Papers

Outbreak of severe acute respiratory syndrome in Hong Kong Special Administrative Region: case report

Moira Chan-Yeung, professor ^a, W C Yu, consultant physician ^b. 

^a Division of Respiratory and Critical Care Medicine, 4/F, Professorial Block, Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, China, ^b Department of Medicine, Princess Margaret Hospital, Hong Kong, SAR, China

Correspondence to: M Chan-Yeung mmwchan{at}hkucc.hku.hk

	Abstract

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Objective: To describe the outbreak of severe acute respiratory syndrome in Hong Kong.
Design: Descriptive case series.
Setting: Hong Kong, Special Administrative Region, China
Results: The outbreak started with a visitor from southern China on 21 February. At the hospitals where the first cases were treated the disease spread quickly among healthcare workers, and then out into the community as family members became infected. By 1 April, 685 cases had been reported with 16 deaths. Symptoms include high fever and one or more respiratory symptoms (including cough, shortness of breath, and difficulty breathing). Changes in lung tissue suggest that part of the lung damage is due to cytokines induced by the microbial agent, which has led to empirical treatment with corticosteroids, broad spectrum antiviral agent, and antibacterial cover. There is strong evidence that a novel coronavirus is the pathogen. Precautions for droplet infection should be instituted, including the wearing of masks and rigorous disinfection and hygiene procedures. On 27 March the Department of Health announced drastic measures, including vigorous contact tracing and examination, quarantine of contacts in their homes, and closure of all schools and universities.
Conclusion: The rapidity of the spread of the disease and the morbidity indicate that the agent responsible is highly infectious and virulent. Strict infection control measures for droplet and contact transmission by healthcare workers, a vigilant healthcare profession, and public education are essential for disease prevention.

What is already known on this topic Severe acute respiratory syndrome is a form of atypical pneumonia that originated in southern China and spread globally in a few weeks The clinical picture, empirical treatment, and the possible mode of disease transmission have been described. The agent responsible is probably a novel coronavirus What this study adds This report gives an account of the daily reported number of cases in Hong Kong, showing how the disease has spread rapidly from healthcare workers to the community, and of the drastic measures the government has finally introduced to attempt to control the disease A vigilant healthcare profession, strict infection control measures, and public education are essential to prevent disease dissemination Early introduction of quarantine procedures for this disease by health authorities should be considered.

	Introduction

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On 12 March 2003, the World Health Organization issued a global alert on atypical pneumonia, called severe acute respiratory syndrome, after reports from the Department of Health of Hong Kong of an outbreak of pneumonia in one of its public hospitals. At about the same time, the WHO received reports of the syndrome from China, Singapore, Vietnam, Thailand, Indonesia, Taiwan, and Philippines, as well as from countries in other continents including Canada, the United States, and Germany. The disease originated in Guangdong at the end of last year and has affected over 300 people and killed five.¹

We here describe the outbreak that occurred in Hong Kong Special Administrative Region.

	Case reports

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History of the outbreak
The outbreak in Hong Kong started when a doctor from southern China arrived on 21 February 2003 and stayed in a local hotel. He had been unwell for a few days before the trip but now became seriously ill and died in a local hospital. However, he had infected his brother-in-law, two nurses in the hospital, and seven guests who had stayed on the same floor of the hotel. One of these hotel guests was admitted into a major public hospital on 24 February and was responsible for the outbreak there affecting at least 88 healthcare workers and 18 medical students. Another major outbreak affecting 237 residents (at the time of writing) in a housing estate was traced back to a patient discharged from the same ward of the public hospital.

The table shows the number of affected healthcare workers in the public hospital and other healthcare facilities, cases in the community, and the total cumulative number of daily reported cases.² At the time of writing, 685 cases had been reported with 16 deaths. The disease, initially affecting mainly healthcare workers, spread rapidly to the community as family members became infected and in turn infected their coworkers and friends. When symptoms developed, they consulted their general practitioners, leading to more healthcare workers developing the disease. It is now known that three of the hotel guests were responsible for the outbreaks in Hanoi, Singapore, and Toronto. There were also smaller clusters arising from individuals having travelled to southern China in the one to two weeks between infection and onset of symptoms.

Laboratory and pathological findings
The local experience indicated that the incubation period is between two and 11 days.³ All patients presented with fever (temperature >38°C), chills, and myalgia. Pulmonary infiltrates appeared in chest radiographs early, even before the start of dyspnoea. Symptoms of cough and sputum were not always present. A few patients had diarrhoea. Lymphopenia was the striking feature, with mild thrombocytopenia. Mild liver dysfunction was noted in most cases.

All sputum, blood, and urine cultures were negative for bacterial pathogens. Direct immunofluorescent stains of nasopharyngeal aspirate failed to show the presence of adenovirus; influenza A and B; parainfluenza 1, 2, and 3; and respiratory syncytial virus. Serological examination at one and 14 days did not show increases in titre of antibodies against mycoplasma, chlamydia, or legionella. In some patients the pneumonic infiltration was rapidly progressive, resulting in severe oxygen desaturation requiring assisted ventilation.

A research team in the University of Hong Kong isolated a virus belonging to the family Coronaviridae from two patients.⁴ Using serological and reverse-transcriptase polymerase chain reaction specific for this virus, they found 45 out of 50 patients with severe acute respiratory syndrome had evidence of infection with this virus but not in the sera of 80 patients with respiratory or other disease or 200 blood donors. However, reverse-transcriptase polymerase chain reaction is currently only used in research laboratories. At present, the diagnosis of severe acute respiratory syndrome remains a clinical one according to WHO definition.¹ Diagnostic features include high fever, one or more respiratory symptoms (including cough, shortness of breath, and difficulty breathing), and close contact with a person who has been diagnosed with severe acute respiratory syndrome.

The open lung biopsy of the patient who provided samples for viral culture showed histological changes typical of adult respiratory distress syndrome.³ There was diffuse alveolar damage, hyaline membrane formation, and minimal mononuclear cell infiltration. Viral inclusion bodies were not found, although this could have been due to sampling error. The changes in lung tissue suggest that part of the lung damage is due to cytokines induced by the microbial agent. This hypothesis forms the basis of treatment with corticosteroids.

Treatment
The following empirical treatment has been suggested by the Hospital Authority, Hong Kong,⁵ based initially on the experience with a small number of cases and subsequently confirmed by favourable results in a proportion of patients:

• Broad spectrum antiviral agentribavirin 8 mg/kg every 8 hours intravenously or 1.2 g every 12 hours orally, with an oral loading dose of 4 g for those with normal renal function test, for 7-14 days depending on the response and the time of tailing off of corticosteroids
• Hydrocortisone 2 mg/kg every six hours or 4 mg/kg every 8 hours intravenously, tail off over one week when there is clear clinical improvement. For severe and rapidly deteriorating cases, methylprednisolone 10 mg/kg every 24 hours intravenously for two days, and then continue with hydrocortisone as above
• Antibacterial coverage for typical and atypical agents for 7-14 days using drugs such as levofloxacin and macrolides.

Patients should be given antiulcer prophylaxis and monitored for haemoglobin concentration, reticulocyte count, and blood glucose and potassium concentrations. The efficacy of this regimen requires careful assessment.

Precautions
The most likely route of transmission is by droplets and direct inoculation of secretions on to mucus membrane. The serious outbreak in the public hospital could have been due to the use of nebulised bronchodilator in the index patient, causing atomisation of infected secretion.⁶ Procedures thought to increase the risk of disease transmission include diagnostic sputum induction, bronchoscopy, endotracheal intubation, and airway suction.⁷

The precautions for droplet infection should be instituted. Patients should wear N-95 masks once symptoms develop and be placed immediately in isolation facilities with negative pressure. Healthcare workers should wear similar masks together with head cover, goggles, gowns, and gloves when caring for these patients. Daily and terminal disinfection should be thorough, with careful washing and disinfection of the bed, handrails, bedside tables, floor, and equipment with hypochlorite solution (1000 ppm). For intubated patients, the use of closed suction system is essential to avoid air leak and enhanced disease transmission.

Healthcare workers should have a high index of suspicion if they or family members develop fever and features suggestive of severe acute respiratory syndrome. They should present themselves to hospitals rather than treating themselves at home and putting their family members at risk. For doctors in the community, it is advisable to wear a N-95 mask in when seeing any patient with respiratory symptoms. Contacts of proved cases should isolate themselves until the incubation period is over. After contact with patients with respiratory symptoms, careful hand hygiene is necessary, with washing with soap and water.

On 27 March the Department of Health finally announced drastic measures, including vigorous contact tracing and examination, quarantine of contacts in their homes, and closure of all schools and universities. A major hospital has been designated for infected patients. On 1 April all residents from the building in the housing estate where the outbreak occurred were evacuated to a holiday camp. Most public gatherings have been postponed to later dates.

	Conclusions

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Severe acute respiratory syndrome is highly infectious and potentially lethal. It caught the medical profession in Hong Kong unaware. The drastic measures introduced by the Hong Kong government, together with intensive education of the public on personal hygiene and the wearing of masks in public places, will, we hope, halt this epidemic. Other health authorities faced with this disease should consider early introduction of quarantine procedures.

	Acknowledgments

Contributors: WCY helped care for the patients. MC-Y collected data for this report and is guarantor.

	Footnotes

Competing interests: None declared.

	References

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1.	World Health Organization. Severe acute respiratory syndrome (SARS). March 12th 2003. www.who.int/csr/2003_03_12/en
2.	Government of Hong Kong Special Administrative Region Department of Health. Atypical pneumonia. www.info.gov.hk/info/infection-c.htm (accessed 7 Apr 2003).
3.	Tsang KW, Ho PL, Ooi GC, Yee WK, Wang T, Chan-Yeung M, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003 Apr 1 [epub ahead of print]. http://content.nejm.org/cgi/reprint/NEJMoa030666v2.pdf (accessed 7 Apr 2003).
4.	Periris JSM, Lai ST, Poon LLM, Guan Y, Yam LYC, Lim W, et al. Coronavirus as a possible cause of severe acute respiratory syndrom. Lancet Online 2003;8 Apr. http://image.thelancet.com/extras/03art3477web.pdf
5.	Hospital Authority. Severe acute respiratory syndrome: clinical guidelines (revised 27 Mar 2003). www.ha.org.hk/hesd/nsapi/?MIval=ha_view_template&group=PRS&Area=CGL (accessed 7 Apr 2003).
6.	Lee N, Hui D, Wu A, Chan P, Cameron P, Joynt GM, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med 3003;7 Apr. www.nejm.org
7.	Centers for Disease Control and Prevention. Severe acute respiratory syndrome (SARS): information for clinicians. www.cdc.gov/ncidod/sars/clinicians.htm (accessed 7 Apr 2003).

(Accepted 3 April 2003)