In a recent retrospective case series study published in the journal Lancet Infectious Diseases, researchers from the United Kingdom (UK) unveil the details of imported, household, and hospital transmission of monkeypox and report the first usage of two specific antiviral agents in the treatment of this disease.
Monkeypox is a zoonotic viral disease and an emerging global health threat capable of cross-border spread and onward transmission. Although much milder than smallpox which belongs to the same viral family, human monkeypox poses distinctive challenges – even to well-resourced healthcare systems.
With the exception of a large outbreak associated with imported rodents in the United States (US) in 2003, monkeypox transmission has been restricted to remote locations in central and west Africa. However, there have been several outbreaks in more densely populated centers in the past five years, raising concern about the global dissemination of the disease.
Currently, there are no licensed treatment approaches for human monkeypox. In the US, two orally bioavailable drugs were approved to treat smallpox in the case of a potential bioterrorism attack, and these were brincidofovir and tecovirimat. However, neither drug has been studied in human efficacy trials.
In the wake of the current outbreak of monkeypox around the world, a research group led by Dr. Hugh Adler from the Liverpool University Hospitals NHS Foundation Trust and the Liverpool School of Tropical Medicine in the UK decided to conduct a retrospective observational study to fully appraise clinical manifestations and treatment efficacy of the aforementioned drugs.
A detailed retrospective case-note review
In this study, researchers have reported various clinical features, virological findings, and responses to off-label drugs in seven patients with monkeypox identified in the UK between 2018 and 2021 through a retrospective case-note review.
All infected individuals managed in dedicated high consequence infectious diseases centers in Liverpool, London, and Newcastle were included in the study. Of note, the usage of novel therapeutics was approved by the relevant National Health Service (NHS) Trust’s medicines governance group.
Moreover, laboratory testing from virology samples (with monkeypox viral PCR) was primarily driven by clinical indications rather than a formally established protocol. Serological testing was not pursued, considering the high specificity of molecular diagnostics; however, serum from four individuals in contact with monkeypox has been tested.
Miscellaneous clinical presentation and drug response
Researchers have reported seven cases of patients with human monkeypox infection diagnosed in the UK. All patients were young with no pre-existing disease, and four of them acquired monkeypox outside of the UK, while three were infected inside the country.
All seven patients had various skin lesions (including papules, vesicles, pustules, ulcers, and scabs) that were positive for monkeypox virus DNA on PCR. Viral DNA was detectable in upper respiratory tract swabs and blood for six patients and urine for four patients. The reactive low mood has been detected in patients as well.
The first three patients in 2018 were treated with oral brincidofovir, which was available via approved and urgent repurposing of an existing supply from a local clinical trial. The patient in 2021 was offered tecovirimat due to its results in animal models and good tolerability. Still, it was difficult to infer the relationship between treatment with these drugs and disease course.
“Although optimum infection control and treatment strategies for this potentially dangerous pathogen are not established, our first-use data suggest brincidofovir has poor efficacy; however, prospective studies of tecovirimat in human monkeypox are warranted,” emphasize study authors.
Implications for current and future outbreaks
This case series underscores the importance of keeping a collaborative network of centers on standby to oversee sporadic, small numbers of patients with high consequence pathogens. Considering the upper respiratory tract viral shedding, infection control measures should be considered in the current and future outbreaks.
“The disease course of the patients we report on were challenging and resource-intensive to manage, even in the high-income setting of the UK,” say study authors. “Our observations in this small series support further research into antivirals to treat this neglected tropical disease,” they add.
In any case, monkeypox outbreaks will continue to emerge in west and central Africa; hence, healthcare workers around the globe must be vigilant to the possibility of monkeypox introduction from travelers presenting with rash and fever, as well as a plethora of other symptoms.