-Introduction
-In November 2002, a worker in an agricultural cooperative in a community in Guangdong Province, China (patient No. 1) developed fever and pneumonia. Later on a cook dealing with wild animals was infected (patient No. 2). Afterward cases of pneumonia increased in the neighboring areas. At the beginning, the Chinese authorities had thought this was a kind of pneumonia caused by Chlamydia, and they reported to the WHO that this outbreak had come to an end. However the situation changed completely after a few months. In fact 305 cases of atypical pneumonia (5 fatalities) had been occurring in the meantime. This was officially announced on February 14 after a blank of approximately three months. Now SARS has spread to 31 countries (regions) and affected 8,141 people, of whom 696 have passed away (as of May 25, 2003). SARS has been definitely identified as a global new emerging infectious disease.
-Symposium
An International Symposium on Severe Acute Respiratory Syndrome (SARS) Outbreaks was organized under the auspices of Taiwan's Ministry of Health in the International Conference Hall of Taipei on April 20~21, 2003. Three hundred people from thirteen countries including Japan, Australia, Hong Kong, Malaysia, India, The Philippines, Indonesia, Vietnam, Thailand, the USA, Mali and Russia participated in the symposium to report on the current situation of the SARS epidemic.
  Before the opening address (Dr. Shing-Jer Twu, MD, MPH, PhD, Minister of Health), the death of the clinical doctor Dr. Carlo Urbani who himself contracted SARS was mourned over, and all the participants rose to pay a silent tribute. The symposium progressed in a solemn atmosphere. This article written by the author who had the opportunity to attend the symposium summarizes the proceedings.
Patient No. 0 in Hong Kong
  A doctor (64 years of age) in Guangdong Province, China, ran a fever on February 21, 2003. However he traveled to Hong Kong in order to attend the marriage of a relative and he put up on the 9th floor of the Metropolitan (MP)Hotel. As a result, he became a superspreader (See Note) and spread the infection to other people. He is called Patient Number Zero. Pneumonia infected 87 health-care providers in H hospital where he and 10 other persons who had stayed on the 9th floor of the same hotel were admitted. The ten guests who became infected in the MP hotel contributed to spread the infection further to Vietnam, Canada, Singapore, the US and various regions of China.
  A male person (airport employee aged 26) who happened to visit the MP hotel developed the disease and was admitted to Prince Wales (PW) Hospital. A nosocomial infection developed and also hit health-care providers, patients and visitors. Their number reached 112. A male individual (33 years of age) who received outpatient treatment in that hospital for kidney failure was one of the victims. Then pneumonia infection spread suddenly in a high-rise condominium (Amoy Garden Block E). In fact, 330 people became infected. The source of infection was determined to be the younger brother of a resident of Amoy Garden.
(Note - Superspreaders are known for spreading tuberculosis, smallpox, staphylococcal infection, etc. Superinfectors, super shedders and cloud cases are synonyms. The example of a hundred people who contracted smallpox from individuals who traveled across England by train in 1913 is famous.)
Vietnam F Hospital and Carlo Urbani
  A businessman who was infected in Hong Kong MP Hotel (US citizen, 48 years of age) contracted SARS on February 26 in Hanoi and was admitted to F Hospital. Twenty-two patients developed influenza-like pneumonia inside this hospital until March 20. The infection was also spreading similarly in Canada, Singapore and in the United States. The WHO dispatched a physician to F Hospital. He reported to the WHO that this pneumonia was a "new type of pneumonia" different from the conventional type. This is how an outbreak of infection with the new type of pneumonia became known to the world. Unfortunately the doctor also contracted the new type of pneumonia inside the hospital and passed away on March 29. The victim was Dr.Carlo Urbani (46 years of age), mentioned earlier in this article.
  This new type of pneumonia is named SARS (Severe Acute Respiratory Syndrome), and the virus at the origin of the disease is called SARS virus. The world has been taking a high toll for the control of the sickness.
Program of the symposium
  Following the keynote report on SARS by Dr. Chien-Jen Chan (Chairman of SARS, Taiwan), the current status of SARS and the control measures, the laboratory test techniques, the economic impact caused by the SARS epidemics and other topics were discussed at the various sessions of the symposium.
Etiology, laboratory tests and epidemiology
  The background leading to the identification of coronavirus as the etiological agent, after going through the Chlamydia hypothesis and the meta-pneumovirus hypothesis (Note: about 8% isolated from specimens of patients afflicted with acute respiratory infection. Paramyxovirus isolated from children with pneumonia in Holland in 2002), was explained. (Note: coronavirus was confirmed finally in infection experiments on monkeys. Significance of monkey infection experiments: it is necessary to satisfy the three Koch's postulates in order to establish a specified pathogen as the etiological agent of a disease. Namely, 1) It must be isolated from a high number of patients with the same disease; 2) it must grow in pure culture; and 3) the same disease must be reproduced when the microorganism is inoculated to healthy animals. However these postulates can be applied in case of bacterial infections, and the six Koch's postulates based on Rivers' revision are applied in case of viral infections. Namely, 1) the microorganism must be isolated from the infected host; 2) it must be cultured in host cells; 3) it must be filterable; 4) a similar disease must be reproduced in the host animals; 5) it must be re-isolated from inoculated animals; and 6) the specific immune response to that virus must be confirmed.)
  Amongst the conditions for establishing that the isolated coronavirus is the causal virus for SARS, 1) - 3) have already been validated by several researchers. The veterinary medicine research team of Erasmus Medical Centre in the Netherlands has successfully reproduced a similar SARS infection in an infection experiment with the virus isolated from cynomolgus monkeys. The team also confirmed the re-isolation of the virus and the formation of specific immunity. As a result, the theories of Chlamydia and meta-pneumovirus were totally rejected. (Koch's postulates for SARS virus; Fouchier RA et al., Nature, 2003, May 15, 423 (6937) 240: Department of Virology, Erasmus Medical Centre, 3015 DE Rotterdam, The Netherlands.)
  Virological studies have shown that FRhK-4 cells of Rhesus monkey kidney origin exhibit a high susceptibility to SARS virus and that these infected cells form a syncytium with fused nuclei. Furthermore observation with the aid of the electronic microscope has shown that the viral particles are released from the cell surface and that they accumulate in the cytoplasm. The release of SARS virus particles bore a close resemblance to the budding pattern of paramyxovirus. In addition, the syncytium of the infected Vero cells was similar to that of the paramyxovirus including the measles virus.
Diagnosis and laboratory test techniques
a. Serological diagnosis: detection of SARS antibody by ELISA or indirect fluorescent antibody technique.
b. Genetic diagnosis (RT-PCR technique): use of sense 5' TACACACCTCAGCGTTG 3' and antisense 5' CACCGAACGTGACGAAT     3' as primers. These primers were utilized for gene detection on 23 specimens in total including nasopharynx specimens, urines and feces     of SARS patients in Amoy Garden. Positive results were obtained in 11% in case of the urines and in 94% in case of the feces. These     results underline the utility of feces specimens and of the RT-PCR technique for the early diagnosis and the confirmation diagnosis. (Dr.     Kwol Yung Uuen, Dr. Ka Fai To) (Note: the WHO's SARS Research Network is currently comparing and assessing the detection     results including seven primers and annealing conditions. At this point of time, the detection rate for the genes by means of PCR is on the     order of 50%, and the risk of obtaining false positive has also been pointed out.)
c. Virus isolation: patient specimens are inoculated into susceptible cells such as Vero cells. This procedure is performed inside BSL-3     level laboratories.
Impact on the economy
  The impact caused by the SARS epidemic upon the economy translates currently into a 26% decrease in revenues for the air travel business and a 23% falldown for the hotel business. In the present context, a severe impact on the world economy is feared. The necessity of working out and implementing SARS control policies at the global level was stressed during the symposium (Details omitted)
The SARS clinical profile progresses in three steps.
First stage: virus growth (seven days). Characteristic: fever over 39C Second stage: immunological hypersensitivity (seven days). Characteristics: new episode of fever and disorders of the immune system Third stage: destruction of the lung functions (seven days). Characteristics: decrease in the lung functions. Approximately three weeks from the initial diagnosis (fever) to death (Hong Kong)
Agents for treatment, antiviral agents
  In the United States where no fatal cases have been reported, antiviral agents are not employed for the treatment of SARS. On the other hand, the fatality rate in Hong Kong where antiviral agents are aggressively used is 15%. In the views of the WHO, there exists as of now no effective treatment agent.
Existence of atypical SARS
  There exist patients presenting major symptoms such as diarrhea instead of pneumonia. These cases may be diagnosed with diseases other than SARS.
The approach in Vietnam
  In Vietnam, 63 individuals have contracted SARS so far, and five of them have passed away. Information on SARS patients has been proactively published, hospitals specialized in SARS have been set up and thorough measures have been taken to isolate the patients and to disinfect the affected areas. This country has successfully controlled SARS without causing panic amid the public.
New zoonosis
  The Chinese Ministry of Agriculture has announced that the gene arrangement of the coronavirus isolated from masked palm civets matched perfectly with the SARS virus, and suggested that those animals were the source of infection. On the other hand, there are also reports that the homology does not perfectly match. Whether it is true or not that the source of infection is masked palm civets, SARS is indubitably a new zoonosis.
Participation in the symposium
  The power of transmission of SARS seems to be weaker than that of measles or influenza. However its fatality rate is high. In respect of social defense where no treatment tools are available, SARS constitutes an extremely serious infectious disease. (SARS has been designated as a new infectious disease by the Ministry of Health, Labour and Welfare on April 3.) This disease has flared up again in Taiwan, where it was supposed to have been brought under control, and in Toronto. Disclosure of information and early detection and isolation of patients are indispensable to the control of SARS. Problems of human rights are also involved in case of patient isolation. Nevertheless isolation should be permitted as a matter of course for the protection of the community and from the point of view of public hygiene. True international cooperation free of political interference will be necessary.
  Fortunately enough Japan has not yet been afflicted with SARS. Although there is still some concern regarding the transportation system for SARS patients, preparations for laboratory testing and isolation wards are ongoing. It will probably be possible to contain secondary and tertiary infections, but a non-emotional and prudent approach will be required.
  This "silent war" caused by SARS, which has engendered a three-month blank, is a challenge for humanity in that it lays down the question of how measures for the control of infectious diseases should be in the 21st century.
  To conclude, I wish to extend my deep gratitude to all the persons related to Interchange Association and to the Ministry of Health, Labour and Welfare for having given me the opportunity to attend the International Symposium on SARS Outbreaks.