At the beginning of the current monkeypox outbreak, experts thought they understood how the virus spread and what the symptoms looked like—but "a very, very wide range of presentation" has changed their expectations, Apoorva Mandavilli writes for the New York Times.

The best-case (and worst-case) scenarios for monkeypox

What does a traditional monkeypox infection look like?

Historically, monkeypox produces a distinct set of symptoms, including large pustules, fever, aches, weakness, and pain. In addition, it was always known to spread through close contact—but many researchers have suggested that it may also spread through sexual contact.

Earlier this year, when cases of monkeypox were initially reported Europe, many scientists were surprised when they learned that the virus was spreading through sexual contact and genital lesions. 

However, Nigerian researchers in 2017 detected a similar pattern when they documented 228 cases, which included young men with genital ulcers. Notably, those cases were the first reported in the country in 40 years. According to World Health Organization (WHO) spokesperson Fadela Chaib, WHO helped Nigeria "mount the local response, with the goal to control spread."

Ultimately, the atypical symptoms in the Nigerian patients were overlooked at the time. "If what is happening in Europe and the global North had not happened, I don't think that paper would be discussed," said Dimie Ogoina, who led a study that described those cases.

"We have this disease that's more than 50 years old, and there's a lot of things we still don't know—and that's because the condition has been largely restricted to Africa," Ogoina added.

Monkeypox is manifesting in 'a very, very wide range of presentation'

In the early days of the current monkeypox outbreak, a man in his 20s visited an ED in Northern California with tiny blisters on his lips, hands, and back. Twelve hours later, he was diagnosed with monkeypox.

However, the man did not have typical monkeypox symptoms. In addition, he did not know when or how he was infected—he said he had not had any sexual contact for months and had not knowingly touched anyone with the condition.

Since the start of the current outbreak, monkeypox patients around the world have developed atypical symptoms, including bumps that look like mosquito bites, pimples, or ingrown hairs. Notably, other patients did not have any visible lesions but felt severe pain when swallowing, urinating, or emptying their bowels, Mandavilli writes.

"Some had headaches or depression, confusion and seizures. Others had severe eye infections or inflammation of the heart muscle," she adds. "At least three of the six deaths reported so far were linked to encephalitis, an inflammation of the brain."

"We really are seeing a very, very wide range of presentation," said Boghuma Titanji, an infectious disease physician at an Atlanta clinic that serves people living with HIV.

So far, scientists have learned that the virus can be present in saliva, semen, and other bodily fluids for weeks after a patient recovers.

In May, Chloe Orkin, an infectious disease physician at Queen Mary University of London, reached out to several international colleagues to compile the largest study of monkeypox so far. Ultimately, hundreds of physicians from 16 countries contributed information about cases.

As they gathered more information about the virus, the researchers revised the reporting forms. They added the possibility of a single pox, lesions in the throat or rectum, and medical complications—characteristics that were "not included in international case definitions of monkeypox," according to Orkin.

Last month, their analysis of 528 patients was published in the New England Journal of Medicine. A few days later, Orkin reached out to several national health agencies, highlighting that the findings should change the case definitions doctors use when diagnosing monkeypox.

For instance, CDC initially said that "people who do not have monkeypox symptoms cannot spread the virus to others." Last month, the agency updated that phrasing to say that "scientists are still researching" asymptomatic transmission.

"It's no longer correct to say it can't be transmitted asymptomatically," Orkin noted. "I think that it means that our working model of how it's spread is incorrect." (Mandavilli, New York Times, 8/26)