The Use of Intraventricular Instillation of Vancomycin to Prevent External Ventricular Drainage Related Infection: A Clinical Prospective Study.

BACKGROUND: External ventricular drainage (EVD)-related infection (ERI) represents an important condition with potential high morbidity with significant impact on patient outcomes. Prophylactic systemic antibiotics are routinely administered to patients with EVD, but they do not significantly lower the incidence of ERIs. Intraventricular treatment with vancomycin appeared to be safe and effective, but most reports are case-reports/-series and retrospective studies. METHODS: A prospective non-randomized case-control study was conducted in a consecutive series of 116 patients treated with EVD insertion. The study includes the group of patients treated with intrathecal vancomycin (Group A, 62 patients) compared with the control group treated with daily intravenous cefazolin (Group B, 54 patients). RESULTS: No statistically significant differences were found between the 2 groups with regard to the duration of catheterization and occurrence of ERI during hospitalization. EVD was replaced in 16 cases (25.8%) in group A and in 12 cases (22.2%) in the control group B (P 0.67). Three cases (4.8%) of ERI have been found in group A and 5 (9.3%) in the control group (P = 0.34). All reported cases of infection in group A were caused by gram-negative agents; on the opposite, cases of infections in the control group B were caused above all by gram-positive bacteria with a statistical difference (P = 0.03). CONCLUSIONS: In this first prospective study on this topic, we found that intrathecal Vancomycin administration in EVDs does not reduce the occurrence of ERI compared with intravenous cefazolin prophylaxis, but induces selection of gram-negative bacteria.

Trends in Utilization of Temporary and Permanent Cerebrospinal Fluid Diversion and Catheter Cerebral Angiography for Patients with Aneurysmal Subarachnoid Hemorrhage in the United States.

INTRODUCTION: We sought to analyze the rate of utilization of methods of cerebrospinal fluid diversion over time in a nationally representative cohort of patients admitted with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The Nationwide Inpatient Sample was queried for patients admitted with aSAH from 2006 to 2018. Patients who received external ventricular drainage (EVD), lumbar drainage, ventriculoperitoneal shunt (VPS), and cerebral angiography were then identified. A Cochrane-Armitage test was conducted to assess the linear trend of proportions of EVD, lumbar drains, VPS, and mean cerebral angiograms per admission. Four regression analyses were conducted to infer the association of baseline variables to EVD, lumbar drain, VPS, and mean number of cerebral angiographies. RESULTS: A total of 133,567 admissions were identified from 2006-2018 involving aSAH. Of these, 41.82% received EVD, 6.22% received lumbar drainage, 10.58% received VPS, and 75.03% had cerebral angiograms. There was an average upward trend of 1.57% in annual EVD utilization, downward trend of -0.28% in utilization of lumbar drainage, no changes in VPS utilization, and an upward trend of 0.04 angiograms per year (P < 0.001). There was a higher proportion of Black patients treated with EVD and VPS in both urban teaching hospitals and large hospitals. CONCLUSIONS: Our results show the temporal trends in utilization of temporary and permanent methods of cerebrospinal fluid diversion and catheter cerebral angiography among patients with aSAH in the United States. The underutilization of VPS following EVD and the differences in EVD and VPS utilization depending on race and hospital size deserve further exploration.

Natural History of Aerosol-Induced Ebola Virus Disease in Rhesus Macaques.

Ebola virus disease (EVD) is a serious global health concern because case fatality rates are approximately 50% due to recent widespread outbreaks in Africa. Well-defined nonhuman primate (NHP) models for different routes of Ebola virus exposure are needed to test the efficacy of candidate countermeasures. In this natural history study, four rhesus macaques were challenged via aerosol with a target titer of 1000 plaque-forming units per milliliter of Ebola virus. The course of disease was split into the following stages for descriptive purposes: subclinical, clinical, and decompensated. During the subclinical stage, high levels of venous partial pressure of carbon dioxide led to respiratory acidemia in three of four of the NHPs, and all developed lymphopenia. During the clinical stage, all animals had fever, viremia, and respiratory alkalosis. The decompensatory stage involved coagulopathy, cytokine storm, and liver and renal injury. These events were followed by hypotension, elevated lactate, metabolic acidemia, shock and mortality similar to historic intramuscular challenge studies. Viral loads in the lungs of aerosol-exposed animals were not distinctly different compared to previous intramuscularly challenged studies. Differences in the aerosol model, compared to intramuscular model, include an extended subclinical stage, shortened clinical stage, and general decompensated stage. Therefore, the shortened timeframe for clinical detection of the aerosol-induced disease can impair timely therapeutic administration. In summary, this nonhuman primate model of aerosol-induced EVD characterizes early disease markers and additional details to enable countermeasure development.

Delayed Disease in Cynomolgus Macaques Exposed to Ebola Virus by an Intranasal Route.

Ebola virus remains a significant public health concern due to high morbidity and mortality rates during recurrent outbreaks in endemic areas. Therefore, the development of countermeasures against Ebola virus remains a high priority, and requires the availability of appropriate animal models for efficacy evaluations. The most commonly used nonhuman primate models for efficacy evaluations against Ebola virus utilize the intramuscular or aerosol route of exposure. Although clinical disease signs are similar to human cases, disease progression in these models is much more rapid, and this can pose significant hurdles for countermeasure evaluations. The objective of the present study was to evaluate the Ebola virus disease course that arises after cynomolgus macaques are exposed to Ebola virus by a mucosal route (the intranasal route). Two different doses (10 pfu and 100 pfu) and delivery methodologies (drop-wise and mucosal atomization device) were evaluated on this study. Differences in clinical disease between dose and delivery groups were not noted. However, a delayed disease course was identified for approximately half of the animals on study, and this delayed disease was dose and administration method independent. Therefore, it appears that mucosal exposure with Ebola virus results in a disease course in cynomolgus macaques that more accurately replicates that which is documented for human cases. In summary, the data presented support the need for further development of this model as a possible alternative to parenteral and small-particle aerosol models for the study of human Ebola virus disease and for countermeasure evaluations.

Assessing the determinants of Ebola virus disease transmission in Baka Community of the Tropical Rainforest of Cameroon.

BACKGROUND: Ebola virus disease (EVD) is a severe, often fatal illness in humans and nonhuman primates caused by the Ebola virus. The recently approved rVSV-EBOV vaccine is not available in many high-risk countries hence prevention is paramount. The design of effective prevention interventions requires an understanding of the factors that expose communities at risk. It was based on this that we investigated the Baka community of Abong-Mbang Health District in tropical rain forest of Cameroon. METHODS: A cross-sectional study was conducted with participants randomly selected from 13 villages in Abong-Mbang by multi-stage cluster sampling. A questionnaire was administered to them to collect demographic information, data on knowledge of EVD, their feeding and health-seeking behaviour. Data was analyzed using the chi-square test. Knowledge of EVD was assessed using an 8 item Morisky Scale. An adapted Threat Capability Basic Risk Assessment Guide was used to determine their risk of exposure to infection. RESULTS: A total of 510 participants, most of whom were hunters (31.4%), farmers (29.8%), and had primary education (62.7%), were included in this study. Although 83.3% participants had heard of EVD, most (71%) did not know its cause. Their source of information was mainly informal discussions in the community (49%). Misconceptions were identified with regards to the cause and mode of transmission. Only 43.1% accepted EVD could be transmitted from human-to-human. Generally, participants' knowledge of EVD was poor. Demographic factors such as level of education, occupation and ethnic group significantly affected knowledge of EVD. The majority of participants were at a very high risk of exposure to infection as they consumed various forms of bush meat and were involved in other risky practices such as scarification and touching of corpses. Although over half of participants seek medical care, most of them preferred traditional medicine. Socio-cultural and service-related factors were deterrent factors to medical care. CONCLUSION: Participants generally had poor knowledge of EVD and were at high risk of infection. We recommend rigorous sensitization campaigns in the study area to educate the population on EVD and clarify the misconceptions identified. EVD surveillance is recommended particularly as outbreaks have often been reported in the Congo Basin.

Effects of Ebola Virus Disease Outbreak on Bush Meat Enterprise and Environmental Health Risk Behavior Among Households in South-East Nigeria.

The 2014 disease outbreak in West Africa of the Ebola virus was the longest, largest, deadliest, and most complex epidemic of its kind in history. It was believed to have originated from bushmeat consumption and exhibited sustained human-to-human transmission. We assessed the effects of the virus outbreak in West Africa on bushmeat enterprise and environmental health risk behaviors among households in Nigeria. We adopted a multistage sampling technique to select 100 respondents. We structured two sets of questionnaires for both bushmeat sellers and consumers. The questionnaire contained information about the respondent's socioeconomic characteristics; perceived causes of the Ebola outbreak; risk behaviors; level of sales; and consumption before, during, and after the Ebola outbreak. We found a significant decrease in the levels of sales and consumption of bushmeat during the outbreak. Consumers perceived touching an infected person, but not eating bushmeat, as a significant mode of Ebola transmission. Although respondents knew about some practices that help to prevent Ebola, they did not practice these to a reasonable extent. We also found that females were 25% more likely than males to consume bushmeat during the outbreak. Given these findings, we recommend that the government should sensitize people and educate them on risk prevention behaviors they should adopt to prevent the transmission of the Ebola disease.

Infection Rates and Risk Factors for Infection Among Health Workers During Ebola and Marburg Virus Outbreaks: A Systematic Review.

Background: Infection in health workers (HWs) has characterized outbreaks of Ebola virus disease (EVD) and Marburg virus disease (MVD). We conducted a systematic review to investigate infection and mortality rates and common exposure risks in HWs in EVD and MVD outbreaks. Methods: We searched the EMBASE and PubMed databases to identify articles posted before 27 December 2017, with no language restrictions. Data on the number, frequency, and mortality of HW infection and exposure risks were extracted. Results: Ninety-four articles related to 22 outbreaks were included. HW infections composed 2%-100% of cases in EVD and 5%-50% of cases in MVD outbreaks. Among exposed HWs, 0.6%-92% developed EVD, and 1%-10% developed MVD. HW infection rates were consistent through outbreaks. The most common exposure risk situations were inadequate personal protective equipment and exposure to patients with unrecognized EVD/MVD. Similar risks were reported in past EVD/MVD outbreaks and in the recent outbreak in West Africa. Conclusions: Many outbreaks reported high proportions of infected HWs. Similar HW infection rates and exposure risk factors in both past and recent EVD and MVD outbreaks emphasize the need to improve the implementation of appropriate infection control measures consistently across all healthcare settings.

Animal models for filovirus infections.

The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates (NHPs), causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.

Development of Potential Small Molecule Therapeutics for Treatment of Ebola Virus Disease.

Ebola virus has caused 26 outbreaks in 10 different countries since its identification in 1976, making it one of the deadliest emerging viral pathogens. The most recent outbreak in West Africa from 2014-16 was the deadliest yet and culminated in 11,310 deaths out of 28,616 confirmed cases. Currently, there are no FDA-approved therapeutics or vaccines to treat Ebola virus infections. The slow development of effective vaccines combined with the severity of past outbreaks emphasizes the need to accelerate research into understanding the virus lifecycle and the development of therapeutics for post exposure treatment. Here we present a summary of the major findings on the Ebola virus replication cycle and the therapeutic approaches explored to treat this devastating disease. The major focus of this review is on small molecule inhibitors.

Overcoming Operational Challenges to Ebola Case Investigation in Sierra Leone.

The Ebola virus disease (EVD) epidemic that hit West Africa in 2013 was the worst outbreak of EVD in recorded history. While much has been published regarding the international and national-level EVD responses, there is a dearth of literature on district-level coordination and operational structures, successes, and failures. This article seeks to understand how the EVD response unfolded at the district level, namely the challenges to operationalizing EVD surveillance over the course of the outbreak in Port Loko and Kambia districts of Sierra Leone. We present here GOAL Global's understanding of the fundamental challenges to case investigation operations during the EVD response, including environmental and infrastructural, sociocultural, and political and organizational challenges, with insight complemented by a survey of 42 case investigators. Major challenges included deficiencies in transportation and communication resources, low morale and fatigue among case investigators, mismanagement of data, mistrust among communities, and leadership challenges. Without addressing these operational challenges, technical surveillance solutions are difficult to implement and hold limited relevance, due to the poor quality and quantity of data being collected. The low prioritization of operational needs came at a high cost. To mediate this, GOAL addressed these operational challenges by acquiring critical transportation and communication resources to facilitate case investigation, including vehicles, boats, fuel, drivers, phones, and closed user groups; addressing fatigue and low morale by hiring more case investigators, making timely payments, arranging for time off, and providing meals and personal protective equipment; improving data tracking efforts through standard operating procedures, training, and mentorship to build higher-quality case histories and make it easier to access information; strengthening trust in communities by ensuring familiarity and consistency of case investigators; and improving operational leadership challenges through meetings and regular coordination, establishing an active surveillance strategy in Port Loko, and conducting an after-action review. Resolving or addressing these challenges was of primary importance, and requisite for the implementation of technical epidemiological complements to EVD case investigation.

Emerging Infectious Diseases in Pregnancy.

It has been recognized for centuries that pregnant women have unique susceptibilities to many infectious diseases that predispose them to untoward outcomes compared with the general adult population. It is thought a combination of adaptive alterations in immunity to allow for the fetal allograft combined with changes in anatomy and physiology accompanying pregnancy underlie these susceptibilities. Emerging infectious diseases are defined as those whose incidence in humans has increased in the past two decades or threaten to increase in the near future. The past decade alone has witnessed many such outbreaks, each with its own unique implications for pregnant women and their unborn fetuses as well as lessons for the health care community regarding response and mitigation. Examples of such outbreaks include, but are not limited to, severe acute respiratory syndrome, the 2009 H1N1 pandemic influenza, Ebola virus, and, most recently, the Zika virus. Although each emerging pathogen has unique features requiring specific considerations, there are many underlying principles that are shared in the recognition, communication, and mitigation of such infectious outbreaks. Some of these key principles include disease-specific delineation of transmission dynamics, understanding of pathogen-specific effects on both mothers and fetuses, and advance planning and contemporaneous management that prioritize communication among public health experts, clinicians, and patients. The productive and effective working collaboration among the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine has been a key partnership in the successful communication and management of such outbreaks for women's health care providers and patients alike. Going forward, the knowledge gained over the past decade will undoubtedly continue to inform future responses and will serve to optimize the education and care given to pregnant women in the face of current and future emerging infectious disease outbreaks.

Strategy and technology to prevent hospital-acquired infections: Lessons from SARS, Ebola, and MERS in Asia and West Africa.

Hospital-acquired infections (HAIs) are serious problems for healthcare systems, especially in developing countries where public health infrastructure and technology for infection preventions remain undeveloped. Here, we characterized how strategy and technology could be mobilized to improve the effectiveness of infection prevention and control in hospitals during the outbreaks of Ebola, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) in Asia and West Africa. Published literature on the hospital-borne outbreaks of SARS, Ebola, and MERS in Asia and West Africa was comprehensively reviewed. The results showed that healthcare systems and hospital management in affected healthcare facilities had poor strategies and inadequate technologies and human resources for the prevention and control of HAIs, which led to increased morbidity, mortality, and unnecessary costs. We recommend that governments worldwide enforce disaster risk management, even when no outbreaks are imminent. Quarantine and ventilation functions should be taken into consideration in architectural design of hospitals and healthcare facilities. We also recommend that health authorities invest in training healthcare workers for disease outbreak response, as their preparedness is essential to reducing disaster risk.

Lessons about Causes and Management of an Ebola Outbreak.

Ebola virus disease (EVD) is one of the deadliest viral diseases. It is characterized by a high mortality rate due to the lack of effective and safe treatments or vaccines and its ability to spread at an unstoppable pace. The West Africa outbreak ended but the disease may strike again at any time. The latest epidemic was, by far, the deadliest to date. The most concern was why this outbreak was so different from the previous ones. We proposed in this review firstly to summarize the principal causes of its unprecedented spread and secondly to identify the steps for an effective management approach of a future Ebola outbreak. Attributes of the affected populations and insufficient control efforts were the main reasons of its amplification. This was complicated by a delayed international response. The health crisis was ignored for months until it got out of control. The management of Ebola presents a multitude of challenges in terms of preparedness and capacity to face an outbreak. In addition to the need for adequate health care facilities, ongoing surveillance tools, appropriate training of health workers and raising population awareness, readiness requires a large scale and coordinated international intervention to support affected and at-risk nations, to intensify their response activities and to strengthen their capacities. Constant interventions after the outbreak are still needed to ensure that vital health and related service institutions in these countries are fully prepared to respond to an eminent epidemic.

Communicating the Ontological Narrative of Ebola: An Emerging Disease in the Time of "Epidemic 2.0".

In this article, we critically analyze the implications of "Epidemic 2.0"-specifically the formative role of social media (as an exemplar of Web 2.0 technology) in disseminating information during epidemics. We use a narrative analysis framework to study the Ebola-related messaging on the official Facebook pages of the World Health Organization (WHO) and the Center for Disease Control (CDC) in the wake of the recent epidemic in Western Africa. Using as our corpus all the messages on these pages between the period of July 1 and October 15, 2014, our analysis traces the development of an ontological Ebola narrative: a specific, historically contingent, ideological plot that reaffirms contemporary Western anxieties around emerging infections. Our analysis focuses on the evolution of this ontological narrative from a) consulting and containment, to b) an international concern, and c) the possibility of an epidemic in the United States.

Molecular mechanisms of Ebola pathogenesis.

Ebola viruses (EBOVs) and Marburg viruses (MARVs) are among the deadliest human viruses, as highlighted by the recent and widespread Ebola virus outbreak in West Africa, which was the largest and longest epidemic of Ebola virus disease (EVD) in history, resulting in significant loss of life and disruptions across multiple continents. Although the number of cases has nearly reached its nadir, a recent cluster of 5 cases in Guinea on March 17, 2016, has extended the enhanced surveillance period to June 15, 2016. New, enhanced 90-d surveillance windows replaced the 42-d surveillance window to ensure the rapid detection of new cases that may arise from a missed transmission chain, reintroduction from an animal reservoir, or more important, reemergence of the virus that has persisted in an EVD survivor. In this review, we summarize our current understanding of EBOV pathogenesis, describe vaccine and therapeutic candidates in clinical trials, and discuss mechanisms of viral persistence and long-term health sequelae for EVD survivors.

Associations between Mental Health and Ebola-Related Health Behaviors: A Regionally Representative Cross-sectional Survey in Post-conflict Sierra Leone.

BACKGROUND: Little attention has been paid to potential relationships between mental health, trauma, and personal exposures to Ebola virus disease (EVD) and health behaviors in post-conflict West Africa. We tested a conceptual model linking mental health and trauma to EVD risk behaviors and EVD prevention behaviors. METHODS AND FINDINGS: Using survey data from a representative sample in the Western Urban and Western Rural districts of Sierra Leone, this study examines associations between war exposures, post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, and personal EVD exposure (e.g., having family members or friends diagnosed with EVD) and EVD-related health behaviors among 1,008 adults (98% response rate) from 63 census enumeration areas of the Western Rural and Western Urban districts randomly sampled at the height of the EVD epidemic (January-April 2015). Primary outcomes were EVD risk behaviors (14 items, Cronbach's α = 0.84) and EVD prevention behaviors (16 items, Cronbach's α = 0.88). Main predictors comprised war exposures (8 items, Cronbach's α = 0.85), anxiety (10 items, Cronbach's α = 0.93), depression (15 items, Cronbach's α = 0.91), and PTSD symptoms (16 items, Cronbach's α = 0.93). Data were analyzed using two-level, population-weighted hierarchical linear models with 20 multiply imputed datasets. EVD risk behaviors were associated with intensity of depression symptoms (b = 0.05; 95% CI 0.00, 0.10; p = 0.037), PTSD symptoms (b = 0.10; 95% CI 0.03, 0.17; p = 0.008), having a friend diagnosed with EVD (b = -0.04; 95% CI -0.08, -0.00; p = 0.036), and war exposures (b = -0.09; 95% CI -0.17, -0.02; p = 0.013). EVD prevention behaviors were associated with higher anxiety (b = 0.23; 95% CI 0.06, 0.40; p = 0.008), having a friend diagnosed with EVD (b = 0.15; 95% CI 0.04, 0.27; p = 0.011), and higher levels of war exposure (b = 0.45; 95% CI 0.16, 0.74; p = 0.003), independent of mental health. PTSD symptoms were associated with lower levels of EVD prevention behavior (b = -0.24; 95% CI -0.43, -0.06; p = 0.009). CONCLUSIONS: In post-conflict settings, past war trauma and mental health problems are associated with health behaviors related to combatting EVD. The associations between war trauma and both EVD risk behaviors and EVD prevention behaviors may be mediated through two key mental health variables: depression and PTSD symptoms. Considering the role of mental health in the prevention of disease transmission may help fight continuing and future Ebola outbreaks in post-conflict Sierra Leone. This sample is specific to Freetown and the Western Area and may not be representative of all of Sierra Leone. In addition, our main outcomes as well as personal EVD exposure, war exposures, and mental health predictors rely on self-report, and therefore raise the possibility of common methods bias. However, the findings of this study may be relevant for understanding dynamics related to EVD and mental health in other major capital cities in the EVD-affected countries of West Africa.

Factors Underlying Ebola Virus Infection Among Health Workers, Kenema, Sierra Leone, 2014-2015.

BACKGROUND: Ebola virus disease (EVD) in health workers (HWs) has been a major challenge during the 2014-2015 outbreak. We examined factors associated with Ebola virus exposure and mortality in HWs in Kenema District, Sierra Leone. METHODS: We analyzed data from the Sierra Leone National Viral Hemorrhagic Fever Database, contact tracing records, Kenema Government Hospital (KGH) staff and Ebola Treatment Unit (ETU) rosters, and burial logs. RESULTS: From May 2014 through January 2015, 600 cases of EVD originated in Kenema District, including 92 (15%) HWs, 66 (72%) of whom worked at KGH. Among KGH medical staff and international volunteers, 18 of 62 (29%) who worked in the ETU developed EVD, compared with 48 of 83 (58%) who worked elsewhere in the hospital. Thirteen percent of HWs with EVD reported contact with EVD patients, while 27% reported contact with other infected HWs. The number of HW EVD cases at KGH declined roughly 1 month after implementation of a new triage system at KGH and the opening of a second ETU within the district. The case fatality ratio for HWs and non-HWs with EVD was 69% and 74%, respectively. CONCLUSIONS: The cluster of HW EVD cases in Kenema District is one of the largest ever reported. Most HWs with EVD had potential virus exposure both inside and outside of hospitals. Prevention measures for HWs must address a spectrum of infection risks in both formal and informal care settings as well as in the community.

A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone.

We describe the management of a Sierra Leonean health care worker with severe Ebola virus disease complicated by diarrhea, significant electrolyte disturbances, and falciparum malaria coinfection. With additional resources and staffing, high quality care can be provided to patients with Ebola infection and adverse prognostic factors in west Africa.