Pathogenesis
Through direct contact with mucous membranes, a break in the skin, or parenterally, Ebola enters and infects multiple cell types. Incubation periods appear shorter in infections acquired through direct injection (6 days) than for contact transmission (10 days).1 Emesis, urine, stool, sweat, semen, cerebrospinal fluid, breast milk, and saliva are actively capable of viral transmission. From point of entry, the virus migrates to the lymph nodes, then to liver, spleen, and adrenal glands. Hepatocellular necrosis leads to clotting-factor derangement and dysfunction resulting in coagulopathy and bleeding and potential liver failure. Necrosis of adrenal tissue may be present and results in impaired steroid synthesis and hypotension. The presence of the virus appears to incite a cytokine inflammatory storm causing microvascular leakage, with the end effect of multiorgan system failure, shock, coagulopathy, and lymphocytopenia from cellular apoptosis.1 With cellular death, immune system function is further disabled, more viral particles are released into the infected host, and body fluids remain infectious postmortem.
Laboratory Findings
Laboratory findings in viral hemorrhagic fevers can vary depending on the exact viral cause and the stage in the disease process. Leukocyte counts in early stages can reveal leukopenia and specifically lymphopenia, while in later stages leukocytosis with a left shift of neutrophils can predominate. Hemoglobin and hematocrit can show relative hemoconcentration, especially if renal manifestations of the disease occur. Thrombocytopenia also develops with viral hemorrhagic fevers, although in late stages thrombocytosis has been seen. Blood urea nitrogen (BUN) and creatinine (Cr) levels will rise with the occurrence of acute renal failure in late stages of the disease. Liver function studies, aspartate aminotransferase (AST) in particular, and alanine aminotransferase (ALT) have been found to rise in severe disease and in late stages due to multifocal hepatic necrosis, with AST typically greater than ALT. An association between elevated AST (~900 IU/L), BUN, Cr, albumin levels, and mortality has been statistically confirmed by McElroy et al4 in the Ebola outbreak in Uganda in 2000 to 2001; findings previously confirmed in the same geographic and temporal outbreak by Rollin et al.5 Survivors did not have nearly the same degree of elevation in liver enzymes, with AST levels averaging ~150 IU/L.5 The authors suggested that normalizing AST levels was perhaps indicative of acute recovery, but some patients still succumbed to complications of the illness.5
Coagulation studies, including prothrombin time, partial thromboplastin time, d-dimer, and fibrin split products will reflect disseminated intravascular coagulation (DIC) in those patients who develop hemorrhagic manifestations, which is common in late stages of the disease. Direct infection of vascular endothelial cells with damage to these cells has been shown to occur in the course of infection, yet nonhuman primate experimental studies and pathology examinations of Ebola victims have implied that DIC plays an important part in the hemorrhagic disease leading to the fatal shock syndrome seen in the most severe cases.6 Observed in 2000 during the care of Sudan species EVD patients in Uganda reported by Rollin et al,5 a distinct difference has been noted in quantitative d-dimer levels between survivors and fatal cases. Case fatalities showed a 4-fold increase in quantitative d-dimer levels (140,000 ng/mL) compared with survivors (44,000 ng/mL) during the acute phase of infection 6 to 8 days postsymptom onset.5
Acute phase reactants, high nitric oxide levels, cytokines, and higher viral loads have also been associated with fatal outcomes.4 McElroy et al4 measured the common acute phase reactant biomarker ferritin in patients of the 2000 Uganda outbreak and found levels to be higher in samples from patients who died and from patients with hemorrhagic complications and higher viral loads. Thus, these authors postulate ferritin is a potential marker for EVD severity.4
Commercially available assays for detection of viral particles are still in development and no point-of-care rapid detection testing is available. No test can reliably be used to diagnose viral hemorrhagic fever prior to symptom onset.7 Enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) of viral particles or tissue cell cultures are available only through the CDC, and are the current most reliable methods to confirm the diagnosis of viral hemorrhagic fevers, including Ebola.
Patient Management in the ED
Standard infection-control procedures in place in US hospitals, when meticulously practiced, should be adequate to prevent transmission of EVD. As Ebola virus is only transmitted through direct contact with infected body fluids and secretions, PPE including mask, gloves, gown, shoe covers, and eye protection (goggles or face shield), should be appropriate. In donning PPE, remember that gloves should be the last item to pull in place and to pull off, turning the gown and gloves inside out. One’s hands should be washed before removing the mask and face shield/goggles, and they should be rewashed after completion of PPE removal. A tight fit of the glove over the elastic wristband of the gown is preferable and can ensure a better barrier to any biohazard. Meticulous hand hygiene after removal and proper disposal of PPE is paramount to successful contact protection. Diligent care should be taken in any procedure that might expose a healthcare provider to body fluids, such as blood draws, central line insertion, lumbar puncture and other invasive procedures. Standard contact isolation methods with the patient in a single room with the door closed is sufficient. Appropriate use of standard hospital disinfectants, including bleach solutions or hospital grade ammonium cleaners are already standard practice and easily implemented. It is recommended that procedures that produce aerosol particles should be avoided in patients with suspected infection; yet in some circumstances, the course of care may require such procedures. In this case, to minimize potential airborne spread, airborne and droplet precautions should also be initiated by placing the patient in a negative pressure room and implementing the use of properly fitted N-95 respirators for all present in the room.8