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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. 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 worldwide, demonstrating again how readily an infectious agent in one region can mushroom into a global emergency.

Monkeypox is a misnomer that results from the fact that it was 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; and cowpox virus, also called vaccinia, which is used in the smallpox vaccine. 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 has been about 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 patient 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 systems are 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. Inflammation of the brain and seizures are rare neurological complications. 

3. How is it transmitted?

Monkeypox doesn’t usually spread easily between people. Close contact with the virus from an infected person or animal — such as touching a lesion or contaminated object — is the main pathway. The pathogen enters the body through broken skin, the respiratory tract or the mucous membranes in the eyes, nose, mouth, rectum and anus. Tests on various patient specimens, including saliva, rectal swabs and semen, have found traces of the virus. 

• Detailed analysis of semen from a 39-year-old man in Italy found infectious virus in a specimen collected six days after his symptoms began. The findings, published Aug. 2 in Lancet Infectious Diseases, suggest genital fluids might be a source of infection.

• Infectious virus also was found in air samples collected during a bed linen change in rooms used to isolate patients, UK researchers reported in a study released in July, ahead of peer-review. That suggests monkeypox may be present in aerosols — suspended skin particles or dust — and not only in larger respiratory droplets, such as from a cough, which fall to the ground close to an infected individual.

• High concentrations of virus particles were also detected on toilets, sinks and other objects used by hospitalized patients, though it’s not yet known whether they could be a source of infection, a study from Germany 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. 

• This is the first time that cases and sustained chains of transmission have been reported in countries where infections aren’t linked to recent travel to places in West or Central Africa, where the disease is endemic.

• Outside those areas, the outbreaks have primarily affected men who have sex with men. Among cases with data on sexual orientation, 97.5% identified as gay, bisexual and other men who have sex with men, according to an Aug. 3 WHO report.

• 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, including bacterial “super infections,” painful ulcerations, and inflammation of the rectum and throat.

• 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. Is monkeypox a sexually transmitted disease?

No. Although it’s one of many pathogens capable of being transmitted during sex, it’s not considered an STD because it also uses other transmission pathways. Sexual behaviors are important risk factors, however. A sexual encounter was the likely source of spread in 91.5% of reported transmission events, according to the WHO report, with the most common setting being a “large event with sexual contacts.” Clubs, raves, saunas and other venues where there is close contact with many people may increase the risk of exposure, especially if people are wearing less clothing. 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 fast is it spreading?

From just a handful of cases in Europe in early May, more than 25,000 cases, mostly in men, were reported from 85 countries by early August, including 11 deaths, according to WHO and data collated by global.health. The virus 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. 

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. In the US, its safety and efficacy are being studied by the AIDS Clinical Trials Group, the research network established in the late 1980s to rapidly assess the safety and efficacy of antiretroviral drugs for HIV infection. In the meantime, it’s available through an expanded-access process from 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 it. The UK Health Security Agency (HSA) also lists cidofovir as an antiviral that can be used. 

8. What about prevention?

Public health experts say limiting spread will require a comprehensive, international vaccination strategy targeting high-risk groups — and adequate vaccine supplies. 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 shots of Imvanex from Bavarian Nordic A/S to close contacts of infected people. It’s a newer smallpox vaccine, based on non-replicating versions of the vaccinia virus, and is the only one also approved for monkeypox in the US, where its sold as Jynneos. (It’s called Imamune in Canada). Immunization requires two injections administered four weeks apart. But supply has been limited, leading to shortages. 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. 

9. Is monkeypox a pandemic threat?

WHO Director-General Tedros Adhanom Ghebreyesus on July 23 declared the outbreak a “public health emergency of international concern” — its highest level of alarm short of a pandemic. The so-called PHEIC (pronounced “fake”) empowers the agency to invoke new measures to curb the virus’s spread. Tedros last declared a PHEIC in January 2020 during the early stages of the Covid-19 outbreak. The WHO assesses the risk across its regions as:

• Moderate in Africa, the Americas, the Eastern Mediterranean and the South-East Asia regions

• Low-moderate in the Western Pacific region

The White House appointed Robert Fenton in August to coordinate the US government’s response and increase equitable access to tests, vaccines and treatments. But former Food and Drug Administration Commissioner Scott Gottlieb said in mid-July that the window for controlling the US outbreak had “probably closed,” with only a small fraction of the cases in the country reported. A case in a pregnant woman was reported in the US, where pediatric infections have also occurred. 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. Tedros warned that in some countries, the communities affected face life-threatening discrimination and so may not seek help, “making the outbreak much harder to track, and to stop.” 

11. 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.

12. 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.  

13. 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 with details from WHO Aug. 3 report, White House monkepox coordinator)

More stories like this are available on bloomberg.com

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