Four unknowns about monkeypox that show it is a neglected disease

When Covid-19 became a pandemic, humanity had only known about the existence of SARS-CoV-2 for a few months, so uncertainties outweighed certainties for months. Monkeypox is nothing like the coronavirus, but it does present a curious paradox: Although the first human case occurred in the 1970s, we know much less than we do today.with more than 1,200 cases detected in 28 non-endemic countries- we would like.
"An old enemy neglected", titled a recent editorial published in The Lancet Infectious Diseases. The virologist from the Icahn School of Medicine at Mount Sinai (United States) expressed himself in similar terms Gustavo Palacios in an interview published in elDiario.es. In it he lamented how little we knew about the disease and "how alone we leave countries that have these problems when we don't have them in the first world."
That is why the WHO had a meeting earlier this month with the aim of addressing the holes in the knowledge of monkeypox and try to fill them. Its director general, Tedros Adhanom Ghebreyesus, warned this week that the possibility of this virus establishing itself in non-endemic countries was "real", although still preventable.
The end of this story is still far away, but the latest report published by the UK Health Security Agency leaves room for optimism. With more than 300 confirmed cases, it is the most affected country outside of Africa and the first to sound the alarm. However, the document shows that the number of detections in England has not stopped falling since the end of May.
This optimism is limited to the countries capable of vaccinating those affected and their contacts, and of tracking the cases to try to control the spread of the disease and that Adhanom's words are not fulfilled. On the other side of the ring are the many unknowns that make it difficult to predict the future of outbreaks that are already the largest observed outside of Africa in all of history.
Since the beginning of the outbreaks, it has been repeated that the human smallpox vaccine —now eradicated— shows a high effectiveness against monkeypox, given the similarity between both viruses, of up to 85%. Some researchers, however, fear that this is a "zombie statistic", a figure that is repeated out of context without being entirely true.
The origin of that 85% is in an observational study conducted in the Democratic Republic of the Congo in the 1980s. The fact that it was not a clinical trial, was based on the tracing of a few hundred contacts, and that decades have passed since its publication invites caution when taking that percentage as something immutable
The biostatistician at Emory University (USA) Natalie Dean explains to elDiario.es that this does not mean that the vaccines do not work, but rather that we cannot know their exact effectiveness. "We have good immunological data on how well they work against monkeypox and that has led to their approval, but the real-world evidence is thinner," she says.
Dean clarifies that, although we can be sure of the benefit of vaccines, "the actual level of effectiveness could be different, higher or lower, than that 85% that is often cited." That is why he defends the evaluation of these drugs: "This information will help guide their use and will show the risk-benefit profile that will guide political decision-makers and individuals."
Bavarian Nordic is a Danish company until recently unknown to the general public. Today it has jumped into the media for being the producer of the only vaccine approved today against monkeypox, Jynneos.
As with the few antivirals developed against smallpox, the enormous demand has made countries like the United States question if they will achieve sufficient quantities to treat the sick and vaccinate their contacts in a ring. Similarly, Spain announced that for the moment it would only vaccinate those infected with the risk of getting seriously ill.
Despite this, the pharmaceutical expert in access to medicines, Belén Tarrafeta, is optimistic, especially after having seen the production capacity achieved with the Covid-19 vaccines. "[Bavarian Nordic] It assures that it can manufacture up to 48 million doses per year, and if it can produce the first million in three months, that would cover the needs of 50,000 infected people and a circle of 19 close contacts," he estimates.
Tarrafeta gives the case of the United Kingdom as an example, which since May has administered about 1,000 doses, which means about 5 for each case. For this reason, and although everything will depend on how the outbreaks develop, he does not consider there to be cause for alarm: "There are no large reserves of latest-generation vaccines, but the manufacturer says that it is capable of meeting the demand within a reasonable".
To all this must be added the reserves of the original vaccines against smallpox, which are estimated at hundreds of millions worldwide. However, its greater side effects make the balance between risks and benefits unclear against a much less dangerous virus. "Using these vaccines is out of the question," said the virologist at the University of Munich (Germany). Gerd Sutter in a newspaper article published in Science.
All this only applies to countries with access to vaccines and medicines. "When we say that monkeypox vaccination has started in earnest, it's important to mention where," criticized the virologist Boghuma Kabisen Titanji. "Not in African countries with ongoing outbreaks, which have seen 1,400 cases and 66 deaths this year alone."
The WHO claims that the case fatality rate for monkeypox has been between 3 and 6% in recent outbreaks, although he cites historical figures of between 0 and 11%. In the current outbreak, 66 people have died in African countries compared to 0 deaths seen to date outside the continent.
Although the outbreaks outside of Africa are not yet over, the explanation may range from the age of those affected – younger children are more vulnerable – to differences in health systems and the health status of each population.
The virologist at the Icahn School of Medicine at Mount Sinai (United States) Gustavo Palacios explained in his interview that, although there was no evidence that the virus circulated in rodents outside of Africa, the opposite could not be confirmed either. "If there was a surveillance system, it could tell you that it doesn't circulate in the animals in the area, but we don't know because there is no support to do it or to look for it in the endemic area."
Finding the origin and reservoirs of animal viruses like this is not easy, and this has been demonstrated by SARS-CoV-2 to date. In the case of monkeypox, it's not even clear where the virus is when it's not infecting humans. Rodents such as squirrels and rats are considered the main reservoirs, but this does not mean that there cannot be more.
Answering this question would allow us to find out if the virus will be controlled or if it will establish itself in other countries. Smallpox was eradicated because it did not have animal reservoirs, but it is almost impossible to kill a virus that infects other living beings. Once again, a small micro-organism has reminded us that we all share the same planet and therefore our health is also a global issue.