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DISEASES : Smallpox

The last naturally acquired case of smallpox in the world occurred in October 1977. Global eradication of the disease was certified by the World Health Organization in 1980, after more that 2 years with no cases identified. Although smallpox is a vaccine preventable disease, immunization programs were stopped in Canada in 1972 for infants, in 1977 for health care workers and in 1988 for Canadian Forces.

Smallpox is caused by the variola virus. Two types of smallpox were identified during the 20th century : variola major and the much milder form of variola minor. Typical variola major epidemics resulted in case-fatality rates of 30% or higher among unvaccinated individuals, whereas the case-fatality rates for variola minor were usually 1% or less.

Currently this virus is maintained in designated laboratories; however there is concern that clandestine stockpiles may exist elsewhere in the world and that these sources may be accessed by terrorists. The virus causing this systemic disease is a potential biological weapon because it can be aerosolized, has a low infective dose and is communicable from person to person. Also, the population is increasingly susceptible since immunization programs were stopped over 20 years ago and there is no treatment.

Symptoms and Signs

The early symptoms of smallpox resemble influenza. There is sudden onset of fever, malaise, headache, vomiting, prostration, severe backache and occasionally abdominal pain and delirium. Two to four days after the onset of illness the fever begins to fall and a deep-seated rash develops. The rash progresses through successive stages of macules, papules, vesicles, pustules and crusted scabs; starting on the face and extremities and then spreading to the trunk. The early lesions may occur in the mouth and pharynx. The scabs are formed by early in the second week and then separate and fall off in about 3-4 weeks. When the scabs separate, pigment-free skin remains and eventually pitted scars form. Historically, in vaccinated individuals the rash was less severe and the stages of the rash were accelerated with crusting by the 10th day.

Fulminating disease with a severe prodrome, prostration, and bleeding into the skin and mucous membranes was observed in less that 3% of variola major cases. These cases were rapidly fatal.

Smallpox can be differentiated from chickenpox by several clinical features. The following table is provided to assist with this differentiation.

Smallpox Chickenpox
Prodromal period 3 day period of chills, headache, backache and severe malaise usually absent in children as rash and constitutional symptoms occur simultaneously
typically rash starts when fever breaks in adolescents and adults there may be a 1 or 2 day prodrome of fever, headache, malaise and anorexia
Rash slow evolution of macules to papules to vesicles to pustules to crusts rapid evolution of macules to papules to vesicles to crusts
the vesicles are multiloculated, non-collapsing the vesicles are monoloculated and collapse on puncture
peripheral distribution of lesions, which are most prominent on the exposed skin surfaces, especially the face central distribution of lesions which appear in crops
rash starts on face and extremities and spreads inward to the trunk where it is relatively sparse
lesions are virtually never seen at the apex of the axilla, but may be seen on the palms and soles rash is sparse distally and is rarely seen on the palms or soles
presence of lesions in the same stage in any one anatomical area presence of lesions in all stages in any one anatomical area
skin lesions are more deep-seated than those of varicella presence of scalp lesions

Mode of Transmission

Smallpox typically spreads from person to person through infected oropharyngeal droplets or aerosols. Direct contact with these droplets or inhalation may cause infection in a susceptible person. Direct transmission can also occur through contact with contaminated clothing or bed linens. Historically, as many as 10 to 20 second-generation cases were often infected from a single case. In a bioterrorist attack the virus would most likely be disseminated through the air in an aerosol cloud.

Incubation Period

The incubation period ranges from 7 to 19 days, most commonly 10-14 days following exposure to onset of illness and 2-4 days more to onset of rash.

Period of Communicability

Cases are typically communicable for about 3 weeks, from just before the appearance of the earliest lesions to the disappearance of all scabs. The person is most contagious during the first week of illness since that is when the viral load is the highest in the saliva. Strict isolation of cases would be essential to prevent the spread of this disease.

Laboratory Diagnosis

Because laboratory confirmation of smallpox is restricted in Canada to the National Medical Laboratory (NML) in Winnipeg, all requests for laboratory testing for smallpox will be approved exclusively by Health Canada's Centre for Emergency Preparedness and Response (CEPR) in collaboration with NML.

Contact should be made with staff at the National Microbiology Laboratory (NML) in Winnipeg prior to the collection of any specimens. The priority contact point is through the NML 24/7 pager at 204-932-2733. Alternatively contact can be made directly with the Head of Special Pathogens (work: 204-789- 6019; cell phone: 204-781-0549) or the Chief, Zoonotic Diseases and Special Pathogens (work:204-789-2134; cell phone 204-782-8914). In addition to the National Microbiology Laboratory, the local medical officer of health should be notified prior to the collection of any specimens on suspect cases of smallpox so that appropriate arrangements can be made.

Requests for smallpox laboratory testing will only be granted upon receipt of telephone notification of suspected smallpox from a local Medical Officer of Health, the Chief Medical Officer of Health or from other health officials whom the Director General of CEPR deems acceptable at the time of notification.

Specimen collection for the purpose of confirming a suspect case of smallpox must be done under strict isolation and preferably by a recently immunized person. These specimens would have to be packaged and transported in a specific manner to a bio-safety level 4 laboratory. Specimens should be handled according to universal precautions and packaged for transport to the Central Public Health Laboratory according to the Transportation of Dangerous Goods regulations.

Specimens of vesicular or pustular fluid or scabs taken from the lesions of a suspect case of smallpox can be examined by negative stain electron microscopy for rapid presumptive diagnosis of smallpox infection. PCR testing and viral isolation would be required for definitive identification and classification of the virus.


There is no proven treatment for smallpox. Research to evaluate new antiviral agents is ongoing. Management of smallpox patients would include supportive therapy in the form of intravenous fluids, antipyretics, and antibiotics for any secondary bacterial infections that may occur.

Post-exposure Prophylaxis

In people exposed to smallpox, administration of the smallpox vaccine within 4 days of exposure may lessen the severity of or even prevent illness.


Vaccination of the general population against smallpox in advance of a bioterrorist attack is not currently recommended and therefore the vaccine is unavailable for this purpose. Smallpox vaccine is not currently available from commercial sources.

Some vaccine is being held by the federal government as a contingency and for the purpose of immunizing laboratory workers who may be exposed to the virus, and persons considered essential for emergency preparedness to protect the interests and lives of Canadians. The federal government has contracted a local manufacturer to secure additional quantities of vaccine for emergency purposes.

The potentially significant side-effects from smallpox vaccine (made from vaccinia virus), including transfer of the vaccine virus to close contacts of the immunized person, must also be considered prior to making any recommendations.


Any case(s) of smallpox should be reported immediately to the local medical officer of health by telephone. The disease should be reported even if it is only suspected and has not yet been confirmed.

For more information
Call the ministry INFOline at 1-800-268-1154
(Toll-free in Ontario only)
In Toronto, call 416-314-5518
TTY 1-800-387-5559
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