On 29 April, a person in Nigeria developed an unusual rash and then travelled to the United Kingdom–carrying monkeypox with them. Since then, the virus has reached more than 70,000 people in over 100 countries. This has shocked health-care professionals around the globe, as the virus’s sustained spread is not similar to previous monkeypox outbreaks in people , due to a virus that lives on animals in Africa.
Almost six months after the virus began to spread, however, vaccination efforts have been made and behavioral changes have been made to contain the current strain, at least in the United States. Researchers warn that the situation could change in a number of ways. The virus could disappear over the next few years or months. The virus could spread to other parts of the world and reach new animal reservoirs ,, making it almost impossible to eradicate. Jessica Justman, an infectious disease physician at Columbia University in New York City, says that there are many factors at work that are working in opposite directions.
Specialists don’t expect that this year’s outbreak will cause the kind of worldwide disruption seen with COVID-19. The monkeypox virus doesn’t seem to be airborne like COVID-19, highly transmissible like smallpox or long-lasting in the body like HIV. It is most common in men who have had sex ,, especially those who have multiple partners or anonymous sex. It can cause severe, painful rashes but it is rarely fatal ; because it is a descendant of the milder ‘clade2’ monkeypox virus from West Africa. The more dangerous ‘clade 1 virus is found in Central Africa. It is unclear whether the strain that is causing the current outbreak of the virus is more transmissible than its Clade 2 ancestors. Elliot Lefkowitz, an academic bioinformatician at The University of Alabama at Birmingham, suggests that the virus could have spread faster to a population whose behavior led to it spreading more quickly.
” I believe we are in a strong position to control the epidemic, but it will largely depend on the behavior of the population,” states Gerardo Chowell Puente, an epidemiologist at Georgia State University, Atlanta.
With so much unknown about the new monkeypox strain, and so much dependent on how people react, it is difficult for us to predict future trends. Researchers have created scenarios to help predict how the outbreak might develop. These are the big questions surrounding monkeypox’s future.
What are the current trends?
Since mid-August, the number of confirmed cases of monkeypox in Europe and the United States has been declining.
Public-health experts credit behavioural changes: A study by the US Centers for Disease Control and Prevention found that nearly half of men who had sex with men had stopped engaging in risky sexual activities because of concerns about the virus. Public-health campaigns that taught people what symptoms to look out for and encouraged them report cases were also likely to be helpful.
Justman states that the monkeypox cases have serious caveats. Many people, and their doctors, may not recognize the symptoms or be afraid to report an infection due to the stigma. She says, “I don’t believe that all those who need to be tested are being tested.”
And some countries in South America, Africa are witnessing the opposite trend. Dimie Ogoina, an infectious-disease specialist at Niger Delta University on Wilberforce Island in Nigeria, says that it is too early to declare victory. In that country, where the current outbreak is likely to have started, cases continue to rise, with a weekly record of 56 reported in September. The Nigeria Centre for Disease Control in Abuja says the country has seen more than 400 cases. That is a small number compared with the United States’ 26,000 cases, but is almost certainly a vast undercount; it is likely that many more are being missed in Nigeria than in the United States, Ogoina says. Ogoina believes that Nigeria doesn’t have a strong disease surveillance programme. Ogoina also expects that many people who get the virus may not recognize it or visit a doctor. Rosamund Lewis (technical lead for monkeypox) at the World Health Organization (WHO), Geneva, Switzerland, says that reported cases will always be underestimated, especially in areas without good surveillance programs.
The WHO hopes to acquire 60,000 test kits to ship to Africa, but it is a logistical challenge to get people tested and diagnosed. Lewis states that it is not clear if the apparent increase in African cases is a result of an actual outbreak or if it is due to more thorough testing. She believes both are involved.
What do models project?
Because so little information is available about monkeypox’s spread and how different factors can affect it, it is unlikely that a model will be accurate for more than a few days. The WHO doesn’t release long-term monkeypox predictions. The CDC publishes a monthly technical report about the outbreak that includes a list of possible scenarios. However, the agency states that it is only moderately confident in its predictions. Its latest report, on 29 September, said that US cases are most likely to plateau or fall over the next month, but it is also possible they could increase exponentially (see go.nature.com/3sxrbmv).
Chowell Puente publishes a weekly forecast for monkeypox online. He follows trends in the United States as well as several European countries. He uses multiple scenarios to create a three-week forecast which has been fairly accurate in capturing real trends. As of 3 October, his forecast predicts that cases will either plateau or decline in the countries he models. Chowell-Puente states that these trends could change if there’s a new public health policy, a change in public behavior, or a mutation of the virus. However, it is unlikely that they will change quickly. Although he hasn’t yet modelled African cases, he says he will in the future.
Other models are more detailed but not necessarily more precise. Researchers at RTI International, a non-profit global research institution based in Research Triangle Park (North Carolina), developed a system that used information from previous monkeypox outbreaks, specifically the clade 2 ones, to project what might happen with the current strain. Previous notable clade 2 outbreaks include a short-lived one in the United States in 2003, which infected more than 70 people, and an outbreak in Nigeria that was spotted in 2017 and led to 146 suspected cases. This strain appears to have caused the current situation based on analyses of viral genomes.
Using information from these outbreaks–and assuming that the virus hasn’t significantly mutated -Donal Bisanzio (a RTI epidemiologist based in Nottingham, UK) estimated viral transmissibility. He and his team modelled how the virus would spread over the course of weeks in a virtual high-income country of 50 million people. In as-yet-unpublished work, the model predicts that if the virtual country did nothing to combat the virus, it could expect around 6,000 cases (that is, infecting 0. 01% of the population) before the outbreak fizzled out. This is due to the fact that the virus is not easily transmissible and because the model assumes that most older people have been vaccinated for smallpox, which is a related virus.
But researchers found that infections would decrease significantly if infected individuals were kept isolated for three weeks (to allow monkeypox to incubate) and if men who sex with women curtailed their sexual activity until the outbreak. A vaccine could be used to reduce the spread of infection.
Wouldn’t vaccination quash the outbreak?
Hundreds of thousands of doses were distributed in Europe and the United States in order to help vaccinate those at high risk. This includes men who have had sex with women and people who have come in contact with people with the virus. The United States expects that less than 2 million doses of the most commonly used vaccine, a repurposed smallpox Jab, will be available this year.
However, it is not clear how this has affected the decrease in case numbers. One preprint suggests that the vaccine does not appear to significantly increase the levels of antibodies that can neutralize monkeypox virus in people who have never received it. This is one component of an immune reaction. By contrast, the CDC has released crude case-rate data from US jurisdictions suggesting that monkeypox incidence–among those people recommended to receive the vaccine–has been more than ten times higher among unvaccinated than vaccinated individuals (see go.nature.com/3yifurf). These data were not adjusted for age, behaviour, or any other differences between the two groups. Numerous clinical trials are underway to test the effectiveness of vaccines.
It is not clear how long the vaccine effects will last. Ogoina, in an unpublished paper, reports that one person unvaccinated was reinfected nine months after he had recovered from his initial infection. This suggests that immunity may be fading faster than scientists anticipated.
But experts don’t believe that the vaccine will be ineffective. The smallpox vaccine was invented some 180 years before the disease was eradicated, but in that time, the variola virus that causes smallpox–a relative of the monkeypox virus–never evolved to resist the jab, Lefkowitz says. And although there are no currently approved treatments for monkeypox, a few antiviral drugs used for smallpox are currently being tested for their efficacy against monkeypox.
What could cause cases to increase?
While the European and US trends are encouraging, Justman warns that if people feel the danger has passed, an increase in risky behavior might lead to a resurgence. She is particularly concerned about the virus’s potential to spread on university campuses, where students live in close quarters and might play sports that involve extended physical contact. She says, “I don’t think things will remain the same.” “They will evolve, and their guidance will evolve .”
Ogoina, in Nigeria, is concerned that the virus could quickly spread to HIV-positive people–nearly 2 million people in Nigeria alone. Although evidence is scarce, records from the 2017 outbreak there suggest that monkeypox is much more deadly in many of these individuals, who often have weakened immune systems.
What if the virus mutates?
Unlike other RNA viruses like HIV or SARS-CoV-2, the monkeypox virus’s DNA is more stable than RNA and tends to accumulate mutations more slowly. A June paper in Nature Medicine surprised researchers when it reported that the virus that was spreading through Europe had picked up single-letter mutations much faster than previous poxviruses had. These mutations appear to have had no effect. They are likely markers of where human antiviral enzymes may have tried to kill the virus, researchers stated. Scientists have also found areas of deletions or rearrangements in some monkeypox genomes; these are common in poxviruses and haven’t yet been linked to a change in function.
It is difficult to predict the likelihood of the virus becoming more easily transmissible in future, Lefkowitz and other experts say. However, it cannot be ruled out. One analysis (not yet peer reviewed) of the mutations in monkeypox DNA caused by human enzyme activity has inferred that the current strain might have first reached humans in 2016, before the outbreak was identified in Nigeria in 2017 (see go.nature.com/3stezeu). Researchers aren’t sure if the virus has been transmitting between humans unnoticed since then or if it has hopped back into animals and crossed over to humans again, possibly aided by a specific mutation. Lefkowitz states that there is no single mutation that makes people more ill or more likely spread the virus.
” We don’t know transmission as well as we know the pathogen,” he says. He says that the likelihood of a worrying mutation occurring increases the longer an outbreak continues.
What if the virus finds a new reservoir?
Researchers are still unsure of the source of monkeypox in Africa. They believe it is a rodent. Rodents are a likely candidate: the 2003 US outbreak happened when rodents imported from Ghana infected pet prairie dogs. The virus has been found in many other mammals, including monkeys as well as anteaters.
Researchers discovered a dog in France with the virus in August. However, it is not known if the animal could transmit the virus to humans. The US CDC updated their guidance to discourage monkeypox-infected people from interacting with animals. Chowell-Puente believes that monkeypox is unlikely to find a permanent home outside of Africa. This is because the virus takes time to adapt to new species and transmit. The current strain seems preferable to humans.
What would it take to eliminate monkeypox altogether?
In areas of animal-to-human transmission, it is impossible to eradicate the virus completely without a vaccine. Ogoina claims that there is no risk of the virus spreading to other parts of Africa, but that African countries have not yet been given vaccines. Because wealthy countries have not yet donated vaccines to countries that can’t afford them, this is why it’s so surprising.
Even if vaccines are available, behavioral changes will be required to reduce monkeypox. This is especially true considering the unanswered questions regarding vaccine effectiveness. Adesola Yoinka-Ogunleye is a London-based epidemiologist at Nigeria Centre for Disease Control. She says, “If monkeypox is not controlled in endemic areas, then we know that we won’t be able to control it,” she said.
This article is reproduced with permission and was first published on October 12 2022.