Smallpox Vaccine was the first vaccine that was developed against a transmissible disease. It is developed from a vaccinia virus that is a poxvirus and is similar to the smallpox virus.

Smallpox vaccine Uses:

• Smallpox disease prevention:

  • Vaccination against smallpox disease is administered to people who have been found to be at high risk of contracting the disease.
  • The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination for the following:
    • Workers in laboratories who have direct contact with cultures or animals that have been exposed to or have been infected with recombinant vaccinia viruses created from replication-competent vaccinia strains, or related orthopoxviruses that can infect humans (eg, monkeypox, cowpox, variola).
    • May also take into account for medical staff providing ACAM2000 smallpox vaccination, treating patients with vaccinia virus infections, or anticipating treating them; adherence to adequate infection prevention measures is also required.

  • In a pre-event vaccination program, the ACIP recommends vaccination for the following:

    • Persons designated by authorities (smallpox response teams) to investigate and follow-up on initial smallpox cases with the likelihood of direct patient contact
    • Teams of medical professionals who work in hospitals and care for patients with smallpox.
    • Those in charge of delivering the smallpox vaccine

  • For post-event vaccination, the ACIP recommends vaccination for the following:

    • Direct victims of a viral release, whether unintentional or malicious
    • Household members of a patient with smallpox who has been diagnosed, are suspected of having it, or who have spent less than three hours there since developing a fever
    • Non-family members who have had 3 hours or less of close contact (6.5 feet or 2 metres) with a smallpox patient who has a rash.
    • Individuals who, in the eyes of public health officials, pose a high risk of contracting smallpox, including healthcare personnel

Smallpox Vaccine dose in Adults

Smallpox Vaccine dose for primary vaccination and revaccination: Percutaneous:

• Not for Intramuscular, intradermal, Intravenous, or SubQ injection:
  • Vaccination by scarification (multiple-puncture technique) only:
  • Note:
    • After 15 to 20 seconds, a drop of blood should be seen at the vaccination site.
    • The same needle should be used three more times if there is no sign of blood, without re-inserting it into the vaccination vial.
       
• A second dose (revaccination) from a different vial or vaccine lot may be given if the patient does not experience a significant cutaneous reaction after the first dose (by day 6 to 8). Use a single drop of vaccine suspension and 15 needle punctures (using the same bifurcated needle) into the superficial skin.
• Consult the CDC or the state or local health department for more advice if there is no reaction to the second dose.

Note:

• The company advises revaccination every three years for people who continue to be at a high risk of contracting smallpox.
• Depending on the type of exposure, the ACIP advises routine, non-emergency revaccination every 3 to 10 years.

Smallpox Vaccine dose in Childrens

Smallpox Vaccine Primary vaccination and revaccination:

• Children and Adolescents <16 years (in emergency conditions only) and Adolescents ≥16 years:

  • Percutaneous: Refer to adult dosing.

Pregnancy Risk Category: C

• [US Boxed Warning] Pregnant women are more at risk of severe adverse reactions.
• Studies on non-animal reproduction have employed this vaccination.
• The Vaccinia vaccine has not been associated with the emergence of congenital abnormalities.
• Rarely, vaccinations have been linked to fetal infections.
• The risk of fetal vaccinia was linked to stillbirth and neonatal death.
• According to the CDC vaccination of pregnant women is not recommended in a preventive setting.
• This includes laboratory personnel and health care workers at risk of occupational exposure to orthopoxviruses.
• If there is a relative contraindication, vaccination is not recommended for the post-event setting.
• After vaccination, avoid pregnancy for at most 4 weeks.

Smallpox vaccine use during breastfeeding:

• If the vaccine virus or antibodies are present in breast milk, it is unknown.
• According to the CDC vaccination of a breastfeeding mother is not recommended in a non-emergency situation.
• This includes individuals working in laboratories and healthcare professionals who may be exposed to orthopoxviruses on the job.
• If there is a relative contraindication, vaccination is not recommended for the postevent setting.
• If the vaccine has to be administered in an emergency, breastfeeding should not be continued. 
• Breastfeeding mothers should take precautions to avoid accidental contact with vaccinees.
• After secondary transfer to a breastfeeding mother, one case of tertiary transmission to an infant was reported.

Dose in Kidney Disease:

No dosage adjustments provided by the manufacturer.

Dose in Liver disease:

No dosage adjustments provided by the manufacturer.

Common Side Effects of Smallpox vaccine:

• Central Nervous System:

  • Lymph Node Pain
  • Headache
  • Fatigue
  • Malaise
  • Feeling Hot
  • Rigors

• Dermatologic:

  • Injection Site Pruritus
  • Erythema
  • Skin Rash

• Gastrointestinal:

  • Nausea
  • Diarrhea

• Local:

  • Erythema At Injection Site
  • Pain At Injection Site
  • Swelling At Injection Site

• Neuromuscular & Skeletal:

  • Myalgia

• Miscellaneous:

  • Decreased Exercise Tolerance

Less Common Side Effects Of Smallpox Vaccine:

• Gastrointestinal:

  • Constipation
  • Vomiting

• Hematologic & Oncologic:

  • Lymphadenopathy

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain

• Respiratory:

  • Dyspnea

Side effects of Smallpox Vaccine (Frequency Not Defined):

• Cardiovascular:

  • Cardiomyopathy (Nonischemic/Dilated)
  • Ischemic Heart Disease
  • Myocarditis
  • Pericarditis

• Central Nervous System:

  • Bell's Palsy
  • Brain Disease
  • Dizziness
  • Encephalitis
  • Guillain-Barre Syndrome
  • Meningitis
  • Paresthesia
  • Seizure
  • Vertigo

• Dermatologic:

  • Contact Dermatitis
  • Eczema (Vaccinatum)
  • Erythema Multiforme
  • Stevens-Johnson Syndrome

• Gastrointestinal:

  • Abdominal Pain
  • Toothache

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Secondary Infection (Including Autoinoculation to Eyelid, Face, Genitalia, Lips, Mouth, Nose, Rectum)
  • Vaccinia (Includes Generalized, Ocular, Progressive, Skin Infection)

• Neuromuscular & Skeletal:

  • Myelitis

• Ophthalmic:

  • Blindness
  • Corneal Injury (Scarring)
  • Keratitis
  • Photophobia

• Miscellaneous:

  • Fever

Contraindications to Smallpox vaccine:

Manufacturer labeling:

• Significant immunodeficiency (eg patients undergoing bone-marrow transplants, individuals with primary and acquired immunodeficiency requiring isolation).
• The immunisation of those who are at high risk of smallpox exposure has very few contraindications.
• It is important to carefully consider the potential risks and benefits before you make the decision to vaccinate.

ACIP contraindications during a pre-event vaccine program

• Grave hypersensitivity to any component of the vaccine;
• Eczema, atopic dermatitis, or any other acute, chronic, or peeling skin disorders in the past or present (or people with household contacts with such conditions)
• Immunosuppression 
• Pregnant or breast-feeding women (or household contact of pregnant women)
• Infants under 1 year old

The use of non-emergent ACIP in laboratory or healthcare staff who are at high risk of occupational exposure to orthopoxviruses is contraindicated. Refer to these rules: primary vaccinations, revaccinations, and close family contacts:

• Atopic dermatitis: History or presence
• Other active exfoliating skin conditions
• immunosuppression
• pregnancy
• Infants

Additional contraindications to primary vaccinees or revaccinees

• Breastfeeding
• serious vaccine component allergy
• Heart disease is a well-known condition.

Additional contraindications to primary vaccines are:

• Three or more major factors that increase the risk of developing a heart attack

ACIP contraindications after an event:

• There are no contraindications absolute to vaccination.

These are all relative contraindications to -

• Severe immunodeficiency, including the following:
  • In the past 4 months, bone marrow transplantation has been performed.
  • HIV infection with CD4 50 Cells/mm3 (or AIDS definition condition if a recent CD4 count is not available).
  • Combination severe immunodeficiency
  • Complete DiGeorge syndrome or
  • Other states with severe immunocompromised conditions may also require isolation.
• Smallpox is a serious infection that can be contracted with a high risk, but there are no known cases.
  • Hypersensitivity to any component of the vaccine, or to the vaccine itself
  • atopic dermatitis,
  • Solid organ transplantation within the last 3 months
  • In the last 4 to 24 month, bone marrow transplantation was performed.
  • HIV infection with CD4 50-199 cells/mm3
  • After transplantation, active graft versus host disease
  • Immunosuppressive therapy (or
  • Another state with immunocompromised status.

Warnings and precautions

• Anaphylactoid/hypersensitivity reactions:

  • Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions must be available during vaccine use.

• Encephalitis: [US Boxed Warning]:

  • After vaccination, cases of encephalitis and encephalomyelitis have been reported.

• Myopericarditis: [US-Bound Warning]

  • Acute myocarditis or pericarditis can be reported after vaccination.

• Ocular complications: [US-Boxed Warning]

  • Ocular complications such as blindness have been reported after vaccination.
  • Side effects may occur in patients with eye disease that requires treatment with ophthalmic steroids.
  • Unintentional infection of the eye can occur after vaccination (due to touching or rub of the eyes), leading to keratitis and corneal scarring.
  • Ophthalmic steroids users may be at higher risk of developing ocular vaccinia.
  • ACIP recommends that people with eye conditions that require steroid treatment delay vaccination until they are better.

• Systemic and skin reactions: [US Boxed Warn]

  • Following immunisation, severe vaccin-induced skin infections, generalised vaccin, erythema multiforme major (including Stevens Johnson syndrome), and severe vaccinial infections were all reported.

• Syncope

  • Syncope can be caused by injectable vaccines. It is most commonly reported in adolescents and young adults within 15 minutes after vaccination.
  • It is important to take precautions to prevent injuries from falling, and to preserve cerebral perfusion in the event of syncope.

• Cardiovascular disease: [US-Boxed Warning]

  • Patients with cardiovascular disease, those at higher risk of getting it, and patients with a family history of it may all have experienced severe adverse effects or be at high risk of experiencing them in the future.
  • Patients with heart disease, including those who have had a prior MI, angina or heart failure, chest pain, shortness of breath with activity or stroke, TIA or those with 3 or more risk factors.

• Exfoliative or Eczema skin conditions: [US-Boxed Warning]

  • After vaccination, eczema has been observed.
  • Patients who have severe skin infections may have eczema, a history of eczema, or other chronic exfoliative skin disorders.
  • These patients should not receive vaccines in non-emergency situations.

Smallpox vaccine (United States: Availability limited to CDC distribution from strategic national stockpile in consultation with local health department): Drug Interaction

Monitoring parameters:

• Observe for anaphylaxis and syncope for 15 minutes after administration.
• Keep the patient in a supine or Trendelenburg position if seizure-like activity accompanied by syncope occurs to restore and maintain cerebral perfusion.

Primary vaccines:

• Keep an eye on the injection site and check back in 6 to 8 days.
• The presence of a significant reaction, such as a vesicular or pustular lesion or a palpable area of induration surrounding a central lesion, indicates that the immunisation was effective.
• In individuals receiving only primary vaccinations, an ambiguous reaction (all responses other than a significant reaction) necessitates revaccination.

Revaccination:

• Successful vaccination is confirmed when a major cutaneous reaction is observed 6 to 8 days postvaccination.
• Previous vaccines may lessen the cutaneous response, which does not always mean the vaccination was ineffective.

How to administer the Smallpox vaccine?

• Only medical professionals skilled in administering the percutaneous smallpox vaccine in a safe and effective manner should administer vaccinations.
• Do not combine with other injections or immunizations.
• For every injection, use a different set of needles and syringes.
• The patient should be vaccinated while sitting or lying down to prevent injuries caused by syncope.
   

Vaccination by scarification (multiple-puncture technique) only:

• Administer by percutaneous injection only; not for IM, intradermal, IV, or subcutaneous injection.
• Allow the area to thoroughly dry before administering the vaccine if alcohol is used to clean the skin. This will prevent the alcohol from inactivating the vaccine.
• Carefully dipping a single-use bifurcated needle into the reconstituted vaccine (following removal of rubber stopper).
• Make sure the needle actually scoops up a drop of the vaccination solution by paying close attention.
• Using a multiple-puncture approach, one drop of vaccine is injected into the skin's outermost layers using a bifurcated needle.
• The preferred place for immunisation is the skin over the deltoid muscle insertion.
• Place the vaccine drop on the clean, dry skin where it will be applied.
• Punctures should be made quickly into the superficial skin of the vaccination site, within a diameter of about 5 mm, while holding the bifurcated needle at a right angle to the skin.
• After roughly 15 to 20 seconds, a drop of blood should start to form from the puncture strokes.
• Use dry, sterile gauze to wipe up any leftover vaccination.
• Use a biohazard trash receptacle to dispose of everything; do not repurpose the bifurcated needle.
• It is necessary to burn, boil, or autoclave all materials.

Avoid scratching the vaccination site, cover it with gauze (holding it in place with first aid adhesive tape), and cover the gauze with a semipermeable barrier (such as a semiocclusive dressing) or clothing to prevent the spread of the virus. The immunisation site shouldn't be treated with ointment or salve. Consistent handwashing helps avoid accidental immunisation. To prevent transmission, vaccine recipients should change bandages away from other people and wash their own linens separately.

Mechanism of action of Smallpox vaccine:

• The Vaccinia virus can be compared to smallpox virus in certain respects.
• Inducing a localized infection of vaccinia virus results in immunity to both vaccinia as well as variola.
• Immunity, neutralising antibody formation, viral multiplication, cellular hypersensitivity, and immunity are all possible side effects of vaccination.

Efficacy:

• Following primary vaccination, more than 95% of people acquire neutralising or hemagglutination-inhibiting antibodies against vaccinia, which may be enhanced with a booster shot.

The beginning of action:

• After vaccination, neutralizing antibodies are visible within 15-20 days.
• After revaccination, the time it takes for neutralizing antibodies to appear may be shorter (7 Days).

Time of action:

• After second doses, neutralising antibody titres (>1:10) persist for 10 years in 75% of patients. After 3 dosages, they also have a 30-year shelf life.

International Brand Names of Smallpox vaccine:

• ACAM2000
• En Zai Shi
• Imvanex
• Ospavir
• TEOVac

Smallpox vaccine Brand Names in Pakistan:

No Brands are available in Pakistan.