Use of a rapid digital microfluidics-powered immunoassay for assessing measles and rubella infection and immunity in outbreak settings in the Democratic Republic of the Congo.

The Democratic Republic of the Congo (DRC) has a high measles incidence despite elimination efforts and has yet to introduce rubella vaccine. We evaluated the performance of a prototype rapid digital microfluidics powered (DMF) enzyme-linked immunoassay (ELISA) assessing measles and rubella infection, by testing for immunoglobulin M (IgM), and immunity from natural infection or vaccine, by testing immunoglobulin G (IgG), in outbreak settings. Field evaluations were conducted during September 2017, in Kinshasa province, DRC. Blood specimens were collected during an outbreak investigation of suspected measles cases and tested for measles and rubella IgM and IgG using the DMF-ELISA in the field. Simultaneously, a household serosurvey for measles and rubella IgG was conducted in a recently confirmed measles outbreak area. DMF-ELISA results were compared with reference ELISA results tested at DRC's National Public Health Laboratory and the US Centers for Disease Control and Prevention. Of 157 suspected measles cases, rubella IgM was detected in 54% while measles IgM was detected in 13%. Measles IgG-positive cases were higher among vaccinated persons (87%) than unvaccinated persons (72%). In the recent measles outbreak area, measles IgG seroprevalence was 93% overall, while rubella seroprevalence was lower for children (77%) than women (98%). Compared with reference ELISA, DMF-ELISA sensitivity and specificity were 82% and 78% for measles IgG; 88% and 89% for measles IgM; 85% and 85% for rubella IgG; and 81% and 83% for rubella IgM, respectively. Rubella infection was detected in more than half of persons meeting the suspected measles case definition during a presumed measles outbreak, suggesting substantial unrecognized rubella incidence, and highlighting the need for rubella vaccine introduction into the national schedule. The performance of the DMF-ELISA suggested that this technology can be used to develop rapid diagnostic tests for measles and rubella.

Sachet water consumption as a risk factor for cholera in urban settings: Findings from a case control study in Kinshasa, Democratic Republic of the Congo during the 2017-2018 outbreak.

BACKGROUND: Behavioural risk factors for cholera are well established in rural and semi-urban contexts, but not in densely populated mega-cities in Sub-Saharan Africa. In November 2017, a cholera epidemic occurred in Kinshasa, the Democratic Republic of the Congo, where no outbreak had been recorded for nearly a decade. During this outbreak, we investigated context-specific risk factors for cholera in an urban setting among a population that is not frequently exposed to cholera. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 390 participants from three affected health zones of Kinshasa into a 1:1 matched case control study. Cases were identified from cholera treatment centre admission records, while controls were recruited from the vicinity of the cases' place of residence. We used standardized case report forms for the collection of socio-demographic and behavioural risk factors. We used augmented backward elimination in a conditional logistic regression model to identify risk factors. The consumption of sachet water was strongly associated with the risk of being a cholera case (p-value 0.019), which increased with increasing frequency of consumption from rarely (OR 2.2, 95% CI 0.9-5.2) to often (OR 4.0, 95% CI 1.6-9.9) to very often (OR 4.1, 95% CI 1.0-16.7). Overall, more than 80% of all participants reported consumption of this type of drinking water. The risk factors funeral attendance and contact with someone suffering from diarrhoea showed a p-value of 0.09 and 0.08, respectively. No socio-demographic characteristics were associated with the risk of cholera. CONCLUSIONS/SIGNIFICANCE: Drinking water consumption from sachets, which are sold informally on the streets in most Sub-Saharan African cities, are an overlooked route of infection in urban cholera outbreaks. Outbreak response measures need to acknowledge context-specific risk factors to remain a valuable tool in the efforts to achieve national and regional targets to reduce the burden of cholera in Sub-Saharan Africa.

Contextual, Social and Epidemiological Characteristics of the Ebola Virus Disease Outbreak in Likati Health Zone, Democratic Republic of the Congo, 2017.

While the clinical, laboratory and epidemiological investigation results of the Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC) in May 2017 have been previously reported, we provide novel commentary on the contextual, social, and epidemiological characteristics of the epidemic. As first responders with the outbreak Surveillance Team, we explain the procedures that led to a successful epidemiological investigation and ultimately a rapid end to the epidemic. We discuss the role that several factors played in the trajectory of the epidemic, including traditional healers, insufficient knowledge of epidemiological case definitions, a lack of community-based surveillance systems and tools, and remote geography. We also demonstrate how a collaborative Rapid Response Team and implementation of community-based surveillance methods helped counter contextual challenges during the Likati epidemic and aid in identifying and reporting suspected cases and contacts in remote and rural settings. Understanding these factors can hinder or help in the rapid detection, notification, and response to future epidemics in the DRC.

Molecular characterization of chikungunya virus during the 2019 outbreak in the Democratic Republic of the Congo.

Early 2019, a chikungunya virus (CHIKV) outbreak hit the Democratic Republic of the Congo (DRC). Though seldomly deadly, this mosquito-borne disease presents as an acute febrile (poly)arthralgia often followed by long-term sequelae. Although Aedes aegypti is the primary vector, an amino acid substitution in the viral envelope gene E1 (A226V) is causing concern as it results in increased transmission by Aedes albopictus, a mosquito with a much wider geographical distribution. Between January and March 2019, we collected human and mosquito samples in Kinshasa and Kongo Central province (Kasangulu and Matadi). Of the patients that were tested within 7 days of symptom onset, 49.7% (87/175) were RT-qPCR positive, while in the mosquito samples CHIKV was found in 1/2 pools in Kinshasa, 5/6 pools in Kasangulu, and 8/26 pools in Matadi. Phylogenetic analysis on whole-genome sequences showed that the circulating strain formed a monophyletic group within the ECSA2 lineage and harboured the A226V mutation. Our sequences did not cluster with sequences from previously reported outbreaks in the DRC nor with other known A226V-containing ECSA2 strains. This indicates a scenario of convergent evolution where A226V was acquired independently in response to a similar selection pressure for transmission by Ae. albopictus. This is in line with our entomological data where we detected Ae. albopictus more frequently than Ae. aegypti in two out of three affected areas. In conclusion, our findings suggest that CHIKV is adapting to the increased presence of Aedes albopictus in DRC.

Lessons Learned from Reinforcing Epidemiologic Surveillance During the 2017 Ebola Outbreak in the Likati District, Democratic Republic of the Congo.

On May 12, 2017, the Democratic Republic of Congo (DRC) publicly declared an outbreak of Ebola virus disease (EVD) in the Likati District of the Bas-Uélé Province, 46 days after the index case became symptomatic. The delayed EVD case detection and reporting highlights the importance of establishing real-time surveillance, consistent with the Global Health Security Agenda. We describe lessons learned from implementing improved EVD case detection and reporting strategies at the outbreak epicenter and make recommendations for future response efforts. The strategies included daily coordination meetings to enhance effective and efficient outbreak response activities, assessment and adaptation of case definitions and reporting tools, establishment of a community alert system using context-appropriate technology, training facility and community health workers on adapted case definitions and reporting procedures, development of context-specific plans for outbreak data management, and strengthened operational support for communications and information-sharing networks. Post-outbreak, surveillance officials should preemptively plan for the next outbreak by developing emergency response plans, evaluating the case definitions and reporting tools used, retraining on revised case definitions, and developing responsive strategies for overcoming telecommunications and technology challenges. The ongoing EVD outbreak in the North Kivu and Ituri provinces of DRC, currently the second largest EVD outbreak in history, demonstrates that documentation of successful context-specific strategies and tools are needed to combat the next outbreak. The lessons learned from the rapid containment of the EVD outbreak in Likati can be applied to the DRC and other rural low-resource settings to ensure readiness for future zoonotic disease outbreaks.

Case Definitions Used During the First 6 Months of the 10th Ebola Virus Disease Outbreak in the Democratic Republic of the Congo - Four Neighboring Countries, August 2018-February 2019.

On August 1, 2018, the Democratic Republic of the Congo (DRC) declared its 10th Ebola virus disease (Ebola) outbreak in an area with a high volume of cross-border population movement to and from neighboring countries. The World Health Organization (WHO) designated Rwanda, South Sudan, and Uganda as the highest priority countries for Ebola preparedness because of the high risk for cross-border spread from DRC (1). Countries might base their disease case definitions on global standards; however, historical context and perceived risk often affect why countries modify and adapt definitions over time, moving toward or away from regional harmonization. Discordance in case definitions among countries might reduce the effectiveness of cross-border initiatives during outbreaks with high risk for regional spread. CDC worked with the ministries of health (MOHs) in DRC, Rwanda, South Sudan, and Uganda to collect MOH-approved Ebola case definitions used during the first 6 months of the outbreak to assess concordance (i.e., commonality in category case definitions) among countries. Changes in MOH-approved Ebola case definitions were analyzed, referencing the WHO standard case definition, and concordance among the four countries for Ebola case categories (i.e., community alert, suspected, probable, confirmed, and case contact) was assessed at three dates (2). The number of country-level revisions ranged from two to four, with all countries revising Ebola definitions by February 2019 after a December 2018 peak in incidence in DRC. Case definition complexity increased over time; all countries included more criteria per category than the WHO standard definition did, except for the "case contact" and "confirmed" categories. Low case definition concordance and lack of awareness of regional differences by national-level health officials could reduce effectiveness of cross-border communication and collaboration. Working toward regional harmonization or considering systematic approaches to addressing country-level differences might increase efficiency in cross-border information sharing.

Evaluation of the influenza sentinel surveillance system in the Democratic Republic of Congo, 2012-2015.

BACKGROUND: The World Health Organization recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data about the performance of established influenza surveillance systems are limited in Africa, including in the Democratic Republic of Congo (DRC). METHODS: We used the Centers for Disease Control and Prevention guidelines to evaluate the performance of the influenza sentinel surveillance system (ISSS) in DRC during 2012-2015. The performance of the system was evaluated using eight surveillance attributes: (i) data quality and completeness for key variables, (ii) timeliness, (iii) representativeness, (iv) flexibility, (v) simplicity, (vi) acceptability, (vii) stability and (viii) utility. For each attribute, specific indicators were developed and described using quantitative and qualitative methods. Scores for each indicator were as follows: < 60% weak performance; 60-79% moderate performance; ≥80% good performance. RESULTS: During 2012-2015, we enrolled and tested 4339 patients with influenza-like illness (ILI) and 2869 patients with severe acute respiratory illness (SARI) from 11 sentinel sites situated in 5 of 11 provinces. Influenza viruses were detected in 446 (10.3%) samples from patients with ILI and in 151 (5.5%) samples from patients with SARI with higher detection during December-May. Data quality and completeness was > 90% for all evaluated indicators. Other strengths of the system were timeliness, simplicity, stability and utility that scored > 70% each. Representativeness, flexibility and acceptability had moderate performance. It was reported that the ISSS contributed to: (i) a better understanding of the epidemiology, circulating patterns and proportional contribution of influenza virus among patients with ILI or SARI; (ii) acquisition of new key competences related to influenza surveillance and diagnosis; and (iii) continuous education of surveillance staff and clinicians at sentinel sites about influenza. However, due to limited resources no actions were undertaken to mitigate the impact of seasonal influenza epidemics. CONCLUSIONS: The system performed overall satisfactorily and provided reliable and timely data about influenza circulation in DRC. The simplicity of the system contributed to its stability. A better use of the available data could be made to inform and promote prevention interventions especially among the most vulnerable groups.

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.

Assessing the Surveillance System for Priority Zoonotic Diseases in the Democratic Republic of the Congo, 2017.

High-functioning communicable disease surveillance systems are critical for public health preparedness. Countries that cannot quickly detect and contain diseases are a risk to the global community. The ability of all countries to comply with the International Health Regulations is paramount for global health security. Zoonotic diseases can be particularly dangerous for humans. We conducted a surveillance system assessment of institutional and individual capacity in Kinshasa and Haut Katanga provinces in the Democratic Republic of the Congo for nationally identified priority zoonotic diseases (eg, viral hemorrhagic fever [VHF], yellow fever, rabies, monkeypox, and influenza monitored through acute respiratory infections). Data were collected from 79 health workers responsible for disease surveillance at 2 provincial health offices, 9 health zone offices, 9 general reference hospitals, and 18 health centers and communities. A set of questionnaires was used to assess health worker training in disease surveillance methods; knowledge of case definitions; availability of materials and tools to support timely case detection, reporting, and data interpretation; timeliness and completeness of reporting; and supervision from health authorities. We found that health workers either had not been recently or ever trained in surveillance methods and that their knowledge of case definitions was low. Timeliness and completeness of weekly notification of epidemic-prone diseases was generally well performed, but the lack of available standardized reporting forms and archive of completed forms affected the quality of data collected. Lessons learned from our assessment can be used for targeted strengthening efforts to improve global health security.

The national and provincial burden of medically attended influenza-associated influenza-like illness and severe acute respiratory illness in the Democratic Republic of Congo, 2013-2015.

BACKGROUND: Estimates of influenza-associated outpatient consultations and hospitalizations are severely limited in low- and middle-income countries, especially in Africa. METHODS: We conducted active prospective surveillance for influenza-like illness (ILI) and severe acute respiratory illness (SARI) at 5 healthcare facilities situated in Kinshasa Province during 2013-2015. We tested upper respiratory tract samples for influenza viruses using a reverse transcription-polymerase chain reaction assay. We estimated age-specific numbers and rates of influenza-associated ILI outpatient consultations and SARI hospitalizations for Kinshasa Province using a combination of administrative and influenza surveillance data. These estimates were extrapolated to each of the remaining 10 provinces accounting for provincial differences in prevalence of risk factors for pneumonia and healthcare-seeking behavior. Rates were reported per 100 000 population. RESULTS: During 2013-2015, the mean annual national number of influenza-associated ILI outpatient consultations was 1 003 212 (95% Confidence Incidence [CI]: 719 335-1 338 050 - Rate: 1205.3; 95% CI: 864.2-1607.5); 199 839 (95% CI: 153 563-254 759 - Rate: 1464.0; 95% CI: 1125.0-1866.3) among children aged <5 years and 803 374 (95% CI: 567 772-1 083 291 - Rate: 1154.5; 95% CI: 813.1-1556.8) among individuals aged ≥5 years. The mean annual national number of influenza-associated SARI hospitalizations was 40 361 (95% CI: 24 014-60 514 - Rate: 48.5; 95% CI: 28.9-72.7); 25 452 (95% CI: 19 146-32 944 - Rate: 186.5; 95% CI: 140.3-241.3) among children aged <5 years and 14 909 (95% CI: 4868-27 570 - Rate: 21.4; 95% CI: 28.9-72.7) among individuals aged ≥5 years. CONCLUSIONS: The burden of influenza-associated ILI outpatient consultations and SARI hospitalizations was substantial and was highest among hospitalized children aged <5 years.