An analysis of seven monkeypox cases in the UK between 2018 and 2021 has revealed that some antiviral drugs may alleviate monkeypox symptoms.
The retrospective study analysed the first cases of in-hospital and household transmission of monkeypox outside of Africa, examining the potential of two antivirals – brincidofovir and tecovirimat – to reduce symptoms of the virus. The brincidofovir antiviral medication displayed little clinical benefit; however, tecovirimat demonstrated potential for remedying monkeypox symptoms.
Currently, there is no standard of care for monkeypox, as optimal infection control and treatment strategies have not been established. The study findings, published in The Lancet Infectious Diseases, may help further global understanding of the clinical features of monkeypox and transmission dynamics.
Dr Hugh Adler, the lead author of the study from Liverpool University Hospitals NHS Foundation Trust, said: “As public health officials are trying to understand what is causing the May 2022 monkeypox outbreaks in Europe and North America – which have affected several patients who reported neither travel nor an identified link to a previously known case – our study offers some of the first insights into the use of antivirals for the treatment of monkeypox in humans.
“Although this latest outbreak has affected more patients than we had previously encountered in the UK, historically monkeypox has not transmitted very efficiently between people, and overall, the risk to public health is low.”
Dr Nick Price of Guy’s & St Thomas’ NHS Foundation Trust, the senior author of the paper, commented: “The cases reported in our study, in addition to the recent outbreaks, highlight the importance of maintaining a collaborative network of centres on standby to manage sporadic, outbreaks of high consequence pathogens, such as monkeypox. The cases we observed were challenging and resource-intensive to manage, even in the high-income setting of the UK. 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.”
The monkeypox outbreak
Monkeypox is a rare disease that the UK Health Security Agency classifies as a High Consequence Infectious Disease (HCID) and is a close relative of the smallpox virus. No licensed monkeypox treatments currently exist, and the duration of the infection is currently unknown due to limited information, although the incubation period ranges from five to 21 days, with patients usually isolated in a specialised facility to mitigate the spread of infection.
The virus is transmitted from animals to humans, predominantly through a bite or by eating improperly cooked, contaminated meat, but in rare cases can be spread via human-to-human transmission. Monkeypox usually occurs in Central and Western African countries; however, the recent outbreak of the disease has seen it travel to the US, Canada, Australia, Spain, Portugal, and the UK.
Monkeypox symptoms include fever, rash, and swollen lymph nodes, with further complications such as inflammation of the lungs and brain, sight-threatening inflammation of the cornea, and secondary bacterial infections also reported. Mortality rates of the virus vary significantly, ranging from 1-10% in the Congo Basin to less than 3% in Nigeria.
Treating monkeypox symptoms with antivirals
The team observed four patients who were treated for monkeypox in HCID units in England between 2018 and 2019, with three of these cases imported from West Africa. The fourth case occurred in a healthcare worker 18 days after initial exposure to monkeypox and is the first example of the virus being transmitted in a hospital setting outside of Africa.
The first three patients were treated with brincidofovir seven days after experiencing the initial rash, but no convincing clinical benefit was observed from the antiviral. The team explained that it is unknown whether administering the drug earlier would have achieved different outcomes, but all patients made a full recovery regardless.
In 2021, three more cases of monkeypox were identified in a family travelling to the UK from Nigeria, two of the cases being the first examples of household transmission outside of Africa. One of the patients was a child, who was observed closely due to the high mortality rate from monkeypox among children, although the illness was mild and they made a full recovery.
One of the patients was treated with tecovirimat, which resulted in a shorter duration of monkeypox symptoms and upper respiratory tract viral shedding than the other patients. Despite yielding promising results, the team explained that due to the small sample size of the cohort, further investigations are required to establish the effectiveness of tecovirimat.
All three of the patients were cared for in a hospital setting for infection control purposes and not because of the severity of the infection. Moreover, no patients experienced serious monkeypox complications such as sepsis or pneumonia, although one experienced a mild relapse six weeks following discharge from the hospital and another developed a deep tissue abscess that required drainage.
Dr Catherine Houlihan, a co-author of the paper from the UK Health Security Agency and University College London, concluded: “During previous outbreaks of monkeypox, patients were considered infectious until all lesions crusted over. In these seven UK cases, viral shedding was observed for at least three weeks following infection. However, data on infectivity remains limited and is an important area for future study.”
The investigators noted that the observational nature and the small number of cases analysed are limitations of the study. Furthermore, they were unable to confirm positive monkeypox PCR test results with laboratory samples of the virus, meaning they could not verify the ongoing shedding of the virus.