By: Swarali S Tadwalkar

PHC 6002: Infectious Disease Epidemiology

Instructor: Dr Aurora Sanchez-Anguiano

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Image source: http://www.healthytravelblog.com/2012/09/25/the-return-of-sars/http://bloomberg.nursing.utoronto.ca/news/teaching-in-a-time-of-crisis-sars-and-the-impact-on-u-of-ts-faculty-of-nursing

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*Viral Respiratory Disease caused by SARS-CoV (SARS Coronavirus)

*Highly contagious atypical pneumonia

*First reported in February 2003 in Asia through a major outbreak

*Importance:

*CDC declared SARS-CoV as a select agent in 2012 meaning it has the potential to pose severe threat to public health and safety

*High transmissibility

*First important infectious disease of the new millenium

* Infection to HCW – Major concern

*Etiologic Agent: SARS Coronavirus (SARS-CoV)

*Transmission: Primarily through droplet infection

*Other sources: Surface contamination and Air-borne

*Natural History: Acute viral infection of respiratory tract

*Viral dynamics not clear though high viral load seen in lower respiratory tract

*Low load in upper respiratory tract and feces in the first 4 days but peaks at approximately 10 days

*High infectivity at febrile stage

*Life-cycle: RNA virus of coronaviridae family

* Important stages: Replication and Transcription

*Replication involves synthesis of full-length negative strand

*Discontinuous Transcription process not fully understood

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Image source: https://socioecohistory.wordpress.com/2012/09/27/new-sars-virus-attacks-arabs-created-by-israeli-and-british-bio-weapons-lab/

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*Pathophysiology: Complex processes leading to degradation of organs

*Primary target - lungs and intestines (epithelial cells, villi, alveoli)

* Immune system - severe lymphocyte depletion

*Clinical Features: Incubation period is 2-10 days

*Fever, Myalgia, headaches, dry non-productive cough

*Others: Diarrhea (25%), shortness of breath, hypoxemia

*Diagnosis: Chest radiography, pulse oximetry, blood cultures, sputum Gram stain and culture, and testing for other respiratory pathogens

*Treatment: Supportive care, infection control measures and broad spectrum antibiotics including fluoroquinolone and macrolide

*Complications: Risk of co-infections, comorbities, respiratory failure

*Prognosis: Can lead to serious medical complications

*May require hospitalization, Intubation or ventilator support

**Primary Reservoir = Human

*Other animal reservoirs for coronaviridae family viruses include cats, pigs, chicken, rats and mice

* Infections include respiratory or enteric manifestations

*Person

*Total deaths = 774 out of 8,098 affected as per WHO

*Canada: Median reported age of death was 75 years

*Peoples’ Republic of China: 71.9% deaths were above 60 years of age

*HongKong, China: 52% deaths were amongst above 65 years olds

*Sex preference: Some studies report higher female CFR while some report vice versa

*Racial preference has not been documented though outbreak was restricted to about two dozen countries alone

*Greater transmission and infectivity was seen among Health care workers perhaps due to exposure to higher viral load

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*Major outbreak in 2003

*No outbreak of SARS seen after that though other forms such as MERS (Middle East Respiratory Syndrome) seen

*Time: No seasonal pattern

*Total incubation period: 1-14 days

*Median incubation period: 4-5 days with mean of 4-6 days

*Epidemic curve

* Person-to-person propagation

* Peaks of different heights

*Onset of outbreak: Nov 2002

*Global alert: March 15, 2003,WHO

Adapted from World Health Organization. Epidemic curves – Severe Acute Respiratory Disease (SARS)http://www.who.int/csr/sars/epicurve/epiindex/en/index1.html

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*Place: About couple of dozen countries were affected

*Most cases occurred in:

*China

*Phillippines

*Vietnam

*Singapore

*Canada

*USA

*Some parts of Europe

*Only 8 cases were seen in US of which almost all had travelled to other parts of the world

Image Source: Boulos International Journal of Health Geographics 2004 3:2 doi:10.1186/1476-072X-3-2

**Intrinsic factors:

*Genetically, HLA (Human Leukocyte Antigen) was identified to be correlated to SARS susceptibility

*Age of the patient: Higher incidence was seen amongst older age group (> 60 years)

*Sex of the patient: Males were more likely to be affected however, amongst HCWs more females were affected

*Children and pregnant women were considered to be at higher risk

*Higher mortality was seen amongst patients with comorbidities such as diabetes, heart diseases etc

*Variation in host response to infection

**Extrinsic Factors

*Pathogenic virus: SARS Coronavirus

*Person-to-person contact: Droplet and Air transmission

* Led to higher transmittance to HCWs and spread of disease to others in population

*Air travel: Led to spread of disease from China to Canada due to travel of infected patients/carriers

*Lack of infection control measures leading to higher transmission in health care settings

*Lack of maintenance of hygienic conditions

*Influence of diet or other lifestyle factors were not identified as major risk factors during the outbreak. However, they may have caused variability in susceptibility and immune response of host

**Concern: Insufficiency of vaccine due to new strain

*Global Alert issued by WHO in March 2003

*Monitoring passengers and crew traveling by air

*Quarantine of infected patients

*Avoiding mass gatherings and activities

* Infection control measures

*Preventing person-to-person contact (using masks)

*Handwashing

*Safety precautions by HCWs in healthcare settings

*Extra precaution during intubation and intensive care to avoid exposure to high viral loads

*Surveillance and timely reporting

*Monitoring fever and cough symptoms amongst children and adults every few hours in schools, offices and other institutions

**Study by Raboud et. Al (2010)

*One of the most extensive epidemiological studies in health-care settings in Ontario, Canada

*Merits: Detailed inclusion/exclusion criteria, extensive statistical analysis

*Demerits: Retrospective nature may have led to recall bias in the study, biological variability may have been a source of confounding

*Donnely et. al (2003)

*Assessed epidemiology of SARS in Hong Kong, China

*Result: Patient’s age was strongly associated with outcome

*Merits: Detailed study design and methods, inclusion/exclusion criteria, large sample-size

*Demerits: Non-stratification by sex, less information on other factors and self-reporting of information

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*Other coronavirus disease forms witnessed: MERS (Middle East Respiratory Syndrome)

*Concern over mutant forms of viral strains making it difficult to determine diagnosis and treatment

*During 2003 SARS outbreak, treatment could not be easily determined making it difficult to treat patients and preventing spread

*Protective efficacy of vaccines still under scrutiny

*Research with novel ideas to manage diseases required

*DNA vaccine could potentially prevent proliferation of RNA virus by hindering replication

** CDC/NCIRD. (2004). Basic Information about SARS. CDC/NCIRD.

* Chan, H. L., Tsui, S. K., & Sung, J. J. (2003). Coronavirus in severe acute respiratory syndrome (SARS). TRENDS in Molecular Medicine, 9: 323-325.

* Donnelly, C. A., Ghani, A. C., Leung, G. M., Hedley, A. J., Fraser, C., Riley, S., et al. (2003). Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. The Lancet, 1-6.

* Gu, J., & Korteweg, C. (2007). Pathology and Pathogenesis of Severe Acute Respiratory Syndrome. The American Journal of Pathology, 170:1136–1147; DOI: 10.2353/ajpath.2007.061088.

*Ng, M., Cheng, S., Lau, K., Leung, G., Khoo, U., Zee, B., et al. (2010). Immunogenetics in SARS: a case control study. Hong Kong Medical Journal, 16(Suppl 4):S29-33.

* Raboud J, Shigayeva A, McGeer A, Bontovics E, Chapman M, et al. (2010) Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada. PLoS ONE 5(5): e10717. doi:10.1371/journal.pone.0010717

* Sampathkumar, P., Temesgen, Z., Smith, T. F., & Thompson, R. L. (2003). SARS: Epidemiology, Clinical Presentation, Management, and Infection Control Measures. Mayo Clinic Proceedings, 78:882-890.

* SARS Epidemiology Working Group, W. (2003). Consensus Document on the Epidemiology of SARS. WHO.

*Any questions??

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