The Democratic Republic of the Congo (DRC) is where mpox was first identified in humans, and it remains the global epicenter of the disease more than fifty years later. The virus responsible, monkeypox virus (MPXV), was actually first spotted in laboratory monkeys in 1958, but the first recognized human infections surfaced in the DRC in the early 1970s. Since then, the country has contended with recurring outbreaks, and a 2024 surge driven by a newly identified viral sub-lineage prompted the World Health Organization to declare a public health emergency of international concern. Understanding how the disease emerged, how it presents clinically, and what tools exist to prevent it requires looking closely at what has unfolded in the DRC and across Central Africa.
How the Virus Got Its Name and Its Start
The name “monkeypox” is itself a historical accident. The virus was identified in 1958 in captive monkeys kept for research, which is how it got its misleading label. Monkeys are not the primary animal reservoir; rodents in Central and West Africa are thought to be the main wildlife hosts. The virus made the jump to humans in the early 1970s, when the first recognized cases were reported in the DRC (then called Zaire).1ScienceDirect (One Health). Mpox: A case study for a one health approach to infectious disease prevention In 2022, the WHO officially adopted the name “mpox” to reduce stigma and confusion, though both names still circulate.
For decades, mpox was considered a rare zoonotic disease, meaning it mostly spilled over from animals to humans rather than spreading efficiently between people. That understanding has shifted considerably. Genomic analysis of the virus circulating during the 2022 global outbreak showed a distinctive pattern of mutations caused by human immune enzymes called APOBEC3 deaminases. Because these mutations accumulate only during human infection, researchers estimated that the virus had been circulating continuously among humans since at least 2016, years before the global outbreak made headlines.2PubMed Central. APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016 That finding represented a fundamental shift: mpox was no longer just a disease that occasionally jumped from animals. It had become a disease sustained by person-to-person spread.
Clades and Why They Matter
Not all mpox viruses behave the same way. The virus is divided into two major groups, or clades. Clade I has historically circulated in Central Africa, primarily in the DRC, while Clade II is associated with West Africa. The Central African clade has long been recognized as the more dangerous of the two, linked to higher rates of severe illness and death compared with its West African counterpart.3PubMed. A contemporary review of clade-specific virological differences in monkeypox viruses Estimates put the case fatality rate for Clade I at roughly 5 to 10 percent, while Clade II causes fatal outcomes far less often but has shown a greater ability to spread beyond endemic regions.4PubMed Central. Comparative analysis of Mpox clades: epidemiology, transmission dynamics, and detection strategies
The situation grew more complicated in 2024 when researchers sequencing virus from patients in South Kivu province, in eastern DRC, identified a novel sub-lineage within Clade I.5PubMed Central. Ongoing mpox outbreak in Kamituga, South Kivu province, associated with monkeypox virus of a novel Clade I sub-lineage, Democratic Republic of the Congo, 2024 Dubbed Clade Ib, this variant caught international attention because it appeared to spread more readily through sexual contact than earlier Clade I strains, which had primarily moved through household and community contact. Mathematical modeling suggested that this additional mode of transmission, particularly among sexual networks involving female sex workers, could explain why Clade Ib generated larger outbreaks than the older Clade Ia lineage.6PubMed Central. Roles of community and sexual contacts as drivers of clade I mpox outbreaks
The rapid spread of Clade Ib across borders led the WHO to declare a public health emergency of international concern in August 2024, the second such declaration related to mpox in two years.7PubMed Central. Note from the editors: WHO declares mpox outbreak a public health emergency of international concern While genomic differences between clades have been documented, researchers are still working to determine exactly which genetic changes drive differences in virulence or transmission.8PubMed Central. Virulence differences of mpox (monkeypox) virus clades I, IIa, and IIb.1 in a small animal model
How Mpox Spreads
Mpox can pass from animals to humans and from person to person, but the relative importance of each route depends on the setting and the viral clade involved. Contact with infected animals, especially rodents and primates, remains a source of new introductions. In one cross-sectional study from the Kamituga health zone in South Kivu, about a quarter of patients reported prior contact with an animal, mainly primates.9BioMed Central / PubMed Central. Epidemiological profile and transmission of mpox in the Kamituga health zone of South Kivu, Democratic Republic of Congo: a cross-sectional prospective study
Human-to-human transmission happens through close physical contact with skin lesions, bodily fluids, or contaminated materials like bedding and clothing. Respiratory droplets can also carry the virus during prolonged face-to-face contact. The Clade Ib outbreaks in eastern DRC added a notable wrinkle: epidemiological investigation found clear links to sexual contacts, with sustained transmission chains running through sexual networks.6PubMed Central. Roles of community and sexual contacts as drivers of clade I mpox outbreaks This does not make mpox a sexually transmitted infection in the narrow sense; it can spread through any close skin-to-skin contact. But sexual contact creates exactly the kind of prolonged, intimate exposure that the virus exploits efficiently.
What the Symptoms Look Like
Mpox typically unfolds in two stages. The first is a prodromal period lasting up to five days, marked by fever (the most commonly reported early symptom), headache, muscle aches, fatigue, and swollen lymph nodes. Lymph node swelling is a distinctive feature that helps clinicians distinguish mpox from smallpox and chickenpox, which do not usually cause it.10PubMed Central. The dermatological manifestations and differential diagnosis of monkeypox: A narrative review Within one to three days of the fever’s onset, a skin rash appears.
The rash follows a fairly predictable evolution. In the first few days, raised bumps (papules), fluid-filled blisters (vesicles), and pus-filled lesions (pustules) dominate. By the second week, pustules give way to crusted scabs, which are the predominant form after day eleven.11PubMed Central. A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: Skin lesion morphology, clinical course, and scarring The scabs eventually fall off, and a person is generally considered no longer infectious once all scabs have separated. The entire course from first symptoms to scab separation can take two to four weeks.
Where the rash appears has varied across outbreaks. Classically, mpox lesions start on the face and spread outward. But in more recent outbreaks, especially those linked to sexual transmission, lesions commonly begin in the genital and perianal areas. A prospective study of hospitalized patients with Clade Ib mpox in South Kivu found that about 89 percent of adults had genital skin lesions, and the genital area had the highest lesion density. The pattern looked different in children: only about 42 percent had genital lesions, and their rash was more evenly distributed across the body.12The Lancet. Clinical characteristics and risk factors for outcomes of hospitalized patients with clade Ib mpox in Kamituga, South Kivu, Democratic Republic of the Congo: a prospective observational cohort study Mucosal lesions, including in the mouth or throat, were also common, appearing in roughly 82 percent of patients in that same cohort.
Who Faces the Greatest Risk
While mpox can infect anyone, certain groups face disproportionately severe outcomes. Children in the DRC have historically borne a heavy burden. One analysis noted an overall case fatality rate of about 10.6 percent among children and adults combined in the DRC, with young children particularly vulnerable because of their developing immune systems.13PubMed Central. High Rates of Miscarriage and Stillbirth among Pregnant Women with Clade I Mpox (Monkeypox) Are Confirmed during 2023-2024 DR Congo Outbreak in South Kivu Province
Pregnant women with mpox face especially devastating consequences. A prospective, multi-center study in the DRC tracked pregnancy outcomes and found that adverse outcomes occurred in about half of the women whose pregnancies could be followed. Fetal loss, including miscarriages and stillbirths, affected 45 percent. Infection during the first trimester carried the highest risk: women infected later in pregnancy had substantially lower rates of adverse outcomes. Other factors associated with worse outcomes included high viral load in skin lesions, HIV co-infection, genital lesions, and direct sexual contact with the person who passed on the virus.14The Lancet. Mpox in pregnant women in the Democratic Republic of the Congo: a prospective, multicentre, observational cohort study Some newborns delivered by infected mothers showed congenital mpox-like lesions, confirming that the virus can cross the placenta and infect the fetus.
People living with HIV, particularly those with weakened immune systems, also face heightened risks. HIV co-infection was a significant predictor of adverse pregnancy outcomes in the study above, and more broadly, immune suppression can allow the virus to replicate more aggressively and delay healing.
The Diagnostic Gap in Central Africa
Confirming mpox requires a laboratory test, ideally a PCR test performed on a swab from a skin lesion. But PCR testing demands trained personnel, reliable electricity, reagents, and cold-chain logistics, all of which are scarce in rural DRC. As a result, diagnosis in the most affected regions is often made purely on clinical grounds, by looking at the lesions. This is unreliable because mpox lesions can closely resemble chickenpox, which is common in the same areas and age groups.15PLOS Neglected Tropical Diseases. Challenges in clinical diagnosis of Clade I Mpox: Highlighting the need for enhanced diagnostic approaches
Rapid antigen tests offer a potential solution by providing results in minutes without laboratory infrastructure. Field evaluations of these tests in the DRC and Uganda, however, have shown mixed performance. One multi-center study found that the overall sensitivity of a rapid antigen test was about 70 percent and the specificity around 89 percent. Performance varied sharply by country: sensitivity was roughly 82 percent in Uganda but only about 55 percent in the DRC.16The Lancet. Field evaluation of a rapid antigen test for mpox in the Democratic Republic of the Congo and Uganda: a multicentre, prospective, diagnostic accuracy study A separate study evaluating five different rapid tests underscored the broader challenge: even though these point-of-care tools could expand diagnostic access, their accuracy is not yet reliable enough to replace PCR in all settings.17PubMed. Performance of five mpox antigen-based rapid diagnostic tests tested on lesion swabs from patients with suspected mpox from the Kinshasa province of DR Congo: a diagnostic accuracy study For now, the most affected communities often rely on an educated guess rather than a confirmed test result.
Vaccines and How Well They Work
No vaccine was developed specifically for mpox, but the virus is closely related to smallpox, and smallpox vaccines provide meaningful cross-protection.18PubMed Central. Systematic Review on the Efficacy, Effectiveness, Safety, and Immunogenicity of Monkeypox Vaccine Three main vaccines are in use or under consideration:
- JYNNEOS (MVA-BN): A modified vaccinia Ankara vaccine that cannot replicate in human cells, giving it a favorable safety profile. Studies have estimated its effectiveness at roughly 82 percent for preventing mpox. It is widely used in the United States and Europe and has been deployed in the DRC’s outbreak response.
- ACAM2000: A replication-competent vaccinia virus vaccine with high effectiveness but a more concerning side-effect profile, including rare cases of heart inflammation and a risk of uncontrolled viral spread in immunocompromised people.
- LC16: A Japanese smallpox vaccine recommended by the WHO for use in affected regions. It has shown strong protective results in animal models and good safety in human trials.
These descriptions draw on systematic and critical reviews of the available evidence.19PubMed Central. Safety and Efficacy of Repurposed Smallpox Vaccines Against Mpox: A Critical Review of ACAM2000, JYNNEOS, and LC1620PubMed Central. Personalized immunization against Mpox Clades I and Ib: Strategies to combat the emerging epidemic Vaccination can be given before exposure (pre-exposure prophylaxis) or shortly after a known contact (post-exposure prophylaxis), with best results when administered within four days of exposure.
The bigger problem in the DRC is not the existence of vaccines but getting them into arms. Vaccine delivery has been slow due to supply constraints, delayed funding, and the logistical difficulties of reaching remote communities. By the second phase of the continental response, only about a third of delivered doses had actually been administered, signaling major gaps between supply and distribution.21BMJ. Mpox in Africa: one year continental response outcomes and way forward Experts have called for integrating mpox vaccination into routine immunization programs and deploying community health workers to reach rural areas where cold-chain systems and health facilities are limited.22PLoS Neglected Tropical Diseases. Mpox in Africa: What we know and what is still lacking
Treatment and the Tecovirimat Disappointment
For years, the antiviral drug tecovirimat (brand name TPOXX) was considered the most promising treatment for severe mpox. It was approved for smallpox based on animal studies and made available for mpox under compassionate-use protocols. But the first large, rigorous trial in humans told a less encouraging story. The PALM007 trial, a randomized, placebo-controlled study conducted in the DRC, found no significant difference between tecovirimat and placebo in the time it took for lesions to resolve: a median of seven days with the drug versus eight days with placebo. Viral clearance from blood, lesions, and throat swabs was also similar between the two groups.23PubMed. Tecovirimat for Clade I MPXV Infection in the Democratic Republic of Congo
One silver lining: overall mortality in the trial was 1.7 percent, well below the 4.6 percent case fatality rate reported in the DRC in 2023. But because both the treatment and placebo groups did better than expected, this likely reflects the benefits of being enrolled in a clinical trial with close medical monitoring, adequate hydration, and wound care rather than any specific drug effect. Commentary on the trial results has described the findings as a crossroads for mpox treatment, highlighting the need for new therapeutic strategies.24PubMed. Tecovirimat at a crossroads: What the PALM007 trial tells us For now, supportive care remains the mainstay of treatment: managing pain, preventing secondary bacterial infections in skin lesions, and ensuring adequate nutrition and hydration.
Long-Term Effects After Recovery
Mpox is sometimes framed as a self-limiting illness, and for most people it is. But “self-limiting” does not mean “no lasting consequences.” A cohort study following mpox survivors in two U.S. cities found that about 58 percent still had at least one persistent problem 11 to 18 months after their acute illness. The majority of these were appearance-related changes, most likely scarring at the sites of former lesions. About half of those with appearance-related issues had them at two or fewer body sites, but for some the scarring was more widespread.25PubMed Central. Long-Term Mpox Sequelae 11 to 18 Months After Acute Illness : A Cohort Study in Two U.S. Cities Scarring in the genital area or on the face can carry significant psychological and social consequences beyond the physical marks themselves.
This study involved Clade IIb infections, which are generally less severe than Clade I. Long-term outcome data from Clade I survivors in the DRC remain scarce, but given the more severe acute disease caused by that clade, lasting effects could be more pronounced. Research on this front is badly needed.
Stigma as a Barrier to Control
Stigma has emerged as one of the most stubborn obstacles to controlling mpox outbreaks, particularly in communities where the disease is linked to sexual transmission. Research on men who have sex with men during the 2022 global outbreak documented how discrimination and social judgment discouraged people from seeking care and accessing timely treatment.26PubMed Central. Mpox-related stigma and healthcare-seeking behavior among men who have sex with men The pattern is not unique to any one community. A qualitative study from Sierra Leone’s 2025 Clade IIb outbreak found that stigma permeated every dimension of the outbreak experience, delaying care-seeking, undermining contact tracing efforts, and adding psychological distress to healthcare workers already stretched thin.27PLOS Global Public Health. Suffering in silence: Stigma, healthcare barriers, and resilience during Sierra Leone’s 2025 clade IIb mpox outbreak—A multi-perspective qualitative study
In the DRC, stigma intersects with poverty, limited healthcare access, and social disruption from conflict. People who suspect they have mpox may avoid health facilities for fear of being ostracized, leading to continued transmission within households and communities. Public health campaigns that frame mpox purely through the lens of sexual behavior risk deepening this stigma. Messaging that emphasizes that mpox spreads through any close physical contact, not just sexual contact, and that anyone can be affected tends to encourage broader testing and earlier treatment.
Everyday Prevention Beyond Vaccination
Vaccines are the most powerful prevention tool, but they are not the only one, and in much of the DRC they remain unavailable. Practical steps that reduce risk include avoiding direct skin contact with anyone who has an unexplained rash or blistering lesions, not sharing bedding or clothing with a sick person, and washing hands frequently with soap and water after caring for someone who is ill. In areas where animal-to-human spillover is a concern, avoiding handling or eating bushmeat from rodents and primates reduces exposure to the virus in its wildlife reservoir.
Healthcare workers face particular risks because they handle patients with active lesions. Standard infection control measures, including gloves, gowns, and eye protection, are recommended but inconsistently available in resource-limited settings. Strengthening basic infection-prevention infrastructure in health facilities across the DRC would reduce transmission to both staff and other patients, with benefits that extend well beyond mpox to other infectious diseases circulating in the same communities.