The first human case of monkeypox was recorded in 1970, yet the viral disease is only getting international attention since it has spread outside Africa to 27 non-endemic countries.

The World Health Organization’s (WHO) Dr Ebrahima Socé  Fall described monkeypox as a “neglected tropical disease” when he opened a two-day meeting called by the WHO’s R&D Blueprint to determine research priorities last Thursday.

“We need to stop the chain of transmission and we believe at this stage we can still stop the chain of transmission in non-endemic countries by ensuring surveillance in certain population groups, cross investigation contact tracing, and maybe vaccination,” said Fall, WHO’s Assistant Director-General for Emergencies Response. 

However, WHO scientist Ana Maria Restrepo stressed at the meeting’s conclusion that the viral disease had to be addressed in the nine African countries where it is endemic.

“The problem starts and has to be resolved at the level of the endemic countries,” said Restrepo, co-convenor of the R&D Blueprint that called the meeting, at the conclusion of the meeting.

“There are researchers of high quality in these countries, and they are doing high-quality research despite the limitations, and our commitment is to support them.” 

Squirrel pox?

The intention of the meeting – attended virtually by over 500 scientists – was to identify research priorities, and when it ended on Friday afternoon, the scientists had identified a long list of unknowns.

One of the big questions is whether there is an “unknown animal reservoir” for monkeypox – with squirrels and rats being fingered as the most likely suspects. The Central African sun squirrel is particularly susceptible to monkeypox – and one researcher suggested the pox might have been more aptly named after it.

“What was the first reservoir?” asked Dr Paul Fine of the London School of Hygiene and Tropical Medicine.  

“We think monkey because of the name monkeypox, but there were studies in a number of other species and it was found in several of them, in particular squirrels, particular the sun squirrel of Central Africa. So one might ask if this name is appropriate. Is it just monkeypox or are there other species very importantly, involved as reservoirs?”

Professor Jean-Jaques Muyembe Tamfum, director of the DRC’s Institute de Recherche Biomedicale, said that the majority of monkeypox cases in his country were children infected by hunting and handling rodents and squirrels.  Adults were exposed to the virus by hunting monkeys.

“The virus enters the body through the broken skin, and spreads in the mucous membranes and eyes, nose and the rest,” said Tamfum.

Complications of monkeypox include bacterial conjunctivitis and even blindness.

Scientists also raised whether rodents could be infected by “spillover” from human waste.

The meeting resolved that a “comprehensive One Health approach” was needed to understand animal-to-human transmission and animal reservoirs.

Mutations and drivers

Genomic sequencing of the current strain of monkeypox spreading internationally shows that it has 47 mutations when compared to a 2018 sample. 

This is surprisingly high, and one hypothesis is that the monkeypox virus has been mutating in an unknown animal – or perhaps more than one animal behind the two different clades – the Central African clade with a mortality rate of around 10% and the West African clade with a 2-3% fatality rate.

Aside from the international spread of monkeypox, there has also been a dramatic increase in cases in endemic countries especially DRC and Nigeria.

Nigeria’s Professor Dimie Ogoina told the meeting that his country was also seeing an increase in cases in areas where it had not previously been seen.

Scientists thus want to unpack what is driving the transmission, as monkeypox is not known to be particularly infectious. In the past, infected people only passed the virus on to about 8-15% of the people living in the same house.

The European outbreaks appear to stem from sexual contact at two events – in Berlin and on the Canary Islands, according to news reports. 

This is not typically how it has been transmitted, and the meeting raised a number of questions about sexual transmission – particularly whether it can be transmitted via semen and vaginal fluid, not just through contact with the infected lesions. 

“Monkeypox manifests in rashes. Would a person still engage in sex with these rashes? We need to look at asymptomatic transmission,” said Ogoina.

Tricky diagnosis

In Nigeria, men are significantly more likely to get monkeypox than women, raising questions about what makes them more vulnerable.

Ogoina, from Niger Delta University, also revealed that people coinfected with HIV and monkeypox had “bigger lesions” and were more likely to have genital lesions – although only five such patients were examined.

“It is very important just to recognise that the vast majority of recent cases, especially in DRC, are suspected cases or their probable cases or possible cases, they’re not confirmed,” stressed Fine.

Some of the symptoms of monkeypox are similar to those of syphilis and chicken pox, and the meeting identified the need for better diagnostics.

“WHO, through our regional offices, is working with African countries, regional institutions, technical and financial partners, to increase the ability to support disease surveillance laboratory diagnostics, readiness and response actions related to monkeypox,” said WHO epidemiologist Maria van Kerkhove. 

“We have to acknowledge the fact that this virus has been circulating for decades, and we now have attention to this. This unfortunately is a sad reality of the world that we live in. But we need to use this as an opportunity to advance our understanding of this virus to help everyone everywhere dealing with monkeypox,” said Van Kerkhove. 

Implementing COVID lessons

Professor Helen Rees, who moderated the two-day meeting, said that COVID-19 had shown the need for rapid global responses to emerging health threats.

Rees called for “partnerships, collaboration, strategies that get us into the field quickly, antivirals and vaccines”. 

“We’re also seeing this interface with One Health, with environmental degradation and climate change. All of these things are coming to the fore. Just to underline this is not a pandemic, this is an outbreak that we are scratching our heads about. But the fact that we should respond now and rapidly is really excellent,” added Rees, a renowned scientist from South Africa’s University of Witwatersrand.

WHO scientist Ana Maria Restrepo concluded the meeting by stressing that it was important to practice what had been preached during COVID-19.

“We talked very much about the new health architecture for response to pandemics, and the lessons learned,” said Restrepo. “We are convinced that showing a good response for this multi-country outbreak is our best example of how we are going to be prepared for the next pandemic. 

“If we do when we all preach, we work together if we collaborate, we use master protocols, if we engage the countries; the communities – if we learn those lessons, and if we put equity at the centre of the discussions, then yes we have learned our lessons and we are moving forward towards being better prepared,” said Restrepo.

Expedited studies

The meeting concluded with experts calling for expedited studies to better understand the disease epidemiology, clinical consequences, and modes of transmission. 

While the smallpox vaccine offers over 80% against monkeypox, it is unclear whether this protection endures – and smallpox vaccination was discontinued in the 1970s. The experts emphasized the need for clinical studies of vaccines and therapeutics to better document their efficacy and understand how to use them in this and future outbreaks. 

The meeting also called for immediate implementation of public health activities including communicating prevention information, enhanced disease surveillance, contact tracing, isolation of cases and optimized care of people with the virus.