Approach

The mainstay of management is supportive care. Antiviral therapy may also be recommended. Detailed guidance on the management of smallpox is currently beyond the scope of this topic as smallpox no longer exists as a naturally occurring disease. In the event of a smallpox outbreak, you should consult your local public health authority for guidance on management as new guidance is likely to be published.

Infection prevention and control

Immediately contact your regional infectious disease unit if there is a clinical suspicion of smallpox.

  • This will trigger procedures to be activated for the safe transfer of the patient to a negative-pressure isolation facility and the notification of the public health team. Patients with suspected smallpox should not be placed in areas of the hospital holding immunosuppressed patients given the risk of nosocomial transmission.

  • It is important to keep records of everyone who has been in close contact with the symptomatic patient (e.g., household contacts, paramedical and medical staff).

  • All suspected cases should be managed by experts, including public health officials, to prevent a potential emergency situation.

Follow your local infection prevention and control protocols.

  • Standard, contact, droplet, and airborne precautions are recommended.

  • Ensure you have appropriate personal protective equipment (PPE) for the assessment of suspected cases. Healthcare workers must wear full PPE including an N95 face mask to protect against transmission of infection by the respiratory route and physical contact with the patient or patient’s bodily fluids. Rigorous donning and doffing of PPE should be undertaken in the presence of a trained observer.[24]

  • Treat all contaminated materials (e.g., linens, hospital gowns) and body fluids/solid waste of patients as potentially infectious. Deceased patients are also considered infectious.

  • Ideally all personnel likely to be in contact with the patient, bodily fluids, or fomites should have been vaccinated with the smallpox vaccine.

Supportive care

Management is primarily supportive with attention to fluid balance, oxygenation, nutrition, symptom relief (e.g., analgesia, anti-emetics), prompt treatment of additional secondary bacterial infections with antibiotics, and management of complications (e.g., sepsis) and prevention of long-term sequelae. Aggressive intravenous fluid replacement may be required. Blood products may be necessary, especially in rare haemorrhagic variants of smallpox. Psychological support for anxiety and depression is important. Clinical management is similar to Mpox (monkeypox).

Antiviral therapy

There are three antivirals approved and/or stockpiled in case of a smallpox outbreak.[31]

  • Tecovirimat: oral tecovirimat is approved in the UK and Europe for the treatment of smallpox. It is approved in the US for the treatment of smallpox, and is available there as oral and intravenous formulations.[32]

  • Brincidofovir: an analogue of cidofovir that is approved in the US for the treatment of smallpox in adults and children (including neonates and infants), and is available as tablets and an oral suspension.[33] 

  • Cidofovir: not approved for the treatment of smallpox, but may be used during an outbreak under an investigational new drug protocol or emergency-use authorisation.

The effectiveness of antiviral therapy for the treatment of smallpox has not been determined in humans because human trials would be unethical. Approvals are based on in vitro and animal studies.

  • The efficacy of tecovirimat for smallpox has been confirmed in two animal model studies, and safety has been confirmed in a phase 3 trial of 359 healthy human volunteers without smallpox infection.[34][32] 

  • The efficacy of brincidofovir has been demonstrated in in vitro and animal studies.

Guidance on the use of antiviral therapy will be provided by public health authorities in the event of a public health emergency involving smallpox.

Intravenous vaccinia immunoglobulin (VIG) may also be stockpiled in some countries for use during an outbreak. It may reduce morbidity and mortality and prevent vaccinial superinfection in patients with eczema, inflammatory skin diseases, or burns.[35]

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