Assessment of the integrated disease surveillance and response system implementation in health zones at risk for viral hemorrhagic fever outbreaks in North Kivu, Democratic Republic of the Congo, following a major Ebola outbreak, 2021.

BACKGROUND: The Democratic Republic of the Congo (DRC) experienced its largest Ebola Virus Disease Outbreak in 2018-2020. As a result of the outbreak, significant funding and international support were provided to Eastern DRC to improve disease surveillance. The Integrated Disease Surveillance and Response (IDSR) strategy has been used in the DRC as a framework to strengthen public health surveillance, and full implementation could be critical as the DRC continues to face threats of various epidemic-prone diseases. In 2021, the DRC initiated an IDSR assessment in North Kivu province to assess the capabilities of the public health system to detect and respond to new public health threats. METHODS: The study utilized a mixed-methods design consisting of quantitative and qualitative methods. Quantitative assessment of the performance in IDSR core functions was conducted at multiple levels of the tiered health system through a standardized questionnaire and analysis of health data. Qualitative data were also collected through observations, focus groups and open-ended questions. Data were collected at the North Kivu provincial public health office, five health zones, 66 healthcare facilities, and from community health workers in 15 health areas. RESULTS: Thirty-six percent of health facilities had no case definition documents and 53% had no blank case reporting forms, limiting identification and reporting. Data completeness and timeliness among health facilities were 53% and 75% overall but varied widely by health zone. While these indicators seemingly improved at the health zone level at 100% and 97% respectively, the health facility data feeding into the reporting structure were inconsistent. The use of electronic Integrated Disease Surveillance and Response is not widely implemented. Rapid response teams were generally available, but functionality was low with lack of guidance documents and long response times. CONCLUSION: Support is needed at the lower levels of the public health system and to address specific zones with low performance. Limitations in materials, resources for communication and transportation, and workforce training continue to be challenges. This assessment highlights the need to move from outbreak-focused support and funding to building systems that can improve the long-term functionality of the routine disease surveillance system.

Ebola Virus Disease Outbreak - Democratic Republic of the Congo, August 2018-November 2019.

On August 1, 2018, the Democratic Republic of the Congo Ministry of Health (DRC MoH) declared the tenth outbreak of Ebola virus disease (Ebola) in DRC, in the North Kivu province in eastern DRC on the border with Uganda, 8 days after another Ebola outbreak was declared over in northwest Équateur province. During mid- to late-July 2018, a cluster of 26 cases of acute hemorrhagic fever, including 20 deaths, was reported in North Kivu province.* Blood specimens from six patients hospitalized in the Mabalako health zone and sent to the Institut National de Recherche Biomédicale (National Biomedical Research Institute) in Kinshasa tested positive for Ebola virus. Genetic sequencing confirmed that the outbreaks in North Kivu and Équateur provinces were unrelated. From North Kivu province, the outbreak spread north to Ituri province, and south to South Kivu province (1). On July 17, 2019, the World Health Organization designated the North Kivu and Ituri outbreak a public health emergency of international concern, based on the geographic spread of the disease to Goma, the capital of North Kivu province, and to Uganda and the challenges to implementing prevention and control measures specific to this region (2). This report describes the outbreak in the North Kivu and Ituri provinces. As of November 17, 2019, a total of 3,296 Ebola cases and 2,196 (67%) deaths were reported, making this the second largest documented outbreak after the 2014-2016 epidemic in West Africa, which resulted in 28,600 cases and 11,325 deaths.† Since August 2018, DRC MoH has been collaborating with partners, including the World Health Organization, the United Nations Children's Fund, the United Nations Office for the Coordination of Humanitarian Affairs, the International Organization of Migration, The Alliance for International Medical Action (ALIMA), Médecins Sans Frontières, DRC Red Cross National Society, and CDC, to control the outbreak. Enhanced communication and effective community engagement, timing of interventions during periods of relative stability, and intensive training of local residents to manage response activities with periodic supervision by national and international personnel are needed to end the outbreak.

The impact of Infection Prevention and control (IPC) bundle implementationon IPC compliance during the Ebola virus outbreak in Mbandaka/Democratic Republic of the Congo: a before and after design.

OBJECTIVES: To assess the impact of refresher training of healthcare workers (HCWs) in infection prevention and control (IPC), ensuring consistent adequate supplies and availability of IPC kits and carrying out weekly monitoring of IPC performance in healthcare facilities (HCFs) DESIGN: This was a before and after comparison study SETTINGS: This study was conducted from June to July 2018 during an Ebola virus disease (EVD) outbreak in Equateur Province in the Democratic Republic of the Congo (DRC). PARTICIPANTS: 48 HCFs INTERVENTIONS: HCWs capacity building in basic IPC, IPC kit donation and IPC mentoring. PRIMARY OUTCOME MEASURES: IPC score RESULTS: 48 HCFs were evaluated and 878 HCWs were trained, of whom 437 were women and 441 were men. The mean IPC score at baseline was modestly higher in hospitals (8%) compared with medical centres (4%) and health centres (4%), respectively. The mean IPC score at follow-up significantly increased to 50% in hospitals, 39% in medical centres and 36% in health centres (p value<0.001). The aggregate mean IPC score at baseline for all HCFs, combined was 4.41% and at follow-up it was 39.51% with a mean difference of 35.08% (p-value<0.001). CONCLUSIONS: Implementation of HCW capacity building in IPC, IPC kit donation to HCF and mentoring in IPC improved IPC compliance during the ninth EVD outbreak in the DRC.

Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment.

BACKGROUND: The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province. METHODS: We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus. FINDINGS: The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Équateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay. INTERPRETATION: The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP12) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures. FUNDING: Defense Biological Product Assurance Office.

2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation.

BACKGROUND: The 2018 Ebola virus disease (EVD) outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures). METHODS: We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp. FINDINGS: A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name "Tumba". This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10-3 substitutions per site per year with "Tumba" vs 1·06 × 10-3 substitutions per site per year without "Tumba"). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail. INTERPRETATION: Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures. FUNDING: Defense Biological Product Assurance Office.

Contribution of Environment Sample-Based Detection to Ebola Outbreak Management.

Detection of chains of transmission is critical to interrupt Ebola virus (EBOV) outbreaks. For >25 years, quantitative reverse transcription polymerase chain reaction performed on biological fluids has been the reference standard for EBOV detection and identification. In the current study, we investigated the use of environmental sampling to detect EBOV shed from probable case patients buried without the collection of bodily fluids. During the 2012 Bundibugyo virus (BDBV) outbreak in the Democratic Republic of the Congo, environmental samples were screened for BDBV RNA by means of real-time polymerase chain reaction. Low levels of BDBV genomic RNA were detected in a hospital and in a house. Detection of BDBV RNA in the house led to the identification of the last chain of transmission still active, which resulted in the safe burial of the person with the last laboratory-confirmed case of this outbreak. Overall, environmental sampling can fill specific gaps to help confirm EBOV positivity and therefore be of value in outbreak management.