A multinational monkeypox outbreak that began appearing in Europe in early May has expanded to hundreds of confirmed and suspected infections across countries where the virus is not normally found, prompting U.S. and European health agencies to intensify surveillance, contact tracing and clinician alerts while investigators work to understand how transmission is occurring.

The World Health Organization reported that by May 21, 92 laboratory-confirmed cases and 28 suspected cases had been reported from 12 non-endemic countries across three WHO regions. By May 26, the organization had been notified of 257 confirmed and roughly 120 suspected cases in 23 non-endemic countries, according to its subsequent situation accounting. No deaths had been reported in those countries.

Monkeypox is endemic in parts of Central and West Africa, and isolated travel-associated infections have previously been diagnosed elsewhere. What makes the current event unusual is the appearance of multiple clusters in countries with no routine transmission, many involving people with no known travel to endemic areas.

The European Centre for Disease Prevention and Control said on May 19 that the United Kingdom had identified an imported case on May 7, followed by separate clusters without travel links. Portugal had confirmed five cases and was investigating more than 20 suspected infections, while Spain was investigating additional cases. Several early patients were men who have sex with men, although public-health agencies have emphasized that anyone exposed through close physical contact can become infected.

WHO’s May 21 assessment said the sudden appearance of cases in several non-endemic countries suggested that undetected transmission may have been occurring for some time. The agency said immediate priorities should include identifying cases quickly, informing people who may be at higher risk and protecting healthcare workers.

The first confirmed U.S. case triggered a broader federal response

The Centers for Disease Control and Prevention confirmed the first U.S. case on May 18 in a Massachusetts resident who had recently traveled to Canada. State testing detected an orthopoxvirus infection, and CDC laboratories confirmed monkeypox. In its initial announcement, CDC said it was collaborating with Massachusetts officials while also tracking clusters in the United Kingdom, Portugal and Spain.

Two days later, CDC issued a nationwide Health Alert Network advisory urging clinicians to consider monkeypox in patients with compatible rashes even when they lacked traditional risk factors such as travel to an endemic country. The advisory described lesions that may be firm, deep-seated and well-circumscribed and asked healthcare providers to consult public-health authorities when cases are suspected.

The U.S. response is focused on case identification rather than broad population restrictions. Public-health teams can isolate infected patients, identify close contacts, arrange laboratory testing and consider post-exposure vaccination or antiviral treatment in selected cases. The federal government already maintains smallpox countermeasures that may have utility against monkeypox because the viruses are closely related orthopoxviruses.

Europe advises contact tracing, diagnostic readiness and targeted countermeasures

By May 23, nine European Union and European Economic Area countries had reported 67 confirmed cases and at least 42 suspected cases. ECDC’s response guidance called for prompt case identification and reporting, contact tracing, stronger orthopoxvirus diagnostic capacity and reviews of available smallpox vaccines, antivirals and protective equipment for healthcare workers.

A separate rapid risk assessment published the same day concluded that the likelihood of spread is particularly elevated among people with multiple sexual partners in the networks where early cases have been identified, while the risk to the broader population remained low. ECDC noted that transmission can occur through contact with infectious skin lesions, contaminated materials or prolonged face-to-face exposure to respiratory droplets.

Those distinctions are important because the outbreak’s epidemiology is still being defined. The clustering among gay, bisexual and other men who have sex with men may reflect where transmission has become established and where case finding is most active; it does not imply that infection is limited to one population. Public-health agencies have cautioned against stigma because monkeypox spreads through close contact and can affect anyone exposed to infectious material.

Clinical recognition may be more difficult than textbook descriptions suggest

Classic monkeypox illness often begins with fever, headache, muscle aches, swollen lymph nodes and fatigue, followed by a rash that progresses through characteristic stages. In the current outbreak, however, some patients have presented first with localized lesions, including genital or perianal lesions, and may not have the complete sequence clinicians associate with infections acquired in endemic settings.

That makes surveillance dependent on clinician awareness. The CDC advisory asks providers to consider monkeypox when patients have unexplained lesions and to use appropriate infection-control precautions while testing is arranged. The first U.S. case was identified after Massachusetts clinicians recognized a suspicious rash and sought specialized testing, illustrating the value of heightened awareness as case definitions evolve.

European agencies are taking a similar approach. ECDC recommends that suspected patients be isolated while diagnostic evaluation proceeds and that contacts be monitored for symptoms. Healthcare workers caring for suspected or confirmed cases should use appropriate personal protective equipment because direct contact with lesions and contaminated materials can transmit the virus.

The immediate challenge is containment while the transmission chain is reconstructed

Unlike a newly discovered pathogen, monkeypox is a known disease with established diagnostic methods and existing countermeasures. The uncertainty lies in why sustained transmission is appearing simultaneously across multiple non-endemic countries and how extensive that transmission already is.

CDC’s emergency alert notes that the Massachusetts patient was isolated and did not pose a continuing public risk, but the broader outbreak requires finding cases that may not yet have been connected epidemiologically. WHO and ECDC have both warned that additional infections are likely to be detected as surveillance expands.

For now, health agencies are not describing the threat to the general population as high. Their strategy is more targeted: identify unusual rashes, test rapidly, isolate confirmed cases, trace close contacts and use existing vaccines or antivirals where clinically appropriate. Whether those measures are sufficient will depend on how quickly investigators can map transmission and whether the clusters remain concentrated within identifiable contact networks or begin spreading more broadly.