Differentials
Hantavirus cardiopulmonary syndrome
SIGNS / SYMPTOMS
Severe respiratory symptoms leading to adult respiratory-distress syndrome.
Symptoms do not present in a biphasic form.
Exposure to specific endemic areas favors Hantavirus.
INVESTIGATIONS
Diagnosis confirmed by polymerase chain reaction test from blood or tissue specimens, or immuno-histochemical testing.
Dengue fever
SIGNS / SYMPTOMS
Presenting signs and symptoms similar to leptospirosis, except conjunctival suffusion, which is not present in dengue fever.
Dengue fever does not present in 2 phases.
INVESTIGATIONS
Positive serologic test will confirm diagnosis and differentiate among etiologic agents.[71]
Malaria infection
SIGNS / SYMPTOMS
Similar presentation involving recent travel, fever, potential renal failure, and hemorrhagic complications.
INVESTIGATIONS
Malaria diagnosis is confirmed with peripheral smear.
Leptospirosis testing will be negative.
Hemorrhagic fevers
SIGNS / SYMPTOMS
Similar presentation in both hemorrhagic fever and leptospirosis.
Hemorrhagic fever will occur after exposure to particular endemic areas, whereas leptospirosis is endemic worldwide.
INVESTIGATIONS
Positive leptospiral testing confirms leptospirosis and will differentiate it from hemorrhagic fever.
Diagnosis is confirmed by multiple polymerase chain reaction assays, serologic tests, and viral isolation.
Rickettsioses
SIGNS / SYMPTOMS
Similar presentation including an undifferentiated febrile illness, often accompanied by headache, fatigue, and malaise.
INVESTIGATIONS
Positive testing for Rickettsia species can include nucleic acid amplification tests and/or serology (e.g., immunofluorescent assay, enzyme-linked immunosorbent assay).
Influenza infection
SIGNS / SYMPTOMS
Differs in epidemiology; influenza peaks in the winter and troughs in the summer.
Shorter incubation period (1 to 2 days).
Renal and hepatic failure and hemorrhagic diathesis are not seen in influenza.
Symptoms do not present in 2 phases.
INVESTIGATIONS
Positive influenza A and B antigen test and/or positive viral culture.
Viral hepatitis
SIGNS / SYMPTOMS
Mainly involved in differential diagnosis for travelers.
Patients usually present with fevers, jaundice, and elevated liver aminotransferases.
Patients can develop acute hepatic failure.
INVESTIGATIONS
Positive acute hepatitis serologies.
Acute fatty liver
SIGNS / SYMPTOMS
May be mistaken for leptospirosis in a pregnant patient.[54]
Jaundice is common.
Hepatic encephalopathy may occur.
Risk factors include a history of alcohol misuse, poor nutritional status, chronic hepatitis B, and overuse of acetaminophen.
INVESTIGATIONS
Elevated INR (>1.5) and prothrombin time.
Acetaminophen level may be elevated; urinary toxicology screen may be positive.
BUN and creatinine elevated.
HELLP syndrome
SIGNS / SYMPTOMS
May be mistaken for leptospirosis in a pregnant patient.[54]
Brisk tendon reflexes are commonly found, as is right upper quadrant abdominal tenderness.
Fever is not usual.
INVESTIGATIONS
Schistocytes, burr cells, and polychromasia on a peripheral blood smear are diagnostic.
Prothrombin time and PTT elevated on coagulation studies.
Uric acid levels typically elevated.
Gestational hypertension
SIGNS / SYMPTOMS
May be mistaken for leptospirosis in a pregnant patient.[54]
Typically develops at >20 weeks' gestation.
INVESTIGATIONS
LFTs and blood chemistry typically within normal parameters.
Uric acid may be elevated.
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 reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
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