Human monkeypox is a zoonosis caused by monkeypox virus, an orthopoxvirus and close relative of the smallpox virus (smallpox). It was first reported in central Africa in 1970 and has historically affected some of the poorest and most marginalized communities in the world.
The clinical syndrome is characterized by fever, rash, and lymphadenopathy. Complications of monkeypox may include pneumonitis, encephalitis, sight-threatening keratitis, and secondary bacterial infections.
Published mortality rates vary substantially and are vulnerable to case ascertainment bias. Case fatality rates ranging from 1% to 10% have been reported in outbreaks in the Congo Basin, and the virus clade circulating in this region appears to be associated with increased virulence. The West African clade, which is responsible for the recent outbreaks in Nigeria, is associated with a lower overall mortality rate consistently below 3%. To date, most reported deaths have occurred in young children and people with HIV.
Human-to-human transmission of monkeypox is well described, including nosocomial and domestic transmission.
However, chains of human-to-human transmission have historically been less recognized. A pooled estimate from a systematic review suggested a secondary attack rate of approximately 8% (range 0 to 11%) among household contacts who were not vaccinated against smallpox.
Understanding of in vivo viral kinetics and infectivity is poor, and the clinical significance of prolonged viremia and skin peeling remains uncertain.
Background
Cases of human monkeypox are rarely seen outside of western and central Africa. There are few data on viral kinetics or the duration of viral shedding, and there are no licensed treatments.
Two oral medications, brincidofovir and tecovirimat, have been approved for the treatment of smallpox and have demonstrated efficacy against monkeypox in animals.
Our objective was to describe the longitudinal clinical course of monkeypox in a high-income setting, along with viral dynamics and any adverse events related to new antiviral therapies.
Methods
In this retrospective observational study, we report the clinical characteristics, longitudinal virological findings and response to unapproved antivirals in seven monkeypox patients who were diagnosed in the United Kingdom between 2018 and 2021, identified through a retrospective note review. of cases.
This study included all patients who were managed at dedicated high consequence infectious diseases (HCID) centers in Liverpool, London and Newcastle, coordinated through a national HCID network.
Results
We reviewed all cases since the inception of the HCID (air) network between August 15, 2018 and September 10, 2021, identifying seven patients . Of the seven patients, four were men and three were women. Three acquired monkeypox in the UK: one patient was a healthcare worker who acquired the virus nosocomially, and one patient who acquired the virus abroad transmitted it to an adult and a child within their household.
Notable features of the disease included viremia, prolonged detection of monkeypox virus DNA in upper respiratory tract smears, reactive moodiness, and one patient had a deep tissue abscess with PCR-positive monkeypox virus. .
Five patients spent more than 3 weeks (range 22-39 days) in isolation due to prolonged PCR positivity.
Three patients were treated with brincidofovir (200 mg once weekly orally), all of whom developed elevated liver enzymes leading to discontinuation of treatment.
One patient was treated with tecovirimat (600 mg twice daily for 2 weeks orally), experienced no adverse effects, and had a shorter duration of viral shedding and illness (10 days of hospitalization) compared to the other six patients. One patient experienced a mild relapse 6 weeks after hospital discharge.
Cutaneous and soft tissue manifestations of monkeypox. Skin and soft tissue features included: (A and D) vesicular or pustular lesions; B and C) macular lesions on palms and soles; (D and E) a subungual lesion; (F and G) more subtle papules and smaller vesicles; (H) and a deep abscess (arrow, image obtained during ultrasound-guided drainage).
Interpretation
Human monkeypox poses unique challenges, even for well-resourced healthcare systems with HCID networks.
Prolonged shedding of viral DNA from the upper respiratory tract after resolution of the skin lesion challenged current infection prevention and control guidance.
There is an urgent need for prospective studies of antivirals for this disease.
Added value of this study
Defined by the UK Health Security Agency as a high consequence infectious disease (HCID), our retrospective case series represents imported, nosocomial and domestic transmission of monkeypox, which has not been previously described in the UK. . We report the first use of antiviral agents in monkeypox patients, with three patients receiving brincidofovir and one receiving tecovirimat.
Brincidofovir was not found to confer any compelling clinical benefit and was associated with impaired liver function tests in all cases. The patient treated with tecovirimat had a shorter duration of symptoms and viral shedding from the upper respiratory tract than the rest of the patients in the series, with no adverse events identified before discharge.
Several of the patients experienced prolonged viremia and viral shedding from the upper respiratory tract after crusting of all skin lesions, leading to prolonged isolation in hospital.
Implications of all available evidence
Monkeypox is an emerging global health threat, capable of spreading across borders and subsequently transmitted. Although optimal infection control and treatment strategies have not been established for this potentially dangerous pathogen, our first-use data suggest that brincidofovir has poor efficacy; however, prospective studies of tecovirimat in human monkeypox are warranted.
The infection control implications of viral shedding from the upper respiratory tract should be considered in future outbreaks.
Contagion
Clinical picture
Diagnosis
Treatment and prevention
|
