The Evolving Epidemiology of Monkeypox
An update on ongoing transmission, vaccination, and testing efforts
In the shadow of the COVID-19 pandemic, the ongoing monkeypox outbreak demands the strained attention and resources of public health professionals. Human monkeypox is a zoonotic Orthopoxvirus that causes symptoms similar to smallpox. Though monkeypox typically arises in humans following transmission from infected animals and has been primarily limited to endemic regions of West and Central Africa, new transmission patterns including pronounced human-to-human spread during the ongoing outbreak have created significant cause for concern.
"As of October 14, more than 73,000 confirmed cases of monkeypox have been reported globally."
As of October 14, more than 73,000 confirmed cases of monkeypox have been reported globally by the CDC, including more than 27,000 cases in the United States, as well as outbreaks across Europe and South America. Most people fully recover from monkeypox infection, but symptoms can include painful lesions and very rare fatal cases can occur in immunocompromised individuals. Despite the low mortality rate, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern in July to mobilize a global response to curtail the spread of the virus. Nonetheless, early response efforts to the outbreak were hampered by long lines for a short supply of vaccines, inefficient testing, and minimal information about recommended quarantine protocols. As a result, monkeypox has gained a firm foothold in at-risk communities across the globe.
Monkeypox transmission in high-risk communities
Public health experts were particularly taken aback by the sudden shift in the epidemiology of monkeypox. Typically thought of as a rare infection with limited human-to-human transmission, the recent outbreak has defied these expectations by spreading rapidly. The unexpected shift in behavior prompted studies characterizing novel mutations in the monkeypox virus that may contribute to increased transmission. These genetic analyses also show that the spread of monkeypox virus belongs to a subclade of the endemic virus in West Africa, which is characteristically associated with less severe clinical presentation.
"Mislabeling monkeypox purely as an STI may have dangerous consequences for preventing transmission."
Notably, reports suggest that approximately 98 percent of the current reported cases are present in men who have sex with men (MSM), prompting some confusion over whether monkeypox is a sexually transmitted infection (STI). In many cases of the ongoing outbreak, transmission has been traced back to sexual contact. However, it is critical to emphasize that sexual contact is not required for viral spread. Mislabeling monkeypox purely as an STI may have dangerous consequences for preventing transmission, as people may mistakenly assume they are not at risk without engaging in sexual contact. Moreover, stigmatizing monkeypox as an STI may discourage people from seeking testing and treatment, leading to further spread the virus.
Monkeypox virus most frequently spreads through skin-to-skin contact with disease-associated rashes or lesions. These exposure events may occur during sexual activity or any other close physical contact. Viral transmission can also occur through respiratory droplets. However, according to the American Society for Microbiology, unlike the recent COVID-19 pandemic, monkeypox is not considered a respiratory virus and does not spread as easily through this route. Some evidence also suggests that monkeypox may spread via fomites (inanimate objects that carry infection). Although the current outbreak disproportionately affects gay and bisexual men, monkeypox has also reached beyond these communities. A recent study focused on emerging pediatric cases in Spain, including several patients under four years of age, demonstrates that monkeypox should be ruled out in individuals with suspicious symptoms regardless of age or sexual orientation.
Early monkeypox vaccination efforts fall short
Due to the prevalence of monkeypox as an endemic virus in Africa, vaccines initially developed for smallpox are known to confer relatively effective protection against monkeypox. In the US, there are currently two vaccines licensed for use against monkeypox: ACAM2000 and Jynneos (trade name Imvanex in Europe). However, ACAM2000 can cause severe adverse reactions in immunocompromised individuals, and given the high prevalence of immunocompromised individuals affected by the current outbreak, ACAM2000 has limited utility. As a result of these limitations, those seeking vaccination in the early stages of the 2022 outbreak faced severe supply shortages and were often turned away from vaccination centers.
"Those seeking vaccination in the early stages of the 2022 outbreak faced severe supply shortages and were often turned away."
As of early August, an estimated 620,000 doses of Jynneos, which requires two doses per person, were shipped to states for immunization. This effort falls far short of the doses needed for an estimated 1.5 to 2 million high-risk Americans. In an effort to stretch the current supply to more individuals, the FDA authorized emergency use of Jynneos via intradermal injection for at-risk adults, forgoing the indicated subcutaneous administration. The intradermal route requires less volume than subcutaneous administration, allowing providers to immunize five individuals using a single Jynneos dose. However, there is minimal evidence to show that this strategy provides effective immunity, and therefore remains a subject for debate.
Coordinating increased monkeypox testing capacity
In any quickly developing infectious outbreak, efficient testing is critical to slowing disease spread. However, there is currently no rapid test for monkeypox, meaning early patients faced turnaround times of up to 10 days before receiving results due to backlogged testing centers.
The nature of monkeypox further complicates testing, as the virus may have an incubation period of up to three weeks during which transmission may occur before an individual develops lesions and tests positive.
"Though the initial outbreak has slowed, monkeypox remains a threat to susceptible populations."
To facilitate testing, the CDC developed an RT-PCR test that was distributed to laboratories across the US via its Laboratory Response Network (LRN). After initial distribution efforts, 78 LRN laboratories implemented the molecular test and reported a total testing capacity of 24,000 specimens per week. The U.S. Department of Health and Human Services also authorized five private laboratories to conduct monkeypox testing to better meet the high demand. Nonetheless, prolonged turnaround times in highly impacted regions suggests the need for greater testing capacity and more efficient sample processing.
A new endemic virus?
Though the initial outbreak has slowed, monkeypox remains a threat to susceptible populations. How the virus will continue to impact previously unaffected regions is unclear. Given the global failure to contain the ongoing outbreak, monkeypox may become widespread enough for it to become endemic in these new areas. With this novel threat, public health professionals will need to focus efforts on continued surveillance of the evolving epidemiology of this pathogen.