Leptospirosis differential diagnosis

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]

Overview

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, Hemoptysis	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	NSAIDs
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	Plasmodium falciparum: 9-14 days Plasmodium vivax: 12-18 days Plasmodium ovale: 18-40 days	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	Epistaxis 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, Hemoptysis	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	Fluoroquinolones, Third generation cephalosporins, Azithromycin

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	++	++	++	-	-	-	-	Bronchial wall thickening Centrilobular nodules Ground-glass attenuation Consolidation	-	-	+	Doxycycline
L. Pneumophila infection	+	+++	+++	-	+	++	+	Often Multifocal	++	+	++	Doxycycline
Influenza	++	++	++	++	++	+/-	+/-	Bi-basal air-space opacities Perihilar reticular and alveolar infiltrates	-	-	-	zanamivir, oseltamivir,
Endocarditis	++	++	+	-	-	-	-	Hazy opacities at lung bases bilaterally	-	+/-	+/-	Vancomycin
Coxiella burnetii infection	++	-	+	+/-	-	+/-	Minimal	Segmental or lobar opacification Occasional pleural effusions	-	+/-	=/-	Doxycycline
Leptospirosis	++	+	++	+	+	++	-	Multiple ill-defined nodules in both lungs.	+++			Doxycycline, azithromycin, amoxicillin
Brucellosis	++	-	+	-	++	+	-	Soft miliary mottling Parenchymal nodules Consolidation Chronic diffuse changes Hilar or paratracheal lymphadenopathy Pneumothorax.	-/+	+/-	+/-	Doxycycline, rifampin

Key;

+, 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	Q fever is characterized by abrupt onset of fever, myalgia, headache, and other constitutional symptoms. Cough is the most prominent respiratory symptom and it is usually dry. Cough is associated with dyspnea and pleuritic chest pain.	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 can be asymptomatic. Headache, nausea, and malaise usually precede the onset of symptoms. Cough is intractable and nonproductive.	Postitve Coombs test Leukocytosis Thrombocytosis	Mycoplasma pneumonia - Case courtesy of Dr Alborz Jahangiri, Radiopaedia.org, rID 45781
Legionellosis	Legionellosis is characterized by cough that is slightly productive. Constitutional symptoms such as chills, myalgia, and arthralgia. Gastrointestinal symptoms such as diarrhea, nausea, and vomiting.	Labs are nonspecific for diagnosing legionellosis Renal and hepatic dysfunction Thrombocytopenia and leukocytosis Hyponatremia	Legionella pneumonia - Case courtesy of Dr Henry Knipe, Radiopaedia.org, rID 31816
Chlamydia pneumonia	There are no specific clinical features of chlamydia pneumonia. Symptoms appear gradually. Chlamydia infection is usually associated with upper respiratory tract symptoms (pharyngitis, sinusitis, etc). It might be associated with extrapulmonary maifestations such as meningitis and Guillain-Barre syndrome.	Chlamydia pneumonia is usually associated with normal WBC count. Diagnosed with the presence of antichlamydial antibody (through complement fixation or direct immunofluoroscence) or direct antigen detection.	Chlamydia-pneumonia - Case courtesy of Dr Andrew Dixon, Radiopaedia.org, rID 14567