Ignored Warnings: Signals from the Monkeypox outbreak in Nigeria five years ago

The Paper's reporter Liu Dong

On 22 September 2017, the Nigerian Centre for Disease Control and Prevention was informed that an 11-year-old boy was suspected of being infected with monkeypox. This is the second human monkeypox case after 39 years.

At the time, the boy had been suffering from a fever of 11 days, blisters and pustules on the skin, mouth and nasal mucosa, accompanied by systemic lymphadenopathy. As the Nigeria Centre for Disease Control launched national monkeypox surveillance, more cases were reported everywhere, with 122 confirmed cases reported in 17 provinces as of September 2018, of which 7 died, with a case fatality rate of 6%.

As a "close relative" of smallpox, one of the deadliest viruses in human history, monkeypox develops similar symptoms but is milder. The monkeypox virus was first discovered in 1958 in animals in the laboratory. The first human case of monkeypox infection was detected in the Congo in 1970. In the early 1980s, monkeypox became one of the most important pox viruses after humans announced the eradication of smallpox. But monkeypox hasn't been known to most people for years, mainly because of its weaker infectivity and low case fatality rate.

In the 8 years since the first cases of monkeypox infection in humans were detected, there have been only a few sporadic outbreaks of human monkeypox cases in central and western Africa. Beginning in 1978, for 39 years, monkeypox almost disappeared. It wasn't until 2017 that it started to appear again.

In the five years since 2017, there have been several large-scale monkeypox outbreaks in Africa. In May 2022, WHO confirmed that monkeypox had triggered a widespread outbreak around the world outside Africa for the first time.

What really happened in 2017? How did this year's monkeypox epidemic affect the rest of the year? How can it help in dealing with today's monkeypox outbreak?

Missed alerts

Prior to this monkeypox outbreak in 2022, monkeypox was mainly found in Africa.

Monkeypox viruses in Africa have two distinct branches: the Congo Basin strain and the West African strain. Initially, only the Congo Basin strains recorded human-to-human transmission, and Congo strains also caused more severe disease and higher case fatality rates. Prior to 1978, there were only a few sporadic reports of milder West African strains in Nigeria.

After nearly 40 years of silence, Nigeria suddenly experienced an unusual outbreak of human monkeypox triggered by West African strains in 2017.

Nigerian scientists reviewed the monkeypox outbreak in the country 2017-2018 in a report published in The Lancet in 2019. At that time, 122 confirmed or suspected cases were recorded in 17 provinces, of which 7 died (case fatality rate 6%). The median age of those infected was 29 years, of whom 84 (69%) were male. Pustular rash occurs in all patients, and fever, itching, headache, and lymphadenopathy are common. The rash affects all parts of the body, with the face being the most affected.

Of the 7 deaths, 5 were males and 2 were females, with an average age of 27 years. According to the report of the attending physician, 4 of the deaths were HIV-positive. Of the four, three stopped antiretroviral treatment more than three months before contracting monkeypox, and one had never received antiretroviral treatment. All four people living with HIV rapidly deteriorated and died. The other two died from sepsis caused by secondary bacterial infection due to skin lesions. Another case was a 1-month-old infant whose mother had died of a similar disease (suspected monkeypox) 2 weeks earlier.

Circulation of cases and contacts suggests that the main routes of transmission of the virus are zoonotic and human-to-human (secondary). Genetic sequencing analysis has shown that there is human-to-human transmission in some confined facilities such as prisons.

What's more, the study found signs of a new human-to-human transmission of monkeypox — many patients are young men, have symptoms of genital organs, and have had sexual contact. Previously, monkeypox was thought to be spread through droplets and contact with body ulcers and scabs, as well as contact with wild animals, while sexual transmission did not attract much attention.

The study authors note that further research is necessary to explore understanding the natural animal hosts of monkeypox viruses and risk factors for virus transmission.

From 2017 to 2022 to date, more than 500 confirmed cases of monkeypox have been detected in Nigeria. However, this alert has never received much attention. There is little attention paid to monkeypox, and most people believe the disease is "only transmitted in Africa".

It was not until May this year, when the first case of monkeypox was reported in the United Kingdom, that suddenly, the monkeypox virus began to spread around the world, especially in developed countries in Europe and the United States, and people began to pay close attention to it.

"The outbreak in Nigeria in 2017 was definitely a warning sign." Anne Rimoin, an epidemiologist at the University of California, Los Angeles (UCLA), an epidemiologist at human monkeypox, said in an interview with Atlantic magazine. "There may be a lot of important information that has been missed, and the parts of this information are now finally being detected."

Five years of "jumping"

For nearly 40 years before 2017, there was hardly a single case of monkeypox reported worldwide. In the five years since 2017, there have been several large outbreaks of monkeypox in Africa. Beginning in May 2022, monkeypox triggered a widespread outbreak around the world outside of Africa for the first time.

It can be seen that 2017 was a key turning point, after the outbreak in Nigeria, monkeypox cases have not disappeared, spreading throughout Africa, and there have been small -- "spillover" of African spread to other continents.

Prior to this outbreak, there were 7 sporadic cases of monkeypox in the UK between 2018 and 2021. Among them, 4 cases were imported from abroad, 2 were family contacts of confirmed cases, and 1 case was a medical worker involved in nursing care. According to an epidemiological survey of the seven monkeypox cases mentioned above, published in The Lancet in May this year, seven people recovered, but the length of hospital stay ranged from 10 to 39 days.

None of the infected were vaccinated against smallpox. However, it is unclear whether the infection was due to a lack of immunity to the pox virus. One patient relapsed six weeks after a sexual act, with enlarged lymph glands in the groin. The authors of the above study speculate that monkeypox viruses may be active in the reproductive organs.

Both the UK in 2018 and the monkeypox outbreak worldwide in 2022 are genetically sequenced to the monkeypox strains of the 2017 Nigeria outbreak. Some scientists have tried to trace the transmission path of this round of monkeypox virus by sequencing the genome of monkeypox viruses, locating them on the evolutionary tree of the virus, and analyzing the mutations.

On May 30, the team of Evolutionary Biologist Andrew Rambaut of the University of Edinburgh in the United Kingdom compared the mutation of the monkeypox virus from 2017 to 2022 with the mutation before 2017, and the genetic mutation of this round of virus is more likely to occur in humans than the animal host. In addition, the researchers speculate that the monkeypox virus has been spreading among people since at least 2017.

Preliminary genetic analysis of the above study suggests that the evolution of the West African branch monkeypox lineage suddenly accelerated sometime between 2017 and 2022. Typically, pox virus mutations are slower, with one or two mutations a year, but by 2022 a staggering 47 mutations have occurred, and 42 of them are of specific types, which Lambot believes is unlikely to happen by random replication error; Instead, it resembles a feature of an immune system mechanism — which is present in both humans and animals — that introduces mutations in an attempt to render the virus dysfunctional.

In an interview with www.thepaper.cn, Lambot explained, "You can think of these mutations as 'scars' or 'footprints' that fight the host's immune system. ”

It is possible to speculate that monkeypox has found a new host since 2017: either it can be transmitted directly among humans, or it can be transmitted to humans through an animal.

Future concerns

At present, some basic questions remain unanswered, such as what exactly is the natural animal host of monkeypox. Although it is more common in rodents, it can also infect a variety of species, including primates and rabbits.

In addition, although previous studies have shown that monkeypox is not highly contagious, the uncertainty of how this wave of outbreaks will spread is still worrying. The possibility of neutral transmission in this monkeypox outbreak has not been fully confirmed.

Studies of the 2017 outbreak in Nigeria have pointed to the role of sexual transmission. Recently, the epidemiological investigation and diagnosis and treatment process of monkeypox cases diagnosed in Italy, Portugal, the United Kingdom and Australia in The European authoritative medical journal Euro Surveillance also showed that most of the patients were young men who had previously had sexual relations with men, and some patients were HIV-positive. In addition, the researchers also detected the monkeypox virus for the first time in the semen of 3 monkeypox patients in Italy. However, this still does not provide accurate evidence that the virus is transmitted through sexual routes (semen or vaginal discharge).

However, the World Health Organization warns that although the majority of current cases are male-male sex, anyone, regardless of their sexual orientation, is at risk of contracting monkeypox if they come into close contact with a patient, their clothing or bed sheets.

A major concern is that monkeypox may not stay in the current predominantly gay male population, and the number of cases may be underestimated.

Maria Van Kerkhove, head of the World Health Organization's New Diseases and Zoonotic Diseases Unit, said in a recent interview with stat, the U.S. health news website, "Our concern is that, so far, the extent of the infection is not known." There may be many more cases that have been missed. ”

Korkhof said, "At the moment it seems that most of the cases are in the gay and gay community. We have not seen an expansion to high-risk groups such as pregnant women, vulnerable groups, and children. So far, we have not seen serious cases. If the virus spreads to susceptible people, then we may see changes in the severity of the disease, which is exactly what we fear. ”

In any case, the unusual pattern and scale of the 2017 outbreak in Nigeria should have been a sign that monkeypox had changed in some way. But the world ignored it. Five years later, a new wave of human monkeypox with new characteristics appeared on a large scale in many countries in Europe and the United States. According to the latest statistics from the US Centers for Disease Control and Prevention (CDC), as of June 7, local time, more than 1,000 monkeypox cases have been reported worldwide, and a global disease outbreak is still in progress.

Responsible Editor: Zhang Wuwei Photo Editor: Le Yufeng

Proofreader: Yijia Xu