All you need to know about Smallpox and Monkeypox



Smallpox is a highly transmissible disease which was one of the most severe infectious diseases affecting humans. Smallpox (variola) virus is a DNA virus, and a member of the genus orthopoxvirus of the Poxviridae family, which also includes vaccinia and monkeypox. In December 1979, the Global Commission for the Certification of Smallpox Eradication declared the world free of smallpox and this declaration was ratified by the World Health Assembly in May 1980.


Monkeypox is a rare disease that is caused by infection with the monkeypox virus. Monkeypox virus is related to but distinct from the viruses that cause smallpox (variola virus) and cowpox. The name monkeypox originates from the initial discovery of the virus in monkeys in a Danish laboratory in 1958.

Human monkeypox was first described in 1970 when regional elimination of smallpox revealed sporadic cases of a disease with similar presentation in rural areas of Democratic Republic of Congo. Outbreaks have since occurred in Nigeria, Republic of Congo, Sierra Leone, Liberia, Cameroon and the Central African Republic. Monkeypox is a zoonosis – an organism transmitted to humans from animals. The animal host is most likely a rodent, although the definitive reservoir has not been identified. Following the global eradication of smallpox in 1977, monkeypox has become the dominant cause of orthopox outbreaks in humans, possibly associated with waning orthopox immunity following cessation of smallpox vaccination (Rimoin et al. 2010).

Spread of monkey pox may occur when a person comes into close contact with lesions, body fluids, respiratory droplets from an infected animal or an infected human; or contact with material contaminated with the virus e.g. bedding. The virus enters the body through broken skin, the respiratory tract or the mucous membranes.

The incubation period is 5 to 21 days, but typically 6 to 16 days following exposure. Most patients experience a mild, self-limiting illness, with spontaneous and complete recovery seen within 3 weeks of onset. However, severe illness can occur and sometimes results in death. The risk of severe disease is higher in children, pregnant women and immunosuppressed individuals.

There are two genetic clades of monkeypox virus: Central African and West African. The Central African clade is associated with more severe disease in humans and a reported case fatality rate of up to 10%. By contrast, the West African clade is associated with milder disease, with a case fatality rate of 3-4%. Monkeypox is included in the national list of High Consequence Infectious Diseases (HCID) in England.

Clinical features

The incubation period is 5 to 21 days, but typically 6 to 16 days following exposure. The initial phase of typical clinical illness usually lasts 1 to 5 days; patients may experience a combination of fever and/or chills, lymphadenopathy, headache, myalgia, backache and exhaustion. Fever is present in most, but not all patients.

This is followed by a second phase where a rash appears, during which time some existing signs and symptoms, including fever, may diminish or disappear. The distribution of the rash and the appearance of individual skin eruptions typically change over time.

The rash may be maculopapular initially, typically starting on the face before spreading peripherally, particularly to the palms of the hands and the soles of the feet. The initial rash classically evolves into vesicles and then pustules, often with umbilication, which eventually crust and then desquamate during the next 2 to 3 weeks. These characteristic pox lesions are typically 0.5 to 1cm diameter and may number from a few to several thousand. Involvement of the oral mucous membranes occurs in many cases; lesions may also occur on the genitals, conjunctivae and cornea in some patients.

Localised rashes are seen occasionally, relating to the site of the initial exposure.

Most patients experience a mild, self-limiting illness, with spontaneous and complete recovery seen within 3 weeks of onset. However, severe illness can occur and sometimes results in death.

History and epidemiology of the disease


Compulsory childhood smallpox vaccination of the UK population commenced in 1853. Smallpox ceased to be endemic in the UK by the 1930s, although importations continued to occur, with outbreaks in England in 1949 and Scotland in 1950. Smallpox vaccination remained routine in infants until 1962, although coverage of vaccination had declined to low levels in many areas. Vaccination as part of outbreak control was better accepted and vaccination of older schoolchildren and adults remained until 1971, when it was replaced with a selective risk group policy (Milward G, 2019).

In response to the threat of a bioterrorist release of smallpox, in 2003 the Department of Health published Guidelines for smallpox response and management in the post- eradication era (smallpox plan).1 This outlined the role of vaccination of response teams who would safely manage and diagnose suspected cases of smallpox. In 2003–04 more than 300 healthcare and ambulance workers were vaccinated, along with a small number of staff in laboratories designated to receive specimens from suspected cases.


Between 2018 and 2022 the UK experienced a small number of imported cases, all from west Africa and with the west African clade. Spread was limited by rapid diagnosis, isolation and care of the cases in HCID centres and the quarantine and surveillance of close contacts. Post exposure vaccination was also advised, and no serious consequences of disease occurred.

In April/May 2022, three separate incidents of monkeypox were recognized. The first was a recognized importation from Nigeria with no secondary spread. The second incident appeared to arise from indigenous transmission. One index case with no travel history infected two other members of the household.

The third incident is still under investigation but appears to indicate transmission largely in gay, bisexual and other men who have sex with men (GBMSM). At the time of writing more than 700 cases have been confirmed, mainly in London, and the vast majority in males. The outbreak appears to be associated with cases in similar populations worldwide including Canada, Portugal, Belgium and Germany.


Monkeypox does not spread easily between people.

Spread of monkeypox may occur when a person comes into close contact with an infected animal (rodents are believed to be the primary animal reservoir for transmission to humans), human, or materials contaminated with the virus. Monkeypox has not been detected in animals in the UK.

The virus enters the body through broken skin (even if not visible), the respiratory tract, or the mucous membranes (eyes, nose, or mouth).

Person-to-person spread is uncommon, but may occur through:

  • contact with clothing or linens (such as bedding or towels) used by an infected person
  • direct contact with monkeypox skin lesions or scabs
  • coughing or sneezing of an individual with a monkeypox rash

Clinical features

The incubation period is the duration/time between contact with the infected person and the time that the first symptoms appear. The incubation period for monkeypox is between 5 and 21 days.

Monkeypox infection is usually a self-limiting illness and most people recover within several weeks. However, severe illness can occur in some individuals.

The illness begins with:

  • fever
  • headache
  • muscle aches
  • backache
  • swollen lymph nodes
  • chills
  • exhaustion

Within 1 to 5 days after the appearance of fever, a rash develops, often beginning on the face then spreading to other parts of the body. The rash changes and goes through different stages before finally forming a scab which later falls off.

An individual is contagious until all the scabs have fallen off and there is intact skin underneath. The scabs may also contain infectious virus material.

Images of individual monkeypox lesions


Areas of erythema and/or skin hyperpigmentation are often seen around discrete lesions.

Lesions can vary in size and may be larger than those shown.

Lesions of different appearances and stages may be seen at the same point in time.

Detached scabs may be considerably smaller than the original lesion.


Clinical diagnosis of monkeypox can be difficult, and it is often confused with other infections such as chickenpox. A definite diagnosis of monkeypox requires assessment by a health professional and specific testing in a specialist laboratory.

Infection prevention and control

Prevention of transmission of infection by respiratory and contact routes is required. Appropriate respiratory isolation is essential for suspected and confirmed cases. Scabs are also infectious and care must be taken to avoid infection through handling bedding, clothing, and so on.

Monkeypox virus is classified as an ACDP Hazard Group 3 pathogen and all laboratory work with live virus must be conducted at full Containment level 3 (CL3), in accordance with the Control of Substances Hazardous to Health Regulations 2002 (as amended).

Clinical laboratories should be informed in advance of samples submitted from suspected or confirmed diagnosis of monkeypox. Laboratories must ensure that appropriate controls commensurate to CL3 are in place to minimise risk to laboratory workers so that they can safely perform laboratory tests that are essential to clinical care.

Possible case

A person with a febrile prodrome compatible with monkeypox infection where there is known prior contact with a confirmed case in the 21 days before symptom onset.

Or, a person with an illness where the clinician has a high suspicion of monkeypox (for example, this may include prodrome or atypical presentations with exposure histories deemed high risk by the clinician, or classical rash without risk factors).

Febrile prodrome consists of fever ≥ 38°C, chills, headache, exhaustion, muscle aches (myalgia), joint pain (arthralgia), backache, and swollen lymph nodes (lymphadenopathy).

Probable case

A person with an unexplained rash on any part of their body plus one or more classical symptom or symptoms of monkeypox infection¥ since 15 March 2022 and either:

  • has an epidemiological link to a confirmed or probable case of monkeypox in the 21 days before symptom onset


  • reported a travel history to West or Central Africa in the 21 days before symptom onset


  • is a gay, bisexual or other man who has sex with men (GBMSM)

Acute illness with fever (>38.5°C), intense headaches, myalgia, arthralgia, back pain, lymphadenopathy.

Actions on a possible or probable case

Test for monkeypox (using designated testing pathway).

Undertake additional contemporaneous tests to rule out alternative diagnoses if clinically appropriate and if not done already.

If admission of patient required for clinical reasons, admit to single room isolation at negative or neutral pressure at local hospital site with RPE PPE (with appropriate IPC arrangements).

Or, if patient not requiring admission for clinical reasons: self-isolation at home (based on assessment by the clinician and following UKHSA guidance).

Or, if patient not requiring admission for clinical reasons but self-isolation at home is not possible for social or medical reasons following clinician assessment: isolation in single room at negative or neutral pressure at local hospital site with RPE PPE pending test result (prioritise probable cases).

Confirmed case

A person with a laboratory confirmed monkeypox infection (monkeypox PCR positive).

Action on a confirmed case

All confirmed cases should be assessed for the need for admission based on either clinical or self-isolation requirements. All cases should be discussed with the high consequence infectious diseases network.

All confirmed cases should be notified to the local health protection team by the clinician.

How to isolate safely at home if you have monkeypox infection

Isolate at home

If you have been diagnosed with monkeypox and you have been advised to self-isolate at home by your doctor, you should not go to work, school or public areas.

If you have a garden, it is fine to use it. As monkeypox spreads via close contact, to protect other members of your household you should keep at least 3 steps (1 metre) away from them even while you are in the garden.

You should only leave your home for essential purposes such as emergencies, urgent medical appointments, or for urgent health and wellbeing issues.

If you need to leave your home, make sure the rash on your body is completely covered for example by wearing long-sleeved top and full-length trousers. Wear a well-fitting surgical face mask or a double-layered face covering while you are outside your home.

Keep the time spent outside your home as short as possible and avoid all contact with objects such as furniture in public spaces. If you need to attend hospital you should walk, cycle or drive yourself there. If you do not have your own vehicle, public transport can be used but you should avoid busy periods, cover any lesions with cloth (for example using scarfs or bandages) and wear a face covering.

Ask friends or relatives to help with buying groceries, other essentials or collecting medication, or order them online. Friends, relatives and delivery drivers should leave items outside your home and should not come inside. They should not touch anything that you have touched.

Do not invite or allow social visitors, such as friends and family, to visit you at home.

Avoid close contact with people you live with

People who live in the same household as someone with monkeypox are at the highest risk of becoming infected themselves because they are most likely to have prolonged close contact. If you live with other people, they will have been advised to isolate at home and provided with public health advice.

You should limit close contact with others in your household and take the following steps to reduce the chance of passing your infection on to the people you live with:

  • sleep in a separate room, if available, and do not share bedding. You may need to change your sleeping arrangements to accommodate this
  • use a separate bathroom from the rest of your household, if available. If you do not have a separate bathroom, follow the cleaning instructions below
  • make sure you use separate towels from other people in your home
  • eat in a separate room. Ask the people you live with to bring your meals to you
  • cover your mouth and nose with disposable tissues when you cough or sneeze and dispose of them in a bag. Place this bag in another bag and follow the instructions for disposing waste. Wash your hands thoroughly with soap and water for 20 seconds
  • clean your hands frequently throughout the day by washing with soap and water for 20 seconds. Care should be taken if there are extensive or ulcerated hand lesions

If you need to spend time in the same room as someone in your household you should avoid physical contact and aim to keep at least 3 steps (1 metre) away from the other person. In addition wearing a well-fitting surgical face mask or double-layered face covering may provide some additional protection.

It is particularly important to avoid close contact with young children, pregnant women and immunosuppressed people as they may be at higher risk of serious illness. Use your own toothbrush, eating and drinking utensils, dishes, towels, washcloths and bed linen. Do not share food and drinks.

If you are no longer able to follow the advice in this section at any time during your self-isolation period you should speak to your doctor as it may be necessary for you to self-isolate in another location.

Cleaning, disinfection and waste disposal

You should handle your own used crockery and cutlery, and if you have one, use a dishwasher to clean and dry these items. If this is not possible, wash your own crockery and cutlery using your usual washing up liquid and warm water and leave them to air dry.

If you have lesions on your hands and you have no access to a dishwasher, wear single use disposable gloves or reusable washing up gloves while washing up. Any reusable gloves should not be shared and should be discarded at the end of your isolation period.

You should regularly clean surfaces that you touch frequently, such as door handles and light switches and use a damp cloth to prevent dust from accumulating on surfaces, especially in your bedroom. You can use your usual household cleaning products for this, such as detergents and bleach.

Personal waste (such as used tissues) and disposable cleaning cloths can be stored securely within disposable rubbish bags.

Vacuum cleaner waste, including disposable filters if your vacuum cleaner has one, should be carefully emptied into a disposable rubbish bag.

As an additional precaution, all disposable rubbish bags should be placed into a second disposable bag, tied securely, before being disposed of as usual with your domestic waste. You should not put any waste into recycling bins until you have ended your self-isolation.

You should do your own laundry. Keep your laundry items separate from the rest of the household’s laundry and wash them using your normal detergent, following manufacturer’s instructions. If possible use the highest temperature which the items can withstand, do not overload the washing machine (aim for half or two-thirds full) and avoid shorter ‘economy cycles’ (those which reduce water and save energy) until you have fully recovered.

When you are taking laundry to the washing machine it is important to avoid shaking the laundry, as this could spread virus particles into the air and onto surfaces in your home. If you are carrying laundry from one room to another you should consider placing dirty laundry in a large plastic bag (such as bin liner) or a container then taking it straight to the washing machine.

If you do not have a washing machine, you can handwash your laundry using warm water and your normal detergent. This might be more effective in a large sink or bathtub. It is important to clean all surfaces when you have finished. Take extra care if using bleach to clean these surfaces: always follow the manufacturer’s instruction for diluting disinfectants, protect your eyes, and thoroughly rinse the disinfectant off every surface, to prevent accidental contact with skin or eyes, once you have finished.

If you have had to travel in a car with a friend or relative, you should wear a well-fitting surgical face mask or double-layered face covering while in the car. Your friend or relative should wipe down all hard surfaces after the journey using a standard detergent or detergent wipes while wearing gloves and surgical face mask or face covering.

Waste should all be double bagged and disposed of as described above.


No cases of monkeypox have been reported in wild animals or pets in the UK but it is possible that pets could become infected or contaminated with the virus through close contact with an infected person and spread the virus to others.

If you have pets you should avoid close contact with them as much as you can and practice good hygiene:

Do not let pets sleep in the bed with you.

Wash your hands before and after handling pets or materials they have had contact with (such as collars, leads, feed and feeding bowls, litter trays, bedding and toys).

You will be contacted by Animal and Plant Health Agency (APHA) who will provide you with advice on how to manage your pets while you are isolating.

Until you hear from APHA, your pets should remain in the house with you but you may let them out for toileting purposes on a lead and maintaining 1 metre distance from other people and animals. Outside visits should be kept to an absolute minimum while you are isolating.

If your pet needs veterinary care while you are isolating at home, do not take your pet to your usual veterinary practice, but call them in advance to ask their advice. You may have to ask someone else to take your pet to the surgery for you.

If you need medical advice

You will have been provided with contact details of the medical team providing your care and they will be in contact with you regularly. You should call this team if you have any concerns. Seek prompt medical attention if your illness is worsening. In an emergency, dial 999 and inform the call handler or operator that you have monkeypox infection.

All non-urgent medical and dental appointments should be cancelled while you are isolating at home. If you are concerned or have been asked to attend in person within the period you are home isolating, discuss this with your medical contact first.

Ending self-isolation

You should self-isolate at home until:

  • you have not had a high temperature for at least 72 hours
  • you have had no new lesions in the previous 48 hours
  • all your lesions have scabbed over
  • you have no lesions in your mouth
  • any lesions on your face, arms and hands have scabbed over, all the scabs have fallen off and a fresh layer of skin has formed underneath

If you meet all of the points above, you may be able to stop self-isolating and you should contact the medical team for further advice.

You should continue to avoid close contact with young children, pregnant women and immunosuppressed people until the scabs on all your lesions have fallen off and a fresh layer of skin has formed underneath. This is because you may still be infectious until the scabs have fallen off.

After your self-isolation has ended you should cover any remaining lesions when leaving the house or having close contact with people in your household until all the scabs have fallen off and a fresh layer of skin has formed underneath.

Resuming sexual activity

Whilst you are self-isolating, you are advised to refrain from sexual activity to reduce the risk of you passing the infection on to your partner.

It is not known how long monkeypox virus remains present in semen and other genital excretions. If you wish to resume sexual activity after your self-isolation has ended, you should use a condom for 8 weeks after your rash has scabbed over and scabs have fallen off. This is a precaution to reduce the risk of spreading infection to your partner.

This guidance will be updated as further information is available.

Look after your wellbeing

Staying at home for a prolonged period can be difficult, frustrating and lonely for some people and you or other household members may feel low. It can be particularly challenging if you don’t have much space or access to a garden.

It is important to remember to take care of your mind as well as your body and to get support if you need it. Stay in touch with family and friends over the phone or on social media. There are also sources of support and information that can help.

The Every Mind Matters website has provides a lot of useful information.

You may be eligible for financial support if you are unable to work

Many people find it helpful to remind themselves why what they are doing is so important. By staying home, you are protecting others and preventing the spread of infection.

The smallpox vaccination

First and second generation smallpox vaccines

Historically, first and second-generation smallpox vaccines were used for population-level and targeted occupational health-related immunisation programmes in the UK. These vaccines are no longer available in the UK.

First generation smallpox vaccines used during eradication were propagated in calf skin and purified from calf lymph. A successful vaccination produced a lesion at the site of administration. Second generation vaccines were propagated in tissue cell culture and produced using modern good manufacturing practices, thus having a lower risk of contamination with adventitious agents (Petersen et al. 2019).

First and second generation vaccines contain a live (replicating) vaccinia virus, mostly based on either the Lister or the New York City Board of Health (e.g. ACAM2000) strains.

  1. assetRoot/04/07/08/32/04070832.pdf

Although these live vaccines were highly effective, they were also associated with risks of other serious adverse events (Auckland C et al, 2005, Gallagher and Lipsitch 2019, Lane et al, 1968, Mora et al, 2009, Morgan et al, 2008). Previous data from Africa suggests that the live vaccines against smallpox may also be up to 85% effective in preventing monkeypox infection.

Third generation smallpox vaccines

Newer third generation smallpox vaccines are now available which have a much-improved side effect profile compared with first and second generation smallpox vaccines. The modified vaccinia Ankara (MVA-BN) (Imvanex®) vaccine, a third generation smallpox vaccine contains a replication defective virus. The virus used in the vaccine is attenuated through multiple passages in chicken embryo fibroblast cells, leading to a substantial loss of its genome including immune evasion and virulence factors. It demonstrates very limited replication capability and low neuropathogenicity in human and animal studies, while retaining immunogenic properties, including demonstrable protective immune responses against a variety of orthopoxviruses (Verheust C et al, 2002). As MVA-BN cannot replicate in mammalian cells it does not produce a lesion at the site of vaccination.

MVA-BN (Imvanex®) was licensed by European Medicines Agency in 2013 for the prevention of smallpox. Data used for licensing was limited due to the eradication of smallpox in 1979 followed by the requirement for containment of the virus. Preclinical studies of MVA-BN have suggested that 2 doses of vaccine are immunogenic, generating antibody levels considered protective against smallpox, and by extrapolation, against monkeypox. In addition, studies have shown that MVA-BN prevented lethal monkeypox in primate challenge models with protection occurring 6 or more days after a single vaccination (Earl et al, (2008). Although the vaccine contains a live virus, this virus has been modified so that it does not replicate in humans, and can only replicate in certain cell lines used for manufacture. Therefore, like vaccines that contain non-replicating vectors (such as the AstraZeneca COVID-19 vaccine), it should be considered as an inactivated vaccine (see chapter 1).

Smallpox MVA-BN vaccine has been recommended by UKHSA for off-license pre-exposure vaccination of a small number of laboratory staff and hospital health care workers at high risk for post exposure vaccination against monkeypox.

There is currently no vaccine licensed in the UK or Europe for immunisation against monkeypox. In September 2019, the Food and Drug Administration (FDA) in the US approved MVA-BN (Jynneos®) (the US labelled equivalent of Imvanex®) for the prevention of monkeypox as well as smallpox (FDA, 2019). Although not specifically licensed for the prevention of monkeypox in Europe, MVA-BN vaccine has been used in the UK in response to the current and previous incidents.

Unlike the live smallpox vaccine, there is very limited evidence on whether MVA-BN can prevent or modify disease when given post-exposure. At day 14, the GMTs induced by a single MVA vaccination was equal to that induced by a live smallpox vaccine (ACAM2000), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively) (Pittman et al, 2019). Based on this immunological response, rapid vaccination is offered because of the potential to prevent infection and/or to modify disease severity for cases with longer incubation periods.


The vaccine comes in packs of 20 single dose vials. The vaccine’s normal appearance is a light yellow to pale white milky suspension.


MVA-BN is supplied frozen in packs of 20 vials. The remaining shelf life at clinic level will depend on previous storage temperature, please refer to documentation on the product.

Frozen vials should be transferred to 2°C to 8°C to thaw or may be thawed for 15 minutes at room temperatures for immediate use. After thawing, vaccine can be stored for up to 8 weeks at 2°C to 8°C. Store in the original package in order to protect from light.


The vaccine should be allowed to reach room temperature before use. Swirl the vial gently before use for at least 30 seconds. The vaccine should be visually inspected for particulate matter and discoloration prior to administration. In the event of any foreign particulate matter and/or variation of physical aspect being observed, do not administer the vaccine.

A dose of 0.5 ml is withdrawn into a syringe for injection and administered by the deep sub-cutaneous route (see chapter 4). The preferred site in adults is the deltoid region of the upper arm.

Dosage and schedule

Pre-exposure vaccination of individuals previously not vaccinated against smallpox

Administer a course of two doses with at least a 28-day interval between doses, for instance:

  • first dose of MVA-BN 0.5ml, then
  • second dose of MVA-BN 0.5ml at least 28 days after the first dose

Individuals who have previously been vaccinated against smallpox with a live smallpox vaccination should receive a single dose of 0.5 ml. Live vaccine was only used up to the 1970s, so apart from the healthcare workers vaccinated in 2003/4, vaccinated individuals will be older, and should have a distinctive scar (which normally looks like a circular 5p size dent in the left upper arm).

In the event of an incident, it is highly unlikely that there will be sufficient time to offer pre-exposure vaccination with two doses for those at risk of occupational exposure. In this scenario, a single dose of vaccine should be offered immediately. Completion of the primary course with a second dose at least 28 days later should be considered on assessment of ongoing risk of exposure. Where the second dose of MVA-BN is given after 28 days, the first dose should not be repeated.

Post-exposure of individuals of any age

Administer a single 0.5ml dose of MVA-BN.

To maximise the chance of preventing infection, MVA-BN should preferably be administered within 4 days from the date of exposure to monkeypox.

Vaccination may still be offered up to 14 days after exposure, with the aim of reducing the symptoms of disease, for those who are not already displaying symptoms. This may be considered

in those at higher risk of serious monkeypox infection (children up to primary school age, the immunosuppressed and pregnant women). Vaccination up to 14 days after exposure may also be offered to those at on-going risk to commence a pre-exposure course.

Individuals who have previously received a two dose course of MVA-BN, with the second dose given in the past two years, do not need a further dose of vaccine after exposure. The exception is those who are immunosuppressed, who may have made a lower or less durable immune response, when an additional dose can be considered.

Booster vaccination

Immunocompetent individuals who have previously been vaccinated against smallpox should receive a single 0.5ml dose of MVA-BN, no less than two years after the primary course if they are considered to be at on-going risk or in the event of an exposure incident.


Equipment used for vaccination, including used vials, ampoules or syringes, should be disposed of by placing them in a proper, puncture-resistant ‘sharps box’ according to local authority regulations and guidance in Health Technical Memorandum 07-01: Safe management of healthcare waste (Department of Health, 2013).

MVA-BN (Imvanex®/Jynneos®/Imvamune®) contains genetically modified organisms (GMOs). Sharps waste and empty vials should be placed into yellow lidded waste bins and sent for incineration; there is no need for specific designation as GMO waste. An appropriate virucidal disinfectant should be available for managing spills in all settings where vaccination is administered. Potentially contaminated gloves and aprons can be disposed in yellow/black striped bags for offensive waste.

Recommendations for the use of MVA-BN smallpox vaccine

Pre-exposure immunisation

The objectives of immunisation are to provide protection in adults at high risk of exposure to monkeypox or other orthopox viruses.

Given the low incidence of infection in the UK, most workers are at very low risk of exposure to monkeypox, so do not require routine pre-exposure vaccination. Unvaccinated staff who are required to see suspected cases should wear full personal protective equipment and avoid direct and close contact.

Staff who work in specialist roles where exposure to orthopox is likely to be more common, should be advised of the possible risk and offered vaccination on the basis of an occupational health risk assessment. This would include:

  • workers in laboratories where pox viruses (such as monkeypox or genetically modified vaccinia) are handled, and others whose work in specialist and reference laboratories with an identifiable risk of exposure (Advisory Committee on Dangerous Pathogens and the Advisory Committee on Genetic Modification, 1990).
  • staff working in High Consequence Infectious Disease (HCID) units
  • staff regularly undertaking environmental decontamination around cases of monkey pox

Pre-exposure vaccination may also be considered for those about to start to provide prolonged or close care for a patient with confirmed monkeypox.

Pre-exposure use in outbreaks and incidents

In situations of on-going community transmission in the UK, MVA-BN may be considered for use in a wider population at potential risk. This includes extension of pre-exposure vaccination recommendations to protect additional health care staff outside of HCID settings who are more likely to see cases in settings or populations where the outbreak is happening. It may also include any population in which community transmission has been detected, and where standard infection control and follow up is challenging and likely to be ineffective.

This would include, for example, a population with a large number of unidentified or anonymous contacts, residential settings where isolation was challenging, such as prisons and care homes, or excluded populations who may not be able to access care (such as homeless populations).

In the May 2022 monkeypox outbreak, UKHSA has therefore advised that pre-exposure vaccination should be extended to a wider group of staff outside of HCID units including

  • designated staff in additional hospital units being stood up to care for monkeypox patients
  • staff in sexual health clinics designated to assess suspected cases

Other health care staff should be able to avoid inadvertent exposure by ensuring that suspected monkeypox cases are triaged to be assessed by the designated staff or by wearing appropriate personal protective equipment.

In June 2022, JCVI advised that a reactive selective vaccination strategy with the aim of interrupting transmission in the subset of individuals at increased risk of exposure should be deployed. They concluded that this would be best way to bring the current outbreak under control.

JCVI proposed that vaccination should be offered as soon as feasible to those gay, bisexual and other men who have sex with men (GBMSM) at highest risk of exposure. The initial priority is to deliver first doses to as many GBMSM in the highest risk group as possible.

Subject to the evolving epidemiology, a second dose may be advised around 2-3 months later to provide longer lasting protection.

The committee agreed that GBMSM at highest risk could be identified amongst those who attend sexual health services, using markers of risk similar to those used to assess eligibility for HIV pre-exposure prophylaxis (PrEP), but applied regardless of HIV status. These risk criteria would include a recent history of multiple partners, participating in group sex, attending sex on premises venues or a proxy marker such as recent bacterial sexually transmitted infection (in the past year).

UKHSA have also advised that vaccination may also be offered to staff members who work in sex on premises venues, such as saunas, if they are regularly exposed to items (e.g. linens) or surfaces likely to be contaminated with body fluids or skin cells. This offer could be combined with supplementary approaches to provide outreach vaccination to high risk GBMSM who may not be in contact with sexual health services. Data from the Reducing Inequalities in Sexual Health during the COVID-19 pandemic (RiiSH-COVID; unpublished) suggests that this accounts for around 10% of GBMSM.

Post exposure vaccination

The objectives of immunisation are to provide protection against infection and to modify disease severity in individuals of any age with recent exposure to monkeypox. Post- exposure vaccination of high risk community or occupational contacts is offered, ideally within 4 days of exposure, although may be offered up to 14 days in those at on-going risk (for example during an outbreak) or those who are at higher risk of the complications of monkeypox – this includes children below the age of 10-11 years (those in school years up to and including year 6 in England and Wales, year 7 in Northern Ireland, and year P6 in Scotland), pregnant women and individuals with immunosuppression.

Previous incomplete vaccination

If the MVA-BN course is interrupted or delayed, it should be resumed using the same vaccine but the first dose does not need to be repeated.

Evidence suggests that those who have previously received a live smallpox vaccine make an antibody response to their first dose of MVA-BN as good or better than after a second dose of MVA-BN in naïve individuals. Anecdotal reports during management of the early imported cases reported in the UK suggests that healthcare workers vaccinated with the Lister/Elstree vaccine in 2003/4 experienced a higher rate of the common side effects, particularly local reactions, after their first dose of MVA-BN. This suggests that live vaccines prime very effectively for immunity and that a single dose of MVA-BN is sufficient to complete a primary course, regardless of interval since receipt of the live vaccine.

Reinforcing vaccination

There are limited data to determine the appropriate timing of booster doses. Studies two years after the second primary dose showed a decline in antibody levels and a fall in the proportion of people with neutralizing antibody. A booster dose given two years after the primary course increases the proportion of recipients with measurable antibody and this appears to be sustained at higher levels two years later.

Where boosting is considered necessary for those at on-going risk of exposure, a single dose of 0.5 ml should be administered, at least two years after the primary course. If a documented exposure occurs more than two years after the primary course, a single dose of 0.5 ml should be administered within 4 days.

In individuals who have received a dose of live vaccine followed by a single dose of MVA- BN, the need for further boosting is unclear. For those at on-going risk of exposure, a booster of MVA-BN may be considered two years after the previous dose of MVA-BN, or, after that, at the time of an additional exposure.

Co-administration with other vaccines

Although no data for co-administration of MVA-BN vaccine with other vaccines exists, in the absence of such data first principles would suggest that interference between inactivated (non-replicating) vaccines with different antigenic content is likely to be limited (see Chapter 11). Based on experience with other vaccines, any potential interference is most likely to result in a slightly attenuated immune response to one of the vaccines. There is no evidence of any safety concerns, although it may make the attribution of any adverse events more difficult.

Similar considerations apply to co-administration of inactivated (or non-replicating) vaccines such as MVA-BN with live vaccines such as MMR. In particular, live vaccines which replicate in the mucosa, such as live attenuated influenza vaccine (LAIV) are unlikely to be seriously affected by concomitant MVA-BN vaccination. As the non-replicating MVA-BN is considered

inactivated, where individuals in an eligible cohort present having recently received one or more inactivated or another live vaccine, MVA-BN vaccination should still be given. The same applies for most other live and inactivated vaccines where MVA-BN vaccination has been received first or where a patient presents requiring two or more vaccines. It is generally better for vaccination with any required vaccines (including MVA-BN, hepatitis A, hepatitis B and HPV) to proceed to avoid any further delay in protection and to reduce the risk of the patient not returning for a later appointment.


The vaccine should not be routinely given to individuals who have had a previously had a sudden life-threatening allergic reaction to a previous dose of MVA-BN or to any ingredient of MVA-BN. MVA-BN includes trace residues of chicken protein, benzonase, gentamicin and ciprofloxacin from the manufacturing process.



Although MVA-BN has not formally been evaluated in pregnancy, animal studies (three studies in female rats) identified no vaccine related fetal malformations. Use of MVA-BN in pregnant women is limited to less than 300 pregnancies without leading to any adverse events on pregnancy. As it is a non-replicating vaccine, there is no theoretical reason for concerns in pregnancy and the adverse events profile would be expected to be similar to that in non-pregnant vaccinees. Whilst it is not routinely recommended for use in pregnancy, any theoretical concern needs to be weighed against the maternal risks from monkeypox in pregnancy (such as a risk of more severe disease from viral infections in the third trimester) and any consequent fetal risks from maternal infection in early pregnancy.


It is not known whether MVA-BN is excreted in human milk, but this is unlikely as the vaccine virus does not replicate effectively in humans. Individuals who are breast feeding and have a significant exposure to monkeypox should therefore be offered vaccination, after discussion about the risks of monkeypox to themselves and to the breast-fed child.

Individuals with underlying medical conditions

Individuals with atopic dermatitis are known to have developed more site-associated reactions and generalized symptoms following MVA-BN vaccination. Individuals in this group therefore need to have a risk assessment before being offered vaccination. The assessment should consider the risk of exposure, the risk of side effects from vaccination and the potential use of alternative preventive interventions.


Although the MVA-BN vaccine is not licensed in children, several paediatric studies of other vaccines using MVA as a vector (often at a considerably higher dose than used in MVA-BN) have been undertaken with a reassuring side effect profile. This includes a TB vaccine trial of approximately 1500 infants, aged approximately 5 to 6 months, and a trial of 200 Gambian infants who received an MVA malaria vaccine with an acceptable safety profile (Tameris et al, 2013, Oto et al, 2011, Afolabi et al, 2016). The adverse event profile with MVA-BN would be expected to be identical to the profile with these TB and malaria candidate vaccines and therefore provides some reassurance of its use in children, including infants. The vaccine should therefore be offered to children considered to be at risk, as children seem to have a more severe presentation of monkeypox.

Immunosuppression including HIV infection

MVA-BN is a replication defective virus and should pose no risk to those who are immunosuppressed. The safety and immunogenicity of MVA-BN in persons living with HIV infection (with CD4 cell counts above 100 cells/mm3) has been demonstrated (Greenberg et al, 2013). However, the immune response to the vaccine could be reduced in severely immunosuppressed individuals. Vaccination should generally proceed in accordance with recommendations, as these individuals are also at significant risk of the complications of monkeypox. Specialist medical advice on other measures may be required and additional doses should be considered for those at ongoing-risk of exposure.

Adverse Reactions

Data from multiple clinical trials shows that MVA-BN has a favourable adverse event profile compared with first and second generation smallpox vaccines (WHO 2013, Frey et al, 2007, Vollmar et al, 2006, von Krempelhuber et al, 2010, Greenberg et al, 2013). Common adverse events include local site reactions and influenza-like symptoms. These events were mainly mild to moderate in intensity and resolved without intervention within seven days following vaccination. Adverse event rates reported after either vaccination dose (1st, 2nd or booster) were similar, but anecdotally the frequency of adverse events, particularly local site reactions, appears to be higher in those who had receive previous live smallpox vaccine.

Unlike the live vaccine, there have been no reports to date of myocarditis/pericarditis or encephalitis after these vaccines.

Live smallpox vaccine

No live smallpox vaccine is licensed for use in the UK, and there is no current indication for live smallpox vaccination for any individual. In response to the threat of a bioterrorist release of smallpox, in 2003 the Department of Health published guidelines for smallpox response and an information pack for non-emergency vaccination of first responders. The pack includes information on administration and types of vaccine. It also has guidance on pre-vaccination screening and exclusion criteria and on work restrictions

following vaccination.2

Vaccination with live vaccination is no longer recommended for people exhuming bodies in crypts, since the theoretical risk involved poses less risk than the live vaccine.

Reporting anaphylaxis and other allergic reactions

Anaphylaxis is a very rare, recognised side effect of most vaccines and suspected cases should be reported via the Yellow Card Scheme ( Chapter 8 of the Green Book gives detailed guidance on distinguishing between faints, panic attacks and the signs and symptoms of anaphylaxis. If a case of suspected anaphylaxis meets the clinical features described in Chapter 8, this should be reported via the Yellow Card Scheme as a case of ‘anaphylaxis’. Cases of less severe allergic reactions (i.e. not including the clinical features of anaphylaxis) should not be reported as anaphylaxis but as ‘allergic reaction’.

As this vaccine is labelled with a black triangle, all adverse reactions occurring in individuals of any age after vaccination should be reported to the MHRA using the Yellow Card Scheme. Anyone can report a suspected adverse reaction to the Medical and Healthcare vaccination/index.htm

products Regulatory Agency (MHRA) using the Yellow Card reporting scheme (www. Any adverse reaction should also be documented in accordance with local procedures.

Management of suspected cases and contacts

Further guidance on the management of contacts and cases of monkeypox can be found at:

The use of smallpox vaccine during a monkeypox incident can be found in this document published by UKHSA: Recommendations for the use of pre and post exposure vaccination during a monkeypox incident. It is available at


Imvanex® in Europe, Jynneos® in the USA and Imvamune® in Canada is manufactured by Bavarian Nordic. Vaccine is available from UKHSA. Contact UKHSA vaccine supply team.


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