Ebola: Lessons from the Latest Pandemic
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The 2014 re-emergence of Ebola virus disease (EVD) quickly became the largest and deadliest outbreak of the disease ever recorded. Originating in Guinea, it spread to neighboring countries and others around the globe. As potentially the firstline health care contacts during a pandemic, all primary care providers need to be aware of the signs and symptoms of EVD so that they can quickly identify, isolate, and treat affected patients. This article describes the history, pathophysiology, diagnosis, and treatment of the disease.
DIAGNOSIS
Patient history
To be diagnosed with EVD, patients must have a history of travel to an EBOV-affected region in the previous 21 days.20 Of particular importance in the US is gathering an accurate travel history from potential EBOV patients. According to the CDC, countries affected by the outbreak include Guinea, Liberia, and Sierra Leone; countries with travel-related cases include Nigeria, Spain, the US, the UK, Mali, and Senegal.21 Practitioners abroad should inquire about patients’ encounters with body fluid of infected individuals, contact with contaminated objects, and interaction with infected animals.
Physical exam
Initial symptoms are nonspecific, with a classic viral prodrome of fever, chills, muscle aches, and general malaise.8 Stage two is characterized by abdominal pain, nausea, vomiting, and diarrhea.8 In the final hemorrhagic stage of the disease, clotting dysfunction leads to subcutaneous and internal bleeding (epistaxis, petechiae, ecchymoses, hematochezia, and melena) and conjunctival hemorrhage.8,22 In this terminal stage of EVD, extreme blood loss causes organ failure, disseminated intravascular coagulation, shock, and death.8
Laboratory testing
Several methods of laboratory diagnosis exist, but all testing must be performed several days after the onset of symptoms; thus, patients with suspected EVD should remain isolated pending test results. At the outset of symptoms, the following laboratory diagnostic tests may be used to determine whether a patient is infected with EBOV:
• Antigen-capture enzyme-linked immunosorbent assay (ELISA)
• Immunoglobulin (IgM) ELISA
• Polymerase chain reaction (PCR)
• Virus isolation.23
IgM and IgG antibodies may be isolated from patients who have recovered from the disease.23 Finally, postmortem testing may be done via immunohistochemistry testing, PCR, or virus isolation.23 The CDC standard is IgG ELISA, which has 93% sensitivity and 98% specificity for EBOV antibody detection (see Table 1).24
Though not definitive, routine laboratory tests may support an EVD diagnosis. The complete blood count of a person with EVD reveals evidence of thrombocytopenia, leukopenia, and lymphopenia.8 Viral attack on hepatocytes results in elevated alanine aminotransferase and aspartate aminotransferase levels, while coagulopathy is reflected by elevated thrombin and prothrombin times (see Table 2).8 A drawback to any type of testing is that it requires advanced technology and safety precautions that are not widely available in the underdeveloped countries where the outbreak is currently taking place.8
Reporting
The CDC recommends immediate isolation of suspected EVD patients and the employment of standard, contact, and droplet precautions, including the use of gowns, gloves, masks, and face protection. Once the patient has been isolated, health care providers should notify their hospital’s Infection Control Program and immediately contact their local health department.20
Treatment
At present, the standard treatment for EVD is supportive care. The CDC recommends the use of IV fluid hydration and the maintenance of electrolytes, oxygen status, and blood pressure, as well as the treatment of any concurrent infection.25 These supportive measures, though noncurative, appear to significantly reduce mortality.
Another proposed treatment for EVD is transfusion of whole blood or plasma from recovered patients in the convalescent phase of infection. Through this technique, patients with early EVD benefit from the effective immune response of recovered individuals via passive immunization. Per WHO recommendations, only patients who have tested negative for EVD twice and have been out of the hospital for 28 days are eligible as potential donors.26 As with all blood product transfusions, the blood of the donor and the recipient must be typed and screened for compatibility.
No vaccines for the prevention of EVD have been approved by the FDA, but several vaccines are undergoing extensive research. Among them are prevaccines and postvaccines. Prevaccines, also known as preventive vaccines, are designed to be administered prior to pathogen exposure. Postvaccines, also referred to as therapeutic vaccines, are used after a person has sustained pathogen exposure, with the goal of stimulating the patient’s immune system to fight the infection.8
EVD vaccines are categorized into two classes: replicating and nonreplicating. Currently available replicating vaccines include recombinant vesicular stomatitis virus, recombinant human parainfluenza virus type 3, rabies virus, and cytomegalovirus.27 Nonreplicating vaccines include inactivated vaccines, replicons, DNA vaccines, recombinant adenoviruses, subunit vaccines, and replication-deficient ebola viruses.27
One prevaccine in particular, the recombinant adenovirus, has produced positive results in providing vaccine protection in NHPs. This vaccine is capable of protecting against multiple strains of ebola viruses, but because the vaccine is based on adenovirus serotype 5, for which a large proportion of the human population has immunity, its overall efficacy is significantly reduced.8,27 Significant progress has been made with the therapeutic vaccine ZMapp in the treatment of EVD in NHPs. ZMapp is a combination of three monoclonal antibodies that, when administered to an infected NHP, cling to the virus and prevent it from further invading healthy cells.8 Because this vaccine has not yet undergone human trials and is still in early experimental stages, special permission from the FDA is required to obtain it.8
Finally, researchers are optimistic that AVI-7357, an antiviral in late stages of clinical trials, will be an effective therapeutic agent for EVD. Its mechanism of action is thought to be inhibition of the VP24 protein; this viral protein is thought to play a role in the switch from viral replication to transcription, and blocking it is believed to effectively obstruct replication of the virus.28 Although much research is underway in the treatment of EVD, none of the proposed treatments has met the standards of FDA approval.
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