Monkeypox: Small study points to a promising antiviral.

• 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 1970Trusted Source, 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 DiseasesTrusted Source, 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.

Trusted Source 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%Trusted Source, 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.

Zoonotic diseases: Why are infections from animals so dangerous to humans?

An international report from 2012, for example, informed that a total of 56 such diseases were responsible for 2.5 billion cases of illness and 2.7 million deaths across the globe each year. These illnesses included rabies, toxoplasmosis, Q fever, Dengue fever, avian influenza, Ebola, and anthrax.

Furthermore, respiratory, flu-like diseases acquired from animals wreaked havoc in the past century. The Spanish flu caused 50 million Trusted Sourcedeaths in 1918, and the Hong Kong flu caused 700,000 deaths in 1968.

So, why are diseases that humans acquire from animals so dangerous? Part of it is due to our immune system. Part of it is natural selection. The specific animal that transmits the virus may also play a role.

Below, we explore some of these factors and how they intertwine.

Animal virus vs. the human immune system

One reason viruses from animals are so dangerous to humans is that people have no means to deal with them. Our immune system was never ‘introduced’ to these novel viruses, so it doesn’t know how to respond to the uninvited guest.

Researchers explain that most of the viruses that enter the human body are successfully destroyed by the immune system or pass through our gastrointestinal system. However, now and then, an animal virus manages to replicate within a human host.

The moment where the animal virus replicates within the body of the first human is crucial. At this critical point, the virus can mutate and evolve “under the selective constraints of the human body for the first time, adapting and improving itself for replication in this new host.”

As this occurs, the human immune system must retaliate. It needs to ‘catch up’ with the virus’ evolution and create an immune response. The human body has never been confronted with this threat before, and therefore, has no pre-existing immunity in its arsenal — so it must devise one fast.

But, this defense — part of the adaptive immune system — takes days or longer to activate. In the meantime, the virus may have already evolved to replicate faster or even escape the immune system’s retaliation.                                                                                                                                     An ‘evolutionary arms race’ 

In other words, the animal virus and the human immune system have entered an ‘arms race’ — and like with any arms race, one of the two competitors could win, or both competitors could reach a stalemate.

Medical News Today spoke to Christopher Coleman, assistant professor of Infection Immunology at the University of Nottingham in the United Kingdom, about animal viruses, human hosts, and the role of evolution and natural selection.

“[T]he general assumption,” he explained, “is that as viruses evolve to a host, they become less dangerous to that host (they want to ensure their own transmission so don’t want to rapidly kill the host before they get a chance [to replicate]).”

Furthermore, a “virus that fully adapts to an animal host may be completely harmless to humans,” Coleman continued.

The scientist — whose main research focuses on ‘highly pathogenic human coronaviruses’ — gave examples of aggressive animal viruses within the coronavirus family. These include the “‘infectious bronchitis virus’ of chickens, ‘feline infectious peritonitis virus’ in cats, or ‘transmissible gastroenteritis virus,’ which is near 100% fatal in piglets.”

“None of these [viruses] are known to infect or cause any disease in humans,” Coleman said.

“On the other hand, a virus that evolves in animals but also has an ability to infect humans may be more deadly if and or when it infects humans.”

This may be especially true when the animals’ immune systems are very different from those of humans, or when the animals have special defense mechanisms that humans lack.

Bats and their ‘hyper-vigilant’ immunity

For instance, the fact that very harmful viruses such as SARS, MERS, and Ebola have all originated in bats begs the question — what do bats have that we don’t?

How can bats fly around carrying viruses that, in some cases, are extremely deadly to humans (such as Ebola), but that do not seem to harm these creatures in the slightest?

A new study, led by Cara Brook, a postdoctoral Miller Fellow at the University of California Berkeley, asked this very question. The research shows how bats’ unique immune capabilities enable them to carry and maintain a high viral load without getting sick themselves.

“[S]ome bats,” explain Brook and colleagues in their paper, “have an antiviral immune response called the interferon pathway perpetually switched on.”

Source - Medical News Today