Leptospirosis

Diagnosis & Treatment

Introduction
• Background: Leptospirosis is a widespread, prevalent zoonotic
infectious disease that can occur in humans and animals and caused by a
type of spiral-shaped pathogenic bacteria called "spirochetes of the genus
Leptospira". It is characterized by sudden onset of fever, rigors, headache,
myalgia, abdominal pain, nausea, vomiting, diarrhea and conjunctival
suffusion or hyperemia (reddish eyes).
• Transmission: Leptospires are commonly spread
by the urine-contaminated water and soil of infected
animals eg: (rodents, dogs, pigs, cattle, sheep, goats
and horses). But a human-to-human transmission is
very rare. It can be transmitted from infected animals
to humans through:
- Direct contact with urine, body fluids or organs of
infected animals.
- Indirect contact with contaminated soil or water or
through ingestion of food or water contaminated by
urine of infected animals.
Diagnosis
(I)- Clinical Diagnosis:

A good clinical history is often helping in

diagnosis of leptospirosis, the important
features based on epidemiologic
exposure history and clinical
manifestations including:

(A)- Risk factors for infection and

high-exposure risk groups (farmers,
veterinarians, military personnel and
ranchers).
(B)- Clinical features and types:
The onset of clinical illness occurs with incubation period between 2–30 days
(typically 5-14 days). Most infections are thought to be asymptomatic and
ranges in severity from mild illness (flu-like illness) to severe form with a
multi-organs affection:
1. Anicteric leptospirosis:
it is a self-limited, milder form of the disease and almost 90% of cases have
this type of illness. Patients do not have jaundice with case fatality rate < 5
%. It is characterized by:
• Fever: patients have remittent fever (38-40°C)
with rigors.
• Myalgia: muscle pain usually involves the calf
muscle and the lower back.
• Headache: characteristically throbbing pain in
head usually located at bilateral temporal or frontal
regions.
• Conjunctival suffusion: there is reddish coloration
of conjunctiva which is very predominant sign and
the most characteristic feature of leptospirosis
which is rarely found in other febrile illnesses & it
occurred in 55% of patients.
2. Icteric leptospirosis (Weil's disease) :
This is the more severe form of leptospirosis,
also known as (Weil's disease). The case fatality
rate for the icteric type is approximately 5% and
about 5-10% of patients have these type of
illness. It is life-threatening illness, characterized
by jaundice and usually associated with other
organs affection. Patients complain from the
same symptoms as in icteric type but severe
with history of jaundice, signs of acute kidney
injury (oliguria /Anuria and proteinuria), dry
cough, anorexia, nausea, vomiting, diarrhea,
abdominal pain and hypotension.
3. Severe leptospirosis : The more severe form of disease with
severe liver and kidney failure and mortality rates among these
patients is 15%. it is similar to icteric leptospirosis but with
features of multi-organs failure are following:

- Liver: hepatic dysfunction including jaundice, hepatomegaly &

tenderness in right hypochondrium are usually detected.
- Kidney: oliguria / anuria and hematuria with complaint of "Cola-
colored urine" and RBC casts in urine microscopy is common.
- Eye: uveitis, sub- conjunctival hemorrhage.
- Cardiovascular system: including septic shock, circulatory
collapse and ventricular arrhythmia.
- CNS: Aseptic meningitis with history of
intense headache.
- Lung: In mild illness patient presents with
only dry cough. In severe cases patients
have cough, hemoptysis, chest pain,
pulmonary alveolar hemorrhage and
respiratory distress may develop and
increase mortality rate to reach 90%.
- Skin: erythematous rashes are seen in
the face, trunks and extremities in many
patients with occasional cases of purpura.
(C)- Differential Diagnosis:

- Malaria.
- Dengue fever.
- Viral hemorrhagic fever.
- Typhoid fever.
- Brucellosis
- Yellow fever.
- EBV Infectious mononucleosis.
- CMV infection.
- Viral hepatitis.
- Ricketts disease.
(II)- Laboratory Diagnosis:

(A)- General investigations:

- CBC: shows slightly leukocytosis with with neutrophilia and thrombocytopenia

may be developed.

- Coagulation profile: Coagulation parameters may be prolonged in severe

leptospirosis in patients with hepatic dysfunction.

- Liver Functions Tests: show an elevation in aminotransferases (SGOT &

SGPT), alkaline phosphatase and bilirubin level in icteric type.

- Renal Function Tests: impaired renal function in severe illness that shows
serum elevation in BUN and creatinine levels.
- Urine Analysis and microscopic examination: revealed proteinuria,
microscopic hematuria and cellular casts.

- ESR & CRP: usually shows moderate to marked elevation.

- Serum Creatinine Phosphokinase (CPK): marked elevation in serum

Creatinine phosphokinase is present with leptospirosis.

- Serum electrolytes: hyponatremia & hypokalemia may be developed in

severe illness due to increased renal excretion of Na and K in urine.

- Lumbar Puncture for CSF analysis: useful only in excluding other causes of
bacterial meningitis. It shows findings consistent with aseptic meningitis with
normal CSF pressure, predominance of lymphocytes and polymorphs,
 protein may be normal or elevated but normal glucose levels.
 - Imaging studies are useful in determining the extent and severity of organ
involvement. This may include chest radiography or computed tomography to
evaluate lung disease.

- ECG: it is important in severe cases of Weil's disease as congestive heart

failure, arrhythmias and cardiogenic shock may occur.

(B)- Confirmatory Laboratory diagnosis :

1- Culture and isolation of leptospires: Isolating the organism by culture allows

definitive diagnosis. Leptospires remain viable in anticoagulated blood for as long
as 11 days but blood cultures may be negative if samples drawn too early or too
late. Leptospires may not be detected in the blood until 4 days after the onset of
symptoms. Culture is difficult, insensitive, requires special media and may take
several weeks.
2- Serological tests:

- Detection of Immunoglobulin M (IgM) by using ELISA: This test can quickly

determine the diagnosis and help in early treatment. However, the test
specificity depends upon the type of antigen used and the presence of
antibodies from previous infections. False positive occurred in the presence
of other diseases such as EBV, CMV infection or viral hepatitis cause false-
positive results.

- Microscopic Agglutination Test (MAT) using a dark field microscope to look

for agglutination: it is the gold standard serodiagnosis for leptospirosis
because this assay has a high sensitivity and allows for the detection of
group specific antibodies and MAT titres > 1:100 are diagnostic of
leptospirosis.
However, in early phase of disease the test has less sensitive as the
antibodies response don not reach detectable levels until the second week
of illness, and it can be affected by treatment.

3- Molecular tests:

Detection of Leptospira DNA using PCR from serum, urine and CSF. PCR
can detect Leptospira DNA in blood even before the antibody response
develops. As PCR detects the presence of Leptospira DNA, it is useful
even after antibiotic treatment has started.
(III)- Diagnostic criteria:
Diagnosis of leptospirosis consists of :
(A)- Good clinical history including epidemiological factors, high-exposure
risk groups and clinical findings of Acute febrile illness with headache,
myalgia associated with a history of exposure to infected animals or an
environment contaminated with animal urine with one or more of the
following:
- Conjunctival suffusion and Calf muscle tenderness, anuria or oliguria
and/or proteinuria, Jaundice.
- Hemorrhagic manifestations (Skin, intestines, lung)
- Symptoms of meningeal irritation.
- Nausea, Vomiting, Abdominal pain, Diarrhea.

(B)- Confirmatory laboratory tests eg; MAT, IgM detection using ELISA or
detection of Leptospira DNA using PCR.
 Treatment
(I)- General supportive care:
A)- IV fluids , correction of electrolytes imbalance and blood transfusion for
bleeding.
B)- Supportive therapy and careful management of renal, hepatic, hematologic,
and central nervous system complications. Ophthalmic drops of mydriatics and
corticosteroids have been used for relief of ocular symptoms.
D)- As with severity of illness in patients in ICU, treatment with pulse-dose
steroids may be used to treat patients with renal failure without dialysis and play a
role early in the management of severe pulmonary disease, circulatory collapse
and septic shock.
E)- Access to mechanical ventilation and airway protection should be available in
the event of respiratory compromise.
(II)- Antimicrobial therapy:
Antimicrobial therapy is indicated for the severe form of leptospirosis and most
leptospiral cases resolve spontaneously, so its use is controversial for the mild
form of leptospirosis as early initiation of antibiotics may prevent the progression
to severe disease and to offer the best clinical outcomes.
(A)- Mild disease: For patients with mild symptoms, doxycycline is the drug of
choice (100 mg orally, twice daily), if not contraindicated. Other options include
azithromycin (500 mg orally, once daily), ampicillin (500-750 mg orally, every 6
hours), amoxicillin (500 mg orally, every 6 hours).

Doxycycline 100mg orally, BID for week – OR

Ampicillin 500-700mg orally, QID - OR
Amoxicillin 500mg orally, QID
Azithromycin or clarithromycin
Ciprofloxacin or Levofloxacin.
(A)- Moderate and severe disease:

Treatment for severe leptospirosis consists of empiric antibiotic therapy.

Intravenous (IV) benzyl penicillin (also known as penicillin-G) is recommended
and considered the first-line antibiotic therapy for severe leptospirosis.

Penicillin G IV 1.5 MU QID– OR

Ceftriaxone 1gm IV once daily - OR
Cefotaxime 1gm IV QID- OR
Erythromycin 500mg IV QID- OR
Ampicillin 1gm IV QID
Thank You