Differentials
Malaria infection
SIGNS / SYMPTOMS
Most common cause of nonspecific febrile illness in returning travelers.[111]
Inadequate or no malaria chemoprophylaxis.
There are no differentiating signs and symptoms.
Co-infection with malaria was seen in up to 5% of patients in West Africa during the 2014 outbreak, so the possibility of dual infection should be considered in all patients.[93]
INVESTIGATIONS
Giemsa-stained thick and thin blood smears: positive for Plasmodium species.
Rapid diagnostic tests: positive for Plasmodium species (note: P ovale is not always detected by some rapid diagnostic tests).
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Marburg virus infection
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms.
Epidemiologic features can help differentiate between the viral hemorrhagic fevers (i.e., exposure to bats, caves, or mining).
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR): positive for Marburg virus RNA.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Crimean-Congo hemorrhagic fever (CCHF)
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms.
Epidemiologic features can help differentiate between the viral hemorrhagic fevers (i.e., animal butchering, tick bite, or exposure to animals).
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR): positive for CCHF virus RNA.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Lassa fever
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms.
Epidemiologic features can help differentiate between the viral hemorrhagic fevers (i.e., exposure to rats in endemic areas).
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR): positive for Lassa virus RNA.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Rift Valley fever
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms.
Epidemiologic features can help differentiate between the viral hemorrhagic fevers (i.e., mosquito exposure, livestock handling, consuming raw animal fluids/tissues).
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR): positive for Rift Valley fever virus RNA.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Yellow fever
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms.
Epidemiologic features can help differentiate between the viral hemorrhagic fevers (i.e., mosquito exposure, lack of immunization).
INVESTIGATIONS
eReverse transcriptase-polymerase chain reaction (RT-PCR): positive for yellow fever virus RNA.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Typhoid infection
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms.
INVESTIGATIONS
Blood or stool culture: positive for Salmonella enterica.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Rickettsial infections
SIGNS / SYMPTOMS
Includes murine typhus, African tick-bite fever, and epidemic typhus.[128]
Eschar is typical.
Lymphadenopathy may be present.
Discrete rash.
INVESTIGATIONS
Serology: positive for Rickettsia species.
Eschar polymerase chain reaction (PCR): positive for Rickettsia species.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Dengue fever
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms.
INVESTIGATIONS
Serology: positive IgM or IgG.
Nonstructural protein (NS1) detection: positive.
Reverse transcriptase-polymerase chain reaction (RT-PCR): positive.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Measles infection
SIGNS / SYMPTOMS
Unvaccinated.
There are no differentiating signs and symptoms in prodromal phase.
Koplik spots (red spots with bluish-white central dot) on buccal mucosa.
Rash typically starts on face and spreads craniocaudally.
INVESTIGATIONS
Serology: positive for measles virus.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Leptospirosis
SIGNS / SYMPTOMS
There are no differentiating signs and symptoms; however, a history of exposure may be helpful.
Exposure to contaminated water or soil contaminated by infected rodents.[129]
More common in tropical climates.
INVESTIGATIONS
polymerase chain reaction (PCR): positive.
Serology: positive.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Seasonal influenza infection
SIGNS / SYMPTOMS
Respiratory signs and symptoms (e.g., cough, nasal congestion) are more common.
INVESTIGATIONS
Viral culture or polymerase chain reaction (PCR): detection of seasonal influenza virus or viral RNA.
CBC: normal.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Gastroenteritis
SIGNS / SYMPTOMS
In the correct epidemiologic text, this can present in a similar way to Ebola virus infection. However, features such as rash, conjunctival injection, and prostration are very rare in gastroenteritis.
INVESTIGATIONS
Stool culture, polymerase chain reaction (PCR), or rapid antigen testing: positive.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Sepsis
SIGNS / SYMPTOMS
Bacterial sepsis with an unclear origin is a common presentation in developing countries. Often turns out to be deep abdominal infection, upper urinary tract infection, endocarditis, or discitis.
Diarrhea is often absent.
INVESTIGATIONS
Blood cultures: positive.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola virus infection is suspected.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Residence in/travel to a country/area or territory with local transmission, or close contact with a confirmed or probable case of COVID-19, in the 14 days prior to symptom onset.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
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