The U.N. health agency chief called for “urgent” scale-up of procurement, donations and rollout to get the vaccine where it is needed most, along with other response measures. File
| Photo Credit: AP

The World Health Organization (WHO) said on Friday (September 13, 2024) it has granted its first authorisation for use of a vaccine against mpox in adults, calling it an important step toward fighting the disease in Africa and beyond.

The pre-qualification of the vaccine by Bavarian Nordic A/S means that donors such as GAVI the Vaccine Alliance and UNICEF can buy it. But supplies are limited because there’s only a single manufacturer.

“This first pre-qualification of a vaccine against mpox is an important step in our fight against the disease, both in the context of the current outbreaks in Africa, and in future,” said WHO Director-General Tedros Adhanom Ghebreyesus.

The U.N. health agency chief called for “urgent” scale-up of procurement, donations and rollout to get the vaccine where it is needed most, along with other response measures.

Under the WHO authorisation, the vaccine can be administered in people aged 18 or above in a two-dose regimen. The approval says that while the vaccine is not currently licensed for those under 18 years old, it may be used in infants, children and adolescents “in outbreak settings where the benefits of vaccination outweigh the potential risks.”

Officials at the Africa Center for Disease Control (CDC) and Prevention said last month that nearly 70% of cases in Congo — the country hardest hit by mpox — are in children younger than 15, who also accounted for 85% of deaths.

On Thursday (September 12, 2024), the Africa CDC said 107 new deaths and 3,160 new cases had been recorded in the past week, just a week after it and WHO launched a continental response plan.

Mpox belongs to the same family of viruses as smallpox but causes milder symptoms such as fever, chills and body aches. People with more serious cases can develop lesions on the face, hands, chest and genitals.

The hands of a patient with skin rashes caused by the mpox virus are pictured at the treatment center of Vijana Hospital in Kinshasa, Democratic Republic of Congo on August 30, 2024
| Photo Credit: Reuters

Dozens of feverish patients lay on thin mattresses on the floor of a makeshift mpox isolation ward in east Democratic Republic of Congo, as overstretched hospital workers grappled with drug shortages and lack of space to accommodate the influx.

Congo is the epicentre of an mpox outbreak that the World Health Organization declared to be a global public health emergency last month.

Vaccines are set to arrive within days to fight the new strain of the virus, while Congo’s President Felix Tshisekedi has allowed a first USD 10 million disbursement to fight the outbreak.

But at the hospital complex in the town of Kavumu, where 900 symptomatic patients have been taken in over the past three months, health workers are desperate for support.

“We run out of medicine every day,” said head doctor Musole Mulamba Muva. “There are many challenges we struggle to overcome with our local means,” he said, noting that donations from international organisations rapidly dwindled.

Last week there were 135 patients in the mpox ward, children and adults combined, crammed between three large plastic tents pitched into damp earth without a floor cover.

Relatives that usually provide the bulk of meals in underfunded public facilities such as the Kavumu hospital were banned from visiting the mpox ward to avoid contamination. “We do not have anything to eat,” said Nzigire Lukangira, the 32-year-old mother of a hospitalised toddler.

“When we ask for something to lower our children’s temperature, they do not give us anything,” she said, coaxing honey into her daughter’s mouth.

The head of Congo’s mpox response team, Cris Kacita, acknowledged that parts of the vast central African country lacked medicine and that dispatching donations, including 115 tonnes of medicine from the World Bank, was a priority.

Traditional remedies

Mpox causes flu-like symptoms and pus-filled lesions and, while usually mild, it can kill. Children, pregnant women and people with weakened immune systems are all at higher risk of complications.

Like other mothers in the Kavumu mpox ward, Lukangira had started improvising with traditional remedies to ease her baby’s pain. They dipped their fingers in potassium bicarbonate or salty lemon juice and popped their children’s blisters. Adult patients did the same to themselves.

Most cases came from the town itself and surrounding villages. Two other makeshift mpox wards have been set up in the area.

Local health ministry representative, doctor Serge Munyau Cikuru, called on the government to continue pushing for vaccines.

Kacita said high-risk contacts and nine priority areas had already been identified for the first vaccination stage.

There were 19,710 suspected cases of mpox reported since the start of the year in Congo by August 31, according to the health ministry. Of those, 5,041 were confirmed and 655 were fatal.

The first 10,000 mpox vaccines are finally due to arrive next week in Africa, where a dangerous new strain of the virus – which has afflicted people there for decades – has caused global alarm.

The slow arrival of the shots – which have already been made available in more than 70 countries outside Africa – showed that lessons learned from the COVID-19 pandemic about global healthcare inequities have been slow to bring change, half a dozen public health officials and scientists said.

Among the hurdles: It took the World Health Organization (WHO) until this month to start, officially, the process needed to give poor countries easy access to large quantities of vaccine via international agencies. That could have begun years ago, several of the officials and scientists told Reuters.

Mpox is a potentially deadly infection that causes flu-like symptoms and pus-filled lesions and spreads through close physical contact. It was declared a global health emergency by the WHO on August 14 after the new strain, known as Clade Ib, began to proliferate from the Democratic Republic of Congo to neighbouring African countries.

In response to Reuters questions about the delays in vaccine deployment, the U.N. health agency said on Friday, August 23, that it would relax some of its procedures on this occasion in an effort to now accelerate poor countries’ access to the mpox shots.

Buying the expensive vaccines directly is out of reach for many low-income countries. There are two key mpox shots, made by Denmark’s Bavarian Nordic and Japan’s KM Biologics. Bavarian Nordic’s costs USD 100 a dose; the price of KM Biologics’ is unknown.

The long wait for WHO approval for international agencies to buy and distribute the vaccine has forced individual African governments and the continent’s public health agency – the Africa Centres for Disease Control and Prevention (CDC) – to instead request donations of shots from rich countries. That cumbersome process can collapse, as it has before, if donors feel they should keep the vaccine to protect their own people.

The first 10,000 vaccines on their way to Africa – made by Bavarian Nordic – were donated by the United States, not provided by the U.N. system.

Helen Rees, a member of the Africa CDC’s mpox emergency committee, and executive director of the Wits RHI Research Institute in Johannesburg, South Africa, said it was “really outrageous” that, after Africa struggled to access vaccines during the COVID pandemic, the region had once again been left behind.

In 2022, after a different mpox strain spread outside Africa, smallpox shots were repurposed by governments within weeks, approved by regulators and used in roughly 70 high and middle income countries to protect those most at risk. Those vaccines have now reached 1.2 million people in the United States alone, according to the U.S. Centers for Disease Control and Prevention (CDC).

But no shots have been available in Africa outside clinical trials. A key reason: Vaccines needed to be greenlit by the WHO before they could be bought by public healthcare groups including Gavi, the Vaccine Alliance.

Gavi helps poorer countries buy shots, supplying childhood vaccines in this way routinely. It administered a global scheme for all vaccines during COVID-19 and has up to USD 500 million to spend on mpox vaccines and logistics.

The Africa CDC has said 10 million doses may be needed across the continent.

But the WHO only this month asked vaccine manufacturers to submit the information needed for the mpox shots to receive an emergency licence – the WHO’s accelerated approval for medical products. It urged countries to donate shots until the process was finalised, in September.

The WHO said it is working with the authorities in Congo to put together a vaccination plan, and on August 23 said Gavi could start talks while it finalised its emergency approval.

Sania Nishtar, chief executive of Gavi, said the WHO’s aim to now act quickly on approvals and improvements in funding showed “the somewhat brighter side of where we are compared to COVID.” Asked to comment on the approval delays, she said, “hopefully this is another learning moment for us.”

WHO criticised

The WHO’s role in approving medical products has revolutionised supply in low-income countries, which often lack the facilities to check new products themselves, but it has also faced criticism for its slow speed and complexity.

The Geneva-based U.N. health agency said it did not have sufficient data during the last mpox emergency in 2022 to start an approval process for the vaccine, and it has been working with manufacturers since then to see if the available data warranted an approval.

Mpox, which includes several different strains, has caused 99,000 confirmed cases and 208 deaths worldwide since 2022, according to the WHO. The tally is likely an underestimate as many cases go unreported.

Infections have been brought under control in rich regions by a combination of vaccines and by behaviour change among the highest-risk groups.

With the main earlier mpox strain, men who have sex with men were most at risk, but the new Clade Ib variant seems to spread more easily through other close contact, including among children, as well as through sexual contact among heterosexual people.

The country currently hardest hit by mpox is Congo. Since January 2023, there have been more than 27,000 suspected cases and 1,100 deaths there, according to government figures, mainly among children.

But the first 10,000 vaccines donated by the United States are not destined for Congo but for Nigeria, as a result of several years of talks between both governments, according to a source involved in the process who was not authorised to speak to the media. Nigeria has had 786 suspected cases this year, and no deaths.

The Nigerian health ministry did not respond to a request for comment; the U.S. Agency for International Development (USAID) said it has also donated 50,000 doses to Congo but the arrival date is not yet finalised.

Children at risk

In Congo, the country’s administration is another part of the problem. Grappling with conflict and multiple competing disease outbreaks, its government has yet to ask Gavi officially for vaccine supplies and took months to talk to donor governments. Its medicines regulator only approved the two main vaccines in June.

Neither Congo’s health ministry nor Japan’s, which is working to donate large amounts of KM Biologics vaccines, responded to requests for comment for this story.

Bavarian Nordic said this week it needs orders now to produce vaccines in volume this year.

Congo’s government has told reporters it hopes to receive vaccine donations next week, but three donor sources told Reuters it is not clear if that will happen. Europe’s pandemic preparedness agency said by email its 215,000 doses will not arrive before September at the earliest.

Bavarian Nordic and Congo are still discussing pre-shipment requirements necessary to ensure proper storage and handling, said a spokesperson for USAID. The vaccines have to be kept at -20C, for example.

In eastern Congo, around 750,000 people are living in camps after fleeing conflict, including seven-year-old Sagesse Hakizimana and his mother Elisabeth Furaha. He is one of more than 100 children to have been infected by mpox in one area near the city of Goma, in north Kivu, according to doctors.

“Imagine fleeing a war and then losing your child to this illness,” said Furaha, 30, rubbing ointment on her son’s rash and adding that his symptoms were easing. He was being treated last week in a repurposed Ebola treatment centre.

“We need a vaccine for this disease. It’s a bad disease that weakens our children.”

Even when shots arrive, questions remain about how to use them: Bavarian Nordic’s vaccine – the most widely used worldwide – is only available for adults. The KM Biologics vaccine can be given to children but is more complex to administer.

Adding to those questions, scientists have not yet agreed what groups should be vaccinated first, although a likely strategy is ring vaccination, where contacts of known cases are prioritised.

“We saw with COVID-19 that the vaccine was available but the population didn’t want it,” says Jean Jacques Muyembe, co-discoverer of the Ebola virus and director of the Institut National de Recherche Biomédicale (INRB) in Kinshasa. He and other scientists said other public health measures like awareness raising in Africa and better diagnosis were also key to stopping the spread of mpox; vaccines are not the only solution.

Some global health experts say the WHO and others should have focused earlier on improving access to mpox vaccines as well as tests for the disease and treatments.

“The processes [at WHO for vaccines] and funding for diagnostics for mpox should have started a few years ago,” said Ayoade Alakija, who co-chairs a global health partnership aiming to make the mpox response more egalitarian.

She said her comment was not a critique of the WHO, which can only prioritise what its member states want. “It is a matter of what the world considers to be a priority, and [that is not] diseases that primarily affect black and brown people.”

In a statement, the WHO said it was “urging all partners including countries, manufacturers and communities to mobilize efforts, increase vaccine donations, reduce prices and provide other necessary support to protect people at risk during this outbreak”.

Jean Kaseya, head of the Africa CDC, said he is working to get African vaccine manufacturers involved to boost supply and lower prices, but that will take time.

New Delhi:
The World Health Organization has declared that an outbreak of mpox, a viral infection that spreads through close contact, represents a global health emergency for the second time in two years. Mpox causes flu-like symptoms and pus-filled lesions.

Here’s your 10-point cheat sheet to this big story

File picture of a doctor examining the ear of a patient suffering from Mpox – an infectious disease caused by the monkeypox virus in the North Kivu province of the Democratic Republic of the Congo
| Photo Credit: Reuters

Vaccines to help curb an escalating mpox outbreak in Democratic Republic of Congo and neighbouring countries may still not reach the central African country for months even as the World Health Organization considers following Africa’s top public health agency in declaring the outbreak an emergency.

On Tuesday, Africa Centres for Disease Control and Prevention declared a public health emergency of continental concern for the first time ever, and on Wednesday, a WHO-led panel meets to decide if it represents a global threat.

ALSO READ: Global mpox infections: Symptoms, treatment, and status of outbreak | Explained

But while experts hoped the meetings would galvanise action worldwide, many obstacles remain, including limited vaccine supply, funding and competing disease outbreaks.

“It is important to declare an emergency because the disease is spreading,” said Jean-Jacques Muyembe-Tamfum, head of Congo’s Institut National pour la Recherche Biomedicale (INRB). He said he hoped any declaration would help provide more funding for surveillance as well as supporting access to vaccines in Congo.

But he acknowledged the road ahead was not easy in a huge country where health facilities and humanitarian funds are already stretched by conflict and outbreaks of diseases like measles and cholera.

“If the big declarations remain just words, it won’t make any material difference,” said Emmanuel Nakoune, an mpox expert at the Institut Pasteur de Bangui in Central African Republic.

Africa CDC said last week it had been granted $10.4 million in emergency funding from the Africa Union for its mpox response, and its director general Jean Kaseya said on Tuesday there was a clear plan to secure 3 million doses of vaccine this year, without elaborating further.

However, sources involved in planning a vaccination roll-out in Congo said only 65,000 doses were likely to be available in the short-term, and campaigns were unlikely to begin before October at the earliest.

There have been more than 15,000 suspected cases of mpox in Africa this year and 461 deaths, mainly among children in Congo, according to Africa CDC. The viral infection is usually mild but can kill, and causes flu-like symptoms and pus-filled lesions.

A new offshoot of the virus has caused outbreaks in refugee camps in the east of Congo this year, and spread to Uganda, Burundi, Rwanda and Kenya for the first time.

Ivory Coast and South Africa are also experiencing outbreaks linked to a different strain of the virus, which spread globally in 2022, largely among men who have sex with men. This outbreak prompted WHO to declare a global emergency before ending it 10 months later.

Then, two vaccines were used – Bavarian Nordic’s Jynneos, and LC16, made by KM Biologics. Outside clinical trials, neither has ever been available in Congo or across Africa, where the disease has been endemic for decades. Only LC16 is approved for use in children.

Congo’s regulators approved the use of the vaccines domestically in June, but the government is yet to officially request any from either the manufacturers or governments like the United States looking to make donations through the global vaccine group, Gavi.

Two years after a global outbreak, fears are rife that a new strain of mpox — previously known as monkeypox — identified in DR Congo and now also in several neighbouring countries could further spread.

Deadlier and more transmissible than previous forms, the mpox strain surging in the Democratic Republic of Congo (DRC) since September, known as the Clade Ib subclade, is spread person-to-person.

The World Health Organization (WHO) said on Sunday it was considering convening an expert committee to advise on whether to declare an international emergency, as it did during the global mpox outbreak in 2022.

The Clade Ib strain causes skin rashes across the whole body, unlike other strains where lesions and rashes are usually limited to the mouth, face and genitals.

The African Union health agency, Africa CDC, registered 14,479 confirmed and suspected cases of the strain and 455 deaths in DRC as of August 3, representing a mortality rate of around three percent.

But researchers in the vast Central African nation say the mortality rate from the strain can be as much as 10 percent among children.

The Congolese government acknowledged last month an “exponential increase” in cases.

“The disease has been seen in the displacement camps around Goma in North Kivu where the extreme population density makes the situation very critical,” Louis Albert Massing, medical coordinator for Doctors Without Borders in DRC said.

“The risks of explosion are real given the enormous population movements” in the conflict-ridden region, which borders several countries, he added.

Already, the Clade Ib strain has jumped national borders — in the last two weeks, cases have been reported in Uganda, Burundi, Rwanda and Kenya, Rosamund Lewis, the WHO’s technical lead for mpox, told AFP.

‘Raging’

Authorities in the four countries have confirmed mpox cases — Burundi in particular has reported 127 cases — without specifying the strain.

The eight-member East African Community (EAC) has urged governments to educate their citizens on how to protect themselves and prevent the spread of the disease.

Lewis, from the WHO, said it was the first time that the four countries lying to the east of DRC had reported mpox cases.

“Rwanda, Burundi, Uganda are countries that don’t have this disease in an endemic way… that means it’s an extension of the outbreak which is raging in the DRC and in Central Africa generally,” she said.

Africa CDC has also reported 35 suspected and confirmed cases, including two deaths, in Cameroon, 146 cases, including one death, in Congo Brazzaville, 227 cases in the Central African Republic, 24 in Nigeria, five in Liberia and four cases in Ghana.

In West Africa, Ivory Coast recently reported six confirmed non-fatal cases, five of which were in the economic capital Abidjan, without specifying the strain.

Detection capacity

Mpox was first discovered in humans in 1970 in the DRC, then called Zaire. It has since been mainly limited to certain West and Central African nations. Humans mainly catch it from infected animals, such as when eating bushmeat.

In May 2022, mpox infections surged worldwide, mostly affecting gay and bisexual men. That spike was driven by a new subtype, dubbed Clade II, which took over from Clade I. Around 140 people died out of about 90,000 cases across 111 countries.

The outbreak is “still raging”, Lewis said, including in South Africa, which has seen 24 cases, three of which were fatal, but she added it was “controlled” and spreading less.

Mpox remains a global health threat, WHO chief Tedros Adhanom Ghebreyesus warned in early July.

Countries are now able to detect cases, Lewis said, pointing to a system of surveillance, laboratories and communication with affected areas. It is hard to know if there has been “a substantial rise” in cases, or whether “it’s just a matter of increased awareness”, said Maria Van Kerkhove, the WHO’s epidemic and pandemic preparedness and prevention director, who confirmed concern over the Clade Ib strain.

“There are some vaccines that are licensed that can be used for mpox,” she said.

Negotiations between the WHO and affected countries are under way to authorise the use of one, Lewis said.

Poxviruses have long been a cause of fear as well as curiosity for humankind. One particularly infamous poxvirus, smallpox, alone may have killed more than 500 million people in the last century.

Smallpox didn’t discriminate between rich, poor, young, old, and killed a third of the individuals whom it infected. The turning point came with evidence of the efficacy of the smallpox vaccine. Thus followed a concerted effort worldwide to administer the vaccine and eventually eradicate the dread disease. This feat has stood as a testament to the power of sustained global public health initiatives.

Mpox’s 15 minutes

Another poxvirus, mpox, was recently in the headlines after a rapidly expanding global outbreak in 2022-2023. The virus was previously called ‘monkeypox’ after a spillover event in a research facility involving monkeys in 1958; the name is considered both wrong and inappropriate today: since then, researchers have identified mpox in many sporadic outbreaks among humans. They have also found multiple mpox lineages have been circulating in humans, adapting by accumulating mutations modulated largely by the APOBEC proteins.

But it wasn’t until 2022 that the disease became widely known, thanks to outbreaks in more than 118 countries and the World Health Organisation (WHO) quickly declaring it a public health emergency. To date, this outbreak has infected almost 100,000 people. Based on WHO data, infections have a mortality rate of 1-10%.

The outbreak was due to one clade (strains of the virus descended from a common ancestor) — called IIb — having developed very high human-to-human transmission through close contact and spread through the sexual route. While the rate of new infections has been dropping, mpox continues to circulate among unvaccinated individuals worldwide. This increases the chance that a more virulent and transmissible strain might emerge and become endemic somewhere.

Expanding, contracting as required

Mpox, like all poxviruses, are DNA viruses. The mpox genome has about 197 kilobases (kb). The core genes are those closely conserved (i.e. preserved during evolution) by various poxviruses plus two sections about 6.4 kb long, one at each end of the genome. Researchers don’t yet know what function these sections serve but suspect they influence how well the poxviruses can infect different hosts.

The mpox genome also has a sequence of bases repeating in a pattern, which researchers believe play a role in the virus’s evolution.

The mpox family of viruses is also known to be able to evade selective evolutionary pressures. It does this by duplicating genes and/or accumulating mutations and expanding its genome significantly — or contracting its genome by deleting gene stretches or inactivating them. Such rhythmic expansions and contractions are called genomic accordions.

Find the accordion

In a study published on April 18 by Nature Communications, researchers at the Icahn School of Medicine in New York and multiple institutions in Spain extensively sequenced the genome of the mpox virus implicated in the 2022 outbreak. They used advanced genome sequencing technologies to piece together a comprehensive genome of the mpox virus from scratch.

They found that the 6.4-kb-long sections of the virus strongly influenced the virus’s human-to-human transmissibility. They also reported that variations in three genes in particular could affect the virus’s evolution. Importantly, 6.4-kb-long sections, which scientists had previously considered to be not so informative, were actually found to be the virus’s genomic accordions.

All mpox genomes can be divided into two distinct yet broad clades: I and II. Clade I is thought to have a higher mortality. Each clade has sub-clades, or lineages, defined by specific evolutionary processes. Researchers have also found evidence of significantly different mpox virulence in animal models. The new study, like others like it, further the idea that the 2022 outbreak largely involved a new lineage of the virus, clade IIb, that was even better adapted to human-to-human transmission than clades I or IIa.

The outbreak in the DRC

Between September 2023 and February 2024, health workers detected a large mpox outbreak detected in the Democratic Republic of the Congo (DRC), centred on a mining village and quickly spreading to a number of regions within the country. This outbreak was associated with a significantly larger spread as well as mortality. Researchers soon confirmed mpox clade I was responsible.

This outbreak differed from earlier ones, which were sporadic and self-contained spillover events, by spreading through human-to-human contact and affecting young adults rather than children. A preprint paper, uploaded by researchers from Belgium, Canada, the DRC, France, Ghana, Nigeria, South Africa, and the U.S., on April 14 describes the genomes of virus samples obtained from 241 individuals suspected to have been infected during the outbreak.

The genomic data suggests a distinct lineage of clade I being associated with human-to-human transmission. The researchers also found evidence — in fragments of the genome that closely resembled viruses isolated and sequenced in recent years — of the hypothesis that this lineage emerged from a very recent zoonotic spillover.

One eye on the genome

As with any viral infection, without urgent intervention, the outbreak has the potential to spread rapidly across national, and even continental, boundaries and emerge as another global outbreak.

To prevent such an outcome, genome sequences from before and during mpox outbreaks have provided well-lit glimpses of the evolutionary dynamics the virus uses to invent new ways to move between and survive in different populations of animals and people.

Thus, through rigorous genomic investigations and coordinated public health efforts, we can mitigate the threat of emerging pathogens and the world’s health security.

The authors are senior consultants at the Vishwanath Cancer Care Foundation and Adjunct Professors at Indian Institute of Technology Kanpur. All opinions expressed are personal.