Leptospirosis

dr. Doni Priambodo Wijisaksono, SpPD-KPTI

Subdivision of Tropical Medicine and Infectious Disease Internal Medicine Department
Dr Sardjito General Hospital/ Faculty of Medicine Gajah Mada University Yogyakarta

Leptospirosis
Leptospirosis is an acute anthropo-zoonotic
infection , caused by pathogenic leptospires and
characterized by a broad spectrum of clinical
manifestations, varying from inapparent infection to
fulminant, fatal disease.
In its mild form, leptospirosis may present as an
influenza-like illness with headache and myalgias.
Severe leptospirosis, characterized by jaundice,
renal dysfunction, and hemorrhagic diathesis, is
referred as Weil's syndrome.
LEPTOSPIRA
Leptospires are spirochetes belonging to the order
Spirochaetales and the family Leptospiraceae. More than 200
serovars make up the 23 serogroups.
Characteristics: Leptospires are coiled, thin, highly motile, aerob,
gram (-) bacteria, with hooked ends and two periplasmic flagella
that permit burrowing into tissue. These organisms are 6 to 20
um long and about 0.1 um wide. Leptospires require special
media and conditions for growth; it may take weeks for cultures
to become positive.
Leptospira interrogans serotype icterohaemorrhagiae. Silver staining of
organisms grown in culture. Notice the tightly coiled body with hooked
ends.
Darkfield microscopy of Leptospira.
A microscopic view of LeptospiraI bacteria
A microscopic view of LeptospiraI bacteria
Epidemiology
A worldwide distribution that affects at least 160
mammalian species
Transmission of leptospires may follow direct contact
with urine, blood, or tissue from an infected animal or
exposure to a contaminated environment; human-to-
human transmission is rare
Epidemics of leptospirosis may result from exposure
to flood waters contaminated by urine from infected
animals
Epidemiology
International average of 0.1-100 cases per 100,000
International Leptospirosis Society: Indonesia as high
leptospirosis insidence and the 3rd world highest mortality
Indonesia: DKI Jakarta, Jawa Barat, Jawa Tengah, Jogjakarta,
Lampung, Sumatera Selatan, Bengkulu, Riau, Sumatera Barat,
Bali, NTB, Sulawesi Selatan, Sulawesi Utara, Kalimantan
Timur, dan Kalimantan Barat.
Jakarta 2002, > 100 leptospirosis (MR 20%).
RSS: 2005-2007 = 18 cases, 2

EPIDEMIOLOGY
Locations where the infection is
commonplace, caused by :
high rainfall,
close human contact with livestock or wild
animals,
poor sanitation or
workplace exposure (rice farming, etc).
Contact of nasal, oral, or eye mucosal
membranes or abraded or traumatized skin with
urine or carcasses of infected animals.
Urine: Indirect exposure through water, soil, or
foods contaminated by urine from infected
animals is the most common route.
Modes of Transmission
Pathogenesis
Enter the host through abrasions in the skin or through intact
mucous membranes, especially the conjunctiva and the lining
of the oro- and nasopharynx.

Multiplication takes place in blood and in tissues, and
leptospires can be isolated from blood and cerebrospinal fluid
(CSF) during the first 4 to 10 days of illness. The most
important known pathogenic properties of leptospires are
adhesion to cell surfaces and cellular toxicity.
In the kidney, leptospires migrate to the interstitium, renal
tubules, and tubular lumen, causing interstitial nephritis and
tubular necrosis.
In the liver, centrilobular necrosis with proliferation of Kupffer
cells may be found.
In severe leptospirosis, vasculitis may ultimately impair the
microcirculation and increase capillary permeability, resulting in
fluid leakage and hypovolemia.
CLINICAL MANIFESTATIONS
biphasic disease, with 7-14 d incubation period, with
involvement of the CNS, kidney and liver

1st phase = leptospiremic - bacteria in blood and
CSF

2nd phase = immune - bacteria seen in urine but not
other organs or blood; serum agglutinating IgM
antibodies present; signs of meningitis possibly due
to inflammation or immune complex


CLINICAL MANIFESTATIONS
Vary from mild to serious or even fatal. More than
90% of symptomatic persons have the relatively mild
and usually anicteric form of leptospirosis, with or
without meningitis.
Severe leptospirosis with profound jaundice (Weil's
syndrome) develops in 5 to 10% of infected
individuals.
The incubation period is usually 1 to 2 weeks but
ranges from 2 to 26 days.
CLINICAL MANIFESTATIONS
Anicteric Leptospirosis may present as an acute influenza-like
illness, with fever, chills, severe headache, nausea, vomiting,
and myalgias. Muscle pain, which especially affects the calves,
back, and abdomen, is an important feature of leptospiral
infection.
The most common finding on physical examination is fever with
conjunctival suffusion. Less common findings include muscle
tenderness, lymphadenopathy, pharyngeal injection, rash,
hepatomegaly, and splenomegaly. The rash may be macular,
maculopapular, urticarial, or hemorrhagic. Mild jaundice may be
present.

CLINICAL MANIFESTATIONS
The start of this second (immune) phase coincides
with the development of antibodies. Symptoms are
more variable than during the first (leptospiremic)
phase.
Severe Leptospirosis (Weil's Syndrome) Weil's
syndrome, the most severe form of leptospirosis, is
characterized by jaundice, renal dysfunction,
hemorrhagic diathesis, and high mortality. This
syndrome is frequently but not exclusively
associated with infection due to serovar
icterohaemorrhagiae.


Weils syndrome
This severe form of leptospirosis primarily manifests as
profound jaundice, renal dysfunction, hepatic necrosis,
pulmonary dysfunction, and hemorrhagic diathesis.
It occurs at the end of the first stage and peaks in the second
stage, but the patient's condition can deteriorate suddenly at
any time. Often the transition between the stages is obscured.
Fever may be marked during the second stage.
Criteria to determine who will develop Weil disease are not well
defined.
Pulmonary manifestations include cough, dyspnea, chest pain,
bloodstained sputum, hemoptysis, and respiratory failure.
Weils syndrome
Vascular and renal dysfunctions accompanied by jaundice
develop 4-9 days after onset of disease, and the jaundice may
persist for weeks.
Patients with severe jaundice are more likely to develop renal
failure, hemorrhage, and cardiovascular collapse. Hepatomegaly
and tenderness in the right upper quadrant may be present.
Oliguric or anuric acute tubular necrosis may occur during the
second week due to hypovolemia and decreased renal perfusion.
Multi-organ failure, rhabdomyolysis, adult respiratory distress
syndrome, hemolysis, splenomegaly (20%), congestive heart
failure, myocarditis, and pericarditis also may occur.
Weil syndrome carries a mortality rate of 5-10%. The most severe
cases of Weil syndrome, with hepatorenal involvement and
jaundice, carry a case-fatality rate of 20-40%. Mortality rate is
usually higher for older patients.


CLINICAL MANIFESTATION
Two types of leptospirosis:

1.Anicteric leptospirosis or self-
limited illness (85% to 90% of the
cases)

2. Icteric leptospirosis or weils
syndrome (5% to 10% )


Conjunctival hemorrhage
in leptospirosis
Laboratory
Related findings range from urinary sediment changes
(leukocytes, erythrocytes, and hyaline or granular casts) and mild
proteinuria in anicteric leptospirosis to renal failure and azotemia
in severe disease.
The ESR is usually elevated
Peripheral leukocyte counts range from 3000 to 26,000/uL, Weil's
syndrome, leukocytosis is often marked.
Mild thrombocytopenia occurs in up to 50% of patients and is
associated with renal failure.
elevated serum levels of bilirubin and alkaline phosphatase as
well as mild increases (up to 200 U/L) in serum levels of
aminotransferases.
In severe leptospirosis, pulmonary radiographic abnormalities
are more common : a patchy alveolar pattern that corresponds to
scattered alveolar hemorrhage.
DIAGNOSIS
A definite diagnosis of leptospirosis is based either on isolation
of the organism from the patient or on seroconversion or a rise
in antibody titer in the microscopic agglutination test (MAT) with
positive clinical and manifestations.
Lepto IHA, Dipstick-assay (LDA), Lateral flow assay,
LEPTO Dri Dot
Leptospires can be isolated from blood and/or CSF during the
first 10 days of illness and from urine for several weeks
beginning at around 1 week.
Cultures may become positive after 2 to 4 weeks, with a range
of 1 week to 4 months.
Dark-field examination of blood or urine frequently results in
misdiagnosis and should not be used.
Stages of icteric and anicteric leptospirosis.
Treatment and Chemoprophylaxis of
Leptospirosis
Purpose of Drug Administration Regimen

Mild leptospirosis Doxycycline, 100 mg orally bid
or
Ampicillin, 500-750 mg orally qid
or
Amoxicillin, 500 mg orally qid

Moderate/severe leptospirosis Penicillin G, 1.5 million units IV qid
or
Ampicillin, 1 g IV qid
or
Amoxicillin, 1 g IV qid
or
Erythromycin, 500 mg IV qid

Chemoprophylaxis Doxycycline, 200 mg orally once a week

NOTE: All regimens used for treatment are administered for 7 days.
PROGNOSIS
Most patients with leptospirosis recover.
Mortality is highest among patients who are
elderly and those who have Weil's syndrome.
Long-term follow-up of patients with renal
failure and hepatic dysfunction has
documented good recovery of renal and
hepatic function.
PREVENTION
Individuals who may be exposed to leptospires
through their occupations or their involvement in
recreational water activities should be informed
about the risks.
Measures for controlling leptospirosis include
avoidance of exposure to urine and tissues from
infected animals and rodent control.
Chemoprophylaxis with doxycycline (200 mg once a
week) has appeared to be efficacious in military
personnel but is indicated only in rare instances of
sustained short-term exposure.