Smallpox

See also our Smallpox Vaccination record.

This disease is notifiable in the UK under the Public Health (Infectious Diseases) Regulations 1988.

Overview

Smallpox is a viral haemorrhagic fever¹ caused by the variola virus which belongs to the same genus as cowpox, monkeypox, orf and molluscum contagiosum.² It used to be a common cause of morbidity and mortality world-wide but it has now been eradicated. Ongoing interest in this disease lies both in the success of the eradication programme and in its potential as a biological weapon.

Historical background

Cases of smallpox have been documented in the 4th century A.D. in China and there is less reliable evidence suggesting that it has been recognized as far back as 1200 B.C.³ Pandemics have since affected Europe and Asia and the disease was introduced into the Americas in the 1600s via infected blankets, where it caused massive fatalities among the indigenous peoples.² In 1796, Edward Jenner developed the basis for vaccination (starting with the related cowpox virus)⁴ and by the early 1900s, smallpox vaccination had become mandatory in developed countries. The last documented natural case was that of an unvaccinated Somali cook on the 26th October 1977 and a further accidental case involving a laboratory worker in Birmingham occurred a year later. The World Health Organisation officially declared it eradicated in 1979.⁵

Relevance today

There have been no known cases of smallpox since 1979. Intense interest remains in this disease as it represents an ideal in medical achievement: complete eradication of a disease. There are currently three laboratories in the world which stock the virus: the Centers for Disease Control and Prevention in Atlanta (USA), at the Institute of Viral Preparations in Moscow (Russia) and the Russian State Research Centre of Virology and Biotechnology in Koltsovo.² The other relevance today lies in the potential of tapping into these stocks for bioterrorism. The effects on the population by a release of this virus would be potentiated by:⁶

• The low population immunity
• Difficulty in diagnosis as health professionals have no experience of cases
• Density and mobility of today's populations

Until recently, the variola virus was thought to infect humans only but more recently, macaque monkeys have developed the disease in laboratory conditions following intense exposure to large amounts of injected and aerosolised virus. There is no natural animal or insect reservoir.⁵ Infection starts in the respiratory tract where the virus replicates before disseminating peripherally to form infective foci within the skin, respiratory and gastrointestinal tracts, kidneys and brain. There are subsequently two clinical forms of the disease depending on the substrain of variola:⁷

• Variola major - this is the more severe and most common form of the disease accounting for > 90% of cases. These patients present with fevers, extensive rashes and there is a 30% mortality rate. There are four subtypes of the variola major picture:
  • Ordinary: most frequent type
  • Modified: occurs in previously vaccinated patients
  • Flat and haemorrhagic: both rare, very severe and usually fatal (> 95% cases⁸)
• Variola minor - this is a much less severe form of the disease which is less common and associated with a mortality rate of < 1%

Transmission⁹

The virus is acquired from inhalation although it can remain viable on fomites for about a week.² It may also be transmitted directly via saliva, respiratory secretions and vesicular fluid. There is an asymptomatic period lasting about 14 days (range: 9-17 days) following inoculation when patients are not infectious - after this time, the virus is excreted from patients' throats. This corresponds to the start of the fever. Infectiousness peaks at about the second or third day of the fever but is ongoing up until the scabs dry over following recovery or the patient dies.

Contacts

• Household contacts: highest secondary infection rate (37-96%; dependant on degree of crowding and level of sanitation)
• Open ward: verifiable outbreaks have been recorded
• Casual contact (e.g. working in same building): transmission much less likely but possible
• Contaminated clothing that is shared may be a source of outbreak as may be sharing enclosed spaces (e.g. buses and trains)

Variola major^9,7

• Incubation (9-17 days): not contagious - exposure to virus followed by incubation. Usually asymptomatic.
• Prodrome (2-4 days): usually contagious - abrupt onset of fever (usually ≤ 39°C), malaise, headache, intense, ill-defined body ache (back, chest, loins), vomiting, anxiety. Too sick to carry on with usual activities.
• Early rash (~4 days): highly contagious - rash emerges as small red spots on the tongue and in the mouth. These develop into sores that beak open and shed the viral load into the mouth and pharynx. As the mouth sores break down, the rash starts to spread to the face, arms and legs and then to the hands and feet (note a 'centrifugal' distribution in contrast to the central distribution of chickenpox). The rash usually spreads to all parts of the body within 24 hours after which the fever subsides a little and the person may start to feel better. By the third day of the rash, the lesions become raised bumps and fill with a thick fluid and develop a characteristic umbilicated central depression. Fever rises again by the fourth day and remains up until the lesions scab over.
• Pustular rash (~5 days): contagious - lesions become firm, rounded pustules. They are hot and tender to touch, as if the patient were sun-burnt.
• Pustules and scabs (~5 days): contagious - pustules begin to form a scab and crust over.
• Resolving scabs (~6 days): contagious - scabs begin to fall off, leaving pitted scars.
• Scabs resolved (~6 days): not contagious - the patient is no longer contagious only once all the scabs have fallen off.

Variola minor⁹

This is more common in previously vaccinated populations or those who have had exposure to the disease:

• Prodrome is similar but the temperature tends to be higher (39.5-40.5°C).
• Early rash is less marked.
• Maculopapular rash starts earlier (days 3-4) and has characteristic areas of distribution:
  • Scalp and face: particularly on the nose
  • Neck: particularly over the trachea and sternocleidomastoid muscles
  • Arms: particularly over heads of radius and ulna and in wrist folds
  • Legs: particularly over the heads of the malleoli
• Vesicles appear earlier (~day 5) and are similar to those of variola major in most ways but are not hot or tender to touch.
• Most crusts are shed by about day 15, when large pitted scars are left behind.

Mild / abortive presentations⁹

These presentations occur when an exposed individual has already been vaccinated (either prior to exposure or during the early inoculation period). There is a high fever of abrupt onset but subsequently a limited rash (≤ 100 lesions) if any at all. However, these patients are contagious and may confer the fulminant variety of smallpox onto unprotected individuals.

• Atypical chickenpox
• Disseminated herpes simplex
• Other causes of rash e.g. measles virus, enterovirus, parvovirus B19, rubella
• Other infective causes e.g. impetigo, scabies, molluscum contagiosum
• Severe adverse reaction to medication / vaccination
• Erythema multiforme

Diagnosis is made on the clinical appearance and progression of the disease as outlined above. Diagnostic algorithms will be distributed in the event of an outbreak.

General measures of a suspected case include:

• Call the duty public health specialist / consultant who will then call the SDE (Smallpox Diagnostic Expert) to come and assess the patient. While you are waiting:
  • Stay at the scene
  • Isolate the patient as best as possible
  • Try and ensure that close contacts remain at the scene
  • Record details of close contacts who have left the scene
• There will be management protocols to which you can refer - see ¹¹ for algorithms but liaise with the on-call public health specialist as to the next step. Algorithms vary according to your situation - scroll to relevant page:
  • If you are at the patient's home - P.52
  • If you are in a GP surgery - P.53
  • If you are in an A&E department - P.54
  • If you are on a general ward - P.55
  • If you are on an intensive care unit - P.56
  • If you are at a port health control unit - P.57
• There is no specific treatment. Patients will be symptomatically managed with an emphasis on adequate analgesia (the blistering is extremely painful), good hydration and where possible, nutritional support. Attention will be paid to skin hygiene (hair may be cut short to facilitate shedding of scabs), eye hygiene and measures to address oedema (e.g. removal of rings before skins swells; occasionally a bolus dose of hydrocortisone is used where there is pharyngeal oedema). Many patients benefit from oral antibiotics as well as topical eye antimicrobials to address secondary skin / eye infections.

Outbreak management

There are several issues relating to the management of an outbreak:

• Care of the patient
• Tracing of contacts
• Dissemination of information to healthcare professionals and to the public
• Vaccination strategy

This is carried out through the combined work of local specialized clinicians in Smallpox Care Centres and the regional Smallpox Diagnosis and Response Groups. The SDE is the trigger to activating local, regional and national strategies. An alert level will be advised by the Chief Medical Officer and all suspected cases are investigated by WHO.¹⁰

Alert levels

• Alert level 0 - there is no credible threat of the disease.
• Alert level 1 - case confirmed outside the UK.
• Alert level 2 - case confirmed within the UK.
• Alert level 3 - outbreak has occurred within the UK.
• Alert level 4 - there is a large (or multiple) outbreak(s) not contained by ring vaccination.
• Alert level 5 - the outbreak has been controlled.

Categorization of Contacts

• Category A contacts - household contacts, anybody who has had interactions (within 2 metres) with an infectious case and those who have had direct contacts with clothing / other articles of infectious cases.
• Category B contacts - the definition is a little loose but these include anybody who has had any prolonged period of sharing a space with an infectious case (work colleagues, co-passengers on plane, train or bus and people who have shared an air-conditioned building with the patient).
• Secondary contacts - people who will have prolonged contact with category A contacts throughout the monitoring period of category A contacts (e.g. household contacts).
• Transient, distant contacts - passing contacts in the street or shops or where there has been sharing of a large, well-ventilated space.

There are specific identification, monitoring and vaccination measures for each of these groups of contacts that will be put into action by the regional Smallpox Diagnosis and Response Group.

The issue of bioterrorism

In the current climate of global unrest and terrorist threats, smallpox has been highlighted as a potential biological weapon. As it has been eradicated, the most likely outbreak is from such an attack.² The threat lies in the fact that it has an airborne route of spread, it is a severe illness with a high fatality rate and those who do survive are left with disfiguring scars and a risk of blindness (see complications). ⁹There are clear instructions for Directors of Public Health and Consultants in Communicable Disease which outline a cascade of urgent management steps but the onus is on all healthcare practitioners to have at least an awareness of the disease, its diagnosis and the management contingencies.⁶

• During the illness: dehydration, bronchopneumonia, osteomyelitis, secondary skin and conjunctival / corneal infections, death.
• Following the illness: severe skin scars, particularly round the face, blindness secondary to corneal scarring, arthritis.

Other than measles and influenza, variola remains one of the most readily communicable infectious diseases.² Mortality is significant with an overall rate of about 30% (up to 90% in non-immune populations⁹).The highest mortality is seen in children aged less than 1 year, in the elderly, in pregnant women and in immunocompromised patients.⁸

The vaccine^7,12

This is a live vaccine made from the related Vaccinia virus (therefore you cannot get smallpox from the vaccine). It involves pricking the vaccine over a 5mm area on the upper arm which is then covered with strict instructions not to scratch the area. It is said to 'take' if there is apparition of a small pustule within a week which scabs over in a fortnight. Vaccination received before or within 3 days of exposure will prevent or reduce the severity of the disease. Vaccination 4-7 days after exposure may reduce the severity of the disease. It produces a high level of immunity for 3-5 years and gradually decreasing immunity thereafter (it lasts no longer than 10 years⁵). A further vaccination confers longer immunity.

Who should be vaccinated⁸

In the event of an outbreak, healthcare workers involved in the primary management of these patients (primarily SDEs and Diagnosis and Response Teams) will be vaccinated on a voluntary basis. Their families will not be vaccinated but following a confirmed case, contacts may be vaccinated according to pre-determined protocols. The side-effects preclude mass vaccination.

Who should not be vaccinated⁸

• Patients who are allergic to any of the vaccine components
• Pregnant and breastfeeding women
• Babies under 12 months old
• Patients who have, or have had, skin conditions (especially eczema and atopic dermatitis)
• Immunocompromised patients e.g. transplant recipients, HIV positive, people who are receiving treatment for cancer or who are taking immuno-suppressive medications

Complications from the vaccination¹³

The overall risk of complications is low but problems can be serious (and include death e.g. encephalitis and certain forms of eczema) and include:

Primary vaccination

• Vaccinia necrosum (~1.0 per million)
• Post-vaccinial encephalitis (~2.9 per million)
• Eczema vacciantum (~12.8 per million)
• Generalized vaccinia (~39.9 per million)
• Accidental infection (~64.9 per million)
• Myopericarditis (~140-600 per million)⁸

Re-vaccination

The complications are the same but at much lower rates.