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Background: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence., Methods: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques., Findings: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2., Interpretation: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence., Funding: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, French National Research Institute for Development, and WHO., Competing Interests: Declaration of interests We declare no competing interests., (Published by Elsevier Ltd.)

Background: Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined., Methods: This retrospective study included patients admitted to 2 EVD treatment units over an 8-month period in 2019 during an EVD epidemic in the Democratic Republic of the Congo., Results: An overall 333 patients (median age, 30 years; 58% female) had at least 1 creatine kinase (CK) measurement (n = 2229; median, 5/patient [IQR, 1-11]). Among patients, 271 (81%) had an elevated CK level (>380 U/L); 202 (61%) had rhabdomyolysis (CK >1000 IU/L); and 45 (14%) had severe rhabdomyolysis (≥5000 U/L). Among survivors, the maximum CK level was a median 1600 (IQR, 550-3400), peaking 3.4 days after admission (IQR, 2.3-5.5) and decreasing thereafter. Among fatal cases, the CK rose monotonically until death, with a median maximum CK level of 2900 U/L (IQR, 1500-4900). Rhabdomyolysis at admission was an independent predictor of acute kidney injury (adjusted odds ratio, 2.2 [95% CI, 1.2-3.8]; P = .0065) and mortality (adjusted hazard ratio, 1.7 [95% CI, 1.03-2.9]; P = .037)., Conclusions: Rhabdomyolysis is associated with acute kidney injury and mortality in patients with EVD. These findings may inform clinical practice by identifying laboratory monitoring priorities and highlighting the importance of fluid management., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Ebola virus disease (EVD) is associated with multisystem organ failure and high mortality. Severe hypoglycaemia is common, life-threatening, and correctable in critically ill patients, but glucose monitoring may be limited in EVD treatment units., Methods: We conducted a retrospective review of patients admitted to EVD treatment units in Butembo and Katwa, Eastern DRC. Glucose measurements were done using a handheld glucometer at the bedside or using the Piccolo xpress Chemistry Analyzer on venous samples., Findings: 384 patients (median age 30 years (interquartile range, IQR, 20-45), 57% female) and 6422 glucose measurements (median 11 per patient, IQR 4-22) were included in the analysis. Severe hypoglycaemia (≤2.2 mmol/L) and hyperglycaemia (>10 mmol/L) were recorded at least once during the ETU admission in 97 (25%) and 225 (59%) patients, respectively. A total of 2004 infusions of glucose-containing intravenous solutions were administered to 302 patients (79%) with a median cumulative dose of 175g (IQR 100-411). The overall case fatality rate was 157/384 (41%) and was 2.2-fold higher (95% CI 1.3-3.8) in patients with severe hypoglycaemia than those without hypoglycaemia (p = 0.0042). In a multivariable Cox proportional hazards model, periods of severe hypoglycaemia (adjusted hazard ratio (aHR) 6.2, 95% CI 3.2-12, p < 0.0001) and moderate hypoglycaemia (aHR 3.0, 95% CI 1.9-4.8, p < 0.0001) were associated with elevated mortality., Interpretation: Hypoglycaemia is common in EVD, requires repeated correction with intravenous dextrose solutions, and is associated with mortality., Funding: This study was not supported by any specific funding., Competing Interests: Declaration of interests SM is employed by Ridgeback Biotherapeutics, and is listed as inventor on the patent application for mAb 114, US Application No.62/087, 087 (PCT Application No. PCT/US2015/060,733) related to anti-Ebola virus antibodies and their use. SM receives royalties paid by the NIH Office of Financial Management (OFM)., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

During the 2018-2020 Ebola virus disease (EVD) outbreak, residents in Goma, Democratic Republic of the Congo, were offered a two-dose prophylactic EVD vaccine. This was the first study to evaluate the safety of this vaccine in pregnant women. Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. In total, 20,408 participants, including 6635 (32.5%) children, received dose 1. Fewer than 1% of non-pregnant participants experienced a serious adverse event (SAE) following dose 1; one SAE was possibly related to the Ad26.ZEBOV vaccine. Of the 1221 pregnant women, 371 (30.4%) experienced an SAE, with caesarean section being the most common event. No SAEs in pregnant women were considered related to vaccination. Of 1169 pregnancies with a known outcome, 55 (4.7%) ended in a miscarriage, and 30 (2.6%) in a stillbirth. Eleven (1.0%) live births ended in early neonatal death, and five (0.4%) had a congenital abnormality. Overall, 188/891 (21.1%) were preterm births and 79/1032 (7.6%) had low birth weight. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group.

During the 2018-2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval.

Competing Interests: JBN is supported by the US National Institutes of Health (grant numbers NIH/FIC 1R25TW011217-01, NIH/FIC 1D43TW010937-01A1, NIH/FIC D43TW011827-01A1, NIH/FIC 1R21TW011706-0, and NIH/NIAID 5U01AI096299-13). FN and AZ are codirectors of the Pan-African Network on Emerging and Re-Emerging Infections funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) within the EU Horizon 2020 Framework Programme. FN and AZ also acknowledge support from the EDCTP Central Africa Clinical Research Network. AZ is a UK National Institute for Health Research senior investigator, and a Mahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize laureate. JJM-T holds National Institutes of Health National Institute of Allergy and Infectious Diseases grants (number 75N91019D00024-P00001-759102000025-5). JK is supported by grant funding from the Canadian Institutes of Health Research and International Development Research Centre (grant numbers MRR-184813 and PPE-185821). ELM is supported by the US National Institutes of Health (grant number 1R01AI182082-01). All other authors declare no competing interests. We thank John L Johnson for critical review and helpful advice. The views and conclusions in this Personal View are those of the authors and do not necessarily represent the views of their institutions.

Background: Several governments from African countries, including the Democratic Republic of the Congo (DRC), implemented stringent public health measures to curb COVID-19 transmission in the early phases of the pandemic. While these restrictive measures are believed to have contributed to lowering case incidence and related mortality in DRC, data on the population's knowledge and adherence are limited. This study aimed to assess the knowledge, perception, attitudes, and practices of COVID-19 preventive measures and associated factors among adult residents of Matadi, thereby generating evidence for a strategy adjustment as the COVID-19 response is transitioning from emergency to control status., Methods: We used data from a population-based cross-sectional study conducted in October 2021. Consenting participants were enrolled through a multi-stage cluster sampling approach and administered a pre-tested structured questionnaire using a mobile application (Epicollect 5). We analyzed adult participants' data using STATA 15.1. Univariable and multivariable analyses were applied to identify factors associated with good knowledge, good perception, positive attitude and good practice., Results: We included 1,269 adult respondents for the secondary analysis. One respondent in six was female. The median age was 36 years (IQR 24-50). Most respondents (76.5%) had good knowledge. Respondents aged 40-49 years and those with vocational education level were 1.7 time (AOR 1.75, 95% CI 1.07-2.87) and twice as likely (AOR 2.06, 95% CI 1.01-4.21) to have good knowledge. Preventive measures were perceived as efficient by 45% of respondents. Good perception was associated with education level, profession, average household monthly income and good knowledge. Only 40% of respondents had a positive attitude. A positive attitude was associated with age, education level, and good knowledge. Respondents having good practice represented 5.8%. Good practice was associated with good knowledge, attitude and perception., Conclusion: Most respondents were knowledgeable, had a good perception of government-related COVID-19 preventive measures, a moderately positive attitude and an extremely low level of good practice. Current COVID-19 preventive strategies, including vaccination rollout, need adjustment into high-efficiency, context-based and risk group-specific interventions. Evidence generated by this study will improve preparedness and response to future outbreaks., Competing Interests: The authors declare no conflict of interest. Authors affiliated with the funding agency facilitated the funding process and the provision of study material. They were involved in the study design, data collection, and interpretation under the leadership of an independent principal investigator from the Democratic Republic of the Congo Ministry of Health., (Copyright © 2024 Munyeku-Bazitama, Okitale-Talunda, Nsio-Mbeta, Mpingabo-Ilunga, Tshiminyi-Munkamba, Umba-Phuati, Kimfuta, Ango-Phukuta, Makindu, Mufwaya-Nsene, Asari, Makimoto, Ahuka-Mundeke, Isono, Makiala-Mandanda and Muyembe-Tamfum.)

Outbreaks of monkeypox (mpox) have historically resulted from zoonotic spillover of clade I monkeypox virus (MPXV) in Central Africa and clade II MPXV in West Africa. In 2022, subclade IIb caused a global epidemic linked to transmission through sexual contact. Here we describe the epidemiological and genomic features of an mpox outbreak in a mining region in eastern Democratic Republic of the Congo, caused by clade I MPXV. Surveillance data collected between September 2023 and January 2024 identified 241 suspected cases. Genomic analysis demonstrates a distinct clade I lineage divergent from previously circulating strains in the Democratic Republic of the Congo. Of the 108 polymerase chain reaction-confirmed mpox cases, the median age of individuals was 22 years, 51.9% were female and 29% were sex workers, suggesting a potential role for sexual transmission. The predominance of APOBEC3-type mutations and the estimated emergence time around mid-September 2023 imply recent sustained human-to-human transmission., (© 2024. The Author(s).)

Background: Bas-Congo virus (BASV), an emerging tibrovirus, was associated with an outbreak of acute haemorrhagic fever in Mangala, Democratic Republic of the Congo, in 2009. In 2012, neutralising antibodies to BASV were detected in the lone survivor and one of his close contacts. However, subsequent serological and molecular surveys were unsuccessful as neither BASV antibodies nor its RNA were detected. In this study, we determined the seroprevalence of BASV infection in Mangala 13 years after the initial outbreak., Methods: We conducted a population-based serological survey from Jan 17 to Jan 23, 2022. Consenting individuals at least 5 years of age, living in Mangala for at least 4 weeks, and who had no contraindication to venepuncture were enrolled. Participants were interviewed using a pre-tested questionnaire for sociodemographic and clinical characteristics. We supplemented the collected serum samples with 284 archived samples from Matadi and Kinshasa. All samples were tested for antibodies to BASV and other tibroviruses using a pseudovirus-based neutralisation test., Findings: Among the 267 individuals from Mangala, the prevalence of BASV antibodies was 55% (95% CI 49-61; n=147). BASV seropositivity odds significantly increased with age (5·2 [95% CI 2·1-12·9] to 83·9 [20·8-337·7] times higher in participants aged 20 years or older than participants aged 5-19 years). Some occupational categories (eg, farmer or public servant) were associated with seropositivity. Only nine (6%) of 160 samples from Matadi and one (<1%) of 124 samples from Kinshasa had neutralising antibodies to BASV. Moreover, we also detected neutralising antibodies to other tibroviruses-Ekpoma virus 1, Ekpoma virus 2, and Mundri virus-in 84 (31%), 251 (94%), and 219 (82%) of 267 Mangala samples; 14 (9%), 62 (39%), and 120 (75%) of 160 Matadi samples; and six (5%), five (4%), and 33 (27%) of 124 Kinshasa samples, respectively., Interpretation: Human infection with BASV and other tibroviruses seems common in Mangala, although no deadly outbreak has been reported since 2009. Exposure to BASV might be highly restricted to Mangala and the increasing prevalence of neutralising antibodies with age suggests regular contact with the virus in this city. Altogether, our findings suggest that human infection with tibroviruses could be common in the study areas and not associated with deadly haemorrhagic or debilitating syndromes., Funding: Japan Agency for Medical Research and Development (AMED) and Japan International Cooperation Agency (JICA) under the Science and Technology Research Partnership for Sustainable Development (SATREPS) and Japan Program for Infectious Diseases Research and Infrastructure from AMED., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Serological surveys offer the most direct measurement to define the immunity status for numerous infectious diseases, such as COVID-19, and can provide valuable insights into understanding transmission patterns. This study describes seroprevalence changes over time in the context of the Democratic Republic of Congo, where COVID-19 case presentation was apparently largely oligo- or asymptomatic, and vaccination coverage remained extremely low., Methods: A cohort of 635 health care workers (HCW) from 5 health zones of Kinshasa and 670 of their household members was interviewed and sampled in 6 rounds between July 2020 and January 2022. At each round, information on risk exposure and a blood sample were collected. Serology was defined as positive when binding antibodies against SARS-CoV-2 spike and nucleocapsid proteins were simultaneously present., Results: The SARS-CoV-2 antibody seroprevalence was high at baseline, 17.3% (95% CI 14.4-20.6) and 7.8% (95% CI 5.5-10.8) for HCW and household members, respectively, and fluctuated over time, between 9% and 62.1%. Seropositivity was heterogeneously distributed over the health zones (p < 0.001), ranging from 12.5% (95% CI 6.6-20.8) in N'djili to 33.7% (95% CI 24.6-43.8) in Bandalungwa at baseline for HCW. Seropositivity was associated with increasing rounds adjusted Odds Ratio (aOR) 1.75 (95% CI 1.66-1.85), with increasing age aOR 1.11 (95% CI 1.02-1.20), being a female aOR 1.35 (95% CI 1.10-1.66) and being a HCW aOR 2.38 (95% CI 1.80-3.14). There was no evidence that HCW brought the COVID-19 infection back home, with an aOR of 0.64 (95% CI 0.46-0.91) of seropositivity risk among household members in subsequent surveys. There was seroreversion and seroconversion over time, and HCW had a lower risk of seroreverting than household members (aOR 0.60 (95% CI 0.42-0.86))., Conclusion: SARS-CoV-2 IgG antibody levels were high and dynamic over time in this African setting with low clinical case rates. The absence of association with health profession or general risk behaviors and with HCW positivity in subsequent rounds in HH members, shows the importance of the time-dependent, and not work-related, force of infection. Cohort seroprevalence estimates in a 'new disease' epidemic seem insufficient to guide policy makers for defining control strategies., (© 2024. The Author(s).)

Background: In 2016, outbreaks of yellow fever in Angola and the Democratic Republic of the Congo led to a global vaccine shortage. A fractional dose of 17DD yellow fever vaccine (containing one-fifth [0·1 ml] of the standard dose) was used during a pre-emptive mass campaign in August, 2016, in Kinshasa, Democratic Republic of the Congo among children aged 2 years and older and non-pregnant adults (ie, those aged 18 years and older). 1 year following vaccination, 97% of participants were seropositive; however, the long-term durability of the immune response is unknown. We aimed to conduct a prospective cohort study and invited participants enrolled in the previous evaluation to return 5 years after vaccination to assess durability of the immune response., Methods: Participants returned to one of six health facilities in Kinshasa in 2021, where study staff collected a brief medical history and blood specimen. We assessed neutralising antibody titres against yellow fever virus using a plaque reduction neutralisation test with a 50% cutoff (PRNT 50 ). Participants with a PRNT 50 titre of 10 or higher were considered seropositive. The primary outcome was the proportion of participants seropositive at 5 years., Findings: Among the 764 participants enrolled, 566 (74%) completed the 5-year visit. 5 years after vaccination, 539 (95·2%, 95% CI 93·2-96·7) participants were seropositive, including 361 (94·3%, 91·5-96·2) of 383 who were seronegative and 178 (97·3%, 93·8-98·8) of 183 who were seropositive at baseline. Geometric mean titres (GMTs) differed significantly across age groups for those who were initially seronegative with the lowest GMT among those aged 2-5 years and highest among those aged 13 years and older., Interpretation: A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the Democratic Republic of the Congo. These findings support the use of fractional-dose vaccination for outbreak prevention with the potential for sustained immunity., Funding: Gavi, the Vaccine Alliance through the CDC Foundation., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.

Background: Although mpox has been detected in paediatric populations in central and west Africa for decades, evidence synthesis on paediatric, maternal, and congenital mpox, and the use of vaccines and therapeutics in these groups, is lacking. A systematic review is therefore indicated to set the research agenda., Methods: We conducted a systematic review and meta-analysis, searching articles in Embase, Global Health, MEDLINE, CINAHL, Web of Science, Scopus, SciELO, and WHO databases from inception to April 17, 2023. We included studies reporting primary data on at least one case of confirmed, suspected, or probable paediatric, maternal, or congenital mpox in humans or the use of third-generation smallpox or mpox vaccines, targeted antivirals, or immune therapies in at least one case in our population of interest. We included clinical trials and observational studies in humans and excluded reviews, commentaries, and grey literature. A pooled estimate of the paediatric case fatality ratio was obtained using random-effects meta-analysis. This study is registered with PROSPERO (CRD420223336648)., Findings: Of the 61 studies, 53 reported paediatric outcomes (n=2123 cases), seven reported maternal or congenital outcomes (n=32 cases), two reported vaccine safety (n=28 recipients), and three reported transmission during breastfeeding (n=4 cases). While a subset of seven observational studies (21 children and 12 pregnant individuals) reported uneventful treatment with tecovirimat, there were no randomised trials reporting safety or efficacy for any therapeutic agent. Among children, the commonest clinical features included rash (86 [100%] of 86), fever (63 [73%] of 86), and lymphadenopathy (40 [47%] of 86). Among pregnant individuals, rash was reported in 23 (100%) of 23; fever and lymphadenopathy were less common (six [26%] and three [13%] of 23, respectively). Most paediatric complications (12 [60%] of 20) arose from secondary bacterial infections. The pooled paediatric case fatality ratio was 11% (95% CI 4-20), I 2 =75%. Data from 12 pregnancies showed half resulted in fetal death. Research on vaccine and immune globulin safety remains scarce for children and absent for pregnant individuals., Interpretation: Our review highlights critical knowledge gaps in the epidemiology, prevention, and treatment of mpox in children and pregnant individuals, especially those residing in endemic countries. Increased funding, international collaboration, and equitable research is needed to inform mpox control strategies tailored for at-risk communities in endemic countries., Funding: None., Translations: For the French, Spanish and Portuguese translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SBD has received honoraria from MSD and Sanofi for taking part in respiratory syncytial virus (RSV) advisory boards and has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD, and Sanofi with fees paid to St George's, University of London. SBD is a member of the UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) RSV subcommittee and Medicines and Healthcare products Regulatory Agency's (MHRA) Paediatric Medicine Expert Advisory Group (PMEAG), but the reviews expressed herein do not necessarily represent those of DHSC, JCVI, MHRA, or PMEAG. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The use of specific anti-Ebola virus therapy, especially monoclonal antibodies, has improved survival in patients with Ebola virus disease. We aimed to assess the effect of monoclonal antibodies on anti-Ebola virus antibody responses in survivors of the 2018-20 Ebola outbreak in the Democratic Republic of the Congo., Methods: In this observational prospective cohort study, participants were enrolled at three Ebola survivor clinics in Beni, Mangina, and Butembo (Democratic Republic of the Congo). Eligible children and adults notified as survivors of Ebola virus disease (ie, who had confirmed Ebola virus disease [RT-PCR positive in blood sample] and were subsequently declared recovered from the virus [RT-PCR negative in blood sample] with a certificate of recovery from Ebola virus disease issued by an Ebola treatment centre) during the 2018-20 Ebola virus disease outbreak were invited to participate in the study. Participants were recruited on discharge from Ebola treatment centres and followed up for 12-18 months depending on recruitment date. Routine follow-up assessments were done at 1, 3, 6, and 12-18 months after inclusion. We collected sociodemographic (age, sex, visit site), clinical (anti-Ebola virus drugs), and laboratory data (RT-PCR and Ct values). The primary outcome was the antibody concentrations against Ebola virus glycoprotein, nucleoprotein, and 40-kDa viral protein antigens over time assessed in all participants. Antibody concentrations were measured by the multiplex immunoassay, and the association between anti-Ebola virus antibody levels and the relevant exposures, such as anti-Ebola virus disease drugs (ansuvimab, REGN-EB3, ZMapp, or remdesivir), was assessed using both linear and logistic mixed regression models. This study is registered at ClinicalTrials.gov, NCT04409405., Findings: Between April 16, 2020, and Oct 18, 2021, 1168 survivors were invited to participate in the Les Vainqueurs d'Ebola cohort study. 787 survivors were included in the study, of whom 358 had data available for antibody responses. 85 (24%) of 358 were seronegative for at least two Ebola virus antigens on discharge from the Ebola treatment centre. The antibody response over time fluctuated but a continuous decrease in an overall linear evolution was observed. Quantitative modelling showed a decrease in nucleoprotein, glycoprotein, and VP-40 antibody concentrations over time (p<0·0001) with the fastest decrease observed for glycoprotein. The probability of being seropositive for at least two antigens after 36 months was 53·6% (95% CI 51·6-55·6) for participants who received ansuvimab, 73·5% (71·5-75·5) for participants who received REGN-EB3, 76·8% (74·8-78·8) for participants who received remdesivir, and 78·5% (76·5-80·5) for participants who received ZMapp., Interpretation: Almost a quarter of survivors were seronegative on discharge from the Ebola treatment centre and antibody concentrations decreased rapidly over time. These results indicate that monoclonal antibodies might negatively affect the production of anti-Ebola virus antibodies in survivors of Ebola virus disease which could increase the risk of reinfection or reactivation., Funding: The French National Agency for AIDS Research-Emergent Infectious Diseases-The French National Institute of Health and Medical Research, the French National Research Institute for Development, and the European and Developing Countries Clinical Trials Partnership., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks. This cross-sectional population-based survey provides an update to previous poliovirus-neutralizing antibody seroprevalence studies in the DRC and quantifies risk factors for under-immunization and parental knowledge that guide vaccine decision making. Among the 964 children between 6 and 35 months in our survey, 43.8% (95% CI: 40.6-47.0%), 41.1% (38.0-44.2%), and 38.0% (34.9-41.0%) had protective neutralizing titers to polio types 1, 2, and 3, respectively. We found that 60.7% of parents reported knowing about polio, yet 25.6% reported knowing how it spreads. Our data supported the conclusion that polio outreach efforts were successfully connecting with communities-79.4% of participants had someone come to their home with information about polio, and 88.5% had heard of a polio vaccination campaign. Additionally, the odds of seroreactivity to only serotype 2 were far greater in health zones that had a history of supplementary immunization activities (SIAs) compared to health zones that did not. While SIAs may be reaching under-vaccinated communities as a whole, these results are a continuation of the downward trend of seroprevalence rates in this region.

Incidence of human monkeypox (mpox) has been increasing in West and Central Africa, including in the Democratic Republic of Congo (DRC), where monkeypox virus (MPXV) is endemic. Most estimates of the pathogen's transmissibility in the DRC are based on data from the 1980s. Amid the global 2022 mpox outbreak, new estimates are needed to characterize the virus' epidemic potential and inform outbreak control strategies. We used the R package vimes to identify clusters of laboratory-confirmed mpox cases in Tshuapa Province, DRC. Cases with both temporal and spatial data were assigned to clusters based on the disease's serial interval and spatial kernel. We used the size of the clusters to infer the effective reproduction number, Rt, and the rate of zoonotic spillover of MPXV into the human population. Out of 1,463 confirmed mpox cases reported in Tshuapa Province between 2013 and 2017, 878 had both date of symptom onset and a location with geographic coordinates. Results include an estimated Rt of 0.82 (95% CI: 0.79-0.85) and a rate of 132 (95% CI: 122-143) spillovers per year assuming a reporting rate of 25%. This estimate of Rt is larger than most previous estimates. One potential explanation for this result is that Rt could have increased in the DRC over time owing to declining population-level immunity conferred by smallpox vaccination, which was discontinued around 1982. Rt could be overestimated if our assumption of one spillover event per cluster does not hold. Our results are consistent with increased transmissibility of MPXV in Tshuapa Province.

Background: The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak., Methods: We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak., Findings: Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD., Interpretation: Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks., Funding: WHO and US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests We declare no competing interests., (Published by Elsevier Ltd.)

Fine-scale knowledge of the changes in composition and function of the human gut microbiome compared that of our closest relatives is critical for understanding the evolutionary processes underlying its developmental trajectory. To infer taxonomic and functional changes in the gut microbiome across hominids at different timescales, we perform high-resolution metagenomic-based analyzes of the fecal microbiome from over two hundred samples including diverse human populations, as well as wild-living chimpanzees, bonobos, and gorillas. We find human-associated taxa depleted within non-human apes and patterns of host-specific gut microbiota, suggesting the widespread acquisition of novel microbial clades along the evolutionary divergence of hosts. In contrast, we reveal multiple lines of evidence for a pervasive loss of diversity in human populations in correlation with a high Human Development Index, including evolutionarily conserved clades. Similarly, patterns of co-phylogeny between microbes and hosts are found to be disrupted in humans. Together with identifying individual microbial taxa and functional adaptations that correlate to host phylogeny, these findings offer insights into specific candidates playing a role in the diverging trajectories of the gut microbiome of hominids. We find that repeated horizontal gene transfer and gene loss, as well as the adaptation to transient microaerobic conditions appear to have played a role in the evolution of the human gut microbiome., (© 2024. The Author(s).)

Aims: to provide insights into the recent Ebola virus disease (EVD) outbreaks on different aspects of daily life in the Democratic Republic of the Congo and propose possible solutions., Methods: We collected information regarding the effects of EVD outbreaks on existing systems in the eastern part of the Democratic Republic of the Congo (DRC). We searched the PubMed database using the terms "impact effect Ebola outbreak system", "Management Ebola Poor Resources Settings", "Health Economic Challenges Ebola" and "Economic impact Ebola systems." Only studies focusing on epidemiology, diagnostics, sequencing, vaccination, therapeutics, ecology, work force, governance, healthcare provision and health system, and social, political, and economic aspects were considered. The search included the electronic archives of EVD outbreak reports from government and partners., Results: EVD outbreaks negatively impacts the functions of countries. The disruption in activities is proportional to the magnitude of the epidemic and slows down the transport of goods, decreases the region's tourist appeal, and increases 'brain drain'. Most low- and medium-income countries, such as the DRC, do not have a long-term holistic emergency plan for unexpected situations or sufficient resources to adequately implement countermeasures against EVD outbreaks. Although the DRC has acquired sufficient expertise in diagnostics, genomic sequencing, administration of vaccines and therapeutics, clinical trials, and research activities, deployment, operation, and maintenance of these expertise and associated tools remains a concern., Limitations: Despite the data search extension, additional reports addressing issues related to social aspects of EVD outbreaks in DRC were not retrieved., Conclusion: National leadership has not yet taken the lead in strategic, operational, or financial aspects. Therefore, national leaders should double their efforts and awareness to encourage local fundraising, sufficient budget al.location, infrastructure construction, equipment provision, and staff training, to effectively support a holistic approach in response to outbreaks, providing effective results, and all types of research activities.

Mpox is a viral zoonosis with endemic circulation in animals and humans in some West and Central African countries. The disease was imported a few times in the past to countries outside the African continent through infected animals or travelers, one of which resulted in an unprecedented global outbreak sustained by human-to-human transmission in 2022. Although timely and reliable diagnosis is a cornerstone of any disease control, availability of accurate diagnostic assays and comparative performance studies of diagnostic assays remains limited despite of the long-known identification of monkeypox virus (MPXV) as a human pathogen since 1970. We laboratory-developed a real-time PCR test (LDT) and evaluated its performance against the commercial TaqMan™ Monkeypox Virus Microbe Detection Assay (Applied Biosystems, Cat A50137). The limit of detection of the LDT was established at 1.2 genome copies/ml. The sensitivity and specificity of both assays were 99.14% and 100%, respectively, and both are capable of detecting both clade I and clade II of MPXV. Our results demonstrate the validity and accuracy of the LDT for confirmation of MPXV infection from lesion swabs samples., (© 2023. The Author(s).)

Background: No distinctive clinical signs of Ebola virus disease (EVD) have prompted the development of rapid screening tools or called for a new approach to screening suspected Ebola cases. New screening approaches require evidence of clinical benefit and economic efficiency. As of now, no evidence or defined algorithm exists., Objective: To evaluate, from a healthcare perspective, the efficiency of incorporating Ebola prediction scores and rapid diagnostic tests into the EVD screening algorithm during an outbreak., Methods: We collected data on rapid diagnostic tests (RDTs) and prediction scores' accuracy measurements, e.g., sensitivity and specificity, and the cost of case management and RDT screening in EVD suspect cases. The overall cost of healthcare services (PPE, procedure time, and standard-of-care (SOC) costs) per suspected patient and diagnostic confirmation of EVD were calculated. We also collected the EVD prevalence among suspects from the literature. We created an analytical decision model to assess the efficiency of eight screening strategies: 1) Screening suspect cases with the WHO case definition for Ebola suspects, 2) Screening suspect cases with the ECPS at -3 points of cut-off, 3) Screening suspect cases with the ECPS as a joint test, 4) Screening suspect cases with the ECPS as a conditional test, 5) Screening suspect cases with the WHO case definition, then QuickNavi™-Ebola RDT, 6) Screening suspect cases with the ECPS at -3 points of cut-off and QuickNavi™-Ebola RDT, 7) Screening suspect cases with the ECPS as a conditional test and QuickNavi™-Ebola RDT, and 8) Screening suspect cases with the ECPS as a joint test and QuickNavi™-Ebola RDT. We performed a cost-effectiveness analysis to identify an algorithm that minimizes the cost per patient correctly classified. We performed a one-way and probabilistic sensitivity analysis to test the robustness of our findings., Results: Our analysis found dual ECPS as a conditional test with the QuickNavi™-Ebola RDT algorithm to be the most cost-effective screening algorithm for EVD, with an effectiveness of 0.86. The cost-effectiveness ratio was 106.7 USD per patient correctly classified. The following algorithms, the ECPS as a conditional test with an effectiveness of 0.80 and an efficiency of 111.5 USD per patient correctly classified and the ECPS as a joint test with the QuickNavi™-Ebola RDT algorithm with an effectiveness of 0.81 and a cost-effectiveness ratio of 131.5 USD per patient correctly classified. These findings were sensitive to variations in the prevalence of EVD in suspected population and the sensitivity of the QuickNavi™-Ebola RDT., Conclusions: Findings from this study showed that prediction scores and RDT could improve Ebola screening. The use of the ECPS as a conditional test algorithm and the dual ECPS as a conditional test and then the QuickNavi™-Ebola RDT algorithm are the best screening choices because they are more efficient and lower the number of confirmation tests and overall care costs during an EBOV epidemic., Competing Interests: The authors declare that they have no competing interests, (Copyright: © 2023 Tshomba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The seroprevalence to orthoebolaviruses was studied in 9594 bats (5972 frugivorous and 3622 insectivorous) from Cameroon, the Democratic Republic of Congo (DRC) and Guinea, with a Luminex-based serological assay including recombinant antigens of four orthoebolavirus species. Seroprevalence is expressed as a range according to different cut-off calculations. Between 6.1% and 18.9% bat samples reacted with at least one orthoebolavirus antigen; the highest reactivity was seen with Glycoprotein (GP) antigens. Seroprevalence varied per species and was higher in frugivorous than insectivorous bats; 9.1-27.5% versus 1.3-4.6%, respectively. Seroprevalence in male (13.5%) and female (14.4%) bats was only slightly different and was higher in adults (14.9%) versus juveniles (9.4%) ( p < 0.001). Moreover, seroprevalence was highest in subadults (45.4%) when compared to mature adults (19.2%), ( p < 0.001). Our data suggest orthoebolavirus circulation is highest in young bats. More long-term studies are needed to identify birthing pulses for the different bat species in diverse geographic regions and to increase the chances of detecting viral RNA in order to document the genetic diversity of filoviruses in bats and their pathogenic potential for humans. Frugivorous bats seem more likely to be reservoirs of orthoebolaviruses, but the role of insectivorous bats has also to be further examined.

Introduction: A serosurvey among health care providers (HCPs) and frontliners of an area previously affected by Ebola virus disease (EVD) in the Democratic Republic of the Congo (DRC) was conducted to assess the seroreactivity to Ebola virus antigens., Methods: Serum samples were collected in a cohort of HCPs and frontliners (n = 698) participants in the EBL2007 vaccine trial (December 2019 to October 2022). Specimens seroreactive for EBOV were confirmed using either the Filovirus Animal Nonclinical Group (FANG) ELISA or a Luminex multiplex assay., Results: The seroreactivity to at least two EBOV-Mayinga (m) antigens was found in 10 (1.4%: 95% CI, 0.7-2.6) samples for GP-EBOV-m + VP40-EBOV-m, and 2 (0.3%: 95% CI, 0.0-1.0) samples for VP40-EBOV-m + NP-EBOV-m using the Luminex assay. Seroreactivity to GP-EBOV-Kikwit (k) was observed in 59 (8.5%: 95%CI, 6.5-10.9) samples using FANG ELISA., Conclusion: In contrast to previous serosurveys, a low seroprevalence was found in the HCP and frontline population participating in the EBL2007 Ebola vaccine trial in Boende, DRC. This underscores the high need for standardized antibody assays and cutoffs in EBOV serosurveys to avoid the broad range of reported EBOV seroprevalence rates in EBOV endemic areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zola Matuvanga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The 2022 global outbreak of human Mpox (formerly monkeypox) virus (MPXV) infection outside of the usual endemic zones in Africa challenged our understanding of the virus's natural history, transmission dynamics, and risk factors. This outbreak has highlighted the need for diagnostics, vaccines, therapeutics, and implementation research, all of which require more substantial investments in equitable collaborative partnerships. Global multidisciplinary networks need to tackle MPXV and other neglected emerging and reemerging zoonotic pathogens to address them locally and prevent or quickly control their worldwide spread. Political endorsement from individual countries and financial commitments to maintain control efforts will be essential for long-term sustainability.

Human Mpox cases are increasingly reported in Africa, with the highest burden in the Democratic Republic of Congo (DRC). While case reporting on a clinical basis can overestimate infection rates, laboratory confirmation by PCR can underestimate them, especially on suboptimal samples like blood, commonly used in DRC. Here we used a Luminex-based assay to evaluate whether antibody testing can be complementary to confirm cases and to identify human transmission chains during outbreak investigations. We used left-over blood samples from 463 patients, collected during 174 outbreaks between 2013 and 2022, with corresponding Mpox and VZV PCR results. In total, 157 (33.9%) samples were orthopox-PCR positive and classified as Mpox+; 124 (26.8%) had antibodies to at least one of the three Mpox peptides. The proportion of antibody positive samples was significantly higher in Mpox positive samples (36.9%) versus negative (21.6%) ( p < 0.001). By combining PCR and serology, 66 additional patients were identified, leading to an Mpox infection rate of 48.2% (223/463) versus 33.9% when only PCR positivity is considered. Mpox infections were as such identified in 14 additional health zones and 23 additional outbreaks (111/174 (63.8% ) versus 88/174 (50.6%)). Our findings highlight the urgent need of rapid on-site diagnostics to circumvent Mpox spread.

Background: Ebola virus disease (EVD) outbreaks have emerged in Central and West Africa. EVD diagnosis relies principally on RT-PCR testing with GeneXpert®, which has logistical and cost restrictions at the peripheral level of the health system. Rapid diagnostic tests (RDTs) would offer a valuable alternative at the point-of-care to reduce the turn-around time, if they show good performance characteristics. We evaluated the performance of four EVD RDTs against the reference standard GeneXpert® on stored EVD positive and negative blood samples collected between 2018 and 2021 from outbreaks in eastern Democratic Republic of the Congo (DRC)., Methods: We conducted a prospective and observational study in the laboratory on QuickNavi-Ebola™, OraQuick® Ebola Rapid Antigen, Coris® EBOLA Ag K-SeT, and Standard® Q Ebola Zaïre Ag RDTs using left-over archived frozen EDTA whole blood samples. We randomly selected 450 positive and 450 negative samples from the EVD biorepositories in DRC, across a range of GeneXpert® cycle threshold values (Ct-values). RDT results were read by three persons and we considered an RDT result as "positive", when it was flagged as positive by at least two out of the three readers. We estimated the sensitivity and specificity through two independent generalized (logistic) linear mixed models (GLMM)., Findings: 476 (53%) of 900 samples had a positive GeneXpert Ebola result when retested. The QuickNavi-Ebola™ showed a sensitivity of 56.8% (95% CI 53.6-60.0) and a specificity of 97.5% (95% CI 96.2-98.4), the OraQuick® Ebola Rapid Antigen test displayed 61.6% (95% CI 57.0-65.9) sensitivity and 98.1% (95% CI 96.2-99.1) specificity, the Coris® EBOLA Ag K-SeT showed 25.0% (95% CI 22.3-27.9) sensitivity and 95.9% (95% CI 94.2-97.1) specificity, and the Standard® Q Ebola Zaïre Ag displayed 21.6% (95% CI 18.1-25.7) sensitivity and 99.1% (95% CI 97.4-99.7) specificity., Interpretation: None of the RDTs evaluated approached the "desired or acceptable levels" for sensitivity set out in the WHO target product profile, while all of the tests met the "desired level" for specificity. Nevertheless, the QuickNavi-Ebola™ and OraQuick® Ebola Rapid Antigen Test demonstrated the most favorable profiles, and may be used as frontline tests for triage of suspected-cases while waiting for RT-qPCR confirmatory testing., Funding: Institute of Tropical Medicine Antwerp/EDCTP PEAU-EBOV-RDC project., Competing Interests: Declaration of interests US CDC provided the Xpert® Ebola cartridges. FIND purchased OraQuick Ebola Rapid Antigen tests and donated to INRB through US CDC partnership. Institute of Tropical Medicine-Antwerp purchased Coris® Ag K-SeT and Standard® Q line Zaïre Ebola Rapid diagnostic tests with the financial support of the EDCTP PEAU- EBOV-RDC project under grant agreement RIA2018EF-2087, and through the FA5 DRC Program funded by the Directorate General for Development Cooperation and Humanitarian Aid (DGD) of the Belgian government. Hokkaido University provided QuickNavi Ebola rapid tests to INRB via Japanese International Cooperation Agency (JICA). Rodolphe Mérieux INRB-Goma Laboratory supported the study with laboratory supplies. DMB is a PhD fellow supported by the Belgian Directorate-general Development Cooperation and Humanitarian Aid. JB-P, ADW, FE-A, BKJ, FM-M, JDK, HK-M, EI-N, PM-K, PM-K, SM-M, MK, AT, PF, NMM, EMM, MAK-M, ET-T, PNF, SR, AL, AN-N, MEM, JMM, JJM-T, KKA, JvG, SA-M declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Recurrent disease outbreaks caused by a range of emerging and resurging pathogens over the past decade reveal major gaps in public health preparedness, detection, and response systems in Africa. Underlying causes of recurrent disease outbreaks include inadequacies in the detection of new infectious disease outbreaks in the community, in rapid pathogen identification, and in proactive surveillance systems. In sub-Saharan Africa, where 70% of zoonotic outbreaks occur, there remains the perennial risk of outbreaks of new or re-emerging pathogens for which no vaccines or treatments are available. As the Ebola virus disease, COVID-19, and mpox (formerly known as monkeypox) outbreaks highlight, a major paradigm shift is required to establish an effective infrastructure and common frameworks for preparedness and to prompt national and regional public health responses to mitigate the effects of future pandemics in Africa., Competing Interests: Declaration of interests JBN is supported by the US National Institutes of Health (NIH; grant numbers NIH/FIC 1R25TW011217-01, NIH/FIC 1D43TW010937-01A1, NIH/FIC D43TW011827-01A1, NIH/FIC 1R21TW011706-0, and NIH/NIAID 5U01AI096299-13). FN and AZ are Co-directors of the Pan-African Network on Emerging and Re-Emerging Infections funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) within the EU Horizon 2020 Framework Programme. FN and AZ also acknowledge support from the EDCTP Central Africa Clinical Research Network. AZ is a UK National Institute for Health Research senior investigator, and a Mahathir Science Award and EU-EDCTP Pascoal Mocumbi Prize laureate. J-JM-T is supported by Africa Centre for Disease Control and Prevention and the Bill and Melinda Gates Foundation, and holds NIH grants (NIH/NIAID grant number 75N91019D00024-P00001-759102000025-5). J-JM-T was part of the group that discovered the Ebola virus in 1976, and was awarded Le Prix Christophe Merieux from Institut de France in 2015 and was the recipient of the third Hideyo Noguchi Africa Prize for Medical Research in 2019 from the Japan Government, for his research to confront Ebola and other emerging and re-emerging pathogens, and for his efforts to train legions of disease fighters in Africa. All other authors declare no competing interests. TdO led the team of South African researchers who discovered the omicron variant of SARS-CoV-2 in November, 2021., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Recent studies suggest measles-induced immune amnesia could have long-term immunosuppressive effects via preferential depletion of memory CD150+ lymphocytes, and associations with a 2-3 year period of increased mortality and morbidity from infectious diseases other than measles has been shown in children from wealthy and low-income countries. To further examine the associations previous measles virus infection may have on immunologic memory among children in the Democratic Republic of the Congo (DRC), we assessed tetanus antibody levels among fully vaccinated children, with and without a history of measles., Methods: We assessed 711 children 9-59 months of age whose mothers were selected for interview in the 2013-2014 DRC Demographic and Health Survey. History of measles was obtained by maternal report and classification of children who had measles in the past was completed using maternal recall and measles IgG serostatus obtained from a multiplex chemiluminescent automated immunoassay dried blood spot analysis. Tetanus IgG antibody serostatus was similarly obtained. A logistic regression model was used to identify association of measles and other predictors with subprotective tetanus IgG antibody., Results: Subprotective geometric mean concentration tetanus IgG antibody values were seen among fully vaccinated children 9-59 months of age, who had a history of measles. Controlling for potential confounding variables, children classified as measles cases were less likely to have seroprotective tetanus toxoid antibody (odds ratio: 0.21; 95% confidence interval: 0.08-0.55) compared with children who had not had measles., Conclusions: History of measles was associated with subprotective tetanus antibody among this sample of children in the DRC who were 9-59 months of age and fully vaccinated against tetanus., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

During the 10th Ebola virus disease (EVD) epidemic in the eastern Democratic Republic of the Congo (DRC) (2018-2020), two experimental EVD vaccines were deployed in North Kivu. This province has been at the centre of conflict in the region for the last 25 years. Amidst ambivalence towards protracted foreign intervention and controversy about introducing two experimental vaccines, the existing literature has focused on mistrust and 'resistance' towards the Ebola response and vaccines. In this article, we examine why people in the eastern DRC did decide to volunteer for a trial of a second EVD vaccine in North Kivu, despite the controversy. Drawing on ethnographic observation, interviews, and focus groups with trial participants conducted between September 2020 and April 2021, we analyse three motivations for participating: protection, health seeking, and expectations surrounding travel requirements. We make three points. First, participation in vaccine trials may be understood locally to have advantages which have not been considered by the trial, because they go beyond medical considerations and are specific to a particular social setting. Second, despite much of the literature focusing on a causal relationship between rumours and 'vaccine hesitancy', some rumours may in fact encourage participation. Third, material objects associated with trial participation - such as participant vaccine cards - can hold social and political meaning beyond the confines of the vaccine clinic, and influence decisions surrounding participation. Empirical investigation of how medical interventions become entangled in political economies is essential to understanding the perceived functions of participation, and thus the reasons why people volunteer in clinical trials. Participants' narratives about their decision-making provide an insight into how international bioethical debates interact with, but may also stand apart from, the situated social and economic realities driving decision-making around clinical trials on the ground. This highlights the need for ethical approaches that foreground the political, social, and economic context., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Monkeypox virus (MPXV), a member of the Orthopoxvirus (OPXV) genus, is a zoonotic virus, endemic to central and western Africa that can cause smallpox-like symptoms in humans with fatal outcomes in up to 15% of patients. The incidence of MPXV infections in the Democratic Republic of the Congo, where the majority of cases have occurred historically, has been estimated to have increased as much as 20-fold since the end of smallpox vaccination in 1980. Considering the risk global travel carries for future disease outbreaks, accurate epidemiological surveillance of MPXV is warranted as demonstrated by the recent Mpox outbreak, where the majority of cases were occurring in non-endemic areas. Serological differentiation between childhood vaccination and recent infection with MPXV or other OPXVs is difficult due to the high level of conservation within OPXV proteins. Here, a peptide-based serological assay was developed to specifically detect exposure to MPXV. A comparative analysis of immunogenic proteins across human OPXVs identified a large subset of proteins that could potentially be specifically recognized in response to a MPXV infection. Peptides were chosen based upon MPXV sequence specificity and predicted immunogenicity. Peptides individually and combined were screened in an ELISA against serum from well-characterized Mpox outbreaks, vaccinee sera, and smallpox sera collected prior to eradication. One peptide combination was successful with ~86% sensitivity and ~90% specificity. The performance of the assay was assessed against the OPXV IgG ELISA in the context of a serosurvey by retrospectively screening a set of serum specimens from the region in Ghana believed to have harbored the MPXV-infected rodents involved in the 2003 United States outbreak.

Bats are at the origin of human coronaviruses, either directly or via an intermediate host. We tested swabs from 4597 bats (897 from the Democratic Republic of Congo (DRC), 2191 from Cameroon and 1509 from Guinea) with a broadly reactive PCR in the RdRp region. Coronaviruses were detected in 903 (19.6%) bats and in all species, with more than 25 individuals tested. The highest prevalence was observed in Eidolon helvum (239/733; 39.9%) and Rhinolophus sp. (306/899; 34.1%), followed by Hipposideros sp. (61/291; 20.9%). Frugivorous bats were predominantly infected with beta coronaviruses from the Nobecovirus subgenus (93.8%), in which at least 6 species/genus-specific subclades were observed. In contrast, insectivorous bats were infected with beta-coronaviruses from different subgenera (Nobecovirus (8.5%), Hibecovirus (32.8%), Merbecovirus (0.5%) and Sarbecovirus (57.6%)) and with a high diversity of alpha-coronaviruses. Overall, our study shows a high prevalence and genetic diversity of coronaviruses in bats and illustrates that Rhinolophus bats in Africa are infected at high levels with the Sarbecovirus subgenus, to which SARS-CoV-2 belongs. It is important to characterize in more detail the different coronavirus lineages from bats for their potential to infect human cells, their evolution and to study frequency and modes of contact between humans and bats in Africa.

Background: By the end of the third wave of the coronavirus disease 2019 (COVID-19) epidemic (May-October 2021), only 3130 of the 57 268 confirmed cases of coronavirus disease 2019 (COVID-19) in the Democratic Republic of the Congo (DRC) were reported in Kongo Central. This province, and especially its capital city, Matadi, has essential trade and exchanges with Kinshasa, the epicenter of the COVID-19 epidemic in DRC. Kinshasa accounted for 60.0% of all cases during the same period. The true burden of COVID-19 in Matadi is likely underestimated. In this study, we aimed to determine the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and associated risk factors after the third wave in Matadi., Methods: We conducted a population-based cross-sectional study in October 2021. Consenting participants were interviewed and tested using an enzyme-linked immunosorbent assay commercial kit. We applied univariable and multivariable analysis to evaluate factors associated with seropositivity and adjusted the seroprevalence for the test kit performance., Results: We included 2210 participants from 489 households. Female participants represented 59.1%. The median age was 27 years (interquartile range, 16-45 years). The crude SARS-CoV-2 seroprevalence was 82.3%. Age was identified as the main risk factor as younger age decreased the seropositivity odds. Accounting for clustering at the household level increased the seroprevalence to 83.2%. The seroprevalence increased further to 88.1% (95% confidence interval, 86.2%-90.1%) after correcting for the laboratory test kit performance., Conclusions: The SARS-CoV-2 seroprevalence was very high, contrasting with reported cases. Evidence generated from this population-based survey remains relevant in guiding the local COVID-19 response, especially vaccination strategies., Competing Interests: Potential conflicts of interest. Co-authors affiliated with the funding agency facilitated the funding process and the provision of study material. They were involved in the study design and data collection and interpretation under the leadership of an independent principal investigator from the Democratic Republic of the Congo Ministry of Health., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Serologic surveys are important tools for estimating the true burden of COVID-19 in a given population. After the first wave of SARS-CoV-2 infections, a household-based survey conducted in Kinshasa, Democratic Republic of the Congo, estimated >292 infections going undiagnosed for every laboratory-confirmed case. To ascertain the cumulative population exposure in Kinshasa after the second wave of COVID-19, we conducted a prospective population-based cross-sectional study using a highly sensitive and specific ELISA kit. The survey included 2,560 consenting persons from 585 households; 55% were female and 45% male. The overall population-weighted, test kit-adjusted SARS-CoV-2 seroprevalence was 76.5% (95% CI 74.5%-78.5%). The seroprevalence was 4-fold higher than during the first wave, and positivity was associated with age, household average monthly income, and level of education. Evidence generated from this population-based survey can inform COVID-19 response, especially vaccination campaign strategies in the context of vaccine shortages and hesitancy.

During the 10th outbreak of Ebola virus disease in the Democratic Republic of the Congo, the Institut National de Recherche Biomédicale strategically positioned 13 decentralized field laboratories with dedicated equipment to quickly detect cases as the outbreak evolved. The laboratories were operated by national staff, who quickly handed over competencies and skills to local persons to successfully manage future outbreaks. Laboratories analyzed ≈230,000 Ebola diagnostic samples under stringent biosafety measures, documentation, and database management. Field laboratories diversified their activities (diagnosis, chemistry and hematology, survivor follow-up, and genomic sequencing) and shipped 127,993 samples from the field to a biorepository in Kinshasa under good conditions. Deploying decentralized and well-equipped laboratories run by local personnel in at-risk countries for Ebola virus disease outbreaks is an efficient response; all activities are quickly conducted in the field.

Background: The control of Ebola virus disease (EVD) outbreaks relies on rapid diagnosis and prompt action, a daunting task in limited-resource contexts. This study develops prediction scores that can help healthcare workers improve their decision-making at the triage-point of EVD suspect-cases during EVD outbreaks., Methods: We computed accuracy measurements of EVD predictors to assess their diagnosing ability compared with the reference standard GeneXpert® results, during the eastern DRC EVD outbreak. We developed predictive scores using the Spiegelhalter-Knill-Jones approach and constructed a clinical prediction score (CPS) and an extended clinical prediction score (ECPS). We plotted the receiver operating characteristic curves (ROCs), estimated the area under the ROC (AUROC) to assess the performance of scores, and computed net benefits (NB) to assess the clinical utility (decision-making ability) of the scores at a given cut-off. We performed decision curve analysis (DCA) to compare, at a range of threshold probabilities, prediction scores' decision-making ability and to quantify the number of unnecessary isolation., Results: The analysis was done on data from 10432 subjects, including 651 EVD cases. The EVD prevalence was 6.2% in the whole dataset, 14.8% in the subgroup of suspects who fitted the WHO Ebola case definition, and 3.2% for the set of suspects who did not fit this case definition. The WHO clinical definition yielded 61.6% sensitivity and 76.4% specificity. Fatigue, difficulty in swallowing, red eyes, gingival bleeding, hematemesis, confusion, hemoptysis, and a history of contact with an EVD case were predictors of EVD. The AUROC for ECPS was 0.88 (95%CI: 0.86-0.89), significantly greater than this for CPS, 0.71 (95%CI: 0.69-0.73) (p < 0.0001). At -1 point of score, the CPS yielded a sensitivity of 85.4% and specificity of 42.3%, and the ECPS yielded sensitivity of 78.8% and specificity of 81.4%. The diagnostic performance of the scores varied in the three disease contexts (the whole, fitting or not fitting the WHO case definition data sets). At 10% of threshold probability, e.g. in disease-adverse context, ECPS gave an NB of 0.033 and a net reduction of unnecessary isolation of 67.1%. Using ECPS as a joint approach to isolate EVD suspects reduces the number of unnecessary isolations by 65.7%., Conclusion: The scores developed in our study showed a good performance as EVD case predictors since their use improved the net benefit, i.e., their clinical utility. These rapid and low-cost tools can help in decision-making to isolate EVD-suspicious cases at the triage point during an outbreak. However, these tools still require external validation and cost-effectiveness evaluation before being used on a large scale., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tshomba et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Promoting children's health is challenging in underresourced regions, with worse outcomes in areas of sociopolitical instabilities. This encapsulates the difficulties faced by the Panzi General Referral Hospital (PGRH) in South Kivu, the Democratic Republic of the Congo. In this retrospective, cross-sectional study of 456 children ≤ 18 years who presented to the pediatric emergency department of PGRH between December 2018 and May 2019, we present demographic and clinical predictors that affect pediatric survival. We note that referrals from external clinics (odds ratio [OR], 0.37; 95% CI, 0.18-0.75), poor maternal education (OR, 0.21; 95% CI, 0.07-0.67), diagnoses of meningitis (OR, 0.37; 95% CI, 0.18-0.75) or malnutrition (OR, 0.21; 95% CI, 0.07-0.67) are risk factors hindering pediatric survival. Paternal unemployment or longer durations of hospital stay, on the other hand, are protective toward survival. These predictors confirm the importance of accessibility and availability of medical resources and knowledge as levers to establish an effective, robust network of pediatric care delivery capable of withstanding South Kivu's unresolved political tumult.

COVID-19 underscores the need to reimagine North-South partnerships and redefine best practices for building public health and research capacity to address emergent health threats and pandemic preparedness in low- and-middle income countries (LMICs). Historically, outbreak and emergency responses have failed to ensure that the Global South has the autonomy and capacity to respond to public health threats in a timely and equitable manner. The COVID-19 response, however, has demonstrated that innovations and solutions in the Global South can not only fill resource and capacity gaps in LMICs but can also provide solutions to challenges globally. These innovations offer valuable lessons about strengthening local manufacturing capacity to produce essential diagnostic, treatment, and prevention tools; implementing high-quality research studies; expanding laboratory and research capacity; and promoting effective cooperation and governance. We discuss specific examples of capacity-building from Rwanda, South Africa, and Senegal. To fulfill promises made to the Global South during the COVID-19 pandemic, restore and resume health service delivery, and effectively prevent and respond to the next health threat, we need to prioritize equitable access to local manufacturing of basic health tools while building health systems capacities in the Global South.

Public health emergencies like SARS, MERS, and COVID-19 have prioritized surveillance of zoonotic coronaviruses, resulting in extensive genomic characterization of coronavirus diversity in bats. Sequencing viral genomes directly from animal specimens remains a laboratory challenge, however, and most bat coronaviruses have been characterized solely by PCR amplification of small regions from the best-conserved gene. This has resulted in limited phylogenetic resolution and left viral genetic factors relevant to threat assessment undescribed. In this study, we evaluated whether a technique called hybridization probe capture can achieve more extensive genome recovery from surveillance specimens. Using a custom panel of 20,000 probes, we captured and sequenced coronavirus genomic material in 21 swab specimens collected from bats in the Democratic Republic of the Congo. For 15 of these specimens, probe capture recovered more genome sequence than had been previously generated with standard amplicon sequencing protocols, providing a median 6.1-fold improvement (ranging up to 69.1-fold). Probe capture data also identified five novel alpha- and betacoronaviruses in these specimens, and their full genomes were recovered with additional deep sequencing. Based on these experiences, we discuss how probe capture could be effectively operationalized alongside other sequencing technologies for high-throughput, genomics-based discovery and surveillance of bat coronaviruses., Competing Interests: KK, KL, DS, JR, AS, ML, NL, JM, NP, AC No competing interests declared, CK, FM, PM, IN, FN, JA, JA, CM, ER, DM were employed by Metabiota Inc, MM, KS, CL are employees of Labyrinth Global Health Inc and were employed by Metabiota Inc, AG is an employee of Development Alternatives Inc and was employed by Metabiota Inc, DJ is an employee of Nyati Health Consulting and was employed by Metabiota Inc, NW is an employee of Metabiota Inc, (© 2022, Kuchinski et al.)

In response to the COVID-19 pandemic, COVID-19 vaccines have been developed, and the World Health Oraganization (WHO) has granted emergency use listing to multiple vaccines. Studies of vaccine immunogenicity data from implementing COVID-19 vaccines by national immunization programs in single studies spanning multiple countries and continents are limited but critically needed to answer public health questions on vaccines, such as comparing immune responses to different vaccines and among different populations., Competing Interests: The authors have declared that no competing interests exist.

Background: A paucity of data is available on virologic and biochemical characteristics of paediatric Ebolavirus disease (EVD), compared to adults., Methods: We conducted a retrospective chart review of children (<16 years old) and a comparator group of young adults (16-44 years) from two treatment centres during the 2018-2020 EVD epidemic in Eastern Democratic Republic of the Congo. Statistical methods included chi-squared and Fisher's exact tests (dichotomous and categorical variables), Mann-Whitney U-test (continuous variables), multivariable linear regression (for determinants of admission viral load), linear mixed-effects models (for analysis of longitudinal viral load), and Cox proportional hazard models (to examine risk factors for mortality)., Findings: We included 73 children and 234 adults admitted from April to October 2019. Paediatric patients commonly had electrolytes imbalances: hypokalaemia in 26/73 (36%), hyperkalaemia in 38/73 (52%), and hyponatraemia in 54/73 (74%). Hypoglycaemia occurred in 20/73 (27%), acute kidney injury in 43/73 (59%), and rhabdomyolysis in 35/73 (48%). Biochemical abnormalities were detected in a similar proportion of children and adults. The viral load (VL, log 10 copies/mL) at admission (7.2 versus 6.5, p =0.0001), the peak viral load (7.5 versus 6.7, p =<0.0001), and the time for viraemia clearance (16 days versus 12 days, p =<0.0001) were significantly different in children. The duration of hospital stay was prolonged in children (20 versus 16 days, p =<0.0001). Risk factors for mortality in children were: VL >7.6 log 10 copies/mL, alanine transaminase >525 U/L, C-reactive protein >100 mg/L, blood urea nitrogen >7.5 mmol/L, rhabdomyolysis, and.acute kidney injury., Interpretation: Paediatric EVD patients, like adults, experience multiorgan dysfunction with life-threatening electrolyte imbalances, hypoglycaemia, kidney injury, liver injury, and rhabdomyolysis. Paediatric patients have significantly higher VLs throughout the course of EVD than adults., Funding: This study was not funded., Competing Interests: SM is employed by Ridgeback Biotherapeutics, and is listed as inventor on the patent application for mAb 114, US Application No.62/087, 087 (PCT Application No. PCT/US2015/060733) related to anti-Ebola virus antibodies and their use. SM receives royalties paid by the NIH Office of Financial Management (OFM)., (© 2022 Published by Elsevier Ltd.)

Background: Health care workers (HCW) are more likely to be exposed to Ebola virus (EBOV) during an outbreak compared to people in the general population due to close physical contact with patients and potential exposure to infectious fluids. However, not all will fall ill. Despite evidence of subclinical and paucisymptomatic Ebola virus disease (EVD), prevalence and associated risk factors remain unknown., Methods: We conducted a serosurvey among HCW in Boende, Tshuapa Province, Democratic Republic of Congo. Human anti-EBOV glycoprotein IgG titers were measured using a commercially available ELISA kit. We assessed associations between anti-EBOV IgG seroreactivity, defined as ≥2.5 units/mL, and risk factors using univariable and multivariable logistic regression. Sensitivity analyses explored a more conservative cutoff, >5 units/mL., Results: Overall, 22.5% of HCWs were seroreactive for EBOV. In multivariable analyses, using any form of personal protective equipment when interacting with a confirmed, probable, or suspect EVD case was negatively associated with seroreactivity (adjusted odds ratio, 0.23; 95% confidence interval, .07-.73)., Discussion: Our results suggest high exposure to EBOV among HCWs and provide additional evidence for asymptomatic or minimally symptomatic EVD. Further studies should be conducted to determine the probability of onward transmission and if seroreactivity is associated with immunity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: The Democratic Republic of the Congo has confronted 13 outbreaks of Ebola virus disease since 1976. Rapid diagnostic tests (RDTs) detecting viral antigens have been developed to circumvent difficulties encountered with RT-PCR for diagnosis in remote low-resource settings, but there is still uncertainty about their performance characteristics and usability during outbreaks. We aimed to assess the field performance of three antigen detection RDTs compared with the gold-standard Cepheid GeneXpert Ebola assay results., Methods: We conducted a retrospective, multicentre observational study using complete and de-identified databases of five mobile laboratories (managed by the Institut National de Recherche Biomédicale) to assess the performance of three Ebola virus disease RDTs (QuickNavi-Ebola, OraQuick Ebola Rapid Antigen Test, and Coris EBOLA Ag K-SeT rapid test) run on blood samples of patients with suspected Ebola virus disease in direct comparison with the Cepheid GeneXpert Ebola assay reference test during the 2018-20 outbreak in the eastern Democratic Republic of the Congo. We estimated the sensitivity and specificity of each test through generalised linear mixed models against the GeneXpert Ebola assay reference test and corrected for cycle threshold value and random site effects., Findings: 719 (7·9%) of 9157 samples had a positive GeneXpert Ebola assay result. The QuickNavi-Ebola RDT had a sensitivity of 87·4% (95% CI 63·6-96·8) around the mean cycle threshold value and a specificity of 99·6% (99·3-99·8). The OraQuick Ebola Rapid Antigen Test had a sensitivity of 57·4% (95% CI 38·8-75·8) and specificity of 98·3% (97·5-99·0), and the Coris EBOLA Ag K-SeT rapid test had a sensitivity of 38·9% (23·0-63·6) against the GeneXpert Ebola assay reference and specificity of 97·4% (85·3-99·6). The QuickNavi-Ebola RDT showed a robust performance with good sensitivity, particularly with increasing viral loads (ie, low cycle threshold values), and specificity., Interpretation: The three RDTs evaluated did not achieve the desired sensitivity and specificity of the WHO target product profile. Although the RDTs cannot triage and rule out Ebola virus infection among clinical suspects, they can still help to sort people with suspected Ebola virus disease into high-risk and low-risk groups while waiting for GeneXpert Ebola assay reference testing., Funding: None., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests WHO donated GeneXpert cartridges and laboratory supplies used during the tenth outbreak of Ebola virus disease in the Democratic Republic of the Congo. WHO, Africa Centers for Disease Control and Prevention, Institute of Tropical Medicine Antwerp, and Japan International Cooperation Agency donated GeneXpert instruments for response purposes. US National Institute of Allergy and Infectious Diseases/National Institutes of Health provided GeneXpert instruments and laboratory supplies in the context of the PALM randomised controlled trial during the tenth outbreak of Ebola virus disease. Centers for Disease Control and Prevention–Atlanta donated OraQuick Ebola Rapid Antigen tests for the response. Denka and Hokkaido University, Sapporo, Japan, provided QuickNavi-Ebola rapid tests via the Japan International Cooperation Agency. Coris Bioconcept supplied Coris K SeT Ag tests via Institut Pasteur de Dakar. DM-B is a Clinical Research During Outbreaks fellow supported by the Belgian Directorate-general for Development Cooperation and Humanitarian Aid. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)