SARS: 1918 Revisited? The Urgent Need for Global Collaboration in Public Health

Abstract

Humanity has but three great enemies: fever, famine and war; of these by far the greatest, by far the most terrible, is fever. Sir William Osler Humanity has been profoundly affected by plagues since the dawn of recorded history. The mother of all plagues, the Black Death, killed more than one third of the population of Europe in the 14th century.1Gottfried RS The Black Death: Natural and Unnatural Human Disaster in Medieval Europe. Free Press, New York, NY1983Google Scholar In more recent times, the great influenza epidemic of 1918, which had an inexplicably devastating mortality in persons between the ages of 20 and 40 years,2Pyle GF The Diffusion of Influenza: Patterns and Paradigms. Rowman & Littlefield, Totowa, NJ1986Google Scholar claimed the lives of 4 times as many soldiers as died on the battlefields of France at the height of World War I, and 25 to 50 million persons worldwide died of H1N1 influenza A.2Pyle GF The Diffusion of Influenza: Patterns and Paradigms. Rowman & Littlefield, Totowa, NJ1986Google Scholar, 3Crosby AW America's Forgotten Pandemic: The Influenza of 1918. Cambridge University Press, Cambridge, England1989Google Scholar The world now faces a new apocalyptic horseman, severe acute respiratory syndrome (SARS), caused by a new human coronavirus (SARS-CoV). Genetic evidence suggests that SARS-CoV is a human-animal recombinant4Peiris JSM Lai ST Poon LL SARS study group et al.Coronavirus as a possible cause of severe acute respiratory syndrome.Lancet. 2003; 361: 1319-1325Abstract Full Text Full Text PDF PubMed Scopus (2361) Google Scholar, 5Ksiazek TG Erdman D Goldsmith CS SARS Working Group et al.A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1953-1966Crossref PubMed Scopus (3375) Google Scholar, 6Drosten C Günther S Preiser W et al.Identification of a novel coronavirus in patients with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1967-1976Crossref PubMed Scopus (3455) Google Scholar, 7Ruan Y Wei CL Ling AE et al.Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4454web.pdfDate: May 2003Google Scholar that made the leap, possibly from a civet or other smaller mammal, to humans in Guangdong Province, southern China.7Ruan Y Wei CL Ling AE et al.Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4454web.pdfDate: May 2003Google Scholar Between November 2002 and June 5, 2003, 8402 persons worldwide have acquired SARS, the vast majority in China (5329 infected; 334 deaths), Taiwan (678; 81), Hong Kong (1748; 283), Singapore (206; 31), Vietnam (63; 5), or Toronto, Canada (216; 31).8World Health Organization Cumulative number of reported probable cases of SARS.Available at: www.who.int/csr/sars/country/2003_06_04/en/print.htmlGoogle Scholar In keeping with its infamous historical predecessors, SARS has resulted in the deaths of 12% of patients with this disease,8World Health Organization Cumulative number of reported probable cases of SARS.Available at: www.who.int/csr/sars/country/2003_06_04/en/print.htmlGoogle Scholar many in some of the most advanced hospitals in the world.9Lee N Hui D Wu A et al.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1986-1994Available at: www.nejm.orgCrossref PubMed Scopus (1894) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 12Booth CM Matukas LM Tomlinson GA et al.Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.JAMA. 2003; 289 (Accessibility verified June 4, 2003.): 2801-2809Available at: http://jama.ama-assn.org/cgi/search?fulltext=greater+toronto+areaCrossref PubMed Scopus (1112) Google Scholar Mortality in persons older than 60 years has exceeded 40%.13Donnelly CA Ghani AC Leung GM et al.Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4453web.pdfDate: May 2003Google Scholar SARS, which produces an unusually severe form of atypical pneumonia, is only the latest in a growing list of emerging infectious diseases detected and characterized since 1977, including legionnaires' disease; Clostridium difficile antibiotic-associated colitis; toxic shock syndrome caused by unique strains of Staphylococcus aureus or Streptococcus pyogenes; hemolytic uremic syndrome and thrombotic thrombocytopenic purpura deriving from food-borne infection caused by Escherichia coli O157:H7; human immunodeficiency virus infection and acquired immunodeficiency syndrome (AIDS); the blurring spectrum of human and animal prion diseases-Creutzfeld-Jakob disease, bovine spongiform encephalopathy, and chronic wasting disease of cervids; and in North America, Hantavirus pneumonitis and West Nile encephalitis. It has become clear that a large and highly developed country such as the United States not only has a powerful self-interest but also a moral obligation to invest in a world-class communicable disease center, such as the Centers for Disease Control and Prevention, to be able to detect and characterize new infectious diseases and contain their spread. The importance and impact of nationally funded organizations of excellence, staffed by the best and brightest and working in global concert with other like-minded organizations, also cannot be overstated. SARS was recognized as a distinct new infectious disease syndrome by Dr Carlo Urbani on February 28, 2003; the viral causation was identified and confirmed by scientists around the world within a month.4Peiris JSM Lai ST Poon LL SARS study group et al.Coronavirus as a possible cause of severe acute respiratory syndrome.Lancet. 2003; 361: 1319-1325Abstract Full Text Full Text PDF PubMed Scopus (2361) Google Scholar, 5Ksiazek TG Erdman D Goldsmith CS SARS Working Group et al.A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1953-1966Crossref PubMed Scopus (3375) Google Scholar, 6Drosten C Günther S Preiser W et al.Identification of a novel coronavirus in patients with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1967-1976Crossref PubMed Scopus (3455) Google Scholar International scientific collaboration, championed by epidemiologists and virologists at the World Health Organization, the US Centers for Disease Control and Prevention, and centers in Singapore, Hong Kong, Canada, and Germany, has been unprecedented14World Health Organization A multicentre collaboration to investigate the cause of severe acute respiratory syndrome.Lancet. 2003; 361: 1730-1733Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 15Gerberding JL Faster…but fast enough? responding to the epidemic of severe acute respiratory syndrome [editorial].N Engl J Med. 2003; 348: 2030-2031Crossref PubMed Scopus (88) Google Scholar and has led to containment of SARS in most of the affected countries, particularly Vietnam, Singapore, and Hong Kong, at the time this editorial was written.8World Health Organization Cumulative number of reported probable cases of SARS.Available at: www.who.int/csr/sars/country/2003_06_04/en/print.htmlGoogle Scholar, 16World Health Organization Update 73 - No new deaths, but vigilance needed for imported cases.Available at: www.who.int/csr/don/2003_06_04/en/print.htmlDate: June 4, 2003Google Scholar SARS is unique among the numerous types of community-acquired pneumonia: (1) it has a prohibitive mortality, considerably higher than most other viral or bacterial community-acquired pneumonias, with the exception of pneumonitis caused by Legionella pneumophila or Hantavirus; (2) mortality has been high in adults, especially those older than 60 years, but clinical disease has been uncommon and mild in children17Hon KLE Leung CW Cheng WTF et al.Clinical presentations and outcome of severe acute respiratory syndrome in children. Lancet [serial online].Available at: http://image.thelancet.com/extras/03let4127web.pdfDate: April 2003Google Scholar; (3) early microbiologic confirmation of SARS has been difficult because the virus is hard to culture in vitro, conventional DNA/RNA detection techniques such as reverse-transcriptase polymerase chain reaction have been relatively insensitive in the early phase of infection,4Peiris JSM Lai ST Poon LL SARS study group et al.Coronavirus as a possible cause of severe acute respiratory syndrome.Lancet. 2003; 361: 1319-1325Abstract Full Text Full Text PDF PubMed Scopus (2361) Google Scholar, 5Ksiazek TG Erdman D Goldsmith CS SARS Working Group et al.A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1953-1966Crossref PubMed Scopus (3375) Google Scholar, 6Drosten C Günther S Preiser W et al.Identification of a novel coronavirus in patients with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1967-1976Crossref PubMed Scopus (3455) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 12Booth CM Matukas LM Tomlinson GA et al.Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.JAMA. 2003; 289 (Accessibility verified June 4, 2003.): 2801-2809Available at: http://jama.ama-assn.org/cgi/search?fulltext=greater+toronto+areaCrossref PubMed Scopus (1112) Google Scholar and seroconversion, which ultimately occurs in nearly all infected individuals, takes up to 20 days11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar; (4) SARS can be extraordinarily contagious,18Centers for Disease Control and Prevention Severe acute respiratory syndrome—Singapore, 2003.MMWR Morb Mortal Wkly Rep. 2003; 52: 405-411PubMed Google Scholar, 19Centers for Disease Control and Prevention Severe acute respiratory syndrome—Taiwan, 2003.MMWR Morb Mortal Wkly Rep. 2003; 52: 461-466PubMed Google Scholar with more than one half of the early cases involving health care workers9Lee N Hui D Wu A et al.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1986-1994Available at: www.nejm.orgCrossref PubMed Scopus (1894) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 12Booth CM Matukas LM Tomlinson GA et al.Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.JAMA. 2003; 289 (Accessibility verified June 4, 2003.): 2801-2809Available at: http://jama.ama-assn.org/cgi/search?fulltext=greater+toronto+areaCrossref PubMed Scopus (1112) Google Scholar; (5) the incubation period of SARS (mean, 6.4 days13Donnelly CA Ghani AC Leung GM et al.Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4453web.pdfDate: May 2003Google Scholar) is much longer than that for other respiratory viruses, and it appears that infected persons are not contagious until they become symptomatic; and (6) most cases probably become infected by droplet spread20Seto WH Tsang D Yung RW Expert SARS Group of Hospital Authority et al.Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS).Lancet. 2003; 361: 1519-1520Abstract Full Text Full Text PDF PubMed Scopus (683) Google Scholar (<10μM respiratory particles inhaled within 2 m of the source), but SARS-CoV can survive for hours on environmental surfaces,21World Health Organization First data on stability and resistance of SARS coronavirus compiled by members of WHO laboratory network.Available at: www.who.int/csr/sars/survival_2003_05_04/enGoogle Scholar and, at least in theory, there appears to be potential for contact transmission and even fecal-oral spread.9Lee N Hui D Wu A et al.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1986-1994Available at: www.nejm.orgCrossref PubMed Scopus (1894) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 19Centers for Disease Control and Prevention Severe acute respiratory syndrome—Taiwan, 2003.MMWR Morb Mortal Wkly Rep. 2003; 52: 461-466PubMed Google Scholar, 22Hong Kong Department of Health Report Main findings of an investigation into the outbreak of severe acute respiratory syndrome at Amoy Gardens.Available at: www.info.gov.hk/dh/ap.htmGoogle Scholar In this issue of the Mayo Clinic Proceedings, Sampathkumar et al23Sampathkumar P Temesgen Z Smith TF Thompson RL SARS: epidemiology, clinical presentation, management, and infection control measures.Mayo Clin Proc. 2003; 78: 882-890Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar provide a succinct review of SARS and a valuable primer for clinicians and infection control practitioners. Although clinical features of SARS are nonspecific, with near-ubiquitous fever and cough, it must be emphasized that coryza and sore throat, which are common with most other human respiratory virus infections, are uncommon in SARS, and the cough is characteristically nonproductive.9Lee N Hui D Wu A et al.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1986-1994Available at: www.nejm.orgCrossref PubMed Scopus (1894) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 12Booth CM Matukas LM Tomlinson GA et al.Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.JAMA. 2003; 289 (Accessibility verified June 4, 2003.): 2801-2809Available at: http://jama.ama-assn.org/cgi/search?fulltext=greater+toronto+areaCrossref PubMed Scopus (1112) Google Scholar In contrast, gastrointestinal symptoms such as diarrhea are common and in some cases may predominate without respiratory symptoms.11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 19Centers for Disease Control and Prevention Severe acute respiratory syndrome—Taiwan, 2003.MMWR Morb Mortal Wkly Rep. 2003; 52: 461-466PubMed Google Scholar Notably, several laboratory findings, rarely seen with other types of community-acquired pneumonia, may prove to be of considerable value as surrogate markers of early SARS: lymphopenia (<1000/μL); mild thrombocytopenia (<150,000/μL); evidence of disseminated intravascular coagulation with elevated D-dimer levels; low-grade rhabdomyolysis with elevated creatine phosphokinase levels; and especially an elevated lactic dehydrogenase level; 1 or more of these abnormalities are seen in up to 90% of patients, particularly in sicker patients.9Lee N Hui D Wu A et al.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1986-1994Available at: www.nejm.orgCrossref PubMed Scopus (1894) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 12Booth CM Matukas LM Tomlinson GA et al.Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.JAMA. 2003; 289 (Accessibility verified June 4, 2003.): 2801-2809Available at: http://jama.ama-assn.org/cgi/search?fulltext=greater+toronto+areaCrossref PubMed Scopus (1112) Google Scholar Until a sensitive, specific, and rapid confirmatory diagnostic test becomes available, for any febrile patient with cough, especially with radiological evidence of pneumonia or acute respiratory distress syndrome (ARDS), who has recently returned from a country where community transmission of SARS is occurring or has occurred or who has had recent close contact with another person suspected of having SARS, an immediate algorithmic approach must be initiated to prevent nosocomial spread. Specific measures include segregating patients with suspected SARS from other patients, ideally in a negative-pressure isolation room; masking the patient; and requiring all health care workers attending to the patient to wear a fit-tested N-95 respirator mask (or powered air-purifying system), a full-length long-sleeved gown and nonsterile gloves, and eye protection with goggles or a face shield.24Centers for Disease Control and Prevention Interim guidance on infection control precautions for patients with suspected severe acute respiratory syndrome (SARS) and close contacts in house-holds.Available at: www.cdc.gov/ncidod/sars/ic-closecontacts.htmDate: April 29, 2003Google Scholar, 25Centers for Disease Control and Prevention Updated interim domestic infection control guidance in the health-care and community setting for patients with suspected SARS.Available at: www.cdc.gov/ncidod/sars/infectioncontrol.htmDate: May 1, 2003Google Scholar Suspicion of SARS must be recorded on all specimens sent to the diagnostic laboratory. As Sampathkumar et al point out, all health care workers attending to the patient must be noted and monitored closely for fever, the earliest sign of occupationally acquired infection. The importance of measures to prevent droplet airborne spread cannot be overemphasized. In a novel analysis of a large cohort of health care workers who had had extensive contact with patients with SARS in 5 Hong Kong hospitals, Seto et al20Seto WH Tsang D Yung RW Expert SARS Group of Hospital Authority et al.Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS).Lancet. 2003; 361: 1519-1520Abstract Full Text Full Text PDF PubMed Scopus (683) Google Scholar found that no health care worker who consistently used a mask, either an N-95 respirator mask or a high-quality surgical mask, became infected (P<.01), even if he or she did not always wear gloves. Hand washing and wearing a gown also appeared to be important in protection against occupationally acquired infection. To prevent spread of SARS in the community, public health authorities must strive to identify every contact of the presumed case, especially health care workers exposed without the benefit of barrier precautions, and place them on home quarantine.24Centers for Disease Control and Prevention Interim guidance on infection control precautions for patients with suspected severe acute respiratory syndrome (SARS) and close contacts in house-holds.Available at: www.cdc.gov/ncidod/sars/ic-closecontacts.htmDate: April 29, 2003Google Scholar, 25Centers for Disease Control and Prevention Updated interim domestic infection control guidance in the health-care and community setting for patients with suspected SARS.Available at: www.cdc.gov/ncidod/sars/infectioncontrol.htmDate: May 1, 2003Google Scholar The epidemiological feature of SARS that gives greatest hope for containing spread is the prolonged incubation period, which allows case-contact investigation and quarantine to be instituted before contacts destined to become ill can spread SARS-CoV to others. Whereas quarantine was ineffective in preventing spread of influenza during the great epidemic of 19182Pyle GF The Diffusion of Influenza: Patterns and Paradigms. Rowman & Littlefield, Totowa, NJ1986Google Scholar, 3Crosby AW America's Forgotten Pandemic: The Influenza of 1918. Cambridge University Press, Cambridge, England1989Google Scholar because of its extremely brief incubation period, isolation of actively infected patients and stringent quarantine of those exposed have been the linchpin of control of SARS in Vietnam, Hong Kong, Singapore, Canada, and perhaps even China.9Lee N Hui D Wu A et al.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1986-1994Available at: www.nejm.orgCrossref PubMed Scopus (1894) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar, 12Booth CM Matukas LM Tomlinson GA et al.Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.JAMA. 2003; 289 (Accessibility verified June 4, 2003.): 2801-2809Available at: http://jama.ama-assn.org/cgi/search?fulltext=greater+toronto+areaCrossref PubMed Scopus (1112) Google Scholar, 13Donnelly CA Ghani AC Leung GM et al.Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4453web.pdfDate: May 2003Google Scholar, 16World Health Organization Update 73 - No new deaths, but vigilance needed for imported cases.Available at: www.who.int/csr/don/2003_06_04/en/print.htmlDate: June 4, 2003Google Scholar Beyond ruling out other treatable causes of community-acquired pneumonia and cutting-edge supportive care for critical illness,26Maki DG Management of life-threatening infection in the ICU.in: Murray MJ Coursin DB Pearl RG Prough DS Critical Care Medicine: Perioperative Management. 2nd ed. Lippincott Williams & Wilkins, Philadelphia, Pa2002: 616-648Google Scholar including lung-protective low-tidal-volume mechanical ventilatory support,27Acute Respiratory Distress Syndrome Network Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Crossref PubMed Scopus (10147) Google Scholar stringent glycemic control,28van den Berghe G Wouters P Weekers F et al.Intensive insulin therapy in critically ill patients.N Engl J Med. 2001; 345: 1359-1367Crossref PubMed Scopus (8192) Google Scholar restrictive use of packed red blood cell transfusions,29Hebert PC Wells G Blajchman MA Transfusion Requirements in Critical Care Investigators Canadian Critical Care Trials Group et al.A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care [published correction appears in N Engl J Med. 1999;340:1056].N Engl J Med. 1999; 340: 409-417Crossref PubMed Scopus (4068) Google Scholar and uncompromising adherence to basic infection control precautions,26Maki DG Management of life-threatening infection in the ICU.in: Murray MJ Coursin DB Pearl RG Prough DS Critical Care Medicine: Perioperative Management. 2nd ed. Lippincott Williams & Wilkins, Philadelphia, Pa2002: 616-648Google Scholar it is still uncertain whether corticosteroids or antivirals, such as ribavirin, both recommended anecdotally by Hong Kong physician-investigators who have treated large numbers of patients,9Lee N Hui D Wu A et al.A major outbreak of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1986-1994Available at: www.nejm.orgCrossref PubMed Scopus (1894) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar will improve outcome in terms of reducing mortality and length of hospitalization. The exuberant, proliferative inflammatory response with alveolar membrane formation seen histopatho-logically5Ksiazek TG Erdman D Goldsmith CS SARS Working Group et al.A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1953-1966Crossref PubMed Scopus (3375) Google Scholar, 10Tsang KW Ho PL Ooi GC et al.A cluster of cases of severe acute respiratory syndrome in Hong Kong.N Engl J Med. 2003; 348 (Accessibility verified June 5, 2003.): 1977-1985Available at: www.nejm.orgCrossref PubMed Scopus (923) Google Scholar, 11Peiris JSM Chu CM Cheng VCC et al.Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4432web.pdfDate: May 2003Google Scholar is extremely similar to that seen in gardenvariety ARDS but also not unlike desquamative interstitial pneumonitis or organizing pneumonia,30Cordier JF Organising pneumonia.Thorax. 2000; 55: 318-328Crossref PubMed Scopus (279) Google Scholar with or without bronchiolitis obliterans,31Epler GR Bronchiolitis obliterans organizing pneumonia.Arch Intern Med. 2001; 161: 158-164Crossref PubMed Scopus (231) Google Scholar conditions that usually respond favorably to corticosteroids. Evidence that moderate doses of corticosteroids may be of benefit in refractory late-phase severe ARDS32Meduri GU Headley AS Golden E et al.Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial.JAMA. 1998; 280: 159-165Crossref PubMed Scopus (829) Google Scholar and unequivocally improve survival in patients with AIDS and severe Pneumocystis carinii pneumonia33Gagnon S Boota AM Fischl MA Baier H Kirksey OW La Voie L Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome: a double-blind, placebo-controlled trial.N Engl J Med. 1990; 323: 1444-1450Crossref PubMed Scopus (310) Google Scholar further suggests that, in patients with SARS and progressive hypoxemic respiratory failure, early treatment with prednisone at a dose of 1 to 2 mg/kg per day may improve survival. In contrast, the efficacy of antivirals such as ribavirin, which has substantial toxicity,12Booth CM Matukas LM Tomlinson GA et al.Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area.JAMA. 2003; 289 (Accessibility verified June 4, 2003.): 2801-2809Available at: http://jama.ama-assn.org/cgi/search?fulltext=greater+toronto+areaCrossref PubMed Scopus (1112) Google Scholar is far less clear, and no antiviral drug or drugs can be recommended at this time. Prospective multicenter randomized trials are urgently needed to determine conclusively the therapeutic role of early use of corticosteroids as well as ribavirin and other candidate antiviral drugs. However, the burning question remains: Will SARS continue to spread? Might it even explode on the world in the coming fall and winter months in the Northern Hemisphere (Table 1)? The huge negative economic impact of SARS in Asia and Canada to date has been sobering,38Simon B The cost of a virus.New York Times. May 23, 2003; Sect W: 1Google Scholar but the very real potential for uncontained global spread is even more sobering. Accelerated efforts to develop a vaccine, with trials in animal models under way, are encouraging. We can take heart that SARS has been successfully contained in most affected countries,8World Health Organization Cumulative number of reported probable cases of SARS.Available at: www.who.int/csr/sars/country/2003_06_04/en/print.htmlGoogle Scholar, 16World Health Organization Update 73 - No new deaths, but vigilance needed for imported cases.Available at: www.who.int/csr/don/2003_06_04/en/print.htmlDate: June 4, 2003Google Scholar at least for now, but most importantly, SARS may have launched a new era of international cooperation in communicable disease control and public health in general.14World Health Organization A multicentre collaboration to investigate the cause of severe acute respiratory syndrome.Lancet. 2003; 361: 1730-1733Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 15Gerberding JL Faster…but fast enough? responding to the epidemic of severe acute respiratory syndrome [editorial].N Engl J Med. 2003; 348: 2030-2031Crossref PubMed Scopus (88) Google Scholar It is no longer acceptable for countries to conceal their outbreaks or other health care problems.39Benitez MA Beijing doctor alleges SARS cases cover-up in China.Lancet. 2003; 361: 1357Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Realizing that each day hundreds of thousands of people from every corner of the globe fly transcontinentally, the world is a rapidly shrinking global village in regard to infectious diseases. It is in every country's selfinterest to be forthcoming and work collaboratively toward a common goal-the prevention of communicable diseases and improvement of the health of every citizen of the world.Table 1Parallels Between 1918 Influenza and SARS*CDC = Centers for Disease Control and Prevention; SARS = severe acute respiratory syndrome.Like more recent strains of the influenza A virus,34Treanor JT Influenza virus.in: Mandell GL Bennett JE Dolin R Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Churchill Livingstone, Philadelphia, Pa2000: 1823-1849Google Scholar the 1918 (H1N1) strain was almost certainly a human-animal recombinant that originated in southern China 35Brownlee GG Fodor E The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin.Philos Trans R Soc Lond B Biol Sci. 2001; 356: 1871-1876Crossref PubMed Scopus (85) Google Scholar, 36Hilleman MR Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control.Vaccine. 2002; 20: 3068-3087Crossref PubMed Scopus (256) Google ScholarIn all likelihood, so is the SARS coronavirus (SARS-CoV)4Peiris JSM Lai ST Poon LL SARS study group et al.Coronavirus as a possible cause of severe acute respiratory syndrome.Lancet. 2003; 361: 1319-1325Abstract Full Text Full Text PDF PubMed Scopus (2361) Google Scholar, 5Ksiazek TG Erdman D Goldsmith CS SARS Working Group et al.A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1953-1966Crossref PubMed Scopus (3375) Google Scholar, 6Drosten C Günther S Preiser W et al.Identification of a novel coronavirus in patients with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1967-1976Crossref PubMed Scopus (3455) Google Scholar, 7Ruan Y Wei CL Ling AE et al.Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection. Lancet [serial online].Available at: http://image.thelancet.com/extras/03art4454web.pdfDate: May 2003Google ScholarH1N1 influenza was extraordinarily contagious presumably because there was so little natural immunity in the general population worldwide36Hilleman MR Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control.Vaccine. 2002; 20: 3068-3087Crossref PubMed Scopus (256) Google ScholarSerologic surveys by the CDC using specimens from US serum banks show no persons with preexisting antibodies to the new SARS virus5Ksiazek TG Erdman D Goldsmith CS SARS Working Group et al.A novel coronavirus associated with severe acute respiratory syndrome.N Engl J Med. 2003; 348: 1953-1966Crossref PubMed Scopus (3375) Google ScholarH1N1 influenza A had high mortality among young and healthy individuals2Pyle GF The Diffusion of Influenza: Patterns and Paradigms. Rowman & Littlefield, Totowa, NJ1986Google Scholar, 3Crosby AW America's Forgotten Pandemic: The Influenza of 1918. Cambridge University Press, Cambridge, England1989Google ScholarSARS has also had a prohibitive mortality8World Health Organization Cumulative number of reported probable cases of SARS.Available at: www.who.int/csr/sars/country/2003_06_04/en/print.htmlGoogle Scholar and has killed previously well health care workers, including the discoverer of SARS, Dr Carlo Urbani37Reilley B Van Herp M Sermand D Dentico N SARS and Carlo Urbani.N Engl J Med. 2003; 348: 1951-1952Crossref PubMed Scopus (72) Google ScholarInfluenza A classically spreads in the late fall and winter months and is rarely seen during the late spring and summer months34Treanor JT Influenza virus.in: Mandell GL Bennett JE Dolin R Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Churchill Livingstone, Philadelphia, Pa2000: 1823-1849Google Scholar; in 1918, influenza continued to occur, inexplicably, all summer3Crosby AW America's Forgotten Pandemic: The Influenza of 1918. Cambridge University Press, Cambridge, England1989Google ScholarSARS has caused epidemic disease all spring and will likely continue to spread slowly throughout the summer monthsIn 1918, pandemic influenza surged worldwide in late August and the fall2Pyle GF The Diffusion of Influenza: Patterns and Paradigms. Rowman & Littlefield, Totowa, NJ1986Google Scholar, 3Crosby AW America's Forgotten Pandemic: The Influenza of 1918. Cambridge University Press, Cambridge, England1989Google ScholarWith SARS, we do not know what will occur, but we must be prepared for the worst; countries, regional and municipal health departments, hospitals, and individual practitioners must be informed and prepared* CDC = Centers for Disease Control and Prevention; SARS = severe acute respiratory syndrome. Open table in a new tab We must hang together or assuredly we shall all hang separately. Benjamin Franklin SARS: Epidemiology, Clinical Presentation, Management, and Infection Control MeasuresMayo Clinic ProceedingsVol. 78Issue 7PreviewSevere acute respiratory syndrome (SARS) is a recently recognized febrile respiratory illness that first appeared in southern China in November 2002, has since spread to several countries, and has resulted in more than 8000 cases and more than 750 deaths. The disease has been etiologically linked to a novel coronavirus that has been named the SARS-associated coronavirus. It appears to be spread primarily by large droplet transmission. There is no specific therapy, and management consists of supportive care. Full-Text PDF