By Jason Gale 

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 Africa with increasing frequency since the 1970s. Monkeypox now represents a serious, evolving threat after sparking outbreaks in dozens of countries this year, mostly in Europe, demonstrating again how readily an infectious agent that emerges in one country can quickly become an international concern.

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 milder. About 30% of smallpox patients died, while the fatality rate for monkeypox in recent times 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 normally transmitted?

Monkeypox doesn’t usually spread easily between people. Contact with the virus from an animal, human or contaminated object is the main pathway. The virus enters the body through broken skin, the respiratory tract or the mucous membranes in the eyes, nose or mouth. Transmission from one person to another is thought to occur through respiratory particles during direct and prolonged face-to-face contact. Vertical transmission from mother-to-unborn baby has also been documented. It can also happen through contact with body fluids or lesion material, or 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, in countries in which monkeypox isn’t normally present.

• Cases don’t involve recent travel to places in West and Central 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 condomless sex.

• Flu-like symptoms haven’t always preceded the rash, and some patients first sought medical care for lesions in the genital and perianal region.

• 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.

• Close skin-to-skin contact during sex is the primary mode of transmission among men who have sex with men.

• Semen from four patients in Italy collected around the time their symptoms appeared was positive for monkeypox DNA in three of the cases. It’s not yet known whether the fluid alone can transmit the infection.

5. 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 enought 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.

6. 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. 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.)

7. How fast is it spreading?

From just a handful of cases in Europe in early May, more than 7,100 cases, mostly in men, were reported across the region, as well as in the Americas, the Middle East, Asia and Australia by early July. One death was reported in an immuno-compromised person. Experts told a WHO meeting that monkeypox had been circulating undetected in Europe since at least April. 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 recent sexual contacts. This may challenge efforts to stem transmission ahead of LGBTQ pride celebrations occurring in major cities around the world. Data from outbreaks in Canada, Spain, Portugal, and the UK suggest venues where men have sex with multiple male partners are helping to drive spread.

8. How is it treated and prevented?

The illness is usually mild and most patients will recover within a few weeks; treatment is mainly aimed at relieving symptoms. For the purposes of controlling an outbreak, the CDC says smallpox vaccine, antivirals, and vaccinia immune globulin can be used. 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 Security Agency, which is offering the Imvanex smallpox vaccine to close contacts. It lists cidofovir and tecovirimat as antiviral drugs that can be used to control outbreaks. Tecovirimat was approved by the European Medical Association for monkeypox in 2022 but isn’t yet widely available, according to the WHO. Newer vaccines based on non-replicating versions of the vaccinia virus have been developed. Bavarian Nordic A/S, the only company with an approved vaccine specifically for monkeypox, will supply the US with more than 4 million doses of its Jynneos immunization in 2022 and 2023, according to the Department of Health and Human Services. The main way to prevent infection is by isolating patients suspected of having monkeypox and ensuring health staff wear appropriate personal protective equipment.

9. 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 the Democratic Republic of the Congo in a 9-year-old boy. Since then, most cases in humans have occurred in rain forest 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.

10. Is monkeypox a pandemic threat?

A meeting of the WHO’s Emergency Committee on June 23 determined that, at present, the event doesn’t constitute a public health emergency of international concern. Just over a week later, Hans Kluge, the WHO Regional Director for Europe, intensified a call for governments and civil society to scale up efforts to prevent monkeypox from establishing itself across a broader area. Small numbers of cases have been reported among household members, heterosexual contacts and non-sexual contacts, as well as among children. Where information is available, close to 10% of patients were reported to have been hospitalized either for treatment or for isolation purposes, Kluge said.