked s chef in Zhongshn township resturnt, where he prepred stemed dishes nd hd contct with snkes, civet cts, foxes, nd rts. He infected his 30-yerold wife (onset Jnury 3), 39-yer-old mle friend who visited him in the hospitl (onset Jnury 5), nd physicin (35-yer-old mn, onset Jnury 4). Ptient 4 ws one of two ptients responsible for infecting t lest three helthcre workers (onset Jnury 4 7). Ptient 5, from Gungzhou, hd no history of niml contct other thn with pet guine pig tht died month before his symptoms begn. He infected hospitl intern (onset Jnury 14) nd six other helthcre workers (onset Jnury 14 22) t Gungdong Trditionl Chinese Medicine Hospitl. Ptient 6, from Shenzhen, hd visited Hong Kong on Jnury 14, the dy before symptom onset. However, he hd no contct history or contct with nimls. He infected work collegue (43-yer-old mn, onset Jnury 29) nd died 14 dys fter becoming ill. Ptient 7, from Zhoqing, ws the only femle index cse. She trveled to Gungzhou 2 weeks before becoming ill, lthough she could not recollect contct with nyone with symptoms of SARS. She worked t mrket but did not sell nimls. She infected her 16-yer-old son (onset Februry 3) nd physicin (25-yer-old womn, onset Jnury 31). The index ptient in the neighboring province of Gungxi ws 26-yer-old mn, who infected severl fmily members. He worked s driver for wild niml deler nd returned home to Gungxi fter becoming ill on Jnury 8, The deler supplied Gungdong mrkets with wild nimls from Gungxi, other Chinese provinces, nd Vietnm. Discussion The epidemic of typicl pneumoni in Gungdong Province tht we describe bers ll the hllmrks of SARS (8 11). It demonstrtes the typicl time course of the epidemic, the prepondernce of cses in urbn res, nd the epidemiologic nd clinicl fetures of the disese. Since the SARS epidemic begn in Gungdong, we hve sought epidemiologic clues bout the origin of the disese. Approximtely 75% of emerging infectious diseses re zoonotic (12), nd evidence is ccumulting tht n niml origin for SARS is probble. However, phylogenetic nlysis nd sequence comprisons of the coronvirus tht cuses SARS (SARS-CoV) indicte tht the virus is not closely relted to ny of the previously chrcterized humn or niml coronviruses (13). The reservoir is still unknown, but SARS-CoV hs been isolted from Himlyn plm civets (Pgum lrvt), nd evidence of infection hs been found in rccoon dog (Nyctereutes procyonoides), Chinese ferret-bdger (Melogle moscht), nd humns working t live niml mrket in Tble 2. SARS cses (%) by month of onset nd occuptionl sttus, Gungdong, Chin, November 2002 April 2003 Occuptionl sttus b Jn 2003 or before no. (%) Feb 2003 (%) Mr 2003 (%) Apr 2003 (%) Totl (%) Retired 2 (9) 44 (10) 46 (23) 32 (16) 124 (15) Worker 2 (9) 40 (9) 28 (14) 22 (11) 92 (11) Student 0 (0) 29 (7) 28 (14) 34 (18) 91 (11) Civil servnt 3 (13) 43 (10) 26 (13) 19 (10) 91 (11) Housewife 0 (0) 20 (5) 28 (14) 30 (15) 78 (9) Food industry worker 9 (39) 20 (5) 4 (2) 19 (10) 52 (6) Frmer 1 (4) 10 (2) 4 (2) 4 (2) 19 (2) Techer 1 (4) 7 (2) 6 (3) 4 (2) 18 (2) Child 0 (0) 9 (2) 4 (2) 4 (2) 17 (2) Other 2 (9) 49 (11) 14 (7) 18 (9) 83 (10) Unknown 3 (13) 157 (37) 14 (7) 8 (4) 182 (21) Totl 23 (100) 428 (100) 202 (100) 194 (100) 847 (100) SARS, severe cute respirtory syndrome. b Excluding helthcre workers or cse-ptients with known exposure Emerging Infectious Diseses Vol. 10, No. 6, June 2004

6 SARS Origin in Chin Tble 3. Prevlence (%) of symptoms on dmission to hospitl, SARS ptients, Gungdong, Chin, November 2002 April 2003 Symptoms All (n = 662) Adults (18 64 y) (n = 534) Children (<18 y) (n = 51) OR (95% CI) p Older persons (> 65 y) (n = 66) OR (95% CI) p Fever (0.2 to 29.3) (0.3 to 37.9) Chills (0.2 to 0.7) (0.3 to 0.8) Mlise (0.2 to 0.7) (0.3 to 1.0) Hedche (0.2 to 0.9) (0.4 to 1.3) Muscle che (0.0 to 0.3) < (0.2 to 0.7) Cough (1.1 to 4.9) (1.1 to 3.8) 0.05 Sputum (0.9 to 3.3) (1.1 to 3.1) 0.03 Sore throt (0.6 to 2.0) (0.1 to 0.8) 0.04 Runny nose (1.1 to 5.7) (0.4 to 2.8) Brething (0.1 to 0.8) (1 to 3.0) 0.05 difficulty Nuse (0.1 to 1.8) (0.3 to 2.0) Vomiting (0.4 to 3.7) (0.4 to 3.3) Dirrhe (0.3 to 2.3) (0.3 to 2.2) SARS, severe cute respirtory syndrome; OR, odds rtio, using dults s the reference group; CI, confidence intervl. Shenzen municiplity (14). Seroprevlence of immunoglobulin (Ig) G ntibody to SARS-CoV is substntilly higher mong trders of live nimls (13.0%) in Gungzhou municiplity thn mong helthy controls (1.2%), nd the highest prevlence of ntibody is mong those who trded primrily msked plm civets (72.7%) (15). The pttern of the Gungdong epidemic is consistent with the clssicl process of emergence from n niml reservoir: the initil introduction of the virus into nonimmune humn popultion followed by the estblishment nd rpid dissemintion of infection (16). The trditionl prctice of using wildlife for food nd medicine, still observed by some persons in southern Chin, offers n effective bridge from nturl niml host to humns. Severl observtions support this hypothesis. Two of the seven index ptients were resturnt chefs; food hndlers (who hndle, kill, or butcher nimls) were overrepresented mong erly-onset cses with no contct history (including the first reported deth, in snke seller); nd ptients with erly onset were more likely thn ptients with lte onset to live ner n griculturl produce mrket (where live wild nimls re generlly offered for sle). However, none of the erly ptients were commercil frmers nor ws living ner frm ssocited with incresed risk, findings tht suggest wild niml rther thn livestock or poultry source. Although trde in wildlife is now illegl in Chin, rnge of mmmlin, vin, nd reptile species cn still be found in some produce mrkets, nd blck mrket in these species probbly exists. Mny such nimls come from outside Gungdong Province, often through Gungxi Province to the west, nd my originte in Vietnm or other prts of Southest Asi. The observtion tht the index ptient in Gungxi Province ws wild niml trder who supplied Gungdong mrkets offers some circumstntil evidence for such link. Our dt hve severl limittions. First, surveillnce for SARS ws only estblished in Februry 2003; thus, informtion on erlier cses ws collected retrospectively nd will be influenced by reporting bis. Second, our nlysis is bsed on cses tht re not lbortory confirmed. Thus, the dignosis relies on clinicl cse definition nd the sensitivity nd specificity re unknown. Third, Tble 4. Prevlence (%) of physicl signs, chest x -ry findings, nd blood count bnormlities on dmission to hospitl, SARS ptients, Gungdong, Chin, November 2002 April 2003 All (n = 662) Adults (18 64 y) (n = 534) Children (<18 y) (n = 51) OR b (95% CI) p Older persons (>65 y) (n = 66) OR b (95% CI) p Vrible Physicl signs Temperture (>38 C) (0.3 to 3.9) (0.1 to 1.2) Rigors (0.2 to 1.3) (0.2 to 1.2) Lethrgy (0.0 to 0.8) (0.1 to 1.1) Mylgi (0.0 to 1.2) (0.0 to 0.6) Cough (1.9 to 3.9) (1.4 to 4.3) Sputum (0.7 to 3.8) (1.8 to 6.4) <0.001 Dyspne (0.0 to 1.8) (0.9 to 4.5) Clinicl test results Abnorml chest x-ry (0.4 to 1.8) (0.4 to 2.0) Leukopeni (<3.5x10 9 /L) (0.5 to 2.7) (0.2 to 1.5) OR, odds rtio; CI, confidence intervl. b Using dults s the reference group. Emerging Infectious Diseses Vol. 10, No. 6, June

7 RESEARCH Tble 5. Cse-cse comprisons of community SARS ptients, Gungdong, Chin, November 2002 April 2003, ccording to contct history nd onset dte No contct history (n = 406) Contct history (n = 103 ) Exposure Erly onset b (n = 19) c Lte onset b (n = 387) c (in previous 2 weeks) Yes No Yes No OR (95% CI) Yes No Yes No OR (95% CI) Visited hospitl (2.89 to 6.73) (0.00 to 1.36) Visited by friend (0.04 to 8.93) (0.00 to 337) Regulr hnd wshing (0.53 to 8.10) (0.06 to 12.55) Trvel history (0.41 to 1.63) (0.00 to 1.36) Animl contct (0.80 to 3.25) (0.09 to 23.02) Visited produce mrket (0.02 to 2.75) (0.00 to 148) Lives ner produce mrket (0.45 to 1.52) Undef. (2.39 to Undef.) Lives ner poultry or livestock frm (0.42 to 8.81) (0.00 to 40.15) SARS, severe cute respirtory syndrome; CI, confidence intervl; OR, odds rtio. b Defined s November 1, 2002 Jnury 31, 2003 for erly onset; Februry 1, 2003 April 30, 2003 for lte onset. c Cses with no contct history nd for whom cse investigtion dt re vilble. cse investigtion dt were only vilble on pproximtely hlf of ll cses becuse of poor trnsfer of dt (regrdless, ll ctegories of cses nd ll reporting districts were similrly ffected). Finlly, informtion on severl erlier cses ws incomplete or my be unrelible (becuse of fer of prosecution ssocited with the trde in wild nimls), nd some persons re no longer trceble. The dt lso highlight severl unnswered questions. The SARS epidemic strted in Gungdong, but how it begn, why it peked so suddenly, why Gungzhou ws so bdly ffected nd other cities spred, nd wht cused the grdul decline re ll uncler. The decline in the epidemic is probbly result of hospitl nd community infection control mesures introduced in erly Februry, including strict isoltion of ptients, use of protective equipment by helthcre workers, prohibition of hospitl visitors, nd guidelines on epidemiologic investigtion. Such mesures my lso explin why lter cses did not trigger such extensive chins of trnsmission. The concentrtion of cses in urbn res my be due to fctors ssocited with ccess to helthcre or to incomplete or poor surveillnce in rurl res. However, in Gungdong Province, emphsis ws plced on reporting from less developed prefectures nd rurl res, including supervisory visits nd review of hospitl records. Mny lrger cities in Gungdong, s well s rurl res, were lso pprently spred by the epidemic. Although the possibility tht SARS my pre-dte the erliest known cse cnnot be excluded, the temporl nd sptil clustering of index cses described in the cse series suggests tht the initil source of the Gungdong epidemic ws either single point source (with the links between cities not identified) or severl point sources in the Perl River bsin. Outbreks in cities ffected lter in the epidemic cn ll be trced to n imported cse. These lter cses re probbly due to horizontl trnsmission rther thn to further contct with the initil source. The reson for the sudden rise in the incidence of cses t the beginning of Februry is uncler, lthough the rise coincides with the dmission of highly infectious index ptient who trnsmitted SARS to helthcre workers t three different hospitls in Gungzhou city nd to lrge number of fmily members (5,17). The bsence of such trigger my explin the much smller outbreks in other cities in the province. The cse-ftlity rte in Gungdong ws lso lower thn documented elsewhere (11,18). The most likely explntion for this lower rte is the younger ge structure of the popultion in minlnd Chin compred to tht of Hong Kong, Tiwn, or Cnd. Children hve slightly different initil signs nd symptoms thn dults perhps becuse symptoms re milder (19), children re less ble to describe their symptoms, or the cse definition is less specific in this ge group. Older persons re more likely to hve Tble 6. Cse series of index cses by municiplity in SARS epidemic, Gungdong, Chin, November 2002 April 2003 Secondry Cse no. City Sex Age Occuption Dte of onset Animl contct trnsmission Cse 1 Foshn M 45 Administrtor nd Nov 16, 2002 Yes Yes villge leder Cse 2 Heyun M 34 Resturnt chef Dec 10, 2002 Unknown Yes Cse 3 Jingmen M 26 Fctory worker Dec 21, 2002 No No Cse 4 Zhongshn M 30 Resturnt chef Dec 26, 2002 Yes Yes Cse 5 Gungzhou M 49 Office worker Jn 2, 2003 No Yes Cse 6 Shenzhen M 46 Office worker Jn 15, 2003 No Yes Cse 7 Zhoqing F 39 Mrket vendor Jn 17, 2003 Probbly Yes SARS, severe cute respirtory syndrome; M, mle; F, femle Emerging Infectious Diseses Vol. 10, No. 6, June 2004

8 SARS Origin in Chin productive cough nd difficulty brething thn younger dults, which suggests either misdignosis or n underlying chest disese. The high proportion of community cse-ptients with no pprent contct history, especilly in Gungzhou city, my be due to indequte trcing, poor reporting of the results of contct investigtion, symptomtic trnsmission, or the nonspecificity of the clinicl cse definition. Similr findings hve been observed in Beijing (20). Little evidence s yet exists for symptomtic infection with SARS, but seroprevlence studies will help determine whether this occurs. Lbortory testing of stored clinicl specimens my lso clrify the specificity of the cse definition, prticulrly if positivity rtes vry during different stges of the epidemic or in cses with no contct history. An lterntive explntion for the bsence of contct history is the continuing existence of n environmentl source; however, this explntion is not borne out by cse investigtion dt. Clrifying this fctor is importnt not only to help understnd the trnsmission dynmics of SARS but lso to lly concerns bout the risk for epidemic spred in the community if SARS is reintroduced. Resolving this issue will be vitl to prospects for preventing the spred of SARS beyond Chin (21). Acknowledgments We thnk Y-Y Liu, Z-H Deng, H-Z Zheng, X-F Yi, M Wng, nd R-H Zhou for their ssistnce with dt colltion nd entry, together with ll our collegues t the district, county nd prefecture centers for disese control in Gungdong, who undertook most of the cse investigtion; ll the frontline helth workers who re cring for ptients with SARS; the World Helth Orgniztion for rrnging two expert tem visits to Gungdong Province in April nd My 2003 to provide dvice nd support; nd the Ministry of Helth, Beijing, nd Gungdong Provincil Helth Bureu for fcilitting these visits. Reserch funding ws received from the Gungdong Committee for the Control of SARS. Dr. Xu Rui-Heng is n epidemiologist nd deputy director of the Gungdong Province Center for Disese Control nd Prevention. He coordintes the provincil communicble disese surveillnce network nd hs reserch interests in the epidemiology of communicble diseses. References 1. World Helth Orgniztion. WHO issues globl lert bout cses of typicl pneumoni: cses of severe respirtory illness my spred to hospitl stff. Genev: The Orgniztion; Mrch 12, 2003 [Accessed Jnury ]. Avilble from: rchive/2003_03_12/en/ 2. Ksizek TG, Erdmn D, Goldsmith CS, Zki SR, Peret T, Emery S, et l. A novel coronvirus ssocited with severe cute respirtory syndrome. N Engl J Med. 2003;348: Drosten C, Gunther S, Preiser W, vn der Werf S, Brodt HR, Becker S, et l. Identifiction of novel coronvirus in ptients with severe cute respirtory syndrome. N Engl J Med. 2003;348: Rosling L, Rosling M. Pneumoni cuses pnic in Gungdong province. BMJ. 2003;326: Zhong NS, Zheng BJ, Li YM, Poon LLM, Xie ZH, Chn KH, et l. 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Epidemiologicl determinnts of spred of cusl gent of severe cute respirtory syndrome in Hong Kong. Lncet. 2003;361: Tylor LH, Lthm SM, Woolhouse MEJ. Risk fctors for humn disese emergence. Philos Trns R Soc Lond B Biol Sci. 2001;356: Rot PA, Oberste MS, Monroe SS, Nix WA, Cmpgnoli R, Icenogle JP, et l. Chrcteriztion of novel coronvirus ssocited with severe cute respirtory syndrome. Science. 2003;300: Gun Y, Zheng BJ, He QY, Liu XL, Zhung ZX, Cheung CL, et l. Isoltion nd chrcteriztion of viruses relted to the SARS coronvirus from nimls in Southern Chin. Science. 2003;302; Centers for Disese Control nd Prevention. Prevlence of IgG ntibody to SARS-ssocited coronvirus in niml trders Gungdong Province. MMWR Morb Mortl Wkly Rep. 2003;52: Morse SS. Fctors in the emergence of infectious diseses. Emerg Infect Dis. 1995;1: Zho Z, Zhng F, Xu M, Hung K, Zhong W, Ci W, et l. Description nd clinicl tretment of n erly outbrek of severe cute respirtory syndrome in Gungzhou, PR Chin. J Med Microbiol. 2003;52: Glvni AP, Lei X, Jewell NP. Severe cute respirtory syndrome: temporl stbility nd geogrphic vrition in cse-ftlity rtes nd doubling times. Emerg Infect Dis. 2003;9: Hon KLE, Leung CW, Cheng WFT. Clinicl presenttions nd outcome of severe cute respirtory syndrome in children. Lncet. 2003;361: Ling W, Zhu Z, Guo J, Liu Z, He X, Zhou W, et l. Severe cute respirtory syndrome, Beijing Emerg Infect Dis. 2004;10: Breimn RF, Evns MR, Preiser W, Mguire J, Schnur A, Li A, et l. Role of Chin in the quest to define nd control SARS. Emerg Infect Dis. 2003;9: Address for correspondence: Meirion Evns, Communicble Disese Surveillnce Centre, Ntionl Public Helth Service for Wles, Abton House, Crdiff CF14 3QX, UK; fx: ; emil: meirion.evns@nphs.wles.nhs.uk Emerging Infectious Diseses Vol. 10, No. 6, June