Virus World

A new lineage of the mpox virus linked to efficient human-to-human transmission has been identified in the Democratic Republic of the Congo (DRC) — and the researchers behind the finding are calling for swift action to 'avert another global mpox outbreak.'

A team of Canadian and international scientists working on the ground in DRC began tracking a large mpox outbreak in the country's Kamituga mining region last year. From October 2023 onward, cases spread rapidly with more than 240 suspected infections identified within five months. Out of roughly 100 confirmed cases, a third were among sex workers, the team wrote in their latest paper. Mpox — previously known as monkeypox — burst onto the global landscape in 2022, spreading to dozens of countries through sexual networks that largely impacted men who have sex with men. Infections can lead to painful lesions and, in more severe cases, sepsis, lung nodules and even death. Genomic analysis of the recent Kamituga outbreak uncovered what lead researcher Dr. Placide Mbala-Kingebeni calls an "alarming" finding: a new, distinct clade Ib lineage of the mpox virus featuring mutations that are a hallmark of efficient transmission between humans. Mbala-Kingebeni's findings were published online this week as a pre-print, meaning the research has not yet been peer-reviewed. 

The researchers say the ongoing situation in Kamituga echoes the 2017 to 2018 outbreak of clade IIb mpox in Nigeria, which is now widely considered a harbinger to the unprecedented global spread of the disease a few years later. Mbala-Kingbeni told CBC News the worldwide spread of mpox in 2022 involved a form of the virus that's thought to cause less severe disease, though some scientists warn underreporting of cases makes it tricky to know the precise differences between each clade. (Clades are subtypes of a virus that arise from a common ancestor. In the case of mpox, the two main clades identified so far are clade I and clade II.) "There is a high risk that this more virulent clade, that's more adapted to human-to-human transmission ... can be transmitted silently from one person to another and be sustained at a global level," added Mbala-Kingbeni, an associate professor at the University of Kinshasa and head of epidemiology and global health at the DRC National Institute of Biomedical Research's Clinical Research Center. Urgent measures are needed — including expanded surveillance, contact tracing and targeted vaccination efforts — to contain this "pandemic-potential" outbreak, the researchers wrote.

Ongoing DRC outbreaks 'alarming'

The team's concern stems, in part, from Kamituga's demographics. The densely-populated region lacks healthcare infrastructure to handle a large-scale outbreak, and the researchers believe the reported cases are likely an underestimate.  It's also a travel hub, with large amounts of movement between the region and neighbouring countries in Africa, such as Rwanda and Burundi, including sex workers who "frequently return to their countries of origin."  "The highly mobile nature of this mining population poses a substantial risk of outbreak escalation beyond the current area and across borders," reads the paper. Toronto-based infectious diseases specialist Dr. Isaac Bogoch, who was not involved in the research, praised the team for showing a "subtle but real" genetic difference in the mpox virus samples from Kamituga. The research further raises alarms about the record-breaking levels of mpox circulating in DRC, he added, and the country's lack of vaccines or therapeutics to contain the spread of the virus. But he cautioned against over-interpreting the results, saying the findings don't prove this new lineage is even more transmissible than before or capable of evading existing treatments and vaccines. Further research is needed, Bogoch stressed, to better understand a virus that's causing massive outbreaks in Africa and is still quietly circulating locally in Canada as well — with more than 20 cases reported in Toronto alone so far this year. The study also doesn't change the existing possibility that a different lineage of mpox could eventually jump internationally, Bogoch added. "Without this mutation we would have this exact same conversation," he said.  "The alarming part to me is we know there's an ongoing outbreak in [DRC], and we still don't have a coordinated global response."

Preprint of the study available in medRxiv (April 15, 2024);

https://doi.org/10.1101/2024.04.12.24305195 

Experts have long understood that a new polio vaccine developed to try to minimize the risks associated with the oral polio vaccine made by Albert Sabin might also cause the problem it was created to sidestep. It’s now clear that theoretical risk is a real one. The Global Polio Eradication Initiative announced Thursday that six children in the Democratic Republic of the Congo and one in Burundi have been paralyzed by viruses from the new vaccine, which is referred to as novel oral polio vaccine, or nOPV2. (The “2” signals the vaccine targets type 2 polioviruses.) In addition, five environmental samples collected from Burundi contained the so-called type 2 circulating vaccine-derived polioviruses, or cVDPV2s. “We are disappointed,” said Ananda Bandyopadhyay, deputy director for technology, research, and analytics on the polio team of the Bill and Melinda Gates Foundation, a partner in the polio eradication effort. “Any such outbreak is disappointing.” The Gates Foundation is one of a half-dozen partners in the Global Polio Eradication Initiative. The others include the World Health Organization; UNICEF, the United Nations Children’s Fund; the Centers for Disease Control and Prevention; Gavi, the vaccine alliance; and the service club Rotary International.

Bandyopadhyay and the polio eradication initiative itself were quick to point out that this turn of events was not unexpected. The live polioviruses used in oral vaccines are manipulated to eliminate their ability to paralyze. Children who receive these vaccines shed live viruses in their stools. In settings where sanitation and hygiene are poor, the viruses can move from child to child, effectively indirectly vaccinating children whom vaccination teams haven’t reached — a feature that has made the Sabin vaccines the workhorse of polio eradication. But if the viruses spread long enough, they can regain the ability to paralyze — a problem that led the polio program to stop using type 2 oral vaccine in 2016, in a bold and ultimately failed effort, known as “the switch,” to stop spread of type 2 viruses from the Sabin vaccines. The injectable polio vaccine, designed by Jonas Salk and used in affluent countries like the United States, does not contain live viruses and therefore doesn’t trigger paralysis. But while it prevents paralysis, it cannot stop transmission of polioviruses — wild type or vaccine derived — which makes it less useful in countries where vaccine-derived viruses are spreading. In recent years, the nearly 35-year-old effort to rid the world of polio has managed to drive numbers of infections with wild viruses down to low levels. Last year, only three countries — Pakistan, Afghanistan, and Mozambique — reported 30 cases. So far this year, there has been only one case detected, in a child in Afghanistan. But as the battle against wild viruses has gained ground, use of the oral vaccine has seeded chains of transmission of the vaccine-derived viruses. In 2022, nearly 800 children or young adults in roughly two dozen countries developed paralytic polio after being infected with one of the vaccine viruses from the Sabin vaccines. Among them was an unvaccinated young man in New York State, this country’s first polio case in nearly a decade.

Of the three original strains of polio — types 2 and 3 have been eradicated, only type 1 remains — the portion of the Sabin vaccines targeting type 2 viruses triggers the vast majority of vaccine-derived polio cases. A few years ago, with support from the Gates Foundation, the novel oral vaccine targeting type 2 viruses was developed. It was put into use in mid-March of 2021 — two years ago. Since then 590 million doses of nOPV2 have been administered in 28 countries. The seven cases of paralytic polio, which stem from two chains of vaccine-derived viruses, are far fewer than would likely have occurred if those hundreds of millions of doses had been the Sabin vaccine, Bandyopadhyay said. An analysis from the Gates Foundation’s polio team suggested that there would have been 30 to 40 new chains of type 2 vaccine viruses over that period, rather than two, he said. Other experts agreed it is important to put the finding in context. “I’m not alarmed. It’s a much better tool than we used to have,” said Walter Orenstein, a polio expert at Emory University. “It’s not perfect,” he said of the new oral vaccine. “But given its rarity, it hopefully will be able to do the job. At least not generate lots of these kinds of outbreaks.” Kim Thompson, president of the nonprofit organization Kid Risk and a mathematical modeler who has worked on polio eradication for decades, said this event is only showing the world that what was assumed about the new oral vaccine is in fact true. “This possibility has always been out there in the cards. And really this is just the proof of concept that the nOPV2 can lose the attenuated mutations and behave like other live polioviruses, and particularly do so in populations where [vaccine] coverage is low,” she said. But Thompson is worried that given the low levels of immunity to type 2 polio, even less frequent outbreaks of vaccine-derived viruses will amplify a problem the polio program is struggling to contain. “The reality is that since we have transmission happening in these areas with low coverage and this immunity gap that exists … there’s more room for these viruses to go. That’s part of the challenge here, is to figure out what to do to stop type 2,” she said.

Helen Branswell

Senior Writer, Infectious Diseases

Helen Branswell covers issues broadly related to infectious diseases, including outbreaks, preparedness, research, and vaccine development. Follow her on Mastodon and Post News.

In past Ebola outbreaks, fatality rates have varied from 25% to 90% - but effective treatments are now available, and patients who receive care early see their chances of survival improve significantly.  An outbreak of Ebola has been declared in the Democratic Republic of the Congo - four months after the last one ended. A case was confirmed in a 31-year-old man on 5 April. He was admitted to an Ebola treatment centre on Thursday, but died hours later. The World Health Organisation's regional director for Africa, Dr Matshidiso Moeti, said: "Time is not on our side. The disease has had a two-week head start and we are now playing catch-up." Overall, this is the 14th Ebola outbreak that the Democratic Republic of the Congo has seen since 1976, which is when the virus was first discovered.

Efforts to stem the current outbreak have already begun, with officials confirming that the patient who died has received a safe and dignified burial.  More than 70 of his contacts are also being traced - and vaccinations in the city of Mbandaka are going to be stepped up. Ebola is transmitted by coming into contact with the bodily fluids of an infected person or contaminated materials.  Early symptoms include muscle aches and a fever, which resemble those seen in other common diseases such as malaria. In past Ebola outbreaks, fatality rates have varied from 25% to 90% - but effective treatments are now available, and patients who receive care early see their chances of survival improve significantly. Dr Moeti added: "The positive news is that health authorities in the Democratic Republic of the Congo have more experience than anyone else in the world at controlling Ebola outbreaks quickly."

The country is now battling two Ebola outbreaks, the coronavirus and the world's largest measles epidemic. A second Ebola outbreak has been confirmed in the Democratic Republic of Congo, some 600 miles from an ongoing epidemic that has claimed more than 2,200 lives. According to the World Health Organization six cases of the highly contagious haemorrhagic fever have been identified and four people have so far died near Mbandaka, the regional capital of Équateur Province.

The outbreak was first announced on local radio by the region's governor, Bobo Boloko Bolumbu, on Monday morning. He said samples from the cases were sent to the INRB, the country’s national medical research organisation in Kinshasa, for secondary confirmation. “The laboratory has given us the information that all the deaths analysed since the 18th of May are a consequence of the Ebola virus,” the governor said. “However, for precision, the samples have been sent to the INRB for quality control. 

“I ask the population to be calm and to continue to respect hygiene measures. Regularly wash your hands with soap. Don’t, say, greet with your hands. Don’t touch ill or dead people who had a fever or bleeding,” he added. DRC's health minister, Eteni Longondo, and the WHO later confirmed the outbreak in Wangata, near Mbandaka. Of the initial six cases, three of  have been confirmed with laboratory testing. Four people have died and two are receiving critical care. ...

A second Ebola patient has died in northwestern Democratic Republic of Congo, the World Health Organization (WHO) said on Tuesday, days into a fresh outbreak of the deadly disease. Genetic testing showed an infection confirmed last week in the city of Mbandaka was a new "spillover event", a transmission from an infected animal, and not linked to any previous outbreaks, said the country's National Institute of Biomedical Research.  The second fatality was a 25-year-old woman who was the sister-in-law of the first case, the WHO said on Twitter. She began experiencing symptoms 12 days earlier, it said. The first patient began showing symptoms on April 5, but did not seek treatment for more than a week. He died in an Ebola treatment centre on April 21. The lag time has health workers rushing to identify contacts who may have been infected, the WHO said.

At least 145 people came into contact with the confirmed cases and their health is being closely monitored, the WHO said, noting later that one of the first cases was a health worker.  Mbandaka, a trading hub on the banks of the Congo River, is a city of over one million where people live in close proximity with road, water and air links to the capital Kinshasa. WHO emergencies director for Africa, Ibrahima Soce Fall, said there was a risk the disease could spread to neighbouring Central African Republic and Congo Brazzaville.  "This is concerning but taking into account the capacity build up and experience in Congo we believe it can be contained," Fall said at a press conference in Geneva. Congo has seen 13 previous outbreaks of Ebola, including one in 2018-2020 in the east that killed nearly 2,300 people, the second highest toll recorded in the history of the hemorrhagic fever. The most recent outbreak ended in December in the east after six deaths. Mbandaka, the capital of Equateur province, has also contended with two previous outbreaks - in 2018 and in 2020. The country's equatorial forests are a natural reservoir for the Ebola virus, which was discovered near the Ebola River in northern Congo in 1976.

The mortality rate among patients in the Democratic Republic of the Congo with severe or critical cases of COVID-19 is nearly 50%, according to a study in The American Journal of Tropical Medicine and Hygiene. The study was the first to explore the clinical characteristics and outcome management of COVID-19 patients in an African country. Jean Nachega, MD, PhD, MPH, FRCP, FAAS, associate professor of epidemiology, infectious diseases and microbiology at University of Pittsburgh and adjunct professor of medicine at Stellenbosch University in Cape Town, and colleagues conducted a retrospective cohort study using data from the Democratic Republic of the Congo (DRC) health ministry’s COVID-19 database that was collected between March 10, 2020, and July 31, 2020. The study included data from 766 patients with COVID-19 admitted to the seven largest health facilities in Kinshasa.

“Whilst it is generally thought that COVID-19 in Africa causes lower mortality rates than in Western countries, COVID-19 is an important disease and does cause mortality in elderly adults with comorbidities,” Sir Alimuddin Zumla, KBE, FRCP, FRCPath, FRSB, senior co-author and professor of infectious diseases and international health at University College London, told Healio. “Physicians should not become complacent.” Among the patients in the study, overall hospital mortality was 13.2% (95% CI, 10.9-15.8), with a higher rate of mortality among patients with severe and critical disease than those with mild or moderate disease (45% vs. 2.6%; P < .001). According to the study, 34.6% of patients had at least one comorbidity and 48.5% had more than one. The most common comorbidities were hypertension (25.4%) and diabetes (14%). Of the patients who died, four were children. “One surprising finding was the high COVID-19 death rate among young patients”— 11.8% among patients aged 20 years or younger — “when compared to the United States, where hospitalization rates and death rates in children and adolescents with COVID-19 are lower than those in adults,” Nachega, told Healio.

Published in American J. Topical Medicine and Hygiene (Oct. 2, 2020):

https://doi.org/10.4269/ajtmh.20-1240