Skip to main content
NCBI home page
UKPMC Funders Author Manuscripts logoLink to UKPMC Funders Author Manuscripts
. Author manuscript; available in PMC: 2025 Oct 17.
Published in final edited form as: Lancet. 2025 Jan 29;405(10478):547–559. doi: 10.1016/S0140-6736(25)00047-9

Epidemiological and Clinical Features of Mpox during the Clade Ib Outbreak in South-Kivu, Democratic Republic of the Congo: a Prospective Cohort Study

Isabel Brosius 1,#, Emmanuel Hasivirwe Vakaniaki 1,2,#, Guy Mukari 3, Papy Munganga 4, Jean Claude Tshomba 5, Elise De Vos 1, Eugene Bangwen 1,6, Yves Mujula 2, Achilleas Tsoumanis 1, Christophe Van Dijck 1, Aimé Alengo 7, Léandre Mutimbwa-Mambo 8, Franklin Mweshi Kumbana 9, Jenestin Babingwa Muunga 9, Divin Mazambi Mambo 9, Jems Wakilongo Zangilwa 9, Steeven Bilembo Kitwanda 9, Sarah Houben 1, Nicole A Hoff 10, Jean-Claude Makangara-Cigolo 2,11, Eddy Kinganda-Lusamaki 2,12, Martine Peeters 12, Anne W Rimoin 10, Jason Kindrachuk 13, Nicola Low 11, Patrick DMC Katoto 14,15, Espoir Bwenge Malembaka 14,16, John H Amuasi 17,18, Olivier Tshiani-Mbaya 2, Dally Muamba Kambaj 19, Richard Kojan 19, Cris Kacita 20, Daniel Mukadi-Bamuleka 2,5,21, Steve Ahuka-Mundeke 2,21, Koen Vercauteren 1, Tony Wawina-Bokalanga 1,2,21, Jean-Jacques Muyembe-Tamfum 2,21, Sabin Sabiti Nundu 1,2,*, Laurens Liesenborghs 1,6,*,$, Placide Mbala-Kingebeni 2,21,*,$
PMCID: PMC7618259  EMSID: EMS209568  PMID: 39892407

Abstract

Background

Clade Ib, a new strain of Clade I monkeypox virus (MPXV), emerged in Eastern Democratic Republic of the Congo (DRC), sparking an international outbreak. Comprehensive studies are needed to assess its transmission dynamics and clinical presentation.

Methods

We conducted a prospective observational cohort study at Kamituga General Hospital in South Kivu, DRC, between May 2 and October 9, 2024. Sociodemographic, exposure and clinical data were collected from mpox suspected cases. Cases were confirmed by Xpert® Mpox polymerase chain reaction (PCR) and followed through hospitalization and on days 29 and 59 post-diagnosis.

Findings

Of 510 included suspected cases, 407 (80%) tested PCR positive. Among confirmed cases, 196 (48%) were women. Age distribution was bimodal, with 58 (14%) children under five, and 267 (66%) individuals aged 15-34 years. Most cases (58%) reported contact with a suspected or confirmed mpox case; primarily colleagues, spouses or sexual partners in adults, and parents or siblings in children. Self-reported comorbidities were rare (5%), including six (2%) human immunodeficiency virus (HIV) infections. Prodromal symptoms were present in 331 (88%) patients, active skin lesions in 394 (97%), mucosal lesions in 324 (82%), and lymphadenopathy in 288 (73%). In adults, 89% had genital skin lesions and mean lesion density was highest in the genital area. In contrast, only 42% of children had genital lesions, as part of a more uniform rash. Among 403 hospitalized patients, two deaths (0·5%) occurred. Among 296 patients with detailed hospital follow-up, complications were primarily genito-urinary (57%) or cutaneous (41%). Four of six pregnant women with recorded outcome (67%) had adverse pregnancy outcomes. On days 29 and 59, few sequelae were reported other than scars.

Interpretation

Clade Ib infections in Kamituga exhibited distinct clinical patterns compared to Clade Ia outbreaks elsewhere in the country and the global Clade IIb outbreak. In adults, the disease primarily affected the genito-urinary system, compatible with sexual transmission, while children mostly manifested extragenital lesions. These findings highlight the need for updated case definitions and targeted public health interventions to address evolving transmission dynamics and mitigate risks for vulnerable groups, including pregnant women and young children.

Funding

European & Developing Countries Clinical Trials Partnership (EDCTP2 and EDCTP3); Belgian Directorate-General Development Cooperation and Humanitarian Aid; Research Foundation – Flanders

Introduction

Mpox is a disease caused by monkeypox virus (MPXV). Historically, human mpox was spread through zoonotic spillover followed by limited human-to-human transmission of MPXV Clade I in Central Africa or MPXV Clade II in West Africa.1 However, in recent years, several lineages of MPXV have been linked to sustained human-to-human transmission, resulting in two major international outbreaks.2

In 2017, a subclade of Clade II, named Clade IIb began circulating in Nigeria through human-to-human transmission, including through sexual contact.3 Its subsequent international spread culminated in the 2022 global outbreak, with over 100,000 documented mpox cases to date. The outbreak overwhelmingly affected adult men – often identifying as men-who-have-sex-with-men –, who predominantly presented with relatively mild disease and localized anogenital or oral lesions.1,4 The overall case fatality rate (CFR) was below 0·1%.2

A similar scenario is currently unfolding with Clade I in the Democratic Republic of the Congo (DRC). The country notified a substantial increase in Clade I MPXV infections over multiple decades, primarily in rural areas, where outbreaks are largely due to zoonotic spillover and predominantly impact children and age groups that have not received prior smallpox vaccination.5,6 Historically, Clade I infections have been associated with a generalized papulopustular rash, with potentially severe outcomes and a reported CFR of 1·4% to 11%. 7–10

In September 2023, however, a new lineage of Clade I MPXV emerged in a densely populated urban and previously largely unaffected region in South Kivu, DRC. 10,11 Phylogenomically, the lineage, named Clade Ib, constitutes a cluster distinct from other Clade I lineages that are now denoted Clade Ia.10 The subsequent human-to-human spread of Clade Ib resulted in 2,672 confirmed mpox cases in South Kivu between January 1 and October 20, 2024.2 Of these, 157 viral strains were sequenced, with 156 showing Clade Ib.12,13 From South Kivu, Clade Ib spread to other provinces and cross-border to neighboring countries. Consequently, in August 2024, both the Africa Center for Disease Control (CDC) and the World Health Organization (WHO) issued emergency declarations.14

Unlike Clade Ia, early reports about Clade Ib mpox in South-Kivu suggested that mainly adolescents and young adults were affected, with lower disease severity and predominantly genital lesions.10,11,13 Clade Ib, emerging in an epidemiological context conducive to sexual transmission, therefore exhibits notable similarities with Clade IIb mpox. However, robust clinical data are lacking. This study describes the epidemiological and clinical characteristics of the Clade Ib mpox outbreak in South Kivu, DRC.

Material and Methods

Study Design, Site and Participants

The Mpox Biology, Outcome, Transmission, and Epidemiology - Kamituga study (MBOTE-Kamituga, clinicaltrials.gov: NCT06652646, www.mbote-mpox.com) is a prospective observational cohort study of mpox patients enrolled at Kamituga General Hospital (KGH), the mpox treatment center for Kamituga and surrounding health zones. Kamituga Health Zone, the initial epicenter of the Clade Ib mpox outbreak, is a mining region in South-Kivu province, eastern DRC, with a population estimated at 242,000 people.15 Preceding initiation of the study, in April 2024, a diagnostic lab and isolation unit with an admission capacity of 37 beds were established.

All individuals suspected of having mpox presenting to the hospital and providing written informed consent were included. Participants underwent a baseline survey and physical examination prior to diagnostic testing. Those who tested positive for mpox were subsequently followed up longitudinally.

Procedures And Data Collection

A standardized case report form (CRF), programmed into a REDCap™ database (Vanderbilt University, Nashville, TN), was used by a study physician to collect data on exposure, socio-demographics, medical history, signs and symptoms. Questions about sexual behaviors were restricted to people over 12 years old. Physical examination at enrolment assessed lesions – including WHO severity score16 –, lymphadenopathy, and complications. No data on race or ethnicity was collected.

Skin lesion and oropharyngeal swabs were tested on-site with Xpert® Mpox cartridges on a 4-module GeneXpert real-time PCR system (Cepheid, Sunnyvale, California CA, USA), which detects non-variola Orthopoxvirus (OPXV) and MPXV Clade II DNA.17 A sample was considered positive for MPXV Clade I, if non-variola OPXV DNA was detected with a cycle threshold (Ct) value below 40 and MPXV Clade II PCR was negative. A subset of samples collected between May 2 and August 30 was shipped to the INRB reference laboratory in Kinshasa for clade confirmation with a Clade Ib-specific PCR.18 Negative samples were retested, using both MPXV-generic, MPXV subclade Ib-specific, and Clade Ia-specific real-time PCR assays.19

All individuals with a positive PCR on skin or oropharyngeal sample were admitted for isolation purposes, regardless of disease severity at presentation, and were followed up by the study team. The evolution of symptoms, signs and complications was documented in a CRF. Patients received supportive care, including symptomatic therapy (analgesia, antipyretics,…), nutritional support, skincare, and antibacterial and antimalarial treatment where indicated. No MPXV-specific antivirals were available. Malaria and HIV rapid diagnostic tests, hemoglobin assays, point-of-care glucometry, and HCG dipstick tests were performed at the discretion of the treating physician. Testing for other sexually transmitted infections, Varicella, bacterial infections, and biochemical analyses were not available. Patients were discharged at the discretion of the treating physician.

Participants were invited for follow-up visits on days 29 and 59 after mpox diagnosis to record residual signs and symptoms. Pregnant women were advised to return to KGH for pregnancy-related complications or labor. Pregnancy outcomes (abortion or delivery, complications during delivery, and fetal outcome) were captured in a dedicated CRF.

Statistical Analysis

Demographic, clinical and behavioral characteristics were described using medians and interquartile ranges (IQR) for continuous variables and counts and percentages for categorical variables. For the representation of the clinical data, participants were categorized into three age groups based on expected physiological and exposure differences: children under five years, children aged five to 14 years, and individuals aged 15 years and older. The latter group is referred to as ‘adults’ throughout the manuscript. The association between sociodemographic and exposure characteristics and MPXV-PCR test results among mpox suspected cases as well as differences in clinical presentation between age categories, was tested using Fisher’s exact test for categorical characteristics and Mann-Whitney non-parametric test for continuous variables. The resulting p-values were corrected for multiple testing with the Benjamini-Hochberg method. The maximum p-value that was considered statistically significant was 0.0057. The time from symptom and lesion onset to resolution were calculated and presented through survival Kaplan-Meier curves. Data were analyzed with R, version 4.3.1.

Ethical Considerations

The study was approved by the Ethics Committee of the University of Kinshasa (approval ID ESP/CE/78/2024) and the University Hospital Antwerp (ID 6383). Written consent was obtained prior to all study procedures from participants aged 18 years and older, and from parents or guardians for minors. Children from 12 to 17 years old received age-appropriate information and signed an assent form. Pictures for publication were taken with additional written consent. All participants received reimbursement of transportation costs and free care and nutrition.

Role Of The Funding Source

The funders had no role in the conceptualization of the study, data acquisition or interpretation, writing of the manuscript, or publication of the findings.

Results

Between May 2 and October 9, 2024, 649 individuals presented with suspected mpox, of which 510 were enrolled (Supplementary Figure 1). Among those included, 407 (80%) tested positive on Xpert® PCR. Of a subset of 253 (62%) positive samples tested with Clade Ib-specific PCR, 248 (98%) were positive. Five were negative on generic OPXV, Clade Ib, and Clade Ia PCR.

Demographics, Exposure And Risk Factors

Of 407 confirmed cases, all residents of South Kivu, 196 (48%) were women (Table 1). The median age was 22 (IQR 18-29, range 1 week to 79 years). Individuals aged 15-34 accounted for 66% of all infections, while children aged 10-14, 5-9, and under five years represented 3%, 4%, and 14%, respectively. (Figure 1A) Travel within three weeks prior to mpox diagnosis was reported by 72 individuals, primarily within South Kivu or to North Kivu (mostly Goma), but not to neighboring countries. The most reported occupations were mine worker – mostly men – (n=94, 24%) and sex worker (n=50, 13%) – mostly women.

Table 1. Demographic profile and exposure risk of suspect mpox cases in Kamituga, DRC, by infection status.

All suspected cases
(n = 510)		 MPXV-positive
(n = 407)		 MPXV-negative
(n = 103)		 Adjusted
p value
Demographics ·· ·· ··
Age, years - median (IQR) 22 (14-29) 22 (18-29) 17 (5-31) 0·016
Age group – n (%) ·· ·· ·· 0·005
          0-4 years 84/510 (17%) 58/407 (14%) 26/103 (25%) ··
          5-9 years 24/510 (5%) 16/407 (4%) 8/103 (8%) ··
          10-14 years 22/510 (4%) 12/407 (3%) 10/103 (10%) ··
          15-34 years 310/510 (61%) 267/407 (66%) 43/103 (42%) ··
          35-49 years 58/510 (11%) 48/407 (12%) 10/103 (10%) ··
          ≥ 50 years 12/510 (2%) 6/407 (2%) 6/103 (6%) ··
Female– n (%) 241/510 (47%) 196/407 (48%) 45/103 (44%) 0·650
Occupation* – n (%) ·· ·· ·· 0·005
          Sex worker 57/497 (12%) 50/396 (13%) 7/101 (7%) ··
          Mine worker 106/497 (21%) 94/396 (24%) 12/101 (12%) ··
          Healthcare worker 4/497 (1%) 4/396 (1%) 0/101 (0%) ··
          Barman 6/497 (1%) 5/396 (1%) 1/101 (1%) ··
          Teacher 3/497 (1%) 2/396 (1%) 1/101 (1%) ··
          Student 53/497 (11%) 34/396 (9%) 19/101 (19%) ··
          Services 86/479 (18%) 80/396 (20%) 6/101 (6%) ··
          Manual worker 82/479 (17%) 63/396 (16%) 19/101 (19%) ··
          Unemployed 6/497 (1%) 2/396 (1%) 4/101 (4%) ··
Exposure ·· ·· ·· ··
Travel in the previous 3 weeks° – n (%) 83/508 (16%) 72/406 (18%) 12/103 (12%) 0·545
Exposure to animal reservoir£ – n (%) 63/440 (14%) 55/347 (16%) 8/93 (9%) 0·273
Sex in the previous 3 weeks – n (%) 324/401 (81%) 282/332 (85%) 42/69 (61%) < 0·001
          Number of partners – median (IQR) 1 (1-3) 1 (1-3) 1 (1-2) 0·331
          More than one partner 132/320 (41%) 118/278 (42%) 13/42 (33%) 0·506
          Consistent use of condoms$ 13/311 (4%) 12/270 (4%) 1/41 (2%) 1·000
Engaged in transactional sex – n (%) 143/395 (36%) 130/328 (40%) 13/67 (19%) 0·014
Contact with suspected or confirmed case – n (%) 285/509 (56%) 237/406 (58%) 48/103 (47%) 0·113
          Potential source cases per participant, n – median (IQR) 1 (1-2) 1 (1-2) 1 (1-2) 0·765
          Multiple or continuous exposure 254/269 (94%) 212/224 (95%) 42/45 (93%) 0·809
          Time since last exposure, days – median (IQR) 3,5 (1-10) 4 (1-10) 2 (1-7) 0·273
          Relation with the potential source case# – n (%) ·· ·· ·· 0·042
              Family (same household) 143/278 (51%) 115/231 (50%) 28/47 (60%) ··
              Family (different household) 12/278 (4%) 6/231 (3%) 6/47 (13%) ··
              Neighbor 19/278 (7%) 14/231 (6%) 5/47 (11%) ··
              Colleague 88/278 (32%) 75/231 (33%) 13/47 (28%) ··
              Sexual 50/278 (18%) 48/247 (19%) 2/47 (4%) ··
                           Sexual partner 12/278 (4%) 11/231 (5%) 1/47 (2%) ··
                           Client of sex worker 17/278 (6%) 16/231 (7%) 1/47 (2%) ··
                           Sex worker 21/278 (8%) 21/231 (9%) 0/47 (0%) ··
              Patient of the participant 2/278 (1%) 2/231 (1%) 0/47 (0%) ··
              Other 5/278 (2%) 5/231 (2%) 0/47 (0%) ··
Type of exposure§ – n (%) ·· ·· ·· ··
              Prolonged (> 15 min) discussion 273/285 (96%) 228/237 (96%) 45/48 (94%) 0·650
              Direct skin to skin contact 278/285 (98%) 231/237 (98%) 47/48 (98%) 1·000
              Sexual contact 114/285 (40%) 100/237 (42%) 14/48 (29%) 0·273
              Care giving 67/285 (24%) 57/237 (24%) 10/48 (21%) 0·809
              Sharing meals and/or eating utensils 254/285 (89%) 214/237 (90%) 40/48 (83%) 0·331
              Sharing bed and/or bedlinen 196/285 (69%) 167/237 (71%) 29/48 (60%) 0·328
              Sharing clothes 35/285 (12%) 28/237 (12%) 7/48 (15%) 0·767
Open in a new tab

Data are median and IQR for numeric variables and n/N (%) for categorical variables. N signifies the number of included individuals with available data. *Sex worker refers to participants self-identifying as sex worker. This may may include both formal sex work and sex in exchange for goods/services. Services include public services such as law enforcement/policemen, traditional chieftain, pastor and state agents, transport services such as taxi drivers and truck drivers, and shop keepers, restaurant owners, hairdressers and security guards. °Travel includes regional travel within the Kivus, but not to neighboring countries £Exposure to animal reservoir is defined as involvement in activities such as hunting, capturing, or consuming rodents, eating bushmeat, or handling or consuming animals found dead. $Consistent use of condoms means the use of condoms for (nearly) all sexual contact. #Spouses were reported as family members. The denominator represents the number of potential source cases. The sum exceeds 100% because the relationship is defined per potential source case, 1 participant can have > 1 potential source case §Multiple answers per participant are possible, the numerator indicates the number of participants that had the specific exposure type with at least one potential source case.

Abbreviations: IQR = interquartile range, min = minutes, MPXV = monkeypox virus

Figure 1. Demographics, Clinical Presentation and Evolution of Clade Ib mpox, South-Kivu, DRC.

Figure 1

Open in a new tab

(A) Age and sex distribution of confirmed mpox participants, (B) Body map indicating the proportion of participants with lesions in a given body region at inclusion for adults (>= 15 years) and children 0-14 years. (C) Body map indicating the mean density of skin lesions per body region at inclusion for individuals of 15 years old and above, and children aged 0 to 14 years old, expressed as number of lesions (n) per percentage of total body surface area (TBSA) according to a modified Lund-Browder chart for estimated TBSA. (D) Body map indicating the proportion of participants with scars per body region on day 59 after diagnosis for adults (>= 15 years) and children 0-14 years. (E) Kaplan-Meier estimates for time from onset of active lesions to resolution, with 95% confidence interval. (F) Kaplan-Meier estimates for time from onset of symptoms to resolution of all symptoms, with 95% confidence Interval.

Among confirmed cases, 58% (n=237) reported contact with one or more suspected or confirmed mpox cases in the three weeks before diagnosis. Among them, 53 children of whom 44 (86%) had contact with a potentially infected household member, either parents (44%) or siblings (56%). Of the 184 adults exposed to a potential case, 75 (42%) indicated a colleague as the potential source of infection, 71 (39%) a household member, mostly spouses (n=50/71, 70%), and 30 (17%) a sexual partner outside the household (Supplementary table 1). Exposure mostly involved skin-to-skin contact (n=231, 98%), prolonged conversation (>15 min) (n=228, 96%), shared meals or utensils (n=214, 90%), and shared bedding (n=167, 71%), or sexual exposure in 42% (n=100).

Of the 332 confirmed mpox patients questioned on sexual behavior, 282 (85%) reported having had sex in the previous three weeks. Among these, 118 (42%) reported more than one sexual partner and 130 (40%) engagement in transactional sex. Only 16% (n=55) of confirmed cases reported contact with wild animals through hunting, handling, or consumption.

Comparing people with suspected mpox who tested positive to those who tested negative, we observed an older age distribution (median age 22 vs 17, p=0·016), and a higher proportion of sex workers (although statistically not significant, 13% vs 7%, p=0·276) and mine workers (24% vs 12%, p=0·042) among the confirmed cases. Compared with non-infected individuals, confirmed cases more often reported sexual intercourse (85% vs 61%, p<0·001), including transactional sex (40% vs 19%, p=0·014), and contact with another potential mpox case in the three weeks before diagnosis (although statistically not significant, 58% vs 47%, p=0·113). There were no relevant differences between male and female participants in terms of demographics and exposure. (Supplementary table 2)

Medical History And Clinical Presentation At Admission

Only 18 (5%) mpox patients reported comorbidities, including malnutrition (n=9), and HIV (n=6) (Table 2). Six (2%) had a scar from smallpox vaccination during childhood Mpox-confirmed patients presented at the hospital a median of seven (IQR 5 – 10) days after the onset of symptoms and five (IQR 4-7) days after the appearance of skin lesions (Table 2). Prodromal symptoms preceded the rash in 331 (88%) of patients. Systemic symptoms such as fatigue, malaise, and myalgia were common, affecting 368 (91%), 310 (77%), and 291 (73%) patients, respectively (Table 2, Supplementary figure 2). The lesions commonly caused itching (93%) or pain (79%). Eye pain and visual problems were reported in 20% and 10% of cases respectively, mostly among adults. Adult mpox patients often had genital pain (n=111 51%), dysuria (n=158 40%), or rectal pain (n=44, 11%). Anogenital symptoms rarely occurred among children.

Table 2. Medical history and clinical presentation of confirmed mpox cases at inclusion in Kamituga, DRC (2024) in relation to age categories.

All confirmed Cases
(n = 407)		 Per age category (years)
0-4 (n = 58) 5-14 (n = 28) ≥15 (n = 321)
Medical history ·· ·· ·· ··
Childhood smallpox vaccination% – n (%) 6/293 (2%) ·· ·· 6/293 (2%)
Previous mpox* – n (%) 4/398 (1%) 2/57 (4%) 0/28 (0%) 2/313 (1%)
Comorbiditiesμ – n (%) 18/400 (5%) 0/56 (0%) 2/28 (7%) 16/316 (5%)
           HIV 6/400 (2%) 0/56 (0%) 1/28 (4%) 5/316 (2%)
                Under ART 3/5 (60%) ·· 1/1 (100%) 2/4 (60%)
           Tuberculosis 5/407 (1%) 0/58 (0%) 1/28 (4%) 4/321 (1%)
           Diabetes 1/407 (0%) 0/58 (0%) 0/28 (0%) 1/321 (0%)
           Chronic liver disease 0/407 (0%) 0/58 (0%) 0/28 (0%) 0/321 (0%)
           Chronic pulmonary disease 1/407 (0%) 0/58 (0%) 1/28 (4%) 0/321 (0%)
           Rheumatic disease 3/407 (1%) 0/58 (0%) 0/28 (0%) 3/321 (1%)
           Arterial hypertension 1/407 (0%) 0/58 (0%) 0/28 (0%) 1/321 (0%)
Malnutrition# – n (%) 9/354 (3%) 5/52 (10%) 3/24 (13%) 1/278 (1%)
           Moderate malnutrition 8/354 (2%) 4/52 (8%) 3/24 (13%) 1/278 (2%)
           Severe malnutrition 1/354 (0%) 1/52 (2%) 0/24 (0%) 0/278 (0%)
Pregnancy – n (%) 21/196 (11%) ·· ·· 21/155 (11%)
           1st trimester 5/20 (25%) ·· ·· 5/20 (25%)
           2nd trimester 10/20 (50%) ·· ·· 10/20 (50%)
           3rd trimester 5/20 (25%) ·· ·· 5/20 (25%)
Clinical presentation ·· ·· ·· ··
Time since onset of symptoms, days – median (IQR) ·· ·· ·· ··
           Any symptom 7 (5-10) 6 (3-8) 5 (4-7) 8 (6-10)
           Lesions 5(4-7) 4 (3-6) 3 (3-4) 5 (4-7)
Prodromal phase± – n (%) 331/375 (88%) 37/48 (77%) 20/25 (80%) 274/302 (88%)
Symptoms – n (%) ·· ·· ·· ··
           Fatigue 368/405 (91%) 48/57 (84%) 25/28 (89%) 295/320 (91%)
           Malaise 310/404 (77%) 32/56 (57%) 24/28 (86%) 254/320 (77%)
           Myalgia 291/400 (73%) 30/53 (57%) 19/27 (70%) 242/320 (73%)
           Pain associated with  lesions 318/402 (79%) 38/54 (70%) 22/28 (79%) 258/320 (79%)
           Itching 372/402 (93%) 48/54 (89%) 27/28 (96%) 297/320 (93%)
           Cough 147/403 (37%) 29/56 (52%) 9/28 (32%) 109/319 (37%)
           Shortness of breath 57/404 (14%) 11/56 (20%) 0/28 (0%) 46/320 (14%)
           Anorexia 233/405 (58%) 20/57 (35%) 20/28 (71%) 193/320 (58%)
           Throat ache / dysphagia 225/402 (56%) 11/54 (20%) 20/28 (71%) 194/320 (56%)
           Abdominal pain 122/400 (31%) 4/53 (8%) 9/28 (32%) 109/319 (31%)
           Nausea / vomiting 93/404 (23%) 7/56 (13%) 8/28 (29%) 78/320 (23%)
           Diarrhea 52/404 (13%) 5/56 (9%) 3/28 (11%) 44/320 (13%)
           Headache 241/399 (60%) 2/52 (4%) 15/28 (54%) 224/319 (60%)
           Confusion 12/404 (3%) 1/56 (2%) 2/28 (7%) 9/320 (3%)
           Convulsions 1/405 (0%) 1/57 (2%) 0/28 (0%) 0/320 (0%)
           Eye pain 80/403 (20%) 0/56 (0%) 2/28 (7%) 78/319 (20%)
           Visual problems 41/403 (10%) 0/56 (0%) 0/27 (0%) 41/320 (10%)
           Rectal pain 45/401 (11%) 1/55 (2%) 0/27 (0%) 44/319 (11%)
           Dysuria 160/402 (40%) 1/54 (2%) 1/28 (4%) 158/320 (40%)
           Hematuria 22/405 (5%) 1/57 (2%) 0/28 (0%) 21/320 (5%)
           Genital pain 112/218 (51%) 1/1 (100%) 0/6 (0%) 111/211 (51%)
Vital signs – n (%) ·· ·· ·· ··
           Temperature > 38 °C 20/400 (5%) 4/57 (7%) 2/28 (7%) 14/315 (5%)
           Tachycardia 55/393 (14%) 4/52 (8%) 11/27 (41%) 40/314 (14%)
           Tachypneaμ 105/345 (30%) 23/50 (46%) 12/22 (55%) 70/273 (30%)
           MAP < 60 mmHg 5/376 (1%) 2/33 (6%) 2/27 (7%) 1/316 (1%)
           Oxygen saturation < 94% 9/393 (2%) 2/56 (4%) 1/28 (4%) 6/309 (2%)
           Capillary refill > 2 sec 18/378 (5%) 3/55 (6%) 3/24 (13%) 12/299 (5%)
Skin lesions – n (%) 396/404 (98%) 55/57 (97%) 28/28 (100%) 313/319 (98%)
           Active lesions£ 394/407 (97%) 54/58 (93%) 28/28 (100%) 312/321 (97%)
           Rash pattern ·· ·· ·· ··
                   Generalized€ 137/394 (35%) 14/54 (26%) 10/28 (36%) 113/312 (35%)
                   Predominantly genital$ 84/393 (21%) 1/54 (2%) 1/28 (4%) 82/311 (21%)
                   Only genital 34/394 (9%) 1/54 (2%) 0/28 (0%) 33/312 (9%)
           Lesion distribution ·· ·· ·· ··
                   Head and neck 287/396 (73%) 48/56 (86%) 23/28 (82%) 217/314 (69%)
                   Chest 218/396 (55%) 32/56 (57%) 20/28 (71%) 167/314 (53%)
                   Abdomen 231/396 (58%) 35/56 (63%) 18/28 (64%) 179/314 (57%)
                   Back 259/396 (65%) 44/56 (79%) 19/28 (68%) 197/314 (63%)
                   Arms 317/396 (80%) 47/56 (84%) 25/28 (89%) 246/314 (78%)
                   Palms of the hands 164/396 (41%) 20/56 (36%) 16/28 (57%) 129/314 (41%)
                   Legs 275/396 (69%) 40/56 (71%) 22/28 (79%) 214/314 (68%)
                   Soles of the feet 99/396 (25%) 11/56 (20%) 5/28 (18%) 84/314 (27%)
                   Genital 314/396 (79%) 18/56 (32%) 17/28 (61%) 280/314 (89%)
                   Anal 133/396 (34%) 15/56 (27%) 8/28 (29%) 111/314 (35%)
           Type ·· ·· ·· ··
                   Macule 57/394 (15%) 13/54 (24%) 3/28 (11%) 41/312 (15%)
                   Papule 209/394 (53%) 39/54 (72%) 20/28 (71%) 150/312 (53%)
                   Vesicle 283/394 (72%) 25/54 (46%) 13/28 (46%) 245/312 (72%)
                   Small pustule 174/394 (44%) 22/54 (41%) 10/28 (36%) 142/312 (44%)
                   Umbilicated pustule 150/394 (38%) 5/54 (9%) 6/28 (21%) 139/312 (38%)
                   Ulcer 90/394 (23%) 2/54 (4%) 3/28 (11%) 85/312 (23%)
                   Crust 156/394 (40%) 13/54 (24%) 4/28 (14%) 139/312 (40%)
Scar 50/394 (13%) 5/54 (9%) 2/28 (7%) 43/312 (13%)
           Monomorphic§ 80/394 (20%) 20/54 (37%) 12/28 (43%) 48/312 (20%)
           Complex lesions‡ 93/391 (24%) 1/54 (2%) 2/28 (7%) 90/309 (24%)
Total lesion count – median (IQR) 42 (17-94) 50 (31-123) 94 (24-184) 39 (16-85)
Mucosal lesions – n (%) 324/394 (82%) 24/54 (44%) 24/28 (86%) 276/312 (82%)
           Oral 99/392 (25%) 11/54 (20%) 12/28 (43%) 76/310 (25%)
           Tonsillar 179/390 (46%) 12/53 (23%) 17/28 (61%) 150/309 (46%)
           Penile 145/203 (71%) 9/29 (31%) 6/13 (46%) 130/161 (71%)
           Vaginal 140/187 (75%) 6/24 (25%) 8/14 (57%) 126/149 (75%)
Lymphadenopathy – n (%) 288/394 (73%) 10/54 (19%) 21/28 (75%) 257/312 (73%)
           Retro–auricular 48/394 (12%) 5/54 (9%) 8/28 (29%) 35/312 (12%)
           Submandibular 88/394 (22%) 9/54 (17%) 15/28 (54%) 64/312 (22%)
           Cervical 26/394 (7%) 1/54 (2%) 2/28 (7%) 23/312 (7%)
           Supra clavicular 2/394 (1%) 0/54 (0%) 0/28 (0%) 2/312 (1%)
           Axillar 22/394 (6%) 0/54 (0%) 1/28 (0%) 21/312 (6%)
           Inguinal 252/394 (64%) 4/54 (7%) 9/28 (7%) 239/312 (64%)
Open in a new tab

Data are median and IQR for numeric variables and n/N (%) for categorical variables. N signifies the number of individuals with available data. %Childhood smallpox vaccination was ascertained by the presence of a vaccination scar. µComorbidities are self-reported. *Previous mpox refers to suspected or confirmed MPXV infection, diagnosed at least 4 weeks prior to presentation. ±Prodromal phase refers to onset of other symptoms prior to onset of lesions. #Nutritional status is evaluated by age: severe malnutrition is defined as MUAC < 11·5 cm for children under 5 years old, BMI for age below -3 SD for children 5 to 19 years old and as BMI below 16 kg/m2 for adults over 19 years old, moderate malnutrition is defined as MUAC 11·5 to 12·5 cm for children under 5 years old, BMI for age -2 to -3 SD for children 5 to 19 years old and as BMI 16 to 18 kg/m2 for adults over 19 years old ¶Tachycardia is defined in relation to age: > 190 bpm for newborns 0 to 1 month, > 160 bpm for infants 1 to 11 months, > 140 bpm for 1 to 2 years, > 120 bpm for 3 to 7 years, > 100 bpm for older children, teens and adults. µTachypnea is defined in relation to age: > 40 brpm for newborns and infants 0 to 1 year, > 30 brpm for 1 to 7 years, > 25 brpm for older children to 12 years, > 20 brpm for teens and adults. £Active lesions are skin lesions that have not evolved to a crust or scar. €Generalized rash are skin lesions that are present on at least 8 out of ten body regions: head and neck, chest, abdomen, back, arms, palms of the hands, legs, soles of the feet, genital or anal. $Predominantly genital rash means that the number of skin lesions on the genitals represent > 50% of the total lesion count. §Monomorphic refers to skin lesions of the same size and appearance. ⱡComplex lesions refers to lesions that are confluent, greater than 2 cm along the largest diameter and/or necrotizing.

Abbreviations: ART = antiretroviral therapy, BMI = body mass index, bpm = beats per minute, brpm = breaths per minute, HIV = human immunodeficiency virus, IQR = interquartile range, MAP = mean arterial pressure, MPXV = monkeypox virus, MUAC = mid upper arm circumference, SD = standard deviation, WHO = world health organization

At inclusion, 20 (5%) mpox cases had a temperature above 38°C (Table 2). Active skin lesions were present in 394 (97%) patients. The median total lesion count at admission was 42 (IQR 17-94, range 1-1420). Most participants (n=314, 80%) had a combination of different lesion types, including vesicles (n=283, 72%), papules (n=209, 53%), small pustules (n=174, 44%), umbilicated pustules (n=150, 38%), ulcers (n=90, 23%) and macules (n=57, 15%). Children up to 14 years old, however, mostly presented with papules (n=59, 72%) and rarely with umbilicated pustules (n=11, 13%).

One third (n=137, 35%) of patients had generalized rash, defined as lesions on at least eight out of ten body regions (Table 2, Figure 1B). Less than half of patients had palmar (n=164, 41%) or plantar (n=99, 25%) lesions. Adults more often had genital skin lesions than children (89% vs 42%, p<0·001). (Figure 1B, Table 2) In adults, the genital area made up > 50% of total lesion count in 21% and was the only lesion localization in 9% (vs 2 and 1%, respectively, in children). Among adults, the genital area had the highest mean lesion density, while in children, lesions were concentrated mostly on the head and neck, abdomen, thorax, arms, and genital area (Figure 1C).

Complex lesions, defined as large (> 2cm in diameter), confluent or necrotic lesions were present in 93 (24%) mostly adult patients (n=90), of whom 89 (99%) reported these lesions in the genital region (Table 2). Mucosal lesions (n=324, 82%) were common across age groups, although genital mucosal lesions were more prevalent in adults compared to children (83% vs 36%, p<0·001). Lymphadenopathy differed significantly over age groups (p<0·001). While frequent in adults (n=257, 73%) and children aged 5-14 years (n=21, 75%), lymphadenopathy was uncommon in children under five years old (n=10, 19%). In adults, the inguinal nodes were primarily affected, while in children submandibular lymphadenopathy was more common.

Outcome And Complications During Hospitalization

Of the 407 MPXV-infected participants, only four (1%) refused hospitalization, and 17 (4%) discharged themselves against medical advice. Two infants died during hospitalization, giving an in-hospital mortality of 0·5% (95% CI 0·1%-1·7%). One infant developed a severe generalized rash with over 1000 lesions and extensive oral mucosal involvement, complicated by secondary bacterial infection, feeding difficulties, dehydration, and ultimately hemodynamic instability and shock. The other infant was moderately malnourished at baseline. Though she developed a severe generalized rash with maximum 392 lesions, there were no other complications, until she developed acute septic shock one week after admission.

Detailed hospital follow-up data were available for 296 (73%) patients. (Table 3) Among those, the median duration of hospitalization was seven (IQR 5-9) days. The total lesion count increased during hospitalization in 189 (64%) participants. The median maximum lesion count was 60 (IQR 25-138, range 1-1420) and occurred a median of 7 days (IQR 6-7) after the onset of lesions. According to the WHO disease severity score, 71 (24%) patients had mild (<25 lesions), 123 (42%) had moderate (25-99 lesions), 57 (19%) had severe (100-249 lesions) and 44 (15%) had grave disease. The median time from onset to resolution of lesions was 14 (95% CI 13-15) days, and of symptoms overall was 18 (95% CI 17-19) days. (Figure 1E and F)

Table 3. Complications at any timepoint during hospitalization for mpox treatment in Kamituga, DRC (2024) in relation to age categories.

Per age category (years)
All confirmed cases (n=296) 0-4 (n=36) 5-14 (n=16) ≥15 (n=244)
Duration of hospitalization – median (IQR) 7 (5-9) 6 (4-7) 5 (4-6) 7 (5-9)
Maximum lesion count – median (IQR) 60 (25 - 138) 56 (17 - 238) 90 (36 - 125) 60 (25 - 126)
WHO severity score – n (%) ·· ·· ·· ··
           Mild (< 25 lesions) 71/295 (24%) 10/35 (29%) 3/16 (19%) 58/244 (24%)
           Moderate (25-99 lesions) 123/295 (42%) 10/35 (29%) 6/16 (38%) 107/244 (44%)
           Severe (100-250 lesions) 57/295 (19%) 7/35 (20%) 7/16 (44%) 43/244 (18%)
           Grave (> 250 lesions) 44/295 (15%) 8/35 (23%) 0/16 (0%) 36/244 (15%)
Any Complications – n (%) 194/296 (66%) 9/36 (25%) 5/16 (31%) 180/244 (74%)
Cutaneous Complications – n (%) 121/296 (41%) 4/36 (11%) 5/16 (31%) 112/244 (46%)
           Superinfection – n (%) 55/296 (19%) 3/36 (8%) 2/16 (13%) 50/244 (21%)
           Abscess – n (%) 21/296 (7%) 1/36 (3%) 1/16 (6%) 19/244 (8%)
           Complex lesion! – n (%) 99/296 (33%) 2/36 (6%) 2/16 (13%) 95/244 (39%)
           Lymph node abscess– n (%) 6/296 (2%) 0/36 (0%) 0/16 (0%) 6/244 (3%)
Genito-urinary complications – n (%) 169/296 (57%) 1/36 (3%) 1/16 (6%) 167/244 (68%)
           Complex lesions‡ of genital mucosa
117/296 (40%) 0/36 (0%) 1/16 (6%) 116/244 (48%)
           Urinary retention 24/296 (8%) 1/36 (3%) 0/16 (0%) 23/244 (9%)
           Urethritis 119/296 (40%) 1/36 (3%) 0/16 (0%) 118/244 (48%)
           Genital edema 120/296 (41%) 1/36 (3%) 1/16 (6%) 118/244 (48%)
           Paraphimosis 2/296 (1%) 0/36 (0%) 0/16 (0%) 2/244 (1%)
           Proctitis 14/296 (5%) 0/36 (0%) 0/16 (0%) 14/244 (6%)
Cardio-pulmonary complications – n (%) 12/296 (4%) 7/36 (19%) 0/16 (0%) 5/244 (2%)
           Hemodynamic instability 3/296 (1%) 2/36 (6%) 0/16 (0%) 1/244 (0%)
           Dehydration 11/296 (4%) 7/36 (19%) 0/16 (0%) 4/244 (2%)
           Hypervolemia 0/296 (0%) 0/36 (0%) 0/16 (0%) 0/244 (0%)
           Respiratory distress 2/296 (1%) 2/36 (6%) 0/16 (0%) 0/244 (0%)
Neuro-ophthalmic complications – n (%) 9/296 (3%) 2/36 (6%) 0/16 (0%) 7/244 (3%)
           Meningitis or encephalitis 2/296 (1%) 2/36 (6%) 0/16 (0%) 0/244 (0%)
           Conjunctivitis or uveitis 8/296 (3%) 1/36 (3%) 0/16 (0%) 7/244 (3%)
           Vision loss or reduced 0/296 (0%) 0/36 (0%) 0/16 (0%) 0/244 (0%)
Metabolic# complications – n (%) 0/296 (0%) 0/36 (0%) 0/16 (0%) 0/244 (0%)
Open in a new tab

Data are median and IQR for numeric variables and n/N (%) for categorical variables. N signifies the number of individuals with available data. ⱡComplex lesions refers to lesions that are confluent, greater than 2 cm along the largest diameter and/or necrotizing. #Registered metabolic complications include hypoglycemia and icterus.

Overall, 194 (66%) of the 296 hospitalized patients experienced complications during observation, including genital oedema (n=120, 41%), urethritis (n=119, 40%, each), complex genital mucosal lesions (n=117, 40%), complex skin lesions (n=99, 33%), secondary bacterial infections (n=55, 19%) or abscess formation (n=21, 7%) (Table 3). Other complications were rare (< 10%).

There were no major differences in disease presentation and complications between male and female participants (Supplementary Tables 3, 4)

Persistent Symptoms At Follow-Up

In total, 208 cases (51%) returned for assessment on day 29 and 103 cases (25%) on day 59. (Table 4) A total of 78 (38%) participants experienced residual symptoms on day 29, and 38 (37%) on day 59. Skin-related symptoms were the most common, affecting 41 (19%) participants on day 29 and 15 (15%) on day 59. Eye symptoms were reported by 22 (11%) participants on day 29 and 18 (18%) on day 59. Five participants described reduced visual acuity on day 29 (2%) and day 59 (5%), and one person reported blindness on day 59 (1%). Other symptoms occurred in < 10% of participants on days 29 and 59. (Table 4)

Table 4. Clinical sequelae at day 29 and day 59 after mpox diagnosis in Kamituga, DRC (2024).

Day 29 (n =208) Day 59 (n = 103)
Deterioration of general health since mpox – n (%) 2/206 (1%) 0/102 (0%)
Medical care for ongoing health issues – n (%) 11/81 (14%) 3/38 (8%)
Persistent symptoms ·· ··
Any – n (%) 78/208 (38%) 38/103 (37%)
Constitutional – n (%) 20/208 (10%) 9/103 (9%)
           Fatigue 9/207 (4%) 4/103 (4%)
           Malaise 5/207 (2%) 0/103 (0%)
           Myalgia 6/207 (3%) 0/103 (0%)
           Headache 11/206 (5%) 5/100 (5%)
           Anorexia 2/208 (1%) 2/102 (2%)
Skin – n (%) 41/208 (19%) 15/102 (15%)
           Pain associated with lesions 5/208 (2%) 0/102 (0%)
           Itching 36/207 (17%) 15/101 (15%)
Psychiatric – n (%) 13/208 (6%) 6/103 (6%)
           Depression 0/207 (0%) 0/103 (0%)
           Anxiety 0/208 (0%) 0/103 (0%)
Respiratory – n (%) 1/208 (1%) 0/103 (0%)
           Cough 13/208 (6%) 6/102 (6%)
           Shortness of breath 9/208 (4%) 6/103 (6%)
Gastro-intestinal – n (%) 7/208 (3%) 6/103 (6%)
           Throat ache / dysphagia 2/208 (1%) 0/103 (0%)
           Abdominal pain 11/208 (5%) 2/103 (2%)
           Nausea / vomiting 5/208 (2%) 0/102 (0%)
           Diarrhea 5/206 (2%) 1/101 (1%)
           Rectal pain 2/208 (1%) 1/103 (1%)
           Pain on defecation 3/208 (1%) 0/103 (0%)
Genito-urinary – n (%) 15/208 (7%) 4/103 (4%)
           Dysuria 5/208 (2%) 0/103 (0%)
           Genital pain 3/172 (2%) 1/87 (1%)
           Dyspareunia 4/159 (3%) 2/86 (2%)
           Vaginal discharge 4/84 (5%) 2/41 (5%)
           Vaginal dryness 6/82 (7%) 4/41 (10%)
           Adhesions of the foreskin 1/107 (1%) 0/52 (0%)
           Painful erection 2/87 (2%) 0/45 (0%)
Eye – n (%) 22/207 (11%) 18/102 (18%)
           Eye pain 9/204 (4%) 4/101 (4%)
           Photophobia 14/203 (7%) 11/100 (11%)
           Itching 15/206 (7%) 12/102 (12%)
           Foreign body sensation 8/203 (4%) 9/99 (9%)
           Reduced visual acuity 5/206 (2%) 5/101 (5%)
           Blindness 0/207 (0%) 1/101 (1%)
Persistent lesions ·· ··
Active skin lesions – n (%) 5/206 (2%) 1/103 (1%)
Scars – n (%) 153/208 (74%) 51/103 (50%)
Mucosal lesions – n (%) 6/208 (3%) 1/103 (1%)
Eye – n (%) 9/208 (4%) 2/103 (2%)
           Eye lid edema 1/207 (1%) 1/102 (1%)
           Palpebral lesion 1/207 (1%) 1/102 (1%)
           Conjunctival lesion 1/207 (1%) 2/102 (2%)
           Conjunctivitis / uveitis 8/207 (4%) 2/102 (2%)
Open in a new tab

Data are n/N (%), with N representing the number of individuals with available data.

On day 29, 153 (74%) participants had scars, and five (2%) had unresolved ulcers. On day 59, only 51 (50%) still had discernible scars (Figure 1D, Supplementary Figure 3, 4), and one (1%) had an unresolved genital ulcer. Residual mucosal lesions were noted in six (3%) participants on day 29 and one participant (1%) on day 59. (Table 4)

Pregnancy Outcomes

Twenty-one infected women (11%) were pregnant at enrollment. During hospitalization, no pregnancy-related complications were reported, and no adverse pregnancy outcomes occurred. After discharge, the final pregnancy outcomes were recorded for six participants, of whom 4/6 (67%) experienced adverse outcomes. Two women suffered spontaneous abortions at 12 and 16 weeks of gestation. Obstetric history data were available for one of them, revealing one prior full-term vaginal delivery and no history of miscarriage. Additionally, two women showed evidence of vertical transmission of MPXV. One fetus died in utero at 24 weeks of gestation, requiring induction of labor. Mpox skin lesions were discernible on the head upon delivery. The other child was born full term via Caesarean section due to prolonged labor complicated by uterine rupture. This newborn also presented with characteristic mpox skin lesions, suffered from asphyxia, and died shortly after birth. The remaining two women delivered healthy full-term babies.

Discussion

This study provides a prospective, detailed characterization of patient profiles in the emerging Clade Ib outbreak in South Kivu. Reflecting the evolving transmission pattern of Clade Ib, mpox predominantly affected adolescents and young adults, though not exclusively. Exposure data indicate that sexual contact is a significant driver of transmission within this group, as corroborated by the prevalent genital presentations among adults. Most patients experience mild to moderate disease, with complications that are primarily genito-urinary in nature, and clinically significant sequelae other than scars are rare. Approximately one-fifth of cases, however, were children, who typically present with more extragenital disease.

The study was conducted in a remote area of Eastern DRC, where access to high-quality healthcare is limited. However, through collaboration with the health authorities, and humanitarian organizations, we enhanced the treatment facilities and care for mpox patients. This enabled the study to be conducted within an ethically sound framework and a suitable environment for high-quality data collection and participant retention.

Nevertheless, working in resource-limited settings comes with inherent limitations. Firstly, while the on-site diagnostic platform allowed for the detection of OPXV DNA, point-of-care Clade-specific confirmation was unavailable. Clade Ib was confirmed in Kinshasa in a subset of over 60% of samples, with the other samples still remaining in Kamituga. Five samples tested negative for Clade Ib, but also for Clade Ia, possibly because of sample degradation. Although not all samples could be confirmed, the results, combined with phylogenomic surveillance data2, strongly suggest that all patients are infected with Clade Ib. Secondly, recruitment relied on passive case detection, and despite low-threshold testing and free care, the PCR positivity rate remained consistently high throughout the study (around 80%). This suggests that a significant proportion of cases in the community may have gone undetected. If these undetected cases involve individuals with atypical presentations, very mild or asymptomatic infections, or severe illness (including community deaths), their absence from the study could bias the results. Thirdly, despite recall efforts, there was substantial loss to follow-up in the consecutive visits, which could impact the representativeness of the data regarding short- and intermediate-term disease outcomes, including sequelae. Finally, resource limitations restricted our ability to perform additional diagnostic testing, including for HIV, and other sexually transmitted infections (STI). Where applicable, patients were referred to the national HIV program for further testing. Further studies on MPXV and HIV co-infection are needed.

Despite these limitations, our findings allow for a comprehensive comparison between this Clade Ib outbreak and other mpox outbreaks. While Clade Ia outbreaks in endemic regions in the DRC are typically driven by zoonotic spillover,6 exposure to wild animals was rare in our cohort. In contrast, 59% of patients recalled contact with another case, of which 42% included sexual contact. Additionally, PCR-positive participants more often reported recent sexual activity, including multiple partnerships and consensual exchanges involving sexual services, compared to PCR-negative participants, suggesting sexual contact as a primary transmission driver. Although we did not collect information on the participants’ gender identity or the gender of their sexual partners due to cultural sensitivities, the balanced gender distribution among participants and the similar clinical presentation between male and female participants suggests that transmission predominantly occurred through heterosexual contact rather than male-to-male sexual contact, as seen during the Clade IIb outbreak.4 Notably, the observed transmission patterns may reflect the specific context in which the virus was introduced—namely, a high prevalence of multiple partnerships and of informal sex work—rather than virus-specific characteristics.

Similar to Clade IIb infections, focal urogenital symptoms and specific urogenital complications were prevalent in adults.1,4,20 Up to one-fifth presented with predominantly genital lesions, and over three-quarters exhibited involvement of the genital mucosa and/or inguinal lymphadenopathy. In contrast, most previous Clade Ia studies reported genital lesions in less than 30% of cases, typically showing a more generalized lesion distribution.7,8,21,22 These findings suggest that the mode of MPXV transmission might determine disease presentation. Interestingly, despite similarities in disease presentation between Clades Ib and IIb, Clade Ib infections in adults appear to be somewhat more severe, with higher total lesion counts and seemingly more frequent secondary bacterial infection, and urogenital and systemic complications.1 This may reflect differences in the affected populations or in virulence between clades.

Contrary to adults, children under 15 years exhibited a more typical clinical presentation featuring widespread lesions in a centrifugal distribution, though with a low frequency of lesions on the palms and soles compared to previous Clade Ia reports.7,8,22–24 Age-specific physiological differences and different transmission modes may explain the observed differences in clinical presentation across age groups.

Unlike Clade Ia outbreaks, where children typically make up three-quarters of cases,5,21,22 they constituted only a minority of cases in this study, being primarily infected within the household. Transmission to children was rarely reported during the global Clade IIb outbreak, although in a Nigerian cohort up to 16% were children under 18 years old.25 Moreover, in other health zones in South Kivu affected by the Clade Ib outbreak and parts of neighboring Burundi, children constitute the majority of mpox cases.2,26 Since our study was limited to a single health zone, caution is advised in generalizing these findings. Further studies on transmission dynamics, especially among children, are essential.

A final important point of comparison with previously documented mpox outbreaks are the outcomes and complications. Follow-up until day 59 revealed few severe sequelae other than scars among Clade Ib infected individuals, although one patient suffered from blindness.7,8 Of particular concern, though, are adverse pregnancy outcomes. In our study, four out of six women with recorded pregnancy outcomes lost their child, corroborating earlier findings of transplacental infections with Clade Ia MPXV.9,27,28 MPXV appears to be a teratogenic pathogen and larger studies on mpox during pregnancy are urgently needed to evaluate the extent of mpox-attributable risk for adverse outcomes.

In-hospital mortality in our cohort was low at 0·5%, with two deaths recorded in children under five. Age-specific vulnerabilities, such as susceptibility to feeding difficulties and dehydration, as well as immaturity of the immune system, may contribute to the higher mortality in this age group, but larger studies on risk factors for mortality are needed. The mortality rate is higher than the 0·2% observed during the global Clade IIb outbreak in 2022—though rates as high as 6% have been reported in Nigeria25 — but lower than the 1·4% to 17% reported for Clade Ia.7–10,29,30 Factors such as viral virulence, transmission mode, reporting bias, population age structure, underlying comorbidities, and healthcare access may all contribute to these observed differences in mortality.

This study provides a comprehensive overview of the Clade Ib outbreak in South Kivu, highlighting shifts in transmission dynamics, clinical presentation, and patient outcomes that differ from previous Clade I and II outbreaks. Future public health interventions – such as enhanced surveillance, integrated patient management, infection control policies, contact tracing and other targeted active case detection strategies – should reflect these evolving patterns of mpox presentation. Pending further research vaccination efforts should prioritize vulnerable populations, including pregnant women.

Supplementary Material

Supplementary material

Research in Context.

Evidence Before This Study

Many mainstream and social media sources have described the Clade Ib variant of monkeypox virus (MPXV) as “the most dangerous and deadly”. We searched PubMed from inception of the database to November 11, 2024, for case series or cohort studies using the terms (“monkeypox”, OR “mpox”, OR “monkeypox virus”) AND “clinical”. To find recent information about Clade Ib, we included an additional search in MedRxiv, and BioRxiv from January to November 11, 2024 with the terms (“monkeypox”, OR “mpox”).”

We identified 133 original research articles describing clinical features of at least 10 mpox cases. Most studies reported on the global Clade IIb mpox outbreak and primarily described adult men who were infected through sexual contact and presented with anogenital or oral lesions. According to aggregated WHO data up to October 31, 2024, overall case fatality rate of Clade IIb was 0·2%. Only eight studies examined Clade I(a) mpox, using retrospective or enhanced surveillance data and one publication described a prospective clinical cohort study. In these earlier studies, the majority of patients were children under 15 years old. For those studies that documented exposure, zoonotic spillover was presumed the main transmission mode. Approximately half of the patients presented with severe or grave disease based on the WHO severity score. Around one-third presented with genital lesions. Few studies have described outcomes of confirmed Clade I patients, with case fatality rates ranging from 1.4% to 10%.

Three early reports (one published, two on preprint servers) on the Clade Ib outbreak noted that most cases involved adults, with a majority involving possible infection through sexual contact, genital lesions and mild disease.

Added Value Of This Study

This prospective cohort study offers a detailed description of the demographic, clinical, and exposure characteristics of a large cohort Clade Ib mpox patients, during the 2024 South-Kivu outbreak. The report provides detailed longitudinal data of disease progression and outcome, including morbidity and mortality by age, adverse pregnancy outcomes, and post-discharge sequelae. Our findings indicate that during the early Clade Ib outbreak, adults were predominantly affected through sexual transmission and presented relatively mild and mainly genital disease. The minority of children affected, however, presented more extra-genital disease manifestations. Mortality was low, but all deaths involved children under five. Four out of six pregnant women with registered pregnancy outcomes lost their child. Post-discharge sequalae other than scars were uncommon.

Implications Of All The Available Evidence

The data from this study show differences and similarities between the Clade Ib, Clade Ia, and Clade IIb mpox outbreaks. Our findings are essential for understanding and responding to the current public health threat of Clade Ib MPXV. They give a balanced view of clinical presentations and outcome, nuancing earlier assumptions on disease severity. The observed differences in clinical presentation compared to previous Clade I outbreaks will enable updates to case definitions and management protocols. Although complications are rare, the potential risks to pregnancies underscore the importance of considering MPXV as a teratogenic agent. Evidence of transmission through sexual contact among adults enables tailored public health messaging. However, the observed household transmission raises concern for young children, who are at higher risk for severe disease and mortality.

Figure 2. Clinical images of skin and genital mpox lesions.

Figure 2

Open in a new tab

(A) Papular, umbilicated and ulcerated lesions on the hand. (B) Umbilicated lesions with high lesion density on the head and neck. (C) Infant with generalized lesion distribution. (D) Infant with umbilicated and confluent lesions in the face. (E) Genital mpox complicated with Fournier’s gangrene in an adult male. (F) Ulcerated and necrotic lesions on the penis and upper thigh in adult male. (G) Complex skin and genital mucosal lesion with labial edema, surrounded by papules and umbilicated genital skin lesions in adult female. (H) Complex genital skin lesion in adult female.

Acknowledgments

We thank all patients who agreed to be included in this cohort and particularly those who provided additional consent for publication of their deidentified images. We acknowledge the dedicated staff of KGH and ALIMA for their continuing expert patient care. We also acknowledge the support of the Health Zone and the Provincial Health Department to facilitate setting up of the study and the KGH for generously disposing the study team of necessary infrastructure to pursue study activities. Finally, we thank our colleagues Inge Van Cauwenberg, Lydia Lunda, Alliance Mbandu, and Plamedi Fatouma from ITM Kinshasa office administrative and logistical support. Finally, we wish to pay special tribute to Marie Stéphanie Smet, whose untimely passing during the course of this study was a profound loss to all of us.

Funding

This work was funded by the Belgian Directorate-General Development Cooperation and Humanitarian Aid and the European & Developing Countries Clinical Trials Partnership EDCTP3 (grant number 101195465). Additional support was provided by the Research Foundation – Flanders (FWO, grant number G096222N to EBo, LL, JJM and 12B1M24N to CVD) and through the African coaLition for Epidemic Research, Response and Training (ALERRT) network. ALERRT is part of the EDCTP2 Programme supported by the European Union under grant agreement RIA2016E-1612. ALERRT is also supported by the United Kingdom National Institute for Health Research. EBa, EDV, and IB are members of the Institute of Tropical Medicine’s Outbreak Research Team, financially supported by the Department of Economy, Science, and Innovation of the Flemish government (EWI).

Footnotes

Conflict of Interest Statement

LL has received institutional consultancy fees from BioNtech and institutional research funding from Sanofi; both not relevant for this work. JK has provided expert witness reports for the Treasury Board of Canada not relevant to this work. JK has also received mpox research funding from the Canadian Institutes of Health Research and the International Development Research Centre in open funding competitions. All other authors declare no conflict of interest.

Author Contributions

Conceptualized the study and wrote the protocol: IB, EHV, EDV, EB, YM, SSN, LL, PMK. Participant inclusion, investigation and data collection: GM, PM, JCT, LMM, FMK, JBM, DMM, JWZ, SBK. Conducted data analysis: IB, EHV, EDV, AT, CVD, SSN, LL. Data management: SH, YM. Secured funding: PKM, LL, JJMT, DM, EBM, PK, NL, AR, JA. Supervision study proceedings: LMM, FMK, CK, DM, SA, JJMT, SSn, LL, PMK. Supervised laboratory procedures: JCT, EKL, JCMC, TW, KV, DM, SA. Writing of the initial manuscript: IB, EHV, NL, SSN, LL, PMK. Reviewed the manuscript: IB, EHV, GM, PM, JCT, EDV, EB, YM, AT, CVD, AAO, LMM, FMK, JBM, DMM, JWZ, SBK, SH, NH, JCMC, EKL, MP, AWR, JK, NL, PK, EBM, JA, OT, DMK, RK, CK, DM, SA, KV, TW, JJMT, SSN, LL, PMK. Had full access to the data: IB, EHV, AT, SSN, LL, PMK. All authors contributed to review and approved the final version of the manuscript.

Declaration of Generative AI and AI-Assisted Technologies in the Writing Process

During the preparation of this work, the authors used ChatGPT-40 as an editing tool. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Data Sharing

De-identified participant data collected for the study will be made available from the corresponding author upon reasonable request (i.e., when ethically viable without violating the protection of participants or other valid ethical, privacy, or security concerns).

References

  • 1.Mitjà O, Ogoina D, Titanji BK, Galvan C, Muyembe JJ, Marks M, et al. Monkeypox. The Lancet. 2023 Jan 7;401(10370):60–74. doi: 10.1016/S0140-6736(22)02075-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.2022-24 Mpox (Monkeypox) Outbreak: Global Trends. [cited 2024 Sep 24]. [Internet] Available from: https://worldhealthorg.shinyapps.io/mpx_global/#43_Case_profile_(overall)
  • 3.Yinka-Ogunleye A, Aruna O, Dalhat M, Ogoina D, McCollum A, Disu Y, et al. Outbreak of human monkeypox in Nigeria in 2017–18: a clinical and epidemiological report. Lancet Infect Dis. 2019 Aug 1;19(8):872. doi: 10.1016/S1473-3099(19)30294-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Thornhill JP, Barkati S, Walmsley S, Rockstroh J, Antinori A, Harrison LB, et al. Monkeypox Virus Infection in Humans across 16 Countries - April-June 2022. N Engl J Med. 2022 Aug 25;387(8):679–91. doi: 10.1056/NEJMoa2207323. [DOI] [PubMed] [Google Scholar]
  • 5.Bangwen E, Diavita R, De Vos E, Hasivirwe Vakaniaki E, Nundu SS, Mutombo A, et al. Mpox in the Democratic Republic of Congo: Analysis of National Epidemiological and Laboratory Surveillance Data, 2010 - 2023. [cited 2024 Oct 23];2024 Available from: https://papers.ssrn.com/abstract=4954317. [Google Scholar]
  • 6.Kinganda-Lusamaki E, Amuri-Aziza A, Fernandez-Nuñez N, Makangara-Cigolo JC, Pratt C, Vakaniaki EH, et al. Clade I mpox virus genomic diversity in the Democratic Republic of the Congo, 2018–2024: Predominance of zoonotic transmission. Cell. 2024 Oct; doi: 10.1016/j.cell.2024.10.017. 0(0) [DOI] [PubMed] [Google Scholar]
  • 7.Ježek Z, Szczeniowski M, Paluku KM, Mutombo M. Human Monkeypox: Clinical Features of 282 Patients. J Infect Dis. 1987 Aug 1;156(2):293–8. doi: 10.1093/infdis/156.2.293. [DOI] [PubMed] [Google Scholar]
  • 8.Jezek Z, Grab B, Szczeniowski M, Paluku KM, Mutombo M. Clinico-epidemiological features of monkeypox patients with an animal or human source of infection. Bull World Health Organ. 1988;66(4):459. [PMC free article] [PubMed] [Google Scholar]
  • 9.Pittman PR, Martin JW, Kingebeni PM, Tamfum JJM, Mwema G, Wan Q, et al. Clinical characterization and placental pathology of mpox infection in hospitalized patients in the Democratic Republic of the Congo. PLoS Negl Trop Dis. 2023 Apr 1;17(4) doi: 10.1371/journal.pntd.0010384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Vakaniaki EH, Kacita C, Kinganda-Lusamaki E, O’Toole Á, Wawina-Bokalanga T, Mukadi-Bamuleka D, et al. Sustained human outbreak of a new MPXV clade I lineage in eastern Democratic Republic of the Congo. Nat Med. 2024 doi: 10.1038/s41591-024-03130-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Masirika LM, Udahemuka JC, Schuele L, Ndishimye P, Otani S, Mbiribindi JB, et al. 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. Eurosurveillance. 2024 Mar 14;29(11) doi: 10.2807/1560-7917.ES.2024.29.11.2400106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Nextstrain / groups / inrb-mpox / clade-I. [cited 2024 Nov 7]. [Internet] Available from: https://nextstrain.org/groups/inrb-mpox/clade-I?c=date_submitted&f_clade_membership=clade%20Ib&f_division=Sud%20Kivu.
  • 13.Murhula Masirika L, Claude Udahemuka J, Schuele L, Nieuwenhuijse DF, Ndishimye P, Boter M, et al. Mapping and sequencing of cases from an ongoing outbreak of Clade Ib monkeypox virus in South Kivu, Eastern Democratic Republic of the Congo between September 2023 to June 2024. medRxiv. 2024 Sep 19;:2024.09.18.24313835 [Google Scholar]
  • 14.WHO Director-General declares mpox outbreak a public health emergency of international concern. [cited 2024 Sep 24]. [Internet] Available from: https://www.who.int/news/item/14-08-2024-who-director-general-declares-mpox-outbreak-a-public-health-emergency-of-international-concern. [PMC free article] [PubMed]
  • 15.Ministère de la santé publique hygiène et prévention P du SKDP de la santé. Pyramide sanitaire des zones de sante 2024. 2024 [Google Scholar]
  • 16.Clinical management and infection prevention and control for monkeypox: Interim rapid response guidance, 10 June 2022. [cited 2024 Nov 12]. [Internet] Available from: https://www.who.int/publications/i/item/WHO-MPX-Clinical-and-IPC-2022.1.
  • 17.Damhorst GL, McLendon K, Morales E, Solis ZM, Fitts E, Bowers HB, et al. Performance of the Xpert™ Mpox PCR assay with oropharyngeal, anorectal, and cutaneous lesion swab specimens. J Clin Virol. 2024 Apr 1;171 doi: 10.1016/j.jcv.2024.105659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Schuele L, Masirika LM, Udahemuka JC, Siangoli FB, Mbiribindi JB, Ndishimye P, et al. Real-time PCR assay to detect the novel Clade Ib monkeypox virus, September 2023 to May 2024. [cited 2024 Nov 18];Euro Surveill. 2024 Aug 8;29(32) doi: 10.2807/1560-7917.ES.2024.29.32.2400486. [Internet] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Li Y, Zhao H, Wilkins K, Hughes C, Damon IK. Real-time PCR assays for the specific detection of monkeypox virus West African and Congo Basin strain DNA. [cited 2024 Nov 19];J Virol Methods. 2010 Oct;169(1):223–7. doi: 10.1016/j.jviromet.2010.07.012. [Internet] [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Català A, Clavo-Escribano P, Riera-Monroig J, Martín-Ezquerra G, Fernandez-Gonzalez P, Revelles-Peñas L, et al. Monkeypox outbreak in Spain: clinical and epidemiological findings in a prospective cross‐sectional study of 185 cases. British Journal of Dermatology. 2022 Nov 1;187(5):765–72. doi: 10.1111/bjd.21790. [DOI] [PubMed] [Google Scholar]
  • 21.Whitehouse ER, Bonwitt J, Hughes CM, Lushima RS, Likafi T, Nguete B, et al. Clinical and Epidemiological Findings from Enhanced Monkeypox Surveillance in Tshuapa Province, Democratic Republic of the Congo During 2011–2015. J Infect Dis. 2021 Jun 4;223(11):1870–8. doi: 10.1093/infdis/jiab133. [DOI] [PubMed] [Google Scholar]
  • 22.Osadebe L, Hughes CM, Shongo Lushima R, Kabamba J, Nguete B, Malekani J, et al. Enhancing case definitions for surveillance of human monkeypox in the Democratic Republic of Congo. PLoS Negl Trop Dis. 2017 Sep 11;11(9) doi: 10.1371/journal.pntd.0005857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Hoff NA, Morier DS, Kisalu NK, Johnston SC, Doshi RH, Hensley LE, et al. Varicella Coinfection in Patients with Active Monkeypox in the Democratic Republic of the Congo. Ecohealth. 2017 Sep 1;14(3):564–74. doi: 10.1007/s10393-017-1266-5. [DOI] [PubMed] [Google Scholar]
  • 24.Hughes CM, Liu L, Davidson WB, Radford KW, Wilkins K, Monroe B, et al. A tale of two viruses: Coinfections of monkeypox and varicella zoster virus in the democratic republic of congo. American Journal of Tropical Medicine and Hygiene. 2021 Feb 1;104(2):604–11. doi: 10.4269/ajtmh.20-0589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Ogoina D, Dalhat MM, Denue BA, Okowa M, Chika-Igwenyi NM, Yusuff HA, et al. Clinical characteristics and predictors of human mpox outcome during the 2022 outbreak in Nigeria: a cohort study. Lancet Infect Dis. 2023 Dec 1;23(12):1418–28. doi: 10.1016/S1473-3099(23)00427-9. [DOI] [PubMed] [Google Scholar]
  • 26.Nizigiyimana A, Ndikumwenayo F, Houben S, Manirakiza M, van Lettow M, Liesenborghs L, et al. Epidemiological analysis of confirmed mpox cases, Burundi, 3 July to 9 September 2024. Euro Surveill. 2024 Oct 17;29(42) doi: 10.2807/1560-7917.ES.2024.29.42.2400647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Mbala PK, Huggins JW, Riu-Rovira T, Ahuka SM, Mulembakani P, Rimoin AW, et al. Maternal and Fetal Outcomes among Pregnant Women with Human Monkeypox Infection in the Democratic Republic of Congo. Journal of Infectious Diseases. 2017 Nov 1;216(7):824–8. doi: 10.1093/infdis/jix260. [DOI] [PubMed] [Google Scholar]
  • 28.Sanchez Clemente N, Coles C, Paixao ES, Brickley EB, Whittaker E, Alfven T, et al. Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis. Lancet Glob Health. 2024 Apr 1;12(4):e572–88. doi: 10.1016/S2214-109X(23)00607-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Breman JG, Steniowski MV, Zanotto E, Gromyko AI, Arita I. Human monkeypox, 1970-79. Bull World Health Organ. 1980;58(2):165. [PMC free article] [PubMed] [Google Scholar]
  • 30.Hutin YJF, Williams RJ, Malfait P, Pebody R, Loparev VN, Ropp SL, et al. Outbreak of Human Monkeypox, Democratic Republic of Congo, 1996 to 1997. Emerg Infect Dis. 2001 Jun;7(3):434–8. doi: 10.3201/eid0703.010311. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary material
EMS209568-supplement-Supplementary_material.pdf (1.1MB, pdf)

Data Availability Statement

De-identified participant data collected for the study will be made available from the corresponding author upon reasonable request (i.e., when ethically viable without violating the protection of participants or other valid ethical, privacy, or security concerns).

RESOURCES