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]

Overview

Leptospirosis must be differentiated from other diseases that cause fever, diarrhea, nausea and vomiting, such as ebola, typhoid fever, malaria, yellow fever, shigellosis, 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).

The table below summarizes the findings that differentiate Leptospirosis from other conditions that cause fever, diarrhea, nausea and vomiting:

Disease	Findings
Ebola	Presents with fever, chills vomiting, diarrhea, generalized pain or malaise, and sometimes internal and external bleeding, that follow an incubation period of 2-21 days.
Typhoid fever	Presents with fever, headache, rash, gastrointestinal symptoms, with lymphadenopathy, relative bradycardia, cough and leucopenia and sometimes sore throat. Blood and stool culture can confirm the presence of the causative bacteria.
Malaria	Presents with acute fever, headache and sometimes diarrhea (children). A blood smears must be examined for malaria parasites. The presence of parasites does not exclude a concurrent viral infection. An antimalarial should be prescribed as an empiric therapy.
Lassa fever	Disease onset is usually gradual, with fever, sore throat, cough, pharyngitis, and facial edema in the later stages. Inflammation and exudation of the pharynx and conjunctiva are common.
Yellow fever and other Flaviviridae	Present with hemorrhagic complications. Epidemiological investigation may reveal a pattern of disease transmission by an insect vector. Virus isolation and serological investigation serves to distinguish these viruses. Confirmed history of previous yellow fever vaccination will rule out yellow fever.
Shigellosis & other bacterial enteric infections	Presents with diarrhea, possibly bloody, accompanied by fever, nausea, and sometimes toxemia, vomiting, cramps, and tenesmus. Stools contain blood and mucous in a typical case. A search for possible sites of bacterial infection, together with cultures and blood smears, should be made. Presence of leucocytosis distinguishes bacterial infections from viral infections.
Dengue	Presence of atypical lymphocytosis in blood differentiate it from leptospirosis.
Others	Viral Hepatitis, rheumatic fever, typhus, and mononucleosis

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)	X	Over legs and trunk pruritic rash May be hemorrhagic	✔	✔	X	Upper gastrointestinal bleeding	Painful lymphadenopathy	X	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.	X	No rash	X	✔	X	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	X	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	✔	✔	✔/X	✔	✔	✔	X	Fever and upper respiratory symptoms	X	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	✔	✔	X	X	✔	X	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, Anit-inflammatory drugs
Typhoid fever	6 to 30 days	No vector Air born disease	✔	X	Blanching erythematous  maculopapularlesions on the lower chest and abdomen	✔	✔	✔	Intestinal bleeding	Rose spots	X	Normal	Blood or stool culture showing salmonella typhi sps.	Residence in endemic area Recent travel to endemic area	Flouroquinolones, Third generation cephalosporins, Azithromycin