The last field case of smallpox occurred in 1977 and, except for a laboratory accident in 1978, there have been no human cases of smallpox since. Smallpox itself is only likely to re-emerge via an accident at the known repositories in Atlanta (US) and Novosibirsk (Russia), or if a misplaced vial of virus from the smallpox era is mishandled. The use of smallpox as a biological weapon has not occurred for over a century. More harm has resulted from vaccination with replication-competent vaccinia amongst military personnel than from actual exposure to smallpox since 1979. If smallpox is suspected, immediately isolate the patient and notify the regional infectious diseases unit. All suspected cases should be managed by experts, including public health officials, to prevent a potential emergency situation. Since smallpox no longer exists as a naturally occurring disease, a single laboratory-confirmed case of smallpox would be considered an outbreak. Many other conditions may present in a similar way to smallpox and, therefore, it is important to keep in mind possible differentials as, since the eradication of smallpox, these are far more likely to be the cause.

Monkeypox is an Orthopoxvirus, a closely related virus to smallpox that causes a very similar, but milder, illness. Monkeypox is difficult to eradicate because of the presence of animal reservoirs in West and Central Africa. Thus, if a smallpox-like syndrome is encountered, it is likely to be caused by another illness (e.g., chickenpox or a drug reaction); if there are epidemiological links with West or Central Africa, monkeypox becomes a possible diagnosis. These epidemiological links may not be immediately obvious if the virus has been introduced by importation of an animal carrier such as an African squirrel. Monkeypox virus infection is a notifiable condition.

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