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National Surveillance Guidelines for Human Infection with Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

Table of Contents

BACKGROUND

The initial goal of emerging respiratory virus (ERV) surveillance is early detection of a case in Canada with an intent to containment. Where containment is no longer feasible, ERV surveillance is geared toward informing public health response to allow appropriate targeting and prioritization of interventions with the goal of mitigating risk and impact.

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a novel coronavirus first reported globally as a human pathogen in September 2012 . It was identified from a specimen collected from a resident of Saudi Arabia who had symptom onset in June 2012 and who died from his infection. Later, it was retrospectively determined that two fatalities associated with an earlier nosocomial cluster in Jordan in April 2012 were also due to this virus.

All locally acquired cases of MERS-CoV have emerged primarily from the Middle East and predominantly from Saudi Arabia. Travel-related cases have also been reported by countries outside of the Middle East; and to date, export to those countries has not been associated with onward transmission except for a few instances of secondary and tertiary transmission to close contacts of cases having had direct or indirect connection to the Middle East. A current list of affected countries is provided in the Government of Canada's Travel Health Notice for MERS-CoVExternal Link.

To date, MERS-CoV has occurred in a pattern of discrete clusters among family, household or nosocomial settings, including limited transmission to relatives, patient visitors, patient roommates and health care workers. Over the last three years, an increasing incidence of primary cases of MERS-CoV in the spring suggests a seasonal pattern. However, the increase in the number and proportion of secondary cases, especially in health care workers (HCWs), identified since March 2014 was largely associated with outbreaks in healthcare facilities and breaches in WHO-recommended infection prevention and control measures. The clinical picture has not changed significantly. The majority of cases are adult males, and individuals with comorbidities experience more severe illness. Secondary cases generally present with milder disease or no symptoms; however, severe illness, including deaths, have been observed in secondary cases including among HCWs. Sustained human-to-human spread in the community has not yet been documented.

Questions around the zoonotic reservoir or role of intermediary animal species persist. However, recent studies support the idea that camels serve as a primary source of MERS-CoV infection in humans, and that other livestock are not involved. However, the exact route of direct or indirect exposure remains unknown. The discovery of the route of transmission between camels and humans remains critical to stopping initial introduction into human populations. Although distantly related, MERS-CoV most closely aligns phylogenetically with SARS-CoV compared to other typical coronaviruses known to cause human infection.

Surveillance Goals and Objectives

Given the evidence to date, the main goals of public health response are early detection and containment.

To accomplish these, the following national surveillance objectives have been developed:

  1. Timely detection of importation of human cases of MERS-CoV infection in Canada
  2. Monitor the incidence and the geographical distribution of new cases over time
  3. Describe and monitor changes in the clinical, epidemiological and virological features of the disease(e.g. clinical features and progression, morbidity, mortality, incubation period, serial interval, infectious period (start, peak, end), mode of transmission, at risk populations)
  4. Notify and disseminate information to stakeholders in order to facilitate timely and appropriate public health activities and provide credible information to the public
  5. To identify knowledge gaps that would better inform public health response.

Case Finding and Investigation

Case Definition

The Public Health Agency of Canada has developed case definitions for classification and reporting of human cases of MERS-CoV.  They are located on the Public Health Agency of Canada website.

Case Identification and Interview

Laboratory-confirmation of a MERS-CoV case is an immediate trigger to launch public health response activities and investigations. However, because collection, shipment, and testing of specimens often require several days or longer, precautionary public health response (e.g. isolation, contact tracing and monitoring) may need to begin before laboratory test results are available for suspected cases where the index of suspicion is high.

The patient and/or family members (if the patient is too ill to be interviewed or has died) should be interviewed within the first 24-48 hours of the investigation to collect basic demographic, clinical, and epidemiological information. A sample case investigation/reporting form for the interview can be found on the Public Health Agency's website. Provinces and territories may choose to use this form, or a similar form adapted for use within their jurisdiction.

Essential Basic Information

Within 24 hours of notification, the following priority data elements (Box 1) should be submitted to the Public Health Agency of CanadaFootnote 1.

Box 1. Priority data elements to be reported
  • Reporting P/T
  • Outbreak or cluster related
  • Case classification (confirmed vs. probable)
  • Sex
  • Age
  • Date of onset of illness
  • Symptoms
  • Whether hospitalized / Date of hospitalization
  • Whether in ICU/Date of ICU admission
  • If deceased/Date of death
  • Lab : date and type of specimen collection, test method and result (when available)
  • History of travel within two weeks of symptom onset
  • Other possible exposures (e.g., ill contact, animal, food) within two weeks of symptom onset

Contact Identification and Monitoring/Management

Close contactsFootnote 2 of confirmed or probable cases should be identified and monitored for the appearance of respiratory symptoms for 14 days after last exposure to the confirmed or probable case, while the case was symptomatic. MERS-CoV testing in Canada should be initiated only after a risk assessment by the clinician, medical health officer, medical/clinical microbiologist and/or infectious disease specialist. Testing of close contacts, whether mildly or severely symptomatic, should be considered on the basis of the risk assessment.

Follow-up should include nucleic acid amplification testing (NAAT) for MERS-CoV and other respiratory pathogens of all close contacts who develop respiratory symptoms within the two weeks of exposure to a confirmed or probable case of MERS-CoV, regardless of severity. Routine testing of asymptomatic contacts is not recommended. If an outbreak is identified, serum and serology can provide ancillary information . However, the delay in results make it of no value for case management. Serologic testing in Canada for MERS-CoV is not available for routine use as it is not validated or quality controlled.

A record of clinical and epidemiologic characteristics of contacts should be maintained including details related to date of first and last common exposure or date of contact with the confirmed or probable case, symptoms, date and type of first symptom onset, date and type of specimen collected, and other data points of interest for the investigation. This will aid in the early understanding of MERS-CoV transmissibility and other clinical epidemiologic features in support of risk analysis and response.

Detailed information related to case and contact follow-up and public health response can be found in the Public Health management of human illness associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV).

Enhanced Surveillance

For the purpose of containment, emerging respiratory virus surveillance is primarily focused on hospital-based surveillance for the early detection and management of severe acute respiratory illness (SARI). This is because it is not possible to elicit travel history and conduct broad surveillance and laboratory testing for all mild cases of respiratory illness in the community. Through targeted communications, individuals should be encouraged to self-monitor for acute respiratory illness within 14 days of (a) travel to, or residence in, affected regions of the Middle East, or to locations where human to human transmission is currently ongoing (e.g. hospitals in South Korea 2015) and/or (b) close contact with someone with such travel history and symptoms of respiratory illness.

For certain emerging respiratory viruses such as MERS-CoV for which a spectrum of illness inclusive of mild or asymptomatic cases is recognized (and for which human-to-human transmission and case amplification have been observed within discrete, high-risk settings or clusters), it may be reasonable to consider laboratory diagnosis among patients who provide exposure history even if their respiratory illness is considered mild or absent after a risk assessment by the clinician, medical health officer, medical/clinical microbiologist and/or infectious disease specialist. Such an approach may contribute to containment and the prevention of unrecognized chains of transmission and outbreak amplification elsewhere.

Certain features that may increase the pre-test likelihood of MERS-CoV diagnosis that should be considered in the risk assessment include attendance at a recognized transmission setting (e.g. health care facility) or exposure to camels or camel products (e.g., raw milk and meat, secretions or excretions, including urine) within a predominantly affected region (e.g. Saudi Arabia).

In regions in Canada where MERS-CoV has been confirmed, in addition to active case and close contact follow-up, enhanced community surveillance may also be warranted to detect unrecognized chains of transmission or sporadic cases. The geographical area targeted will need to be assessed and defined by the suspected exposures of the confirmed case under investigation. The duration of the enhanced surveillance will depend on the findings of the investigation and whether there is evidence indicating that sustained transmission may be occurring in the area. A minimum of one month (representing approximately two incubation periods) of enhanced surveillance is a reasonable starting point.

Enhanced activities may include:

  • Establish mechanisms for rapid transfer of specimens from front line laboratories to Provincial Public Health Laboratories (PPHLs) and the National Microbiology Laboratory (NML) consistent with the testing algorithm in your jurisdiction
  • Inform clinicians in the community of the need for increased vigilance and triggers for identification, testing, and notification

Recommended enhanced surveillance goals and activities for various scenarios

The most recent risk assessment for Canada can be accessed through the following: Summary of Assessment of Public Health Risk to Canada Associated with MERS-CoV

Recommended enhanced surveillance goals and activities* for various scenarios
PH Response Goals Scenario Surveillance, Investigation and other Epidemiological Activities
  • * In all scenarios, continue routine surveillance for respiratory pathogens in Canada
Containment

Goal: Gather information to understand the virus (focussed on individual level intervention)

MERS-CoV with no human transmission Cases outside of Canada
  • Monitor disease outside of Canada (review data from origin country)
  • Develop case definitions, surveillance guidelines, testing guidelines, and reporting requirements
  • Conduct risk assessment to identify potential risk for Canadians
  • Develop testing capacity within Canada at the Provincial level, including protocols and quality assurance (proficiency panels)

Cases within Canada

  • Sharing of epidemiological information (reports) via CNPHI Public Health Alert, teleconferences etc. in a timely manner
  • Conduct active case and contact investigations
  • Collect surveillance information from cases to - determine epidemiology and to inform risk assessment (report cases using the Emerging Respiratory Pathogens and SARI Case Report Form or a jurisdictional equivalent) with the aim of helping to contain transmission.
  • Determine clinical spectrum of illness, disease incidence and mortality
  • Determine person, place, time features and, where possible, evaluate incubation period, serial interval, infectious period (start, peak, end) and specimens from which virus may be detected, including type of specimen and optimal timing
  • Refine case definitions, surveillance guidelines, testing guidelines and protocols, and reporting requirements
MERS-CoV with sporadic or limited human transmission

*e.g. Virus has caused sporadic cases or small clusters of disease in people but has not resulted in human-to-human transmission sufficient to sustain community-level outbreaks

Cases outside of Canada
  • Monitor disease outside of Canada (review data from origin country)
  • Develop case definitions, surveillance guidelines, testing guidelines and protocols, and reporting requirements
  • Conduct risk assessment to identify potential risk for Canadians
  • Prepare for virus introduction and spread of virus in Canada

Cases within Canada

  • Conduct active case finding and contact
  • tracing to determine epidemiology and to inform risk assessment (report cases using the Emerging Respiratory Pathogens and SARI Case Report Form or a jurisdictional equivalent)
  • Determine clinical spectrum of illness, disease incidence and mortality
  • Determine person, place, time features and, where possible, evaluate incubation period, serial interval, infectious period (start, peak, end) and specimens from which virus may be detected, including type of specimen and optimal timing
  • Improve laboratory and public health linkages in regards to MERS-CoV to improve ability to identify cases and clusters.
  • Sharing of epidemiological information (reports) via CNPHI Public Health Alert, teleconferences etc. in a timely manner
  • Mobilise resources to conduct active investigations
  • Refine case definitions, surveillance guidelines and reporting requirements, and contact follow-up forms as needed.
Mitigation

Goal: Identify risk factors to target interventions (focussed on population level interventions)

MERS-CoV with sustained human transmission detected

*e.g. Virus is able to sustain community-level outbreaks

Cases outside of Canada
  • Monitor disease outside of Canada (review data from origin country)
  • Develop case definitions, surveillance guidelines, testing guidelines and protocols, and reporting requirements
  • Conduct risk assessment to identify potential risk for Canadians
  • Prepare for virus and spread of virus in Canada

Cases within Canada

  • Intense case finding (report cases using the Emerging Respiratory Pathogens and SARI Case Report Form or a jurisdictional equivalent) until sufficient information is acquired. After the first 100 cases in Canada, report core data elements of cases using an electronic line-list format
  • Sharing of information via CNPHI Public Health Alert, teleconferences, online etc. in a timely manner
  • Improve laboratory and public health linkages in regards to MERS-CoV to improve ability to identify cases and clusters.
  • Conduct cluster and outbreak investigations with a view to more systematically characterize clinical and epidemiologic features, including risk factors and their mitigation
  • Determine clinical spectrum of illness and mortality and identify those at higher risk of infection and/or serious outcomes
  • Determine person, place, time features and, where possible, evaluate incubation period, serial interval, infectious period (start, peak, end) and specimens from which virus may be detected, including optimal timing
  • Mobilize resources to help with investigations
  • Monitor outbreaks in health care settings to determine infectivity and severity of virus
  • Refine case definitions, surveillance guidelines and reporting requirements, and contact follow-up forms as needed.
MERS-CoV with widespread human transmission detected

*e.g. Virus has caused outbreaks across large geographic regions (beyond the community level)

Cases outside of Canada
  • Prepare for virus and spread of virus in Canada
  • Monitor disease outside of Canada (review data from origin country)

Cases within Canada

  • Aggregate level national case reporting
  • Monitor health services utilization to determine the pathogenicity of virus and the impact on the health-care system and severity of disease. (e.g. through hospital networks: CIRN SOS, IMPACT & ILI sentinel networks)
  • Use of sentinel networks to systematically collect and characterize virus circulating in the community, identify virus mutations or evolution and monitor medically-attended illness by key epidemiologic features (age, comorbidity, etc.) if relevant.
  • Conduct special studies (e.g. household, community transmission, seroprevalence
  • )
  • Sharing of information via CNPHI Public Health Alert, teleconferences, online etc. in a timely manner

Laboratory Testing

Laboratory testing should be conducted in accordance with the Canadian Public Health Laboratory Network's Protocol for Microbiological Investigations of Severe Acute Respiratory Infections (SARI). Follow infection prevention and control guidelines when collecting respiratory specimens. Be aware of approaches in your jurisdiction.

Laboratory confirmation is obtained by detection of the virus using (a) MERS-CoV specific nucleic acid amplification test (NAAT) with up to two separate targets and/or sequencing; or (b) virus isolation in tissue cultureFootnote 3; or (c) serology on serum tested in a WHO collaborating center with established testing methods. Initial screening tests specific for MERS-CoV can be performed in select laboratories (i.e. primarily provincial public health laboratories); however, such cases are considered probable pending NML confirmation.  Laboratories with specimens that screened positive for MERS CoV should forward these to their local public health laboratory (PHL) that can facilitate confirmatory testing at the NML.

Testing of Contacts: Testing of contacts should be considered on the basis of the risk assessment in consultation with public health, the provincial public health laboratory, the attending physician and infectious disease specialists. Testing methodology depends on the clinical context. NAAT on nasopharyngeal and oropharyngeal specimens (nasal specimens are not acceptable) should be considered the primary method for testing for asymptomatic or acute infection to facilitate clinical management or infection control decisions. Serology can be used to identify cases for epidemiologic purposes but must be done using well validated methods which are currently available only in select WHO collaborating laboratories.

Testing in Symptomatic Patients: In symptomatic persons, it is strongly advised that both an NPS and lower respiratory specimen such as sputum, endotracheal aspirate, or bronchoalveolar lavage (BAL) should be collected when possible using appropriate PPE used for aerosol generating procedures as described in the interim infection prevention and control guidance for MERS-CoV for acute care settings. (Note: some virology laboratories may not have protocols for the identification of viruses from sputum. Discuss specimen types with your local laboratory). If a lower respiratory tract specimen is not available, upper respiratory tract specimens including both a nasopharyngeal (not nasal swab) and an oropharyngeal specimen should be collected using PPE appropriate for caring for patients on contact and droplet precautions. The two (nasopharyngeal/oropharyngeal) can be combined in a single collection container and tested together. For pediatric patients, a nasopharyngeal aspirate is a suitable replacement to for a nasopharyngeal swab.

Among patients for whom the index of suspicion for MERS-CoV is high, a negative finding on initial testing of a nasopharyngeal/oropharyngeal swab cannot not be used to rule out infection; such patients should be retested using a lower respiratory specimen. For patients in whom adequate lower respiratory samples are not possible, investigators ought to consider a repeat nasopharyngeal and pharyngeal specimen or induced sputum. In some cases, initial results may be inconclusive and further epidemiologic and laboratory investigations should be carried out.

Although other specimens such as blood, stool and urine have occasionally been used to successfully detect emerging respiratory viruses such as MERS-CoV and some avian influenza viruses, respiratory specimens remain the primary focus for clinical diagnostic purposes. Other specimens can be considered on a case by case basis or as part of special investigations. (http://www.who.int/csr/disease/coronavirus_infections/MERS_CoV_investigation_guideline_Jul13.pdf

Serology may aid in epidemiologic investigations and population level risk analyses. Although, serologic diagnosis is considered confirmatory by the WHO and may be used to identify cases when other laboratory diagnoses are not possible, Canada does not currently have a validated or well-controlled assay for serologic confirmation. Serology is not recommended as a confirmatory method unless it can be confirmed in a WHO collaborating center with established testing methods.

Other laboratory investigations should be conducted according to local guidance for diagnosis and management of community-acquired pneumonia inclusive of other potentially more likely etiologies. Examples of other etiologies include Streptococcus pneumoniae, Haemophilus influenzae B, Legionella pneumophila, other recognized primary bacterial pneumonias, influenza and other respiratory viruses. As demonstrated by a case with dual influenza and MERS-CoV infections, co-infection can occur. Identification of one causative agent should not exclude MERS-CoV where the index of suspicion may be high.

Risk Analysis and Summary

Descriptive analysis of cases should be performed in terms of person, place, and time. For investigations that yield multiple cases, graphical and/or tabular descriptions of cases by date of onset or reporting date (where date of onset missing or unknown) (i.e. epidemic curve), geographical location (e.g. maps), relationship (i.e. transmission or family trees) and demographic characteristics (e.g. distribution by age and sex) should be developed.

Key epidemiological (e.g. estimation of an incubation period, serial interval, infectious period and peak, description of transmission routes and patterns, attack rates by age, occupation, exposure history, risk factors for infection and severe outcomes, etc.) and clinical (e.g. spectrum of illness severity, ideal specimen type, proportion of cases who develop pneumonia, require hospitalization, critical care, and/or die) parameters should be characterized to enhance understanding of the spectrum and dynamics of disease associated with MERS-CoV infection.

Studies and specific investigations

WHO has developed a Case-control study to assess potential risk factors related to human illness caused by Middle East Respiratory Syndrome Coronavirus (MERS-CoV) which can be found on their coronavirus websiteExternal Link.

Useful protocols can also be found on the website of the Consortium for the Standardization of Influenza Seroepidemiology (CONSISE)External Link.

Special investigations that may better or more systematically and efficiently inform the above risk analysis and summary should also be undertaken. These special investigations can be conducted at various jurisdictional levels (from local to national) based on need and resource capacity.

Infection control

Recommendations for infection prevention and control measures for patients presenting with suspected or confirmed infection or co-infection with MERS-CoV in acute care settings are posted on the Agency's website. This guidance will be updated as new information becomes available.

Reporting Results

Reporting Cases

Provinces and Territories are asked to report all confirmed and probable cases of MERS-CoV within 24 hours of provincial / territorial notification to the Influenza and Other Respiratory Infectious Diseases Division at the Public Health Agency of Canada.

Provinces and Territories are asked to use the Emerging Respiratory Pathogens and Severe Acute Respiratory Infection (SARI) Case Report Form which can befound on the Agency's website, or a jurisdictional equivalent containing the same data fields. Priority data elements as outlined in Box 1 should be submitted within 24 hours.

Completed forms can be faxed (without first page) to 1-800-332-5584 and an email notification (do not attach form) should be sent to HSFLUEPI@phac-aspc.gc.ca. Alternatively, P/Ts may elect to submit data elements through routine reporting methods (e.g. via the integrated Reportable Disease Information System).

For questions after regular business hours (8:00 - 5:00pm ET) please contact the Agency Medical Officer on-call at 613-952-7940.

Reporting of cases by provincial and territorial public health authorities and laboratories should follow the process outlined in Figure 1.

Figure 1. Process for national and international public health notifications for emerging respiratory pathogens.

Figure 1. Process for national and international public health notifications for emerging respiratory pathogens

Text Equivalent - Figure 1

Reporting results of a study investigation

Early reporting of investigation results of MERS-CoV cases in Canada is strongly encouraged, even before analyses are complete. In addition, even preliminary data can be critical in the early assessment of international spread and inform decision making.

Useful Links

  1. Public Health Agency of Canada: http://www.phac-aspc.gc.ca/eri-ire/coronavirus/index-eng.php
  2. World Health Organization: http://www.who.int/csr/disease/coronavirus_infections/en/External Link
  3. European Centre for Disease Prevention and Control: http://www.ecdc.europa.eu/en/healthtopics/coronavirus-infections/whats-new/Pages/whats_new.aspxExternal Link
  4. United States Centres for Disease Control and Prevention: http://www.cdc.gov/coronavirus/mers/index.htmlExternal Link

Footnote 1
See Figure 1 on page 14 for the process for public health notification of emerging respiratory pathogens.
Footnote 2
A close contact is defined as a person who provided care for the patient, including health care workers (except those wearing appropriate PPE), family members or other caregivers, or who had other similarly close physical contact OR who stayed at the same place (e.g. lived with or otherwise had close prolonged contact within two metres) as a probable or confirmed case while the case was ill.
Footnote 3
Virus isolation in tissue culture should be performed in a BSL3 facility only. Canada's National Microbiology Laboratory (NML) has this capacity.