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Ebola: Lessons from the Latest Pandemic

Clinician Reviews. 2015 September;25(9):34-40
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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.

PATHOPHYSIOLOGY AND TRANSMISSION
Ebola virus (EBOV) is an enveloped RNA virus of the family Filoviridae.8 Five viruses of the Ebolavirus genus have been described: EBOV, Tai Forest virus, Reston virus, Sudan virus, and Bundibugyo virus. Except for Reston virus, each of these viruses causes hemorrhagic fever with high mortality.

EVD is a zoonotic disease, meaning that outbreaks typically begin by passage of the virus from an animal vector to a human host. In this case, it is thought that the viral reservoir consists of several species of fruit- and insect-eating bats native to West Africa.8,9 The vector that transmits the virus from bats to humans is not well understood, but reports name nonhuman primates (NHP) and pigs as possible culprits.8 Though EBOV is not typically transmitted through food, the practice of consuming “bushmeat”—hunted wild animals such as bats, monkeys, and rodents—has been linked to transmission of the virus. According to the CDC, the mechanism for this mode of transmission is likely through the butchering and processing of infected animals.10 It is important to note that only wild animals hunted in endemic regions of Africa carry the risk for transmission. To date, there have been no reports of EBOV transmission via contact with any animal, wild or domestic, in this country.

Once the virus has infected a human host, transmission of the disease continues from person to person via contact with infected bodily fluids. The three main modalities of virus transmission in under­developed countries include nosocomial transmission (improper sterilization techniques), funeral preparation, and community transmission.11 The most infectious substances are blood, feces, and vomit, but the virus has also been found in saliva, tears, breast milk, sweat, urine, and semen.12

Though controversial, evidence now suggests that EBOV can survive in semen for more than three months, even in patients who have fully recovered from the disease.13 To prevent sexually transmitted EBOV exposure, the WHO recommends that convalescent EVD patients use barrier methods such as condoms and female condoms to prevent the exchange of bodily fluids during sexual activity.13

Like other pathogens requiring droplet precautions, EBOV can only enter an uninfected individual through nonintact skin or mucous membranes, or parenterally. Transmission may also take place via fomites, or contaminated surfaces and objects which have not been properly sanitized.12 Studies suggest that the virus cannot survive on fomites for extended periods at room temperature; however, when refrigerated to 40°F, EBOV survived for more than three weeks.14 The incubation period for EBOV ranges from two to 21 days, with an average of 11 days.8

Current research indicates that the virus is not transmissible until symptoms appear, and therefore, infected patients are not contagious during the incubation period.15 The amount of EBOV in body fluid is referred to as viral load and has been determined to be a contributing factor in the transmission of the virus. As the viral load rises, symptoms worsen and the patient becomes more contagious.16 Patients with EVD are most contagious in the later stages of the disease (when viral load is highest) and shortly after death.16

With the recent infection of health care workers in Spain and Texas, there has also developed public concern regarding the possibility of contracting EBOV infection from pets. Currently, the CDC has no documented cases of domesticated animals contracting EVD or spreading the virus.17 Nonetheless, any pets in the home of EVD patients will be evaluated and managed by local health officials (via quarantine, surveillance, and possible euthanasia).17 In Spain, a nurses’ aide infected with the disease lost the fight to keep her dog, and health officials euthanized the 12-year-old mixed breed while his owner was in quarantine.18 By contrast, the King Charles Spaniel of Texas nurse Nina Pham was quarantined for three weeks and later reunited with his family.19 The divergent treatment of pets in the two cases illustrates how public concern about EVD ultimately influences decision-making.

Detailed study of the pathophysiology of EVD is difficult due to the virulence of EBOV and its high mortality, which are reflected by its classification as a biosafety level 4 (BSL-4) organism. Handling and study of organisms with BSL-4 designation require sophisticated laboratory equipment and advanced safety technology only available in developed countries. Further, ethical concerns dictate that the virus be studied in animal models rather than in humans. As such, mouse, guinea pig, and NHP models provide most of the available data.

EBOV evades immune system detection and destruction because of its extensively glycosylated lipid bilayer envelope.8 Once inside a suitable host, the virus reproduces by hijacking immune cells: monocytes, macrophages, and dendritic cells. Simultaneously, infection incites large-scale inflammation via cytokines, lymphocyte apoptosis resulting in lymphopenia, inhibition of innate and acquired humoral and cellular immune responses, and disruption of the clotting cascade.8

In later stages of infection, EBOV targets hepatocytes and endothelial cells.8 Liver dysfunction leads to interruption of clotting factor production, thus causing coagulopathy. Endothelial dysfunction is responsible for “leakage” of blood from vessels into skin, mucous membranes, and the gastrointestinal tract.8

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