Mpox Clade I Outbreak Explained: What Made 2024 Different

On August 14, 2024, the World Health Organization declared the mpox upsurge in the Democratic Republic of the Congo (DRC) and a growing number of African countries a Public Health Emergency of International Concern, the highest alarm the agency can sound. It was the second mpox emergency in two years. The first, in 2022, involved a different branch of the virus (clade IIb) moving through sexual networks around the world. The 2024 emergency was driven by clade I, including a new subclade called Ib. This article explains what separated the two events, what the numbers really show, and how the emergency ended on September 5, 2025.

Educational content, not medical advice. Talk to your doctor before changing any medication, treatment, or routine. Information here reflects published research and public health agency reports, but every person's situation differs.

This piece focuses on the clade I emergency. For a general introduction to the virus, its biology, and how it was first recognized, see Mpox and Monkeypox Virus Explained.

What is mpox, and where did clade I come from?

Mpox is a disease caused by the monkeypox virus (MPXV), a member of the Orthopoxvirus genus, the same group that includes the virus that caused smallpox. The name is misleading. The virus was discovered in 1958 in monkeys kept for research in Denmark, but monkeys are not known to be its natural reservoir. WHO says the reservoir is unknown, although various small mammals, including squirrels and monkeys, are susceptible. The first reported human case was a nine-month-old boy in the DRC in 1970, according to the WHO mpox fact sheet.

The timing of that first human case matters. Smallpox was declared eradicated in 1980, and routine smallpox vaccination ended worldwide afterward. Smallpox vaccines also protect, to a degree, against related poxviruses, so each year since has added a larger group of people with no cross-protection. WHO notes that mpox then emerged steadily in central, east, and west Africa, and that since 2005 thousands of cases have been reported in the DRC every year. To see how the original orthopoxvirus threat was beaten, read Smallpox: The Variola Virus Explained, and for the first vaccine ever made, The Jenner Smallpox Vaccination.

Think of the end of smallpox vaccination like removing a fire break from a forest. For decades the break did not matter, because nothing was burning nearby. Once a related fire (mpox) began to spread, the unprotected ground behind the break was larger every year.

How do scientists name the branches?

Scientists group MPXV into two clades, which are major branches of a virus family tree. Clade I was formerly called the Congo Basin clade and clade II the West African clade. Each splits again: clade I into Ia and Ib, and clade II into IIa and IIb. According to the WHO Disease Outbreak News from August 30, 2024, subclade Ib was identified in South Kivu province of the DRC in 2023, and subclade Ia covers all other clade I strains.

Two emergencies, four subclades

The simplest way to understand why 2024 felt different from 2022 is to compare the branches side by side. The table below pulls together what the WHO and the U.S. Centers for Disease Control and Prevention (CDC) have published.

Subclade	Where it circulated	Main spread pattern	Severity signal	Source
Ia	Endemic provinces of the DRC and Central Africa	Animal spillover, household contact, and sexual contact	Highest fatality of the clades; DRC estimate about 4.5% for clade I in 2023	CDC EID review, 2025; WHO IHR Committee, 2025
Ib	Emerged in South Kivu, DRC, in late 2023; later East and Southern Africa	Sexual contact among adults first, then households	Suspected-case fatality in South Kivu stayed under 1%	CDC EID review, 2025
IIa	West Africa	Not a driver of the 2024 emergency; WHO noted clade II activity intensifying or emerging in West Africa in 2025	Clade II historically lower severity than clade I	WHO IHR Committee, 2025; CDC EID review, 2025
IIb	Global 2022 outbreak	Mainly sexual networks among men who have sex with men outside Africa	Global fatality about 0.2%	CDC EID review, 2025

Two points in that table are easy to miss. First, the clade Ib sub-lineage that triggered the alarm was not the deadliest branch. Clade Ia, which circulates mostly in endemic DRC provinces, has the higher fatality rate. Second, the CDC review estimates the global fatality of clade IIb at about 0.2%, which is why the 2022 outbreak produced few deaths in wealthy countries.

The takeaway is that "clade I" is not a single threat. It is a bundle of at least two with different behaviors, which is why headlines that treat it as one virus with one fatality rate are misleading.

How clade Ib emerged in South Kivu

Clade Ib was identified in late 2023 in South Kivu, a province in eastern DRC, where sexual contact was a major driver of transmission, according to a CDC Emerging Infectious Diseases review published in August 2025. The European Centre for Disease Prevention and Control (ECDC) reported that among 51 hospitalized cases from September 2023 to January 2024, 24 were sex workers in the Kamituga mining area of South Kivu, and sexual transmission of clade I had been documented earlier in 2023 in a cluster of six cases in Kwango province (ECDC update, April 5, 2024).

Researchers recognized this as a new lineage by reading its genome. The CDC review describes three features of clade Ib:

• Low genetic diversity. The viruses sampled were very similar to each other, which suggests they descend from a recent common ancestor.
• A 1,142-base-pair deletion. A stretch of the genome that includes a gene called CCP is missing.
• APOBEC3-linked mutations. These are a particular pattern of single-letter changes in the viral DNA.

Why the APOBEC3 pattern matters

APOBEC3 is a family of human enzymes that edits DNA as part of the body's antiviral defense. When a poxvirus replicates inside human cells, these enzymes leave a recognizable pattern of mutations behind. Zoonotic spillover (jumps from animals) does not leave this signature, because the virus passed through animal cells instead. A genome packed with APOBEC3 edits is therefore evidence that the virus has been passing from human to human for many replication cycles.

The best analogy is a photocopier that stamps a faint watermark on every copy. If a document carries one watermark, it was copied once. If it carries dozens, it has been copied from copy to copy. The CDC review treats the APOBEC3 pattern in clade Ib as an indicator of sustained human-to-human spread, which is exactly what makes a subclade capable of driving its own outbreak without any new animal contact. Spillover of the animal-to-human kind is a separate story, told in How Viruses Jump From Animals to Humans.

What the missing gene means in practice

The deletion has a practical consequence that surprised some laboratories. According to the CDC review, some PCR tests designed specifically to detect clade I miss clade Ib because the target stretch of DNA is gone. Labs are advised to also use generic orthopoxvirus or MPXV assays. A virus can look absent simply because the test was built to find a version of it that no longer exists.

The same deletion has been proposed as an explanation for lower severity in clade Ib, but the CDC authors note that animal studies have given conflicting results. That is a fair statement of where the science stands: the missing gene is a clue, not a proven cause.

What the case counts actually show

Counting mpox in the DRC is hard. The ECDC noted in April 2024 that only about 10% of cases in the country were laboratory-confirmed, so most figures are suspected cases, and deaths are recorded only among suspected cases. The table below assembles the main published snapshots. Treat the totals as lower-bound estimates, not clean statistics.

Date	Figure	Source
2023 to March 29, 2024	18,922 suspected cases and 1,007 deaths in the DRC	ECDC, April 5, 2024
January to March 29, 2024	4,488 cases and 279 deaths, a 6.7% fatality among reported cases	ECDC, April 5, 2024
2024 up to August 14	More than 15,600 DRC cases and 537 deaths, already above the 2023 total	WHO news release, August 14, 2024
Early September 2024	More than 20,000 DRC cases (over 5,000 confirmed) and over 600 deaths	ECDC, citing Africa CDC and WHO AFRO
July 22 to October 31, 2024	1,607 confirmed cases and 1 death in Burundi	CDC EID review

Two things stand out. The DRC death counts are much higher than the Burundi count, and the gap is not mainly about the virus subclade. The Burundi figure is a count of confirmed cases, while the DRC figures mix confirmed and suspected cases, and only a minority of DRC cases were tested. A suspected-case denominator that includes people who never had mpox lowers the apparent fatality rate; a death count drawn from hospitals that only see the sickest raises it.

Who was getting sick?

In the DRC, children under 15 made up the majority of cases and deaths. The ECDC reported in April 2024 that children under 15 were 70% of cases and 88% of deaths, and its September 2024 update, citing Africa CDC, gave 66% of cases and 82% of deaths. The CDC review reports that over 80% of suspected clade Ia cases in the DRC were in children under 15. The figures differ because the periods, provinces, and case definitions differ, but every source points the same way.

The CDC lists several reasons for the high child share: spread within and between close households, a large young population, misdiagnosis of other diseases such as measles, poor sanitation, limited health care access, and food insecurity and malnutrition. Notably, the CDC says there are no consistent reports of schools driving transmission.

How fatality changed over time

The WHO emergency committee statement published on October 30, 2025 reports a clear trend. In the DRC's clade Ia endemic provinces, case fatality fell from above 3% when the emergency was declared to about 1.6% in 2025 and about 1% by August 2025. The sources we reviewed do not establish why. Plausible contributors include wider testing, more patients reaching care, and a changing mix of confirmed versus suspected cases. The DRC did expand its testing sites from nine to 28, and when a country adds that much testing, the denominator grows and the apparent fatality rate can drop even if the virus itself has not changed.

Why some people die and others recover

Mpox is mainly a skin disease, but in severe cases the burden of lesions is heavy. Like all viruses, MPXV hijacks host cells to copy itself; the general process is covered in How Viruses Work: From Infection to Replication. In the PALM007 clinical trial in eastern DRC, hospitalized patients had a mean lesion count of 487, with a range from one to more than 10,000. Roughly one in five participants also had malaria, and 6% had severe acute malnutrition (i-base summary of the trial).

Those co-existing conditions change the picture. A child with severe malnutrition has less immune reserve, and a child with malaria is fighting two infections at once. Extensive open lesions are also an entry point for bacteria, which is one reason supportive care, such as wound care, nutrition, and hydration, is central to treatment.

PALM007 offers a revealing number. Among 597 hospitalized patients, overall mortality was low, about 1.7%, in both treatment and placebo groups, while the DRC reported clade I fatality of about 4.5% in 2023. The trial was not designed to test the effect of hospital care, but the gap may reflect who gets enrolled and how cases are counted as much as hospital care, so it cannot be read as a measured benefit of admission.

Why the 2022 playbook did not transfer

In 2022, wealthy countries controlled clade IIb with a combination of targeted vaccination, rapid testing, contact tracing, and community messaging. That playbook assumes a functioning health system, accessible vaccines, and a transmission network that public health teams can identify and reach. Much of eastern DRC had none of these in 2024.

• Contact tracing depends on stable addresses, phones, and a trained workforce. In conflict zones, none can be assumed.
• Isolation requires a room where a patient can be separated. In crowded displacement settings, that is rarely possible.
• Access to care depends on roads, transport, and staffed facilities, all of which are strained in areas affected by long-running conflict.

The WHO emergency committee noted that clade Ib spread along trucking corridors in East and Southern Africa. That is a sensible pattern: a virus that spreads through close contact will follow people who travel for work and whose work puts them in repeated contact with new communities. The fire-spreading analogy fits again. A grass fire needs fuel and wind, and in this outbreak, long-distance trade routes supplied the wind.

Vaccines: what worked, and how long it took

The key vaccine against mpox is MVA-BN, a modified vaccinia Ankara vaccine made by Bavarian Nordic and sold under the names Jynneos, Imvanex, and Imvamune. It is a non-replicating vaccine, meaning the vaccine virus cannot multiply in human cells, which makes it suitable for many people with weakened immunity. The CDC review cites roughly 66–86% protection against clade IIb, with two doses outperforming one.

Several milestones shaped the 2024 response:

1. September 13, 2024: WHO added MVA-BN to its prequalification list, the first mpox vaccine to be prequalified. Prequalification is the quality check that lets United Nations agencies buy a product for distribution.
2. October 8, 2024: WHO extended prequalification to adolescents aged 12 to 17, after the European Medicines Agency recommended the extension on September 19, 2024.
3. Single-dose strategy: WHO recommended using one dose instead of two in outbreaks when supply is limited. Estimated effectiveness before exposure was about 76% for one dose and about 82% for two (Health Policy Watch).
4. Off-label use for children: WHO said the DRC could use MVA-BN off-label for children, since most DRC cases were in children and the vaccine had not been approved for under-18s at the time.

By the time of the WHO committee's fifth meeting, about 1.6 million MVA-BN doses had been delivered to 13 African countries, with about 1 million administered in ten of them. In the DRC, a second product, the LC16m8 vaccine, had been given to about 40,000 people through a bilateral arrangement.

The inequity problem

Supply was the visible constraint. When WHO prequalified the vaccine, Bavarian Nordic said, as reported by Health Policy Watch, that it expected to produce two million doses by the end of 2024 and potentially 13 million by the end of 2025. Set against a continent where most cases were in children and the vaccine was not yet registered for anyone under 18, that is a narrow pipeline. The pattern is familiar from earlier outbreaks: countries with endemic disease are rarely first in line for new countermeasures. For a related case study in a different virus, see Ebola Virus Explained.

The lesson here is less about blame than about logistics. A vaccine in a stockpile in Europe saves no one in South Kivu until it is licensed for local use, shipped through a cold chain, paired with trained vaccinators, and accepted by communities.

Treatment: the tecovirimat surprise

For years, tecovirimat (brand name TPOXX) was considered the leading antiviral for severe mpox, mainly based on animal and laboratory evidence. In 2025 the clinical trials arrived, and they changed the conversation.

PALM007, a double-blind, placebo-controlled trial in the DRC, randomized 597 patients to tecovirimat (295) or placebo (302). Results published in the New England Journal of Medicine in 2025 showed no benefit on the primary endpoint: there was no overall difference in time to lesion resolution between tecovirimat and placebo. Deaths were equal in the two arms by day 56 (five in each), and viral clearance in blood, throat, and lesion samples was similar (i-base).

The CDC review adds that tecovirimat also did not improve lesion resolution in a U.S. study of clade IIb, and that prolonged use can select for drug-resistant virus. The WHO fact sheet states that there is "no proven effective antiviral treatment" for mpox to date. In practice, care is supportive: managing pain, protecting skin, maintaining nutrition and hydration, and treating secondary infections.

What a null result means

A negative trial does not prove a drug is useless in every circumstance. PALM007 enrolled hospitalized patients, 64% of them aged 2 to 18, and fewer than 1% were living with HIV, so it says little about people with severely weakened immunity. The result held whether treatment began early or late. What it does mean is that a stockpile of tecovirimat is not a substitute for vaccination, and that research on better antivirals remains an open need.

How the emergency ended

On September 5, 2025, WHO Director-General Tedros Adhanom Ghebreyesus determined that the mpox upsurge no longer constituted a PHEIC, after the Emergency Committee met on September 4. The reasoning, set out in the committee's statement, was sustained declines in cases in the DRC, Burundi, Sierra Leone, and Uganda.

The committee's risk ratings for severity, demographics, geographic spread, and extraordinary events all moved from "high" or "moderate" in August 2024 to "low" in September 2025, while response capacity stayed at "moderate." More than 80% of global cases over the previous 12 months were in the WHO African Region.

Ending an emergency declaration is not the same as ending the outbreak. The committee noted flare-ups in Guinea and Liberia, clade II activity intensifying or emerging in West Africa in 2025, and travel-related clusters in places such as the United Kingdom. WHO extended its standing recommendations for mpox until August 20, 2026, a date that has since passed, so check WHO for their current status. Globally, clade IIb has been declining since August 2024 but remains linked outside Africa mainly to transmission among men who have sex with men.

Is mpox still an emergency?

No. The 2024 PHEIC ended in September 2025, and WHO's standing recommendations were extended through August 20, 2026. We could not confirm from WHO pages whether they were renewed after that date. That arrangement is meant for threats that are no longer acute but still need monitoring: countries are asked to keep surveillance, testing, and vaccination programs in place.

What people commonly get wrong about clade I

Myth 1: Clade I is always deadlier than clade II. The ranges do point that way, but the comparison hides large variation. Clade Ia has the highest fatality; clade Ib has had a suspected-case fatality under 1% in South Kivu. Location, age, nutrition, and access to care shape outcomes as much as the clade does.

Myth 2: Mpox is a "gay disease." In 2022, clade IIb spread mainly through sexual networks of men who have sex with men outside Africa, but the virus does not recognize sexual orientation. In the 2024 clade Ib outbreak, early spread was among adults through sexual contact, then within households, including to children. Anyone in close contact with an infected person or contaminated materials can be exposed.

Myth 3: It spreads like COVID-19. WHO describes transmission as mainly through close contact, including skin-to-skin, mouth-to-skin, and face-to-face contact with respiratory particles, plus contaminated objects such as bedding and clothing. It can also pass from mother to baby. That is a narrower pathway than casual airborne spread. For how fast-moving respiratory outbreaks differ, see How Pandemics Spread and What Stops Them.

Myth 4: The vaccine failed. The central problem in 2024 was supply and delivery, not a lack of effective vaccine. By September 2025 the WHO committee reported about 1.6 million MVA-BN doses delivered to 13 African countries and about 1 million administered in ten of them. How vaccines train the body to respond is explained in How Vaccines Actually Work.

Myth 5: A drug will fix this. Tecovirimat did not shorten disease in the DRC trial. For now, prevention (vaccination, early recognition, and care) is the strongest tool.

What this means

The clade I emergency was not a story about one new virus. It was a story about a long-known pathogen, a shrinking wall of smallpox immunity, one sub-lineage that learned to spread person to person, and a health system in a conflict zone that could not apply the standard tools. What ended the emergency was not a single breakthrough. It was the combination of vaccines finally reaching people, more testing, more patients reaching care, and a decline in cases across the highest-burden countries.

The practical lessons are narrow and durable. Genomic surveillance can spot a new lineage early, but only if the tests can see it. Fatality rates mean little without knowing the denominator. And a vaccine that exists is not a vaccine that is delivered. Those questions will matter again for the next outbreak, whatever the pathogen.

FAQs

Q: Is clade I mpox more dangerous than the 2022 outbreak? A: Generally yes, but it depends on the subclade and the setting. The CDC review estimates the global fatality of clade IIb at about 0.2%, while a DRC estimate for clade I in 2023 was about 4.5%. Clade Ib, however, had a suspected-case fatality under 1% in South Kivu, so the picture is not uniform.

Q: What is clade Ib and how is it different from clade Ia? A: Clade Ib is a subclade first identified in South Kivu, DRC, in late 2023. Its genome shows APOBEC3 mutations that indicate sustained human-to-human spread, and a 1,142-base-pair deletion. Clade Ia is the historically endemic form, which spreads through animal spillover, household contact, and sexual contact and carries the highest fatality.

Q: Why did WHO declare a PHEIC in August 2024? A: On August 14, 2024, WHO cited the emergence of a new clade, its rapid spread in eastern DRC, and cases in neighboring countries. At that point, more than 100 laboratory-confirmed clade Ib cases had been reported in Burundi, Kenya, Rwanda, and Uganda, which had not previously reported mpox, and the DRC had more than 15,600 cases and 537 deaths that year.

Q: Does the mpox vaccine protect against clade I? A: The MVA-BN vaccine is used against clade I in several African countries. The efficacy figures available, roughly 66–86% for clade IIb according to the CDC review, come mainly from clade II data, so clade-specific effectiveness is still being studied. WHO prequalified the vaccine in September 2024 and extended it to ages 12 to 17 in October 2024.

Q: Does tecovirimat work against mpox? A: In the PALM007 trial of 597 patients in the DRC, tecovirimat did not shorten the time to lesion resolution compared with placebo and did not change mortality. A U.S. study in clade IIb also found no improvement. WHO says there is no proven effective antiviral, so care is mainly supportive.

Q: Why are children so heavily affected in the DRC? A: The CDC cites spread within and between close households, a large young population, misdiagnosis of other diseases such as measles, poor sanitation, limited health care access, and food insecurity and malnutrition. ECDC reported that children under 15 accounted for 70% of cases and 88% of deaths in early 2024.

Q: Is the global mpox emergency still in effect? A: No. WHO ended the PHEIC on September 5, 2025, after sustained declines in the DRC, Burundi, Sierra Leone, and Uganda. WHO standing recommendations for mpox were extended until August 20, 2026, and flare-ups in places such as Guinea and Liberia were still being tracked when the committee's statement was published.

Sources

• World Health Organization. WHO Director-General declares mpox outbreak a public health emergency of international concern. August 14, 2024.
• World Health Organization. Mpox fact sheet. - World Health Organization. Disease Outbreak News: Mpox, clade Ib, Sweden. August 30, 2024.
• World Health Organization. Fifth meeting of the IHR Emergency Committee regarding the upsurge of mpox 2024. Published October 30, 2025.
• World Health Organization Prequalification. WHO grants approval for use of Bavarian Nordic's mpox vaccine in adolescents. October 18, 2024.
• CDC. Emerging Infectious Diseases review of mpox clades I and II. August 2025.
• CDC. Clade I mpox in children in Africa.
• European Centre for Disease Prevention and Control. Outbreak of mpox caused by monkeypox virus clade I in the DRC. April 5, 2024.
• European Centre for Disease Prevention and Control. Epidemiological update, week 37/2024.
• i-base. Detailed results from PALM007. Full trial report: New England Journal of Medicine 2025;392:1484-1496.
• Health Policy Watch. WHO prequalifies first mpox vaccine, recommends single dose. September 13, 2024.

---

Read next:

• H5N1 Bird Flu Pandemic Risk: 2026 Update
• Measles Virus Explained
• How the Human Immune System Fights Viruses: A Step-by-Step Guide