[Ebola and Marburg virus disease]. / Ebola-Virus- und Marburg-Viruserkrankung.

Viral hemorrhagic fevers (VHF) are serious, often fatal diseases that affect humans and non-human primates. The nomenclature of these diseases has changed in that they are now referred to as viral diseases because the previously named symptoms of fever or hemorrhages are not obligatory. In this article, the focus will be on the VHFs Ebola and Marburg viral disease with the potential for human-to-human transmission; these diseases are so-called high-consequence infectious diseases (HCID), some with considerable potential for epidemic spread and the risk of nosocomial transmission.

A narrative review of high-level isolation unit operational and infrastructure features.

High-level isolation units (HLIUs) are specially designed facilities for care and management of patients with suspected or confirmed high-consequence infectious diseases (HCIDs), equipped with unique infrastructure and operational features. While individual HLIUs have published on their experiences caring for patients with HCIDs and two previous HLIU consensus efforts have outlined key components of HLIUs, we aimed to summarise the existing literature that describes best practices, challenges and core features of these specialised facilities. A narrative review of the literature was conducted using keywords associated with HLIUs and HCIDs. A total of 100 articles were used throughout the manuscript from the literature search or from alternate methods like reference checks or snowballing. Articles were sorted into categories (eg, physical infrastructure, laboratory, internal transport); for each category, a synthesis of the relevant literature was conducted to describe best practices, experiences and operational features. The review and summary of HLIU experiences, best practices, challenges and components can serve as a resource for units continuing to improve readiness, or for hospitals in early stages of developing their HLIU teams and planning or constructing their units. The COVID-19 pandemic, a global outbreak of mpox, sporadic cases of viral haemorrhagic fevers in Europe and the USA, and recent outbreaks of Lassa fever, Sudan Ebolavirus, and Marburg emphasise the need for an extensive summary of HLIU practices to inform readiness and response.

Community knowledge, attitude and practices regarding zoonotic viral haemorrhagic fevers in five geo-ecological zones in Tanzania.

BACKGROUND: Viral haemorrhagic fevers (VHF) cause significant economic and public health impact in Sub-Saharan Africa. Community knowledge, awareness and practices regarding such outbreaks play a pivotal role in their management and prevention. This study was carried out to assess community knowledge, attitude and practices regarding VHF in five geo-ecological zones in Tanzania. METHODS: A cross-sectional study was conducted in Buhigwe, Kalambo, Kyela, Kinondoni, Kilindi, Mvomero, Kondoa and Ukerewe districts representing five geo-ecological zones in Tanzania. Study participants were selected by multistage cluster sampling design. A semi-structured questionnaire was used to collect socio-demographic and information related to knowledge, attitude and practices regarding VHFs. Descriptive statistics and logistic regression were used for the analysis. RESULTS: A total of 2,965 individuals were involved in the study. Their mean age was 35 (SD ± 18.9) years. Females accounted for 58.2% while males 41.8%. Most of the respondents (70.6%; n = 2093) had never heard of VHF, and those who heard, over three quarters (79%) mentioned the radio as their primary source of information. Slightly over a quarter (29.4%) of the respondents were knowledgeable, 25% had a positive attitude, and 17.9% had unfavourable practice habits. The level of knowledge varied between occupation and education levels (P < 0.005). Most participants were likely to interact with a VHF survivor or take care of a person suffering from VHF (75%) or visit areas with known VHF (73%). There were increased odds of having poor practice among participants aged 36-45 years (AOR: 3.566, 95% CI: 1.593-7.821) and those living in Western, North-Eastern and Lake Victoria zones (AOR: 2.529, 95% CI: 1.071-6.657; AOR: 2.639, 95% CI: 1.130-7.580 AOR: 2.248, 95% CI: 1.073-3.844, respectively). CONCLUSION: Overall, the knowledge on VHF among communities is low, while a large proportion of individuals in the community are involved in activities that expose them to the disease pathogens in Tanzania. These findings highlight the need for strengthening health educational and promotion efforts on VHF targeting specific populations.

Common pathways targeted by viral hemorrhagic fever viruses to infect the placenta and increase the risk of stillbirth.

Viral hemorrhagic fevers (VHF) are endemic to Africa, South America and Asia and contribute to significant maternal and fetal morbidity and mortality. Viruses causing VHFs are typically zoonotic, spreading to humans through livestock, wildlife, or mosquito vectors. Some of the most lethal VHF viruses also impart a high-risk of stillbirth including ebolaviruses, Marburg virus (MARV), Lassa virus (LASV), and Rift Valley Fever Virus (RVFV). Large outbreaks and epidemics are common, though the impact on the mother, fetus and placenta is understudied from a public health, clinical and basic science perspective. Notably, these viruses utilize ubiquitous cellular surface entry receptors critical for normal placental function to enable viral invasion into multiple key cell types of the placenta and set the stage for maternal-fetal transmission and stillbirth. We employ insights from molecular virology and viral immunology to discuss how trophoblast expression of viral entry receptors for VHF viruses may increase the risk for viral transmission to the fetus and stillbirth. As the frequency of VHF outbreaks is expected to increase with worsening climate change, understanding the pathogenesis of VHF-related diseases in the placenta is paramount to predicting the impact of emerging viruses on the placenta and perinatal outcomes.

Standard of care for viral haemorrhagic fevers (VHFs): a systematic review of clinical management guidelines for high-priority VHFs.

The Sudan virus disease outbreak in Uganda in 2022 showed our vulnerability to viral haemorrhagic fevers (VHFs). Although there are regular outbreaks of VHFs with high morbidity and mortality, which disproportionally affect low-income settings, our understanding of how to treat them remains inadequate. In this systematic review, we aim to explore the availability, scope, standardisation, and quality of clinical management guidelines for VHFs. We identified 32 guidelines, 25 (78%) of which were low quality and did not have supporting evidence and eight (25%) of which had been produced or updated in the past 3 years. Guidance on supportive care and therapeutics had little detail and was sometimes contradictory. Guidelines based on uncertain evidence are a risk to patients, an ethical challenge for clinicians, and a challenge to implementing trials due to heterogeneous standards of care. We recommend a standard living guideline framework to improve the quality, scope, and applicability of guidelines. Furthermore, investments into trials should aim to identify optimal treatment strategies for VHFs and prioritise affordable and scalable interventions to improve outcomes globally.

Emergence of deadly viral haemorrhagic fever disease outbreaks in West Africa.

Recent viral hemorrhagic fever (VHF) disease outbreaks caused by Ebola virus (EBOV) and Marburg virus (MARV) in West Africa are unique and alarming. The intents of this editorial are to highlight what is known about these viruses and the disease outbreaks that they cause in the African continent and elsewhere and to raise awareness of a related virus called Lassa virus (LASV) that causes endemic viral hemorrhagic fever infections and frequent outbreaks in West Africa.

Sudan virus disease outbreak in Uganda in 2022: the case of patient zero.

In 2000, Uganda reported the first Ebola disease outbreak, and since then, the nation has had several other outbreaks. CASE PRESENTATION: On September 15, 2022, a Ugandan man aged 24 years presented with a history of fever, hematemesis, and hematochezia. A clinical suspicion of a viral hemorrhagic fever was raised, the patient was isolated, and the authorities were notified. Clinical samples subjected to real-time polymerase chain reaction analysis confirmed Sudan virus disease (SVD) caused by the Sudan Ebola virus species. The patient died 3 days later. By November 30, 2022, there had been a total of 142 confirmed cases of SVD in Uganda, with 56 (39.4%) fatalities. The case described in this report is the first patient who was hospitalized during this outbreak. CONCLUSIONS: SVD has a high mortality rate despite the best supportive management. Therefore, it is important to focus on preventive measures to control outbreaks of this disease.

Multi-Pathogen Innovative (5 in 1) Vaccine for Viral Haemorrhagic Fevers will Save More Lives.

Mankind has developed strategies to mitigate calamitous pandemics, by using vaccines. Eradication of some diseases was successful through usage of vaccines. Lassa, Yellow, Crimean-Congo, Marburg and Ebola viruses need special attention. Lassa fever, that now has a candidate vaccine, was discovered in 1969 when two missionary nurses died in Nigeria, while Yellow fever has a vaccine from its 17D attenuated strain. Crimean-Congo haemorrhagic fever is a widespread tick-borne viral disease, and the nucleoprotein and glycoproteins are identified for inclusion in a vaccine. Marburg virus is highly pathogenic with mortality rate of 90%. Ebola virus outbreak in West Africa in 2013-2016 necessitated an early introduction of a vaccine. The classical vaccine platforms are commonly used for human vaccines, and next-generation platforms, are being developed. Development of a novel multivalent vaccine against viral haemorrhagic fevers will eliminate the difficulties of single vaccines and may lead to the eradication of these diseases.

L'Humanité a développé des strategies pour atténuer les pandémiescalamiteuses, en utilisant des vaccins. L'éradication de certaines maladies a été réussie grâce à l'utilisation de vaccins. Les virus de Lassa, de la fièvre jaune, de la fièvre de Crimée-Congo, de Marburg et d'Ebola méritent une attention particulière. La fièvre de Lassa, qui dispose aujourd'hui d'un candidat vaccin, a été découverte en 1969 lors du décès de deux infirmières missionnaires au Nigeria, tandis que la fièvre jaune dispose d'un vaccin à partir de sa souche atténuée 17D. La fièvre hémorragique de Crimée-Congo est une maladie virale répandue, transmise par les tiques, et la nucléoprotéine et les glycoprotéines sont identifiées pour être incluses dans un vaccin. Le virus de Marburg est hautement pathogène avec un taux de mortalité de 90 %. L'épidémie de virus Ebola en Afrique de l'Ouest en 2013- 2016 a nécessité l'introduction rapide d'un vaccin. Les plateformes vaccinales classiques sont couramment utilisées pour les vaccins humains, et des plateformes de nouvelle sont en cours de développement. Le développement d'un nouveau vaccin multivalent contre les fièvres hémorragiques virales éliminera les difficultés des vaccins uniques et pourrait conduire à l'éradication de ces maladies. Mots clés: Innovant ; Multi-pathogène ; Développement de vaccins; Fièvres hémorragiques virales.

The number of cases, mortality and treatments of viral hemorrhagic fevers: A systematic review.

BACKGROUND: Viral hemorrhagic fevers (VHFs) are a group of diseases, which can be endemo-epidemic in some areas of the world. Most of them are characterized by outbreaks, which occur irregularly and are hard to predict. Innovative medical countermeasures are to be evaluated but due to the field specificities of emerging VHF, challenges arise when implementing clinical studies. To assess the state of the art around VHFs, we conducted a systematic review for all reports and clinical studies that included specific results on number of cases, mortality and treatment of VHFs. METHODS: The search was conducted in January 2020 based on PRISMA guidelines (PROSPERO CRD42020167306). We searched reports on the WHO and CDC websites, and publications in three international databases (MEDLINE, Embase and CENTRAL). Following the study selection process, qualitative and quantitative data were extracted from each included study. A narrative synthesis approach by each VHF was used. Descriptive statistics were conducted including world maps of cases number and case fatality rates (CFR); summary tables by VHF, country, time period and treatment studies. RESULTS: We identified 141 WHO/CDC reports and 126 articles meeting the inclusion criteria. Most of the studies were published after 2010 (n = 97 for WHO/CDC reports and n = 93 for publications) and reported number of cases and/or CFRs (n = 141 WHO/CDC reports and n = 88 publications). Results varied greatly depending on the outbreak or cluster and across countries within each VHF. A total of 90 studies focused on Ebola virus disease (EVD). EVD outbreaks were reported in Africa, where Sierra Leone (14,124 cases; CFR = 28%) and Liberia (10,678 cases; CFR = 45%) reported the highest cases numbers, mainly due to the 2014-2016 western Africa outbreak. Crimean-Congo hemorrhagic fever (CCHF) outbreaks were reported from 31 studies in Africa, Asia and Europe, where Turkey reported the highest cases number (6,538 cases; CFR = 5%) and Afghanistan the last outbreak in 2016/18 (293 cases; CFR = 43%). Regarding the 38 studies reporting results on treatments, most of them were non-randomized studies (mainly retrospective or non-randomized comparative studies), and only 10 studies were randomized controlled trials. For several VHFs, no specific investigational therapeutic option with strong proof of effectiveness on mortality was identified. CONCLUSION: We observed that number of cases and CFR varied greatly across VHFs as well as across countries within each VHF. The number of studies on VHF treatments was very limited with very few randomized trials and no strong proof of effectiveness of treatment against most of the VHFs. Therefore, there is a high need of methodologically strong clinical trials conducted in the context of VHF.

An updated review and current challenges of Guanarito virus infection, Venezuelan hemorrhagic fever.

Guanarito virus (GTOV) is a member of the family Arenaviridae and has been designated a category A bioterrorism agent by the US Centers for Disease Control and Prevention. It is endemic to Venezuela's western region, and it is the etiological agent of "Venezuelan hemorrhagic fever" (VHF). Similar to other arenaviral hemorrhagic fevers, VHF is characterized by fever, mild hemorrhagic signs, nonspecific symptoms, thrombocytopenia, and leukopenia. Patients with severe disease usually develop signs of internal bleeding. Due to the absence of reference laboratories that can handle GTOV in endemic areas, diagnosis is primarily clinical and epidemiological. No antiviral therapies are available; thus, treatment includes only supportive analgesia and fluids. GTOV is transmitted by contact with the excreta of its rodent reservoir, Zygodontomys brevicauda. The main reasons for the emergence of the disease may be the increase in the human population, migration, and changes in land use patterns in rural areas. Social and environmental changes could make VHF an important cause of underdiagnosed acute febrile illnesses in regions near the endemic areas. Although there is evidence that GTOV circulates among rodents in different Venezuelan states, VHF cases have only been reported in the states of Portuguesa and Barinas. However, due to the increased frequency of invasions by humans into wildlife habitats, it is probable that VHF could become a public health problem in the nearby regions of Colombia and Brazil. The current Venezuelan political crisis is causing an increase in the migration of people and livestock, representing a risk for the redistribution and re-emergence of infectious diseases.

Viral haemorrhagic fevers and malaria co-infections among febrile patients seeking health care in Tanzania.

BACKGROUND: In recent years there have been reports of viral haemorrhagic fever (VHF) epidemics in sub-Saharan Africa where malaria is endemic. VHF and malaria have overlapping clinical presentations making differential diagnosis a challenge. The objective of this study was to determine the prevalence of selected zoonotic VHFs and malaria co-infections among febrile patients seeking health care in Tanzania. METHODS: This facility-based cross-sectional study was carried out between June and November 2018 in Buhigwe, Kalambo, Kyela, Kilindi, Kinondoni, Kondoa, Mvomero, and Ukerewe districts in Tanzania. The study involved febrile patients seeking health care from primary healthcare facilities. Blood samples were collected and tested for infections due to malaria, Crimean-Congo haemorrhagic fever (CCHF), Ebola virus disease (EVD), Marburg virus disease (MVD), Rift Valley fever (RVF) and yellow fever (YF). Malaria infections were tested using rapid diagnostics tests while exposure to VHFs was determined by screening for immunoglobulin M antibodies using commercial enzyme-linked immunosorbent assays. The Chi-square test was used to compare the proportions. RESULTS: A total of 308 participants (mean age = 35 ± 19 years) were involved in the study. Of these, 54 (17.5%) had malaria infection and 15 (4.8%) were positive for IgM antibodies against VHFs (RVF = 8; CCHF = 2; EBV = 3; MBV = 1; YF = 1). Six (1.9%) individuals had both VHF (RVF = 2; CCHF = 1; EVD = 2; MVD = 1) and malaria infections. The highest co-infection prevalence (0.6%) was observed among individuals aged 46‒60 years (P < 0.05). District was significantly associated with co-infection (P < 0.05) with the highest prevalence recorded in Buhigwe (1.2%) followed by Kinondoni (0.9%) districts. Headache (100%) and muscle, bone, back and joint pains (83.3%) were the most significant complaints among those infected with both VHFs and malaria (P = 0.001). CONCLUSIONS: Co-infections of VHF and malaria are prevalent in Tanzania and affect more the older than the younger population. Since the overlapping symptoms in co-infected individuals may challenge accurate diagnosis, adequate laboratory diagnosis should be emphasized in the management of febrile illnesses.

Comparison of ARIMA and LSTM for prediction of hemorrhagic fever at different time scales in China.

OBJECTIVES: This study intends to build and compare two kinds of forecasting models at different time scales for hemorrhagic fever incidence in China. METHODS: Autoregressive Integrated Moving Average (ARIMA) and Long Short-Term Memory Neural Network (LSTM) were adopted to fit monthly, weekly and daily incidence of hemorrhagic fever in China from 2013 to 2018. The two models, combined and uncombined with rolling forecasts, were used to predict the incidence in 2019 to examine their stability and applicability. RESULTS: ARIMA (2, 1, 1) (0, 1, 1)12, ARIMA (1, 1, 3) (1, 1, 1)52 and ARIMA (5, 0, 1) were selected as the best fitting ARIMA model for monthly, weekly and daily incidence series, respectively. The LSTM model with 64 neurons and Stochastic Gradient Descent (SGDM) for monthly incidence, 8 neurons and Adaptive Moment Estimation (Adam) for weekly incidence, and 64 neurons and Root Mean Square Prop (RMSprop) for daily incidence were selected as the best fitting LSTM models. The values of root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of the models combined with rolling forecasts in 2019 were lower than those of the direct forecasting models for both ARIMA and LSTM. It was shown from the forecasting performance in 2019 that ARIMA was better than LSTM for monthly and weekly forecasting while the LSTM was better than ARIMA for daily forecasting in rolling forecasting models. CONCLUSIONS: Both ARIMA and LSTM could be used to build a prediction model for the incidence of hemorrhagic fever. Different models might be more suitable for the incidence prediction at different time scales. The findings can provide a good reference for future selection of prediction models and establishments of early warning systems for hemorrhagic fever.

Viral-Induced Inflammatory Coagulation Disorders: Preparing for Another Epidemic.

Several viral infectious diseases have emerged or re-emerged from wildlife vectors that have generated serious threats to global health. Increased international travel and commerce increase the risk of transmission of viral or other infectious diseases. In addition, recent climate changes accelerate the potential spread of domestic disease. The coronavirus disease 2019 (COVID-19) pandemic is an important example of the worldwide spread, and the current epidemic will unlikely be the last. Viral hemorrhagic fevers, such as dengue and Lassa fevers, may also have the potential to spread worldwide with a significant impact on public health with unpredictable timing. Based on the important lessons learned from COVID-19, it would be prudent to prepare for future pandemics of life-threatening viral diseases. The key concept that connect COVID-19 and viral hemorrhagic fever is the coagulation disorder. This review focuses on the coagulopathy of acute viral infections since hypercoagulability has been a major challenge in COVID-19, but represents a different presentation compared with viral hemorrhagic fever. However, both thrombosis and hemorrhage are understood as the result of thromboinflammation due to viral infections, and the role of anticoagulation is important to consider.

[Epidemiology of Viral Hemorrhagic Fever in Africa].

A variety of viral hemorrhagic fevers such as Ebola virus disease exist in Africa and impose a great threat in public health due to their high fatality. It is considered to be difficult to eradicate the etiological agents of viral hemorrhagic fever because they have non-human natural hosts. Therefore, the importance of public health measures remains high in addition to the urgent need for the development of medicines for treatment and prevention. Furthermore, public health measures directly lead to the accumulation of epidemiological knowledge about the diseases. As an infectious disease consultant for the World Health Organization, I have been involved with public health activities including the development of clinical guidelines, the establishment of laboratory diagnostic systems, the training for infection, prevention and control, the planning of budget for outbreak response, and the analysis of epidemiological data. On the last point, I reported the situation of Ebola virus disease outbreak in Liberia, 2014-2015 and Lassa fever outbreak in Nigeria, 2018-2019 describing the risk factors, morbidity, and mortality of the diseases.

Containment of a fatal and highly infectious disease outbreak.

This case study was designed based on several experience with several viral haemorrhagic fevers (VHFs) outbreaks responded to in Uganda between 2000 and 2016. Fictitious scenarios have been included to facilitate learning of the users. The major goal of the case study is to facilitate learners to appreciate incident detection and the incident management processes for control and containment of a fatal and highly infectious viral disease outbreak. This case study is targeted towards health scientists of medicine, nursing, biomedical laboratory and public health background. We specifically orient learners on clinical presentation of viral infections and laboratory tests considered for incident detection, conducting a risk assessment for an infectious disease, Infection Prevention and Control in the outbreak setting, skills of incident management, analysis and interpretation of epidemiological data to aid epidemic response and control decisions.

Is the COVID-19 pandemic masking the deadlier Lassa fever epidemic in Nigeria?

With the COVID-19 officially declared a pandemic, Nigeria alongside other countries is directing all its resources and manpower to contain this pandemic. However, the existence of Lassa fever (LF), a more severe, zoonotic, endemic and viral haemorrhagic fever caused by Lassa virus with higher case fatality ratio (CFR) rages on across Nigeria while receiving little or no public health attention. The simultaneously increasing cases of COVID-19 and LF across Nigeria would be catastrophic unless infection prevention and control measures toward both LF and COVID-19 outbreaks are considered alongside.

Knowledge, attitudes and practices towards viral haemorrhagic fevers amongst healthcare workers in urban and rural public healthcare facilities in the N'zérékoré prefecture, Guinea: a cross-sectional study.

BACKGROUND: The 2013-2016 Ebola epidemic in West Africa began in Guinea's Forest region, a region now considered to be at high risk for future epidemics of viral haemorrhagic fevers (VHF). Good knowledge, attitudes and practices towards VHF amongst healthcare workers in such regions are a central pillar of infection prevention and control (IPC). To inform future training in IPC, this study assesses the knowledge, attitudes and practices (KAP) towards VHF amongst healthcare workers in public healthcare facilities in the most populated prefecture in Forest Guinea, and compares results from urban and rural areas. METHODS: In June and July 2019, we interviewed 102 healthcare workers in the main urban and rural public healthcare facilities in the N'zérékoré prefecture in Forest Guinea. We used an interviewer-administered questionnaire adapted from validated KAP surveys. RESULTS: The great majority of respondents demonstrated good knowledge and favourable attitudes towards VHF. However, respondents reported some gaps in preventive practices such as VHF suspect case detection. They also reported a shortage of protective medical equipment used in everyday clinical work in both urban and rural healthcare facilities and a lack of training in IPC, especially in rural healthcare facilities. However, whether or not healthcare workers had been trained in IPC did not seem to influence their level of KAP towards VHF. CONCLUSIONS: Three years after the end of the Ebola epidemic, our findings suggest that public healthcare facilities in the N'zérékoré prefecture in Forest Guinea still lack essential protective equipment and some practical training in VHF suspect case detection. To minimize the risk of future VHF epidemics and improve management of outbreaks of infectious diseases in the region, current efforts to strengthen the public healthcare system in Guinea should encompass questions of supply and IPC training.

Evaluation of viral haemorrhagic fever surveillance system with focus on Ebola virus disease, Bawku municipality- Upper East Region, Ghana, 2011-2015.

BACKGROUND: We evaluated the Viral haemorrhagic fever (VHF) surveillance system from 2011 to 2015 in the Bawku Municipality, Upper East region, Ghana to determine whether the goals of the surveillance system are being met and to assess the performance of the system attributes. DESIGN: Descriptive secondary data analysis. SETTING: Bawku Municipality. DATA SOURCE: Review VHF surveillance records, interviewed community-based surveillance volunteers (CBSVs) and reviewed vital events registers. We also assessed the system attributes by reviewing records and interviewing key stakeholders involved in VHF surveillance system with focus on Ebola using checklist and semi structured questionnaire developed based on the Centers for Disease Control and Prevention (CDC) guidelines. MAIN OUTCOME MEASURE: System attributes of the VHF surveillance system. RESULTS: Population under surveillance was 105,849. The system required detail information about suspected cases. However, it had a simple and clear standard case definitions, and was well integrated with the IDSR. There is a regular and timely flow of information. The system captured 155 suspected cases nationwide from 2011 to 2015 and all tested negative. Of these, Upper East Region reported 10 suspected cases including 4 suspected cases from Bawku Municipality. CONCLUSION: The VHF surveillance system achieved its objectives. However, poor data quality, inadequately trained surveillance officers, and inadequate financial support are threats to the effectiveness of the system. FUNDING: This work was supported by Ghana Field Epidemiology and Laboratory Training Program (GFELTP), University of Ghana.