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  Vol. 129 No. 11, November 2003 TABLE OF CONTENTS
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Initial Otolaryngological Manifestations of Severe Acute Respiratory Syndrome in Taiwan

Hsin-Chi Chen, MD; Yi-Ho Young, MD; Jyh-Perng Luo, MD; Hui-Ju Tsai, MD; Sung-Jung Ho, MD; Chi-Huang Yeh, MD; Lien-Chi Huang, MD

Arch Otolaryngol Head Neck Surg. 2003;129:1157-1160.

ABSTRACT

Objective  To provide a clue for screening severe acute respiratory syndrome (SARS), a highly transmissible disease with health care workers at particular risk, in the early stage from an otolaryngological perspective.

Design  Prospective study.

Setting  Community hospital.

Patients  Between April 17 and April 26, 2003, 32 consecutive patients with SARS were encountered. Investigation consisted of local examination of ear, nose, and throat fields; palpation of the nuchal areas; and plain chest radiography. Analyses of throat swab samples using reverse transcription–polymerase chain reaction were conducted.

Results  Clinical manifestations included fever in 31 patients (97%), followed by cough, dyspnea, chill, headache, sore throat, diarrhea, rhinorrhea, and otalgia. Neither the pharyngeal wall nor the tonsillar area demonstrated hyperemia. There was no lymphadenopathy in the neck. Plain chest radiographs revealed consolidation in 25 (78%) of 32 patients. Results of reverse transcription–polymerase chain reaction analysis targeting the novel coronavirus present in throat swab samples were positive in 19 (66%) of 29 patients tested. Twenty-eight patients required supplemental oxygen, and 14 patients were intubated with mechanical ventilation. Twenty-eight patients survived and 4 patients died.

Conclusions  When presented with a patient with flulike symptoms such as fever and/or cough, but no pharyngeal hyperemia or neck lymphadenopathy, physicians should be alerted to the possibility of SARS. In contrast, evidence of inflammatory signs in the otolaryngological field may explain the flulike symptoms, and serve as a differential diagnostic tool between influenza and SARS.



INTRODUCTION
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ON APRIL 23, 2003, a major outbreak of severe acute respiratory syndrome (SARS) occurred at the Municipal Ho-Ping Hospital, a community hospital in Taipei, Taiwan. This was 2 months after the World Health Organization reported outbreaks of a severe form of atypical pneumonia in Hanoi, Hong Kong, and Singapore.1 The term severe acute respiratory syndrome (SARS) was coined following the reports from the Department of Hong Kong, Special Administrative Region.2 Later, multicountry outbreaks of SARS were reported,3-7 and the infectious foci were recognized as a novel coronavirus.8

One of us (H.-C.C.), an otolaryngologist, had been consulted to examine the ear, nose, and throat fields in 32 consecutive patients in the early stage of SARS during the period April 17 through April 26. Since SARS is highly transmissible from person to person, and health care workers are particularly at risk,3-4,9 the aim of this article was to provide a clue for screening SARS in the early stage from an otolaryngological perspective.


METHODS
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Between April 17 and April 26, 2003, 32 consecutive patients with SARS at the Municipal Ho-Ping Hospital were encountered. Each patient underwent a detailed history taking to ascertain possible contact with each other. Initial investigation consisted of local examination of ear, nose, and throat fields; palpation of the bilateral nuchal areas; complete blood cell counts; serum biochemical study; and plain chest radiography. Analysis of throat swab samples using reverse transcription–polymerase chain reaction were conducted to confirm the diagnosis of SARS.

Our case definition was based on the criteria for SARS established by the Centers for Disease Control and Prevention,2 that is, fever (temperature >38°C), a chest radiograph showing evidence of consolidation, a history of exposure to an index patient suspected to have SARS or direct contact with a person who became ill after exposure to an index patient. Secondary cases were defined as persons in whom SARS developed who had had direct contact with the index patients or who had been exposed to him or her in the medical ward. Patients who contracted the disease from these persons were defined as tertiary cases.4

Since patient age was strongly associated with the outcome of SARS,10-11 the 32 patients were divided into 3 age groups: 13 patients aged 14 to 29 years, 6 patients aged 30 to 45 years, and 13 patients older than 45 years.

After April 24, all patients were administered antiviral (ribavirin) and antibacterial (levofloxacin) agents initially, and placed immediately in negative-pressure isolation facilities.


RESULTS
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PATIENTS AND CONTACT HISTORY

On March 26, a resident of Hong Kong's Amoy Gardens flew to Taiwan and took a 2-hour train to visit his brother. The latter became Taiwan's first SARS fatality, and a female passenger (index patient A) on the train also became a case. On April 9, patient A came to the emergent service of Ho-Ping Hospital because of fever and cough for 3 days. Plain chest radiography revealed consolidation in the bilateral lower lung fields. She stayed in the emergent service for 3 hours, and was transferred to another medical center where probable SARS was confirmed. During the same time, a 42-year-old male worker from laundry room of the hospital (index patient B) came to the emergent service to collect the contaminated clothes of patient A. Later, on April 16, patient B had febrile illness and diarrhea, and was admitted to ward 8B. During admission, patient B walked about the ward, talking to people without wearing a mask. Subsequently, a total of 19 health care workers on ward 8B contracted the infection, leading to the outbreak of SARS in the hospital. Patient B was finally diagnosed as having SARS and died. On April 24, the entire hospital was sealed off, and all the staff, patients, and their households were quarantined.

A total of 32 patients were diagnosed as having SARS. Seven were men and 25 were women, with their ages ranging from 14 to 82 years (mean ± SD age, 40 ± 17 years). These patients consisted of 9 inpatients or their households and 23 health care workers (72%), including 16 nurses (50%), 4 workers, and 3 physicians. The 3 physicians included 2 medical physicians in ward 8B (cases 3 and 24) and 1 surgeon in the emergent service (case 2). Index patients were attributed to 2 patients (patients A and B), 8 patients could be traced as secondary cases, and 11 patients as tertiary cases (Figure 1). The interval between exposure to the index patient or ward and the onset of fever ranged from 3 to 6 days, with a median incubation period 4 days. Figure 1 demonstrates the epidemiological link in these patients. Since patients A and B lacked initial otolaryngological information, both cases were excluded in this study.



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Epidemiological linking of Ho-Ping Hospital (Taipei, Taiwan) patients with severe acute respiratory syndrome. A and B indicate index patients; numbers in circles, case numbers in Table 1; ES, emergent services; and ICU, intensive care unit.



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Characteristics of 32 Patients With SARS Outbreak at the Municipal Ho-Ping Hospital, Taipei, Taiwan


CLINICAL MANIFESTATION

Clinical manifestation consisted of fever in 31 patients (97%), followed by cough in 27 (84%), dyspnea in 22 (69%), chill in 21, headache in 13, sore throat in 11, diarrhea in 7, rhinorrhea in 6, and otalgia in 3. Because flulike symptoms such as fever and cough persisted, all patients underwent an otolaryngological examination. However, neither the pharyngeal wall nor the tonsillar area demonstrated hyperemia or inflammatory reaction. Instead, the pharyngeal wall revealed "drying" features, without moisture on the mucous membrane. Otoscopic examination was unremarkable in all patients; referred otalgia was considered in 3 patients. There was no lymphadenopathy in the nuchal areas including submental, submandibular, and upper, middle, or lower cervical lymph nodes. Plain chest radiographs revealed consolidation in 25 (78%) of 32 patients, demonstrating either diffuse interstitial infiltration or patchy, focal, or lobar consolidation. Results of reverse transcription–polymerase chain reaction analysis targeting the novel coronavirus present in throat swab samples were positive in 19 (66%) of 29 patients tested.

TREATMENT AND OUTCOME

Twenty-eight patients required supplemental oxygen, and 14 patients were intubated with mechanical ventilation. Twenty-eight of these 32 patients survived and 4 patients, all older than 45 years, died. Table 1 summarizes the characteristics of these 32 patients.


COMMENT
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In March 2003, the Department of Health in Taiwan in conjunction with the Centers for Disease Conrol and Prevention began implementing measures to limit the spread of SARS in Taiwan.7 For example, 10-day quarantine periods for travelers arriving from the affected area were enforced. Airport checkpoints were set up to screen people coming into Taiwan, where they are given temperature checks and asked to fill out health declaration forms. Patients with probable cases of SARS are asked to wear N-95 masks and be placed immediately in negative-pressure isolation facilities. In addition, health care workers are advised to wear similar masks along with head cover, goggles, gowns, and gloves when having contact with any patients with SARS.9 Because of extensive business and cultural ties, Taiwan has heavy travel volume from China via Hong Kong, leading to potential risk for importation and spread of SARS, which resulted in a major outbreak of SARS at our community hospital in late April.

The initial clinical features of SARS are nonspecific. The most common symptom of SARS is fever, representing 97% of patients in this series (case 1 was the only exception), a rate that is comparable to reports (94%) from the Hong Kong group.10 The second most common symptom is dry cough, representing 84% of patients in the present series. Thus, fever and dry cough as the initial manifestations of SARS are hard to differentiate from other viral infections. Although diagnostic delay may contribute to the spread of the epidemic, overdiagnosis of SARS will provoke a panic condition in a community. Based on this study, evidence that includes unremarkable findings in the ears, nose, pharynx, tonsils, and larynx as well as lack of palpable lymph nodes in the neck, may raise the suspicion of SARS in a patient with flulike symptoms.

Of note, the otolaryngologist (H.-C.C.) who examined the 32 patients with SARS in the early stage, and, further, stayed with the SARS patients on the same floor 24 hours daily for consecutive 7 days during the quarantine period, remained asymptomatic. How can this phenomenon be explained?

The reason may be attributed to wearing an N-95 mask when performing local examinations of the ears, nose, and throat during the period April 17 to April 24 (week 1). After the hospital was sealed off, the author wore a P-100 mask and a head cover, goggles, gowns, and gloves when in contact with the SARS patients from April 24 through April 30 (week 2). In contrast, 3 physicians (2 in the medical ward and 1 in the emergent service) contracted SARS from the patients during week 2. This indicates that in the mid-stage of SARS (week 2), the infectious ability increases, leading to the medical physicians' being affected, whereas fewer otolaryngologists or family physicians contracted SARS from the patients, possibly due to less infectious ability during the early stage (week 1). This finding suggests that in the early stage of SARS, manifested as fever or cough, the concentration of virus in the upper respiratory tract is presumably lower, since local examination of the ears, nose, and throat revealed no inflammatory signs. The flulike symptoms during the early stage of SARS are largely related to the effect of viral replication and cytolysis.12 In addition, most patients do not demonstrate reactive lymphadenopathy in the neck. Restated, less infectious ability may be attributed to a lower level of viral shedding. When the virus "loading" to the lower respiratory tract occurs as the disease progresses, the concentration of virus becomes more transmissible, thus contributing to many medical physicians and nurses contracting SARS at week 2.

Other potential explanations for fewer otolaryngologists contracting the disease from SARS patients may include less intensive or reduced exposure, compared with physicians involved in the primary care of the patients. Furthermore, there may be some unknown factor that might protect these individuals.

Clinicians must stay alert and be familiar with the rapidly changing epidemiology of the SARS infection. A clear picture of its clinical manifestation will help physicians be aware of SARS. For example, negative otolaryngological findings and lack of reactive lymphadenopathy in a patient with fever and cough may raise the suspicion for SARS. In contrast, evidence of inflammatory signs in otolaryngological fields may explain the flulike symptoms, and thus serve as a differential diagnostic tool between influenza and SARS. Early recognition and prompt quarantine can minimize SARS transmission and prevent nosocomial clusters. In addition, appropriate therapy may diminish community fears, in order to fight against this novel global contagious infectious disease.

Based on this study, we draw the following 4 conclusions: (1) there are no positive otolaryngological physical findings in SARS; (2) an otolaryngologist can contract SARS while examining a patient who has SARS; (3) SARS cannot be contracted by just being in the same part of the hospital as a SARS patient; and (4) a SARS epidemic within a hospital will severely limit or cease its function.


CONCLUSIONS
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SARS represents a novel coronavirus that causes lower respiratory tract infection. When presented with a patient with flulike symptoms such as fever and cough, but no pharyngeal hyperemia or neck lymphadenopathy, physicians should be alerted to the possibility of SARS. In contrast, evidence of inflammatory signs in the otolaryngological fields may explain the flulike symptoms, and serve as a differential diagnostic tool between influenza and SARS.


AUTHOR INFORMATION
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Corresponding author and reprints: Yi-Ho Young, MD, Department of Otolaryngology, National Taiwan University Hospital, 1 Chang-Te St, Taipei, Taiwan (e-mail: youngyh{at}ha.mc.ntu.edu.tw).

Submitted for publication June 16, 2003; final revision received July 29, 2003; accepted August 18, 2003.

This study was supported by grant NSC 91-2314-B002-299 from the National Science Council, Taipei, Taiwan.

From the Departments of Otolaryngology (Dr Chen) and Medicine (Drs Luo, Tsai, Ho, Yeh, and Huang), Municipal Ho-Ping Hospital; and Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine (Dr Young), Taipei, Taiwan. The authors have no relevant financial interest in this article.


REFERENCES
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1. Acute respiratory syndrome in China—update 3: disease outbreak reported. Geneva, Switzerland: World Health Organization, 2003. Available at: http://www.who.int/csr/don/2003_2_20/en. Accessed March 31, 2003.
2. Severe acute respiratory syndrome (SARS). Atlanta, Ga: Centers for Disease Control and Prevention, 2003. Available at: http:/www.cdc.gov/ncidod/sars/. Accessed March 31, 2003.
3. Tsang KW, Ho PI, Oo GC, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348:1977-1985. FREE FULL TEXT
4. Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348:1986-1994. FREE FULL TEXT
5. Poutanen SM, Low DE, Henry B, et al. Identification of severe acute respiratory syndrome in Canada. N Engl J Med. 2003;348:1995-2005. FREE FULL TEXT
6. Hsu LY, Lee CC, Green JA, et al. Severe acute respiratory syndrome (SARS) in Singapore: clinical features of index patient and initial contacts. Emerg Infect Dis. 2003;9:713-717. ISI | PUBMED
7. Twu SJ, Chen TJ, Chen CJ, et al. Control measures for severe acute respiratory syndrome (SARS) in Taiwan. Emerg Infect Dis. 2003;9:718-720. ISI | PUBMED
8. Ksiazek TG, Erdman D, Goldsmith C, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348:1953-1966. FREE FULL TEXT
9. Dwosh HA, Hong HHL, Austgarden D, Herman S, Schabas R. Identification and containment of an outbreak of SARS in a community hospital. CMAJ. 2003;168:1415-1420. FREE FULL TEXT
10. Donnelly CA, Ghani AC, Leung GM, et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003;361:1761-1766. FULL TEXT | ISI | PUBMED
11. Hon KLE, Leung CW, Cheng WFT, et al. Clinical presentation and outcome of severe acute respiratory syndrome in children. Lancet. 2003;361:1701-1703. FULL TEXT | ISI | PUBMED
12. Peiris 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. 2003;361:1767-1772. FULL TEXT | ISI | PUBMED






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