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Preface

Summary

1. Timeline

2. Virology

3. Transmission

4. Epidemiology

5. Prevention

6. Case Definition

7. Diagnostic Tests

8. Clinical Presentation and Diagnosis

9. SARS Treatment

10. Pediatric SARS



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3. Transmission

Bernd Sebastian Kamps, Christian Hoffmann


The SARS coronavirus (SARS Co-V) is predominantly spread in droplets that are shed from the respiratory secretions of infected persons. Fecal or airborne transmission seem to be less frequent.

There is growing evidence that a majority of patients might not effectively transmit the virus to other individuals: in Singapore, 162 individuals (81%) of all probable SARS cases had no evidence of transmission of a clinically identifiable illness to other persons (MMWR 52: 405-11). This is in accordance with results from epidemiological studies which indicate that SARS is moderately rather than highly transmissible (Riley).

In some instances, however, so-called "superspreader" patients are able to transmit the SARS virus to a large number of individuals. Superspreaders and nosocomial amplification were the driving factors behind the early 2003 outbreaks.

Routes of Transmission

The fact that the majority of new infections occurred in close contacts of patients, such as household members, healthcare workers, or other patients who were not protected with contact or respiratory precautions, indicates that the virus is predominantly spread by droplets or by direct and indirect contact (CDC, Seto).

The presence of virus in the stool suggests the possibility of oral-fecal transmission (Drosten, Peiris 2003b). This is reminiscent of characteristics of other coronaviruses (Cho), and feces are therefore potentially an additional route of transmission. In the Amoy Gardens outbreak (see Chapter 4: Epidemiology, Hong Kong), the SARS virus may have been spread through the sewage systems of the buildings (for details, see Government of Hong Kong Special Administrative Region).

The airborne spread of SARS does not seem to be a major route of transmission. However, the apparent ease of transmission in some instances is of concern. In particular, the cases in the original Hong Kong cluster that originated at the Metropole hotel (MMWR 52:241-8) and in the Amoy Gardens Outbreak (Government of Hong Kong Special Administrative Region) indicate that the possibility of airborne transmission of the SARS virus, although probably a rare event, cannot be ruled out. Clusters among healthcare workers exposed during high-risk activities (i.e., endotracheal intubation, bronchoscopy, sputum induction) seem to confirm airborne transmission via a contaminated environment (i.e., re-aerosolization when removing protective equipment, etc.)

There are currently no indications that any goods, products or animals arriving from areas with SARS outbreaks pose a risk to public health. The WHO does not recommend any restrictions in this regard (http://www.who.int/csr/sars/goods2003_04_10).

Factors Influencing Transmission

Whether the transmission of a viral pathogen leads to the manifestation of the disease is determined by the intricate interplay of a multitude of still largely undefined viral and host factors.

As in other infectious diseases, the size of the inoculum, i.e., the number of infectious particles that are transmitted from one person to another, is probably of major importance. The size of the inoculum is determined by

  • the viral load in the secretion of the index patient, and
  • the distance to the index patient (face-to-face contact, crowded locations, i.e., a sneeze in the elevator)

Surprisingly, in the first few days after the onset of SARS-related symptoms, the amount of virus detected in secretion from the respiratory tract seems to be relatively low. Findings from sequential quantitative RT-PCR analyses of nasopharyngeal aspirates suggest that the viral load might peak only at around day 10 after the onset of symptoms and then decrease to the levels obtained on admission at day 15 (Peiris 2003b). In the stool, the virus appears to peak at day 13-14 (Peiris 2003b).

Infectivity might therefore be variable over time, even during the symptomatic phase of the disease, and transmission more likely to happen in the later phase of the illness.

In one study, severe disease was associated with acquisition of the disease through household contact. People infected in this way may have a higher dose or duration of viral exposure than people exposed through social contact (Peiris 2003a).

Patient Factors in Transmission

The most important factor is probably the viral load in infectious body secretions; so far, there is no indication that strains with different virulence are responsible for various degrees of infectivity.

Asymptomatic Patients

There are currently few data as to whether individuals can be infected with the SARS virus but remain asymptomatic, and if so, whether asymptomatic persons can transmit infection.

Preliminary findings suggest that some individuals that only developed mild symptoms may have antibodies to the SARS virus, although they did not develop SARS. Seroconversion without any disease has also been documented.

There is no direct evidence of transmission from an asymptomatic person. Indirect evidence that it may occur rarely includes a report that contact tracing in Hong Kong failed to identify a known symptomatic SARS contact in a small percentage of reported cases (WHO, Update 53).

Symptomatic Patients

It is now generally believed that only symptomatic patients may spread the SARS virus efficiently. However, transmission appears not to proceed in an explosive way. As stated above, 81% of all probable SARS cases in Singapore had no evidence of transmission of a clinically identifiable illness to other persons (MMWR 52: 405-11).

This is consistent with observations from the early Toronto outbreak, when suspected cases without pneumonia were initially sent home to spend their time in isolation. Some patients did not respect the isolation requirements and had interaction with the community. Despite that, apart from an outbreak in a religious group, no disease was seen in the community.

Another study, by Avendano et al., reports that 14 infected healthcare workers, who spent a mean of 4.5 days at home after the onset of symptoms, infected 2 out of 33 household contacts, in spite of unprotected contact within the home environment.

Finally, a report from the Philippines describes a patient who became symptomatic on April 6, had close contact with 254 family members and friends, traveled extensively in the Philippines and attended a prayer meeting and a wedding before becoming hospitalized on April 12. The contacts were placed under home quarantine for 9 days, with twice-daily temperature monitoring by health workers. Only two individuals (and questionably a third person) developed SARS, which represents an infection rate of less than 1% for the non-hospital contacts (WER 22/2003).

In comparison with other infectious diseases that are spread via the respiratory route (i.e., influenza), SARS seems therefore moderately transmissible.

Superspreaders

The term "superspreading" has been used to describe situations in which a single individual has directly infected a large number of other people (MMWR 52: 405-11MMWR 52: 405-11). In the Singapore epidemic, of the first 201 probable cases reported, 103 were infected by just five source cases (Table 1).

A common feature of superspreading is nosocomial transmission, with hospitals serving as sources for disease amplification (MMWR 52: 405-11). However, some superspreaders may spread disease among social contacts (MMWR 52: 461-5), and the initial index patient and superspreader reported from Hong Kong spread the virus in the Metropole hotel (MMWR 52: 241-8).

The most probable explanation for the phenomenon of superspreading is extensive viral shedding by the patients. This may be due to advanced disease or possibly co-morbidities that result in high viral loads. However, additional data on the natural history of SARS are needed to understand other factors that might be associated, i.e., other transmission routes or inadequate infection control measures. In some circumstances, transmission of the SARS virus is therefore highly efficient.

Table 1: Superspreaders: Number of infected persons and outcome

Age

City

O- H*

Co-morbid
conditions

Infected persons**

Outcome

Reference

64

Hong Kong

7

n.a.

13 p+s

dead

MMWR 52: 241-8

47

Hanoi

3

none

20 p

dead

WER 78: 73-4

26

Hong Kong

>5

none

112

alive

Lee, NEJM

22

Singapore

4

none

21 p, 3 s

alive

MMWR 52: 405-11

27

Singapore

3

none

23 p, 5 s

alive

MMWR 52: 405-11

53

Singapore

n.a.

Diabetes, ischemic heart disease

23 p, 8 s

dead

MMWR 52: 405-11

60

Singapore

n.a.

Chronic kidney disease, diabetes

62 p+s

alive

MMWR 52: 405-11

64

Singapore

3

Ischemic heart disease, left ventricular failure

12 p, 3 s

alive

MMWR 52: 405-11

n.a.

Toronto

6

Congestive heart failure

44 p

dead

Donald Low

43

Taiwan

6

Diabetes, peripheral vascular disease

137 p

dead

MMWR 52: 461-6

* Days between onset of illness and hospitalization

** p = probable case; s = suspected case

n.a. = not available

 

The Unsuspected Patients

SARS patients with chronic illnesses occurring concurrently with fever and/or pneumonia and who have a plausible diagnosis are the most challenging to the public health and healthcare systems (MMWR 52: 405-11).

Unrecognized cases of SARS have been implicated in recent outbreaks in Singapore (MMWR 52: 405-11), Taiwan (MMWR 52: 461-5), and Toronto. Despite efforts to implement extensive control measures, these cases led to nosocomial clusters and subsequent spread to other healthcare facilities and/or community settings. Several factors might contribute to difficulties in recognizing cases of SARS. Early symptoms of SARS are non-specific and are associated with other more common illnesses. Patients with SARS who are immunocompromised or who have chronic conditions (e.g., diabetes mellitus or chronic renal insufficiency) might not have fever when acutely ill or have symptoms attributable to the underlying disease, delaying the diagnosis of SARS (MMWR 52: 405-11). Finally, some patients might not reveal useful contact information (e.g., exposure to an implicated healthcare facility) for fear of being stigmatized by the local community or causing their friends and families to be quarantined (MMWR 52: 405-11).

These experiences demonstrate that spread among health care workers can occur despite knowledge about the epidemiology and transmission of SARS. To reduce the number of unrecognized cases, the Singapore Ministry of Health recommends a strategy to quickly identify febrile or symptomatic persons with chronic illnesses or any recent healthcare facility contact as suspected cases for isolation (MMWR 52: 405-11; see also Chapter 5: Prevention).

High-Risk Activities

The rapid spread of SARS among healthcare workers in Hanoi, Vietnam, and in hospitals in Hong Kong confirmed the potentially highly contagious nature of the virus. Medical personnel, physicians, nurses, and hospital workers are among those commonly infected. Attack rates in access of 50% have been reported (MMWR 52:226-8). SARS infection of health care workers is probably related to increased contact with respiratory secretions, contact with patients during a more contagious phase of critical illness, contact with particular patients at increased likelihood of spreading SARS (i.e. superspreaders), or exposure to aerosol-generating patient care procedures (MMWR 52: 433-6).

In particular, diagnostic and therapeutic procedures inside the hospitals, such as diagnostic sputum induction, bronchoscopy, endotracheal intubation, and airway suction are potent aerosol-generating procedures, and are now being recognized as high-risk activities situations. Other potentially aerosol-generating procedures include BiPAP, during which air might be forced out around the facemask and thereby aerosolize secretions, and HFOV, during which exhaust from the ventilator tubing is more likely to escape without passing through an antibacterial/antiviral filter (MMWR 52: 433-6).

In Canada, a cluster of SARS cases occurred among health care workers despite apparent compliance with recommended infection control precautions. The probable transmission event was an endotracheal intubation of a patient who was in his second week of illness with clinical deterioration and a severe cough (MMWR 52: 433-6).

Another serious outbreak in a public hospital in Hong Kong could have been magnified by the use of a nebulized bronchodilator (albuterol; 0.5 mg through a jet nebulizer, delivered by oxygen at a flow rate of 6 liters per minute, four times daily for a total of seven days), causing atomization of the infected secretions (Lee).

Transmission during Quarantine

There has been at least one report of SARS Co-V transmission during quarantine (WER 22/2003). Three family contacts of a SARS patients became infected during hospital quarantine because strict isolation was not observed. This illustrates the fundamental principle of not "cohorting" suspect cases. Patients diagnosed with SARS may or may not be infected with the SARS virus, but they are at risk of contracting the infection if they are grouped with infected patients.

Transmission after Recovery

How long patients should remain in isolation depends on whether, and to what extent, patients continue to shed virus from the respiratory tract or from feces after overt clinical symptoms have stopped. Currently, at least 14 days of home quarantine are recommended following discharge. There have thus far been no reports of transmission after discharge.

Animal Reservoirs

There is limited data regarding the role of animals in the origin, transmission and reservoir of SARS CoV. Available data suggest that (Field)

  • Early SARS cases were associated with animal markets
  • SARS-like viruses were detected in apparently healthy animals in at least 2 wild animal species in one market place
  • Preliminary experimental studies in pigs and poultry suggest these species are not likely to play a role in the spread of the SARS coronavirus
  • Several coronaviruses infect multiple host species
  • Antibody studies in people working in markets show a higher antibody prevalence among market workers in comparison to the general population

Conclusion

The SARS virus is not easily transmissible outside of certain settings. For a major local outbreak to occur there needs to be

  • an infectious patient, and
  • a close community or "tribe", i.e., healthcare workers, military populations, travel groups, religious gatherings, or funerals, with close interactions (kissing, hugging).

This gives some hope that SARS will not spread in a totally uncontrolled manner in the community.

The "ideal" conditions for efficient transmission of the SARS virus seem to be:

  • The patient is highly infectious, shedding great quantities of infectious virus
  • The patient has co-morbidities that mask the symptoms and signs of SARS
  • The patient is admitted to a hospital with contact to multiple persons because of the diagnostic work-up, possibly including high-risk procedures such as bronchoscopy, endotracheal intubation, use of nebulizers, etc.


References

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  2. CDC. Outbreak of Severe Acute Respiratory Syndrome - Worldwide, 2003. MMWR 2003;52:226-8. http://www.cdc.gov/mmwr/preview/mmwrhtm l/mm5211a5.htm
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