Does a lower dose of monkeypox vaccine work?
1:52
(CNN) --
Of the tens of thousands of monkeypox cases around the world this year, there have been a dozen virus-related deaths and, for the first time, some of them have been outside of Africa, in countries where the virus does not usually spread.
More than 31,000 cases of monkeypox have been reported worldwide since Jan. 1, more than 10,000 of them in the United States.
Most people have recovered at home with no long-term problems.
But doctors are working to understand why monkeypox can be serious and, rarely, deadly.
According to the latest figures from the World Health Organization, there have been two deaths from monkeypox in Spain, one in Brazil, one in Ecuador and one in India, all so-called non-endemic countries.
So far, none of these deaths have been in the United States.
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In a recent social media question-and-answer session, Dr. Rosamund Lewis, technical lead for the monkeypox response for WHO, says that the lack of a clear understanding of the severity of the disease is one of the the reasons why infectious diseases are so challenging.
"When people are exposed to infectious agents, they respond in different ways," he said.
Some develop no symptoms or only mild problems, such as a low-grade fever.
They recover and move on with their lives.
Others, however, develop very serious complications.
We're recording it now," he said. Lewis says the WHO has asked all countries for more information about the circumstances surrounding monkeypox deaths.
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A man in Spain recounts how he lived with monkeypox 4:09
Two previously healthy men die in Spain
Two recent cases, in particular, have set off alarm bells.
A report by Dr. Isabel Jado, director of Spain's National Institute of Microbiology, says the two deaths in that country occurred in men aged 44 and 31.
Their cases appear to be unrelated.
The men did not know each other and were not from the same area.
Before contracting monkeypox, they were healthy with no underlying risk factors for serious illness, such as a weakened immune system.
Both developed encephalitis, or inflammation of the brain, which can be caused by viral infections.
They eventually fell into a coma and died.
Andrea McCollum, an epidemiologist and smallpox virus expert at the US Centers for Disease Control and Prevention (CDC), says that encephalitis is a very rare condition associated with monkey pox.
It has been reported in people with monkeypox in West Africa and in a patient in the USA in 2003 during a small outbreak linked to imported prairie dogs.
"Why some of these patients have encephalitis is something we don't know," McCollum told CNN.
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The severity of monkeypox probably depends on the person's underlying health, the health resources they have access to, and the strain of virus they have been infected with.
In the Congo Basin, in central Africa, according to McCollum, about 11% of monkeypox cases are fatal, largely because the population has not even been vaccinated against the smallpox virus, which would protect against monkey pox.
In West Africa, monkeypox is fatal in 1% of cases, based on data mainly from Nigeria.
It also shows that people who die from monkeypox often have risk factors that lower their immune function, such as poorly controlled HIV.
Babies are at higher risk for severe illness because they don't have a fully functioning immune system, McCollum said.
Pregnant women also have reduced immunity and may be at higher risk of contracting monkeypox.
The strain of the virus circulating in West Africa, the same one now circulating in the US and other non-endemic countries, is thought to cause milder disease than the Congo Basin strain.
Outside of these endemic settings, not much is known about how and why cases can become severe.
Public health officials say they are trying to learn as they go.
How do I know if I have monkeypox?
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Serious illness, but no deaths, in the United States
A report on the first cases in the United States indicates that of the 954 patients for whom information is available, approximately 1 in 12, or 8%, has been hospitalized.
"We are aware of quite a few patients who have been hospitalized," McCollum said.
Doctors are reporting that some of the complications they're treating are urogenital or infections that spread to the eyes, "so it's still a very serious disease," she said.
McCollum says officials are also hearing that some patients need to be hospitalized for pain management.
In other cases, people who have risk factors, such as reduced immunity, are admitted so doctors can monitor them closely.
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In a case he recently consulted, the confluent lesions covered an area of the person's body: "It's when you have so many lesions that they all merge."
This can cause the skin to be so altered that it causes fluid loss problems, and the person has to be treated almost like a burn patient until their skin heals.
People most at risk of severe monkeypox infections are people with advanced HIV, as their immune function may be compromised;
pregnant people;
toddlers and babies;
people with eczema or atopic dermatitis, as they have many breaks in their skin that can make the monkeypox rash much worse;
those with at least one other complication, such as severe nausea and vomiting, diarrhea and dehydration, pneumonia, a secondary skin infection;
or other disease at the same time.
The CDC recommends that antiviral therapies be considered for people in these groups, including an experimental treatment called Tpoxx, which is being given to monkeypox patients as part of a clinical trial.
monkey pox