Dysglycaemia in Ebola virus disease: a retrospective analysis from the 2018 to 2020 outbreak.

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.

Knowledge, attitudes, practices, and perception of COVID-19 preventive measures among adult residents of Matadi (Democratic Republic of the Congo) after the third epidemic wave.

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.

Optimizing the timing of an end-of-outbreak declaration: Ebola virus disease in the Democratic Republic of the Congo.

Following the apparent final case in an Ebola virus disease (EVD) outbreak, the decision to declare the outbreak over must balance societal benefits of relaxing interventions against the risk of resurgence. Estimates of the end-of-outbreak probability (the probability that no future cases will occur) provide quantitative evidence that can inform the timing of an end-of-outbreak declaration. An existing modeling approach for estimating the end-of-outbreak probability requires comprehensive contact tracing data describing who infected whom to be available, but such data are often unavailable or incomplete during outbreaks. Here, we develop a Markov chain Monte Carlo-based approach that extends the previous method and does not require contact tracing data. Considering data from two EVD outbreaks in the Democratic Republic of the Congo, we find that data describing who infected whom are not required to resolve uncertainty about when to declare an outbreak over.

COVID-19 seroprevalence cohort survey among health care workers and their household members in Kinshasa, DR Congo, 2020-2022.

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.

Sustained human outbreak of a new MPXV clade I lineage in eastern Democratic Republic of the Congo.

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.

Rhabdomyolysis, acute kidney injury, and mortality in Ebola virus disease: retrospective analysis of cases from Eastern Democratic Republic of the Congo, 2019.

BACKGROUND: Skeletal muscle injury in Ebola virus disease (EVD) has been reported, but its association with morbidity and mortality remains poorly defined. METHODS: Retrospective study of patients admitted to two EVD Treatment Units, over an eight-month period in 2019, during a large EVD epidemic in the Democratic Republic of the Congo. RESULTS: 333 patients (median age 30 years, 58% female) had at least one creatine kinase (CK) measurement (total 2,229 CK measurements, median 5 (IQR 1-11) per patient). 271 patients (81%) had an elevated CK (>380U/L), 202 (61%) had rhabdomyolysis (CK>1,000 IU/L), and 45 (14%) had severe rhabdomyolysis (≥5,000U/L). Among survivors, the maximum CK level was median 1,600 (IQR 550 to 3,400), peaking 3.4 days after admission (IQR 2.3 to 5.5) and decreasing thereafter. Among fatal cases, the CK rose monotonically until death, with maximum CK level of median 2,900 U/L (IQR 1,500 to 4,900). Rhabdomyolysis at admission was an independent predictor of AKI (aOR 2.2 [95%CI 1.2-3.8], p=0.0065) and mortality (aHR 1.7 [95%CI 1.03-2.9], p=0.037). CONCLUSIONS: Rhabdomyolysis is associated with AKI and mortality in EVD patients. These findings may inform clinical practice by identifying lab monitoring priorities and highlighting the importance of fluid management.

Seroprevalence of Bas-Congo virus in Mangala, Democratic Republic of the Congo: a population-based cross-sectional study.

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.

Lower Limb Paralysis Associated with Chikungunya in Kinshasa, the Democratic Republic of the Congo: Survey Report.

Polio-associated paralysis is one of the diseases under national surveillance in the Democratic Republic of the Congo (DRC). Although it has become relatively rare due to control measures, non-polio paralysis cases are still reported and constitute a real problem, especially for etiological diagnosis, which is necessary for better management and response. From September 2022 to April 2023, we investigated acute flaccid paralysis (AFP) cases in Kinshasa following an alert from the Provincial Division of Health. All suspected cases and their close contacts were investigated and sampled. Among the 57 sampled patients, 21 (36.8%) were suspects, and 36 (63.2%) were contacts. We performed several etiological tests available in the laboratory, targeting viruses, including Poliovirus, Influenza virus, SARS-CoV-2, Enterovirus, and arboviruses. No virus material was detected, but the serological test (ELISA) detected antibodies against Chikungunya Virus, i.e., 47.4% (27/57) for IgM and 22.8% (13/57) for IgG. Among suspected cases, we detected 33.3% (7/21) with anti-Chikungunya IgM and 14.3% (3/21) of anti-Chikungunya IgG. These results highlight the importance of enhancing the epidemiological surveillance of Chikungunya.

Co-Circulating Monkeypox and Swinepox Viruses, Democratic Republic of the Congo, 2022.

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.

Immunological response to fractional-dose yellow fever vaccine administered during an outbreak in Kinshasa, Democratic Republic of the Congo: results 5 years after vaccination from a prospective cohort study.

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 (PRNT50). Participants with a PRNT50 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.

Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine constitutes a valuable tool to control Ebola virus disease outbreaks. This retrospective cohort study aimed to assess the protective effect of the vaccine against death among patients with confirmed Ebola virus disease. METHODS: In this retrospective cohort analysis of patients with confirmed Ebola virus disease admitted to Ebola health facilities in the Democratic Republic of the Congo between July 27, 2018, and April 27, 2020, we performed univariate and multivariate analyses to assess case fatality risk and cycle threshold for nucleoprotein according to vaccination status, Ebola virus disease-specific treatments (eg, mAb114 and REGN-EB3), and other risk factors. FINDINGS: We analysed all 2279 patients with confirmed Ebola virus disease. Of these 2279 patients, 1300 (57%) were female and 979 (43%) were male. Vaccination significantly lowered case fatality risk (vaccinated: 25% [106/423] vs not vaccinated: 56% [570/1015]; p<0·0001). In adjusted analyses, vaccination significantly lowered the risk of death compared with no vaccination, with protection increasing as time elapsed from vaccination to symptom onset (vaccinated ≤2 days before onset: 27% [27/99], adjusted relative risk 0·56 [95% CI 0·36-0·82, p=0·0046]; 3-9 days before onset: 20% [28/139], 0·44 [0·29-0·65, p=0·0001]; ≥10 days before onset: 18% [12/68], 0·40 [0·21-0·69; p=0·0022]; vaccination date unknown: 33% [39/117], 0·69 [0·48-0·96; p=0·0341]; and vaccination status unknown: 52% [441/841], 0·80 [0·70-0·91, p=0·0011]). Longer time from symptom onset to admission significantly increased risk of death (49% [1117/2279], 1·03 [1·02-1·05; p<0·0001]). Cycle threshold values for nucleoprotein were significantly higher-indicating lower viraemia-among patients who were vaccinated compared with those who were not vaccinated; the highest difference was observed among those vaccinated 21 days or longer before symptom onset (median 30·0 cycles [IQR 24·6-33·7]) compared with patients who were not vaccinated (21·4 cycles [18·4-25·9], p<0·0001). INTERPRETATION: To our knowledge, this is the first observational study describing the protective effect of rVSVΔG-ZEBOV-GP vaccination against death among patients with confirmed Ebola virus disease admitted to an Ebola health facility. Vaccination was protective against death for all patients, even when adjusted for Ebola virus disease-specific treatment, age group, and time from symptom onset to admission. FUNDING: Médecins Sans Frontières. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

2020 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation.

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.

Impact of Ebola epidemics on the daily operation of existing systems in Eastern Democratic Republic of the Congo: a brief review.

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.

Structural Features and Genetic Diversity in Gag Gene of Rare HIV-1 Subtypes from the Democratic Republic of Congo.

Type-1 HIV (HIV-1) group M (HIV-1M) genetic diversity is highest in the Congo Basin where the epidemic ignited a century ago. HIV-1M has diversified into multiple subtypes, sub-subtypes, and circulating and unique recombinant forms (CRFs/URFs). An unanswered question is why some rare subtypes never reached epidemic levels despite their age. Several studies identified the role of HIV-1M accessory genes nef and vpu in virus adaptation to human hosts and subsequent spread. Other reports also pointed out the pivotal role of gag in transmissibility, virulence, and replication capacity. In this study we characterized the HIV-1 gag gene of 148 samples collected in different localities of the Democratic Republic of the Congo (DRC) between 1997 and 2013. We used nested polymerase chain reaction (PCR) to amplify the whole gag gene. PCR products were sequenced either by Sanger method or by next generation sequencing on Illumina MiSeq or iSeq100 platforms. Generated sequences were used for subsequent analyses using different bioinformatic tools. Phylogenetic analysis of the generated sequences revealed a high genetic diversity with up to 22 different subtypes, sub-subtypes, CRFs. Up to 15% (22/148) URFs were identified, in addition to rare subtypes such as H, J, and K. At least two amino acid motifs present in the gag gene have been shown to modulate HIV-1 replication, budding, and fitness: the P(T/S)AP and the LYPXnL motifs. Structural analysis revealed the presence of P(T/S)AP in all the 148 sequences with the majority (136/148) bearing the PTAP. Three samples presented a duplication of this motif. The LYPXnL motif was identified in 38 of 148 sequences. There was no clear link between the frequency of these motifs and HIV-1M subtypes. In summary, we confirmed a high genetic diversity of HIV-1M in the DRC. We observed the presence of amino acid motifs important for viral replication and budding even in some rare HIV-1 subtypes. Their impact on viral fitness needs be further evaluated by in vitro studies.

Effect of anti-Ebola virus monoclonal antibodies on endogenous antibody production in survivors of Ebola virus disease in the Democratic Republic of the Congo: an observational cohort study.

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.

Clade I-Associated Mpox Cases Associated with Sexual Contact, the Democratic Republic of the Congo.

We report a cluster of clade I monkeypox virus infections linked to sexual contact in the Democratic Republic of the Congo. Case investigations resulted in 5 reverse transcription PCR-confirmed infections; genome sequencing suggest they belonged to the same transmission chain. This finding demonstrates that mpox transmission through sexual contact extends beyond clade IIb.

Cost-effectiveness of incorporating Ebola prediction score tools and rapid diagnostic tests into a screening algorithm: A decision analytic model.

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.

The cost of public health interventions to respond to the 10th Ebola outbreak in the Democratic Republic of the Congo.

The 10th Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) drew substantial attention from the international community, which in turn invested more than US$1 billion in EVD control over two years (2018-2020). This is the first EVD outbreak to take place in a conflict area, which led to a shift in strategy from a pure public health response (PHR) to a multisectoral humanitarian response. A wide range of disease control and mitigation activities were implemented and were outlined in the five budgeted Strategic Response Plans used throughout the 26 months. This study used the budget/expenditure and output indicators for disease control and mitigation interventions compiled by the government of DRC and development and humanitarian partners to estimate unit costs of key Ebola control interventions. Of all the investment in EVD control, 68% was spent on PHR. The remaining 32% covered security, community support interventions for the PHR. The disbursement for the public health pillar was distributed as follows: (1) coordination (18.8%), (2), clinical management of EVD cases (18.4%), (3) surveillance and vaccination (15.9%), (4) infection prevention and control/WASH (13.8%) and (5) risk communication (13.7%). The unit costs of key EVD control interventions were as follows: US$66 182 for maintaining a rapid response team per month, US$4435 for contact tracing and surveillance per identified EVD case, US$1464 for EVD treatment per case, US$59.4 per EVD laboratory test, US$120.7 per vaccinated individual against EVD and US$175.0 for mental health and psychosocial support per beneficiary. The estimated unit costs of key EVD disease control interventions provide crucial information for future infectious disease control planning and budgeting, as well as prioritisation of disease control interventions.