Pan-ebolavirus serology study of healthcare workers in the Mbandaka Health Region, Democratic Republic of the Congo.

Although multiple antigenically distinct ebolavirus species can cause human disease, previous serosurveys focused on only Zaire ebolavirus (EBOV). Thus, the extent of reactivity or exposure to other ebolaviruses, and which sociodemographic factors are linked to this seroreactivity, are unclear. We conducted a serosurvey of 539 healthcare workers (HCW) in Mbandaka, Democratic Republic of the Congo, using ELISA-based analysis of serum IgG against EBOV, Sudan ebolavirus (SUDV) and Bundibugyo ebolavirus (BDBV) glycoproteins (GP). We compared seroreactivity to risk factors for viral exposure using univariate and multivariable logistic regression. Seroreactivity against different GPs ranged from 2.2-4.6%. Samples from six individuals reacted to all three species of ebolavirus and 27 samples showed a species-specific IgG response. We find that community health volunteers are more likely to be seroreactive against each antigen than nurses, and in general, that HCWs with indirect patient contact have higher anti-EBOV GP IgG levels than those with direct contact. Seroreactivity against ebolavirus GP may be associated with positions that offer less occupational training and access to PPE. Those individuals with broadly reactive responses may have had multiple ebolavirus exposures or developed cross-reactive antibodies. In contrast, those individuals with species-specific BDBV or SUDV GP seroreactivity may have been exposed to an ebolavirus not previously known to circulate in the region.

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.

2017 Outbreak of Ebola Virus Disease in Northern Democratic Republic of Congo.

BACKGROUND: In 2017, the Democratic Republic of the Congo (DRC) recorded its eighth Ebola virus disease (EVD) outbreak, approximately 3 years after the previous outbreak. METHODS: Suspect cases of EVD were identified on the basis of clinical and epidemiological information. Reverse transcription-polymerase chain reaction (RT-PCR) analysis or serological testing was used to confirm Ebola virus infection in suspected cases. The causative virus was later sequenced from a RT-PCR-positive individual and assessed using phylogenetic analysis. RESULTS: Three probable and 5 laboratory-confirmed cases of EVD were recorded between 27 March and 1 July 2017 in the DRC. Fifty percent of cases died from the infection. EVD cases were detected in 4 separate areas, resulting in > 270 contacts monitored. The complete genome of the causative agent, a variant from the Zaireebolavirus species, denoted Ebola virus Muyembe, was obtained using next-generation sequencing. This variant is genetically closest, with 98.73% homology, to the Ebola virus Mayinga variant isolated from the first DRC outbreaks in 1976-1977. CONCLUSION: A single spillover event into the human population is responsible for this DRC outbreak. Human-to-human transmission resulted in limited dissemination of the causative agent, a novel Ebola virus variant closely related to the initial Mayinga variant isolated in 1976-1977 in the DRC.

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.

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.

Ecologic Features of Plague Outbreak Areas, Democratic Republic of the Congo, 2004-2014.

During 2004-2014, the Democratic Republic of the Congo (DRC) declared 54% of plague cases worldwide. Using national data, we characterized the epidemiology of human plague in DRC for this period. All 4,630 suspected human plague cases and 349 deaths recorded in DRC came from Orientale Province. Pneumonic plague cases (8.8% of total) occurred during 2 major outbreaks in mining camps in the equatorial forest, and some limited outbreaks occurred in the Ituri highlands. Epidemics originated in 5 health zones clustered in Ituri, where sporadic bubonic cases were recorded throughout every year. Classification and regression tree characterized this cluster by the dominance of ecosystem 40 (mountain tropical climate). In conclusion, a small, stable, endemic focus of plague in the highlands of the Ituri tropical region persisted, acting as a source of outbreaks in DRC.

Ebola Virus Disease in Pregnancy: Clinical, Histopathologic, and Immunohistochemical Findings.

Here we describe clinicopathologic features of Ebola virus disease in pregnancy. One woman infected with Sudan virus in Gulu, Uganda, in 2000 had a stillbirth and survived, and another woman infected with Bundibugyo virus had a live birth with maternal and infant death in Isiro, the Democratic Republic of the Congo in 2012. Ebolavirus antigen was seen in the syncytiotrophoblast and placental maternal mononuclear cells by immunohistochemical analysis, and no antigen was seen in fetal placental stromal cells or fetal organs. In the Gulu case, ebolavirus antigen localized to malarial parasite pigment-laden macrophages. These data suggest that trophoblast infection may be a mechanism of transplacental ebolavirus transmission.

Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo.

A >600% increase in monkeypox cases occurred in the Bokungu Health Zone of the Democratic Republic of the Congo during the second half of 2013; this increase prompted an outbreak investigation. A total of 104 possible cases were reported from this health zone; among 60 suspected cases that were tested, 50 (48.1%) cases were confirmed by laboratory testing, and 10 (9.6%) tested negative for monkeypox virus (MPXV) infection. The household attack rate (i.e., rate of persons living with an infected person that develop symptoms of MPXV infection) was 50%. Nine families showed >1 transmission event, and >6 transmission events occurred within this health zone. Mean incubation period was 8 days (range 4-14 days). The high attack rate and transmission observed in this study reinforce the importance of surveillance and rapid identification of monkeypox cases. Community education and training are needed to prevent transmission of MPXV infection during outbreaks.

Ebola virus disease in the Democratic Republic of the Congo, 1976-2014.

The Democratic Republic of the Congo has experienced the most outbreaks of Ebola virus disease since the virus' discovery in 1976. This article provides for the first time a description and a line list for all outbreaks in this country, comprising 996 cases. Compared to patients over 15 years old, the odds of dying were significantly lower in patients aged 5 to 15 and higher in children under five (with 100% mortality in those under 2 years old). The odds of dying increased by 11% per day that a patient was not hospitalised. Outbreaks with an initially high reproduction number, R (>3), were rapidly brought under control, whilst outbreaks with a lower initial R caused longer and generally larger outbreaks. These findings can inform the choice of target age groups for interventions and highlight the importance of both reducing the delay between symptom onset and hospitalisation and rapid national and international response.

The effect of immunization on measles incidence in the Democratic Republic of Congo: Results from a model of surveillance data.

BACKGROUND: Measles continues to be a leading cause of vaccine-preventable disease mortality among children under five despite a safe and efficacious vaccine being readily available. While global vaccination coverage has improved tremendously, measles outbreaks persist throughout sub-Saharan Africa. Since 2010, the Democratic Republic of Congo (DRC) has seen a resurgence of measles outbreaks affecting all 11 provinces. These outbreaks are mainly attributed to gaps in routine immunization (RI) coverage compounded with missed supplementary immunization activities (SIAs). We utilized national passive surveillance data from DRC's Integrated Disease Surveillance and Response (IDSR) system to estimate the effect of immunization on measles incidence in DRC. METHODS: We investigated the decline in measles incidence post-immunization with one dose of measles containing vaccine (MCV1) with and without the addition of supplementary immunization activities (SIAs) and outbreak response immunization (ORI) campaigns. Measles case counts by health zone were obtained from the IDSR system between January 1, 2010 and December 31, 2013. The impact of measles immunization was modeled using a random effects multi-level model for count data with RI coverage levels and mass campaign activities from one year prior. RESULTS: The presence of an SIA (aIRR [95% CI] 0.86 [0.60-1.25]) and ORI (0.28 [0.20-0.39]) in the year prior were both associated with a decrease in measles incidence. When interaction terms were included, our results suggested that the high levels of MCV1 reported in the year prior and the presence of either mass campaign was associated with a decrease in measles incidence. CONCLUSIONS: Our results highlight the importance of a two-dose measles vaccine schedule and the need for a strong routine immunization program coupled with frequent SIAs. Repeated occurrences of large-scale outbreaks in DRC suggest that vaccination coverage rates are grossly overestimated and signify the importance of the evaluation and modification of measles prevention and control strategies.

Antecedent causes of a measles resurgence in the Democratic Republic of the Congo.

INTRODUCTION: Despite accelerated measles control efforts, a massive measles resurgence occurred in the Democratic Republic of the Congo (DRC) starting in mid-2010, prompting an investigation into likely causes. METHODS: We conducted a descriptive epidemiological analysis using measles immunization and surveillance data to understand the causes of the measles resurgence and to develop recommendations for elimination efforts in DRC. RESULTS: During 2004-2012, performance indicator targets for case-based surveillance and routine measles vaccination were not met. Estimated coverage with the routine first dose of measles-containing vaccine (MCV1) increased from 57% to 73%. Phased supplementary immunization activities (SIAs) were conducted starting in 2002, in some cases with sub-optimal coverage (≤95%). In 2010, SIAs in five of 11 provinces were not implemented as planned, resulting in a prolonged interval between SIAs, and a missed birth cohort in one province. During July 1, 2010-December 30, 2012, high measles attack rates (>100 cases per 100,000 population) occurred in provinces that had estimated MCV1 coverage lower than the national estimate and did not implement planned 2010 SIAs. The majority of confirmed case-patients were aged <10 years (87%) and unvaccinated or with unknown vaccination status (75%). Surveillance detected two genotype B3 and one genotype B2 measles virus strains that were previously identified in the region. CONCLUSION: The resurgence was likely caused by an accumulation of unvaccinated, measles-susceptible children due to low MCV1 coverage and suboptimal SIA implementation. To achieve the regional goal of measles elimination by 2020, efforts are needed in DRC to improve case-based surveillance and increase two-dose measles vaccination coverage through routine services and SIAs.

Human Monkeypox in the Kivus, a Conflict Region of the Democratic Republic of the Congo.

Monkeypox (MPX) is a zoonotic Orthopoxvirus infection endemic in central and western Africa. Human MPX cases occur in the central and northern regions of the Democratic Republic of the Congo (DRC), and this is the first report of confirmed MPX cases in the forested areas of North and South Kivu Provinces, with a detailed epidemiological investigation for one case. The location of each case is within areas predicted to be suitable for MPX virus transmission based on an ecological niche model. Phylogenetic analysis places these viruses in the Congo Basin clade.

Field evaluation of measles vaccine effectiveness among children in the Democratic Republic of Congo.

BACKGROUND: Large-scale measles outbreaks in areas with high administrative vaccine coverage rates suggest the need to re-evaluate measles prevention and control in the Democratic Republic of Congo (DRC). Monitoring of measles Vaccine Effectiveness (VE) is a useful measure of quality control in immunization programs. We estimated measles VE among children aged 12-59 months in the Democratic Republic of Congo (DRC) using laboratory surveillance data from 2010-2012. METHODS: We used the case-based surveillance system with laboratory confirmation to conduct a case-control study using the test negative design. Cases and controls were selected based on presence (n=1044) or absence (n=1335) of measles specific antibody IgM or epidemiologic linkage. Risk factors for measles were assessed using unconditional logistic regression, stratified by age. RESULTS: Among children 12-59 months, measles vaccination was protective against measles [aOR (95%C)], 0.20 (0.15-0.26) and estimated VE was 80% (95% CI 74-85%). Year of diagnosis, 2011: 6.02 (4.16-8.72) and 2012; 8.31 (5.57-12.40) was a risk factor for measles when compared to 2010. Compared to Kinshasa, children in Bas-Congo, Kasai-Oriental, Maniema and South Kivu provinces all had higher odds of developing measles. Measles VE was similar for children 12-23 months and 24-59 months (80% and 81% respectively). CONCLUSIONS: Repeated occurrences of measles outbreaks and lower than expected VE estimates suggest the need to further evaluate measles vaccine efficacy and improve vaccine delivery strategies in DRC.

Transmission of Ebola viruses: what we know and what we do not know.

Available evidence demonstrates that direct patient contact and contact with infectious body fluids are the primary modes for Ebola virus transmission, but this is based on a limited number of studies. Key areas requiring further study include (i) the role of aerosol transmission (either via large droplets or small particles in the vicinity of source patients), (ii) the role of environmental contamination and fomite transmission, (iii) the degree to which minimally or mildly ill persons transmit infection, (iv) how long clinically relevant infectiousness persists, (v) the role that "superspreading events" may play in driving transmission dynamics, (vi) whether strain differences or repeated serial passage in outbreak settings can impact virus transmission, and (vii) what role sylvatic or domestic animals could play in outbreak propagation, particularly during major epidemics such as the 2013-2015 West Africa situation. In this review, we address what we know and what we do not know about Ebola virus transmission. We also hypothesize that Ebola viruses have the potential to be respiratory pathogens with primary respiratory spread.

Description of a large measles epidemic in Democratic Republic of Congo, 2010-2013.

BACKGROUND: Although measles mortality has declined dramatically in Sub-Saharan Africa, measles remains a major public health problem in countries like the Democratic Republic of Congo (DRC). Here, we describe the large measles epidemic that occurred in the Democratic Republic of Congo between 2010 and 2013 using data from the national surveillance system as well as vaccine coverage surveys to provide a snapshot of the epidemiology of measles in DRC. METHODS: Standardized national surveillance data were used to describe measles cases from 2010 to 2013. Attack rates and case fatality ratios were calculated and the temporal and spatial evolution of the epidemic described. Data on laboratory confirmation and vaccination coverage surveys as a part of routine program monitoring are also presented. FINDINGS: Between week 1 of 2010 and week 45 of 2013, a total of 294,455 cases and 5,045 deaths were reported. The cumulative attack rate (AR) was 0.4%. The Case Fatality Ratio (CFR) was 1.7% among cases reported in health structures through national surveillance. A total of 186,178 cases (63%) were under 5 years old, representing an estimated AR of 1.4% in this age group. Following the first mass vaccination campaigns, weekly reported cases decreased by 21.5%. Results of post-vaccination campaign coverage surveys indicated sub-optimal (under 95%) vaccination coverage among children surveyed. CONCLUSIONS: The data reported here highlight the need to seek additional means to reinforce routine immunization as well as ensure the timely implementation of Supplementary Immunization Activities to prevent large and repeated measles epidemics in DRC. Although reactive campaigns were conducted in response to the epidemic, strategies to ensure that children are vaccinated in the routine system remains the foundation of measles control.

Elimination of cholera in the democratic Republic of the Congo: the new national policy.

We evaluated published and unpublished data on cholera cases and deaths reported from clinical care facilities in the 56 health districts of the Democratic Republic of Congo to the National Ministry of Health during 2000-2011. Cholera incidence was highest in the eastern provinces bordering lakes and epidemics primarily originated in this region. Along with a strong seasonal component, our data suggest a potential Vibrio cholerae reservoir in the Rift Valley lakes and the possible contribution of the lakes' fishing industry to the spread of cholera. The National Ministry of Health has committed to the elimination-rather than control-of cholera in DRC and has adopted a new national policy built on improved alert, response, case management, and prevention. To achieve this goal and implement all these measures it will require strong partners in the international community with a similar vision.

Sentinel surveillance for influenza-like illness, severe acute respiratory illness, and laboratory-confirmed influenza in Kinshasa, Democratic Republic of Congo, 2009-2011.

Little is known about influenza in central Africa. We conducted sentinel surveillance for influenza-like illness, severe acute respiratory illness, and laboratory-confirmed influenza at 5 sites in Kinshasa, Democratic Republic of Congo, from January 2009 through April 2011. We obtained samples from 4156 patients, of whom 605 (15%) had specimens containing laboratory-confirmed influenza virus. Apart from the period of pandemic influenza due to influenza A virus subtype H1N1, which occurred during August-December 2009, influenza activity peaked at least once each year from January through March, predominantly among children. These data can guide interventions to reduce the burden of influenza in the Democratic Republic of Congo and central Africa.

Dynamics of cholera outbreaks in Great Lakes region of Africa, 1978-2008.

Cholera outbreaks have occurred in Burundi, Rwanda, Democratic Republic of Congo, Tanzania, Uganda, and Kenya almost every year since 1977-1978, when the disease emerged in these countries. We used a multiscale, geographic information system-based approach to assess the link between cholera outbreaks, climate, and environmental variables. We performed time-series analyses and field investigations in the main affected areas. Results showed that cholera greatly increased during El Nino warm events (abnormally warm El Ninos) but decreased or remained stable between these events. Most epidemics occurred in a few hotspots in lakeside areas, where the weekly incidence of cholera varied by season, rainfall, fluctuations of plankton, and fishing activities. During lull periods, persistence of cholera was explained by outbreak dynamics, which suggested a metapopulation pattern, and by endemic foci around the lakes. These links between cholera outbreaks, climate, and lake environments need additional, multidisciplinary study.