Pulling Back the Curtain

Mpox circulated in Nigeria for 8 years before it sparked a global outbreak. What happened? And could it have been stopped?

On 1 May 2017, a 35-year-old man with lesions all over his body came to the university hospital in Port Harcourt, an oil industry hub and the capital of Rivers state in southern Nigeria. A deep ulcer had eaten into the shaft of his penis. “It actually looked like it was going to drop off,” says Bolaji Otike-Odibi, the dermatologist who treated him.

Tests—and her experience—ruled out chickenpox, syphilis, and molloscum contagiosum, a viral infection that causes pearl-like bumps on the skin. “I asked all my colleagues,” Otike-Odibi recalls. “It was something we had never seen before.”

She took a sexual history of the man, who lived in Eleme, an hour’s drive east. He told her he had multiple sexual partners and that a condom had broken during intercourse a few days before the sores appeared.

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During the man’s hospital stay, which lasted 45 days, a second patient was admitted with similar lesions, including on his genitals, and a similar sexual history. He tested positive for HIV, but that didn’t explain his condition. “We were worried that this was an epidemic,” Otike-Odibi says.

The first two patients were discharged; in the subsequent months another two who fit the same profile arrived. Both had more advanced HIV infections and both died. “I took their pictures, I took their histories, because I knew that one day, somebody will tell me what this thing is,” Otike-Odibi says. “This is not normal. This thing means something.”

She didn’t find out what it meant until September of that year, when patients with similar symptoms started to come to a university hospital in Yenagoa, the capital of Bayelsa state, a 3-hour drive west of Port Harcourt. Many were young men with genital lesions, and many also had HIV. Ultimately, tests revealed those patients had monkeypox, a viral disease that had only been documented in Nigeria three times, with the last case occurring 39 years earlier.

When stories started to appear in the Nigerian press, some with photos of the pockmarked patients, Otike-Odibi realized her mysterious patients must have had the same disease. “I discussed with my colleagues and said: ‘This looks like those people we had earlier this year, do you remember?’” Otike-Odibi recalls. “And they all answered, ‘Yes, it looks like them.’”

Five years later, monkeypox exploded into a global epidemic, mainly in men who have sex with men (MSM). The World Health Organization (WHO) soon declared it a Public Health Emergency of International Concern (PHEIC) and renamed the disease “mpox” to avoid stigmatizing and racist reactions. The PHEIC was lifted in May 2023 after cases dropped sharply, but all in all, nearly 100,000 people in 116 countries have become infected so far.

Studies have shown that the virus causing this worldwide outbreak had its origins in Nigeria—and that it spread between people, under the radar, for at least 2 years before Otike-Obidi saw the four men.

Science traveled across Nigeria and spoke with mpox patients, doctors, scientists, and public health officials to piece together the early history of the outbreak. Powerful genomic studies have now pinpointed when the virus jumped from animals to humans and how it slowly spread across the country. But other questions are more difficult to answer. Why did the Nigerian outbreak fail to trigger international alarms? Why didn’t sexual transmission—never documented before 2017—receive more attention? And could this outbreak have been stopped before it went global?

In retrospect, it might seem obvious that a series of perplexing cases popping up in different cities, repeatedly involving frightening, painful genital lesions in young men and women, was an emerging sexually transmitted infection. But there is often a fog when new or little-known diseases break out—and in this case, the fog was thick.

The lessons are all the more urgent because a separate mpox outbreak has exploded this year in the Democratic Republic of the Congo (DRC), where a new, deadlier variant recently sped through a mining town, clearly driven by men visiting women sex workers. It then spread to Goma, a city of nearly 2 million, and related cases have cropped up the past month in nearby Uganda, Burundi, Rwanda, and Kenya, none of which had ever seen mpox before. On 15 August, Sweden reported that a person who had traveled to Africa was infected with a related virus as well.

The growing outbreak led WHO Director-General Tedros Adhanom Ghebreyesus to declare a PHEIC for the second time on 14 August. “This is something that should concern us all,” said Tedros, who expressed hope that the PHEIC would help better coordinate the global response and attract new funds to help countries in need. “The potential for further spread within Africa and beyond is very worrying.”

Mpox received its original name after it was discovered in Asian monkeys in a Danish laboratory in 1958. But “monkeypox” was a misnomer: The natural hosts of the virus, a relative of smallpox, are primarily small, forest-dwelling rodents in Africa, such as Gambian pouched rats, rope squirrels, and dormice. Outbreaks begin when people come in contact with these animals.

The first human case ever detected, in 1970 in the DRC, was a 9-month-old boy, and until recently most patients have been children. Nigeria had two cases the next year, and one more in 1978, bringing the total at that point to 36. “Evidence is that this rare and sporadic disease is not highly transmissible and does not appear to be a public health problem,” a WHO report about the 1978 case stated.

But mpox was inadvertently given an opportunity to spread more widely. In 1980, WHO declared that smallpox—an ancient scourge that killed up to 30% of those infected—had been eradicated. Vaccination against the smallpox virus could end, a global commission announced. That vaccine likely protected against mpox as well, and the commission acknowledged that more mpox cases might emerge. Still, there had only been 45 documented mpox cases until then, all in West and Central Africa, and its final report noted, again, that the virus did not have “the potential for epidemic spread.”

Between 1981 and 1986, an aggressive WHO-led surveillance program identified 338 people infected in the DRC by the “Congo Basin” mpox variant (renamed clade I in 2022 to avoid stigmatizing the region). The disease had a 10% fatality rate, in contrast with the “West Africa” (now clade II) virus, for which the fatality rate is estimated at 1%. But outbreaks always petered out. Even a startling upsurge in 1996 that lasted more than 1 year and included 511 suspected cases was no cause for alarm, researchers insisted. “There is no evidence to date that person-to-person transmission alone can sustain monkeypox in the local population,” one study asserted.

A freak outbreak in the United States in 2003 seemed to confirm this. Seventy-two people in six states became infected by pet prairie dogs that had been housed together with rodents imported from Ghana. The outbreak, caused by clade II virus, did not kill anyone in the U.S. and ended within one month. A report in The New England Journal of Medicine (NEJM) stressed that “even in the total absence of immunity provided by smallpox vaccination” mpox could not sustain itself in humans.

That same year, epidemiologist Anne Rimoin of the University of California, Los Angeles began to collaborate with a team led by microbiologist Jean-Jacques Muyembe of the DRC’s National Institute for Biomedical Research to improve local surveillance of mpox. “It made sense to me that there was probably a lot more disease out there and nobody was seeing it,” Rimoin says.

She was right. “The incidence of monkeypox has dramatically increased in the DRC,” the team reported in 2010. One district had seen 760 cases over a two-year period. Waning immunity clearly played a role: More than 90% of the affected people had never received a smallpox vaccine. Boys living and hunting in forested areas were at the highest risk.

But still, one outbreak after another faded away. The DRC does not have roads crisscrossing the country or busy international airports, and the virus never even made it from the remote villages where it emerged to Kinshasa, the capital—let alone to the rest of the world.

All those years, Nigeria didn’t report a single mpox case.

That changed in 2017, with the outbreak that surfaced in Bayelsa state. The first suspected case there was an 11-year-old boy who checked into a private hospital in Yenagoa on 11 September with what looked like a severe case of chickenpox. Over the next 11 days, increasingly painful big blisters and pustules appeared all over his body, including the soles of his feet and the palms of his hands—regions that chickenpox rarely affects. An astute doctor, searching through pictures on the internet, wondered whether it might be mpox.

The boy was sent across town to the Niger Delta University Teaching Hospital (NDUTH), which had one infectious disease specialist, Dimie Ogoina. After examining the boy, Ogoina agreed the symptoms seemed consistent with mpox and notified the recently formed Nigeria Centre for Disease Control and Prevention (NCDC). A team came to investigate and take samples, sending them to the Pasteur Institute of Dakar for testing. It didn’t seem like an urgent public health threat.

But more suspected cases soon streamed into the hospital’s isolation ward. An NCDC report on 16 October finally provided confirmation that at least three cases were mpox and noted another 74 suspected cases in 11 of Nigeria’s 36 states. What seemed like a one-off now had the markings of a serious outbreak. “They were calling me from BBC and all over the place,” Ogoina remembers.

As the outbreak grew, so did fear and stigma. The boy, who recovered, faced a harsh welcome when he returned home. “They started calling him ‘monkey boy’ in the neighborhood,” says his uncle, who was also infected and asked that his name not be used. A barber refused to cut the boy’s hair. The family’s restaurant saw its business plummet.

When a rumor spread that the military was injecting children with the mpox virus, some schools closed and the president made a statement to calm the panic. A major newspaper wrongly described mpox as “a new airborne Ebola-like viral disease” and another said church leaders “maintained that the outbreak of the disease was spiritual.”

The surge in cases soon overwhelmed the isolation ward at NDUTH, and one doctor, Oru Inetsol Oru, became infected himself. His lesions were painful and itchy, he recalls, and he was angered by colleagues who teased him mercilessly, especially for putting calamine lotion on his facial sores. “They said I looked like a popular Nigerian cartoon,” Oru says.

Ogoina became increasingly perplexed. He had read that outbreaks in the DRC typically sputtered out and the virus rarely occurred outside remote villages. Was Nigeria now seeing repeated jumps from animals to humans? Or was the virus moving between people, and if so, how?

The uncle and the boy had played with a monkey in the neighborhood, and the uncle had regularly visited slaughterhouses for the restaurant. But other clues pointed in a different direction. In this outbreak, most cases weren’t children but young men, many with genital lesions. More than 60% said they recently had multiple sexual partners. A woman infected with mpox also had genital lesions. Several patients had undiagnosed HIV infections. The uncle, too, revealed to Ogoina that he had had genital lesions. He had visited a sex worker a week before becoming ill, he said, which he suspected led to the infection of his nephew and other family members. “I was feeling guilty, very guilty, even to now I’m feeling it,” the uncle says.

By mid-November 2017, NCDC had identified 146 suspected cases in 22 of Nigeria’s 36 states. Clearly, the virus had been spreading under the radar—“cryptically,” as epidemiologists say—for some time. Two-thirds of lab-confirmed mpox cases were in adults, and twice as many men as women were affected. There were three family clusters, and Oru’s case. Still, NCDC initially concluded there was no evidence of “sustained” human-to-human transmission.

But as more case clusters started to appear, including one in a prison, “we began to say that we are seeing that this virus is being sustained in a human population,” says Adesola Yinka-Ogunleye, an epidemiologist who led NCDC’s investigative team and is now working on a Ph.D. at University College London.

Ogoina says he had a “hunch” early on that sex was helping spread the virus. He felt too few Nigerian clinicians were looking for sexual transmission and that NCDC was overly cautious about publicly raising the possibility. “Dimie was convinced about the sexual aspects of onset,” Yinka-Ogunleye says. But she was not so sure, given that the virus can also spread through other types of contact with people or shared objects.

Ogoina says he met particularly strong skepticism about sexual transmission outside of Nigeria. At one meeting, “they were not interested in the work,” he says. “In fact, they asked me to be quiet.” Reviewers tried to “kill” papers he submitted, he says. He reads from one 2019 review: “It is quite reckless to speculate [about] possible sexual transmission as no epidemiological data are available in the literature.” (Only two previous reports about mpox mentioned genital lesions, one a 1987 paper that reviewed 282 mpox cases in the DRC, and the other a 2005 look back at the U.S. outbreak. Neither suggested sex spread the virus.)

All of this made both Ogoina and Yinka-Ogunleye cautious. A paper they published in PLOS ONE in April 2019 mentioned that sexual transmission was “plausible in some of these patients”—but not until page eight. It drew little attention.

In any case the Nigerian outbreak seemed to be petering out. Suspected cases dropped from a high of 198 in 2017 to 65 in 2019, and 35 in 2020, with only eight confirmed (see graphic, right). Ogoina now says surveillance had simply weakened. Yinka-Ogunleye thinks the decline was real, abetted by COVID-19 social distancing restrictions in 2020.

Yet there were other red flags that the outbreak in Nigeria was larger and more threatening than realized. Between 2018 and 2021, the United Kingdom, the U.S., Israel, and Singapore reported a total of nine mpox cases. All involved travelers from Nigeria. Three were men who had genital lesions. Nobody connected the dots.

In early May 2022, cases of mpox started to pop up in Portugal, Spain, and the U.K., nearly all in MSM who had attended gay festivals or visited bathhouses. Suddenly, the disease had virologists’ attention. Within weeks, a team led by microbial genomicist João Paulo Gomes of Portugal’s National Institute of Health reported that the genome of an mpox virus isolated from a Portuguese case closely matched the clade II viruses that had turned up earlier in the U.K., Israel, and Singapore in travelers from Nigeria.

Before May was over, evolutionary biologists Áine O’Toole and Andrew Rambaut at the University of Edinburgh posted an eye-opening analysis about the history of the outbreak. The mpox virus mutates more quickly and in easily recognizable ways when attacked by APOBEC3, a human enzyme that apparently has evolved to cripple viruses. By comparing the sequences of viruses exported to the U.K. from Nigeria in 2018 with ones that had just surfaced in Europe and the U.S., O’Toole and Rambaut found 42 substitutions had occurred—far more than would be expected in four years without the pressure from APOBEC3.

“What we’re seeing are scars in the virus genome that has been attacked by the enzyme, but they are not quite enough to stop it spreading,” O’Toole says. She and Rambaut concluded there had been sustained human-to-human transmission “since at least 2017.”

Rambaut’s lab later teamed up with Gomes and researchers in Nigeria to analyze how APOBEC3 affected the virus before it left Africa. Sequence data from 42 genomes from 2017 to 2021 and one from 1971 showed it had likely circulated continuously in humans since as early as 2015, they reported in November 2023. The data also suggested the epidemic began with a single infection, likely a spillover from a wild animal.

A study based on 112 additional genomes led by molecular biologist Christian Happi, who heads the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemer’s University in Ede, Nigeria, added details about the geographic spread. In a preprint posted in June, Happi’s team concluded that the virus likely jumped from animals around July 2014 in Rivers state, home of Port Harcourt, or nearby Abia state. From there, it was repeatedly introduced to other parts of Nigeria, including Lagos, a city of 15 million people, and Abuja, the capital, each of which has a busy international airport.

The spread was sluggish. A model based on the genomic evidence suggests cases doubled every two years, and outside of the South South (a region that includes Rivers, Bayelsa, and four other states), most human-to-human transmission chains died out. “There is exponential growth, but it is really slow,” says Edyth Parker, first author of the preprint, who splits her time between Scripps Research and ACEGID.

But why did the virus spill over to humans in the first place, after nearly four decades without cases in Nigeria? In one scenario, Rambaut says, the virus might have infected a new rodent species that had no defenses against it and that came in contact with humans. Climate change, abundant harvests, or other environmental factors might have caused populations of an existing rodent reservoir to surge. Or perhaps humans had more contact with rodents because of, say, deforestation.

A more mundane explanation is that mpox had repeatedly spilled over for decades but was confused with chickenpox and never noticed—and the virus never spread for long. Over time, as immunity waned, the odds of sustained transmission grew: By 2016, only 10% of the nearly 200 million Nigerians had been vaccinated against smallpox, and a mere 2.6% still had protective levels of immunity, according to a model published in 2021.

The animal source remains a mystery. A 2023 study of 240 rodents in Bayelsa, Rivers, and two other South South states found five animals from three species that had antibodies and DNA of orthopox viruses, the genus to which mpox belongs. These clues “indicate the potential role of these animals in the circulation and transmission,” the researchers wrote, but the tests could not confirm the presence of mpox virus itself.

Whatever the wild animal source, the South South provided a hospitable environment for an outbreak to take hold and spread among humans. The region is the center of the country’s oil and gas industry, which brings in workers from far and wide, most of them men. “They have the money to spend, and so this actually attracts the sex workers,” Otike-Odibi says. Port Harcourt has Nigeria’s third-busiest international airport, and many oil and gas workers frequently return home for holidays, potentially transporting the virus around the country—and the world.

Urban centers likely allowed the Nigerian outbreak to persist and grow, says Michael Worobey, an evolutionary biologist at the University of Arizona who collaborated with O’Toole and Rambaut on the study. In a 2021 Science paper, Worobey showed that SARS-CoV-2 needed the megacity of Wuhan, China, for the COVID-19 pandemic to take off. “If you drop that virus into a human being in a rural area, 99% of the time it’s going to go extinct,” he says. Mpox “seems part of the same story. … It takes a city.”

There’s no evidence the mutations the virus has gained along the way have boosted its ability to spread through sex, for example by enabling it to infect sperm cells or genital mucosa more readily. “I think the sexual epidemics are just the product of the very chance event of getting into a sexual transmission network that is very efficient at transmitting mpox,” Rambaut says.

On a drizzly afternoon in October 2022, nurses brought Adeola Fowotade, a physician at University College Hospital, Ibadan, to a gut-wrenching scene inside a cubicle with blue curtains: the lifeless body of a patient collapsed on the floor. A nurse had found him convulsing and tried to resuscitate him. When she opened his mouth, she saw foam and black particles. She noticed an unusual odor, too, and found packets of rat poison by his bed. The man had taken his own life.

His story spotlights a Nigerian reality that may have helped mpox fly under the radar: the fear of seeking care for sexually transmitted infections in general—and the stigma around gay sex in particular.

Fowotade had first seen the 40-year-old man three days earlier, after he was admitted with extensive, painful lesions on his genitals, palms, and chest. The man explained he had been married but also alluded to a same-sex partner who had similar lesions. Testing confirmed he had mpox and was also positive for HIV, which had caused his immune system to collapse.

Fowotade assured him his health would soon return once he started taking anti-HIV drugs. “I sat with him for two hours, telling him stories of people who have had these kinds of things, they are fine,” she says. “But he just kept staring at me. I knew he was really very upset.”

No one knows why the man died by suicide, but fear and shame may well have played a role. In Nigeria, gay sex is a criminal offense punishable by up to 16 years in prison. “There is a lot of blame game,” Fowotade says. “Our cultural beliefs, and even our religious attachment, makes us believe that some of these things are sins, or they are things that are stigmatizing. So even though people do them, they will deny it with their last drop of blood.”

The mix of Nigerian law and cultural taboos has made it harder to establish the nature of sexual transmission in Nigeria. Ogoina finally reported convincing evidence of heterosexual mpox spread in 16 patients—including three men who had visited commercial sex workers—in NEJM in May 2023. (The paper also documented that people without symptoms could transmit the virus, further complicating efforts to trace outbreaks.)

Evidence for spread among MSM in the country has been more elusive. The global outbreak was largely driven by the sexual networks at large festivals and bathhouses—which Nigeria does not have—that help infections spread at high speeds. Some of the sparse evidence in Nigeria comes from a clinic in Abuja called TRUST, which cares for many MSM—about 40% of whom are married to women—and transgender people. Run by the Institute for Human Virology, Nigeria (IHVN), TRUST took blood from 150 volunteers after the 2022 global outbreak and tested it for mpox antibodies. They didn’t find any evidence of past infection. And in a detailed study of 160 patients seen between February 2022 and January 2023, Ogoina and other clinicians found just 5% were MSM, versus 98% globally. But the authors noted that laws prohibiting same-sex relations may have led to an “underascertainment” of MSM “due to fear of stigma and victimization.” IHVN and University College Hospital, Ibadan have stored samples that may offer a clearer picture of how widely mpox spread prior to 2022—and whether it circulated in MSM communities.

In retrospect, Ogoina says he may not know whether some of his patients were MSM because it did not occur to him to ask. “I did not really focus on that,” he says.

For 52 years, mpox was restricted to a dozen countries in sub-Saharan Africa. Could it have been stopped before spreading worldwide?

Some have argued the world should have paid more attention to Ogoina’s findings from 2017. “He discovered the origin of the monkeypox outbreak—and tried to warn the world,” an online story posted by National Public Radio declared in July 2022. Nature put Ogoina on its list of 10 scientists who helped shape science that year, dubbing him the “monkeypox watchman.” The next year, Time included him in its list of the 100 most influential people in the world.

Ogoina says he felt simultaneously shocked and privileged by the worldwide praise, seeing it as evidence that a doctor working at a small Nigerian hospital with few resources could make an important observation. He has enjoyed the acclaim, too—his office features a life-size poster of himself, dressed in a tuxedo, that lists his accolades. But he acknowledges his warnings were subdued. He says some people have asked him, “Why didn’t you make more noise?” But the evidence wasn’t all that convincing, he says, and he made little headway persuading NCDC epidemiologists and other clinicians to explore the hypothesis. “They didn’t look for it,” he says. “I was the only one.”

The Global North could have done more to help Nigeria respond to its outbreak when it surfaced, says Ogoina, who chaired the Emergency Committee that unanimously advised Tedros to declare the second global emergency on 14 August. After all, that’s “where resources and global health decision-making reside,” he says, and it neglected mpox for decades. But he adds that “African governments must also take ownership of the health of their populations.”

Happi says Nigeria could have tried harder to stop the outbreak. “If it had stepped up surveillance in 2017 and used mpox vaccines to stop chains of transmission, the country could have eliminated the virus then,” he contends. Oyewale Tomori, a prominent Nigerian virologist who heads the West Africa National Academy of Scientists, agrees that the country has neglected the problem. “Monkeypox has been with us the last 50 years, and we didn’t do anything,” Tomori says. “We’re waiting for outsiders to come and do for us.”

Rambaut says stopping the virus in Nigeria would have been challenging, because few believed at the time that sustained human-to-human transmission was even possible. And if clandestine sex work and MSM networks were significant drivers of the spread, health workers would have struggled to find, treat, and isolate infected people.

Now, however, the nature of the outbreak is clear—and the virus is still spreading in Nigeria. Since the 11-year-old boy showed up at Ogoina’s hospital, Nigeria has documented more than 4,500 suspected cases. The U.S. government this spring donated 10,000 doses of an mpox vaccine to Nigeria. It’s a drop in the bucket compared with European and U.S. vaccination efforts, and Nigeria hasn’t even decided who to vaccinate.

And the new clade I variant from the DRC is banging on the world’s door. There’s far less fog this time: Scientists have warned of the threat for several months, and African countries have been on high alert. The European Union on 14 August donated 215,000 doses of mpox vaccine to the Africa Centres for Disease Control and Prevention (Africa CDC), which itself dedicated $10.4 million to bolster the response. Africa CDC Director-General Jean Kaseya separately declared a Public Health Emergency of Continental Security to strengthen countries’ “collective will” and create a joint action plan.

Kaseya criticized the world at large for not offering Africa more support during the first mpox PHEIC, in 2022 and 2023. “When this declaration ended, cases in Africa continued to increase, and today, we are facing the consequence of not having appropriate assistance,” he said. “If we don’t deal with mpox as we need to do, we can be surprised.”