SARS (Severe Acute Respiratory Syndrome)
SARS (Severe Acute Respiratory Syndrome)
Severe acute respiratory syndrome (SARS) is the first emergent and highly transmissible viral disease to appear among humans during the twenty-first century. Patients with SARS develop flulike fever, headache, malaise, dry cough, and other breathing difficulties. Many patients develop pneumonia, and in 5–10% of cases, the pneumonia and other complications are severe enough to cause death. SARS is caused by a virus that is transmitted usually from person to person—predominantly by the aerosolized droplets of virus infected material.
Many flu causing viruses have previously originated from Guangdong province in China because of cultural and exotic cuisine practices that bring animals, animal parts, and humans into close proximity. In such an environment, pathogens can more easily genetically mutate and make the leap from animal hosts to humans. The first cases of SARS showed high rates among Guangdong food handlers and chefs.
Chinese health officials initially remained silent about the SARS outbreak, and no special precautions were taken to limit travel or prevent the spread of the disease. The world health community, therefore, had no chance to institute testing, isolation, and quarantine measures that might have prevented the subsequent global spread of the disease.
Although not discovered until epidemiologists began to probe the subsequent 2003 outbreak, epidemiologists traced the first known case of what was eventually known as SARS to a November 2002 case in Guangdong province. By mid-February 2003, Chinese health officials tracked more than 300 cases, including five deaths in Guang dong province from what was at the time described as an acute respiratory syndrome.
On February 21, 2003, Liu Jianlun, a 64-year-old Chinese physician from Zhongshan hospital (later determined to have been a “super-spreader,” a person capable of infecting unusually high numbers of contacts) traveled to Hong Kong to attend a family wedding despite the fact that he had a fever. Epidemiologists subsequently determined that Jianlun passed on the SARS virus to other guests at the Metropole Hotel where he stayed—including American businessman Johnny Chen, who was en route to Hanoi, three women from Singapore, two Canadians, and a Hong Kong resident. Jianlun's travel to Hong Kong and the subsequent travel of those he infected allowed SARS to spread from China to the infected travelers’ destinations.
Chen, the American businessman, grew ill in Hanoi, Viet Nam, and was admitted to a local hospital. Chen infected 20 health care workers at the hospital including noted Italian epidemiologist Carlo Urbani who worked at the Hanoi World Health Organization (WHO) office. Urbani provided medical care for Chen and first formally identified SARS as a unique disease on February 28, 2003. By early March, 22 hospital workers in Hanoi were ill with SARS.
Unaware of the problems in China, Urbani's report drew increased attention among epidemiologists when coupled with news reports in mid-March 2003 that Hong Kong health officials had also discovered an outbreak of an acute respiratory syndrome among health care workers. Unsuspecting hospital workers admitted the Hong Kong man infected by Jianlun to a general ward at the Prince of Wales Hospital because it was assumed he had a typical severe pneumonia—a fairly routine admission.
The first notice that clinicians were dealing with an usual illness came—not from health notices from China of increasing illnesses and deaths due to SARS—but from the observation that hospital staff, along with those subsequently determined to have been in close proximity to the infected persons, began to show signs of illness. Eventually, 138 people, including 34 nurses, 20 doctors, 16 medical students, and 15 other health-care workers, contracted pneumonia.
One of the most intriguing aspects of the early Hong Kong cases was a cluster of more than 250 SARS cases that occurred in a cluster of high-rise apartment buildings—many housing health care workers—that provided evidence of a high rate of secondary transmission. Epidemiologists conducted extensive investigations to rule out the hypothesis that the illnesses were related to some form of local contamination (e.g., sewage, bacteria on the ventilation system, etc.). Rumors began that the illness was due to cockroaches or rodents, but no scientific evidence supported the hypothesis that the disease pathogen was carried by insects or animals.
Hong Kong authorities then decided that those suffering the flulike symptoms would be given the option of self-isolation, with family members allowed to remain confined at home or in special camps. Compliance checks were conducted by police.
One of the Canadians infected in Hong Kong, Kwan Sui-Chu, return to Toronto, Ontario, and died in a Toronto hospital on March 5, 2003. As in Hong Kong, because there were no alerts from China about the SARS outbreak, Canadian officials did not initially suspect that Sui-Chu had been infected with a highly contagious virus, until Sui-Chu's son and five health care workers showed similar symptoms. By mid-April 2003 Canada reported more than 130 SARS cases and 15 fatalities.
Increasingly faced with reports that provided evidence of global dissemination, on March 15, 2003, the World Health Organization took the unusual step of issuing a travel warning that described SARS as a “worldwide health threat.” WHO officials announced that SARS cases, and potential cases, had been tracked from China to Singapore, Thailand, Vietnam, Indonesia, Philippines, and Canada. Although the exact cause of the “acute respiratory syndrome” had not, at that time, been determined, WHO officials issuance of the precautionary warning to travelers bound for South East Asia about the potential SARS risk served notice to public health officials about the potential dangers of SARS.
Within days of the first WHO warning, SARS cases were reported in United Kingdom, Spain, Slovenia, Germany, and in the United States.
WHO officials were initially encouraged that isolation procedures and alerts were working to stem the spread of SARS, as some countries reporting small numbers of cases experienced no further dissemination to hospital staff or others in contact with SARS victims. However, in some countries, including Canada, where SARS cases occurred before WHO alerts, SARS continued to spread beyond the bounds of isolated patients.
WHO officials responded by recommending increased screening and quarantine measures that included mandatory screening of persons returning from visits to the most severely affected areas in China, Southeast Asia, and Hong Kong.
On March 29, 2003, Dr. Urbani, the scientist who initially reported a SARS case, died of complications related to SARS contracted while investigating the outbreak.
Mounting reports of SARS showed an increasing global dissemination of the virus. By April 9, 2003, the first confirmed reports of SARS cases in Africa reached WHO headquarters, and, eight days later, a confirmed case was discovered in India.
WHO took the controversial additional step of recommending against non-essential travel to Hong Kong and the Guangdong province of China. The recommendation, sought by infectious disease specialists, was not controversial within the medical community, but caused immediate concern regarding the potentially widespread economic impacts.
In China, fear of a widespread outbreak in Beijing caused a late, but intensive, effort to isolate SARS victims and halt the spread of the disease. By the end of April 2003, schools in Beijing were closed as were many public areas. Despite these measures, SARS cases and deaths continued to mount. According to the World Health Organization, by the end of the outbreak in July 2003, 8098 people worldwide had contracted SARS, and 774 had died from complications of the disease. In the United States eight people had laboratory evidence of SARS infection and all of the patients had recently traveled out of the country to places with SARS outbreaks.
The 2003 SARS outbreak then subsided almost as quickly as it arose.
In 2004, Chinese officials reported new cases of possible SARS in Beijing and in Anhui Province with at least one confirmed death. Almost 100 contacts were placed under medical observation. Chinese authorities reported outbreaks of SARS affecting laboratory workers who were exposed to the virus. In late 2004, four more unlinked, community-acquired cases of SARS were found in Guangdong province, and, although the source of this outbreak was unconfirmed, it is suspected to have originated in wild animals, most likely those found in food markets.
At the end of April 2003, SARS public health officials expressed concern that SARS had the potential to become a global pandemic. Scientists, public health authorities, and clinicians around the world struggled to both treat and investigate the disease.
Global efforts at isolation, quarantine, and observation proved effective and a pandemic did not occur, however, and the last SARS infection in humans was reported in China in 2004.
As of May 2007, the Centers for Disease Control and Prevention (CDC) and World Health Organization reported no current cases of SARS anywhere in the world.
Scientists scrambled to isolate, identify, and sequence the pathogen responsible for SARS. Modes of transmission characteristic of viral transmission allowed scientists to place early attention on a group of viruses termed coronaviruses—some of which are associated the common cold. There was a global two-pronged attack on the SARS pathogen, with some efforts directed toward a positive identification and isolation of the virus and other efforts directed toward discovering the genetic molecular structure and sequence of genes contained in the virus. The development of a genomic map of the precise nucleotide sequence of the virus would be key in any subsequent development of a definitive diagnostic test, the identification of effective anti-viral agents, and perhaps a vaccine.
The development of a reliable and definitive diagnostic test was considered of paramount importance in keeping SARS from becoming a global pandemic. A definitive diagnostic test would not only allow physicians earlier treatment options, but would also allow the earlier identification and isolation of potential carriers of the virus.
Without advanced testing, physicians were initially forced to rely upon less sensitive tests that were unable to identify SARS prior to 21 days of infection, in most cases too late to effectively isolate the patient.
In mid-April 2003, Canadian scientists at the British Columbia Cancer Agency in Vancouver announced that they had sequenced the genome of the coronavirus most likely to be the cause of SARS. Within days, scientists at the Centers for Disease Control (CDC) in Atlanta, Georgia, offered a genomic map that confirmed more than 99% of the Canadian findings. Both genetic maps were generated from studies of viruses isolated from SARS cases. The particular coronavirus mapped had a genomic sequence of 29,727 nucleotides—average for the family of coronavirus that typically contain between 29,000 and 31,000 nucleotides.
Proof that the coronavirus mapped was the specific virus responsible for SARS would eventually come from animal testing. Rhesus monkeys were exposed to the virus via injection and inhalation and then monitored to determine whether SARS-like symptoms developed, and then if sick animals exhibited a histological pathology (i.e., an examination of the tissue and cellular level pathology) similar to findings in human patients. Other tests, including polymerase chain reaction (PCR) testing, helped positively match the specific coronavirus present in the lung tissue, blood, and feces of infected animals to the exposure virus.
Identification of a specific pathogen can be a complex process, and positive identification requires thousands of tests. All testing is conducted with regard to testing Koch's postulates—the four conditions that must be met for an organism to be determined to the cause of a disease. First, the organism must be present in every case of the disease. Second, the organism must be able to be isolated from the host and grown in laboratory conditions. Third, the disease must be reproduced when the isolated organism is introduced into another, healthy host. The fourth postulate stipulates that the same organism must be able to be recovered and purified from the host that was experimentally infected.
SARS has an incubation period range of 2–7 days, with an average incubation of about four days. In some cases incubation has taken 10 days, and, in a very rare number of cases, as long as 14 days. Much of the inoculation period allows the virus to be both transported and spread by an asymptomatic carrier. With air travel, asymptomatic carriers can travel to anywhere in the world. The initial symptoms are non-specific and common to the flu. Infected cases then typically spike a high fever 100.4°F (38°C) as they develop a cough, shortness of breath, and difficulty breathing. SARS often fulminates (reaches it maximum progression) in a severe pneumonia that can cause respiratory failure and results in death in about 10% of its victims.
No definitive therapy has been demonstrated to have clinical effectiveness against the virus that causes SARS. Antibiotics, antiviral medications, corticosteroids, and supportive therapies such as fluids and ventilation are the mainstays of treatment for SARS.
Isolation and quarantine remain potent tools in the modern public health arsenal. Both procedures seek to control exposure to infected individuals or materials. Isolation procedures are used with patients with a confirmed illness. Quarantine rules and procedures apply to individuals who are not currently ill, but are known to have been exposed to the illness (e.g., been in the company of a infected person or come in contact with infected materials).
Isolation and quarantine both act to restrict movement and to slow or stop the spread of disease within a community. Depending on the illness, patients placed in isolation may be cared for in hospitals, specialized health care facilities, or, in less severe cases, at home. Isolation is a standard procedure for TB patients. In most cases, isolation is voluntary; however, isolation can be compelled by federal, state, and some local law.
WORDS TO KNOW
ASYMPTOMATIC: A state in which an individual does not exhibit or experience symptoms of a disease.
DISSEMINATION: The spreading of a disease in a population, or of disease organisms in the body, is dissemination. A disease that occurs over a large geographic area.
NUCLEOTIDE SEQUENCE: A particular ordering of the chain structure of nucleic acid that provides the necessary information for a specific amino acid.
Before the advent of vaccines and effective diagnostic tools, isolation and quarantine were the principal tools to control the spread of infectious disease. The term “quarantine” derives from the Italian quarantine and quaranta giorni and dates to the plague in Europe. As a precautionary measure, the government of Venice restricted entry into the port city and mandated that ships coming from areas of plague—or otherwise suspected of carrying plague—had to wait 40 days before being allowed to discharge their cargos. The legal basis of quarantine in the United States was established in 1878 with the passage of Federal Quarantine Legislation in response to continued outbreaks of yellow fever, typhus, and cholera.
During the later years of the nineteenth century and throughout the twentieth century, the law bent toward protecting the greater needs of society. Quarantine was often used for political, as well as medical, reasons; it was implemented to contain and discourage immigration. In other cases, such as with tuberculosis (TB), quarantine, proved effective and courts wielded wide authority to isolate, hospitalize, and to force patients to take medications.
The public discussion of SARS-related quarantine in the United States and Europe renewed tensions between the needs for public heath precautions that safeguard society at large and the liberties of the individual.
States governments within the United States have a general authority to set and enforce quarantine conditions. At the federal level, the CDC's Division of Global Migration and Quarantine is empowered to detain, examine, or conditionally release (release with restrictions on movement or with a required treatment protocol) individuals suspected of carrying certain listed communicable diseases.
IN CONTEXT: REAL-WORLD RISKS
With regard to severe acute respiratory syndrome (SARS) the Centers for Disease Control and Prevention (CDC) states that “available information suggests that persons with SARS are most likely to be contagious only when they have symptoms, such as fever or cough. Patients are most contagious during the second week of illness. However, as a precaution against spreading the disease, CDC recommends that persons with SARS limit their interactions outside the home (for example, by not going to work or to school) until 10 days after their fever has gone away and their respiratory (breathing) symptoms have gotten better.”
“To date, no cases of SARS have been reported among persons who were exposed to a SARS patient before the onset of the patient's symptoms. If transmission of SARS recurs, there are some common-sense precautions that you can take that apply to many infectious diseases. The most important is frequent handwashing with soap and water or use of an alcohol-based hand rub. You should also avoid touching your eyes, nose, and mouth with unclean hands and encourage people around you to cover their nose and mouth with a tissue when coughing or sneezing.”
SOURCE: Centers for Disease Control and Prevention
In 2003 the CDC recommended SARS patients be voluntarily isolated, but did not recommend enforced isolation or quarantine. Regardless, CDC and other public heath officials, including the Surgeon General, sought and secured increased powers to deal with SARS. On April 4, 2003, U.S. President George W. Bush signed Presidential Executive Order 13295 that added SARS to a list of quarantinable communicable diseases. The order provided heath officials with the broader powers to seek “… apprehension, detention, or conditional release of individuals to prevent the introduction, transmission, or spread of suspected communicable diseases…”
Other diseases on the U.S. communicable disease list, specified pursuant to section 361(b) of the Public Health Service Act, include “Cholera; Diphtheria; infectious Tuberculosis; Plague; Smallpox; Yellow Fever; and Viral Hemorrhagic Fevers.”
Canada, hit early and much harder by SARS than the United States, responded by closing schools and some hospitals in impacted areas. Canadian health officials advised seemingly healthy travelers from areas with known SARS cases to enter into a 10-day voluntary quarantine. Once in isolation, individuals were asked to frequently take their temperature and remain separated from other family members. Within a month, almost 10,000 people were in some form of quarantine. Canadian government officials, including then Prime Minister Jean Chrétien, publicly complained when, on April 23, the WHO recommended a three-week postponement of non-essential travel to Toronto. After criticism and intense lobbying of WHO by Chrétien's government and Canadian public health officials, WHO discontinued the recommendation on April 30, 2003. When Canada's cases of SARS spiked, Toronto was returned to the WHO list and was not removed until July 2, 2003. WHO officials kept in place similar warnings about travel to Beijing and Hong Kong.
Faced with a more immediate danger and larger numbers of initial cases, an authoritarian government in Singapore was less hesitant in ordering quarantine of victims and those potentially exposed to the virus. One of the three Singapore women initially infected in Hong Kong was later identified as a super-spreader who infected more than 90 people. She recovered, but both her mother and father died of SARS.
During the 2003 outbreak, passengers arriving in Singapore coming from other countries with SARS were required to undergo questioning by nurses in isolation garb and then required to walk through a thermal scanner calibrated to detect an elevated body temperature. Soldiers immediately escorted those with elevated temperatures into quarantine facilities. Those subsequently allowed to remain in their homes were monitored by video cameras and electronic wristbands.
Health authorities assert that the emergent virus responsible for SARS will remain endemic (part of the natural array of viruses) in many regions of China, and that outbreaks could continue on a seasonal basis.
In the aftermath of the 2003 SARS outbreak, a Chinese official publicly apologized for a slow and inefficient response to the 2003 SARS outbreak. Allegations that officials covered up the true extent of the spread of the disease caused the dismissal of several local administrators including China's public health minister and the mayor of Beijing. This admission was politically significant for the new leadership in China, and encouraging to many in the public health services. Reporting procedures and compliance to international health regulations still, however, show wide differences and sensitivities to political issues not only for China but many other nations and or local regions.
The 2003 SARS outbreak provided a test of recent reforms in International Health Regulations designed to increase surveillance and reporting of infectious diseases—and to enhance cooperation in preventing the international spread of disease. Although not an act of bioterrorism, because the same epidemiologic principles and isolation protocols might be used to both initially determine and initially respond to an act of bioterrorism, intelligence and public heath officials closely monitored the political, scientific, and medical responses to the SARS outbreak. In many regards, the SARS outbreak provided a real and deadly test of public health responses, readiness, and resources.
Dr. Carlo Urbani, an Italian physician and specialist in infectious diseases, was among the first to recognize SARS as a new infectious disease threat. Along with other virus hunters, Dr. Urbani's skill, bravery and dedication helped save lives, but cost him his own. The following is an report of his death as published in the New England Journal of Medicine.
SARS and Carlo Urbani
On February 28, the Vietnam French Hospital of Hanoi, a private hospital of about 60 beds, contacted the Hanoi office of the World Health Organization (WHO). A patient had presented with an unusual influenza-like virus. Hospital officials suspected an avian influenza virus and asked whether someone from the WHO could take a look. Dr. Carlo Urbani, a specialist in infectious diseases, answered that call. In a matter of weeks, he and five other health care professionals would be dead from a previously unknown pathogen.
We now know that Hanoi was experiencing an outbreak of severe acute respiratory syndrome (SARS). Dr. Urbani swiftly determined that the small private hospital was facing something unusual. For the next several days, he chose to work at the hospital, documenting findings, arranging for samples to be sent for testing, and reinforcing infection control. The hospital established an isolation ward that was kept under guard. Dr. Urbani worked directly with the medical staff of the hospital to strengthen morale and to keep fear in check as SARS revealed itself to be highly contagious and virulent. Of the first 60 patients with SARS, more than half were health care workers. At a certain moment, many of the staff members made the difficult decision to quarantine themselves. To protect their families and community, some health care workers put themselves at great personal risk, deciding to sleep in the hospital and effectively sealing themselves off from the outside world.
In some ways, the SARS outbreak in Hanoi is a story of what can go right, of public health's coming before politics. First-line health care providers quickly alerted the WHO of an atypical pneumonia. Dr. Urbani recognized the severity of the public health threat. Immediately, the WHO requested an emergency meeting on Sunday, March 9, with the Vice Minister of Health of Vietnam. Dr. Urbani's temperament and intuition and the strong trust he had built with Vietnamese authorities were critical at this juncture. The four-hour discussion led the government to take the extraordinary steps of quarantining the Vietnam French Hospital, introducing new infectioncontrol procedures in other hospitals, and issuing an international appeal for expert assistance. Additional specialists from the WHO and the Centers for Disease Control and Prevention (CDC) arrived on the scene, and Médecins sans Frontiéres (MSF, or Doctors without Borders) responded with staff members as well as infection-control suits and kits that were previously stocked for outbreaks of Ebola virus. The Vietnam French Hospital has been closed temporarily, and patients with SARS are cared for in two wards of the public Bach Mai Hospital, with the assistance of a team from MSF. No new cases in health care workers have been reported, and the outbreak in Vietnam appears to be contained. By dealing with the outbreak openly and decisively, Vietnam risked damage to its image and economy. If it had decided to take refuge in secrecy, however, the results might have been catastrophic.
IN CONTEXT: EFFECTIVE RULES AND REGULATIONS
The 2003 severe acute respiratory syndrome (SARS) outbreak did not spread within the United States. In response to the 2003 SARS outbreak, the Centers for Disease Control and Prevention (CDC) states that its responses to the outbreak were as follows: That the “CDC:
- Worked closely with WHO and other partners in a global effort to address the SARS outbreak of 2003.
- Activated its Emergency Operations Center to provide round-the-clock coordination and response.
- Committed more than 800 medical experts and support staff to work on the SARS response.
- Deployed medical officers, epidemiologists, and other specialists to assist with on-site investigations around the world.
- Provided assistance to state and local health departments in investigating possible cases of SARS in the United States.
- Conducted extensive laboratory testing of clinical specimens from SARS patients to identify the cause of the disease.
- Initiated a system for distributing health alert notices to travelers who may have been exposed to cases of SARS.”
SOURCE: Centers for Disease Control and Prevention
Dr. Urbani would not survive to see the successes resulting from his early detection of SARS. On March 11, he began to have symptoms during a flight to Bangkok. On his arrival, he told a colleague from the CDC who greeted him at the airport not to approach him. They sat down at a distance from each other, in silence, waiting for an ambulance to assemble protective gear. He fought SARS for the next 18 days in a makeshift isolation room in a Bangkok hospital. Dr. Carlo Urbani died on March 29, 2003.
SARS is a pandemic of our global age. In just a few weeks, SARS had spread through air travel to at least three continents. Conversely, in the same amount of time, researchers working in no fewer than 10 countries have collaborated to identify the virus, sequence its genome, and take steps toward rapid diagnosis. It is now hoped that the large strides taken in basic research will quickly lead to therapeutic advances or a vaccine.
Health care workers continue to be on the front line. Apart from the index patient, all the patients in the Vietnamese outbreak who died were doctors and nurses. In Hong Kong, approximately 25 percent of patients with SARS have been health care professionals, including the chief executive of the hospital authority. The intensive care wards are full—a situation that is exacerbated by the staffing difficulties presented by the hundreds of SARS cases affecting medical personnel. It is becoming difficult to import additional infection-control equipment, since countries where the suits are manufactured are holding onto their stocks as they brace themselves for outbreaks of SARS within their own borders. Once effective drug therapy has been found, similar problems may arise with availability and distribution, especially if the effective treatment turns out to involve a relatively rare and expensive drug, such as ribavirin.
It remains to be seen whether the number of new SARS outbreaks will ebb or whether what we have seen to date is indeed the leading edge of a much larger pandemic. Currently, the attack rate in Hong Kong is approximately 2 cases per 10,000 population over the course of two months. This rate compares favorably with the seasonal attack rates of influenza-like illness, which reached 50 cases per 10,000 population in one week this winter in Europe.
In 1999, Dr. Urbani was president of MSF-Italy and a member of the delegation in Oslo, Norway, that accepted the Nobel Peace Prize. Although he would be gratified that so much has been accomplished with respect to SARS in such a short time, he would certainly point out that the other diseases he worked with—such as the human immunodeficiency virus and AIDS, tuberculosis, and malaria, which kill millions of people each year—deserve to be treated with similar urgency. Whatever the future direction of SARS, it is clear that Dr. Urbani's decisive and determined intervention has bought precious time and saved lives. We remember Dr. Urbani with a mixture of pride in his selfless devotion to medicine and unspeakable grief about the void his departure has left in the hearts of his colleagues around the world.
Source Information: From Médecins sans Frontiéres (Doctors without Borders) U.S.A. (B.R.), Belgium (M.V.H.), Vietnam (D.S.), and Italy (N.D.)
Brigg Reilley, M.P.H., Michel Van Herp, M.D., M.P.H., Dan Sermand, Ph.D., and Nicoletta Dentico, M.P.H.
“SARS AND CARLO URBANI.” NEW ENGLAND JOURNAL OF MEDICINE. MAY 15, 2003. <HTTP://CONTENT.NEJM.ORG/CGI/CONTENT/FULL/348/20/1951> (ACCESSED JUNE 11, 2007).
See AlsoContact precautions; Developing Nations and Drug Delivery; Emerging Infectious Diseases; Influenza; Influenza Pandemic of 1918; Influenza, Tracking Seasonal Influences and Virus Mutation; Isolation and Quarantine; Notifiable Diseases; Pandemic Preparedness; Personal Protective Equipment; Standard Precautions; Vaccines and Vaccine Development.
Ksiazek T.G., et al. “A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome.” New England Journal of Medicine. 10.1056. April 10, 2003.
Rosenthal, E. “From China's Provinces, a Crafty Germ Spreads.” New York Times. April 27, 2003.
Centers for Disease Control and Prevention (CDC). “Severe Acute Respiratory Syndrome (SARS).” <http://www.cdc.gov/ncidod/sars/index.htm> (accessed May 30, 2007).
World Health Organization. “Investigation into China's Recent SARS Outbreak Yields Important Lessons for Global Public Health.” <http://www.wpro.who.int/sars/docs/update/update_07022004.asp> (accessed May 30, 2007).
Brenda Wilmoth Lerner