Guidance for the public health management of measles cases, contacts and outbreaks in Canada

On this page

• Acronyms
• Executive summary
• Definitions
• Introduction
  • Roles and responsibilities
  • Objectives
  • Background
  • Epidemiological characteristics of measles
• Epidemiology in Canada
  • Measles immunization programs in Canada
• Surveillance and reporting
• Public health management
  • Health equity and psychosocial considerations
  • Case management
  • Contact tracing and management
  • Gatherings during outbreaks of measles
  • Management of travellers
• Healthcare facilities
• Laboratory guidelines for the diagnosis of measles
  • Specimen collection
  • Interpretation of laboratory results
  • Roles and responsibilities of laboratories
• Immunization
  • Immunization during outbreaks
  • Measles immunizing agents authorized for use in Canada
  • Post-exposure prophylaxis
  • Vaccine supply
• Strategic communications during a measles outbreak
• Analysis of an outbreak
• Appendix A. Persons involved in developing the guidance
• Appendix B. Provincial/territorial legislatures for reporting communicable diseases
• Appendix C. Federal/provincial/territorial measles reporting requirements
• Appendix D. National measles case report form
• Appendix E. Sample measles case investigation form
• Appendix F. Laboratory guidelines for the diagnosis of measles
• Footnotes
• References

Acronyms

CMRSS

Canadian Measles and Rubella Surveillance System

CSF

cerebrospinal fluid

DSId

Distinct Sequence Identifier

EIA

enzyme immunoassay

FPT

federal/provincial/territorial

HCP

healthcare provider

Ig

immunoglobulin

IgG

immunoglobulin G

IgM

immunoglobulin M

IPC

infection prevention and control

MeaNS

Measles Virus Nucleotide Surveillance database

MMR

measles, mumps and rubella

MMRV

measles, mumps, rubella and varicella

NML

National Microbiology Laboratory

NP

nasopharyngeal

PAHO

Pan American Health Organization

PCR

polymerase chain reaction

PEP

post-exposure prophylaxis

PHA

public health authority

PHAC

Public Health Agency of Canada

PRNT

plaque reduction neutralization test

PT

provincial/territorial

QO

quarantine officer

RT-PCR

reverse transcriptase polymerase chain reaction

SSPE

sub-acute sclerosing panencephalitis

VTM

viral transport media/medium

WHO

World Health Organization

Executive summary

Canada has been free of endemic measles since 1998, when elimination status was achieved. However, cases continue to occur as long as individuals travel to and from countries where disease activity is ongoing, especially in individuals and communities who are unimmunized or under-immunized. These imported cases have led to secondary spread which can result in outbreaks.

This guidance document focuses on the public health management of measles cases, contacts and outbreaks in Canada; to minimize domestic transmission of measles, reduce the severity of measles in contacts at risk of severe disease and reduce the impact of this vaccine preventable disease on the health of people living in Canada. It includes advice on case and contact management, outbreak control, public health management of measles cases on airplanes, laboratory testing, post-exposure prophylaxis (PEP), national surveillance standards and international reporting obligations.

Information and recommendations on measles-containing vaccines can be found in the Canadian Immunization Guide: Part 4. Immunizing agents, Measles vaccines. On the National Advisory Committee on Immunization website, detailed recommendations on measles post-exposure prophylaxis are available.

This document replaces the Guidelines for the prevention and control of measles outbreaks in Canada, which was published in the Canada Communicable Disease Report in October 2013.

Definitions

Case

See section Case finding and classification for case definitions.

Conclusion of an outbreak

The conclusion of an outbreak should be defined as at least 46 days^{Footnote a} following the rash onset date of the last outbreak-associated case, in order to account for delays in case reporting, subclinical and/or undiagnosed cases.

Contact

See section Contact definition.

Endemic case

A case that is epidemiologically-linked or virologically linked to a chain of transmission that has continued uninterrupted for a period of greater than or equal to 12 months in Canada.

Epidemiological linkage

A case has an epidemiological linkage if, during the 7 to 21 days prior to rash onset, one or more of the following criteria are met:

• contact (as defined in section Contact definition) with one or more case(s)
• exposure to a geographic area where measles is endemic or an outbreak of measles is occurring
• exposure to a community or setting experiencing a measles outbreak

Healthcare setting

For the purpose of this document, healthcare settings include any facility or location where health care is provided and includes emergency care, pre-hospital care, acute care, long-term care, chronic/complex care, home care, ambulatory care and other facilities or locations in the community where care is provided (e.g., infirmaries in schools and residential facilities).^{Footnote 1}

Healthcare provider

Healthcare providers (HCPs) include individuals who provide health care or support services such as nurses, physicians, dentists, nurse practitioners, paramedics, emergency first responders, allied health professionals, unregulated HCPs, clinical instructors, and students.

Imported case

A case that acquired measles outside of Canada during the case's incubation period (7 to 21 days prior to rash onset), as supported by epidemiological and/or virological evidence.

Import-related case

A case that had a locally acquired infection occurring as part of a chain of transmission originated by an imported case, as supported by epidemiological and/or virological evidence (i.e., viral genetic evidence that is inconsistent with acquisition in Canada).

Note: if the chain of transmission has been circulating in Canada for greater than or equal to 12 months then refer to definition of an endemic case.

Measles outbreak

As measles is eliminated in Canada, cases not acquired through international travel indicate an outbreak. In Canada, a measles outbreak is defined as:

• two or more cases, at least one of which is confirmed, that are linked, either epidemiologically, virologically, or both

or

• a single case with unknown source(see definition for Unknown source case) as it indicates the presence of measles transmission in Canada

Multi-jurisdictional outbreak

An outbreak in which the infection is spread over more than one province/territory.

Unknown source case

A confirmed case for which the source of infection was not identified (not imported nor epidemiologically or virologically linked to another known case).

Virological linkage

Cases are designated as virologically linked by the National Microbiology Laboratory (NML) based on viral genetic sequencing.

Introduction

This technical guidance was developed by the Public Health Agency of Canada (PHAC), in collaboration with federal/provincial/territorial (FPT) public health authorities (PHAs) and experts with an interest in this subject matter. It provides guidance to PHAs in the event a case of measles is suspected or confirmed within their jurisdictions.

This guidance should be read and applied in conjunction with relevant existing FPT and local legislation, guidelines, regulations, agreements and policies.

This guidance is based on the Canadian context, and it applies a flexible and risk-based approach. This allows PHAs to tailor their response based on the unique situation within their jurisdiction, while ensuring those at highest risk are first to receive intervention.

Roles and responsibilities

A successful response to the management of measles cases and outbreaks is often a shared responsibility between governments (FPT, local/municipal, Indigenous), public health, health care and community sectors. Recent outbreaks have highlighted the importance of effective and timely communication and a coordinated response horizontally across sectors and vertically across levels of government. The PHA leading the response is generally responsible for implementing the activities recommended within this guidance. However, for activities that may fall outside of the PHA's scope (e.g., under the responsibility of other public health or healthcare organizations or professionals, event organizers, or operators of community settings), the role is clearly stated, and advice is included as appropriate.

Objectives

This guidance was prepared primarily to assist PHAs in their investigation and management of measles cases, contacts and outbreaks to:

• prevent complications as a result of measles infection.
• limit secondary spread of measles.
• support maintenance of Canada's measles elimination status.

PHAs may need to adapt the guidance and key recommendations as appropriate to their respective contexts, risk assessment and response activities.

Background

Measles is a highly infectious disease caused by the measles (rubeola) virus, a member of the Paramyxoviridae family. Serious complications such as respiratory failure, encephalitis, deafness and blindness can result from measles infection. It can also be fatal.

Before widespread global vaccination in 1980, measles caused an estimated 2.6 million deaths worldwide each year. According to the World Health Organization (WHO), measles remains a major cause of illness and death globally^{Footnote 2}, despite the availability of an effective vaccine.

Measles elimination is defined as the lack of a circulating endemic genotype for at least one year in the presence of a well-performing surveillance system.^{Footnote 3} In Canada, measles elimination status was achieved in 1998.^{Footnote 4Footnote 5}, and in 2000 in the United States^{Footnote 6} In 2016, the Region of the Americas became the first region of the WHO to achieve measles elimination status^{Footnote 7}, however, this was not sustained as, by 2018, measles had re-established in countries where it was previously eliminated. In November 2024, the Americas once again achieved elimination status.^{Footnote 8}

Measles transmission in a population is dependent on several factors, including population immunity from vaccination and among older adults from past natural infection. A highly immune population indirectly conveys protection to non-immune individuals through herd immunity.^{Footnote 9} However, some cases can occur among fully vaccinated people.

Maintaining elimination of measles will require enhanced surveillance activities; identifying and improving vaccination coverage in non-immune populations; and providing education, both to the public and to health professionals, on topics such as the importance of vaccination, risks of acquiring measles when travelling and early recognition of signs and symptoms.

Epidemiological characteristics of measles

The following epidemiological characteristics of measles form the basis of recommendations in this guidance:

• Transmission:
  • Measles spreads through the air via inhalation of infectious respiratory particles (i.e., airborne transmission)^{Footnote 10Footnote 11Footnote 12Footnote 13Footnote 14} and direct contact with infectious nasal or throat secretions onto mucous membranes.^{Footnote 11Footnote 15}
    • Infectious measles particles may remain suspended in the air for up to two hours.^{Footnote 12Footnote 13}
  • Less commonly, measles can also spread via contact with contaminated surfaces or objects (i.e., transfer of infectious particles from a fomite onto mucous membranes via unclean hands).^{Footnote 16}
    • Infectious measles particles may remain viable on surfaces for a short period of time, though evidence does not indicate a specific duration.^{Footnote 10Footnote 17}
• Incubation period:
  • The maximum range for the incubation period from exposure to rash onset is 7 to 21 days.
    • Average length of time from exposure to first symptom onset is 10 days but can range from 7 to 18 days.^{Footnote 18Footnote 19}
    • Average length of time from exposure to rash onset is 14 days but the rash can appear as late as 21 days.^{Footnote 18Footnote 20}
• Infectious period:
  • With rash: four days before rash onset to four days after rash onset (with the first day of rash being day zero).^{Footnote bFootnote 18Footnote 21Footnote 22Footnote 23}
  • Without rash: for 10 days after first symptom onset.
  Note: Individuals who are immunocompromised (with or without a rash) may have prolonged excretion of the virus in respiratory tract secretions; these individuals may remain contagious for the entire duration of their illness.^{Footnote 21Footnote 24Footnote 25}
• Signs and symptoms:
  • Usual presentation of measles is characterized by fever, cough, coryza or conjunctivitis and a generalized maculopapular rash that typically begins on the face and spreads down the body (i.e., to the trunk and then the arms and legs).
  • Atypical presentation of measles can be seen in breakthrough cases or cases who are immunocompromised.
    • Breakthrough cases may present with modified measles, which is generally milder (i.e., less fever, cough, coryza or conjunctivitis).^{Footnote 26}
    • Cases who are immunocompromised often have more severe disease. They may also present without a rash or with an atypical rash.^{Footnote 25Footnote 27Footnote 28}

Epidemiology in Canada

In the pre-vaccine era, measles was quite common in Canada, with 400 to 800 cases per 100,000 population reported in peak years. In 1963, a measles vaccine was made available in Canada and routine one-dose immunization programs were in place in all provinces and territories by the 1970s. Thereafter, in 1996/1997, in response to high measles incidence rates and the goal to eliminate endemic measles by the year 2000, both a routine two-dose measles mumps and rubella (MMR) vaccine schedule and second dose catch-up programs were introduced across Canada.^{Footnote 29}

In Canada, publicly funded immunization programs have resulted in high vaccination coverage and, subsequently, low measles incidence rates. As a result, the last case of endemic measles occurred in 1997. In 1998, Canada achieved measles elimination status and has sustained it since. Canada's annual incidence rate has been below three cases per 100,000 population since measles has been eliminated, which is greater than a 99% decline in measles incidence compared to the pre-vaccine era.^{Footnote 30}

Measles immunization programs in Canada

High measles vaccination coverage is a cornerstone of measles elimination and control in Canada. Immunization programs may include routine or catch-up schedules.

For more information about recommendations for measles-containing vaccines, refer to the Canadian Immunization Guide: Part 4. Immunizing agents, Measles vaccines, Recommendations for use.

Surveillance and reporting

Timely and enhanced measles surveillance has taken place through the Canadian Measles and Rubella Surveillance System (CMRSS) since its development in 1998, following measles elimination in Canada. CMRSS continuously monitors measles, rubella, and congenital rubella syndrome/infection at the national level through the weekly solicitation of confirmed-case reports from all provinces and territories, (including zero reporting) to PHAC. See Appendix D for the National Measles Case Report Form. PHAC verifies that cases meet the national confirmed case definition, then reports all confirmed cases to the Pan American Health Organization (PAHO) on a weekly basis. The surveillance system aims to support national and international reporting obligations; facilitate timely case detection and response; ensure thorough epidemiological and laboratory investigation of cases; inform national immunization strategies; and document the maintenance of elimination of these diseases.

Every effort should be made to ensure that reporting of confirmed cases in Canada continues on a weekly basis, as outlined in the CMRSS protocol. Measles cases that are identified through an outbreak investigation should also be reported to PHAC as part of routine weekly provincial/territorial (PT) measles reporting. It is essential that reporting timelines be followed throughout the duration of an outbreak. PHAC can provide support in the form of evidence summaries, advice, and human resources should a request be made by the affected jurisdiction(s).

For Canada's current measles situation, please refer to Measles and rubella weekly monitoring reports.

Public health management

Health equity and psychosocial considerations

Measles may have a greater impact on certain population groups, in terms of illness experience (e.g., duration, severity), due to social, economic, health, and/or other factors (e.g., risk of developing severe measles infection, poverty, barriers to health care, crowded or congregate living settings). PHAs should consider these factors, in addition to health equity and psychosocial implications, when implementing measures, while still aiming to minimize transmission of measles. Public health messaging should be clear, consistent and sensitive to the needs of populations with social, economic, cultural or other vulnerabilities.

Case management

Case finding and classification

When a measles case is detected, prompt case finding should take place to identify additional cases. Potential cases and contacts are considered persons under investigation until they can be classified (Table 1). All individuals classified as suspect cases of measles should undergo laboratory testing to rule out measles and be classified according to the case definitions.

A case should be classified as primary if they are not immune to measles and have never been vaccinated.

Conversely, a case should be classified as breakthrough if they have one of the following:

• a history of vaccination at least 14 days prior (can include one or more doses of a measles-containing vaccine)
• previous serological evidence of immunity

The confirmed and probable case definitions in Table 1 are aligned with the national surveillance case definition for measles.

Case investigation and public health management activities

HCPs must notify their local PHA of suspect, probable and confirmed measles cases as soon as possible (refer to Appendix B and Appendix C), in accordance with jurisdictional reporting requirements. Case investigation should not be delayed while laboratory results are pending. All reports of confirmed, probable and suspected measles cases should be investigated as soon as possible.

As part of case management activities, PHAs should:

• provide active monitoring of a case and ensure compliance with isolation measures through regular communication, recognizing that frequency may vary by PHA and the local context.
  • PHAs may determine the type of monitoring, if any, based on a risk assessment and available resources.
• provide advice about self-care, when to contact an HCP and how to seek medical care safely.
• assess and minimize the risk of transmission to others by providing public health measures advice (refer to section Isolation of cases for details).

Data collection

Information should be collected by public health professionals to facilitate public health follow-up and the completion of epidemiologic investigations by public health professionals.

The following information should be collected for every measles case:

• laboratory confirmation of the diagnosis
• vaccination history
• demographic information (e.g., name, age, sex, geographic location, occupation)
• clinical details including rash onset, healthcare visits, presence of comorbidities, complications, and case's outcome
• the potential exposure setting(s) (i.e., locations where the case may have exposed others), and likely source(s) of infection
• travel history within and outside of Canada
• details of household members and other contacts that were exposed during the case's infectious period
  • includes specific individuals identified by the case as well as groups of individuals who may have been exposed during an event or while at the same location

PT guidelines typically include information collection forms that can be used during case investigation. An enhanced measles case investigation form, like the one located in Appendix E, could be used to collect this information. Additional information may also be collected at the discretion of the PHA.

Individuals at increased risk of complications from measles infection

Some people have an increased risk of complications from measles infection,^{Footnote 15} this includes:

• individuals who are immunocompromised
• infants and children under 5 years of age
• individuals who are pregnant

Compared to individuals who are immunocompetent, individuals who are immunocompromised have a higher risk of developing prolonged or severe measles, and of suffering complications or death.^{Footnote 32} Viral pneumonitis is the most frequent severe complication in these individuals. Individuals at highest risk include those who have severely impaired cell-mediated immunity, such as those with a recent stem cell transplant, primary T-cell dysfunction, uncontrolled human immunodeficiency virus infection, or acute lymphoblastic leukemia. The risk of severe disease also remains high for people with other forms of immunosuppression caused by malignancy, high doses of steroids, or other types of immunosuppressive drugs.^{Footnote 17Footnote 33Footnote 34Footnote 35Footnote 36Footnote 37Footnote 38}

Infants are more likely to develop complications and require hospitalization.^{Footnote 33} Measles encephalitis occurs in approximately one of every 1,000 reported cases and may result in permanent brain damage.^{Footnote 39} Measles infection can cause subacute sclerosing panencephalitis (SSPE); a rare but fatal disease with an estimated mortality rate of 95%.^{Footnote 39Footnote 40} Approximately 4 to 11 per 100,000 cases of measles result in SSPE and the risk of SSPE increases in infected individuals under 5 years of age to 18 per 100,000 cases.^{Footnote 35Footnote 36Footnote 41Footnote 42}

Although there is no evidence of congenital malformations resulting from maternal measles infection, measles infection during pregnancy can result in complications, such as prematurity and fetal loss.^{Footnote 43} When measles infection occurs in late pregnancy, congenital infection is possible. The most frequently reported maternal complications include pneumonia, hepatitis and death.^{Footnote 44Footnote 45}

Clinical management of cases

No specific antiviral therapy is available for measles. Medical care is supportive.

Medical treatment or intervention administered by an HCP or within a healthcare setting is beyond the scope of this guidance.

Isolation of cases

Case management activities are the same for primary and breakthrough cases.

Suspect and probable cases should follow the same recommended public health measures as confirmed cases, including isolation, while laboratory results are pending. Of note, case management activities may need to be modified for individuals who are immunocompromised as they may be infectious for longer due to prolonged viral shedding.^{Footnote 21Footnote 25}

Length of isolation

It is recommended that cases isolate as soon as possible (i.e., from the start of symptoms, even if mild) until four days after the appearance of a rash, with the first day of rash being day zero.

Cases who do not develop a rash should isolate for 10 days, with day one being the first day of symptom onset. Isolation can also be discontinued earlier if they have a negative result on a PCR test. However, performing repeat testing for the purpose of discontinuing isolation is not recommended.

Individuals with measles who are immunocompromised may be infectious for longer, due to prolonged viral shedding, and may not display typical symptoms, including a rash.^{Footnote 21Footnote 25} Isolation requirements for these individuals should be made in consultation with the treating physician, and take into consideration the level and type of immunosuppression.

Isolation psychosocial considerations

In some situations, PHAs may need to modify isolation approaches, including the location of isolation, based on the case's living circumstances (e.g., housing instability, housing conditions, congregate living setting, overcrowded housing or limited resources). Local PHAs should help determine the location where a case isolates in collaboration with the individual and their HCP, as appropriate, and facilitate/provide the necessary supports for successful isolation.

PHAs should facilitate contact with local leadership and organizations that can provide direct support in situations where there are challenges accessing necessities while isolating (e.g., individuals live alone or in a home where all household members are in isolation together). In addition, isolation can have financial, social, and psychological impacts, which can be considerable.

Isolation recommendations

For the purpose of this document, “home” will be used as an all-encompassing term to refer to the case's place of isolation. When hospital care is not required, cases should isolate at home and away from others. This means that cases should not attend public settings such as childcare facilities, schools, post-secondary institutions, workplaces, healthcare settings (except when seeking medical care), places of worship and other group settings. If the case must leave their home to receive medical care, they should inform the HCP about their suspect, probable or confirmed measles diagnosis before the appointment, so that proper precautions to protect others can be taken.

In most instances, by the time a measles case is diagnosed, household members who have spent time at home with the infectious case are likely to have experienced a high degree of exposure (refer to section Immunization for more information on PEP of contacts). However, for any household members who have not had contact with the case during their infectious period (e.g., returning home from travel, shared custody agreements), the PHA should ensure the individual meets the criteria for expected immunity to measles before they enter the case's isolation location. Individuals who are not required to be in the home (e.g., visitors) should be advised that they should not enter the home during the case's isolation period.

Though preventing spread to non-immune household members may be challenging due to the nature of measles transmission, cases should implement measures to limit further exposure of household members during the isolation period. As such, cases should avoid being in a shared space with others, when possible. This is particularly important for non-immune household members who are at high risk of complications from measles.

Cases may also be encouraged to practise the following public health measures to help limit further exposure to household members while infectious:

• Avoid contact with others. This includes direct contact such as kissing and indirect contact such as using shared items.
• Wear a mask when in shared spaces that others may access, even if others are not present at the time (refer to section Masks for details).
• Improve indoor ventilation by opening windows and doors or by running the heating, ventilation and air conditioning system fan, when possible.
• Cover coughs and sneezes with a tissue or elbow; throw any used tissues into a plastic-lined waste container as soon as possible, and clean hands immediately afterwards.
• Practise proper hand hygiene by washing hands regularly with soap and water for at least 20 seconds or using a hand sanitizer containing at least 60% alcohol.
• Clean and disinfect frequently touched surfaces and objects, such as toys, phones, doorknobs, tables, and counters.

An individual's ability or willingness to practise recommended public health measures may be impacted by various factors (e.g., social and economic challenges, individual skills and abilities, social or geographic isolation). PHAs may need to adjust public health measure advice or help find solutions to potential barriers, according to the case's situation.

Masks

Based on evidence from other respiratory infectious diseases, properly worn, well-constructed and well-fitting masks (e.g., respirators, medical masks) can be an effective tool to reduce the spread of potentially infectious respiratory particles.^{Footnote 46Footnote 47Footnote 48Footnote 49} Therefore, in theory, mask wearing by the case or contact(s) may help reduce the risk of measles transmission; however, direct evidence has not been established in the context of measles, particularly for mask use as source control.

When mask wearing is recommended for:

• personal protection (i.e., to protect an individual from becoming infected): the individual should wear a well-fitting respirator.
• source control (i.e., to limit the spread of infectious respiratory particles to others): the individual should wear a well-fitting respirator. If a respirator is unavailable, the individual can wear a well-fitting medical mask.

Individuals should not wear a mask if they:

• are under 2 years of age.
• have trouble breathing while wearing the mask.
• are unable to put on or remove the mask without assistance.

If a case must leave their place of isolation for essential reasons (e.g., seeking medical care), they should properly wear a well-fitting mask to reduce the risk of spread to others.

PHAs should follow a risk-based approach when recommending mask use for the case and their household members during the case's isolation period. Some factors that may influence a PHA to recommend mask use include the presence of household members who do not meet criteria for expected immunity, are at risk for severe complications of measles or have not received PEP.

Below are examples of when mask use could be considered, to limit further exposure of household members:

• Cases are encouraged to wear a well-fitting respirator (or medical mask, if a respirator is not available) when they:
  • must be in a shared space with a household member.
  • are using a living space that may be accessed by other household members (e.g., kitchen, washroom, hallway), even if others are not currently in that space.
• Household members are encouraged to wear a well-fitting respirator when they:
  • must be in a shared space with a case (e.g., when providing care to a case, especially one who cannot wear a mask such as a child under 2 years of age). They should also practise the public health measures listed under Isolation recommendations.
  • are entering a space within two hours of the case occupying the space.

Contact tracing and management

PHAs should quickly identify contacts through contact tracing activities to mitigate the risk of onward spread and severe disease. PHAs should perform a risk assessment to determine which contacts should be prioritized for contact tracing and, consequently, management. Once identified, contacts should be assessed for expected immunity and be provided with appropriate information and recommended interventions.

The prioritization of contacts is of particular importance when there are large numbers of contacts, and it is not feasible to investigate all of them.

Contact definition

Based on considerable evidence from outbreak investigations, measles transmission occurs more frequently following exposures at a close distance or for a prolonged period of time (e.g., sharing a home, being in the same classroom).^{Footnote 50Footnote 51Footnote 52Footnote 53}

However, it is possible for measles to be transmitted without close contact or from a transient exposure (e.g., in a very large space, or an indoor space without being in that space at the exact same time as the infectious case), although this is reported much less frequently in the literature.^{Footnote 12Footnote 13Footnote 54Footnote 55}

For the purpose of identifying all potentially exposed individuals, a contact is defined as an individual who has either:

• spent any length of time in a shared space with a probable or confirmed measles case during that case's infectious period
• spent any length of time in an enclosed indoor space within two hours after a probable or confirmed measles case left the space, during that case's infectious period

See section Epidemiological characteristics of measles for information on the infectious period.

Contact risk assessment and prioritization

PHAs should determine the extent of contact tracing and management to be completed, based on a risk assessment. Factors such as the characteristics of the case and contacts, exposure type and exposure setting may be considered. A risk assessment can help to inform PHAs which contacts should be prioritized, which is especially important when investigation of all contacts is not feasible (e.g., during a large outbreak).

Table 2 provides several factors that may be included in the risk assessment and provides a summary of considerations to inform prioritization of contact tracing and management activities. More detailed information on contact tracing and management can be found in sections Contact tracing and Contact management, respectively.

Contact tracing

In Canada, local PHAs are responsible for initiating contact tracing. Once an HCP reports a probable or confirmed case, the PHA should aim to identify all contacts as soon as possible. For reports of a suspect case, PHAs may initiate contact tracing activities if there is high degree of suspicion of measles and based on their local resources.

Prioritization of contacts may be considered based on their intensity of exposure:

1. household members living with the case
2. individuals who had face to face contact with the case, regardless of the duration of exposure
3. individuals who were in an enclosed space and within close proximity of the case,^{Footnote f} particularly within:
   • healthcare facilities (e.g., patient room, waiting room)^{Footnote g}
   • childcare/school/recreational settings (e.g., classroom, school bus)^{Footnote h}
   • congregate living settings (e.g., shelters, dormitories)
   • workplace settings (e.g., shared workspace, lunchroom)

Note: Upon completion of a risk assessment, the PHA may de-prioritize contacts for tracing if the exposure is deemed lower-risk, particularly if:

• it occurred in an outdoor setting.
• the contact was wearing a respirator at the time.

Identifying contacts through mass communication

In some situations or settings, a large group of people may have been exposed to an infectious case, whether directly or indirectly (i.e., within two hours after the case has left the area). Examples of settings where this may occur include restaurants, shopping centres, stadiums, and transportation stations. As such, PHAs may face challenges identifying individual contacts and determining their exposure risk level. Further, PHAs may have resource constraints that impact the feasibility of tracing large groups of contacts.

In such situations, it may be appropriate for PHAs to initiate a mass communication to the public to inform individuals about the potential exposures, signs and symptoms of measles infection and information on completing a self-assessment to determine if they are immune (e.g., checking vaccination records). Individuals should be encouraged to self-identify to an HCP or PHA to facilitate prompt public health investigation if they are non-immune and at increased risk of complications from measles infection and/or if they develop symptoms. Individuals should be advised that, if they are symptomatic, they should notify their HCP before presenting to an in-person appointment, so that proper precautions to protect others can be taken.

Communication may be done through various media methods, including a news release, social media post, radio or television announcement, or other methods.

For mass communication related to air travel, refer to section Contact tracing for air travel.

Contact management

Once a list of contacts has been collated and prioritized based on the type of exposure, it is then important to identify additional risk factors for each contact to inform prioritization for contact management. PHAs should consider prioritizing contacts who do not meet the criteria for expected immunity in the following groups, and in the order presented, while also considering whether the contact is eligible for the use of PEP:

1. People at increased risk of complications from measles infection, including:
   • individuals who are immunocompromised
   • infants and children under 5 years of age
   • individuals who are pregnant
2. Healthcare workers
3. People from communities that are known to be un- or under immunized
4. Other healthy contacts

Criteria for expected immunity

A contact will require contact management if they do not meet at least one of the following criteria for expected immunity:

• year of birth before 1970^{Footnote iFootnote 56}
  • This criterion should not be used to inform expected immunity for HCPs. Assessment of immunity for HCPs should be carried out in accordance with existing occupational health and/or IPC policies. Further details on expected immunity for HCPs can be found within the Canadian Immunization Guide.
• history of laboratory-confirmed measles infection
• receipt of two doses of a measles-containing vaccine (given at least 4 weeks apart) administered after 12 months of age
• documented evidence of previous positive measles serology

Note: if an individual is immunocompromised, further assessment of immunity is needed to determine appropriate actions. This information can be found within the National Advisory Committee on Immunization Updated recommendations on measles post-exposure prophylaxis.

Contacts exposed to a breakthrough case

Evidence suggests that, in general, measles cases who have received at least one dose of measles-containing vaccine transmit less frequently than measles cases who have not received a measles-containing vaccine. However, transmission is still possible in such instances.^{Footnote 35Footnote 51Footnote 57Footnote 58Footnote 59Footnote 60}

Therefore, contact management activities for any individual exposed to a breakthrough case should proceed as usual. However, when this is not feasible (e.g., during an outbreak when there are many contacts that require management), the PHA may consider whether the case was a breakthrough infection in their risk assessment, to inform further prioritization. For example, some contacts who were exposed to a breakthrough case may be deemed lower priority, as breakthrough cases are typically less infectious.

Post-exposure prophylaxis for eligible contacts

Due to the short window of opportunity for the use of measles-containing vaccine (72 hours) and immunoglobulins (Ig) (six days) for PEP, prompt action is necessary. Specifically, PHAs should have an established plan in place to ensure administration of PEP can be done in a timely manner. Contacts who do not meet the criteria for expected immunity should be informed about PEP and prompt referral to an appropriate HCP able to carry out the prophylaxis should occur.

For more information on PEP recommendations, refer to the Canadian Immunization Guide, Part 4. Immunizing agents, Measles vaccines.

Public health measures for contacts

Contacts who do not meet criteria for expected immunity may be considered for exclusion from public settings such as childcare facilities, schools, and post-secondary educational institutions at the discretion of the PHA. In addition, they may be required to quarantine at home and avoid workplaces or other public settings, including travel or gatherings. If exclusions occur, the period of exclusion should extend from five days after the first exposure and up to 21 days after the last exposure, or until four days after rash onset if the individual develops measles.

Decisions to exclude the contact from daycare/school/workplace/other settings should consider the following:

• administration of PEP to the contact, including the PEP timing and protocol
• resources available to the PHA and their overall contact management approach (i.e., whether more or less restrictive)
• number of people in the setting that are expected to not have measles immunity
• presence of individuals at increased risk of complications from measles in that setting
• intensity of exposure that the contact experienced
• contact's previous vaccination history (i.e., if they have received one dose of a measles-containing vaccine)
• contact's ability to adhere to public health measures
• reliability of the contact to comply with early recognition of symptoms and initiation of isolation.

During contact management, PHAs should undertake the following with all identified contacts (i.e., those who meet criteria for expected immunity and those who do not):

• provide information on the signs and symptoms of measles and how it is transmitted
• advise them to self-monitor for signs and symptoms of measles from five days after the first exposure to 21 days after last exposure to a case, regardless of whether they received PEP
  • When feasible, PHAs may conduct active monitoring of contacts to help with early identification of symptoms and provide additional supports, as necessary.
• advise them to isolate immediately if symptoms develop and call their HCP or local PHA for advice

In addition, PHAs may recommend that contacts who do not meet criteria for expected immunity:

• avoid contact with others, particularly those who also do not meet criteria for expected immunity to measles or are at high risk of complications from measles, even if they have been vaccinated
• wear a well-fitting mask if:
  • in a shared indoor space that others in the home may access
  • accessing indoor public spaces for essential reasons (e.g., seeking medical care)

Refer to section Masks for more information on mask use.

PHAs should consider various factors (e.g., health equity, psychosocial, economic, home environment) that may impact a contact's adherence to public health recommendations or requirements (e.g., exclusion, quarantine, public health measures). PHAs should provide necessary supports that enable contacts to comply with public health advice.

Gatherings during outbreaks of measles

Gatherings refer to events of all sizes, in both private and public settings. These include social or religious functions, sports activities, shopping excursions, concerts, conferences, and meetings. During a measles outbreak, PHAs should communicate with event organizers and advise whether they should proceed with gatherings that may pose a risk for transmission or involve populations that may not be immune to measles or are at increased risk of complications from measles.

For gatherings that proceed, PHAs should collaborate with organizers to inform participants about the potential for disease transmission before attending. Potential attendees should be advised to stay home if they are sick or have any symptoms consistent with a measles infection. Depending on the type of gathering, it may be appropriate for information on measles vaccination to be provided.

Organizers should follow the advice of their local PHA on masking in the event of a measles outbreak in the community. If masks are recommended at the gathering, the organizer should consider having a supply of masks available to provide to participants.

Organizers can also refer to PHAC's general advice on reducing the spread of respiratory infectious diseases for more information on measures that individuals can use to protect themselves and others.

If a gathering is identified as a potential exposure site, PHAs should work closely with event organizers to gather information that can help support contact tracing activities.

Refer to section Identifying contacts through mass communication for more information on contact tracing activities for large exposures.

Management of travellers

Measles is not endemic in Canada, so when a suspect, probable, or confirmed case of measles is being investigated, the travel history both within Canada and outside of Canada should be collected. Travel within 21 days prior to rash onset should be considered in order to identify the likely source of infection. A history of travel while infectious will also have implications for contact tracing and public health management. If the case travelled to, resides in, or has close contacts in another jurisdiction within Canada, the PHA that identified the case should use established mechanisms for communicating about cases and contacts within Canada.

When contacts or exposure locations requiring public health follow-up are identified in another country, the identifying PT PHA should notify the Vaccine Preventable Diseases team within the PHAC at vpd-mev@phac-aspc.gc.ca. They will forward the relevant information to the appropriate authority of the affected country through Canada's International Health Regulations (IHR) Focal Point. If there is an urgent need to notify another country outside of business hours (8 am to 4 pm Eastern time), the PHA should contact the Health Portfolio Operations Centre (hpoc-cops@phac-aspc.gc.ca).

When multiple jurisdictions are involved, it is not always clear who should report confirmed cases to PHAC. Case reporting is important for describing and monitoring the epidemiology, impact and spread of measles. Therefore, the PT jurisdiction where the case resides is asked to report it to PHAC. Exceptionally, this decision rule could be flexible though jurisdictions must designate a primary reporter, taking into consideration travel itinerary and the public health response or intervention that was implemented.

International arrivals at ports of entry

If a communicable disease of concern (as defined in the Quarantine Act or listed in the Schedule to the Quarantine Act), such as measles, is suspected on board a marine conveyance (e.g., a cruise or cargo ship), the conveyance operator shall inform a PHAC quarantine officer (QO) as soon as possible before arrival at its first Canadian port of entry, as required under section 34(2)(a) of the Quarantine Act.

For air travel, ill travellers who have disembarked the aircraft and are suspected of a communicable disease of concern (as defined in the Quarantine Act or listed in the Schedule to the Quarantine Act), such as measles, must report to a screening officer upon their arrival, who will refer the traveller to a QO. If a communicable disease of concern is suspected before the aircrafts arrival to Canada, per section 34(2)(a) of the Quarantine Act, a conveyance operator must notify a QO of the suspected case on board as soon as possible prior to arrival by way of existing notification protocols (e.g., airport authority who will in turn notify a QO).

If the QO has reasonable grounds to suspect the traveller has or may have a communicable disease of concern, such as measles, the QO will conduct a health assessment. Based on their findings, the QO may order the traveller to undergo a medical examination (Quarantine Act section 22(1)), order the traveller to report to a public health authority (Quarantine Act section 25(1)), or order other measures authorized under the Quarantine Act. When indicated, the QO will ensure the appropriate local or PT PHA is notified. They may also secure the conveyance manifest or collect travellers' contact information (passenger locator card) for the potentially exposed travellers to facilitate contact tracing by the PHA, where appropriate.

Contact tracing for air travel

When a measles case travels by plane while they are infectious (four days before and after rash onset), there is the potential for measles transmission to contacts on the plane. For flights that arrived in the past 21 days, it is recommended that the lead PHA issue a public advisory containing the affected flight number, route, and date in order to advise the public of the exposure. No action is required for flights that occurred over 21 days, as this is the maximum incubation period when secondary cases may appear. Timely issuance of public advisories allows for notification of flight passengers as well as individuals that may have been exposed at the airport. In addition to the public advisory, at their discretion based on risk assessment, timeliness and available resources, PHAs may choose to request the flight manifest to directly notify passengers on the flight of potential exposures. Fulsome advice for managing measles exposure on a plane has been developed and is available at the following: Process for contact management for measles cases communicable cases during air travel.

Contact tracing for other travel modalities

Contact tracing for measles exposures on other conveyances such as buses, trains or ferries, should utilize a risk-based approach. The infectious period, the duration of travel, and the potential for PEP can be used to determine if a public advisory to warn other travellers of the potential exposure is warranted.

Healthcare facilities

For the management of suspect or confirmed measles in the healthcare setting, please refer to PHAC's Updated infection prevention and control recommendations for measles in healthcare settings.

Guidance for management of healthcare workers exposed to measles should refer to PHAC's Prevention and Control of Occupational Infections in Health Care guidance.

Laboratory guidelines for the diagnosis of measles

Diagnosis of measles requires careful evaluation of clinical, laboratory and epidemiological data and can be challenging. As endemic transmission has been interrupted in Canada, the incidence of measles is low and sporadic cases that occur should be carefully investigated.

The very low incidence of measles in elimination settings results in a corresponding decrease in the positive predictive value of IgM serological testing, complicating the interpretation of positive IgM serology results, particularly for those who would otherwise not meet the definition of a probable case.^{Footnote 61}

Furthermore, in a highly vaccinated population, cases may occur in previously immunized individuals, for whom serology may be uninterpretable. Therefore, molecular detection (PCR) of the virus is preferred to confirm the diagnosis of suspected cases. This also allows for the genotyping of measles viruses, which is the only way to distinguish a confirmed case (due to wild-type measles virus) and a post-vaccine reaction that mimics measles infection.

The measles viral genetic sequence changes little during transmission within an outbreak and therefore genotyping and sequence characterization of measles viruses from cases can confirm or identify transmission chains, linking cases virologically and helping to inform case investigations. Viral sequence analysis can also provide evidence of importation, directly or in support of epidemiological evidence. Timely acquisition of appropriate specimens in every suspected measles case and communication and information sharing between public health and the laboratory are essential to fully leverage the assistance and expertise of the laboratory. Furthermore, the WHO Measles and Rubella Laboratory Network recommends that national reference laboratories genotype as many cases of measles as possible, but at least 80% of sporadic cases and 80% of outbreaks. During outbreaks, it is advisable to genotype as many cases as possible to detect overlapping importation events and to study the natural history of the outbreak. In large outbreaks, the WHO network advises the collection of virological specimens from 5–10 cases early in the outbreak, with ongoing monthly sampling. Additional samples should be collected from cases arising in new areas or if the epidemiological links are not well-defined.

This section is based on recent experiences in measles diagnostics around the world and follows the principles of the guidelines of the WHO's Manual for the Laboratory-based Surveillance of Measles, Rubella, and Congenital Rubella Syndrome.

A comprehensive description of measles diagnostics can be found in the Manual of Clinical Microbiology. More detailed laboratory guidelines for the diagnosis of measles in Canada, including information on the application of measles genotyping to investigation of measles cases and chains of transmission, can be found in Appendix F.

Specimen collection

Upon suspicion of measles, clinicians should immediately collect specimens for virus detection and serology and for the purpose of laboratory confirmation. Molecular detection by PCR of the virus is preferred, and is required for viral sequencing, however its utility is limited by its relatively short window for collection. Serology (detection of measles specific IgM antibody) provides a longer collection window from rash onset and so provides a complementary means for laboratory confirmation.

For viral detection by PCR, throat swabs or nasopharyngeal swabs should be collected as soon as possible, and within seven days from the onset of rash for maximum sensitivity. Measles virus may be still detected up to 14 days from the onset of rash, but with rapidly decreasing sensitivity. Specimens should be collected using a swab approved for virus isolation and placed in virus transport media.

Although nasopharyngeal or throat swab specimens are preferred, the measles virus can also be detected in urine, which should be collected within seven days from the rash onset, for maximum sensitivity. Similarly, to the swab specimens, measles virus may be still detected up to 14 days from the onset of rash, but with rapidly decreasing sensitivity.

For the investigation of suspect cases with recent immunization with measles vaccine, specific real-time reverse transcriptase polymerase chain reactions (RT-PCRs) have been designed to detect and distinguish measles vaccine (genotype A) from wild-type virus, thereby providing a more rapid result than traditional genotyping.^{Footnote 62Footnote 63} It is important to communicate the vaccine history to the laboratory so that the vaccine PCR is performed in a timely manner.

For diagnostic serological testing, a serum specimen should be collected as soon as possible, when the patient is first seen and within 28 days of rash onset. For IgM serology, a sample collected before four days and after 28 days from rash onset may yield a false negative result. For IgG serology, the first (acute) sample should be collected within seven days from rash onset and a second (convalescent) sample 10 to 21 days after the first.

Interpretation of laboratory results

In order to properly interpret laboratory results and to assess the performance of measles diagnostic assays, both clinical and epidemiologic information need to be considered along with the laboratory information (e.g., prior vaccination history, travel history, timing of sample collection relative to onset of symptoms). Therefore, communication and information sharing between public health and the laboratory are essential.

A positive IgM result in a suspect case with history of exposure to an area with known measles activity or with an epidemiological link to a confirmed case, or positive RT-PCR result, are diagnostic for measles infection.

A positive measles PCR result plus a positive measles vaccine-specific PCR result indicates detection of measles vaccine strain and should not be classified as a case.

A positive measles PCR result with a negative measles vaccine-specific PCR result should be referred for measles genotyping for further characterization. Due to their specificity, the measles vaccine-specific PCR tests may not be as sensitive as the measles detection PCR. False negative vaccine-specific PCR results may occur in some post-vaccine reactions.

Seroconversion or a diagnostically significant increase (typically four-fold but may vary depending on the IgG assay used) of measles IgG in a patient with rash and no history of recent measles-containing vaccine is also diagnostic for measles.

Negative results by RT-PCR or negative IgM antibody detection results are not sufficient to rule out measles infection. As described in Appendix F, a number of factors may result in false negative results such as the timing of specimen collection, in relation to rash onset.

Serological results for previously vaccinated individuals (i.e., breakthrough cases) will likely not follow the paradigm associated with acute primary measles in naive individuals. Anti-measles IgM antibody response may be weak or not detectable, and a rapid elevation of anti-measles IgG titre would be expected causing strong positive anti-measles IgG results in acute sera and the likely absence of a significant rise in IgG titre in the convalescent sera.^{Footnote 64Footnote 65} In these individuals, the timely collection of specimens for measles virus detection (RT-PCR) is recommended.

Roles and responsibilities of the laboratories

Provinces and territories generally have the responsibility of front-line diagnostics of suspected measles cases. The PT PHA should have a method in place for informing and updating physicians and local health authorities regarding the issues surrounding measles laboratory investigations, particularly regarding the appropriate collection and handling of specimens. The PHAs should also ensure that there is a procedure in place to collect relevant patient and clinical information that must accompany the specimens, and that the specimens are transported to the testing laboratory safely and efficiently.

PT laboratories should ensure that health professionals are aware of the appropriate timing, storage and transport of the specimens for measles diagnostics (refer to Appendix F for more details). PT laboratories normally perform serological testing for measles IgM and IgG, and they should ensure that the results are reported with a turnaround time of no more than 72 hours. When there are large outbreaks, or outbreaks continue for extended periods of time, provinces may need to set up measles testing at more sites, and with faster turnaround times. In large outbreaks, where PEP may need to be determined by IgG serological testing, test turnaround time should be under 24 hours. They should ensure that their testing methods are accredited and participate in regular proficiency programs. PT laboratories should have a mechanism in place to send specimens for molecular testing (if not done on site) and genotyping to the NML.

The NML is a WHO Regional Reference Laboratory for measles and rubella and provides genotyping ideally for all cases of measles in Canada. As the WHO accredited measles laboratory in Canada, the NML is responsible for depositing measles sequences to the WHO global measles database. This database is used for tracking measles viral genotypes and sub-genotype lineages and in so doing, monitoring the efforts of measles elimination. The NML conducts additional sequencing, including that of the whole genome, as needed, to provide additional virological information, and interpretation thereof, for outbreak investigation and enhanced surveillance for the purpose of the ongoing documentation of the status of endemic circulation of measles in Canada.

The NML also provides regular measles serology and molecular proficiency testing panels to PT laboratories. The NML assists PT laboratories for technology transfer, test evaluation, troubleshooting and speciality testing, like SSPE serology.

For more information, refer to Appendix F and the NML's Guide to Services: Measles, Mumps and Rubella Unit.

Immunization

The Canadian Immunization Guide is the best source for up-to-date information on immunization recommendations in Canada. For the purposes of this document, a high-level summary of recommendations and considerations for immunization in response to cases or outbreaks of measles in Canada is provided.

Immunization during outbreaks

Immunization efforts during an outbreak are focused on reducing the magnitude and length of the outbreak and interrupting the spread of the virus. Maximum population immunity through routine vaccination against measles, including maintenance of high measles vaccination coverage rates (e.g., >95%), is the best tool to mitigate the size of measles outbreaks and reduce the need for measles post-exposure prophylaxis. Administration of post-exposure prophylaxis to individuals who were exposed to measles and who do not meet criteria for expected immunity is important to reduce the number of cases and reduce the severity of illness in individuals.

Supplementary efforts to achieve high immunization coverage against measles should be considered, including public health interventions such as immunization campaigns. The extent of an immunization campaign should be determined based on the public health objective (e.g., limit spread in the community), the feasibility of the intervention, and the level of risk in the community.

These efforts include reducing missed opportunities for measles immunization and increasing access to measles immunization campaigns or catch-up campaigns to immunize individuals who are not immune to measles. HCPs should use the opportunity of a confirmed measles case to remind and recall individuals who are not up to date with their measles vaccines.

Outreach efforts to sensitize the population to the importance of being immunized against measles should also be done. Measles vaccine coverage should be monitored closely, and vaccine uptake should be thoroughly documented for different population groups as well as at the individual level.

Measles immunizing agents authorized for use in Canada

Measles-containing vaccines authorized for use in Canada are available as combination vaccines, either as MMR vaccine or measles, mumps, rubella and varicella (MMRV) vaccine.

Ig products are available through the Canadian Blood Services or Héma-Québec.

For more information about the authorized measles-containing vaccines and Ig products that may be used for measles PEP in Canada, refer to the Canadian Immunization Guide: Part 4. Immunizing agents, Measles vaccines, Preparations authorized for use in Canada. The Canadian Immunization Guide is updated as the recommended use of authorized products change.

Post-exposure prophylaxis

PEP is recommended for select individuals who do not meet criteria for expected immunity and, when indicated, it should be given as soon as possible after exposure. Measles-containing vaccine or Ig may be used as per the Canadian Immunization Guide: Part 4. Immunizing agents, Measles vaccines.

Despite the use of measles-containing vaccine or Ig for post-exposure management, measles infection may occur. Exposed individuals should be provided with the recommendations outlined in section Public health measures for contacts.

For healthcare workers who have been exposed to measles refer to Prevention and Control of Occupational Infection in Health Care.

Vaccine recommendations

Post-exposure vaccination of individuals who do not meet criteria for expected immunity represents an important risk mitigation strategy.

For more detailed recommendations, refer to the Canadian Immunization Guide: Part 4. Immunizing agents, Measles vaccines, Post-exposure prophylaxis.

Immunoglobulin recommendations

Post-exposure use of Ig may prevent or modify disease. When indicated, it should be given as soon as possible after exposure.

It should be noted that Ig provides only short-term protection and requires postponing the administration of measles-containing vaccine.

For more detailed recommendations, refer to the Canadian Immunization Guide, Part 4. Immunization agent, Measles vaccines, Post-exposure prophylaxis.

Contraindications and precautions

For more information on safety, adverse events following immunization, contraindications and precautions regarding measles-containing vaccines and Ig, refer to the product monographs available through Health Canada's Drug Product Database and the Canadian Immunization Guide, Part 4. Immunizing agents, Measles vaccines, Safety and adverse events.

Vaccine supply

The status of measles-containing vaccines supply should be considered before undertaking population-based immunization initiatives as part of an outbreak response or catch-up campaigns. As with any new immunization initiative, vaccine supply should be considered in advance through consultation with FPT counterparts coordinated through the Vaccine Supply Working Group and the Canadian Immunization Committee.

While MMR vaccine supply has been stable in recent years, factors such as measles immunization programs and the broader use of MMRV vaccine could all affect the availability of MMR vaccine.

In the event of an actual or projected shortage of measles-containing vaccine during an outbreak, the identification of priority groups may be necessary. In the United Kingdom, the following priority order was considered: routine immunization for infants and children, immunization of rubella-susceptible women of child-bearing age, and immunization of susceptible (measles, mumps or rubella) healthcare workers, followed by immunization of other susceptible individuals as defined by the epidemiology of the outbreak. When possible, prioritization should take place in consultation with the Canadian Immunization Committee and the Vaccine Supply Working Group.

Strategic communications during a measles outbreak

In a large or multi-jurisdictional measles outbreak situation, communications protocols between federal, provincial and territorial governments are essential to ensure:

• a clear understanding of communication roles and responsibilities between partners involved in the outbreak response.
• efficient relationships and information-sharing and planning processes among communications staff of involved partners.
• efficient and effective use of communication resources.

The roles and responsibilities for the communications around a measles outbreak mirror those established for the management of any outbreak. If the outbreak is limited to one province or territory, that jurisdiction or regional PHA within the jurisdiction is responsible for leading the communications. If the outbreak spreads to more than one province or territory, PHAC collaborates and aligns public communications with the affected jurisdictions. PHAC is the lead for communicating internationally about a measles outbreak in Canada. Regardless of the communications lead, information sharing during an outbreak is essential in order to ensure coordinated communications across all jurisdictions.

Analysis of an outbreak

As a measles outbreak progresses, a descriptive analysis (person, place, and time) should be ongoing. The analysis should be conducted by the lead organization responsible for the outbreak investigation. Depending on the nature of the outbreak, these analyses could be shared with other provinces and territories and PHAC via the Canadian Network for Public Health Intelligence, or other established mechanisms.

At the conclusion of the outbreak, consider analyzing and reporting the outbreak. The lead jurisdiction should aim to produce a report within one year of the outbreak conclusion and make this report publicly available to other jurisdictions in Canada so that they can learn from recent experiences. It is recommended that the following data elements be evaluated:^{Footnote 66}

• the total number of cases and incidence rate of infection
• an epidemiologic description of the index case
• analysis of demographic characteristics (e.g., age, sex, geographic location)
• analysis of case classification (imported, import-related, unknown, epidemiological link to unknown source case)
• analysis of exposure settings (e.g., household, daycare, air travel)
• characterization of case vaccination status and immune status (e.g. cases too young to be immunized, cases born before 1970, cases not immunized as per the National Advisory Committee on Immunization recommendations, cases with medical contraindication to immunization, cases with documented philosophical/religious exemption, breakthrough cases
• analyzing and understanding the chains of transmission (including the number of cases in each chain), integrating, with the assistance of the laboratory, the information obtained from viral genetic analyses
• description and analysis of the performance characteristics of laboratory tests and of specimens or their collection (e.g., false positive or negative findings, if particular specimens such as urine or throat swabs were useful in the outbreak, test performance with respect to time since onset)
• identification of risk factors or groups most affected; assessment of regional vaccination coverage
• the effectiveness of the IPC measures, if applicable
• vaccine effectiveness by comparing attack rates of vaccinated and unvaccinated cases
• consider estimating the effective reproductive number

Appendix A. Persons/organizations involved in developing the guidance

This guidance was prepared by: MI Salvadori, Z Regalado, M Pople, K Graham, J Hiebert, K Meghnath, F Lalonde.

The contributions from the following PHAC programs are gratefully acknowledged: Infectious Diseases and Vaccination Programs Branch (IDVPB): Centre for Communicable Diseases and Infection Control [Infection Prevention and Surveillance Division]; Centre for Emerging and Respiratory Infections and Pandemic Preparedness [Public Health Measures Guidance Division, Surveillance and Epidemiology Division]; Centre for Immunization Surveillance and Programs [Immunization Support and Knowledge Mobilization, National Advisory Committee on Immunization Secretariat], Centre for Vaccine and Therapeutics Readiness [Routine Medical Countermeasure Programs and Supply Chain Division], Vice Presidents Office; Regulatory, Operations and Emergency Management Branch (ROEMB): Centre for Border and Travel Health [Operations and Coordination]; Science and Policy Integration Branch (SPIB): Health Equity Policy Directorate [Health Equity Integration]; National Microbiology Laboratory (NML): Science Reference and Surveillance [Viral Diseases].

PHAC gratefully acknowledges the expert contributions of: S Deeks, V Dubey, K Klein, M Naus, S Nolt, MI Salvadori, S Wilson.

PHAC gratefully acknowledges the contributions of: the Communicable and Infectious Diseases Steering Committee.

PHAC gratefully acknowledges the contributions of: Justice Canada: Business and Regulatory Law Portfolio [Health Legal Services]; Health Canada: Communications and Public Affairs Branch [Strategic Communications Directorate].

Appendix D. National measles case report form

For readers interested in the PDF version, the document is available for downloading or viewing:

National Measles Case Report Form (PDF, 21 KB, 1 page)

Appendix E. Sample measles case investigation form

For readers interested in the PDF version, the document is available for downloading or viewing:

Sample Measles Case Investigation Form (PDF, 105 KB, 3 pages)

Appendix F. Laboratory guidelines for the diagnosis of measles

Introduction

The purpose of the laboratory guidelines is to provide information related to specimen collection and transportation, as well as laboratory testing methods and interpretation of laboratory test results for suspected measles cases. A comprehensive description of measles diagnostics can be found in the Manual of Clinical Microbiology^{Footnote 67} and in the WHO Manual for the Laboratory Diagnosis of Measles and Rubella Virus Infection.^{Footnote 68} Measles laboratory testing is performed at the NML and in many provincial laboratories. Specific information is available from each laboratory conducting measles tests and should be consulted.

Summary

The RT-PCR assay is the most sensitive and reliable test for the definitive diagnosis of measles infection, but its sensitivity can be influenced by the following:

• timing of the specimen collection in relation to onset of illness
• specimen integrity and storage and transport conditions
• prior vaccination history

Throat or nasopharyngeal swabs collected within the first seven days of rash onset are the preferred specimens for RT-PCR.

Urine specimens collected within the first seven days post-rash onset are also suitable for measles virus detection by RT-PCR. Collection of both specimens (throat swab and urine) is particularly useful for the detection of sporadic cases. During outbreaks, it may be advisable to collect and test only throat swabs to reduce the burden in specimen collection and on the laboratory.

Serological testing of an acute serum specimen for measles-specific IgM class antibody is predictive for the diagnosis of measles, but not in sporadic cases without a history of travel or epidemiological link to a confirmed measles case, for which false positive results are likely to occur. False negatives may also occur depending on the time of sample collection. Measles cases with a history of measles vaccination may not have a detectable IgM response.

Collection of an acute serum specimen and a convalescent serum specimen 10 to 21 days later may show a seroconversion for IgM and/or IgG antibody in those cases in which the measles RT-PCR assay and IgM antibody were negative or indeterminate at onset of illness, thus identifying additional cases.

Serological results for previously vaccinated individuals (breakthrough infections in those with previous immunity) will likely not follow the paradigm associated with acute primary measles in naïve or unvaccinated individuals. Anti-measles IgM antibody response may be weak or not detectable and a rapid elevation of anti-measles IgG titre would be expected causing strong positive anti-measles IgG results in acute sera and the likely absence of a significant or four-fold rise in IgG titre in the convalescent sera.^{Footnote 66Footnote 67} In addition, the window for the detection of measles virus by RT-PCR may be shorter in these cases.^{Footnote 65Footnote 69Footnote 70}

A negative RT-PCR result is not sufficient to rule out a suspected measles case. A single IgM result, negative or positive, may not be sufficient to confirm or exclude the diagnosis, especially in sporadic cases. It is therefore important to evaluate RT-PCR, IgM and IgG seroconversion results in the context of the clinical and epidemiological data. PAHO recommends that cases be classified by public health teams, including laboratorians and epidemiologists, after review of laboratory results and epidemiology confirmation.^{Footnote 71}

Specimen collection

For virus detection (RT-PCR) or isolation (culture)

Throat and Nasopharyngeal specimens

Throat and nasopharyngeal (NP) swab specimens are preferred and should be collected using a swab approved for virus isolation. Swabs should be placed in a small volume (2 to 3 mL) of standard viral transport media (VTM) for a minimum of one hour to allow the virus to elute. If more than one swab has been collected (for example both throat and NP), they can be combined in the same tube. Swabs may be dacron, nylon, rayon tipped either flocked or non-flocked. Calcium alginate swabs are not acceptable as they inhibit PCR reactions. Charcoal swabs or swabs in Ames media used for swabbing for bacterial pathogens such as group A Streptococcus are not acceptable. Swabs with wooden or aluminum shafts are also not acceptable.

Specimens should be collected as close as possible to the onset of rash, and within five days for viral isolation and seven days for RT-PCR. Measles virus may still be detectable by RT-PCR up to 14 days but with much lower sensitivity.

Specimens in VTM should be kept at 4°C and shipped on ice to the laboratory to arrive within 48h from collection. Alternatively, eluted specimens can be frozen at -70°C and sent to the lab on dry ice to prevent thawing and to preserve the quality of the specimen. Cycles of freezing and thawing reduce the titre of infectious virus, which negatively impacts the ability to isolate the virus in cell culture and may also reduce the sensitivity of RT-PCR. Prior to freezing, the swab should be removed as follows. The tube should be vigorously mixed (for example by vortex) for approximately 15 seconds, the swab withdrawn from the liquid, pressed against the tube to elute residual liquid and then removed entirely. The remaining liquid can be transferred to a suitable sterile vessel for freezing and transport (for example a cryovial with external threads and an o-ring gasket to provide a leak-proof seal).

Urine specimens

Measles virus is found in urine in exfoliated cells and it can be isolated or detected by RT-PCR with good sensitivity if urine is collected as soon as possible after the onset of rash, with the same timing as for throat and NP swabs. While both urine and throat swabs are useful for the detection of sporadic cases, consideration can be given to collecting only the throat swab during outbreaks to reduce the burden on laboratory resources. Specifically, specimens should be collected within five days for viral isolation and seven days for RT-PCR. Measles virus may still be detectable by RT-PCR up to 14 days but with much lower sensitivity.

• An ideal volume of 50 mL urine (minimum 10) should be collected in a sterile container.
• Specimens should be kept at 4°C.
• As soon as possible, and preferably within 24h, urine should be centrifuged at 500 x g for 10 minutes, preferably at 4°C. The sediment should be resuspended in a final volume of approximately 2 mL of sterile VTM, tissue culture medium or phosphate-buffered saline (PBS). If no pellet is visible, remove all liquid except for approximately 1 to 2 mL at the bottom of the tube and add an equal volume of VTM, tissue culture medium or PBS. Transfer the resuspended sediment to a suitable sterile cryovial.
• The processed urine specimen can be sent to the laboratory on ice for arrival within 48h of collection. Alternatively, it should be frozen at -70°C, within 48h or sooner, and shipped to the lab on dry ice to avoid thawing, as with the throat and NP swabs.
• Unprocessed urine should not be frozen.

Oral fluid specimens

Oral fluid obtained by collecting the crevicular fluid exuding between the gums and the teeth is a non-invasive and convenient specimen that allows detection of both IgM and virus by RT-PCR. Oral fluid testing has been used with good success in low resource settings, and it is also being used in some high resource countries. The sensitivity and specificity for IgM and virus detection approach those of serology and RT-PCR, in research settings, but the quality of the results varies in the field.^{Footnote 72} At this time, this technique is not recommended for routine diagnosis of measles in Canada.

Serology specimens

The first (acute) serum specimen should be collected as soon as possible upon presentation of measles.

For IgG testing of seroconversion, a second (convalescent) serum specimen should be collected 10 days to 21 days after the first sample.

For IgM testing, samples collected before four and after 28 days from the onset of symptoms may yield false negative results.

Specimen storage and transport

Specimens for virus detection and isolation (throat/NP swabs and sedimented urine) can be stored at 4ºC and shipped on ice for arrival at the laboratory within 48 hours from collection. Serum specimens for IgM serology can be stored at 4ºC and shipped on ice for arrival at the laboratory within three days from collection. Otherwise, samples should be frozen (-70°C or below for throat/NP swabs and sedimented urine and -20°C or below for serum) and shipped on dry ice. Specimens should not be allowed to freeze and thaw as this may reduce the sensitivity of the test. Shipping of specimens shall be done by a Transportation of Dangerous Goods certified individual in accordance with the Transportation of Dangerous Goods Regulations.^{Footnote 73} For additional information regarding classification of specimens for the purposes of shipping, consult either Transportation of Dangerous Goods Regulations, Part 2, Appendix 3 or International Air Transport Association, Dangerous Goods Regulations, section 3.6.2, as applicable.

Measles virus detection

Reverse transcriptase polymerase chain reaction

RT-PCR is the most sensitive and the most specific test available for a confirmatory diagnosis of a measles infection, provided an appropriate specimen is taken as early as possible after rash onset. Best sensitivity is achieved when the specimen is collected within seven days from the rash onset. After that time detection of the virus is still possible, but with rapidly decreasing sensitivity.

Commercial kits for RT-PCR detection of measles do exist, but reference laboratories typically use in-house methods. The NML uses two real-time RT- PCR methods targeting the nucleoprotein (N) and the haemagglutinin (H) gene.^{Footnote 74}

A positive RT-PCR result provides confirmation of measles infection however a negative RT-PCR result does not exclude the possibility of a measles infection and should not be used to rule out a suspected measles case.

For the investigation of suspect cases with recent immunization with measles vaccine, specific real-time RT-PCRs have been designed to detect and distinguish measles vaccine (genotype A) from wild-type virus, thereby providing a more rapid result than traditional genotyping.^{Footnote 62Footnote 63} It is important to communicate the vaccine history to the laboratory so that the vaccine PCR is performed in a timely manner.

Factors influencing reverse transcriptase polymerase chain reaction results

A positive RT-PCR result may be obtained in individuals with history of recent measles vaccination. In these cases, genotyping by sequencing is required to distinguish between a wild-type measles infection and measles vaccine reaction. Measles vaccine-specific RT-PCR tests have been developed and validated for the purpose of decreasing the turnaround time in distinguishing vaccine reactions from measles cases.^{Footnote 62Footnote 63}

Although the analytic sensitivity of RT-PCR is approximately 20 copies of measles virus RNA, the overall clinical sensitivity is affected by pre-analytical factors, which may result in a false negative result. Refer to section Specimen collection above, and the list below:

• timing of specimen collection, in relation to onset of illness
  • The window for the detection of measles virus by RT-PCR may be shorter in cases with vaccination history.^{Footnote 65Footnote 69Footnote 70}
• specimen type and quality
• rapid transportation of the specimen to the laboratory
  • Specimens for virus detection should be delivered to the laboratory within 48 hours of sample collection, unless kept frozen at -70°C or below.
• appropriate storage of specimens
• avoidance of freeze/thawing specimens

Measles virus isolation

Measles virus isolation requires growing B95a or Vero/hSLAM cells which are inoculated with the specimen. Cytopathic effects may become visible four to five days later, at which time measles virus can be identified by immunofluorescence or RT-PCR. Up to three sub-passages (each four to five days) may be necessary.

Measles virus isolation is not as sensitive or rapid as RT-PCR and it is much more dependent on specimen quality and storage conditions. It also has a much longer turnaround time than RT-PCR. For these reasons, culture isolation is no longer used for primary diagnosis of measles infection. Nevertheless, it is useful to isolate measles strains from new outbreaks and sporadic cases in order to build a strain repository that can be used for additional analyses such as whole genome sequencing and for the preparation of proficiency panels.

Serology tests

Immunoglobulin M

The presence of measles-specific IgM antibodies is indicative of primary/acute measles infection, when accompanied by clinical signs of measles and a history suggesting exposure to measles. Confirmation of IgM results by RT-PCR detection of the measles virus is recommended whenever possible, because false IgM results may occur.

Positive IgM results without acute measles infection

A positive IgM result in a case with rash and without any history of travel to endemic areas or any epidemiological link to a suspected case is most likely a false-positive.^{Footnote 75} IgM testing kits may produce false-positive measles IgM results in patients with rheumatoid factor, other acute infections, with high titres of measles IgG, or for unknown reasons.

A measles-specific positive IgM result may occur in patients who received a measles-containing vaccine, up to 56 days prior to the time of testing. There are no serological tests available to distinguish positive IgM results due to the vaccine or wild type strains of measles.

Negative IgM results in the presence of acute measles infection

Negative results may occur when the serum sample is collected before four days from the rash onset, when IgM may not have developed to a sufficient titre to be detected by the enzyme immunoassays (EIA) or in a population of high vaccine coverage, measles infection may develop in previously vaccinated individuals, who may not have a detectable IgM response. False negative results may also occur for unknown reasons as no diagnostic test is 100% sensitive.

Immunoglobulin G

The presence of measles-specific IgG is indicative of a recent or remote exposure to measles virus, either by wild type infection or by vaccination. There are no available tests to distinguish IgG antibodies due to vaccination or natural infection.

Seroconversion (i.e., negative to positive result) or a diagnostically significant (typically four-fold but may vary depending on the IgG assay used) or greater rise in IgG titre between the acute and convalescent sera is indicative of measles infection. This requires a delay in the collection of the second (convalescent) serum sample of 10 days or more after the collection of the first (acute) serum sample. However, this may be the only way to conclusively demonstrate a measles infection when RT-PCR is not available, and the IgM result is negative or unreliable.

EIAs measure IgG titre as continuous OD value (sometimes converted to International Units) and therefore it is important to perform end-point titrations of a sample, as opposed to a single dilution run, in order to conclusively determine the difference in titres between acute and convalescent sera.

Previously vaccinated individuals (breakthrough infections in those with previous immunity) may represent an exception to the significant rise in titre paradigm in that rapid elevation of anti-measles IgG titre would be expected causing strong positive anti-measles IgG results in acute sera and the likely absence of a significant rise in IgG titre in the convalescent sera.^{Footnote 64Footnote 65Footnote 69}

Determination of the presence of measles-specific IgG, which may be done with a quantitative method, is used to gauge the immune status of an individual, most often for occupational reasons. The presence of measles-specific IgG, as determined using a validated EIA is a good indication of immunity to measles and has generally good qualitative agreement with protective neutralizing antibodies measured by the gold standard, the plaque reduction neutralization test (PRNT).^{Footnote 68Footnote 76Footnote 77Footnote 78} EIA methods typically have less concordance for sera falling within the low positive to equivocal range. While PRNT has higher sensitivity, it is time-consuming, requiring up to seven days for a result, labour-intensive and not easily standardized or implemented in reference laboratories, making it not feasible or practical for routine assessments of immunity. EIA methods on the other hand are commercially available, fast (results typically generated in a few hours), can be highly multiplexed with several specimens at once and can often be automated.

The protective level of measles IgG has been estimated between 120^{Footnote 79} and 200 mIU^{Footnote 80}, but is not precisely known.^{Footnote 61Footnote 76}

Measles virus genotyping

Measles virus genotyping is used to distinguish post-vaccine rash from wild type measles infection. Genotyping is also an important surveillance tool to identify the source of importations and to link cases in outbreaks. The measles nucleotide sequence changes little during transmission within an outbreak and therefore it is a reliable tool to confirm or exclude epidemiological links. The WHO Measles and Rubella Laboratory Network recommends that national reference laboratories genotype as many cases of measles as possible, but at least 80% of sporadic cases and 80% of outbreaks. It is not necessary to genotype all cases of a large outbreak, but it is still advisable to genotype as many cases as possible to detect overlapping importation events and to study the natural history of the outbreak.

Measles genotyping has been standardized according to WHO guidelines^{Footnote 78} and is available at the NML. A portion of the nucleoprotein (N) gene is amplified by RT-PCR and the amplicon sequenced. The genotype is determined by comparison of the 450 nucleotides that code for the carboxy-terminus of the nucleoprotein to WHO-standardized genotype reference sequences (the N450). Sequences for measles samples are deposited in WHO's global Measles Virus Nucleotide Surveillance database (MeaNS)^{Footnote 81} and further analyzed by comparison to the different measles strains in the database, within the same genotype. This analysis can provide confirmation of the source of importation or an epidemiological link to other cases.

While 24 genotypes were initially identified, only 2 have been detected since 2021: B3 and D8.^{Footnote 82} As a result, the WHO global measles laboratory network has adopted a practice of designating a unique 4-digit identifier to the exact and precise N450 sequence termed the Distinct Sequence Identifier (DSId). These DSIds provide a sub-genotype nomenclature that can be used to define and track measles strains. However, there are notable limitations in that a difference in DSId does not immediately exclude relatedness of cases, as the measles viral genome does evolve or change over time. The results need to be interpreted in the context of sequences from other contemporary cases and the relatedness of those sequences. Genotypes, on the other hand, are collections of measles viral strains or lineages (DSIds) with similar genetic sequences. Therefore, viral genetic sequence differences captured by genotypes are broad enough such that the detection of a different genotype between cases excludes a link between the cases.

As a result of having a global measles sequence database, to which all WHO accredited laboratories are required to submit their sequence data from measles cases in a timely fashion (within two months of specimen receipt), it is possible to identify measles strains (DSIds) that are actively circulating internationally. These are designated by the WHO as “named strains” to reflect their epidemiologically active status and distinguish them from less active strains. Due to their active status, it is possible that these strains are repeatedly detected and imported into countries that have eliminated endemic virus.

For measles molecular epidemiology and outbreak analysis, especially for the purposes of documenting elimination of endemic virus, it is sometimes necessary to sequence additional regions of the genome, beyond the N450 region, such as the non-coding region between the matrix and fusion genes (roughly 1000 nucleotides in length) or the whole genome (roughly 15,000 nucleotides in length), in order to accurately distinguish the chains of transmission, particularly in the case of repeated importations of a named strain.

As the WHO accredited measles laboratory in Canada, NML deposits all measles viral sequences obtained from measles cases in the WHO measles database, MeaNS. The MeaNS database is an invaluable resource to monitor measles molecular epidemiology around the world and health professionals can register on the MeaNS database website to access public data.

For genotyping, the specimen type and handling are the same as for RT-PCR. An aliquot of all specimens confirmed positive for measles RT-PCR by laboratories within the provinces and territories should be sent to the NML for genotyping. Specimens with measles RT-PCR positive results obtained at the NML are automatically reflexed to genotyping. To meet the reporting obligations to support Canada's documentation of the elimination of endemic measles, PAHO requires that at least 80% of cases and outbreaks are genotyped.

Special situations

Sub-acute sclerosing panencephalitis

SSPE is a rare but fatal complication caused by persistent measles virus infection in the central nervous system (CNS). The virus cannot be readily detected by RT-PCR in the cerebrospinal fluid (CSF), although some reports have demonstrated detection in CNS tissue, such as brain biopsies. However, the relative levels of measles IgG in serum and in the CSF is the typical laboratory method used to confirm the diagnosis, together with the characteristic clinical, neurological and pathological evidence of SSPE.^{Footnote 83}

This test is performed at NML and it requires paired CSF and serum specimens. Total IgG and total albumin concentrations (mg/L) in both serum and CSF must be determined and provided. Paired serum and CSF samples are tested using the Euroimmun kit for antibodies of the IgG class against measles virus in CSF. The ratio of measles-specific antibodies in the CSF and the serum in comparison to the ratio of total IgG or total albumin in the CSF and the serum is used to determine whether there is an indication of measles-specific antibody production in the CNS.

Measles cases in individuals with presumed immunity

While rare, in a population with high vaccination coverage and enhanced surveillance, measles cases can be detected in individuals with presumed immunity, either due to vaccination or presumed natural immunity.^{Footnote 65Footnote 69Footnote 70} Lab test results for individuals with breakthrough infections in those who were vaccinated but did not develop immunity from the vaccine are expected to be similar to those for naïve individuals, as described in sections Measles virus detection and Serology tests, above. Breakthrough infections in those with previous immunity can be difficult to diagnose. This section is based on recent experiences in measles diagnostics in Canada and internationally, which has been incorporated into the laboratory guidelines of the World Health Organization Measles and Rubella Laboratory Network.

• The best method to confirm measles cases in breakthrough infections is viral detection by RT-PCR. However, the window for the collection of specimens with the best possibility of obtaining a positive result may be shorter. Collection of suitable specimens (throat/NP swabs, urine) should be done as soon as possible after rash onset.
• Measles breakthrough infection cases may not have detectable measles-specific IgM antibodies, resulting in negative, or indeterminate, measles IgM results.
• Measles-specific IgG antibodies may rapidly rise in response to the infection resulting in elevated results (high reactivity) in the acute specimen.
  • The rapid rise may result in the absence of a diagnostically significant difference in the IgG levels between acute and convalescent sera.
  • Titres of measles neutralizing antibodies of ≥40,000 milli-international units in the acute specimen, as measured by PRNT assay, have been demonstrated in some studies to be characteristic of breakthrough infections.^{Footnote 68Footnote 84Footnote 85}
  • Breakthrough measles infections can also be characterised by the detection of high avidity measles IgG antibodies in the acute sera.
• The use of specialized serological methods such as IgG avidity testing and measurement of the titre of neutralizing antibodies by PRNT can assist in classifying cases as breakthrough infections but are not necessary for laboratory confirmation of cases. The NML has the ability to perform these methods. However, they are considered research methods and are done by special request with a lengthy turn-around time. It's important to note that these methods typically do not provide laboratory confirmation of measles but instead are used for retrospective outbreak analysis. The best method for case confirmation and diagnosis remains viral detection by RT-PCR.
• Negative measles IgM and/or RT-PCR results do not, on their own, exclude, or rule-out, measles infection. Communication between the laboratory and public health to review all information about the case, including differential diagnoses, is essential for test interpretation and classification of these cases.

Interpretation of laboratory results

• A positive RT-PCR result by itself or a positive IgM result in a patient with typical clinical symptoms or with history of travel in an area with known measles activity or with an epidemiological link to a confirmed case is diagnostic of measles.
• A negative RT-PCR result must be evaluated keeping in mind the time of collection of the specimen (must be collected within seven days from the rash onset), prior vaccination history and the conditions of storage and shipping to the laboratory.
• When measles vaccine-specific RT-PCR tests are performed, a positive measles PCR result plus a positive measles vaccine-specific PCR result indicates detection of measles vaccine strain, and should be classified as not a case.
  • A positive measles PCR result with a negative measles vaccine-specific PCR result should be referred for measles genotyping for further characterization. Due to their specificity, the measles vaccine-specific PCR tests may not be as sensitive as the measles detection PCR. False negative vaccine-specific PCR results may occur in some post-vaccine reactions.
• IgG seroconversion or a diagnostically significant increase in IgG titre in a patient who presented with rash is also diagnostic of measles. The interpretation of an IgG increase is problematic in previously vaccinated patients where a significant increase (such as four-fold) is less likely to be detected, or it was not measured by an end-point dilution method.
• With the low prevalence of measles virus in Canada, the positive predictive value of measles IgM tests, which do not have perfect specificity and sensitivity, are reduced. Positive IgM results in a patient with rash and without a history of exposure to measles are potentially false positives and should be confirmed by RT-PCR or evidence of seroconversion.
• An IgM positive result in a patient who received a measles-containing vaccine up to 56 days before the test may be caused by the vaccine. Seroconversion is also not a useful diagnostic test in this case. Detection of the measles virus by RT-PCR is needed to confirm the diagnosis. Genotyping, or vaccine-specific RT-PCR, is required to exclude vaccine strain infection.
• A negative IgM result may occur in a measles case if the specimen was collected too early after the rash (before 4 days). A second sample can be collected 10 to 21 days later and tested for IgM and IgG, if a timely RT-PCR specimen is not available.
• A negative IgM result may occur in individuals who were previously vaccinated. In these individuals, detection of the measles virus by RT-PCR is needed.
• During outbreaks, diagnosis of measles cases is sometimes done on a positive IgM result only, on history of exposure only, or on the clinical presentation. However, this is not acceptable for confirmation of sporadic cases which require lab confirmation. Positive measles IgM results in these situations are potentially false positives which should be confirmed by additional laboratory data (RT-PCR or evidence of seroconversion) or epidemiological data. The Pan American Health Organization recommends that cases be classified by public health teams, including laboratorians and epidemiologists, after review of laboratory results and epidemiology confirmation.

Measles testing at the National Microbiology Laboratory

The NML provides the following services:

• Measles RT-PCR (two targets)
• RT-PCR for the detection of measles vaccine virus for vaccine/wild-type differentiation
• Measles genotyping
• Serology for confirmation of SSPE
• Proficiency panels for laboratories conducting measles RT-PCR (including vaccine-specific RT-PCR) and measles serology (IgM and IgG)
• Culture isolation of measles virus (not for diagnostic purposes)

For more details, please consult the National Microbiology Laboratory Guide to services.

Detailed protocols for detection of measles virus by RT-PCR are available from NML on request. The NML will assist laboratories who desire to implement RT-PCR by sharing protocols, providing training and distributing an annual molecular measles panel. Laboratories who conduct measles virus RT-PCR are requested to refer positive specimens to the NML to be genotyped for measles surveillance and reporting to the PAHO and WHO.

The NML can also assist with outbreak investigations by applying specialized methodology such as whole genome sequencing (investigating chains of transmission) and specialized serological methods, such as IgG avidity and/or measles PRNT to investigate measles cases in individuals with presumed immunity.