Author Institution: Department of Infectious Diseases and Department of Research Administration, Summa Health System ; Akron City Health Departmen

Boyer, Jere

Erme, Margo

File, Thomas

Myers, Joseph

The Ohio Journal of Science

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BRIEF NOTEWhat You Need to Know About SARS1THOMAS FILE, JERE BOYER, MARGO ERME, AND JOSEPH MYERS, Department of Infectious Diseases and Department of ResearchAdministration, Summa Health System, Akron, OH 44304; Akron City Health Department, Akron, OH 44308OHIO J SCI 103 (4):70-72, 2003INTRODUCTIONThe World Health Organization (WHO) was informedby the Chinese Ministry of Health on 11 February 2003that there were 305 cases of an acute respiratorysyndrome of unknown etiology (WHO 2003a). Thesecases occurred in six municipalities in GuangdongProvince of southern China during 16 November 2002 -9 February 2003 (WHO 2003a).As determined by a consensus of worldwide publichealth officials in March 2003, surveillance case defi-nitions for Severe Acute Respiratory Syndrome (SARS)includes both "suspect" and "probable" cases (MMWR2003a; CDC 2003a) (See below).As of late February 2003, the Centers for DiseaseControl and Prevention (CDC) and WHO referred to thenew outbreak as Severe Acute Respiratory Syndrome(SARS) (MMWR 2003a). By 17 April 2003, there were3,389 suspected/probable cases of SARS in 25 countrieswith 165 deaths or a case-fatality proportion of 5%(WHO 2003b). By 1 May 2003, at least 5,865 suspected/probable cases of this disease had been reported toWHO from 27 different countries. At that time therewere 391 deaths (case-fatality proportion of 6.7%)(WHO 2003c). As of 30 April 2003, there had been 289cases of suspect or probable (only 56 were probable)SARS reported in the US with no known deaths (MMWR20030. On 8 May 2003, WHO assigned a case-fatalityrate of 15% (Foxnews 2003), greater than the 3% ini-tially assigned by WHO (MMWR 2003b), and far greaterthan the 2.8% fatality rate of the 1918 Influenza pan-demic. This appears rather surprising considering thatthe latest WHO data (7 May 2003) indicates 495 deathsworld-wide with 6,903 suspect/probable cases resultingin a 7% case-fatality rate (WHO 2003d).CASE DEFINITIONSA "suspect" case of SARS is defined as a respiratoryillness of unknown etiology with onset since 1 February2003, and with the following criteria (MMWR 2003a):1) measured temperature >100.4°F (>38°C); 2) one ormore clinical findings of respiratory illness (for example,cough, shortness of breath, difficulty breathing, hypoxic,or radiographic findings of either pneumonia or acuterespiratory distress syndrome); and 3) travel within tendays of onset of symptoms to an area with suspectedor documented community transmission of SARS. This'Manuscript received 12 May 2003 and in revised form 19 May2003 (#03-10).would exclude areas with secondary cases limited tohealth care workers, direct household contacts, or closecontact within ten days of onset of symptoms witheither a person with a respiratory illness and travel to aSARS area, or a person under investigation or suspectedof having SARS.A "probable" case is defined as a suspect case witheither radiographic evidence of pneumonia or respiratorydistress syndrome or autopsy findings consistent withrespiratory distress syndrome without an identifiablecause (CDC 2003a). On 29 April 2003, CDC's interimsurveillance case definition for SARS had been updatedto include laboratory criteria for evidence of infectionwith the SARS-associated coronavirus (MMWR 20030.The basis of the revised definition is that the virus cannow be detected by polymerase chain reaction (PCR),serological methods, or viral isolation methods. Al-though, at this time, no instances of SARS-associatedcoronavirus had been detected in persons who wereasymptomatic, there remains the possibility of "sub-clinical" infection. In such cases laboratory detectionmay be able to identify patients with mild respiratoryillness or those who are asymptomatic.CLINICAL DESCRIPTIONWhat is the clinical description of SARS? Most patientswith SARS have traveled to Mainland China, Hong Kong,Singapore, or Hanoi. More recently there has been analarming increase in SARS cases in and around Toronto,Ontario (MMWR 2003e). Close contact with a SARSpatient can also be a risk factor. SARS generally beginswith a fever above 100.4° F and may include headache,malaise, and myalgia. The fever may be accompaniedwith chills and rigors. Rash, neurologic, and gastro-intestinal findings are usually absent but several patientshave had diarrhea. The incubation period appears to be2-7 days although several cases may have had a 10-dayincubation period. Three to seven days after initial symp-toms appear, a lower respiratory phase begins withonset of dry, nonproductive cough and dyspnea pos-sibly progressing to hypoxemia (CDC 2003b and MMWR2003c)). As many as 20% of such patients will require in-tubation and placement on a ventilator (MMWR 2003c).Laboratory results early in the course of SARS usuallyshow a decrease in lymphocytes with total white bloodcell counts either normal or decreased. Later, during therespiratory phase of disease, about half of the patientsshow leukopenia and thrombocytopenia (MMWR2003a). Creatine phosphokinase and hepatic trans-aminase are elevated. Chest x-rays may be normalOHIO JOURNAL OF SCIENCE T. FILE, J. BOYER, M. ERME, AND J. MYERS 71throughout the illness (MMWR 2003d). Many patients,however, will present with patchy interstitial infiltratesduring the lower respiratory phase of disease whenviewed in lung radiograms. Severity of the illness is highlyvariable, ranging from mild illness to death.CAUSE OF DISEASEWhat is the cause of the infection? On 24 March 2003,CDC announced that the causative agent of SARS wasidentified as a previously unrecognized coronavirus(MMWR 2003b). Initial identification was made by elec-tron microscopy and confirmed by direct immuno-staining, indirect immunofluorescent antibody assay, andreverse transcriptase-polymerase chain reaction withsequencing of a portion of the polymerase gene (MMWR20030- The family of Coronaviruses has been poorlystudied because they are difficult to culture. Until now,coronaviruses have been associated with the "commoncold" (Wilson and others 2001) and diarrhea (Brooks andothers 2001) in humans and infections in animals,worldwide. The case for coronaviruses causing moresevere disease in humans, such as bronchitis, was verytenuous (Tan 2002).The Coronaviruses (Brooks and others 2001; Murryand others 1998) have a lipoprotein envelope and areshaped as long helical structures that measure 80 to 220nm. These viruses get their name from the solar corona-like appearance surrounding the virion that is producedby the 20 nm long glycoprotein, petal-shaped projectionsthat appear on the surface of the envelope. The viruscontains a single-stranded positive sense RNA (likemessenger RNA) that is the longest genome knownamong RNA viruses (approximately 30,000 bases). If theagent of SARS replicates like other human corona-viruses, it will do so in the cytoplasm of the infectedcell. The virus would attach itself to cell receptors bymeans of the glycoprotein spikes on the viral envelope.The virus is then internalized by endocytosis. Afteruncoating, the viral genomic RNA is translated to producean RNA dependent RNA polymerase in the cytoplasm.The new viral polymerase transcribes about sevenmessenger RNAs, specific for viral proteins. The newlysynthesized genomic RNA interacts with newly synthe-sized nucleocapsid protein and associates with the viralglycoprotein modified membranes of the Golgi appa-ratus, thus forming virions. Mature virions migrate to thehost cell membrane where they may exit or wait untilcell death. Whether this process occurs with the agentof SARS is currently unknown.Also of interest, coronaviruses readily change theirgenetic makeup with a high frequency of mutations andrecombination between new strains. These activities areeven higher than for most RNA viruses and may be thereason for the appearance of the new SARS coronavirus(Ksiazek and others 2003). It is likely that SARS is arecombinant of animal viruses. Several animal corona-viruses have been known to cause serious disease in-cluding avian infectious bronchitis virus of chickens andcoronavirus infections of rats (Brooks and others 2001).Porcine respiratory coronavirus caused widespreadepidemics in pigs in Europe during the 1980s. Antibodiesto coronaviruses of one genus are cross-reactive withthose of other genera.PUBLIC HEALTH MEASURESIn order to protect the general population from SARSexposure, a number of recommendations have beenmade by WHO, CDC, and health care professionals (CDC2003b). Currently there is no treatment, other thansupportive, and no vaccine is available (CDC 2003c).Although the mechanism of SARS transmission is some-what unclear, it does appear that droplet and contacttransmission predominates (CDC 2003d). As with mostagents of disease, avoidance is still the best protection.As such, the WHO has issued a travel advisory to avoidgoing to endemic areas such as China, Singapore, HongKong, and Vietnam. Although Toronto was included inthe advisory, as of 1 May 2003, it has been removed.People should avoid anyone who may have SARS orcontact with SARS patients. Persons working with sus-pected cases of SARS should use appropriate handwashing and respiratory and contact precautions (CDC2003d). It may be that once transmission is betterdefined, eye protection may also be worthwhile. Coro-naviruses are very stable in the environment. They cansurvive on surfaces for up to 3 hours and can betransmitted by droplets, hand contamination, fomites,and small particles (MMWR 2003b). Coronavirus-likeparticles have been isolated from diarrhea and stoolspecimens (Brooks and others 2001). This has led tosome speculation that SARS may be spread throughsewage or poor toilet hygiene. Again, appropriate handwashing is important (CDC 2003d).POSTWORDDuring the 1970s there was a general attitude thatwe had learned all we need to know about infectiousdiseases. After all, we could treat or prevent most bac-terial diseases and were able to prevent many viralinfections. We could not have been more wrong. Soonthere was Legionnaires' Disease, AIDS, multiple anti-biotic resistant agents, and a whole new host of viraldiseases. SARS is only the latest of what will be manyinfectious diseases on the horizon.If there is a lesson to learn with SARS and its rapidspread, it is that physicians, health care workers, publichealth officials, and indeed, governments cannot hidefrom new infectious agents. They do not go away. It ispossible that if isolation and quarantine methods wereused early, the impact of SARS would have been lessened.Unfortunately, this was not done and SARS is the latestworldwide concern of health professionals.As you are aware, our knowledge of SARS and theviral causative agent is evolving daily. It is difficult forthe authors to decide when it is time to end the researchand writing process. As such, it is our suggestion that, ifyou are interested in the topic, you should access severalwebsites for the most recent information. Such websitesmight be: www.cdc.gov/ncidod/sars/; www.who.int/csr/sars/en/; and www.medscape.com.ACKNOWLEDGMENTS. The authors thank Kenneth Rosenthal, PhD, Professor72 SARS: THE LATEST PANDEMIC VOL. 103of Microbiology and Immunology at the Northeastern Ohio UniversitiesCollege of Medicine, Rootstown, OH, for his excellent review ofour manuscript. We also thank Mrs. Barbara Will for her clericalendeavors.LITERATURE CITEDBrooks JF, Butel JS, Morse SA. 2001. Medical Microbiology. 23rd ed.New York: Lange Medical Books/McGraw-Hill, p 488-91.[CDC] Centers for Disease Control and Prevention. 2003a. LJpdatedInterim US Case Definition of Severe Acute Respiratory Syndrome(SARS). Available at: h t t p : / / w w w . c d c . g o v / n c i d o d / s a r s /casedefinition.htm.[CDC] Centers for Disease Control and Prevention. 2003b. Basicinformation about SARS. Available at: http://www.cdc.gov/ncidod/sars/factsheet.htm.[CDC] Centers for Disease Control and Prevention. 2003c. Treatment.Available at: http://www.cdc.gov/ncidod/sars/treatment.htm.[CDC] Centers for Disease Control and Prevention. 2003d. Informationfor Close Contacts of SARS Patients. Available at: http://www.cdc.gov/ncidod/sars/factsheetcc.htm.[Foxnews] Fox News Channel. 2OO3.: SARS Deadlier Than Thought,WHO Says. Available at: h t t p : / / w w w . f o x n e w s . c o m /printer_friendly_story/0,3566,86310,00.html.Ksiazek TG, Erdman D, Goldsmith C, Sherif MS, Zaki R, Peret T,Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, NghiemKH, Dowell S, Ling A-E, Humphrey C, Shieh W-Guarner J,Paddock CD, Rota P, Fields B, DeRisi J, YangJ-Y, Cox N, HughesJ, LeDuc JW, Bellini WJ, Anderson LJ. 2003. A Novel CoronavirusAssociated with Severe Acute Respiratory Syndrome. (Abstract)Available at: http:/ /content.nejm.org/cgi/content/abstract/NEJMoa030781v2. (Article to appear in NEJM May 15).[MMWR] Morbidity and Mortality Weekly Report. 2003a. Outbreakof Severe Acute Respiratory Syndrome - Worldwide, 2003- MorbidMortal Weekly Rep 52:226-8.[MMWR] Morbidity and Mortality Weekly Report. 2003b. Update:Outbreak of Severe Acute Respiratory Syndrome - Worldwide,2003. Morbid Mortal Weekly Rep 52:241-6.[MMWR] Morbidity and Mortality Weekly Report. 2003c. PreliminaryClinical Description of Severe Acute Respiratory Syndrome.Morbid Mortal Weekly Rep 52:255-6.[MMWR] Morbidity and Mortality Weekly Report. 2003d. Severe AcuteRespiratory Syndrome and Coronavirus Testing - United States,2003. Morbid Mortal Weekly Rep 52:297-302.[MMWR] Morbidity and Mortality Weekly Report. 2003e. Update:Severe Acute Respiratory Syndrome — United States, 2003. MorbidMortal Weekly Rep 52:332-6.[MMWR] Morbidity and Mortality Weekly Report. 2003f. Update:Severe Acute Respiratory Syndrome - United States, 2003. MorbidMortal Weekly Rep 52:388-90.Murry PR, Rosenthal KS, Kobayashi GS, Pfaller MA. 1998. MedicalMicrobiology. 3rd ed. St. Louis (MO): Mosby. p 540-2.Tan JS. 2002. Expert Guide to Infectious Diseases. Philadelphia:American College of Physicians, p 395.Wilson WR, Sande MA, Drew WL, Henry NK, Relman DA, SteckelbergJM, Gerberding JL. 2001. Current Diagnosis and Treatment inInfectious Diseases. New York: Lange Medical Books/McGraw-Hill, p 98-100.[WHO] World Health Organization. 2003a. Disease outbreak reported:acute respiratory syndrome in China. Available at: http://www.who.int/cst/don/2003_2_20/en.[WHO] World Health Organization. 2003b. Cumulative Number ofReported Probable Cases of Severe Acute Respiratory Syndrome(SARS). Available at: ht tp: / /www.who.int/csr/sarscountry/2003_04_17/en.[WHO] World Health Organization. 2003c. Cumulative Number ofReported Probable Cases of Severe Acute Respiratory Syndrome(SARS). Available at: ht tp:/ /www.who.int/csr/sarscountry/2003_05_01/en.[WHO] World Health Organization. 2003d. Cumulative Number ofReported Probable Cases of Severe Acute Respiratory Syndrome(SARS). Available at: ht tp:/ /www.who.int/csr/sarscountry/2003_05_07/en.

Brief Note  What You Need to Know About SARS

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Brief Note What You Need to Know About SARS

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