Monkeypox: Why the sudden concern?

Just as the world adapts to a new normal after the COVID-19 pandemic, a new outbreak of a not-so-new virus has been making headlines. But why the sudden concern?

In west and central Africa, annual incidence of human monkeypox is in the hundreds, with the few cases detected outside these regions tied to either travel to Africa or contact with imported infected rodents. [Lancet Infect Dis 2022;doi:10.1016/S1473-3099(22)00354-1]

In this current outbreak, the first case of monkeypox was reported to the UK Health Security Agency on May 7, 2022, in the UK, and occurred in an individual with travel history to Nigeria. Another two cases were detected 1 week later in two occupants of the same household who had neither travel history to Africa nor contact with the first case.

One of the major concerns is that there are no “substantial links” between the cases of monkeypox and areas in Africa where the disease is endemic, remarked author of the Lancet commentary, Professor Alimuddin Zumla from the Centre for Clinical Microbiology, University College London, London, UK, and co-authors.

“This could indicate that the monkeypox virus might already have been spreading undetected in Europe for a while, with human-to-human transmission occurring due to close physical contact with infected asymptomatic or symptomatic people,” Zumla said.

In the 2 weeks since the first detected case in the present outbreak in the UK, the number of cases have “surpassed the total number of cases detected in the UK and outside monkeypox-endemic Africa zones since the first discovery of monkeypox in 1970 as a human pathogen,” he continued.

The reason behind these incidents is yet unknown, with a change in transmission properties or increased virulence being potential causes.

These sentiments were echoed in an opinion paper published by Adjunct Assistant Professor Amesh Adalja and Professor Tom Inglesby from the Johns Hopkins Center for Health Security and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, US.

“Few clinicians practising in the US have ever seen a case of monkeypox infection,” they said. Recent events have highlighted the increased importance of identifying the infection in order to swiftly and accurately manage the disease and prevent an outbreak. [Ann Intern Med 2022;doi:10.7326/M22-1581]

 

Why the sudden outbreak?

A member of the orthopoxvirus family, monkeypox in humans first came to attention during the campaign to eradicate another member of this family, smallpox. An intensive programme to eradicate smallpox globally was initiated in 1967 and was successful, leading to a declaration of smallpox eradication at the 33rd World Health Assembly in 1980. [https://www.cdc.gov/smallpox/history/history.html, accessed 20 June 2022]

One theory behind the recent increase in monkeypox outbreaks is the diminished population immunity to smallpox, given that smallpox vaccination programmes were ceased decades previously, wrote Adalja and Inglesby.

“The [monkeypox] virus had not been detected outside of Africa before 2003. The highest rates of illness in Africa have historically been noted in children who had not received smallpox vaccination. It is also possible that changes in land use are putting more people in proximity to animals that carry the virus,” they said.

Furthermore, secondary human-to-human contagion has been limited in the past despite cases being imported by travellers who were exposed in endemic regions.

 

Identifying and diagnosing cases

There is currently no commercially available test to detect monkeypox, said Adalja and Inglesby. In the US, state public health laboratories can conclusively diagnose the infection through PCR testing of skin lesions or fluid. Physicians should be on the lookout for certain symptoms ie, febrile illness and a rash which begins in the mouth and moves to the face and extremities in a centrifugal pattern. This would be of particular concern in the presence of lymphadenopathy.

 

Utilizing smallpox treatments 

At present, there is no standard-of-care treatment for monkeypox, though in the past, treatments for smallpox have been utilized for this infection.

A retrospective, observational study from the UK published in The Lancet looked at seven patients (four men, three women) who had been diagnosed with monkeypox in the UK between 2018 and 2021. [Lancet Infect Dis 2022;doi:10.1016/S1473-3099(22)00228-6]

Patient data were obtained from the high consequence infectious diseases (HCID) network. Of the seven patients, three acquired the infection while in the UK (one patient was a healthcare worker who acquired the virus nosocomially, and one patient acquired the virus while abroad and transmitted it to an adult and child within their household).

Disease features included viraemia, prolonged monkeypox virus DNA detection in upper respiratory tract swabs, reactive low mood, and monkeypox virus PCR-positive deep tissue abscess. Prolonged PCR-positivity led to >3 weeks of isolation in five patients. 

The patients were treated with either oral brincidofovir or tecovirimat, both of which are approved for the treatment of smallpox and have shown benefits in animals with monkeypox.

The three patients treated with brincidofovir (200 mg QW) experienced elevated liver enzyme levels warranting treatment cessation. Conversely, the one patient who was treated with tecovirimat (200 mg BID for 2 weeks) did not experience adverse effects and additionally, had a shorter duration of disease and viral shedding (hospitalized for 10 days) compared with the other patients.

 

Steps moving forward

Between January 1 and June 15, 2022, there have been 2,103 laboratory confirmed and one probable case of monkeypox reported to the WHO from 42 countries across the Regions of the Americas, Africa, Europe, Eastern Mediterranean, and Western Pacific. A majority (84 percent) were reported in Europe. [https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON393, accessed 20 June 2022]

“The most pressing immediate challenge is to unravel the epidemiology of this outbreak,” remarked Adalja and Inglesby. Questions that need to be answered include the reason behind the outbreak and how the virus is spreading (eg, social networks, clusters).

According to Zumla, the current focus should be on preventing further transmission and protecting high-risk individuals and healthcare workers.

“[C]ontainment efforts will rely on enhanced case finding, isolation, contact tracing, and postexposure vaccination,” said Adalja and Inglesby. They noted the vital role played by primary care, urgent care, and emergency medicine physicians, dermatologists, and individuals working in sexually transmitted infection clinics in identifying new cases of monkeypox.

 

A name change in sight

On June 14, 2022, WHO Director-General Dr Tedros Adhanom Ghebreyesus announced that a potential name change for the monkeypox virus, its clades, and subsequent disease is in the works. This announcement was in response to an article by several scientists who called for nomenclature for infectious diseases to be “neutral, non-discriminatory, and non-stigmatizing.” [https://virological.org/t/urgent-need-for-a-non-discriminatory-and-non-stigmatizing-nomenclature-for-monkeypox-virus/853, accessed 20 June 2022]