Early on the morning of May 17, Erica Shenoy, MD, PhD, an infectious disease physician and associate chief of the Infection Control Unit at Massachusetts General Hospital in Boston, awoke to an unexpected email from her colleague, Nesli Basgoz, MD. Basgoz had been treating a patient with a range of symptoms — fever, swollen lymph nodes, and a rash — but she had been unable to identify the patient’s illness.
The day prior, though, public health officials in the United Kingdom (UK) had sent out an alert about a handful of cases of mpox (formerly known as monkeypox) — a viral disease endemic in central and western Africa but infrequently seen in other countries. Basgoz thought her patient might fit the diagnostic criteria described by the UK clinicians.
The next morning, Basgoz sent the email to Shenoy with the subject line: Infection control for possible monkeypox. “I get up around 5 or 5:15, so I called her right away,” Shenoy recalls. Within the hour, the two were conferring with public health officials about how to test their patient, isolation measures, and potential treatments.
That patient became the first known case of mpox in the United States in 2022, but they haven’t been the last. As of June 15, the Centers for Disease Control and Prevention (CDC) has confirmed 71 cases of the disease in 17 states and the District of Columbia, with 1,879 cases worldwide in 35 countries.
Earlier this week, the AAMC and the CDC published a resource guide on mpox to help inform clinicians on how to identify and treat monkeypox. The CDC also has a guide to the 2022 mpox outbreak on its web site for patients and clinicians.
While the current outbreak is growing, the threat to the general U.S. population remains low. However, the CDC and the World Health Organization (WHO) recently issued alerts to doctors and public health officials to be on the lookout for suspected cases.
The Biden-Harris administration is also taking the outbreak seriously, increasing its stockpiles of the antiviral Tecovirimat and the two available vaccines — ACAM2000 (a live replicating virus delivered through the skin) and JYNNEOS (a two-dose nonreplicating virus delivered via injection four weeks apart). Both are smallpox vaccines that have been shown to be about 85% effective in preventing mpox and may also provide some protection against severe disease in those already infected.
Raj Panjabi, MD, special assistant to the president and senior director for global health security and biodefense at the National Security Council, is leading efforts to contain the mpox outbreak in the United States.
He and Shenoy spoke with AAMCNews about the current outbreak, including signs and symptoms of the illness, how it spreads, testing, treatments, and the race to raise awareness among providers and the public.
What is mpox?
Shenoy: Mpox is what we call a viral zoonotic infection, which means that one of the reservoirs [of the virus] is in animals, and it can be transmitted to humans through interactions with those animals. Once in humans, it can spread person to person. Mpox results in a rash that looks like smallpox; however, it is much less severe in terms of outcomes.
What are the signs and symptoms of mpox — and have those been different in this current outbreak?
Shenoy: The classic presentation that’s described is that people will have an incubation period of four to 21 days, during which they have no symptoms. Then there’s a stage called the prodromal stage, where the patient might experience nonspecific symptoms like a fever or headache. And then what distinguishes mpox from smallpox is the patient gets lymphadenopathy or swelling of the lymph nodes. The rash follows about one to four days after that. But what’s been atypical during this outbreak has been very minimal or absence of some of those prodromal symptoms.
Panjabi: There are a couple of things that are unusual about this outbreak. Number one, patients can present with a rash without fever. That’s different than the typical patient, who presents with a fever, flu-like symptoms, and then a rash. Second, historically, people with mpox have disseminated vesicles or pustules across the body — the face, arms, and trunk of the body. But a lot of the initial patients we’re seeing are actually having a more confined, subtle rash around their genitalia and anus. So that can masquerade as other conditions that might be given the classification of an STI [sexually transmitted infection]. Mpox is a contact-based infection.
So we’re asking health care providers: If you see [suspected] herpes, if you see [suspected] syphilis, if you see an STI that looks like mpox, we ask you to think about that not at the end of your differential diagnostic pathway, but at the beginning. That will ensure we’re helping those patients get care and will help us understand how much undetected spread we have as well.
How does mpox spread?
Shenoy: Mpox is primarily spread through close intimate contact with someone who’s infected and, specifically, direct contact with the lesions that form as part of the rash. Currently, the epidemiology is showing a strong association with men who have sex with men (MSM), but there have been cases outside of that population. It is very important to understand that risk relates to the mode of spread, and you can have close physical contact between individuals, regardless of whether they are MSM or not. There’s also a lot of very appropriate outreach from public health and other groups to the communities that are more affected right now. There is no role for stigma, but there is a role for awareness so that people can protect themselves and know what to do if they’re concerned about an exposure or if they develop symptoms.
What is the likelihood of being infected by someone you are not intimate with?
Shenoy: What we know is that this virus does not spread easily between people. It really does require close contact. For a point of reference, last year, there were two cases in the United States. They were both travelers from West Africa. There were hundreds of potential contacts, including people on the airplane, and there were no secondary cases. In fact, my colleague Dr. Kimon Zachary and I recently reviewed the risk of transmission from mpox cases diagnosed outside of Africa from 2000 up until this outbreak. While our focus was specifically on risk in health care settings, what we found was a single documented transmission in a health care setting and two cases from household transmission. … In studies from Africa, the attack rate in households is about 9%. So that plays into the fact that you need really close physical contact, and possibly prolonged face-to-face contact, to transmit the virus.
Should we be worried about this virus? Is this the next COVID-19 pandemic?
Shenoy: No one can say where this is going and obviously, for most of us, our frame of reference is the past two-plus years of COVID — but that’s not the right frame of reference for mpox. Number one, mpox requires close contact and is not spread easily. Two, we’ve got vaccines, and for those who develop severe disease or who are at risk of severe disease, we do have treatments. We have a really robust public health response of active case finding and contact tracing, which is essential to both break chains of transmission and understand the epidemiology. So it’s early days, but we are fortunate that this is the milder form of mpox, we have therapeutics if we need them, and there have been no deaths so far.
What are the therapeutics?
Shenoy: Let’s start with vaccines. There are two vaccines: the ACAM2000 and the JYNNEOS. These can be used for post-exposure prophylaxis — that is, if you are identified after an exposure and that exposure is high risk. The vaccine is given ideally really soon after exposure, within four days, but it can be given up to 14 days [after exposure]. Within four days, it’s expected to reduce the risk of even developing the infection and up to 14 days, it’s expected to reduce the severity of the infection. Vaccines may also be used for pre-exposure prophylaxis — that’s when it’s given in the absence of an exposure to individuals who may be at higher risk. That includes those working with viruses like mpox in research or clinical labs, among other groups.
Turning to treatment, one antiviral that’s being used is Tecovirimat. This is an antiviral that’s given either to people who have severe disease or to people without severe disease who are at risk of getting really sick. So that would be the immunocompromised, women who are pregnant or recently pregnant, and young children. [All of the antivirals and vaccines have been purchased by the federal government and are available to patients and providers free of charge.]
What efforts are being deployed to contain the current outbreak?
Panjabi: We are taking a two-pronged approach. One, we want to make sure we test infected individuals, isolate them, and care for them. The second is we want to offer vaccines to those who’ve had a high-risk exposure or contact with those who are infected.
Right now, the average time between symptom onset and [diagnosis of mpox] is about 18 days. … We really need folks to present for testing earlier. That’s why we’re speaking to community leaders and health care providers, including the vast coalition that is the AAMC and all of your institutions, to educate providers but also the public on what mpox is and what to look for.
Today, more than 400 PCR orthopox tests have been performed through our Laboratory Response Network, which is a network of over 67 labs at the state and local health department level. But there is actually a lot of spare capacity to do over 1,000 tests a day.
We’re also doing secondary contact tracing through state and local health departments. That’s really critical because if health departments know someone is at high risk, they can offer a vaccine to help prevent that person from getting an infection, or help delay the infection, or reduce the impact of infection. As of Friday, we’ve delivered over 1,400 vaccine courses to state and local jurisdictions.
We have sufficient vaccines on hand for us to be able to vaccinate the current population at risk. And then we have additional smallpox vaccine that has been purchased … enough that we could vaccinate larger numbers of the U.S. population should we need that. Let’s just say we don’t think that is even a remote possibility. But we’re at the point where we’re discussing when we move from post-exposure prophylaxis to pre-exposure prophylaxis of certain subpopulations who are at higher risk.
