The Severe Acute Respiratory Syndrome outbreak – what lessons have been learned?

Severe acute respiratory syndrome (SARS) is the first new infectious disease of the twenty-first century that poses a threat to international health. Originating in southern China in November 2002, it was brought to Hong Kong in February 2003 and then rapidly spread worldwide though mostly to Asian countries. At the end of the epidemic in July 2003, the global cumulative total was 8,098 cases with 774 deaths in 29 countries/regions on five continents (mortality 9·6%).[1] Of the ten most-affected countries/regions, seven were in Asia (mainland China, Hong Kong, Taiwan, Singapore, Vietnam, the Philippines, and Thailand).[1,] [2] Mainland China and Hong Kong together accounted for 87% of cases and 84% of deaths. It was a terrible experience for all of us, with tremendous suffering from morbidities and loss of lives, break-point straining of healthcare resources, disruption of everyday life and a great setback for travel and business around the world, particularly in Asia. In Hong Kong, for instance, commercial aircraft movements dropped by 49% during the peak of the SARS outbreak in May 2003,[3] and hotel occupancy rates plunged to an all-time low of 17%, against 83% in May 2002.[4] The devastation inflicted on tourism, business and the economy was unprecedented in the history of modern medicine.[5] It is now the right time to reflect on what we have learned from this outbreak. On the positive side, medical scientists and healthcare professionals have stood up to the challenge, and have shown the highest level of dedication and professionalism in fighting bravely in the front line to contain the infection, and in disseminating promptly information regarding clinical features, radiological features, modes of transmission, and the results and problems of different treatments.[6,] [7,] [8,] [9,] [10] Using modern molecular technology and the coordination of the World Health Organization, medical scientists have been quick to identify and characterise the novel coronavirus as the causative virus of SARS (SARS-CoV).[11,] [12,] [13] Laboratory tests, though far from ideal, have been developed to detect antibodies and SARS-CoV RNA.[14] However, governments and medical and health authorities now realise that we were poorly prepared for this SARS onslaught and our response was less than satisfactory. The Government and Hospital Authority of Hong Kong have therefore commissioned the independent SARS Expert Committee and the Hospital Authority Review panel on the SARS Outbreak respectively to conduct reviews on the capacity of the healthcare system and propose ways to prepare better for any future outbreaks. The Reports chronicled the outbreak, defined the deficiencies of the system, and made recommendations for strengthening surveillance and reporting systems, for comprehensive contingency planning, for clear command and control structures, and for developing effective communications.[15] A Centre for Health Protection will be set up with the responsibility, authority and accountability for the prevention and control of communicable diseases. A number of questions regarding the virus and the disease remain unanswered. The SARS-CoV is a new pathogen for humans, thought to have originated in wild game animals such as Himalayan palm civet cats, which 'jumped species' to infect humans in the recent past. Anecdotal reports together with a study in wild game animals market in southern China showing a higher seropositivity for SARS-CoV in wild animal traders than controls, appear to support this hypothesis.[16] Its precise origin, animal reservoirs and pathogenesis, modes of transmission other than by droplets and fomites, infectivity during the incubation period and after clinical recovery, and endemicity, are still unknown. A recent report found no transmission on an aircraft by a person with presymptomatic SARS.[17] The treatment for SARS is largely anecdotal, and there are no controlled trials to support or refute any treatment modalities. Current understanding, obtained from observational studies, combined with general virology principles, suggests three pathogenic stages of SARS, namely viral replication, inflammatory pneumonitis and residual pulmonary fibrosis.[11,] [18,] [19] While these stages can be identified conceptually, one should appreciate that they often overlap chronologically and vary remarkably in duration, as some patients appear to have rapidly progressive disease while others present in a more indolent fashion.[20] Historically, before SARS was even defined by the WHO, early patients were treated with a broad spectrum anti-viral agent, ribavirin, and corticosteroid.[6] The apparent good progress and recovery of the first few patients led to the adoption of this combination as the standard treatment for SARS in Hong Kong and elsewhere,[6,] [7,] [9,] [18,] [21,] [22] although there was considerable skepticism about its safety and efficacy.[23,] [24,] [25] Ribavirin was considered to have caused significant anaemia, haemolysis and liver dysfunction in Canadian SARS patients, although the incidence of these was lower among Hong Kong patients who received a lower dose.[7,] [9] High dose corticosteroid has been associated, as expected, with sepsis, particularly ventilator associated pneumonia and even systemic fungal infection.[26] More recently, about 12% (49/418) of Hong Kong patients with SARS were found to have avascular necrosis (AVN) of the hips and knees on MRI examination (unpublished and preliminary data). This high incidence strongly suggests that SARS-CoV may have been a contributory factor to AVN as corticosteroids are not uncommonly used in patients suffering from rejection of transplanted organs without such a high incidence of AVN. This is supported by the other extrapulmonary manifestations in SARS, including residual diastolic cardiac dysfunction and liver dysfunction in SARS.[27,] [28] Further cross-sectional analysis might help delineate the pathogenesis of AVN in SARS. Ribavirin and corticosteroid as an initial treatment for SARS is now considered scientifically unsound in Hong Kong and worldwide. However, there is consensus that high-dose methylprednisolone, 250–500 mg daily for three to six days, can be lifesaving for patients with radiographically deteriorating pulmonary consolidation, increasing oxygen requirement and respiratory distress (e.g. a respiratory rate of 30/min), i.e. the syndrome of 'critical SARS'.[29] A recent retrospective study revealed that administration of a combination of Kaletra (ritonavir 400 mg and lopinavir 100 mg), an antiprotease designed for treatment of HIV infection, and ribavirin appeared to be associated with reduced mortality, intubation rate, and the need for pulse corticosteroid rescue therapy (Dr CM Chu, personal communication). This finding, the only clinical observation showing some efficacy of a combined antiviral treatment, has been adopted in the design of a controlled trial in Hong Kong, in case SARS should ever recur. Other sequalae of SARS include inability to concentrate, hair loss, anxiety and depression, which could be stress-related, consequences of 'SARS treatment' or a complication of SARS-CoV infection. Longitudinal assessment of lung function is being studied in Hong Kong in survivors of SARS, and preliminary findings suggest a restrictive defect. This is consistent with findings of residual fibrosis and sometimes traction bronchiectasis revealed by high resolution CT studies.[30] Reassuringly, SARS patients, who were typically discharged after two to three weeks, do not appear to have infected their close contacts, strongly suggesting that recovering patients are probably not very infective. The SARS outbreak is a sober reminder in this age of heavy air travel and globalization that any emerging infectious disease can spread rapidly around the world. A number of important lessons have been learned. First, to control an emerging infection quickly and to prevent spread across boundaries, outbreaks must be reported as early as possible to neighbouring countries and regions and to the World Health Organization (WHO). Second, health authorities must be prepared for major outbreaks, by having infection-control and quarantine guidelines capable of being implemented as soon as the outbreak is reported.[15] Third, the WHO has demonstrated its unique value in issuing international alerts, coordinating international medical and scientific efforts and collating and disseminating information and advice. The WHO website must have been one of the most frequently visited in the first half of the year. And fourth, with the distinct possibility that this new SARS coronavirus has crossed the species barrier from animals to human, we need to revisit the human-animal habitat, especially the closeness between man and animals in southern China where wild game cuisines are so popular. This provides an ecosystem for the interaction of wild game animal virus and human virus, allowing genetic recombination or assortment to produce deadly new variants to infect humans. The south China live animal market study[16] should lead to sober reflection on the wisdom of the wild-game-eating habits in Hong Kong and southern China. At this time we cannot predict whether the SARS epidemic will return (12 January 2004). However, we must remain vigilant, and the two laboratory-acquired cases (Singapore announced on 9 September 2003 and Taiwan announced on 17 December 2003) and the one confirmed case and two suspected cases in Guangzhou, Guangdong, China up to date (12 January 2004), none laboratory-acquired, serve as a grim warning to us all.[31] This time, the lesson has been learned, and the international medical and health community has reacted promptly to disseminate information, provide appropriate quarantine and to implement train and airport health check measures. The WHO has also drawn attention to the most recent biosafety guidelines for SARS laboratories handling SARS specimens,[32] and has sent a team to China to help investigate the source of the infection. The press announcement on 5 January 2004 by the University of Hong Kong and Guangzhou Institute of Respiratory Diseases that the strain of the virus in the Guangdong patient confirmed to have SARS is almost identical to the strain in civet cats has led to prompt action from the Guangdong authorities. They have slaughtered 10,000 civet cats in the province and have imposed an immediate ban on the farming, transport, sale, and consumption of civet cats, badgers and raccoon dogs.[31] Tens of thousands of people travel between Hong Kong and Guangdong province every day, and the port control, health and hospital authorities and healthcare professionals in Hong Kong are on full alert. With such alertness and preparedness at regional and international levels, we should be able to contain and control not only a major SARS resurgence, but any outbreak of other major infectious diseases in the future. (Asia has borne the brunt of the SARS outbreak, and Respirology, official journal of the Asian Pacific Society of Respirology, published a SARS Supplement in November 2003, covering clinical virology and pathogenesis, epidemiology, radiology, clinical features and diagnosis, pharmacotherapy, ventilatory and intensive care, prognosis, outcome and sequalae, hospital infection control and admission strategies, and public health measures. The articles are written by hands-on clinicians, public health experts and medical scientists at the forefront of the battle against SARS who have contributed significantly to the current literature on the disease. Interested readers are invited to read the Supplement by visiting the [website](http://www.blackwellpublishing.com/journal.asp?ref=1323-7799&site=1), and clicking 'SARS supplement authored and edited by hands-on clinicians for all clinicians' )

2007-01-21T14:32:48Z

None declared.

2004-10-16T00:00:00Z

2006-08-01T00:00:00Z

the-severe-acute-respiratory-syndrome-outbreak-what-lessons-have-been-learned

2004-10-16T00:00:00Z

The SARS outbreak was the first new infectious disease of the twenty-first century that posed a major threat to international health. Originating in southern China in November 2002, it rapidly spread worldwide and caused 774 deaths. In this article Prof Wah-kit Lam and Prof Kenneth Tsang examine the lessons to be learned from this outbreak.