Leptospirosis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [2]


Leptospirosis must be differentiated from other diseases that cause fever, diarrhea, nausea and vomiting, such as ebola, typhoid fever, malaria, yellow fever, and other enteric bacterial infections. Moderate to severe leptospirosis must be differentiated from dengue fever.

Differential diagnosis

Differential diagnosis list for leptospirosis is very large due to diverse symptomatics. For forms with middle to high severity, the list includes dengue fever and other hemorrhagic fevers, hepatitis of various etiologies, viral meningitis, malaria and typhoid fever. Light forms should be distinguished from influenza and other related viral diseases. Specific tests are a must for proper diagnosis of leptospirosis. Under circumstances of limited access (e.g., developing countries) to specific diagnostic means, close attention must be paid to anamnesis of the patient. Factors like certain dwelling areas, seasonality, contact with stagnant water (swimming, working on flooded meadows, etc) and/or rodents in the medical history support the leptospirosis hypothesis and serve as indications for specific tests (if available).

Differential Diagnosis for Hemorrhagic fever

Disease Incubation period Vector Symptoms Physical signs Lab findings Other findings Treatment
Fever Cough Rash Joint pain Myalgia Diarrhea Common hemorrhagic symptoms Characterestic physical finding Icterus Plasma Creatine kinase Confirmatory test
Leptospirosis 2 to 30 days Rodents

Domestic animals

Fever last for 4-7 days, remission for 1-2 days and then relapse + Present over legs Hemorrhagic rash + +

(Severe myalgia is characteristic of leptospirosis typically localized to the calf and lumbar areas)

+ Conjunctival hemorrhage,


Conjunctival suffusion + Elevated Microscopic agglutination test of urine History of exposure to soil or water

contaminated by infected rodents

Recent history travel to tropical, sub tropical areas or humid areas

Dengue 4 to 10 days Aedes mosquito Fever last for 1-2 days,

remission for 1-2 days and then relapse for 1-2 days (Biphasic fever pattern)

- Over legs and trunk

pruritic rash May be hemorrhagic

+ + - Upper gastrointestinal bleeding Painful lymphadenopathy - Normal Serology showing positive IgM or IgG Recent travel to South America, Africa, Southeast Asia Supportive care

Avoid aspirin and other NSAIDs

Malaria Female Anopheles Fever present daily or on alternate day or every 3 days depending on Plasmodium sps. - No rash - + - Bloody urine Hepatosplenomegaly + Normal Giemsa stained thick and thin blood smears Recent travel to South America, Africa, Southeast Asia Anti malarial regimen
Ebola 2 to 21 days. No vector

Human to human transmission

Air born disease

+ + Maculopapular

non-pruritic rash with erythema

Centripetal distribution

+ + +

May be bloody in the early phase


Mucosal bleeding

Sudden onset of high fever with conjunctival injection and early gastrointestinal symptoms - Normal RT-PCR Recent visit to endemic area especially African countries Isolation of the patient,

supportive therapy

Influenza 1-4 days No vector

Air born disease

+ + +/- + + + - Fever and upper respiratory symptoms - Normal Viral culture or PCR Health care workers

Patients with co-morbid conditions

Symptomatic treatment

Oseltamivir or zanamivir

Yellow fever 3 to 6 days Aedes or Haemagogus species mosquitoes + + - - + - Conjunctival hemorrhage,


Relative bradycardia

(Faget's sign)

+ Normal RT-PCR,

Nucleic acid amplification test,

Immuno-histochemical staining

Recent travel to  Africa, South and Central America, and the Caribbean.

Tropical rain forests of south America

Symptomatic treatment,

Anti-inflammatory drugs

Typhoid fever 6 to 30 days No vector

Air born disease

+ - Blanching erythematous 

maculopapularlesions on the lower chest and abdomen

+ + + Intestinal bleeding Rose spots - Normal Blood or stool culture showing salmonella typhi sps. Residence in endemic area

Recent travel to endemic area


Third generation cephalosporins,


Differentiating psittacosis from other diseases

Clinical feature Cough Sputum Dyspnea Sore throat Headache Confusion Diarrhea Chest radiograph changes Hyponatremia Leukopenia Abnormal Liver function tests Treatment
Psittacosis ++ - + - +++ + Minimal
  • No changes seen
- + - Doxycycline
C.pneumoniae pneumonia + + + +++ ++ + -
  • Minimal changes observed
- - - Doxycycline, Azithromycin
M. pneumoniae pneumonia ++ ++ ++ - - - - - - + Doxycycline
L. Pneumophila infection + +++ +++ - + ++ + Often Multifocal ++ + ++ Doxycycline
Influenza ++ ++ ++ ++ ++ +/- +/- - - - zanamivir, oseltamivir,
Endocarditis ++ ++ + - - - -
  • Hazy opacities at lung

bases bilaterally

- +/- +/- Vancomycin
Coxiella burnetii infection ++ - + +/- - +/- Minimal - +/- =/- Doxycycline
Leptospirosis ++ + ++ + + ++ -
  • Multiple ill-defined nodules in both lungs.
+++ Doxycycline, azithromycin, amoxicillin
Brucellosis ++ - + - ++ + - -/+ +/- +/- Doxycycline, rifampin


+, occurs in some cases

++, occurs in many cases,

+++, occurs frequently

Leptospirosis must be differentiated from other diseases that cause atypical pneumonia such as Q fever and legionella pneumonia:

Disease Prominent clinical features Lab findings Chest X-ray
Q fever
  • Antibody detection using indirect immunofluorescence (IIF) is the preferred method for diagnosis.
  • PCR can be used if IIF is negative, or very early once disease is suspected.
  • C. burnetii does not grow on ordinary blood cultures, but can be cultivated on special media such as embryonated eggs or cell culture.
  • A two-to-three fold increase in AST and ALT is seen in most patients.
Q fever pneumonia - - Case courtesy of Royal Melbourne Hospital Respiratory, Radiopaedia.org, rID 21993
Mycoplasma pneumonia
Mycoplasma pneumonia - Case courtesy of Dr Alborz Jahangiri, Radiopaedia.org, rID 45781
Legionella pneumonia - Case courtesy of Dr Henry Knipe, Radiopaedia.org, rID 31816
Chlamydia pneumonia
Chlamydia-pneumonia - Case courtesy of Dr Andrew Dixon, Radiopaedia.org, rID 14567


  1. 1.0 1.1 1.2 1.3 Irfan M, Farooqi J, Hasan R (2013). "Community-acquired pneumonia". Curr Opin Pulm Med. 19 (3): 198–208. doi:10.1097/MCP.0b013e32835f1d12. PMID 23422417.