Primary prevention
Smallpox can be prevented by vaccination. Vaccines are based on the closely related vaccinia virus because it is less harmful than the variola virus, and due to the cross-protection afforded by the immune response to orthopoxviruses. Routine vaccination against smallpox ceased in the 1970s in most countries. However, smallpox vaccines are stockpiled in case of an emergency. Consult your local public health authority for guidance on how to obtain vaccines and their use.
Attenuated live virus (replication-deficient) vaccines
Third-generation vaccines are attenuated live virus (replication-deficient) vaccines based on modified vaccinia Ankara (available as modified vaccinia Ankara Bavarian Nordic strain, or MVA-BN). These vaccines represent more attenuated vaccine strains specifically developed by further passage in cell culture or animals.
MVA-BN is available under different brand names (i.e., Imvanex®, Imvamune®, and Jynneos®). These vaccines are available in some countries, although availability may be limited to public health authorities.
Imvanex® is approved in Europe for active immunization against smallpox in adults.
Jynneos® is approved in the US for the prevention of smallpox in adults who are considered to be at high risk for infection.
LC16 (a minimally-replicating vaccine) may be available in some countries (e.g., Japan).
A phase 3 trial found that immune responses with Jynneos® were not inferior compared with patients who received ACAM2000®, and no safety concerns were identified. Typical severe adverse effects associated with replication-competent vaccinia virus strains were not observed. However, the trial was small (220 participants received at least one dose of Jynneos®) and the follow-up time was limited to 29 days.[16]
Replication-deficient vaccines have fewer contraindications and cautions, and are associated with fewer serious adverse events compared with replication-competent vaccines. There is also no risk for inadvertent inoculation and autoinoculation with replication-deficient vaccines. There is insufficient data to determine the risks of third-generation vaccines in pregnant and breastfeeding women.
These vaccines are administered subcutaneously (two doses given 28 days apart). Protection begins 2 weeks after the second dose.
Live replication-competent vaccines
First-generation vaccines (e.g., Dryvax®, Wetvax®/Aventis Pasteur smallpox vaccine) and second-generation vaccines (e.g., ACAM2000®) are not available to the general public. However, they may be stockpiled in case of an emergency.[17][18]
First-generation vaccines from the smallpox eradication program may be held in national reserves but do not meet current safety and manufacturing standards and are not recommended at this time.
ACAM2000® is approved in the US for the prevention of smallpox in people in people ≥1 year of age who are considered to be at high risk for smallpox infection.
Contraindications include history of severe allergic reaction (e.g., anaphylaxis) after a previous dose of the vaccine, atopic dermatitis, other exfoliative skin conditions, immunosuppression, history of drugs or treatments that cause immunosuppression, HIV infection (regardless of immune status), transplant recipients, autoimmune disease, eye disease being treated with topical corticosteroids, pregnancy and breastfeeding, age <1 year, allergy to vaccine component, and underlying heart disease or cardiac risk factors. Contraindications may apply to primary vaccines, revaccinees, or household contacts. In the event of a smallpox emergency, the risk for adverse events is usually outweighed by the risk for severe smallpox disease, and contraindications may not apply.[19]
Although first- and second-generation vaccines are usually contraindicated in pregnant women, a systematic review and meta-analysis found that the overall risk associated with maternal smallpox vaccination appears to be low. Outcomes of smallpox vaccination in 12,201 pregnant women were included. No association with spontaneous abortion, preterm birth, or stillbirth was identified. Vaccination in the first trimester was associated with a small increased risk of congenital defects (based on limited data). While fetal vaccinia appears to be a rare consequence of maternal smallpox vaccination, it is associated with a high rate of fetal loss.[20]
Inoculation with traditional vaccinia may rarely cause eczema vaccinatum, generalized vaccinia, or potentially fatal progressive vaccinia. See Complications.[21]
There are many other potential rare adverse effects including superinfection of the vaccination site or regional lymph nodes, cellulitis, unintentional transfer of vaccinia virus (e.g., accidental autoinoculation of other body parts, ocular vaccinia), fetal vaccinia, myopericarditis, dilated cardiomyopathy, cardiac ischemia, encephalitis, and even death.
Vaccine adverse events may be managed with intravenous vaccinia immune globulin and antiviral agents.
These vaccines are administered percutaneously as a single dose using a multiple puncture technique with a bifurcated needle. If inoculation is successful, a lesion develops at the site of vaccination (known as "a take"). Protection occurs within 28 days. Duration of immunity is unknown.
In the UK, pre-exposure vaccination is recommended for certain people at risk of occupational exposure (e.g., healthcare workers, workers in laboratories where orthopoxviruses are handled).[22]
In the US, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) recommends that people who are at occupational risk for exposure to orthopoxviruses (e.g., research laboratory personnel who work with orthopoxviruses, clinical laboratory personnel who perform diagnostic testing for orthopoxviruses, designated response team members) should be vaccinated with either ACAM2000® or Jynneos®. People who administer live replication-competent smallpox vaccines (e.g., ACAM2000®) or who care for patients with infection with replication-competent orthopoxviruses should also be offered the vaccine.[23]
A booster dose is recommended in people who are at ongoing risk for occupational exposure to orthopoxviruses. The booster dose is recommended every 2 years (Jynneos®) or 3 years (ACAM2000®) for people working with more virulent orthopoxviruses such as variola virus or monkeypox virus, or every 10 years (Jynneos® or ACAM2000®) for those working with less virulent orthopoxviruses such as vaccinia virus.
Resources on smallpox vaccination are available from public health authorities; check your local guidance.
Secondary prevention
Surveillance and containment (ring vaccination) are key to preventing smallpox outbreaks and involve the following principles:[46]
Identifying cases, confirming diagnosis (with polymerase chain reaction testing), and reporting cases
Isolating patients
Identifying face-to-face contacts
Vaccinating contacts
Vaccinating those who have been/might be associates of a first-ring contact.
Epidemiologic evidence indicates that vaccination with a smallpox vaccine within 3 days of exposure will prevent or significantly modify smallpox in the vast majority of people. Vaccination from 4-7 days will also likely modify the severity of the disease and protect against a fatal outcome. Vaccination will not protect patients who already have a rash. Contacts should be vaccinated against smallpox, ideally within 3 days. It is especially important that all household contacts be vaccinated, as well as all medical staff who come into contact with the patient. Symptomatic contacts should be isolated.[1]
Vaccinia immune globulin (VIG) may be considered if smallpox vaccination is contraindicated.
Use of this content is subject to our disclaimer