LEPTOSPIROSIS

Division of Infectious and Tropical Diseases, Department of

Internal Medicine, University of Sumatera Utara/ Adam Malik
Hospital, Medan, Indonesia.
DEFINITION

• Leptospirosis is an a word wide zoonotic disease caused by leptospira

Interrogan transmitted directly or indirectly from animals to human .
• The leptospira serovars are naturally carried in the renal tubules of
rodents, wild and domestic animals.
• Emerging Infectious disease
• The clinical manifestation are highly variable:
• Mild (unicteric) 90%
• Severe (icteric/Weil’s disease) 10%
Morphology

■ The Leptospira appear tighly

coiled thin flexible
Sprichetes 5 – 15 microns
long.
■ Fine spiral of 0.1 – 0.2
microns
■ One end appears bent forms
a hook
■ Actively motile
■ Seen best with dark field
Microscopy
MODES OF TRANSMISSION
Infection is acquired from contact through skin, mucosa/ conjunctiva with water or
soil contaminated with the urine of rodents, carrier or diseased animals
in the environment.
Ingestion of contaminated water may also cause infection.
 HIGH RISK GROUP

Exposure depends on chance contacts between human and infected animals

or contaminated environment through occupational and/or recreational
activities. Some groups are at higher risk to contact the disease such as:

• Workers in the agricultural sectors • Military personnel

• Sewerage workers
• Livestock handlers
• Pet shops workers
• Travelers who are not previously
exposed to the bacteria in their
environment especially those
travelers and/or participants in
jungle adventure trips or outdoor
sport activitie.
• Search and rescue workers in high
risk environment
• Disaster relief workers (e.g. during
floods)
• People involved with
outdoor/recreational activities such
as water recreational activities, jungle
trekking, etc.
• People with chronic disease and open
skin wounds.
PATHOPHYSIOLOGY

■ Infection  leptospires appear in the blood  invade all tissues and

organs particularly affecting the liver and kidney  cleared from the body
by the host's immune response
■ May also settle in the convoluted tubules of the kidneys  shed in
the urine for a few weeks to several months or longer
■ Subsequently cleared from the kidneys and other organs (may persist
in the eyes for much longer)
■ Produces endotoxin  attach onto the endothelial cells  capillary vasculitis
(endothelial necrosis and lymphocytic infiltration)
■ Vasculitis and leakage  petechiae, intraparenchymal bleeding and bleeding
along serosa and mucosa
■ Lost of fluids into the third space  hypovolaemic shock and vascular
collapse
■ Humans react to an infection by producing specific anti-Leptospira
antibodies
■ Seroconversion
– as early as 5–7 days after the onset of disease
– sometimes only after 10 days or longer
– IgM appear somewhat earlier than IgG and generally remain detectable for
months or even years but at low titre.
clinical manifestations

The incubation period is usually 10 days, with a range of 2 to 30 days.

The clinical manifestations are highly variable. Typically, the disease presents in four
broad clinical categories :
(i) a mild, influenza-like illness (ILI);
(ii) Weil's syndrome characterized by jaundice, renal failure, hemorrhage and myocarditis
with arrhythmias;
(iii) meningitis / meningoencephalitis;
(iv) pulmonary hemorrhage with respiratory failure.

Clinical diagnosis is difficult because of the varied and non-specific presentation.

Confusion with other diseases, e.g. dengue and other hemorrhagic fevers, malaria,
typhoid, melioidosis, influenza, etc. is particularly common in the tropics.
May Present with Major Complications

■ Nephritis
■ Hepatitis
■ Manifestation in eye
■ Muscular lesion
■ Many infection are mild and subclinical
Weil’s Syndrome

■ Is a severe form of leptospirosis that causes continuous fever, stupor, and a

reduction in the blood’s ability to clot, which leads to bleeding within tissues.
Blood test reveal anemia. By the third to sixth day, signs of kidney damage and
liver injury appear. Kidney abnormalities may cause blood in the urine and
painful urination. Liver injury tends to be mild and usually heals completely
Typical course of Leptospirosis
The acute Septicaemic phase

■ bacterial migration into the blood stream, leptospiremia occurs. Clinically this phase is
characterized by a sudden onset of fever (could up to 390-400), with other accompanied flu-like
symptoms such as chillness, headache, sore throat, myalgia, nausea, and vomiting. More
burdensome symptoms such as cough, hemoptysis, dyspnea, abdominal pain with persistent
vomiting may also occurs. In some severe form, aseptic meningitis can develop.
■ During this leptospiremia, pathogen can be isolated through blood, cerebrospinal fluid and other
tissues, but not from urine.
■ This bacteremia phase lasts approximately for 4 – 7 days. Subsequent dissemination to organs
may follow in this phase.
■ Myalgia is severe particularly in calves, back and abdominal muscles. Liver is moderately
enlarged. Hematologically, platelet count typically falls potentially causing thrombocytopenic
purpura or frank bleeding. Serum creatinine increases, with normal creatinine clearance unless
tubular necrosis or glomerulonephritis already develop; with accompanied proteinuria in
urinalysis.
The secondary (immune) phase

■ Immune phase, which occurs immediately or within 2-3 days after, the patient generates
antibodies towards Leptospira. The antibody response mainly involve IgM class that displays
strong agglutination properties and could last for up to several months.
■ During mild infection, signs and symptoms may not be as apparent. However in more severe
cases, meningeal or hepatorenal manifestation is predominant.
■ In such severe form, septicemia and immune phase typically merge and is difficult to
distinguish clinically, showing persistently high fever, jaundice, frank hemorrhage into skin,
mucous membranes or lungs. Hepatomegaly and icteric sclera are clinically more noticeable in
this phase. Purpura and ecchymosis are visible. Renal failure develop, causing oliguria, with
accompanied shock, and myocarditis. Pulmonary edema and pulmonary hemorrhage with
hemoptysis may also occur which highly associated with mortality. .
Diagnosis
■ A good clinical history is often the key to accurate diagnosis in leptospirosis.
■ The problem in the diagnosis of leptospirosis are the most cases underdiagnosed because
symptoms and sign are often nonspecific and serologic confirmation is rarely available.
■ Laboratory studies are used for the purposes: to confirm the diagnosis and to determine the
extent of organ involvement and severity of complication
■ Laboratory studies used to diagnosis of leptospirosis include the following:
■ leptospira immunoglobulin M (IgM or IgM/immunoglobulin G (IgG) enzyme linked
immunoabsorbant assay (ELISA), including rapid diagnostic kits usable in the field
■ Real-time DNA polymerase chain reaction (PCR) of blood, urine, and cerebrospinal fluid
(CSF)
■ Microscopic agglutination testing (MAT); criteria standard for serologic identification of
leptospira, available at reference laboratories, Single titer ≥1:200 or 4-fold rise in serum
drawn between the first and fourth week of illness is considered diagnostic
■ Culture of leptospira from body fluids or tissue (criterion standard, but requires specific
media and several weeks’ incubation, thus usually limited to reference laboratory)
■ Determining the extent of organ involvement and severity of complications may
include the following:
■ complete blood cell (CBC) count, renal function test, coagulation test, liver function
test, CSF analysis, chest radiography,
■ biliary tract ultrasonography, Electrocardiography (ECG )
 The WHO-SEA Guidelines of Leptospirosis Diagnostic
Suspected
Acute febrile illness (>38.50C)
And/or severe headache with:
 Myalgia
 Prostration AND/OR
 Conjunctival suffusion, AND
 History of exposure to leptospira -  Meningeal irritation
contaminated environment
Probable (At primary health care level) Confirmed
Suspect case with any two of the following: A confirmed case of Leptospirosis is a suspect
 Calf tenderness or probable case with any one of the following:
 Cough with or without hemoptysis  Isolation of leptospirosis from clinical
 Jaundice specimen
 Hemorrhagic manifestations  Positive PCR result
 Sero-conversion from a negative to positive
 Anuria/oliguria and/or proteinuria or four-fold rise in titer by MAT
 Breathlessness  Titer MAT of 400 and greater in a single
 Cardiac arrhythmias sample
 Skin rabies
Probable (At secondary and tertiary health care levels)
 Base on availability of laboratory facilities a
probable case of leptospirosis is a suspect case
with a positive rapid IgM test AND OR supportive
serologic findings (i.e, a MAT titer equal 200 in a
single sample and or any three following
 Urinary findings: proteinuria, pus cells, blood
 Relative neutrophilia (>80%) with lymphopenia
 Platelets <100.000/cu mm
 Elevated serum bilirubin > 2mg %: liver enzymes
moderately
 Raised serum alkaline phosphatase,
S amylase, CPK
Purpose of Drug Administration Regimen

Treatment
 Mild Leptospirosis Doxycycline 100 mg orally bid or
Ampicillin 500-700 mg orally qid or
Amoxicilin 500 mg orally qid
Azithromycin or clarithromycin
Ciprofloxacin or levofloxacin

 Moderate/severe leptospirosis Penicilin G 1,5 million units IV qid or

Ampicilin 1 g IV qid or
Amoxicilin 1 g IV qid or
Ceftriaxone 1 g IV once daily or
Cefotaxime 1 g IV qid or
Erythromycin 500 mg IV qid

Chemoprophylaxis Doxycycline 200 mg orally once a week

Azithromycin 250 mg orally or twice a week

Note: All regiment used for treatment are administered for 7 days