The main topics based on their importance as epidemiological indicators of the potential impact of the SARS epidemic and the potential for prevention, containment, elimination and eradication focused in this overview are: incubation period, period of communicability, mode and risk factors for infectious agent transmission, the significance of asymptomatic infection, stability of SARS-CoV in environment, the significance of animal reservoirs and prevention of SARS-CoV transmission.
Many countries reported median incubation period of four-five days, and a mean of four-six days with minimum incubation period of one day reported from China and Singapore and the maximum of fourteen days reported by China; Hong Kong SAR estimated of the mean of 6,37 days. The time from infection to onset of symptoms was 16,69 days and 95% of the patients experienced the onset of symptoms within 14,22 days (1). Several countries (Canada, Singapore, Viet Nam, Taiwan and WHO European Region) observed the maximum incubation period of ten days. For public health policy purposes WHO recommended to apply the maximum incubation period of ten days.
Period of communicability.
The experience in Singapore indicates that severely ill patients or those experiencing rapid clinical deterioration, usually during the second week of disease, present the highest communicability. It is important to note that secondary cases occur seldom when clinical cases are isolated within five days of disease onset (2).
These epidemiological observations correlate with the results of laboratory investigations (RT-PCR): virus excretion from the respiratory tract starts on 0-2 days from illness onset (31% samples positive), increases between 3-5 days (43% positive), while the greatest degree of virus excretion is found within 6-14 days (57-60% positive) of disease. Virus excretion declines between 15-17 days (35% positive), and a further decline is noted between 21-23 days (13% positive) following onset of disease.
Virus shedding in stool begins within 3-5 days (57% positive) following onset of disease with a maximum between 6-14 days (86-100% positive). A decline in virus shedding is observed on 15-17 days (33% positive) following onset of disease. Virus shedding in urine is positive on tenth day from onset of disease among 50% of all cases, while 35% are positive on day 16 and 21% positive on day 21 (3). There is some clinical evidence that communicability starts in the early predromal period and at 1-2 days after the onset of symptoms. Communicability is the highest in the second week of clinical disease.
In Hong Kong SAR 1,2% of family and social contacts under surveillance and 2,4% of contacts under home confinement developed SARS. In Singapore a small number of "superspreading events" accounted for a very large number of secondary cases: five probable SARS cases contaminated 103 of the total 206 reported cases. Each of these patients infected over ten health care workers or visitors and household and/or social contacts (4).
WHO guidelines on the clinical management and medical follow-up of patients with SARS were reviewed in light of the epidemiological findings on the period of communicability. There were no data of communicability or infectious agent transmission after ten days following the resolution of fever. This is consistent with he total period of isolation following fever defervescence recommended by WHO (5, 6).
Mode and risk factors for infectious agent transmission.
Primary mode of infectious agent transmission is through direct contact of the mucous membrane (eyes, nose, mouth) with respiratory droplets and/or through exposure to fomites. Contamination have occurred primarily in persons with close contact with SARS patients in health care and household settings. Transmission to casual and social contacts has occurred as a result of intense exposure to a SARS patient in workplaces, hotels, airplanes, trains, taxis or in high-risk transmission settings such as hospitals and households. The finding that each patient infected on average three contact persons is consistent with a disease spread by direct contact with virus droplets containing virus that spread only few meters.
Aerosolising procedures in hospitals, and other events that promote the aerolisation of infectious respiratory droplets and other potentially infectious materials (faeces or urine), may increase the degree of transmission. In Hong Kong SAR households SARS virus was aerosolised within the confines of very small bathrooms and may have been inhaled, ingested or transmitted indirectly by contact with fomites as the aerosol settled.
The role of faecal-oral transmission has not been confirmed; there is no current evidence that this mode of transmission plays a key role in the transmission of SARS-CoV. However, in some SARS outbreaks diarrhea has been reported as a dominating clinical symptom (73% in Hong Kong SAR, 50% in Viet Nam, 57% in Taiwan and 28% in Canada, Ontario). Therefore, given that viral load and excretion were greatest in stool, faecal-oral transmission could be an important mode of transmission.
In health care facilities, households and other closed environments contamination of materials or objects by infectious respiratory secretions or other body fluids (saliva, urine, faeces) could play a role in virus transmission.
There have been no reports of food or waterborne virus transmission. However, more than one third of the early SARS cases in Southern China reported before February 1, 2003 were notified among food handlers, and from November 16, 2002 to April 16, 2003 42,8% of SARS cases who worked in kitchens (7).
The group at highest risk for SARS-infection was clearly defined: health care workers, especially those involved in procedures generating aerosols, accounted for 21% of all cases, ranging from 3% of reported probable cases in the USA to 43% in Canada. Risk factors include household contact with a probable SARS case, increasing age, male gender and the presence of co-morbidities. The care and slaughter of wildlife animals for human consumption in the wet markets of Southern China could be also a risk factor.
The transmission of SARS-CoV in Hong Kong SAR has been attributed in part to environmental contamination, with a possible animal vector as well rodents and cockroaches as mechanical vectors (8, 9).
Occupational risk (attack rate percentage by occupational risk group) was high in Hanoi French Hospital: for any doctor 16%, nurse 35%, administrative staff 2% and other staff with a patient contacts 53%. The secondary attack rate among contacts of one well-tracked case was 6%. In one chain of a virus transmission four contact generations were identified (7).
Air travel as a risk factor was associated with limited number of cases: a total of 29 secondary cases have been linked to probable SARS cases who travelled while symptomatic. No evidence of confirmed virus transmission on flights was found after the March 27, 2003 travel advisory in which WHO recommended exit screening of passengers departing from areas reporting local transmission and other measures to reduce opportunities for further international spread associated with air travel (7).
The long persistence of SARS-CoV in the environment may be a risk factor for contamination. The presence of SARS-CoV RNA was demonstrated on the carpet and elevator areas three months after the index case left the hotel in Hong Kong.
Children were rarely affected by SARS. Epidemiological investigations have found no evidence of SARS-CoV transmission in schools. There have been two reports of SARS transmission from children to adults and no reports of transmission from children to other children. No perinatal virus transmission to infants was detected. There has been no known virus transmission in public access buildings and public transport.
The significance of asymptomatic infection.
There were no reports of the SARS-CoV transmission from asymptomatic individuals. However, there were several reports on SARS-CoV positivity and seroconversion in persons who did not meet the case definitions for a SARS case. WHO recommended that the proportion of contacts who develop symptomatic and asymptomatic SARS-infection and the public health significance of positive laboratory findings in asymptomatic persons and people with symptoms that do not reach the criteria for a suspect or probable SARS case should be determined.
Stability of the SARS-CoV in environment.
SARS-CoV is stable at room temperature in baby stool for three hours, in normal stool for six hours, in diarrheal stool for four days and in urine at least for 24 hours. Virus loses infectivity after exposure to different commonly used disinfectants and fixatives at room temperature including 10% acetone, 10% formaldehyde and paraformaldehyde, 10% clorox, 2% phenol and 75% ethanol for less than five minutes. Heat at +56ºC kills the virus at around 10 000 units per 15 minutes. A minimal reduction in virus concentration appears after 21 days at +4ºC and -80ºC and reduction in virus concentration by one log at stable room temperature for two days. Virus has been isolated from stool on paper and plastered wall after 36 hours, on a plastic surface and stainless steel after 72 hours and on a glass slide after 96 hours. Environmental samples collected from hospital walls and ventilation systems have tested PCR-positive (10).
The role of food in the transmission of SARS-CoV is not known. WHO has issued the following recommendation following the finding of coronavirus-infected animals and the receiving of information on notification of one third of early SARS cases in food handlers in Southern China: "As a precautionary measure, persons who might come into contact with risk animal species or their products, including body fluids and excretions, should be aware of the possible health risks, particularly during close contact such as handling and slaughtering and possibly food processing and consumption".
There was no epidemiological data to suggest that contact with goods, products or animals shipped from SARS-affected areas has been the source of SARS-infection in humans (11).
The significance of animal reservoirs.
It is of important epidemiological significance to establish whether or not SARS is a zoonotic infection, which has crossed the species barrier.
Domestic animals. Hong Kong SAR has reported of spontaneous SARS-infection from multiple pet (cat, dog) households by PCR on oropharyngeal and rectal swabs. Rats, mice, pigs and rabbits are resistant to SARS-infection while rodent droppings have tested PCR-positive in outbreak settings. Common domestic poultry species (chickens, turkeys, ducks, geese, quail) have shown no evidence of illness or viral excretion. SARS-CoV was detected on the body surface and gut contents of cockroaches by PCR; they may act as mechanical vectors of SARS-CoV transmission (7).
Wildlife animals. There is evidence that SARS-CoV natural infection may occur in several wildlife animal species indigenous to South-East Asia. Seven species have tested positive either by PCR and/or serology including palm civets, raccoon dog, Chinese ferret badger, cynomolgus macaques, fruit bats, snakes and wild pigs. Serological studies of animals and vegetable traders within Guangdong market showed that 40% of the wild animal traders, 20% of the wild animal butchers, 5% of the vegetable traders and 13% of the animal handlers were seropositive for SARS-CoV. None of those tested reported SARS-like clinical symptoms in the preceding six months (7). At present, no confirmed evidence exists to suggest the role of wild animal species in the epidemiology of SARS outbreaks, but information on the potential role of animals in the transmission of SARS-CoV to human population as a source of human infection and as animal reservoirs of SARS-CoV is important to the understanding of SARS epidemiology.
Prevention of SARS-CoV transmission.
Containment of the SARS-CoV intensive transmission in different parts of the world have confirmed the efficacy of traditional public health measures that include early case identification and isolation, vigorous contact tracing, home quarantine of close contacts for the duration of the maximum incubation period, and public information and education to encourage prompt reporting of disease symptoms. To prevent secondary cases, suspect or probable cases should be isolated within five days of disease onset.
If virus transmission in a hospital setting is suspected, active nosocomial surveillance of health care workers and patients for fever and other "ïnfluenza-like" illness symptoms, appropriate case management, including isolation and rapid epidemiological investigation, is essential. Implementation of aggressive airborne, contact and droplet precautions have provided effective protection for health care workers. For the staff, caring for SARS patients, strict adherence to contact, droplet precautions (hand hygiene, gloves, gowns, eye protection) and airborne precautions (including the use of masks/respirators) have proved to be effective. Removal, cleaning and decontamination of personal protective equipment should be done carefully as it may increase the potential risk of self-contamination. SARS patient care protocols should be developed and in place prior to the need for high-risk procedures, including intubation of SARS patient. In households, stringent application of contact and droplet precautions provides effective protection.
- Donnelly CA, Ghani AC, Leung CM et al. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet, 2003,361:1761-1766.
- Gay N, Ma S. Presentation on the modelling of data from Singapore. Global Meeting on the Epidemiology of SARS. WHO, Geneva, Switzerland, 16-17 May 2003.
- Peiris JSM, Chu CM, Cheng VC et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet, 2003,361:1767-1772.
- WHO Update 83. One hundred days into the outbreak, June 18, 2003.
- WHO Management of severe acute respiratory syndrome (SARS). Revised 11 April 2003.
- WHO Hospital discharge and follow-up policy for patients who have been diagnosed with sever acute respiratory syndrome (SARS). Revised 28 March 2003.
- WHO Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). WHO/CDS/CSR/GAR/2003.11
- Guan Y, Zheng BJ, He YQ et al. Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China. Science,2003,302:276-278.
- Ng SKC. Possible role of an animal vector in the SARS outbreak at Amoy Gardens. Lancet, 2003,362:570-572.
- WHO First data on stability and resistance of SARS coronavirus compiled by members of WHO laboratory network. 4 May 2003.
- WHO Information to WHO Member States regarding goods and animals arriving from SARS-affected areas. 11 April 2003.