Differential Diagnosis| Ebola Virus Disease

<< Ebola Virus Disease: Epidemiology, Clinical Presentation, and Diagnostic and Therapeutic Modalities (Pharmacology CME)

Differential Diagnosis

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Differential Diagnosis

Differential Diagnosis

The initial signs and symptoms of EVD are similar to many other more common infectious diseases endemic to West Africa;therefore, a high index of suspicion must be maintained. Clinicians should be familiar with common tropical diseases including other hemorrhagic fevers (especially Lassa fever), as well as malaria, cholera, typhoid fever, and influenza. (See Table 2.)

Table 2_ Differential Diagnosis Of Ebola Virus Disease

Lassa Fever

Lassa fever, an acute hemorrhagic disease similar to EVD, belongs to the group Arenavirus and is caused by an RNA virus. Hosts are infected rodents, and transmission occurs through inhalation and contact with mucous membranes and nonintact skin. The incubation period is 6 to 17 days. The severity of disease can range from mild, febrile infections to severe infections with cardiovascular collapse, encephalopathy, and multiorgan failure. Infection is characterized by fever, headache, myalgias, bleeding, exudative pharyngitis, upper and lower respiratory tract symptoms, and abdominal pain. The tonsillar exudate and neurological symptoms may help differentiate Lassa fever from EVD, though definitive diagnosis is made by antigen or antibody detection tests or reverse transcription polymerase chain reaction (RT-PCR). Laboratory abnormalities include thrombocytopenia, proteinuria, and elevations of liver enzymes (specifically, aspartate transaminase). Similar to infection with Ebola virus, infection control measures with Lassa fever should include airborne precautions. Early treatment with ribavirin can decrease mortality due to Lassa fever.23,31


Although progress has been made, the burden of malaria in Africa continues to be significant, with over two-thirds of malaria deaths occurring in children aged < 5 years. Cases in Africa account for 80% to 85% of malaria cases and 90% of malaria deaths worldwide.32 The 5 species that frequently infect humans are Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi. Transmission occurs from the bite of the female Anopheles mosquito. Malaria classically presents with paroxysmal fevers occurring every other or every third day. Symptoms can occur anywhere from 7 days to several months after exposure. Patients exhibit high fever, chills and rigor, sweats, and headache. Nausea, vomiting, cough, diarrhea, myalgias, and abdominal pain may be present, as well. Clinical examination often reveals a pale and jaundiced patient with or without hepatosplenomegaly, and laboratory abnormalities typically include anemia and thrombocytopenia. The gold standard for diagnosis is identification of the parasite on thick and thin blood smears. Although rapid diagnostic tests (RDTs) are available, there is variability in the clinical performance of RDT assays, with better performance at higher levels of parasitemia, though meta-analyses report sensitivities and specificities exceeding 90%.33 Resistance is common in many areas, and increasing resistance has been noted. Therefore, treatment is dictated by local patterns of resistance, the species of Plasmodium, and the severity of disease.23,34


Cholera is an acute diarrheal disease caused by the gram-negative rod, Vibrio cholerae. Every year there are millions of cases of cholera, including a recent large outbreak in Haiti. Infection occurs from ingestion of the bacterium in contaminated water or food. The incubation period ranges from hours to 3 days. Most people infected with the bacteria remain asymptomatic. Cholera infection is characterized by large-volume, painless diarrhea without abdominal pain or fever. The absence of the latter 2 symptoms may help clinicians discriminate between cholera and EVD. The greatest cause of morbidity and mortality from cholera results from severe dehydration, metabolic acidosis, electrolyte abnormalities, and subsequent hypovolemic shock or arrhythmia.

Children are particularly susceptible to neurological manifestations (eg, seizure or coma as a result of dehydration) and death. Like Ebola, cholera is extremely virulent, although there is no direct person-to-person transmission. All infected patients should be placed on contact precautions. The mainstay of therapy is rehydration and correction of electrolyte abnormalities, and the majority of infections can be treated successfully with oral rehydration salts. Antimicrobial therapy with single-dose doxycycline or azithromycin should be considered in patients with moderate to severe illness.23,35

Typhoid Fever

Typhoid fever is a life-threatening illness caused by the gram-negative bacterium, Salmonella Typhi. On a yearly basis, there are approximately 21.5 million infections and 200,000 deaths from typhoid fever globally, making the disease one of the most serious global infectious disease threats to public health. Humans are the only reservoir, and transmission occurs from contaminated food and water, as well as fecal-oral contamination. A small number of people become chronic carriers after recovering from typhoid fever and are responsible for much of the transmission of the organism. Incubation is approximately 7 to 14 days. Fever, constipation, vomiting, abdominal pain, cough, chills, and myalgia characterize the presentation. Mild frontal headache and malaise may be seen, as well as relative bradycardia, though this is not a discriminating feature in children. The characteristic rash, which lasts 2 to 5 days, is blanching and maculopapular (rose spots) and located on the trunk. It is common to see changes in mental status and severe organ dysfunction as the disease progresses. The diagnosis is primarily clinical; however, the gold standard is isolation of the organism from cultures of blood, vomitus, or stool. Hyponatremia, hypokalemia, leukopenia, and anemia are common. Until susceptibilities are available, antibiotics should be empiric and broad-spectrum. First-line treatment for patients who acquire an infection in Africa is oral ciprofloxacin or ofloxacin.36-38


Influenza viruses are orthomyxoviruses, with epidemics being caused by types A and B. Children aged < 2 years are at particularly high risk of hospitalization and mortality from influenza infection. The incubation period is normally 1 to 4 days, and it is spread from person to person through respiratory droplets or contact with contaminated surfaces. Patients characteristically present with fever, malaise, myalgias, cough, and headache, though it is not uncommon for patients to also have abdominal pain, nausea, vomiting, and/or diarrhea. The respiratory tract symptoms are typically more prominent and the gastrointestinal symptoms less severe than in patients with EVD. Secondary bacterial infections, especially pneumonia, are a significant cause of severe disease and death, and clinicians should keep this is mind when evaluating patients. Diagnosis can be made with RDTs from nasopharyngeal secretions, although treatment is based on clinical symptoms and history of exposure and should not be withheld while awaiting diagnostic confirmation. The foundation of treatment is supportive care. However, if diagnosed within 48 hours of onset or in a patient with severe disease or at high risk for influenza complications,39 treatment can be initiated with 1 of the 2 classes of antiviral medications currently available: the neuraminidase inhibitors (oseltamivir and zanamivir) and adamantanes (rimantadine and amantadine).23,40


Gastrointestinal complaints can be prominent features of EVD in children and, early in the course, may be confused with infectious gastroenteritis due to viruses, bacteria, or parasites. Diagnosis can be made by stool culture, PCR, antigen testing, or direct examination. Management is directed toward the underlying cause, and careful laboratory and imaging studies should be obtained. Patients should be appropriately resuscitated with circulatory support and antibiotic therapy, as indicated.41,42

Other Diseases

Other diseases in the differential to consider are bacterial sepsis, shigellosis, louse-borne relapsing fever, meningitis, measles, viral hepatitis, and leptospirosis.25

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Publication Information

Marlie Dulaurier, MD;Katherine Moyer, DO;Rebecca Wallihan, MD

Publication Date

July 2, 2016

CME Expiration Date

August 2, 2019

CME Credits

4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits.
Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 0.5 Pharmacology CME credits

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CME Information

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