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[ Above / Left: a monkeypox lesion. The lesions in cases that are part of the 2022 outbreak are often first seen on genitalia or the anus. Spread to other parts of the body is possible but doesn't always occur. ]

For the first time in history, the world is facing an international outbreak of monkeypox. The World Health Organization has declared a public health emergency, which enhances coordination and the sharing of resources and information among nations.

Doctors have detected more than 16,000 cases across the globe, from Argentina to the United Arab Emirates. The CDC has reported nearly 2,900 cases in the U.S. as of Friday.

Such a broad geographic spread suggests "widespread human-to-human transmission is currently underway," said Dr. Maria van Kerkhove, with the World Health Organization, in June. This transmission has "likely been ongoing for several weeks, if not months," she noted.

Two studies, published last month, demonstrate the virus is spreading, undetected, in some communities of Portugal and the U.K. — because, by and large, the cases are not linked to each other or linked to a common place or activity. So health officials don't know where people are catching it, and many cases aren't being diagnosed, the scientists conclude.

Here in the U.S., officials don't know where one of the cases caught monkeypox. "There could be community level transmission that is happening. And that's why we want to really increase our surveillance efforts," Jennifer McQuiston, who's deputy director of the Division of High Consequence Pathogens and Pathology at the Centers for Disease Control and Prevention, said Friday. "I want to emphasize that this could be happening in other parts of the United States."

This gap in detection may be because the symptoms of monkeypox in this outbreak can be much more subtle than in past cases.

As a result, health officials are asking health-care workers – and individuals who may have been exposed – to be on the lookout for signs of monkeypox, especially signs of a rash.

But what does that rash often look like? Turns out, it's not what medical textbooks show, says infectious disease doctor Donald Vinh at McGill University. Those images depict people with their trunk or hands covered with pus-filled blisters. What's happening in this outbreak can be much more subtle, Vinh and other doctors involved with the outbreak say.

In fact, some patients have only one or two small lesions that can easily be confused with lesions caused by several sexually transmitted diseases, such as herpes and syphilis.

"I think that's actually supercritical," Vinh says, "Because you can see how these patients can be missed. But they are still contagious and may propagate the disease."

Vinh has been helping to treat 5 people with monkeypox at McGill University Health Centre in Montreal. The outbreak in that city includes at least 50 cases, he says.

On a morning earlier this summer, a colleague called to discuss a patient, newly diagnosed with monkeypox, who had only one lesion.

"The patient's skin lesion that he sampled to confirm the diagnosis is extremely subtle. It's not what you're seeing on the Google pictures of monkeypox," he says.

In textbooks (and on many agency websites), monkeypox is described as a disease that begins with flu-like symptoms, including a fever, tiredness and a single swollen lymph node. Then about a week later, a rash appears, first on the face and then on the extremities. This rash contains painful blisters that eventually fill with pus and crust over. Eventually it can cover the trunk or whole body.

"So in the classic monkeypox, described in textbooks, you're supposed to have two phases," Vinh says.

But in this current outbreak, many people's symptoms don't fit this profile at all, say Vinh and several doctors involved with these cases.

For starters, the rash often isn't on the face or extremities at all. Instead, it typically begins on the genitals or the anus. And sometimes it doesn't spread to other parts of the body.

"You don't have head-to-toe skin pox lesions," Vinh says. "Instead it's localized to just one region of the body, like the genital regions. And some people have just one or two pox. So it's not numerous."

"Sometimes it's not even a pox," he says, "but rather an ulcer or a crater."

But even if only a small part of the body is affected, monkeypox isn't necessarily a mild illness. "The rash can be really painful, and some patients have reported needing prescription pain medicine to manage that pain," says the CDC's Jennifer McQuiston. "The sores can also cause long term scarring on the skin."

And what about those flu-like symptoms? Sometimes they don't appear at all, Vinh and other doctors have found. Or they can appear after the skin lesions appear. Sometimes patients have a single swollen lymph node and sometimes they don't. Some patients have inflammation of the rectum, infectious disease specialist Agam Rao, with the CDC, told JAMA.

At one clinic in Montreal, a patient with monkeypox had one tiny lesion on his penis which wasn't painful: "Never had other rash/lesion elsewhere. Never had [a] fever, " Dr. Sebastien Poulin, of the Clinique l'Agora, explained on Twitter.

"The bottom line of this tweet will be; «We must have a high index of suspicion for 'atypical' MonkeyPox cases»" he wrote.

Given this broad range of symptoms, health officials in the U.K. are casting a wide net when it comes to looking for new cases. They're asking people to be on the onlook any type of rash.

"The risk to the UK population remains low, but we are asking people to be alert to any new rashes or lesions, which would appear like spots, ulcers or blisters, on any part of their body," the agency wrote Tuesday.

"Although this advice applies to everyone, the majority of the cases identified to date have been among men who are gay, bisexual and men who have sex with men, so we are asking these people in particular to be aware of the symptoms, particularly if they have recently had a new sexual partner."

In general, monkeypox spreads primarily through close contact with an infected person, including contact with the rash or skin lesions. That contact can occur during sex, epidemiologist Mateo Prochazka explained on a Facebook video last week. Prochazka consults for the U.K. Health Security Agency and identifies as a gay man.

"Because of the way we have contact with one another during sex, usually skin to skin for a period of time, the risk of transmitting the virus to each other is higher," he said. "And that means that gay men, especially gay men that have intense sexual networks, might be seeing an increase in these cases just because of their potential behavior and the number of contacts they have.

"So it's less about sexual identity and more about sexual networks," he added.

Although surveillance, so far, has focused on men who have sex with men, countries are now broadening the scope of their search, said the WHO's Dr. Maria van Kerkhove. "We should say, so far, that surveillance is biased toward [men who have sex with men] at the moment, and we are working with countries to expand that surveillance to other types of clinics, ID clinics, emergency departments."

Here's some CDC slides from the end of June 2022 showing different ways that Monkeypox can appear:  https://emergency.cdc.gov/coca/ppt/2022/062922_slides.pdf