Orthopoxvirus Agent Information Sheet

Boston University
Research Occupational Health Program (ROHP)
617-358-7647

Agent

Orthopoxviruses are one of several genuses that cause Poxvirus Diseases.  There are several species of Orthopoxviruses which can infect both animals and humans.  Most notable of these species is the Variola virus which causes smallpox.  After an extensive vaccination campaign, smallpox was declared eradicated in 1980. Other Orthopoxvirus species are Vaccinia virus which has been used to develop the smallpox vaccine, Cowpox and Mpox.

The Vaccinia Virus is the “live virus” used in the prevention of smallpox. It is a “pox”-type virus related to smallpox. When given to humans as a vaccine, it helps the body to develop immunity to smallpox. The smallpox vaccine does not contain the smallpox virus and it cannot cause smallpox. The different strains of vaccinia virus used in research and clinical settings present different levels of risk.

• Non-attenuated vaccinia strains such as Western Reserve, NYCBOH (New York City Board of Health), Copenhagen or Lister, present a greater risk to humans based on an increased ability to replicate in human cells.
• Highly attenuated strains such as MVA (Modified Vaccinia Ankara), NYVAC, ALVAC and TROVAC are unable to replicate or replicate poorly in human cells and do not initiate infection in humans.
• Vaccinia vectors used in clinical trials may be replication competent or may be non-replicating. Vectors may also be attenuated or non-attenuated. There may be some risk of transmission with the use of non-attenuated replication competent vaccinia vectors.

Disease/Infection

According to the BMBL 6th Edition, Vaccinia virus is the leading agent of laboratory-acquired poxvirus infections.

Mpox is similar to smallpox but is rarely fatal.  People with weakened immune system, who are pregnant or breastfeeding and with eczema or children 8 years or younger are at most risk of dying or becoming ill.  Although rarely fatal, this virus can be very painful and can leave scarring.

Cowpox is closely related to variola virus which causes smallpox.  In 1796, Edward Jenner, an English surgeon noticed that milkmaids exposed to cowpox were subsequently immune to smallpox.

Pathogenicity

Laboratory-acquired poxvirus infections of most concern are from the orthopoxviruses that infect humans: variola virus (causes smallpox; human-specific), Mpox virus (causes smallpox-like disease), cowpox virus (causes skin pustule, generalized rash), and vaccinia virus (causes skin pustule, systemic illness). No current variola research is being done in the United States. Laboratory-acquired exposures to orthopoxviruses and subsequent infections have been reported. In the United States, 14 Orthopoxvirus infections were reported during  2004–2014 among personnel working in diagnostic and research facilities (https://www.cdc.gov/poxvirus/occupational-exposures/index.html).

• Special Populations at Risk
  Complications are serious for those with eczema or who are immunocompromised.

Biosafety Information

There are two types (or clades) of Mpox.  Laboratory testing has indicated that the current outbreak is mostly associated with the West African clade II of Mpox virus. The West African clade of the Mpox virus is not subject to select agent regulations (42 CFR § 73). Jun 29, 2022

Risk Group/BSL
BSL2: Vaccinia and Cowpox

BSL3 Virus: Mpox belonging to the Central African clade I is federally regulated as a select agent.

Modes of Transmission

Virus may be transmitted to contacts of individuals who have been vaccinated recently with ACAM2000.

Host Range/Reservoir
Humans

Symptoms
Vaccinia causes a virus disease of skin induced by inoculation – vesicular or pustular lesion, area of induration or erythema surrounding a scab or ulcer at inoculation site. The clinical picture resembles influenza, and 2-4 days after fever subsides, a rash can develop with lesions containing infectious virus. These lesions can occur on the face, extremities, palms and soles, then trunk. Lesions progress through stages as following: macules, papules, vesicles, pustules, then crusted scabs.

• Encephalitis is an inflammation of the brain. Signs and symptoms may include fever, headache, and neurological changes.
• Vaccinia necrosum is a progressive destruction of the skin and tissues at the vaccination site occurs mainly in those who are immunocompromised.
• Eczema Vaccinatum is a severe and destructive infection of the skin affected by eczema or other chronic skin disorders caused by spread of vaccinia virus and occurs in those who have eczema or other chronic skin conditions.
• Generalized Vaccinia – vaccination lesions that develop away from the vaccination site.
• Localized reaction – may occur at the site of exposure as well.
• Headache, fever, fatigue, muscle aches may accompany localized reaction and more severe
• Vaccinia keratitis can also occur; corneal involvement occurs after autoinoculation but is uncommon, with reports of approximately 1.2 cases per 1 million primary vaccinations.

Death is most often the result of postvaccinial encephalitis or progressive vaccinia.

Incubation Period

Vaccinia
Incubation period is 7-19 days; commonly 10-14 days to onset of illness and 2-4 additional days to onset of rash

• Fever followed 2-4 days later with rash on face, extremities, palms and soles, then trunk.
• Cutaneous lesions: macules, papules, vesicles, pustules, scabs.
• Period of communicability: From earliest sign of lesions to disappearance of all scabs.

Mpox
Incubation: 6-13 days (out to 21 days)

• Prodrome of fever, headache, chills, lymphadenopathy (not infectious)
• 1-3 days after onset of fever, a rash develops, typically appearing on the face and then spreads to arms and legs, including palms and soles
• Cutaneous lesions: macules, papules, vesicles, pustules, scabs
• All lesions appear in the same stage
• Illness lasts 2-4 weeks, communicable until last scab falls off with fresh skin intact
• Period of communicability: From earliest sign of lesions to disappearance of all scabs

Cowpox
Incubation: 2-4 days

• Rash on hands, arms and face, papules and vesicles where contact occurred
• Other areas of the body are rarely affected
• Vesicles may be surrounded by erythematous and edematous skin; break easily, bleeding ulcers that dry and are subsequently covered by purple-black eschar.
• Lymphadenopathy of regional lymph nodes may be noted.
• Spontaneously heal after about two months, non-responsive to antibiotics

Viability
Like all enveloped viruses they are susceptible to:

• Disinfectants:  Sodium hypochlorite 1%, phenolic compounds, formaldehyde and paraformaldehyde fixation, formaldehyde fumigation,  B-propiolactone, and lipid solvents
• Physical inactivation:  Heating serum for 1 hour at 60°C; gamma irradiation, autoclaving and incineration

Survival Outside Host

Orthopoxviruses are stable in a wide range of environmental temperatures and humidity.

Vaccinia: Lyophilized vaccinia virus maintains potency for 18 months at 4-6° C, may be stable when dried onto inanimate surfaces

Information for Lab Workers

Laboratory PPE and Engineering Controls

Personal protective equipment includes but is not limited to gowns with tight wrists and ties in back, disposable gloves, combination safety glass and mask or a face shield. Facilities for washing and changing clothing after work should be available.

Laboratory Setting (growing virus cultures or handling experimentally infected animal tissues):

• Strongly recommend vaccination for people directly handling non attenuated specimens
• Use of Biosafety Cabinets should be used for aerosol generating procedures
• Designated biosafety level practices.  Mpox requires BSL-3 protection, consider PAPR

Clinical Setting

• Clinical laboratories can handle potentially infected clinical samples under BSL2 practices
• CDC has updated guidelines for current monkeypox outbreak and now recommending standard, droplet and airborne precautions
• Standard, contact, and droplet infection control PPE, including but is not limited to:
  • gowns with tight wrists and ties in back
  • disposable gloves
  • combination safety glass and mask or a face shield

Containment

Research should be conducted using Biosafety Level 3 with monkeypox, Biosafety Level 2 for vaccinia and cowpox research. Gloves and gowns should be worn when handling infected laboratory animals and when there is the likelihood of direct skin contact with infectious materials. Animal studies may be performed at ABSL-3. BSL-2 practices, containment equipment, and facilities are recommended for activities using clinical materials and diagnostic quantities of infectious cultures.

In Case of Exposure/Disease

• • • For injuries in the lab which are major medical emergencies (heart attacks, seizures, etc…):
    • Medical Campus: call or have a coworker call the Control Center at 617-358-9090.
    • Charles River Campus: call campus security at 617-353-2121.
      You will be referred to or transported to the appropriate health care location by the emergency response team.
    • For lab exposures (needle sticks, bite, cut, scratch, splash, etc…) involving animals or infectious agents, or for unexplained symptoms or illness call the ROHP 24/7 hour number (1-617-358-ROHP (7647); or, 8-ROHP (7647) if calling from an on-campus location) to be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you to the appropriate health care location.
    • Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
    • Provide the wallet-size medical surveillance card to the physician.

Vaccination

Two vaccines ACAM2000 and JYNNEOS are now available and recommended for preexposure prophylaxis for persons at risk for exposures.

The vaccinia vaccination is contraindicated for those individuals with eczema, immunocompromised, pregnant, and cardiac disease. Two vaccines ACAM2000 and JYNNEOS are now available and recommended for preexposure prophylaxis for persons at risk for exposures.

The Advisory Committee on Immunization Practices recommends routine vaccination for laboratory personnel who directly handle cultures or animals contaminated or infected with:

• replication-competent vaccinia virus
• recombinant vaccinia viruses derived from replication-competent vaccinia strains (e.g., inserted foreign gene)
• or other orthopoxviruses that infect humans (e.g., camelpox, cowpox, Mpox virus)

Vaccination is not recommended for workers that only work with replication-deficient poxvirus strains and vectors.

Laboratory personnel working with replication-competent vaccinia viruses and recombinant viruses developed from replication-competent vaccinia viruses (Vaccinia and Cowpox) should be revaccinated at least every 10 years. Those who handle more virulent orthopoxviruses (e.g., Mpox virus) should be revaccinated every two years after the primary series if receiving Jynneos and 3 years if receiving ACAM2000.

Smallpox/Mpox vaccine (JYNNEOS™) can prevent smallpox, Mpox, vaccinia, and other diseases caused by orthopoxviruses. The vaccine is made using live non-replicating vaccinia virus and cannot cause smallpox, Mpox, or any other disease.

JYNNEOS™ is approved by the Food and Drug Administration (FDA) for prevention of smallpox and Mpox disease in adults 18 years or older at high risk for smallpox or Mpox infection.

CDC recommends JYNNEOS™ for certain laboratory workers and emergency response team members who might be exposed to the viruses that cause orthopoxvirus infections.

CDC recommends consideration of the vaccine for people who administer ACAM2000®, another type of smallpox vaccine, or who care for patients infected with orthopoxviruses. The Smallpox (Vaccinia) Vaccine, Live ACAM2000 is contraindicated for those individuals with eczema, who are immunocompromised, are pregnant or have cardiac disease).

JYNNEOS is usually administered as a series of 2 injections, 4 weeks apart. People who have received smallpox vaccine in the past might only need 1 dose.

Mpox researchers are boosted every 2 years.

Vaccinia and Cowpox researchers are boosted every 10 years.

Certain people at increased risk of a condition called myocarditis (swelling of the heart muscle), including adolescent or young adult males, might consider waiting 4 weeks after JYNNEOS™ vaccination before getting an mRNA COVID-19 vaccine.

• Persons who are at continued risk for occupational exposure to orthopoxviruses, and who received an ACAM2000 primary vaccination, should receive a booster dose of JYNNEOS as an alternative to a booster dose of ACAM2000.

Information for First Responders/Medical Personnel

Public Health Issues

Routine vaccination is no longer carried out as smallpox has now been eradicated; only used in armed forces and laboratories. The CDC Smallpox Response Plan is a more detailed public health strategy that would guide the public health response to a smallpox emergency and many of the federal, state, and local public health activities that must be undertaken in a smallpox outbreak.

Diagnosis/Surveillance

Monitor for symptoms; confirmation by identification of skin lesion and history of contact, identification of virus by PCR or serology.

First Aid

If you have been exposed to an Orthopoxvirus in a laboratory accident:

• Irrigate the site of exposure
  • If exposure was by needle stick or other route that breaks the skin, scrub the site with soap and water for 15 minutes and cover with a bandage. While rinsing, apply pressure around the injury to express blood from the site.
  • If exposure was by a splash to the eyes or mucous membranes, remove contacts and irrigate thoroughly with water for 15 minutes at an eyewash station.
• Report the exposure
  • Immediately report the exposure to your laboratory supervisor and Research Occupational Health Program.
• Monitor yourself for signs and symptoms after the exposure
  • Monitor yourself for general signs and symptoms (e.g., fever, lymphadenopathy), and lesions or swelling at the exposure site:
    • For Vaccinia virus, monitor daily for 14 days after exposure
    • For other Orthopoxviruses, monitor daily for 21 days after exposure
• If you develop skin lesions or a fever, immediately consult Research Occupational Health Program
  • Consult ROHP and specify the route and dose of exposure, the poxvirus strain (including the vector construct for recombinant strains), and your smallpox vaccination history.
  • Skin lesions can be infectious. To minimize the risk of transmission to other people, cover the wound with gauze, a semipermeable membrane dressing to absorb exudates, and a layer of clothing (if possible). Change wound dressings frequently to prevent accumulation of exudates and maceration and dispose of in a plastic bag with bleach.

First Aid

Perform one of the following actions:

Post Exposure Prophylaxis

If ACAM2000 and JYNNEOS vaccine is administered within 3-4 days after exposure to vaccinia virus or Mpox, it may prevent disease, or decrease the severity of disease and risk of death.

Treatment

Vaccinia

• Symptomatic care and treatment of secondary bacterial infections
• Vaccinia immune globulin (VIG)

Monkeypox

• Treatment is symptomatic and supportive, including prevention and treatment of secondary bacterial infection
• Vaccinate close contacts within 4 days and up to 14 days after initial contact with a confirmed Mpox case
• Tecovirimat is the preferred agent under compassionate use (CDC) for treatment for Mpox in adults & children
• Cidofovir & Brincidofovir are alternative antivirals
• Vaccinia Immune Globulin (VIG) can be used to control a Mpox outbreak

Cowpox

• Symptomatic care and treatment of secondary bacterial infections

Special Issues

The CDC provides information on a variety of topics relating to variola, Mpox, and vaccinia viruses online at https://www.cdc.gov. For non-emergency information on potential human infections, smallpox vaccination, or treatment options, the CDC Poxvirus Inquiry Line can be contacted at 404-639-4129 or CDC-Info can be reached at 800-232-4636. To obtain smallpox vaccine, CDC Drug Services can be reached by phone at 404-639-3670 or by email at drugservice@cdc.gov. Clinicians or health departments may contact the CDC Emergency Operations Center in critical circumstances.

• CDC’s Emergency Operations Center: (770) 488-7100
• poxvirus@cdc.gov

References

Biosafety in Microbiological and Biomedical Laboratories; Deborah E. Wilson, DrPH, CBSP Director Division of Occupational Health and Safety National Institutes of Health Bethesda, Maryland L. Casey Chosewood, M.D. Director Office of Health and Safety Centers for Disease Control and Prevention Atlanta, Georgia; US Government Printing Office, Washington DC. 5th Edition; 2007

Control of Communicable Diseases Manual. David L. Heymann. Washington DC, USA: American Public Health Association Press, 19th edition, 2008

https://www.cdc.gov/vaccinesafety/vaccines/Smallpox-Vaccine.html

https://www.cdc.gov/poxvirus/occupational-exposures/accidental-exposure.html

Petersen BW, Harms TJ, Reynolds MG, Harrison LH. Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses — Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015. MMWR Morb Mortal Wkly Rep 2016;65:257–262. DOI: http://dx.doi.org/10.15585/mmwr.mm6510a2

Rao AK, Petersen BW, Whitehill F, et al. Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022. MMWR Morb Mortal Wkly Rep 2022;71:734–742. DOI: http://dx.doi.org/10.15585/mmwr.mm7122e1external icon

MMWR, June 3, 2022, / Vol 71 #22
Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022

Rev. 12/6/23