Rubella virus : Infectious substances pathogen safety data sheet

For more information on Rubella virus, see the following:

• Diseases and conditions: Rubella

Section I – Infectious agent

Name

Rubella virus

Agent type

Virus

Taxonomy

Family

Matonaviridae

Genus

Rubivirus

Species

rubellae

Synonym or cross-reference

Rubella virus (RuV) causes rubella, which has also been referred to as German measles^{Footnote 1Footnote 2}.

Characteristics

Brief description

RuV is a pleomorphic enveloped virus ranging from 50 to 90 nm in length and width, with an average diameter of 70 nm^{Footnote 3Footnote 4}.The shape ranges from spherical to elongated tube-like structures that can measure up to 150 nm long^{Footnote 3}. It has a positive-sense, single-stranded RNA genome that measures around 9.6-10 kb. The GC content of the genome is around 70% and it contains two open reading frames (ORFs). The 5’ ORF measures around 6.3 kb and encodes the non-structural proteins, while the 3’ ORF measures around 3.2 kb and encodes the structural proteins. The three structural proteins include the capsid, and two envelope glycoproteins, E1 and E2. The non-structural proteins include p150 and p90, and are responsible for transcription and replication.

Properties

The virus life cycle begins with RuV attaching to susceptible host cells and entering via clathrin-mediated endocytosis^{Footnote 3}. The viral genome escapes the endosome in a pH and calcium-dependent manner where the fusion of membranes is facilitated by the E1 membrane fusion protein. Replication of the genome takes place in the cytoplasm, and the newly transcribed nucleocapsid core, E1, and E2 proteins assemble and bud into the Golgi complex to form viral particles. These will traffic through the secretory pathway to be released at the plasma membrane.

Section II – Hazard identification

Pathogenicity and toxicity

Rubella: Disease is often subclinical, but it can also be associated with mild illness, with symptoms including low grade fever, a generalized maculopapular rash, and lymphadenopathy^{Footnote 1Footnote 2}. Headache, malaise, mild conjunctivitis (particularly in adults), sore throat, cough, and rhinorrhea may also be present. These signs and symptoms may appear up to 5 days before the rash. The rash persists for 1-5 days and will first develop on the face and neck before progressing down the rest of the body^{Footnote 1Footnote5}. Joint symptoms like arthritis or arthralgia involve the fingers, wrists, and knees and take around 1 month to resolve^{Footnote 1}. These symptoms are more common in women than in children and men, occurring in up to 70% of cases^{Footnote 1Footnote5}. Hemorrhagic complications occur in 1 of every 3000 cases of rubella and are more common in children than in adults^{Footnote 1}. Post-infectious encephalitis occurs in approximately 1/6000 rubella cases, but incidences of 1/500 have also been reported^Footnote5. The mortality rate for cases of encephalitis ranges from 20% to 50% and occurs more frequently in adults than children^{Footnote 1}. Otherwise, mortality generally does not occur in cases of postnatal rubella.

Congenital rubella syndrome (CRS): RuV infection during early pregnancy can result in miscarriage, fetal death, or congenital defects, such as hearing loss, cataracts, and heart defects^{Footnote 5}. During the first 2 months of gestation, there is a 65% to 85% likelihood of the fetus being affected, with an outcome of congenital defects or spontaneous abortion^{Footnote 1}. The likelihood of developing a single defect drops to 30% to 35% during the third month of fetal life. Infection during the fourth month is associated with a 10% risk of developing a single congenital defect. Signs and symptoms of congenital rubella may be termed temporary (e.g., low birth weight), permanent (e.g., deafness), or developmental (e.g., myopia). Common manifestations include deafness, cataract or glaucoma, congenital heart disease, and mental retardation. Case fatality rates have been reported following various outbreaks: 34% in Vietnam from 2011-2012, 28% in Greece in 1993, and 26% in Panama in 1986^{Footnote 6Footnote 7Footnote 8}.

Epidemiology

RuV is maintained in human populations and distributed globally, but is much less prevalent in countries with vaccination programs^{Footnote 4}. Prior to the development of rubella-containing vaccines (RCVs), outbreaks would occur every 3-8 years^{Footnote 2}. From 1964 to 1965, an outbreak occurred in the United States, resulting in 12.5 million cases of rubella, 10,000 fetal deaths or therapeutic abortions, and 20,000 cases of CRS^{Footnote 1Footnote 2}. The first rubella vaccine was subsequently developed between 1965 and 1967 and became licensed for use in the United States by 1969. Outbreaks occur in populations without sufficient levels of immunity^{Footnote 9}. In 2013, 11,000 cases of rubella and 13 cases of CRS were reported in Japan, and Poland and Romania also experienced outbreaks in 2012. Cases occurred predominantly in males due to vaccine efforts primarily targeting females. Following RuV infection, most individuals develop lifelong protection^{Footnote 1}. In 2023, the global annual rubella burden was estimated to be 35,714 cases^{Footnote 10}. The global burden of CRS in 2010 was around 105,000 cases, but more recent estimates suggest a decline in incidence with 32,000 cases of CRS globally in 2019^{Footnote 11Footnote 12}. Between 2020-2023, there have been 3 cases of rubella or CRS reported in Canada^{Footnote 13}. Generally, children have a milder course of disease compared to adults, and fetuses infected transplacentally in early pregnancy have a high risk of developing severe defects or dying^{Footnote 1}.

Host range

Natural host(s)

Humans are the only natural host of RuV^{Footnote 2Footnote 9}.

Other host(s)

Congenital RuV infection has been established using experimentally infected ferrets, non-human primates, rats, and rabbits^{Footnote 14}.

Infectious dose

The minimum infectious dose of RuV is estimated to be less than 10 infectious viral units when administered by nasopharyngeal spray^{Footnote 15}.

Incubation period

The incubation period ranges from 12 to 23 days, averaging around 18 days^{Footnote 1}.

Communicability

The preferred mode of transmission of RuV is through inhalation of airborne droplets and its reproductive number (Ro) is 7^{Footnote 1Footnote 16}. Transmission through direct contact with nasopharyngeal secretions from infected individuals is also possible as well as through fomites^{Footnote 1Footnote 17}. RuV is also transmitted transplacentally from infected mother to fetus^{Footnote 1}. The virus is most contagious while the rash is erupting, but it may be shed from the throat from 10 days before to 15 days after the onset of rash. Infants with congenital rubella shed large quantities of virus from body secretions for many months and therefore may transmit the infection to individuals who care for them. Patients with subclinical cases of illness may also transmit the infection to others. Individuals vaccinated against rubella do not transmit the virus.

Section III – Dissemination

Reservoir

None.

Zoonosis

None.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

There are no approved antivirals against RuV; however, the nucleoside analogs, NM107 and AT-527, demonstrated some activity against the rubella virus vaccine strain in vitro^Footnote18.

Susceptibility to disinfectants

Rubella virus is inactivated by 1% sodium hypochlorite, 70% ethanol, chlorine, deoxycholate, β-propiolactone, ethylene glycol, formaldehyde, trypsin, formalin, ether, chloroform, and acetone^{Footnote 1Footnote19Footnote20}.

Physical inactivation

RuV is inactivated following exposure to temperatures of 56°C for 30 minutes, 70°C for 4 minutes, or 100°C for 2 minutes and also becomes rapidly degraded when frozen at −20°C ^{Footnote19Footnote20}. The virus may also be inactivated by ultraviolet light and a pH of less than 6.8 or greater than 8.1.

Survival outside host

Rubella virus has a half life of 1 hour at 57ºC outside of the host^{Footnote 21}.

Section V – First aid/medical

Surveillance

RuV can be detected in throat swabs, oral fluids, nasopharyngeal secretions, urine, and cataract tissue using reverse transcription polymerase chain reaction (RT-PCR)^{Footnote 9}. IgM antibodies are detectable at five days after rash in sera or oral fluids and can be detected using IgM capture enzyme linked immunosorbent assay (ELISA) or indirect IgM ELISA. A plaque reduction neutralization test (PRNT) may also be used if the neutralizing capacity of antiserum needs to be quantified. Congenital rubella may be diagnosed through the detection of virus by RT-PCR in amniotic fluid^{Footnote 1}.

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.

First aid/treatment

There is no specific treatment for rubella^{Footnote 1}. The treatment of symptoms is indicated for patients with fever and arthritis or arthralgia.

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 Canadian Biosafety Handbook.

Immunization

The measles-mumps-rubella (MMR) and measles-mumps-rubella-varicella (MMRV) vaccines have been developed and various formulations are available for use in Canada^{Footnote 22}. The vaccine is recommended for routine immunization of children and susceptible adolescents and adults. Susceptible women of reproductive age who are not yet pregnant should be vaccinated and should delay pregnancy by at least 4 weeks following immunization. MMR and MMRV vaccines are contraindicated in pregnancy due to possible risk of disease transmission to the fetus, but there is no evidence suggesting a teratogenic risk from the vaccine. Susceptible pregnant women should become vaccinated post-partum, including those who are breastfeeding.

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

Prophylaxis

The MMR and MMRV vaccines are effective pre-exposure prophylaxis measures with 95% or more vaccine recipients aged 12 months or older demonstrating serologic evidence of immunity following one dose of a rubella-containing vaccine^{Footnote 1}. Post-exposure vaccination with MMR vaccine or human immunoglobulin (Ig) does not prevent or change the severity of rubella after exposure^{Footnote 22}.

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

Section VI – Laboratory hazard

Laboratory-acquired infections

A survey of personnel working for various private companies and public institutions involved in diagnostics and research and development were surveyed to capture the incidence of LAIs in Belgium from 2007 to 2012^{Footnote 23Footnote 24}. One case of rubella was reported; however, no additional details on the patient, mode of transmission, or severity of disease were provided. In Japan between 1979 and 1988, 306 hospitals employing 698 doctors and 8654 technicians, were surveyed for laboratory-acquired infections^{Footnote 24}. There was a total of 177 probable infections, which included 6 cases of rubella, but no additional details are available.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

Oral fluids, nasopharyngeal secretions, cataract tissue, urine, synovial fluid, and amniotic fluid may contain the virus^{Footnote 1Footnote 9}.

Primary hazards

Inhalation of airborne or aerosolized infectious material is the primary hazard associated with exposure to RuV^{Footnote 1}.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

Rubivirus rubellae is a Risk Group 2 Human Pathogen and Risk Group 1 Animal Pathogen^{Footnote 25}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures are required.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are 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, post mortem 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 primary hazard, inhalation of aerosols, of Rubivirus rubellae justifies the use of a BSC or other primary containment devices for activities with open vessels; 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 device 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 are 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.

For diagnostic laboratories handling primary specimens that may contain Rubivirus rubellae, 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 between the surface and the disinfectant before clean up (Canadian Biosafety Handbook).

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 (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard 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 context

Controlled activities with Rubivirus rubellae require a Pathogen and Toxin 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
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations
• National notifiable disease (human)
• Provincial notifiable disease (Rubella, congenital rubella infection, and congenital rubella syndrome). All provinces and Territories.                                     

Last file update

January, 2025

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, directives and standards applicable to the import, transport, and use of pathogens and toxins 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.

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