Monkeypox treatment: Smallpox antiviral shows promise

• In a new study, researchers describe seven cases of monkeypox that occurred in the United Kingdom between 2018 and 2021, the first cases of in-hospital and household transmission outside of Africa.
• These monkeypox patients received two antiviral medications as treatment, one of which reduced the length of symptoms.
• All patients made a full recovery following treatment.

The monkeypox virus, which is related to smallpox, is endemic to Central and West Africa. It can cause a range of symptoms including headache, skin lesions, fever, body aches, swollen lymph nodes, and fatigue.

Since the first report of monkeypox in 1970, cases of monkeypox in humans have rarely occurred outside of the African continent. However, since early May 2022, several cases have emerged in Europe, Australia, Canada, and the United States.

Although doctors can reliably identify and diagnose monkeypox, much remains unknown about the virus, including the dynamics of its transmission, the full range of symptoms it causes, and how best to treat it.

In a new clinical study that appears in The Lancet Infectious Diseases, researchers describe the first cases of in-hospital and household transmission of monkeypox outside of Africa.

They detail the clinical features of the infection and its management, including the use of an antiviral drug that could reduce the length of the contagious period and time of recovery.

Monkeypox cases in the United Kingdom

The report looks at seven cases of monkeypox occurring in the United Kingdom between 2018 and 2021. In three of these cases, the individuals acquired the virus in the U.K. These represent the first cases of in-hospital and household transmission of monkeypox outside ofAfrica. In the remainder of the cases, the individuals became infected with the virus in Nigeria.

Dr. Nick Price of Guy’s & St Thomas’ NHS Foundation Trust in London, U.K., senior author of the paper, explained the importance of sharing these data:

“Until now, monkeypox has been a rare, imported condition in the U.K. and the NHS [National Health Service] High Consequence Infectious Diseases Network has treated all seven of the U.K.’s confirmed cases until 2021. Outbreaks outside of Africa are unusual but in recent days, significant outbreaks have been reported in several European countries, including the U.K., and further afield globally. Clinical trial data is lacking and we are pleased to share some of our collective experience in managing this previously rare and sporadic condition.”

The symptoms described include fever, headache, night sweats, and skin lesions, with complications including deep tissue abscesses, pain, and low mood. However, none of the patients experienced severe complications from the infection, such as lung inflammation or sepsis.

In previous outbreaks, doctors considered patients no longer to be infectious when all their skin lesions had crusted. This study, however, found viral DNA in the respiratory tract of several patients for at least 3 weeks — indicating that they were still infectious after skin lesions had crusted.

This is an important finding, as most cases of monkeypox previously have occurred in parts of the world where PCR testing is not readily available, and so these data had not been available either.

Antiviral treatment

The study also trialed the use of two antiviral medicines — brincidofovir and tecovirimat — which doctors have traditionally used to treat smallpox. Tecovirimat is now approved for the treatment of monkeypox in the European Union and the U.S. It is not approved for this use in the U.K.

Although treatment with brincidofovir led to short-term reductions in viral load, these improvements were not lasting and the patients developed side effects affecting the liver, meaning that their treatment had to be stopped early.

One person received tecovirimat, and doctors observed a shortening in the length of their symptoms and of the time this person was contagious.

Although the researchers cannot say for sure whether this was a direct result of tecovirimattreatment, the results suggest tecovirimat could help to prevent progression to severe disease and shorten the time spent in hospital. They recommend a 2-week course of treatment in order to fully clear the virus.

Speaking to Medical News Today, Dr. Stephen Morse, professor of epidemiology at the Columbia University Medical Center, and director of the Infectious Disease Epidemiology Certificate Program, noted that “tecovirimat is the most effective known antiviral for the orthopoxviruses, which includes smallpox — now officially eradicated — monkeypox, and others.”

“The mechanism of action of the drug, and the relatedness of these viruses, suggests that tecovirimat should be equally effective for other orthopoxviruses, but rigorous comparisons have not been possible because of small case numbers,” he added.

Complex management

Most of the patients whose cases the researchers described in this study experienced a relatively mild illness and made a full recovery. However, all the patients were young, had no preexisting conditions, and became infected with the West African clade of monkeypox, which is typically milder than the Congo Basin clade.

The Congo Basin clade of monkeypox has a case fatality rate of 10.6%, compared to 3.6% for the West African clade.

Despite the mild symptoms experienced by patients, the authors highlight the challenging nature of managing monkeypox, even in the high-income context of the U.K.

They say that healthcare workers should remain alert to the possibility of monkeypox in travelers with a fever and rash. They also say networks of specialist treatment centers will be important to help manage monkeypox patients.

“The cases reported in our study, in addition to the recent outbreaks, highlight the importance of maintaining a collaborative network of centers on standby to manage sporadic, outbreaks of high consequence pathogens, such as monkeypox,” says Dr. Price.

“The cases we observed were challenging and resource-intensive to manage, even in the high-income setting of the U.K. With international travel returning to pre-pandemic levels, public health officials and healthcare workers around the world must remain vigilant to the possibility of new cases of monkeypox,” he adds.

It is important to note that this study is observational and based on a small number of cases — seven in total, and only one patient treated with tecovirimat. The authors say that more research is needed into the use of antivirals to treat the disease.

Dr. Morse also emphasized this aspect. While he called this “an interesting case report series, [with] the individual patients […] well characterized,” he cautioned that “the numbers are too small to draw conclusions.”

Still, according to him, the study brings care for people who become ill with monkeypox one step further.

“[T]his paper adds to the suggestion that tecovirimat should be useful in treating human monkeypox infections as well as the others. The drug has an excellent safety profile, tested in human volunteers,” Dr. Morse told us.

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