Monkeypox Spread to 29 Non-Endemic Nations Unprecedented

The near-simultaneous emergence of monkeypox in the United States, Europe, and other regions where it rarely is seen has raised questions whether the virus could become endemic beyond West and Central Africa, where it is common.

“There are scientists talking about whether monkeypox could become endemic in the United States and whether we can contain it,” Jennifer McQuiston, DVM, MS, deputy director of the CDC’s Division of High Consequence Pathogens and Pathology, said at a recent press conference.¹ “We are working very hard to contain it. In the United States, our containment strategy is focused on identifying cases, making sure they’re isolated to prevent ongoing spread, identifying their contacts, and making sure they get vaccine offered to them. It’s too early to know whether monkeypox could become endemic.”

Surprisingly, most cases appearing globally do not report travel to the endemic regions of Africa, according to the World Health Organization (WHO). Although a “small number” of travelers had been to Nigeria, the WHO noted it was unusual for monkeypox to appear without travel to endemic regions in West and Central Africa.

“Most confirmed cases with travel history reported travel to countries in Europe and North America,” the WHO reported.² “The confirmation of monkeypox in persons who have not traveled to an endemic area is atypical, and even one case of monkeypox in a non-endemic country is considered an outbreak.”

The sudden and unexpected appearance of monkeypox in non-endemic countries suggests there might have been “undetected transmission for some unknown duration of time followed by recent amplifier events,” the WHO said. “The public health risk could become high if this virus exploits the opportunity to establish itself in non-endemic countries as a widespread human pathogen.”

The CDC reports genetic sequencing of one U.S. case matches that of a 2017-2018 monkeypox outbreak in Nigeria. Thus, the virus may have been circulating relatively undetected until this sudden emergence in non-endemic countries. The amplifier event remains unknown, but the WHO references “extended sexual networks” of men who have sex with men (MSM) regarding global spread.

The 2022 outbreak began in early May with the first cases in the United States and the United Kingdom, with common factors in most of the cases including international travel and MSM. As of June 7, there were 35 monkeypox cases reported in 14 states and Washington, DC. More than 1,000 cases were reported in 28 other non-endemic nations, including the U.K. (302 cases), Spain (198), Portugal (166), Canada (80), Germany (80), and France (66), the CDC reported.³

In the United States, 16 of the first 17 cases were men who identify as MSM, gay, or bisexual. Fourteen reported international travel. One case was in a woman who reported only heterosexual contact. “Current epidemiology suggests person-to-person community transmission,” the CDC reported.⁴

“I want to emphasize that this could be happening in other parts of the United States. There could be community-level transmission happening,” McQuiston said. “That is why we really want to increase our surveillance to encourage physicians that if they see a rash and suspect monkeypox to go ahead and test for that.”

A Complicated Message

Emergence of monkeypox in MSM complicates the public health message for the CDC, which is trying to raise awareness without creating the kind of stigma seen in the early, infamous days of the HIV/AIDS pandemic.

“Anyone can get monkeypox, and we are carefully monitoring for this in any population, including those who are not identifying as men who have sex with men,” McQuiston said. “In addition to the broad [outreach], we are also making efforts to raise awareness in the LGBTQ+ community.”

MSM may be reluctant to reveal contacts because of the social stigma aspect, possibly undermining contact tracing and giving monkeypox enough of a foothold to become an endemic infection in the United States, says William Schaffner, MD, a professor of preventive medicine at Vanderbilt University.

“I’m a little wary about whether tracing chains of transmission with classic public health shoe-leather epidemiology can eliminate this infection,” Schaffner says. “I’m sure it can curtail it, but I’m not sure it can eliminate it because not everyone will be willing to acknowledge their close personal contacts. Indeed, sometimes the contacts are anonymous or use false names. These are the kind of things when you have socially disapproved behaviors that result in challenges. There may be smoldering monkeypox in our population for some time. I hope that is not the case, but it wouldn’t surprise me.”

Another possible confusing factor is that, although monkeypox clearly is spreading through sexual contact, it is not a traditional sexually transmitted disease (STD) that transmits through semen and vaginal fluids, said Laura Hinkle Bachmann, MD, MPH, chief of the CDC’s Division of STD Prevention, at a clinical briefing.⁵

“We do not currently have evidence that monkeypox is sexually transmitted in the typical sense,” Bachmann said. “But it can be transmitted during sexual and intimate contact as well as with personal contact in shared bedding and clothing. Anyone can spread monkeypox through contact with body fluids, monkeypox sores, or respiratory droplets when they’re close to someone who has the infection. Some of these more recent cases started in the genital or in the perianal area.”

Indeed, the CDC investigation of the first U.S. cases emphasized this distinction, noting the initial appearance “of lesions in the anogenital area observed in the current outbreak differs from the typical appearance or occurrence beginning on the face, oral mucosa, and hands and feet, then spreading to other parts of the body.”

Monkeypox usually is self-limiting but may be severe in children, pregnant women, or the immunocompromised. “Right now, there have been no deaths reported in this outbreak, either in the United States or other countries,” McQuiston said. “That being said, we don’t want to minimize this condition. The rash caused by monkeypox virus can spread widely across the body and sensitive areas like the genitalia. It can be really painful, and some patients have needed prescription pain medication.”

The U.S. cases have recovered or are in recovery, with the CDC advising they stay home and away from others until all scabs have been replaced by new, healthy skin.

Another factor that could aid the establishment of endemicity is the fact most people in the United States are susceptible to monkeypox. Smallpox vaccine is protective against monkeypox, and many older people still bear the bifurcated needle scars on their arms. However, with smallpox eradicated in the wild in the 1970s, vaccinations ended. That means a large portion of the global population is now susceptible to monkeypox — and smallpox, which is known to be held in frozen samples in the United States and Russia. There are supplies of smallpox vaccine and a newer two-shot regimen that also will work against monkeypox.

“We expect individuals who have received the smallpox vaccine [in the past] to have some protection from monkeypox,” Brett Petersen, MD, MPH, deputy chief of the CDC’s Poxvirus and Rabies Branch, said at the clinical briefing.⁵ “We don’t know exactly how long that protection lasts. In the monkeypox outbreak in the United States in 2003, there were individuals who had been vaccinated against smallpox as a child who did become infected with monkeypox virus.”

The 2003 outbreak was caused by prairie dogs — housed with African rats that carried monkeypox — that were sold as pets. Forty-seven cases occurred, and two children almost died.

Diagnostic Uncertainty

Typically, monkeypox is preceded by flu-like symptoms, headache, swollen lymph nodes, and exhaustion.

“When the rash develops, it usually starts as macules that then move to papules, vesicles, pustules, and then scabs,” McQuiston said. “There’s also a typical sequence for the rash that starts in the tongue or mouth as an enanthem and progresses to the face, to the arms and legs, to the hands and feet, including the palms and soles. Pain and pruritis can be prominent. But again, this is all said with the caveat that the clinical presentations may not be typical in this particular situation.”

Indeed, a suspected patient rash at Vanderbilt University Medical Center probably was poison sumac, says Schaffner. “The determination that it was not monkeypox was made by our state public laboratory, which did a brilliant job of rapidly turning around the specimen that we sent them,” he says. “That issue was resolved for us very quickly.”

Since few clinicians have seen monkeypox, a degree of diagnostic uncertainty is expected. The CDC has posted some photos to aid in the identification on its outbreak update page.³

“Two of the illnesses I’ve heard as potentially being confused with monkeypox — and they are much more common in the United States — are chickenpox and hand, foot, and mouth disease,” Schaffner notes. “This is mostly pediatric, but not entirely, and can have lesions both in the mouth and on the body.”

Monkeypox is not considered a pandemic threat, partly because it primarily transmits through close contact. The first human case was diagnosed a half-century ago in the Democratic Republic of Congo, where it now is endemic, with about 1,300 cases by June of this year. As critics have observed, much like the Ebola virus, monkeypox now is on the public health radar largely because it has emerged in wealthy non-endemic countries.

An orthopox virus akin to smallpox but much milder and less transmissible, monkeypox was so named after a colony of primates became sick in a research lab in Denmark in 1958.⁶ However, the name is a misnomer, since it is thought the natural reservoir for monkeypox are various African squirrels and rodents, which may have crossed over into humans via the consumption of these animals as bushmeat. Thus, like SARS-CoV-2, monkeypox is another zoonotic infection that jumped from animals to humans.

The current monkeypox outbreak involves the milder West African clade of the virus, which produces a mortality rate of 3.6% in endemic nations as opposed to a 10.6% death rate for the Congo Basin clade, the WHO reported.

Patient Isolation, N95s

With monkeypox emerging in the United States, public health officials are calling for a high suspicion for cases and placement of probable or confirmed patients in isolation, with healthcare workers wearing both eye protection and N95 respirators.

“Though not reported in this current outbreak, the risk of healthcare-associated infections has been documented in the past in both endemic and non-endemic areas,” the WHO warned in its report.

The CDC infection control recommendations for patients with suspected or confirmed monkeypox⁷ are summarized as follows:

• Place the patient in a single room with a dedicated toilet. Keep door closed, if possible, but no special air handling is required. However, an airborne isolation room should be used for intubation and any other procedures likely to spread oral secretions. Limit transporting the patient outside the room to medically essential purposes. If the patient is transported, they should wear a medical mask for source control and any exposed lesions should be covered with a sheet or gown.
• Medical waste may be considered hazardous; consult local and federal regulations. Consult with local health authorities when discontinuing isolation precautions. Use an Environmental Protection Agency-registered disinfectant with an emerging viral pathogens claim. Soiled laundry should be handled in a way to avoid contact with lesion materials.

“Soiled laundry should be gently and promptly contained in an appropriate laundry bag and never be shaken or handled in manner that may disperse infectious material,” the CDC recommended. “Activities such as dry dusting, sweeping, or vacuuming should be avoided. Wet cleaning methods are preferred.”

PPE used by healthcare personnel who enter the patient’s room should include:

• gloves;
• gown;
• eye protection;
• an N95 filtering facepiece or equivalent, or a higher-level respirator.

“This is definitely what we have adopted in terms of preparedness efforts, so we are making sure that staff are aware of the use of a higher level of respiratory [protection], like a fitted N95,” says Marie Wilson, MSN, RN, CIC, a member of the communication committee at the Association for Professionals in Infection Control and Epidemiology.

Respirators are a good idea because a hospitalized patient with progressive monkeypox could have respiratory involvement. “The patient may be capable of expelling tiny particles, and if they can’t wear a source control [mask], the [N95] will really reduce the risk to healthcare workers, as well as the eye protection — protect those mucous membranes of the eyes,” Wilson says.

Expect Surge Near Term

With the CDC urging clinicians to search for cases and send isolates for confirmatory testing, it is expected cases of suspected and confirmed monkeypox will increase.

Infection preventionists can expect to immediately become involved if a case presents at their hospital ED or an affiliated clinic, Erica Shenoy, MD, PhD, associate chief of infection control at Massachusetts General Hospital, noted at a briefing held by the Infectious Diseases Society of America.⁸

“The way we think about many communicable diseases is the mantra of identify, isolate, and inform,” Shenoy said. “The identify piece is the clinician receiving a call or seeing a patient in the emergency department, and having the information they need from public health to have monkeypox on the differential [diagnosis]. Then, we have to isolate the patient and implement transmission-based precautions. The last step is inform, and in most institutions that means infection control and prevention is going to be involved.”

In these situations, the infection prevention department is acting as an extension and liaison with public health. “We’re the conduit to that external partner that will be critical in making an accurate diagnosis and confirmation of these patients as well as helping to facilitate any follow-up that needs to occur for exposed healthcare workers or other individuals related to the care of that patient,” Wilson says.

The key is acting as close to the exposure period as possible, and finding any staff or patients who were in contact with the infected individual.

“The closer you get to the event, the more reliable that information is,” Wilson says. “If we do need to perform any post-exposure prophylaxis or just monitoring for the 21 days after potential exposure, we have a good, accurate list. Whether therapeutics are administered really depends on the exposure. If we identify the [index case] early and isolate early, then the risk of exposure should be drastically reduced.”

Part of this is assessing incoming patients, which Wilson also is handling for COVID-19 at her hospital in the Northwest. “It may vary based on the location and what the other concerns are,” she says. “In my region, we are still concerned about COVID as well, so it is going to be a bit more general screening for respiratory illnesses, travel [history], early symptoms of monkeypox, skin appearance, and any unexplained rashes.”

PEP and Health Workers

When should a healthcare worker be given post-exposure prophylaxis (PEP) with the monkeypox vaccine? The CDC has issued guidance to assess the risk of exposures and make decisions on PEP and monitoring the worker for the 21-day incubation period. (See Table 1.)

“Those with a high degree of exposure are recommended to be monitored as well as receive post-exposure prophylaxis vaccination,” Petersen said. “[This] would include unprotected contact between a person’s skin or mucus membranes and the skin lesions or body fluids from a patient. For example, inadvertent splashes of patient saliva to the eyes or oral cavity, ungloved contact with a patient or contaminated materials [such as] linens or clothing.”

Shaking soiled linens may suspend dried exudates in the breathing zone, a high-risk exposure if the healthcare worker is not wearing an N95 mask.

“An intermediate degree of exposure would carry a recommendation for monitoring as well as informed clinical decision made on [an] individual basis to determine whether benefits of PEP outweigh risks,” Petersen said.

Intermediate exposures include turning, bathing, or assisting with the transfer of a monkeypox patient while wearing gloves but not a gown.

In general, healthcare workers without full PPE who are exposed to monkeypox patients can remain on duty with regular symptom evaluation.

“[They] should undergo active surveillance for symptoms, which includes measurement of temperature at least twice daily for 21 days following the exposure,” the CDC recommended. “Prior to reporting for work each day, the healthcare worker should be interviewed regarding evidence of fever or rash.”

REFERENCES

1. Centers for Disease Control and Prevention. CDC media telebriefing: Update on 2022 U.S. monkeypox investigation. June 9, 2022.
   
2. World Health Organization. Multi-country monkeypox outbreak: Situation update. June 4, 2022.
3. Centers for Disease Control and Prevention. U.S. monkeypox 2022: Situation summary. Reviewed June 14, 2022.
4. Minhaj FS, Ogale YP, Whitehill F, et al. Monkeypox outbreak — nine states, May 2022. MMWR Morb Mortal Wkly Rep 2022;71:764-769.
5. Centers for Disease Control and Prevention. What clinicians need to know about monkeypox in the United States and other countries. May 24, 2022.
6. von Magnus P, Andersen EK, Petersen KB, Birch-Andersen A. A pox-like disease in cynomolgus monkeys. Acta Path Microbiol Scand 1959;46:159-176.
7. Centers for Disease Control and Prevention. Infection prevention and control of monkeypox in healthcare settings. Last reviewed May 22, 2022.
8. Infectious Diseases Society of America. IDSA media briefing: Monkeypox — what experts know. June 1, 2022.