A panel of experts in infectious disease and public health shared their insights into some of the factors driving an international outbreak of monkeypox during a virtual event June 9 sponsored by the Yale Institute for Global Health.

During the hour-long event, the panelists discussed the origins of monkeypox, its sudden appearance in the U.S. and measures that states, and national and international organizations can take to address the recent uptick in cases.

Watch the full panel discussion here.

As of June 6, the U.S. Centers for Disease Control and Prevention (CDC) was reporting 1,019 confirmed or suspected cases of monkeypox in 29 countries where the virus does not typically spread. Monkeypox is a rare infectious disease that is in the same viral family as smallpox. As of June 14, there were 72 cases of monkeypox in the U.S, according to the CDC. No one has died from monkeypox in the U.S. this year.

While the sudden global appearance of monkeypox is unusual, the virus itself is not new, the experts said.

“This isn’t a mysterious virus that we hadn’t identified before,” said panelist Anne Rimoin, a professor of epidemiology and the Gordon-Levin Endowed Chair in Infectious Diseases and Public Health at the UCLA Fielding School of Public Health. “This is a known pathogen that did exactly what we predicted it could potentially do.”

Rimoin went on to explain that monkeypox was first discovered in primates in the Netherlands, and the first detected human case was in the Democratic Republic of the Congo (DRC) in 1970. Intensive disease surveillance in the DRC followed, which aided in establishing that the smallpox vaccine provided immunity for other pox viruses, including monkeypox.

“The reasons [to doubt future monkeypox spread were expectations that] we’re going to see improved health care … increased urbanization, increased travel, more reliance on commercial food products as opposed to bush meat,” Rimoin said. “That’s not what happened … we had a complete destruction of the health system, there was prolonged civil war, people were forced into the forest … you saw all of these comorbidities.”

Saad Omer, director of the Yale Institute of Global Health who served as the moderator, asked Nathan Grubaugh, associate professor of epidemiology at the Yale School of Public Health, about the genomics involved in the current evolution and spread of the monkeypox virus. The Grubaugh lab specifically investigates the emergence, evolution and spread of viruses through epidemiological models and pathogen genomics.

Grubaugh said experts have determined that most of the current sequenced cases of monkeypox appear to belong to one major West African clade, which is thought to be less virulent and to mutate slowly. Monkeypox generally mutates one to two times per year and has caused zero reported fatalities in non-endemic countries, he said. COVID-19, by comparison, mutates thousands of times a year and has led to over a million deaths in the U.S. alone.

“This branch leading up to the major clade … has about 40 mutations that accumulated over four years [and] that’s about 10 times more than we thought,” Grubaugh said. These factors appear to indicate that there is probably a much larger outbreak of monkeypox happening in Western and Central Africa than has been reported, he said.

Akiko Iwasaki, Yale Sterling Professor of Immunology and Molecular, Cellular and Developmental Biology and an investigator with the Howard Hughes Medical Institute, spoke about immunology and monkeypox and the availability of vaccines to fight the virus.

Iwasaki said existing smallpox vaccines may help promote immunity to monkeypox. She said there is consistent data supporting smallpox immunity lasting for longer than the CDC timeframe of three to five years after vaccination. But routine smallpox vaccinations among the American public stopped in 1972, leading to gaps in immunity in current younger populations.

“The population immunity provided by a smallpox vaccine is around a quarter of the population,” Omer said in amplifying Iwasaki’s remarks “It’s not just the immunity part, it’s the demography [that matters].”

Rimoin then directed the discussion towards monkeypox in the U.S., claiming that there likely have been multiple introductions of the virus in the U.S. population. As a result, Rimoin emphasized a need for “situational awareness” in the U.S., including sufficient syndrome surveillance, available clinical information, risk communication, scaling-up of research and expansion of diagnostic capacity at both local and national levels.

Grubaugh took it further, reasoning that improving the management of local transmission will heavily depend on the rollout of frontline diagnostics.

“We need to roll out frontline tests … to reduce both the resulting times of having tests that are sent from a lab and then sent to another lab, and also to increase testing capacity,” he said. “We are working with several different PCR tests to …allow different diagnostic labs to be able to look at results [and] select what tests they want to do for internal validations until we actually have some commercial options available.”

There are also efforts to streamline monkeypox sequencing and assays by fitting sequencing into the COVIDSeq testing system, which provides highly accurate detection of mutations. Conducting clinical studies to determine the tissues and parts of the body affected by the virus could help improve diagnostics and shed light on transmission.

Iwasaki also discussed the vaccination pipeline. She said JYNNEOS is currently the only FDA-approved monkeypox vaccine. The strategic national stockpile has other smallpox vaccines that could also be deployed if needed, such as the more traditional vaccinia virus vaccine called ACAM2000.

“At this point of the infection that is going on, I don’t think the general public needs to be vaccinated,” Iwasaki said. “Of course, we can never underestimate the viruses. There may be future variants that … could be more transmissible.”

Omer corroborated Iwasaki’s perspective on vaccination, claiming that it would be beneficial to “build a button but not press it,” as investments and preparations could prove to be very beneficial in hindering the potential spread of monkeypox.

During the discussion, Omer also raised concerns about disinformation and stigma. Monkeypox is commonly transmitted through close personal contact. And although some of the initial clusters of monkeypox cases in Europe have been reported among men who have sex with men, anyone can get monkeypox if they come in close contact with a person who is infected or with clothing or bedding where the virus is present. It is essential to address stigma and incorporate various communities to get ahead of the virus, Omer said.