Differentials
Dengue fever
SIGNS / SYMPTOMS
Residence in/travel to dengue-endemic region.
Less likely to present with biphasic illness and more likely to have a rash and adenopathy.
INVESTIGATIONS
Serologic testing confirms diagnosis, but treatment for both diseases is identical (i.e., supportive).
Malaria
SIGNS / SYMPTOMS
Residence in/travel to malaria-endemic region.
Jaundice is not uncommon, but hemorrhagic complications are rare. Occasionally, periodic fever is present, but there is no true biphasic illness.
INVESTIGATIONS
Detection of Plasmodium parasites in thick or thin smears.
Zika virus infection
SIGNS / SYMPTOMS
Residence in/travel to Zika-endemic region or unprotected sexual contact with infected individual.
Maculopapular, pruritic rash is characteristic.
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR) is positive for Zika.
Serology is positive for Zika.
Chikungunya virus
SIGNS / SYMPTOMS
Residence in/travel to chikungunya-endemic region.
Prominent joint symptoms (e.g., polyarthritis and carpal tunnel syndrome are common).
Hyperpigmentation of skin and intertriginous lesions are common.
INVESTIGATIONS
ELISA/indirect fluorescent antibody is positive for chikungunya antibodies.
RT-PCR is positive for chikungunya viral RNA.
Leptospirosis
SIGNS / SYMPTOMS
More prolonged, less toxic disease. Renal failure may occur with a generally mild transaminitis.
Severe icterohemorrhagic leptospirosis (Weil disease) is difficult to differentiate from yellow fever.
INVESTIGATIONS
Aminotransferase levels only mildly elevated.
Detection of Leptospira in blood and urine.
Response to treatment with antibiotics.
Acute hepatitis
SIGNS / SYMPTOMS
Hemorrhage is rare and occurs late due to hepatic failure.
INVESTIGATIONS
Hepatitis serologies reveal diagnosis in icteric patients.
Louse-borne relapsing fever
SIGNS / SYMPTOMS
Relapsing disease (in contrast to biphasic disease of yellow fever), which does not recur after the toxic phase.
Exposure history differs from that of yellow fever, with epidemic transmission associated with poor living conditions. There is some overlapping, but more restricted, geographic distribution in northern Africa, including countries north of the Sahara desert.
Renal disease, if present, occurs late and rash is more common.
INVESTIGATIONS
Response to antibiotics within 24 hours.
Confirmation of diagnosis is by a blood smear or serologic tests.
Lassa fever
SIGNS / SYMPTOMS
Residence in/travel to Lassa fever-endemic region.
Contact with infected body fluids, or butchering/consumption of meat from infected rodents.
Symptoms such as hearing loss/impairment, sore throat, and a dry nonproductive cough may help differentiate.
Not usually associated with jaundice.
INVESTIGATIONS
RT-PCR is positive for Lassa virus RNA.
Serology is positive for Lassa virus antibodies.
South American hemorrhagic fevers (SAHF)
SIGNS / SYMPTOMS
Residence in/travel to SAHF-endemic region.
Exposure to infected rat excreta or contact with an infected person.
Neurologic symptoms (e.g., seizures).
Not usually associated with jaundice.
Difficult to differentiate from other viral hemorrhagic fevers.
INVESTIGATIONS
RT-PCR is positive for Junin virus, Guanarito virus, Machupo virus, Chapare virus, or Sabia virus RNA.
Serology is positive for Junin virus, Guanarito virus, or Machupo virus antibodies.
Ebola virus infection
SIGNS / SYMPTOMS
Residence in/travel to Ebola-endemic region.
Contact with infected body fluids, or butchering/consumption of meat from infected animals.
Not usually associated with jaundice.
Difficult to differentiate from other viral hemorrhagic fevers.
INVESTIGATIONS
RT-PCR is positive for Ebola virus RNA.
Serology is positive for Ebola virus antibodies.
Marburg virus infection
SIGNS / SYMPTOMS
Residence in/travel to Marburg-endemic region.
Exposure to bats, caves, or mining in endemic area, or contact with infected body fluids.
Not usually associated with jaundice.
Difficult to differentiate from other viral hemorrhagic fevers.
INVESTIGATIONS
RT-PCR is positive for Marburg virus RNA.
Serology is positive for Marburg virus antibodies.
Rift valley fever (RVF)
SIGNS / SYMPTOMS
Residence in/travel to RVF-endemic region.
History of livestock handling through occupational exposure, or consuming raw animal fluids or tissue, in endemic regions.
May also be associated with severe liver damage.
INVESTIGATIONS
RT-PCR is positive for RVF virus RNA.
Serology is positive for RVF virus antibodies.
Crimean-Congo hemorrhagic fever (CCHF)
SIGNS / SYMPTOMS
Residence in/travel to CCHF-endemic region.
History of tick exposure, livestock handling, or contact with infected body fluids.
Macular or petechial rash is common.
May also be associated with severe liver damage.
Difficult to differentiate from other viral hemorrhagic fevers.
INVESTIGATIONS
RT-PCR is positive for CCHF virus RNA.
Antigen-capture ELISA is positive for CCHF virus RNA.
Serology is positive for CCHF virus antibodies.
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.
The situation is evolving rapidly; see our COVID-19 topic for further information.
INVESTIGATIONS
Real-time RT-PCR: positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
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