Hi there and welcome. My name is Jessica Fairley and this is Henry Wu. We are infectious disease physicians at the Emory University TravelWell Center and we will be describing key concepts about the evaluation and management of patients with possible Ebola virus disease. We have two main objectives for this lecture. First is to describe the typical presentation and differential diagnosis of patients with suspected Ebola virus disease, abbreviated as EVD. Therefore, the first part of the lecture will describe the typical signs and symptoms of patients with EVD. As you will see, these symptoms overlap significantly with other infectious diseases seen in travelers. Secondly, we aim to describe the approach and necessary precautions for evaluating a patient with suspected EVD. This is the core of the lecture, and will provide the foundation for approaching and managing, managing a person under investigation for EVD. Recognizing the clinical symptoms of Ebola virus disease, as well as the differential diagnosis of patients under investigation, is necessary for the subsequent risk assessment when working these patients up for EVD. Symptoms of EVD can be nonspecific, but tend to have an acute onset around eight to ten days after exposure. However, the incubation period could vary significantly, anywhere from two to 21 days. The most common symptom is fever. A report of chills without documented fever is also concerning and can suggest EVD in the appropriate context. There have been reports of patients with EVD presenting without fever, with some estimates totaling up to 15% of cases. With this information, the Centers for Disease Control modified their case definition to include cases as suspect, even in the absence of fever. Other common symptoms include significant malaise, body aches, and anorexia. Furthermore, gastrointestinal symptoms are frequent, but tend to present at three to five days into the illness. These include abdominal pain, nausea, vomiting, and especially diarrhea, which is typically watery and voluminous. Also, one may see headache, chest pain, shortness of breath, rash, and confusion. Conjunctival injection, and sore throat also occur. Hemorrhagic signs are present in the minority of patients, about 18%, and are a late complication. This is why the name was changed from hemorrhagic fever to Ebola virus disease for this 2014 to 2015 epidemic. The first few days of illness may not be severe. Therefore, this must be taken into account. MIld illness does not rule out EVD. Laboratory findings can be helpful in assessing possible EVD, but these too are nonspecific. Leukopenia is often characteristic early in the illness, followed by elevated neutrophils later on. Thrombocytopenia, like many viral infections, can be present along with transaminases and elevated creatinine. Elevated liver enzymes can be marked, and multi-organ failure is characteristic of severe illness. Lastly, both bacteremia and co-infection with malaria have been noted in West Africa. Therefore, an alternative diagnosis does not always rule out EVD. The case fatality rate is estimated at 50 to 70 percent in West Africa, depending on the location and study. Since most patients evaluated as a PUI, or person under investigation, and non-endemic countries will not have EVD, it is imperative to have the differential diagnosis of EVD at your fingertips. Many of the non-specific symptoms and lab abnormalities overlap with infections that are endemic to West Africa. In terms of general traveler related illnesses, Travelers' diarrhea, influenza, and other viral syndromes, such as Epstein Barr Virus and mononucleosis syndromes, are in the differential diagnosis. Sexually transmitted diseases, urinary tract infections, and acute HIV infection can present as febrile syndromes as well. Remember, with an incubation period of 21 days for EVD, PUIs may have common everyday infections picked up by sick contacts, even at home, like strep throat, viral gastral eneritis and other common viral illnesses. Additionally when considering specific travel to West Africa, the differential diagnosis includes malaria, including the serious falciparum malaria, typhoid fever and meningococcal meningitis. Arborviral illnesses like dengue fever are also possible and have very similar laboratory profiles as EVD. And lastly, other viral hemorrhagic fevers like Lassa fever, are also endemic to areas that overlap with Ebola transmission. This figure pictorially represents the challenge of travel-related illnesses. While the majority of patients will have a common, typically low consequence illness like travelers diarrhea, influenza, or another self limiting illness, there's a subset of patients that re, that require more urgent evaluation and treatment. That is represented in the smaller oval, and contains potentially fatal infections that require timely treatment. These include malaria, typhoid fever, pneumonia, meningococcal disease, leptospirosis, among others. An even smaller circle, remember this is outside high transmission areas, includes EVD, which is highly pathogenic, and requires extensive infection control precautions. Therefore, while the chance of a non-EVD infection is highly likely, the consequence nature of EVD dictates a specialized approach. Furthermore, this is also a reminder that EVD is not the only high consequence pathogen on the differential, and that any protocol put in place for EVD evaluation needs to recognize that other more common illnesses, like malaria, need immediate attention and treatment, and therefore evaluation should not be delayed. This outbreak has shown that people directly caring for patients with EVD have the highest risk of contracting the infection. This includes healthcare workers and family members. Transmission requires direct contact with infected bodily fluids including blood, urine, saliva, sweat, feces, vomitus, breast milk, and semen. Fomites such as contaminated nee, needles and syringes can also transmit infection. A large source of transmission in West Africa has been deceased patients who are being prepared for burial. Individuals preparing these patients are at very high risk for contracting Ebola. Only symptomatic patients are at risk for transmitting infection, and even in this situation, the risk of transmission appears to correlate with the viral lode of the infected patient. And now, Dr. Wu will describe the approach and necessary precautions for evaluating a patient with suspected EVD. >> Given the potentially severe consequences of the Ebola virus disease and risk to caregivers, all clinical care settings where patients may present, should be prepared in advance. In this section, I will outline the key steps in the screening, triage, and evaluation of potential cases. These steps form the basis of the United States Centers for Disease Control and Prevention's Ebola preparedness guidelines for US healthcare providers. For viewers from other countries, we encourage you to review the recommendations from your own public health agencies. However, the general issues to consider are similar in all practice settings. The key parts of a preparedness plan can be summarized in three steps, identify, isolate, and inform. For Ebola diagnosis and management in the US, the CDC has identified three levels of healthcare providers, front line healthcare facilities, Ebola assessment hospitals, and Ebola treatment centers. Front line healthcare facilities include any hospital emergency department or urgent care clinic where patients with possible Ebola virus disease may present. At the next level, Ebola assessment hospitals are designated centers that are particularly prepared to evaluate patients. Finally, Ebola treatment centers are those designated centers prepared to manage those with confirmed disease. As we discuss the key aspects of identifying and managing patients with possible Ebola virus disease, it is important to consider your own institution's role. Note, even if your practice setting is not a front line health care facility or a designated center, it is still very important to have a preparedness plan, since it is possible for a patient with Ebola to present in almost any clinical setting. The first key step is identifying patients who might have Ebola virus disease. Therefore, all clinical institutions should have a patient screening procedure. In your institution, consider where the screening process should take place. In clinics that primarily see patients by appointment, it would be ideal to incorporate screening into your telephone call script to reduce the chance that patients with potential infection present unexpectedly. However, since unexpected arrivals can always occur, clinics and front line healthcare facilities should also incorporate screening into their check-in procedures. The CDC has developed a case definition for a person under investigation for Ebola virus disease, or PUI for, in short. Because of the potentially severe consequences of Ebola disease, this case definition is designed to be extremely sensitive and screen for patients with even remote possibility of infection. That is, the primary goal is to reduce the chance a case will be missed, even at the expense of picking up, picking up many patients who do not have Ebola infection. The PUI case definition has two essential criteria, clinical and epidemiologic. Meeting the clinical criteria requires the presence of a symptom consistent with Ebola virus disease. This includes elevated body temperature or subjective fever or other symptoms, including severe headache, fatigue, muscle pain, vomiting, diarrhea, abdominal pain, or unexplained hemorrhage. Note that the fever criteria does not have a fixed temperature threshold and even a subjective complaint of fever can meet this criteria. Secondly, an epidemiological risk factor within 21 days before the onset of symptoms must be present. A window of 21 days is chosen because this is the upper limit of the incubation period. This next slide outlines the various epidemiologic risk categories CDC has defined for possible Ebola exposures. Each of these categories contains various examples. High-risk exposures include percutaneous or mucosal exposures to blood or bodily fluid from a person symptomatic, with symptomatic Ebola virus disease or a bodily fluid exposure without proper personal protective equipment, also called PPE. Exposures with some risk include direct or close contact with a patient with symptomatic Ebola virus disease without appropriate PPE. Low-risk exposures include travel to a country with widespread Ebola transmission. CDC has also speci, specified some groups of individuals who have no identifiable risk, and this includes those who have had contact with the patient with Ebola vir, virus disease prior to symptom onset. While the risk category level may factor into the decision making process for determining the level of testing, care, and quarantine needed, note that even the low cat, risk category is enough to meet the PUI epidemiologic criteria. For this reason, even when there is no known history of contact with patients with Ebola, any individual with symptoms consistent with Ebola virus disease who has recently traveled to a country with widespread Ebola transmission can meet PUI criteria. Since we do not have the time to go over all the examples within each risk category, I encourage all viewers to review the criteria on the CDC website at the link below. Furthermore, the PUI case definition can be revised at any, any time, so regular review of CDC's current guidelines is important. When a PUI is identified, immediate action to isolate the patient and implement infection control measures is critical, given the risk of transmission to health care providers and other patients. First and foremost, the PUI must be immediately directed to a designated private room. To safely manage PUI, CDC has provided guidance for US health care institutions regarding environmental infection control, PPE, disinfection, and waste management. Attention to personal protective equipment is critical to protect health care workers. Absolutely essential are standard droplet and contact precautions. However, given the recent cases of Ebola transmission to healthcare workers in Dallas, enhanced PPE guidelines have been recommended. These include en, many en, enhancements, including the use of a face shield, double gloving, and strict PPE donning and doffing procedures. Even higher levels of PPE are needed for patients with bleeding, vomiting, copious diarrhea, those who require an aerosol-generating procedure, or those hospitalized with confirmed Ebola virus disease. Formal training and practice are essential since these PPE guidelines are significantly different from the routine droplet and contact precautions US healthcare workers are familiar with. Though, many outpatient clinics are not considered front line healthcare facilities, having a minimal supply of PPE may still be important in the case of an unexpected PUI arrival. Your local health department should be informed of any PUI immediately. This can even include PUI's that are not seen in clinic but are identified over the telephone. State and local health departments play a critical role in actively monitoring PUI. Furthermore, local health authorities might also need to arrange safe transport of a PUI to an evaluation center or facilitate Ebola virus testing as needed. Next, we discuss some of the practical issues regarding the evaluation of PUI at front line healthcare facilities and Ebola assessment centers. As always, a thorough history taking is critical, including the nature and timing of symptoms, a detailed travel history, and inquiry of potential exposure to patients with Ebola infection, clinical specimens, or zoonotic exposures, such as contact with fruit bats or primates. Assessing malaria chemoprophylaxis use and previous vaccinations for travel related illnesses, including influenza, can be helpful. A detailed physical exam, which can be challenging while wearing PPE, is nonetheless important to look for signs suggestive of, of Ebola or other conditions. Testing for Ebola virus includes virus isolation and various assays that detect viral antigens, IGM antibodies, or viral RNA. Notably, the virus may not be detected in the early part of illness. Therefore, negative Ebola testing does not necessarily rule out infection if the PUI is tested in the first three days of symptomatic illness. Furthermore, since the capacity to perform Ebola virus testing is limited to designated public health laboratories at this time, it may not be practical to perform Ebola testing on all PUI. Given all of these limitations, Ebola testing decisions should be made on a case-by-case basis with your local health department. Other testing may be important, particularly because the differential diagnosis of the ill traveler from West Africa is wide. For PUI with fevers, in our institution, we routinely perform complete blood counts, liver, and kidney function tests, malaria rapid diagnostic testing and blood smears, and blood cultures. We perform other tests depending on the clinical presentation, for example, a rapid influenza assay in those with respiratory symptoms or stool studies and those with diarrhea. Given the real possibility of other life threatening infections, such as malaria or typhoid fever, and circumstances where testing capat, capacity is limited or a PUI is critically ill, empiric antimalarial and antibiotic therapy should be considered. By far, the vast majority of PUI presenting in the US will not have Ebola disease. However, it is also important to remember that non-Ebola infections can present with or complicate Ebola virus disease. Co-infections with Ebola and malaria have been described. Therefore, it is important to remember that a confirmed non-Ebola diagnosis does not rule out the possibility of Ebola infection, especially when the patient does not clinically improve as expected. Given the numerous steps necessary to effectively identify and isolate PUI and the importance of informing public health authorities in a timely manner, having a preparedness plan is critical. Depending on your institution, the objective of your plan can very. PUI may present to clinics that are not in frontline healthcare facilities. Therefore, in many situations, screening for PUI before arrival should be a top priority, so they may be triaged directly to an Ebola evaluation center. However, because of the small chance a PUI could present unexpectedly, a plan should still be in place to screen all arriving patients, and isolate as needed. Frontline healthcare facilities, such as emergency departments, can play potentially play a major role in evaluating PUI, especially when transfer to an evaluation center is not feasible. These facilities should review their capacity to care for PUI and perform the various tests needed to work up ill travelers. Furthermore, it is absolutely essential that frontline healthcare facilities are familiar with their local health departments and the protocols for Ebola virus testing or PUI transport to Ebola assessment hospitals. Given the many critical steps in safely evaluating PUI, as you develop your plan, it is important to engage key stakeholders in your institution, including clinical staff, infection control preventionists, or infectious disease consultants, your clinical laboratory, environmental services, waste management, and health care administrators. Finally, even a perfectly designed plan can stumble if those implementing it have not practiced. Formal PPE training, practice drills, and table-top exercises are important. Process improvement is also key and following a drill or implementation, a performance review can identify gaps in the protocol or areas needing improvement. >> To summarize, Ebola virus disease is a serious and contagious infection. Initial presentation is nonspecific and resembles many other, more common infections, especially early on in the illness. As demonstrated, infection control is critical, and all patients need to be approached as a possible EVD case. Therefore, all facilities should assess their local capacity and develop action plans to triage, evaluate, and treat these patients, while protecting the safety of the providers, the patient and the community.
