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.

Factors Associated with Reliable Contact Tracing During the 2021 Ebola Virus Disease Outbreak in Guinea.

BACKGROUND: In 2021, an Ebola virus disease (EVD) outbreak was declared in Guinea, linked to persistent virus from the 2014-2016 West Africa Epidemic. This paper analyzes factors associated with contact tracing reliability (defined as completion of a 21-day daily follow-up) during the 2021 outbreak, and transitively, provides recommendations for enhancing contact tracing reliability in future. METHODS: We conducted a descriptive and analytical cross-sectional study using multivariate regression analysis of contact tracing data from 1071 EVD contacts of 23 EVD cases (16 confirmed and 7 probable). RESULTS: Findings revealed statistically significant factors affecting contact tracing reliability. Unmarried contacts were 12.76× more likely to miss follow-up than those married (OR = 12.76; 95% CI [3.39-48.05]; p < 0.001). Rural-dwelling contacts had 99% lower odds of being missed during the 21-day follow-up, compared to those living in urban areas (OR = 0.01; 95% CI [0.00-0.02]; p < 0.01). Contacts who did not receive food donations were 3× more likely to be missed (OR = 3.09; 95% CI [1.68-5.65]; p < 0.001) compared to those who received them. Contacts in health areas with a single team were 8× more likely to be missed (OR = 8.16; 95% CI [5.57-11.96]; p < 0.01) than those in health areas with two or more teams (OR = 1.00; 95% CI [1.68-5.65]; p < 0.001). Unvaccinated contacts were 30.1× more likely to be missed compared to vaccinated contacts (OR = 30.1; 95% CI [5.12-176.83]; p < 0.001). CONCLUSION: Findings suggest that contact tracing reliability can be significantly influenced by various demographic and organizational factors. Considering and understanding these factors-and where possible addressing them-may be crucial when designing and implementing contact tracing strategies during future outbreaks in low-resource settings.

A community-based contact isolation strategy to reduce the spread of Ebola virus disease: an analysis of the 2018-2020 outbreak in the Democratic Republic of the Congo.

INTRODUCTION: Despite tremendous progress in the development of diagnostics, vaccines and therapeutics for Ebola virus disease (EVD), challenges remain in the implementation of holistic strategies to rapidly curtail outbreaks. We investigated the effectiveness of a community-based contact isolation strategy to limit the spread of the disease in the Democratic Republic of Congo (DRC). METHODS: We did a quasi-experimental comparison study. Eligible participants were EVD contacts registered from 12 June 2019 to 18 May 2020 in Beni and Mabalako Health Zones. Intervention group participants were isolated to specific community sites for the duration of their follow-up. Comparison group participants underwent contact tracing without isolation. The primary outcome was measured as the reproduction number (R) in the two groups. Secondary outcomes were the delay from symptom onset to isolation and case management, case fatality rate (CFR) and vaccination uptake. RESULTS: 27 324 EVD contacts were included in the study; 585 in the intervention group and 26 739 in the comparison group. The intervention group generated 32 confirmed cases (5.5%) in the first generation, while the comparison group generated 87 (0.3%). However, the 32 confirmed cases arising from the intervention contacts did not generate any additional transmission (R=0.00), whereas the 87 confirmed cases arising from the comparison group generated 99 secondary cases (R=1.14). The average delay between symptom onset and case isolation was shorter (1.3 vs 4.8 days; p<0.0001), CFR lower (12.5% vs 48.4%; p=0.0001) and postexposure vaccination uptake higher (86.0% vs 56.8%; p<0.0001) in the intervention group compared with the comparison group. A significant difference was also found between intervention and comparison groups in survival rate at the discharge of hospitalised confirmed patients (87.9% vs 47.7%, respectively; p=0.0004). CONCLUSION: The community-based contact isolation strategy used in DRC shows promise as a potentially effective approach for the rapid cessation of EVD transmission, highlighting the importance of rapidly implemented, community-oriented and trust-building control strategies.

Neglected tropical diseases in Republic of Guinea: disease endemicity, case burden and the road towards the 2030 target.

Neglected tropical diseases (NTDs) predominantly affect vulnerable and marginalized populations in tropical and subtropical areas and globally affect more than one billion people. In Guinea, the burden of NTDs is estimated to be >7.5 disability-adjusted life years per million inhabitants. Currently the Guinea NTDs master plan (2017-2020) has identified eight diseases as public health problems: onchocerciasis, lymphatic filariasis, trachoma, schistosomiasis and soil-transmitted helminthiasis, leprosy, human African trypanosomiasis and Buruli ulcer. In this review we discuss the past and the current case burden of the priority NTDs in Guinea, highlight the major milestones and discuss current and future areas of focus for achieving the 2030 target outlined by the World Health Organization.

Vector-Borne and Zoonotic Diseases in the Eastern Mediterranean Region: A Systematic Review.

BACKGROUND AND OBJECTIVE: World Health Organization Eastern Mediterranean Region (WHO EMR) has 40% people in the world in need of humanitarian assistance. This systematic review explores selected vector-borne and zoonotic diseases (VBZDs) of importance to EMR in terms of disease burden across countries and periods, disaggregated across sex, age groups, education levels, income status, and rural/urban areas, related vector or animal source reduction measures, and public health, social and economic impacts and related interventions. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and reviewed articles in PubMed, Embase, and WHO Global Index Medicus published between 1st of January 2011 and 27th of June 2022. Thirteen VBZDs with at least one reported outbreak in the last five years in the region or prioritized as per previous analysis at the WHO global and regional level and based on expert consultations, were included as part of the analysis. RESULTS: The review included 295 studies-55% on leishmaniasis and dengue combined, and 75% studies from Pakistan, Kingdom of Saudi Arabia, and Iran combined. Hospital-based and nationally representative studies constituted 60% and 10% respectively. Males were predominantly affected in most diseases; children reported high burden of Leishmaniasis, whereas elderly had a higher burden of Dengue Fever and Middle East Respiratory Syndrome. Although very few studies reported on socioeconomic differences in burden, the ones that reported showed higher burden of diseases among the disadvantaged socioeconomic groups such as the poor and the less educated. More than 80% studies reported an increase in burden over the years. CONCLUSION: The literature is scanty for most of the diseases reviewed and the number of studies from countries with humanitarian challenges is very low. The need for more nationally representative, population-based studies calls for prioritizing research investments.

Investing in preparedness for rapid detection and control of epidemics: analysis of health system reforms and their effect on 2021 Ebola virus disease epidemic response in Guinea.

The 2014-2016 West Africa Ebola Virus Disease (EVD) Epidemic devastated Guinea's health system and constituted a public health emergency of international concern. Following the crisis, Guinea invested in the establishment of basic health system reforms and crucial legal instruments for strengthening national health security in line with the WHO's recommendations for ensuring better preparedness for (and, therefore, a response to) health emergencies. The investments included the scaling up of Integrated Disease Surveillance and Response; Joint External Evaluation of International Health Regulation capacities; National Action Plan for Health Security; Simulation Exercises; One Health platforms; creation of decentralised structures such as regional and prefectural Emergency Operation Centres; Risk assessment and hazard identification; Expanding human resources capacity; Early Warning Alert System and community preparedness. These investments were tested in the subsequent 2021 EVD outbreak and other epidemics. In this case, there was a timely declaration and response to the 2021 EVD epidemic, a lower-case burden and mortality rate, a shorter duration of the epidemic and a significant reduction in the cost of the response. Similarly, there was timely detection, response and containment of other epidemics including Lassa fever and Marburg virus disease. Findings suggest the utility of the preparedness activities for the early detection and efficient containment of outbreaks, which, therefore, underlines the need for all countries at risk of infectious disease epidemics to invest in similar reforms. Doing so promises to be not only cost-effective but also lifesaving.

Investigation of and Strategies to Control the Final Cluster of the 2018-2020 Ebola Virus Disease Outbreak in the Eastern Democratic Republic of Congo.

Background: On April 10, 2020, while the independent committee of the International Health Regulation was meeting to decide whether the 10th Ebola outbreak in the Demogratic Republic of Congo still constituted a Public Health Emergency of International Concern, a new confirmed case was reported in the city of Beni, the last epicenter of the epidemic. This study aimed to understand the source of this cluster and learn from the implemented control strategies for improved response in the future. Methods: We conducted a combined epidemiological and genomic investigation to understand the origins and dynamics of transmission within this cluster and describe the strategy that successfully controlled the outbreak. Results: Eight cases were identified as belonging to this final cluster. A total of 1028 contacts were identified. Whole-genome sequencing revealed that all cases belonged to the same cluster, the closest sequence to which was identified as a case from the Beni area with symptom onset in July 2019 and a difference of just 31 nucleotides. Outbreak control measures included community confinement of high-risk contacts. Conclusions: This study illustrates the high risk of additional flare-ups in the period leading to the end-of-outbreak declaration and the importance of maintaining enhanced surveillance and confinement activities to rapidly control Ebola outbreaks.

Case Report: COVID-19 and Lassa Fever Coinfection in an Ebola Suspected Patient in Guinea.

In this case report, we describe a clinical presentation and therapeutic history of a unique case diagnosed with Lassa fever and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a 23-year-old man from Yomou prefecture in southeast Guinea identified with suspected Ebola Virus Disease (EVD) in the midst of an ongoing outbreak of that disease in the same region. On May 3, 2021, he was admitted to the Nzérékoré Epidemic disease treatment center where his clinical condition deteriorated significantly. Laboratory testing performed on the same day reveals a negative EVD polymerase chain reaction (PCR). Three days later, the patient was tested positive for SARS-CoV-2 and Lassa fever by reverse transcriptase PCR (RT-PCR) assays. Laboratory examination also indicated severe hematological and biochemical deteriorations in the patient. This case substantiates the need for systematic differential diagnosis during epidemic-prone disease outbreaks to better manage severely unwell patients.

Novel Use of Capture-Recapture Methods to Estimate Completeness of Contact Tracing during an Ebola Outbreak, Democratic Republic of the Congo, 2018-2020.

Despite its critical role in containing outbreaks, the efficacy of contact tracing, measured as the sensitivity of case detection, remains an elusive metric. We estimated the sensitivity of contact tracing by applying unilist capture-recapture methods on data from the 2018-2020 outbreak of Ebola virus disease in the Democratic Republic of the Congo. To compute sensitivity, we applied different distributional assumptions to the zero-truncated count data to estimate the number of unobserved case-patients with any contacts and infected contacts. Geometric distributions were the best-fitting models. Our results indicate that contact tracing efforts identified almost all (n = 792, 99%) of case-patients with any contacts but only half (n = 207, 48%) of case-patients with infected contacts, suggesting that contact tracing efforts performed well at identifying contacts during the listing stage but performed poorly during the contact follow-up stage. We discuss extensions to our work and potential applications for the ongoing coronavirus pandemic.

Evaluation of Early Warning, Alert and Response System for Ebola Virus Disease, Democratic Republic of the Congo, 2018-2020.

The 10th and largest Ebola virus disease epidemic in the Democratic Republic of the Congo (DRC) was declared in North Kivu Province in August 2018 and ended in June 2020. We describe and evaluate an Early Warning, Alert and Response System (EWARS) implemented in the Beni health zone of DRC during August 5, 2018-June 30, 2020. During this period, 194,768 alerts were received, of which 30,728 (15.8%) were validated as suspected cases. From these, 801 confirmed and 3 probable cases were detected. EWARS showed an overall good performance: sensitivity and specificity >80%, nearly all (97%) of alerts investigated within 2 hours of notification, and good demographic representativeness. The average cost of the system was US $438/case detected and US $1.8/alert received. The system was stable, despite occasional disruptions caused by political insecurity. Our results demonstrate that EWARS was a cost-effective component of the Ebola surveillance strategy in this setting.

Development and implementation of the Ebola Exposure Window Calculator: A tool for Ebola virus disease outbreak field investigations.

During an Ebola virus disease (EVD) outbreak, calculating the exposure window of a confirmed case can assist field investigators in identifying the source of infection and establishing chains of transmission. However, field investigators often have difficulty calculating this window. We developed a bilingual (English/French), smartphone-based field application to assist field investigators in determining the exposure window of an EVD case. The calculator only requires the reported date of symptoms onset and the type of symptoms present at onset or the date of death. Prior to the release of this application, there was no similar electronic capability to enable consistent calculation of EVD exposure windows for field investigators. The Democratic Republic of the Congo Ministry of Health endorsed the application and incorporated it into trainings for field staff. Available for Apple and Android devices, the calculator continues to be downloaded even as the eastern DRC outbreak resolved. We rapidly developed and implemented a smartphone application to estimate the exposure window for EVD cases in an outbreak setting.

Ebola Virus Transmission Initiated by Relapse of Systemic Ebola Virus Disease.

During the 2018-2020 Ebola virus disease (EVD) outbreak in North Kivu province in the Democratic Republic of Congo, EVD was diagnosed in a patient who had received the recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) (Merck). His treatment included an Ebola virus (EBOV)-specific monoclonal antibody (mAb114), and he recovered within 14 days. However, 6 months later, he presented again with severe EVD-like illness and EBOV viremia, and he died. We initiated epidemiologic and genomic investigations that showed that the patient had had a relapse of acute EVD that led to a transmission chain resulting in 91 cases across six health zones over 4 months. (Funded by the Bill and Melinda Gates Foundation and others.).

Public Health Program for Decreasing Risk for Ebola Virus Disease Resurgence from Survivors of the 2013-2016 Outbreak, Guinea.

At the end of the 2013-2016 Ebola virus disease outbreak in Guinea, we implemented an alert system for early detection of Ebola resurgence among survivors. Survivors were asked to report health alerts in their household and provide body fluid specimens for laboratory testing. During April-September 2016, a total of 1,075 (88%) of 1,215 survivors participated in the system; follow up occurred at a median of 16 months after discharge (interquartile range 14-18 months). Of these, 784 acted as focal points and reported 1,136 alerts (including 4 deaths among survivors). A total of 372 (91%) of 408 eligible survivors had >1 semen specimen tested; of 817 semen specimens, 5 samples from 4 survivors were positive up to 512 days after discharge. No lochia (0/7) or breast milk (0/69) specimens tested positive. Our findings underscore the importance of long-term monitoring of survivors' semen samples in an Ebola-affected country.

Impact of mass vaccination campaigns on measles transmission during an outbreak in Guinea, 2017.

OBJECTIVE: To estimate the time-dependent measles effective reproduction number (Rt) as an indicator of the impact of three outbreak response vaccination (ORV) campaigns on measles transmission during a nationwide outbreak in Guinea. METHODS: Rt represents the average number of secondary cases generated by a single primary case in a partially immune population during a given time period. Measles Rt was estimated using daily incidence data for 3952 outbreak-associated measles cases in Guinea in 2017 for the time periods prior to, between, and following each of three ORV campaigns using a simple and extensible mathematical model. RESULTS: Rt was estimated to be above the threshold value of 1 during the initial growth period of the outbreak until the first ORV campaign began on March 13 (Rt = 1.60, 95% CI: 1.55-1.67). It subsequently dropped below 1 and remained <1 through the end of the year (range: 0.71-0.91), although low levels of transmission persisted. CONCLUSIONS: Reduction in Rt coincided with implementation of the ORV campaigns, indicating success of the campaigns at maintaining measles transmission intensity below epidemic growth levels. However, persistent measles transmission remains an issue in Guinea due to insufficient levels of herd immunity. Estimation of Rt should be further leveraged to help decision makers and field staff understand outbreak progress and the timing and type of vaccination efforts needed to halt transmission.

Assessment of a health facility based active case finding system for Ebola virus disease in Mbandaka, Democratic Republic of the Congo, June-July 2018.

BACKGROUND: The ninth outbreak of Ebola Virus Disease (EVD) in the Democratic Republic of the Congo occurred in Équateur Province from 8 May-24 July 2018. A system of health facility (HF)-based active case finding (ACF) was implemented in Mbandaka, a regional capital with four confirmed EVD cases, following completion of contact tracing. The goal of this HF-based ACF system was to look for undetected EVD cases among patients that visited HFs beginning one week prior to the system's implementation. METHODS: From 23 June - 24 July 2018, ACF teams visited HFs in Mbandaka and reviewed all medical records as far back as 17 June for any consultations meeting the suspected EVD case definition. The teams then assessed whether to validate these as suspected EVD cases based on factors such as recovery, epidemiological links, and their clinical judgement. ACF teams also assessed HFs' awareness of EVD symptoms and the process for alerting suspected cases. We calculated descriptive statistics regarding the characteristics of reviewed consultations, alert cases, and visited HFs. We also used univariate and multivariate random effects logistic regression models to evaluate the impact of repeated ACF visits to the same HF on the staff's awareness of EVD. RESULTS: ACF teams reviewed 37,746 consultations, of which 690 met the definition of a suspected case of EVD. Two were validated as suspected EVD cases and transferred to the Ebola Treatment Unit for testing; both tested negative. Repeated ACF visits to the same HF were significantly associated with improved EVD awareness (p < 0.001) in univariate and multivariate analyses. CONCLUSION: HF-based ACF during EVD outbreaks may improve EVD awareness and reveal many individuals meeting the suspected case definition. However, many who meet this definition may not have EVD, depending on the population size covered by ACF and amount of ongoing EVD transmission. Given the burdensome procedure of testing suspected EVD cases, future HF-based ACF systems would benefit from improved clarity on which patients require further testing.

Subsequent mortality in survivors of Ebola virus disease in Guinea: a nationwide retrospective cohort study.

BACKGROUND: A record number of people survived Ebola virus infection in the 2013-16 outbreak in west Africa, and the number of survivors has increased after subsequent outbreaks. A range of post-Ebola sequelae have been reported in survivors, but little is known about subsequent mortality. We aimed to investigate subsequent mortality among people discharged from Ebola treatment units. METHODS: From Dec 8, 2015, Surveillance Active en ceinture, the Guinean national survivors' monitoring programme, attempted to contact and follow-up all survivors of Ebola virus disease who were discharged from Ebola treatment units. Survivors were followed up until Sept 30, 2016, and deaths up to this timepoint were recorded. Verbal autopsies were done to gain information about survivors of Ebola virus disease who subsequently died from their closest family members. We calculated the age-standardised mortality ratio compared with the general Guinean population, and assessed risk factors for mortality using survival analysis and a Cox proportional hazards regression model. FINDINGS: Of the 1270 survivors of Ebola virus disease who were discharged from Ebola treatment units in Guinea, information was retrieved for 1130 (89%). Compared with the general Guinean population, survivors of Ebola virus disease had a more than five-times increased risk of mortality up to Dec 31, 2015 (age-standardised mortality ratio 5·2 [95% CI 4·0-6·8]), a mean of 1 year of follow-up after discharge. Thereafter (ie, from Jan 1-Sept 30, 2016), mortality did not differ between survivors of Ebola virus disease and the general population. (0·6 [95% CI 0·2-1·4]). Overall, 59 deaths were reported, and the cause of death was tentatively attributed to renal failure in 37 cases, mostly on the basis of reported anuria. Longer stays (ie, equal to or longer than the median stay) in Ebola treatment units were associated with an increased risk of late death compared with shorter stays (adjusted hazard ratio 2·62 [95% CI 1·43-4·79]). INTERPRETATION: Mortality was high in people who recovered from Ebola virus disease and were discharged from Ebola treatment units in Guinea. The finding that survivors who were hospitalised for longer during primary infection had an increased risk of death, could help to guide current and future survivors' programmes and in the prioritisation of funds in resource-constrained settings. The role of renal failure in late deaths after recovery from Ebola virus disease should be investigated. FUNDING: WHO, International Medical Corps, and the Guinean Red Cross.

Investigation of a cross-border case of Lassa fever in West Africa.

BACKGROUND: Infectious disease prevention and control strategies require a coordinated, transnational approach. To establish core capacities of the International Health Regulations (IHR), the World Health Organization (WHO) developed the Integrated Diseases Surveillance and Response (IDSR) strategy. Epidemic-prone Lassa fever, caused by Lassa virus, is an endemic disease in the West African countries of Ghana, Guinea, Mali, Benin, Liberia, Sierra Leone, Togo and Nigeria. It's one of the major public health threats in these countries. Here it is reported an epidemiological investigation of a cross-border case of Lassa fever, which demonstrated the importance of strengthened capacities of IHR and IDSR. CASE PRESENTATION: On January 9th, 2018 a 35-year-old Guinean woman with fever, neck pain, body pain, and vomiting went to a hospital in Ganta, Liberia. Over the course of her illness, the case visited various health care facilities in both Liberia and Guinea. A sample collected on January 10th was tested positive for Lassa virus by RT-PCR in a Liberian laboratory. The Guinean Ministry of Health (MoH) was officially informed by WHO Country Office for Guinea and for Liberia. CONCLUSION: This case report revealed how an epidemic-prone disease such as Lassa fever can rapidly spread across land borders and how such threat can be quickly controlled with communication and collaboration within the IHR framework.