The global eradication of smallpox more than 40 years ago was one of the greatest achievements in public-health history, vanquishing a cause of death, blindness and disfigurement that had plagued humanity for at least 3,000 years. But, on the downside, it also led to the end of a global vaccination program that provided protection against other pox viruses. That includes monkeypox, which has been spilling over from its animal hosts to infect humans in West and Central Africa with increasing frequency since the 1970s. Now monkeypox has sparked unprecedented outbreaks in Europe, the US and elsewhere, demonstrating again how readily an infectious agent that emerges in one region can mushroom into a global emergency.
1. What’s monkeypox?
Monkeypox is a misnomer resulting from the fact that it was first discovered at the Statens Serum Institut in Copenhagen in 1958, when outbreaks of a pox-like disease occurred in monkeys kept for research. While monkeys are susceptible to it, just like humans are, they aren’t the source. The virus belongs to the Orthopoxvirus genus, which includes the variola virus, the cause of smallpox; the vaccinia virus, which is used in the smallpox vaccine; and cowpox virus. Monkeypox is less contagious than smallpox and the symptoms are generally milder. About 30% of smallpox patients died, while the fatality rate for monkeypox in recent years is around 3% to 6%, according to the World Health Organization.
2. What does monkeypox do?
After an incubation period of usually one to two weeks, the disease typically starts with fever, muscle aches, fatigue and other flu-like symptoms. Unlike smallpox, monkeypox also causes swelling of the lymph nodes. Within a few days of fever onset, patients develop a rash, often beginning on the face then spreading to other parts of the body. The lesions grow into fluid-containing pustules that form a scab. If a lesion forms on the eye, it can cause blindness. The illness typically lasts two to four weeks, according to the WHO. The person is infectious from the time symptoms start until the scabs fall off and the sores heal. Mortality is higher among children and young adults, while people whose immune system is compromised are especially at risk of severe disease. Pregnancy also carries a high risk of severe congenital infection, pregnancy loss, and maternal morbidity and mortality.
3. How is it transmitted?
Monkeypox doesn’t usually spread easily between people. Close contact with the virus from an infected animal, human or contaminated object is the main pathway. Most reported cases in the 2022 outbreaks have been linked to skin-to-skin contact with someone infected with this virus, such as during sex. The pathogen enters the body through broken skin, the respiratory tract or the mucous membranes in the eyes, nose, mouth, rectum and anus. Clubs, raves, saunas, sex parties and other activities where there is close contact with many people may also increase the risk of exposure, especially if people are wearing less clothing. Tests on patient saliva, rectal swabs, semen, urine and fecal samples found traces of the virus that could indicate the infectious potential of these bodily fluids and their potential role in disease transmission by close physical contact during sexual activity, a study from Spain found. Transmission from mother-to-unborn baby has also been documented. It can also happen indirectly through contact with contaminated clothing or linens. Common household disinfectants can kill it.
4. What’s unusual this time?
There have been multiple chains of human-to-human transmission occurring, including in sexual networks.
• Cases don’t involve recent travel to places in Africa where the disease is endemic.
• Although anyone can get monkeypox, most cases occur in men. In endemic areas of Africa, it was thought that was related to hunting practices, whereas in the current outbreak, most individuals are men aged 21 to 40 years who have sex with men, people with multiple sexual partners, or people who practice condom-less sex. Close skin-to-skin contact during sex is the primary mode of transmission in such cases.
• Flu-like symptoms haven’t always preceded the rash, and some patients first sought medical care for lesions in the genital and perianal region.
• Some patients experience complications, such as tonsillitis and inflammation of the rectum.
• In some cases, the lesions are mostly located at these sites, making them hard to distinguish from syphilis, herpes simplex virus, shingles and other more common infections, according to the US Centers for Disease Control and Prevention.
5. How fast is it spreading?
From just a handful of cases in Europe in early May, more than 16,000 cases, mostly in men, were reported across dozens of countries by late July, according to data collated by global.health. The WHO said five fatal cases have been reported, all in Africa. Monkeypox has probably been circulating undetected in Europe since at least April. In the US, caseloads tripled in July, with the virus reported in more than 40 states. Preliminary research estimates that among cases who identify as men who have sex with men, the virus has a reproduction number greater than 1, which means more than one new infection is estimated to stem from a single case. A UK study found anonymous sex has proved to be a barrier to effective contact tracing, with only 28% of men able to provide the names of all recent sexual contacts. Data from outbreaks in Canada, Spain, Portugal, and the UK suggest venues where men have sex with multiple partners are helping to drive spread.
6. How is it treated?
The illness is usually mild and most patients will recover within a few weeks; treatment is mainly aimed at relieving symptoms. About 10-to-15% of cases have been hospitalized, mostly for pain and bacterial infections that can occur as a result of monkeypox lesions. The CDC says smallpox vaccine, antivirals, and vaccinia immune globulin can be used to treat monkeypox as well as control it. Tecovirimat, also known as Tpoxx, was approved by the European Medical Association for monkeypox in 2022, but isn’t yet widely available, according to the WHO. In the US, it’s available through the Strategic National Stockpile, though some physicians have said lengthy delays for test results and the “very daunting task” of completing the necessary paperwork have frustrated efforts to prescribe the medication for infected patients. The UK Health Security Agency (HSA) also lists cidofovir as an antiviral that can be used.
7. What about prevention?
Limiting spread will require a comprehensive, international vaccination strategy and adequate supplies, public health experts Michael Osterholm and Bruce Gellin wrote in a July 19 editorial in the journal Science. Vaccination against smallpox can be used for both pre- and post-exposure and is as much as 85% effective in preventing monkeypox, according to the UK health agency, which is offering the Imvanex smallpox vaccine from Bavarian Nordic A/S to close contacts. It’s a newer vaccine based on non-replicating versions of the vaccinia virus that’s sold as Jynneos in the US and Imamune in Canada. Supply is limited, according to Osterholm and Gellin, who said more research is needed to determine whether intradermal, as opposed to intramuscular, administration and other dose-sparing approaches can provide adequate immune protection. Bavarian Nordic will provide the US with almost 7 million doses of Jynneos by mid-2023, according to the Department of Health and Human Services, which said on July 15 that more than 300,000 shots had been made available to states and jurisdictions since late May. (Bavarian Nordic said July 18 that it also has signed supply contracts with other, unspecified countries.) Immunization requires two injections administered four weeks apart. Otherwise, the main way to prevent infection is by isolating patients with the infection, monitoring their contacts, and ensuring health staff wear appropriate personal protective equipment.
8. Is monkeypox a pandemic threat?
WHO Director-General Tedros Adhanom Ghebreyesus declared the outbreak a so-called public health emergency of international concern, or PHEIC (pronounced “fake”), on July 23. The step will empower the agency to invoke new measures to curb the virus’s spread. He last declared a PHEIC in January 2020, during the early stages of the Covid-19 pandemic. Monkeypox is concentrated among gay, bisexual and other men who have sex with men, especially those who have had multiple, recent sexual partners, Tedros said. That fact means the contagion can be stopped with “the right strategies in the right groups.” On the flipside in some countries, the communities affected face life-threatening discrimination, he said. “There is a very real concern that men who have sex with men could be stigmatized or blamed for the outbreak, making the outbreak much harder to track, and to stop,” Tedros said on July 21.
9. Can it be stopped?
Former Food and Drug Administration Commissioner Scott Gottlieb said in mid-July that the window for controlling the US outbreak “has probably closed” and that only a small fraction of the cases in the country have been reported, with infections now occurring across the broader population. Pediatric infections have occurred in multiple countries, including the US and Spain. In the Netherlands, doctors reported a case in a boy under 10 with an immune impairment. Unable to identify how he was infected, they speculate that the virus may be present in the general population and that respiratory transmission may have played a role.
10. Do all infections cause disease?
Possibly not. Retrospective testing of 224 clinical samples collected in May for sexually transmitted infection screening found evidence of asymptomatic monkeypox infection in three men. The finding, by researchers at the Institute of Tropical Medicine in Antwerp, Belgium, was reported in a study released July 5 before it was peer-reviewed and published. Asymptomatic carriership was previously thought to play a negligible role in the spread of orthopoxviruses, the authors said. The existence of asymptomatic infections indicates that the virus might be transmitted to close contacts in the absence of symptoms, which suggests that identifying and isolating only symptomatic patients won’t be enough to contain the outbreak, and that vaccinating high-risk individuals is needed. Interestingly, one of the asymptomatic men in the study predated the first detected symptomatic case in Belgium by several days, wasn’t linked to other known cases and hadn’t traveled abroad or attended any mass gatherings. The authors said that might suggest that the virus circulated in Belgium before the outbreak was detected.
11. Where does monkeypox come from?
The reservoir host or main carrier of monkeypox disease hasn’t yet been identified, although rodents are suspected of playing a part in transmission. It was first diagnosed in humans in 1970 in Congo in a 9-year-old boy. Since then, most cases in humans have occurred in rainforest areas of West and Central Africa. In 2003, the first outbreak outside of Africa occurred in the US and was linked to animals imported from Ghana to Texas, which then infected pet prairie dogs. Dozens of cases were recorded in that outbreak.
12. Has the monkeypox virus mutated?
The monkeypox virus might be undergoing adaptive changes to make it better suited to the human host. Analysis of the genetic sequence of the virus collected from patients in Europe indicates that the current outbreak in non-endemic countries is caused by a strain that likely diverged from the monkeypox virus that sparked a 2018-19 Nigerian outbreak, according to a June 24 study in Nature Medicine. The authors, from Portugal’s National Institute of Health in Lisbon, identified some 50 genetic changes or differences compared with the original strain, including several mutations the authors associate with increased transmissibility. The changes are roughly 6-to-12 times more than scientists would expect based on the observed evolution of orthopoxviruses, they said. The strain belongs to the West African clade, or branch on the evolutionary tree, that usually has a case-fatality rate of less than 1%. (That compares with 10% for a second clade called Congo Basin, which appears on the US government’s bioterrorism agent list as having the potential to pose a severe threat.)
(Updates to add complications in section 4, hospitalizations in section 6, and section 9 on outlook for stopping spread and pediatric cases.)
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