Tecovirimat approved in Europe for the treatment of orthopoxvirus disease
The European Medicines Agency has recommended that the antiviral drug tecovirimat be approved for the treatment of smallpox, monkeypox, and cowpox in adults and children with body weight at least 13 kg. It is also indicated to treat complications due to replication of vaccinia virus following smallpox vaccination.
Tecovirimat is a synthetic small antiviral molecule which inhibits orthopoxvirus peripheral membrane protein (VP37) activity. Its effectiveness was predicted from studies that showed improved survival in animals. The most common adverse effects are headache and nausea.
Although naturally occurring smallpox was eradicated in 1980, there have been long standing concerns that the variola virus could be used as a bioweapon. Cases of monkeypox have been reported in various countries over the last few years, with 3 cases reported in the UK this year.
Tecovirimat is approved in the US for the treatment of smallpox.
Human smallpox has been eradicated since 1977, but monkeypox is endemic in West and Central Africa. Cases of monkeypox have also been reported in the UK, the US, Israel, and Singapore.
If smallpox is suspected, the patient should be isolated immediately and the regional infectious diseases unit notified. All suspected cases should be managed by experts, including public health officials, to prevent a potential emergency situation. Monkeypox is also a notifiable condition.
Many other conditions present in a similar way, so it is important to keep in mind possible differentials as, since the eradication of smallpox, these are far more likely to be the cause.
Management is centred around isolation of the patient, infection control measures, and supportive care. Antiviral therapies are also now available.
Smallpox is prevented by vaccination, and is only recommended for laboratory staff working with orthopox viruses, and public health and health care response team members.
Viruses belonging to the Poxvirus family (genus Orthopoxvirus) that can naturally infect humans and mammals include variola virus (smallpox), monkeypox virus, vaccinia virus, cowpox virus, buffalopox virus, camelpox virus, and cantagalo virus. This topic focuses on human disease associated with smallpox and monkeypox infection.
Smallpox was a serious, contagious, and often fatal infectious disease caused by the variola virus. It was declared eradicated in 1980 following a global immunisation campaign led by the World Health Organization, with the last known natural case reported in Somalia in 1977. Smallpox infection generally resulted in acute onset fever and malaise, followed by a distinctive skin rash (i.e., raised firm lesions with umbilication) mainly occurring on the face, arms, and legs. It was mainly transmitted between humans through the respiratory route (i.e., via saliva droplets); however, transmission from direct contact with infected bodily fluids was also reported. The incubation period of variola virus was 7 to 17 days with rash typically appearing 4 to 7 days later; the most infectious period was during the first week of illness.
Monkeypox is a rare disease that is clinically nearly identical to smallpox, although usually less serious. There is one distinctive feature of monkeypox, which is marked lymphadenopathy. The monkeypox virus can be transmitted to humans from different wild animals, such as non-human primates and rodents, although its natural host reservoir is unknown. Similar to smallpox, it can spread from human to human by the respiratory route or by direct contact with infected bodily fluids. The incubation period is usually 7 to 14 days, and disease typically lasts for 2 to 4 weeks.
History and exam
Tom Blanchard, DTM&H, PhD, FRCP
Consultant in Infectious Diseases
Department of Infectious Diseases and Tropical Medicine
North Manchester General Hospital
TB is the principal investigator on an MRC/Wellcome/Newton Fund grant to make a Zika vaccine based on recombinant modified vaccinia Ankara.
Jimmy Whitworth, MD, FRCP
Professor of International Public Health
London School of Hygiene & Tropical Medicine
JW declares that he has no competing interests.
Ashley Styczynski, MD, MPH
Epidemic Intelligence Service Officer
Poxvirus and Rabies Branch
Centers for Disease Control and Prevention
AS declares that she has no competing interests.
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