Measles virus: Infectious substances pathogen safety data sheet

For more information on measles virus, see the following:

• Measles
• National case definition: Measles
• Measles and Rubella weekly monitoring reports

Section I - Infectious agent

Name

Measles virus

Agent type

Virus

Taxonomy

Family

Paramyxoviridae

Genus

Morbillivirus

Species

hominis

Synonym or cross-reference

Formerly known as morbilli, also known as measles virus, MeV, MV, rubeola virus, measles morbillivirus, English measles, red measles, 5-day measles and hard measles^{Footnote 1Footnote 2Footnote 3}. Etiologic agent of measles, Koplik's spots, subacute sclerosing panencephalitis, measles inclusion body encephalitis^{Footnote 1Footnote 2Footnote 3}.

Characteristics

Brief description

Measles virus (MV) is characterized by enveloped, pleomorphic virions of approximately 100-300 nm in diameter, which contain a single-stranded, negative-sense, non-segmented RNA genome of approximately 15.9 kb^{Footnote 4Footnote 5}. The genome encodes six structural proteins: nucleocapsid protein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), haemagglutinin protein (H), and large protein (L)^{Footnote 5}. The nucleocapsid is surrounded by a membrane in which two viral glycoproteins, H and F, are embedded^{Footnote 6}. Only one serotype of MV has been described^{Footnote 4}.

Properties

Following exposure, measles virus infects immune cells (dendritic cells, macrophages, thymocytes, T and B cells) in the respiratory tract through binding of the H protein to the signalling lymphocytic activation molecule (SLAM, also known as CD150) on the surface of target cells, which triggers a modification of the F protein that associates with the H protein and fuses the viral envelope and the host cell membrane^{Footnote 4}. Infection of host immune cells then facilitates virus spread to non-lymphoid organs where progeny virions infect endothelial and epithelial cells through binding of the nectin-4 receptor^{Footnote 4}.

The viral genome also encodes two non-structural proteins, V and C, which are primarily involved in inhibition of the innate immune response^{Footnote 4}.

Section II - Hazard identification

Pathogenicity and toxicity

Symptoms of measles usually develop 8-14 days following exposure^{Footnote 4}. The prodromal phase lasts approximately 3-5 days and is characterized by fever accompanied by cough, coryza, and/or conjunctivitis^{Footnote 7Footnote 8}. Koplik's spots, characterized by small whitish spots on the buccal mucosa that precede onset of rash by 1-2 days, occur in approximately 70% of cases and are widely considered as pathognomonic for measles, although their diagnostic reliability has been questioned in recent years^{Footnote 1Footnote 4Footnote 9Footnote 10}. The characteristic measles rash presents as a maculopapular exanthema, with little pruritus, formed by large irregular and confluent plaques^{Footnote 1}. The rash begins on the face and neck and spreads in a single outbreak over 3-4 days to the entire body, including the palms of the hands and soles of the feet^{Footnote 1}. Rash and conjunctivitis are present in nearly all immunocompetent patients and are associated with the immune response against measles virus; conversely, immunocompromised patients may not mount an immune response against the virus and therefore may not develop these symptoms^{Footnote 4}. Acute infection is also characterized by a profound immunosuppression, rendering the patient highly susceptible to secondary infections^{Footnote 4}. In vaccinated individuals, clinical symptoms may be milder and of shorter duration, or absent (referred to as modified measles)^{Footnote 4Footnote 8}. Atypical measles was described in the 1970-1980s and occurred primarily in those who previously received the inactivated (killed) measles vaccine; this syndrome is characterized by a maculopapular rash that can progress to include vesicular, petechial or purpuric lesions, which is accompanied by pneumonia and pulmonary infiltrates with or without pleural effusion^{Footnote 11Footnote 12Footnote 13}. Although rare, cases of atypical measles are still reported^{Footnote 13}. In uncomplicated measles cases, clinical signs resolve approximately one week after rash onset^{Footnote 7Footnote 8}.

Complications occur in approximately 30% of measles cases and vary depending on age and predisposing factors^{Footnote 1Footnote 14}. The most common complications include pneumonia, otitis media (middle ear infection), laryngotracheobronchitis (croup), and diarrhea; these may be caused directly by measles virus but are more likely to result from secondary viral or bacterial infections^{Footnote 4}. Pneumonia is estimated to occur in 1-6%, otitis media in 7-9%, and diarrhea in 8% of measles cases in children in developed countries^{Footnote 1Footnote 11}. Further, measles patients may develop vitamin A deficiency, in part due to the acute-phase immune response^{Footnote 4}. This deficiency is associated with increased severity; sequelae include xerophthalmia, keratitis, keratoconjunctivitis, conjunctival lesions, and blindness^{Footnote 4Footnote 7}.

Neurological complications associated with measles are uncommon but can cause serious sequelae and death^{Footnote 4}. Acute disseminated encephalomyelitis occurs in approximately 1 per 1,000 measles cases, often within 2 weeks of infection; symptoms include fever, fatigue, headache, nausea, vomiting, seizures, coma, and death^{Footnote 4}. Measles inclusion body encephalitis is considered very rare and occurs within 6-12 months of exposure, primarily affecting immunocompromised patients; symptoms include cognitive impairment, seizures, blindness, hearing loss, coma, and death^{Footnote 4}. Subacute sclerosing panencephalitis (SSPE) is a fatal complication of measles with an estimated frequency of 6.5-11 per 100,000 measles cases^{Footnote 4}. SSPE is characterized by persistent infection of the brain with hypermutated viruses and typically occurs several years post-infection in those that were infected at a young age; symptoms include behavioural abnormalities, cognitive impairment, myoclonus, seizures, coma, and ultimately death within 1-3 years of onset^{Footnote 4Footnote 15}.

In pregnant women, measles may cause spontaneous abortion, premature labour, low birth weight, and possibly maternal death; measles during later pregnancy is associated with severe respiratory complications and perinatal infection of the newborn^{Footnote 4}. These complications are not restricted to women in developing countries, as complications including pneumonitis, hepatitis, premature labour, spontaneous abortion, and death were reported in pregnant women in the United States^{Footnote 16}.

In addition to causing profound acute immunosuppression, measles can also cause prolonged immunosuppression, termed immune amnesia, which is associated with increases in overall morbidity and mortality for months to years post-infection^{Footnote 11Footnote 17}.

Epidemiology

Measles is solely maintained in human populations and occurs worldwide^{Footnote 7Footnote 18}. Before the measles vaccination program began in 1963, there were as many as 3-4 million cases of measles per year in the United States, of which approximately 500,000 cases were reported each year to the Centers for Disease Control and Prevention (CDC)^{Footnote 19}. Of these, approximately 48,000 were hospitalized, 1,000 developed encephalitis, and 400-500 died from measles^{Footnote 19}. Since then, widespread use of measles-containing vaccine has led to a greater than 99% reduction in measles cases relative to the pre-vaccine era^{Footnote 19}.

Annual reported measles incidence decreased by 88% from 2000 to 2016 from 145 to 18 cases per 1 million population; global resurgence to 120 cases per 1 million population occurred in 2019, which ultimately declined to 17 in 2021^{Footnote 18}. Large and disruptive outbreaks were reported in 22 countries^{Footnote 18}. A 90-95% threshold of herd immunity is recommended to prevent endemic measles circulation^{Footnote 4}, and all six World Health Organization (WHO) regions have committed to measles elimination^{Footnote 18}. Although none of the WHO regions has achieved and sustained measles elimination targets, by the end of 2021, 76 (39%) countries had been verified by independent regional commissions as having achieved or maintained measles elimination status^{Footnote 18}. WHO's Region of the Americas achieved verification of measles elimination in 2016; however, endemic measles transmission was re-established in Venezuela (2016) and Brazil (2018)^{Footnote 18}. Since 2016, endemic transmission has been re-established in eight other countries (Albania, Cambodia, Lithuania, Mongolia, Slovakia, the Czech Republic, the United Kingdom, and Uzbekistan) that had previously achieved verification of measles elimination^{Footnote 18}. Epidemics continue to occur on a cyclical basis (2-5 years) in endemic areas of the world^{Footnote 1}, and a global resurgence occurred in 2019^{Footnote 18}.

The COVID-19 pandemic has greatly impacted vaccination programmes and surveillance systems as well as increasing vaccine hesitancy, causing a global resurgence of measles^{Footnote 4}. One example of this is in the European Region where between January and October 2023, the WHO reported 30 000 measles cases up 30 fold compared to 941 cases in all of 2022^{Footnote 20}.

Canada achieved measles elimination in 1998, although imported cases continue to occur and can lead to outbreaks^{Footnote 21}. A total of 2,218 cases were reported in Canada during 2000-2020^{Footnote 22}, with increased cases in 2007 and 2011 due to importation^{Footnote 23Footnote 24}. In 2007, an outbreak responsible for 94 cases occurred in Quebec, with transmission within several unrelated networks of unvaccinated individuals despite an estimated population immunity of 95%^{Footnote 23}. In 2011, the largest measles outbreak in North America since elimination occurred in Quebec, with 21 measles importations linked to a large outbreak in France and 725 cases^{Footnote 24}. A superspreading event triggered by one importation resulted in sustained transmission and 678 cases^{Footnote 24}. The overall incidence was 9.1 per 100,000; the highest incidence was in adolescents 12-17 years old (75.6 per 100,000), comprising 56% of case patients^{Footnote 24}. Between 2016 and 2020, 19 measles outbreaks were reported in Canada^{Footnote 21}. Amongst cases with available information, 53% were unvaccinated and 46% were vaccinated, with 40% being imported^{Footnote 21}. The majority of index cases (n = 17) reported travel outside of Canada during their incubation period, while the other two index cases included one case who did not travel outside Canada but was potentially exposed to an international case at a Canadian port and one case who did not report any travel outside Canada or exposure to a traveller^{Footnote 21}. The median age of measles outbreak cases was 17 years (range 0-58 years)^{Footnote 21}.

Unvaccinated individuals are at a greatly increased risk of infection and disease due to measles virus relative to individuals properly vaccinated with measles-containing vaccine (MCV)^{Footnote 25Footnote 26}. Complications associated with measles are most frequent in children less than 5 years, adults older than 20 years, pregnant women, and individuals that are immunocompromised or malnourished^{Footnote 4}. Measles burden and associated case fatality rates (CFR) are greater in developing countries^{Footnote 14Footnote 27}. CFRs are influenced by factors such as age, nutritional and immunological status, vaccination, and access to healthcare^{Footnote 7}.

The annual number of estimated measles deaths decreased by 83% from 761,000 in 2000 to 128,000 in 2021, with an estimated 56 million deaths prevented by vaccination. Measles CFRs vary significantly between and within regions countries^{Footnote 4}. Measles is an uncommon cause of death in developed countries, in which the CFR is generally less than 0.1%^{Footnote 11}. CFRs can increase to approximately 5% in endemic areas (e.g., developing regions of Africa and Asia)^{Footnote 7}. A mean CFR of 2.2% was estimated in low-to-middle income countries between 1990 and 2015, with a predicted decrease to 1.3% for 2016-2030^{Footnote 28}.

Host range

Natural host(s)

Humans are the only natural host of measles virus^{Footnote 4}.

Other host(s)

Non-human primates (NHPs) are susceptible to measles virus infection and develop clinical disease due to infection; they therefore served as essential experimental animal models during early studies of measles virus^{Footnote 29}. Serological evidence of measles virus infection has been reported in NHPs held in captivity in zoos and primate centers, with humans serving as the source of exposure^{Footnote 30}. However, measles virus does not circulate amongst NHPs in their natural habitat, as their population size and density are insufficient to maintain measles transmission^{Footnote 7Footnote 30}.

Infectious dose

Infectious dose for humans extrapolated to be 0.2 organism by intranasal spray^{Footnote 31}.

Incubation period

The incubation period ranges from 8-14 days, although a possible incubation period of up to 23 days was reported^{Footnote 4Footnote 32Footnote 33}.

Communicability

Measles is one of the most contagious human diseases with an estimated basic reproduction number (R₀) of 12-18; this represents the average number of secondary cases generated by a primary case in a completely susceptible population^{Footnote 4Footnote 34}. Preferred routes of transmission include direct contact with mucous membranes and by inhalation^{Footnote 8Footnote 35}. Measles virus is maintained by human-to-human transmission through direct exposure to respiratory droplets or secretions over short distances, through aerosols produced by infected individuals, and to a lesser extent, by fomites contaminated with infectious secretions^{Footnote 8Footnote 35}. Airborne transmission of measles is well-established^{Footnote 36Footnote 37Footnote 38}. Suspended aerosols can remain infectious for several hours^{Footnote 39}. The role of mechanical ventilation systems in airborne measles transmission has been described in previous outbreaks^{Footnote 37Footnote 40}. Although rare, transmission by injection is possible as vaccine-associated measles cases have been reported^{Footnote 41}.

Measles virus has been isolated from peripheral blood mononuclear cells (PBMC) for up to 7 days and from urine for up to 10 days after the onset of rash in otherwise healthy children and adults^{Footnote 42}. However, prolonged measles virus shedding, as defined by detection of measles virus RNA in at least one specimen obtained 30-61 days after rash onset, was reported in both HIV-infected and -uninfected children^{Footnote 32}.

Section III - Dissemination

Reservoir

Humans are the only natural host and reservoir of measles virus^{Footnote 4}.

Zoonosis

Reverse zoonotic transmission from humans to captive NHPs has been reported, with spontaneous measles outbreaks described in many primate centers around the world^{Footnote 30}. Amongst NHPs held in captivity in zoos and primate centers, antibodies against measles virus have been detected in apes (chimpanzee, gorilla, orangutan, gibbon) with seropositivity ranging from 0-62%; in Old World monkeys (macaques, guenon, baboon, mandrill, proboscis, patas, colobus) with seropositivity ranging from 0-98%; and in New World monkeys (squirrel monkey, spider monkey, capuchin, marmoset, woolly, howler, three-striped night monkey), with seropositivity ranging from 1-22%^{Footnote 30}.

Vectors

None.

Section IV - Stability and viability

Drug susceptibility/resistance

Susceptible to ribavirin in vitro, with limited data on clinical use of ribavirin^{Footnote 43Footnote 44Footnote 45Footnote 46Footnote 47}.

Susceptibility to disinfectants

Susceptible to povidone-iodine, formaldehyde, 1% sodium hypochlorite, 70% ethanol, glutaraldehyde, phenolic disinfectants, peracetic acid, hydrogen peroxide^{Footnote 48Footnote 49Footnote 50}.

Physical inactivation

Measles virus (Edmonston strain) can be inactivated by heat at 56°C for 30 minutes^{Footnote 51} or at 37°C for 4 hours^{Footnote 52}. Inactivation of the MV _vac2 GFP strain occurs by heat treatment at 37°C for 23 hours and at pH below 5 or above 10^{Footnote 52}. Inactivation by UV radiation at 1.5 x 10² µW/mm was determined in measles virus-infected Vero cells^{Footnote 52}.

Survival outside host

Measles virus can survive as suspended aerosols for several hours and on surfaces for less than 2 hours^{Footnote 40Footnote 53}.

Section V - First aid/medical

Surveillance

Monitor for symptoms. Different laboratory methods are used for definitive diagnosis, with the detection of specific anti-measles IgM antibodies by ELISA and the detection of viral RNA by RT-PCR being the most widespread^{Footnote 4}. The detection of seroconversion or a substantial increase in anti-measles IgG antibody titre in paired acute-phase and convalescent-phase sera is rarely used for diagnosis; however, IgG avidity assays are increasingly used to distinguish between a recent primary contact with measles virus and infection after previous vaccination^{Footnote 4}. Although more time-consuming and less sensitive, isolation of measles virus in cell culture can also be performed, notably using the Vero/hSLAM cell line, a recombinant cell line with a receptor for measles virus^{Footnote 4Footnote 54}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

There are no specific drugs approved for the treatment of measles, and current evidence is considered insufficient to recommend the routine use of antivirals, such as ribavirin, in patients with this disease^{Footnote 4}. Treatment is mainly supportive to manage nutrition, dehydration, and pain^{Footnote 4}. Vitamin A supplementation is recommended for all acute cases^{Footnote 14}. High doses of corticosteroids, or intravenous (IV) immunoglobulin or plasmapheresis, sometimes also combined with antiviral treatment or vitamin A supplementation, may be considered in severe cases, such as acute disseminated encephalomyelitis or measles inclusion body encephalitis^{Footnote 4}. Subacute sclerosing panencephalitis (SSPE) is often treated with isoprinosine with or without ribavirin; alternative treatments include IV immunoglobulin, intrathecal interferon-α, and amantadine^{Footnote 4}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

In Canada, measles vaccine is available as measles-mumps-rubella (MMR) or measles-mumps-rubella-varicella (MMRV) vaccine^{Footnote 27}. Measles-containing vaccine (MCV) is recommended for routine immunization of children and for immunization of children and adolescents who missed measles immunization on the routine schedule, and for susceptible adults born in or after 1970^{Footnote 27}. Adults born before 1970 are presumed to have acquired natural immunity to measles; however, susceptible health care workers, travellers to destinations outside of Canada, and military personnel should receive MMR vaccine, regardless of year of birth^{Footnote 27}. Formulations authorized for use in Canada include M-M-R^®II (live attenuated combined MMR vaccine), PRIORIX^® (live attenuated combined MMR vaccine), PRIORIX-TETRA^® (live attenuated combined MMRV vaccine), and ProQuad^™ (live attenuated combined MMRV vaccine)^{Footnote 27}.

MMR and MMRV vaccines are contraindicated in persons with a history of anaphylaxis after previous administration of the product and in persons with proven immediate or anaphylactic hypersensitivity to any component of the product, with the exception of egg allergy for MMR and MMRV vaccines^{Footnote 27}. Children with a known or suspected family history of congenital or hereditary immunodeficiency that is a contraindication to vaccination with live vaccine should not receive live vaccines unless their immune competence has been established^{Footnote 27}. MMRV vaccine can be contraindicated in persons with impaired immune function, including primary or secondary immunodeficiency disorders^{Footnote 27}. MCVs are contraindicated in individuals with active, untreated tuberculosis (TB) as a precautionary measure^{Footnote 27}. MMR and MMRV vaccines are generally contraindicated in pregnancy because there is a theoretical risk to the fetus^{Footnote 27}.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

Post-exposure prophylaxis with MCV can be administered within 72 hours of exposure in unvaccinated or inadequately vaccinated individuals to prevent disease or reduce severity^{Footnote 14Footnote 27}. Administration of human immunoglobin (Ig) within 6 days of exposure in susceptible individuals for whom MCV is contraindicated may prevent or reduce severity of disease^{Footnote 14Footnote 27}.

MMR and MMRV vaccines and Ig are contraindicated in persons with a history of anaphylaxis after previous administration of the product and in persons with proven immediate or anaphylactic hypersensitivity to any component of the product, with the exception of egg allergy for MMR and MMRV vaccines^{Footnote 27}. Human Ig preparations should not be given to people with known isolated IgA deficiency unless the benefit outweighs the risk, in which case the product should be given with caution and under close observation^{Footnote 27}.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI - Laboratory hazard

Laboratory-acquired infections

One case of a laboratory acquired infection up to 1974^{Footnote 55}.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents.

Sources/specimens

Whole blood, serum, throat and nasopharyngeal secretions, nasal aspirates, bronchial lavage samples, conjunctiva, urine, oral fluid, brain and skin biopsy samples^{Footnote 4Footnote 15}.

Primary hazards

Accidental parenteral inoculation, exposure of mucous membranes to infectious material, and inhalation of airborne or aerosolized infectious material are the primary hazards associated with exposure to measles virus^{Footnote 8Footnote 35Footnote 48}.

Special hazards

None.

Section VII - Exposure controls/personal protection

Risk group classification

Measles virusis a Risk Group 2 Human Pathogen and Risk Group 1 Animal Pathogen.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the CBS to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, PM rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

The airborne transmissibility and low infectious dose of measles virus justify the use of a BSC or other primary containment devices for activities with open vessel; centrifugation to be carried out in sealed safety cups or rotors that are unloaded using a mechanism that prevents their release. Respiratory protection to be considered when BSC or other primary containment devices cannot be used; inward airflow is required for work involving large animals or large scale activities.

Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

Pregnant laboratory employees should take extra precautions due the high transmission potential increasing pregnancy risks.

For diagnostic laboratories handling primary specimens that may contain Measles virus, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII - Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials to be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX - Regulatory and other information

Canadian regulatory information

Controlled activities with measles virus require a Human Pathogens and Toxins licence issued by the Public Health Agency of Canada.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
  • Quarantine Act
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• National Notifiable Disease (human)

Last file update

March, 2024

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright ^© Public Health Agency of Canada, 2024, Canada