LEPTOSPIROSIS

Leptospirosis
an infectious disease.
characterized by a broad spectrum of clinical manifestations (from inapparent
infection to fulminant, fatal disease).

Mild form:
present as an influenza-like illness with headache and myalgias.

Severe leptospirosis:Weil's syndrome

jaundice, renal dysfunction, and hemorrhagic diathesis
ETIOLOGIC AGENTS
Leptospires
Spirochetes
order Spirochaetales
family Leptospiraceae.

The pathogenic leptospires are divided into serovars according to their

antigenic composition.
More than 200 serovars make up the 23 serogroups.
Leptospires
are coiled, thin, highly motile organisms with hooked ends and two
periplasmic flagella that permit burrowing into tissue.

6 to 20 um long and about 0.1 um wide.

Stain poorly but can be seen microscopically by dark-field examination and

after silver impregnation staining.

Require special media and conditions for growth; it may take weeks for
cultures to become positive
Morphology
The Leptospira appear tighly coiled thin flexible Spritochetes
Fine spiral of 0.1 – 0.2 microns
One end appears bent forms a hook.
Actively motile
Seen best with dark field Microscopy.

Greater Understanding with Electron Microscopy

Electron Microscopy show thin axial filament and a delicate membrane
In dark field it may appear as chain of miniature cocci.
Comparative Morphology of
Spritochetes
EPIDEMIOLOGY
Zoonosis with a worldwide distribution that affects at least 160 mammalian
species
Rodents, especially rats, are the most important reservoir, although other
wild mammals, dogs, fish, and birds may also harbor these
microorganisms.

Establish a symbiotic relationship with their host and can persist in the renal
tubules for years
Some serovars are associated with particular animals:
icterohaemorrhagiae/copenhageni : rats
Grippotyphosa: voles
Hardjo:cattle
Canicola :dogs
pomona : pigs.

Transmission
May follow direct contact with:
urine
blood
or tissue from an infected animal
exposure to a contaminated environment
human-to-human transmission is rare.

Excreted in the urine and can survive in water for many months
Water is an important vehicle in their transmission.
Epidemics may result from exposure to flood waters contaminated by urine
from infected animals

Most commonly in the tropics because of:

climate
poor working and hygienic conditions favor the pathogen's survival.

Certain occupational groups are at especially high risk; included are:

veterinarians
agricultural workers
sewage workers
slaughterhouse employees
workers in the fishing industry
Occupation

Certain occupational groups such as agriculture workers in rice and cane

fields, miners and sewer cleaners are potential victims

Recreational exposure and domestic animal contact are also prominent

sources
Recreational water activities, such as canoeing, windsurfing, swimming, and
waterskiing, place persons at risk for leptospirosis
In a recent study in the Netherlands, 14% of patients with confirmed
leptospirosis had acquired the infection while traveling in tropical
countries, mostly in Southeast Asia.
Common during the rainy season in the tropics.
How Man gets Infected
Water the great source
Drinking
Swimming
Bathing, as the urine of Rodents chronically infected contaminate
water sources

Children get infected when in contact with infected Dogs

PATHOGENESIS
Leptospires may enter the host through:
abrasions in the skin or through intact mucous membranes (conjunctiva
and the lining of the oro- and nasopharynx)
Drinking of contaminated water may introduce leptospires through the
mouth, throat, or esophagus.

After entry of the organisms: leptospiremia develops

subsequent spread to all organs.
Multiplication takes place in blood and in tissues.
leptospires can be isolated from blood and cerebrospinal fluid (CSF) during
the first 4 to 10 days of illness.

Can damage the wall of small blood vessels leading to vasculitis with leakage
and extravasation of cells, including hemorrhages.
The most important known pathogenic properties are adhesion to cell
surfaces and cellular toxicity.

Vasculitis is responsible for the most important manifestations of the disease.

Mainly infect the kidneys and liver, any organ may be affected.
In the kidney they migrate to the interstitium, renal tubules, and tubular
lumen, causing interstitial nephritis and tubular necrosis.

Hypovolemia:
due to dehydration
altered capillary permeability may contribute to the development of renal
failure.

In the liver, centrilobular necrosis with proliferation of Kupffer cells may be

found

Pulmonary involvement
result of hemorrhage inflammation.
Invasion of skeletal muscle
results in swelling, and focal necrosis.
In severe leptospirosis, vasculitis may ultimately impair the microcirculation
and increase capillary permeability, resulting in fluid leakage and
hypovolemia.
When antibodies are formed, leptospires are eliminated from all sites in the
host except:
the eye,
the proximal renal tubules,
the brain, where they may persist for weeks or months.

The systemic immune response is effective in eliminating the organism but

may also produce symptomatic inflammatory reactions.
Meningitis: immunologic mechanism
Sequence of Leptospira Infection
CLINICAL MANIFESTATIONS
In symptomatic cases:
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.

Presenting with Jaundice is significant and Important, Serious Manifestation

Renal failure:
during the second week of illness.
Hypovolemia and decreased renal perfusion contribute to the
development of acute tubular necrosis with oliguria or anuria
Manage by Dialysis
Pulmonary involvement
resulting in cough, dyspnea, chest pain, and blood-stained sputum, and
sometimes in hemoptysis or even respiratory failure.
Hemorrhagic manifestations are seen in Weil's syndrome: epistaxis,
petechiae, purpura, and ecchymoses
severe gastrointestinal bleeding and adrenal or subarachnoid hemorrhage are
detected rarely.

severe leptospirosis
Rhabdomyolysis
Hemolysis
Myocarditis
Pericarditis
congestive heart failure
cardiogenic shock
adult respiratory distress syndrome
multiorgan failure
 LABORATORY AND RADIOLOGIC FINDINGS
Related findings range from:
urinary sediment changes:
Leukocytes erythrocyteshyaline or granular casts)
mild proteinuria in anicteric leptospirosis
renal failure and azotemia in severe disease.

Erythrocyte sedimentation rate (ESR) is usually elevated.

In anicteric leptospirosis, peripheral leukocyte counts range from 3000 to
26,000/uL
in 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

Mild increases (up to 200 U/L) in serum levels of aminotransferases.
In Weil's syndrome, the prothrombin time may be prolonged
corrected with vitamin K.
Levels of creatine phosphokinase
elevated during the first week of illness

When a meningeal reaction develops:

polymorphonuclear leukocytes predominate initially and the number of
mononuclear cells increases later.
The protein concentration in the CSF may be elevated
CSF glucose levels are normal.
DIAGNOSIS
A definite diagnosis is based on:
isolation of the organism from the patient
rise in antibody titer in the microscopic agglutination test (MAT).
Serology - ELISA
Several Immunoassays are available as commercial kits
Detection of IgM and razing titers of IgG will guide in association with clinical
history will help in Diagnosis

Leptospires can be isolated

from blood and/or CSF : first 10 days of illness
from urine for several weeks beginning at around 1 week.
Cultures may become positive after 2 to 4 weeks.
Sometimes urine cultures remain positive for months or years after the start
of illness.

Diagnosis of leptospirosis is confirmed:

Enzyme-Linked Immunosorbent Assay (ELISA)
PCR.

Treatment
Penicillin
Drug of choice
For severe cases:
intravenous administration of penicillin G, amoxicillin, ampicillin, or
erythromycin.
In milder cases:
oral treatment with tetracycline, doxycycline, ampicillin, or amoxicillin
Other antibiotics:
cephalosporins, are highly active against leptospires in vitro

Patients with severe leptospirosis and renal failure may require dialysis.
Those with Weil's syndrome may need transfusions of whole blood and/or
platelets.
Intensive care may be necessary.
PROGNOSIS
Most patients recover.
Mortality is highest among patients who are elderly and those who have
Weil's syndrome.
Leptospirosis during pregnancy is associated with high fetal mortality
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, vaccination of animals, and rodent
control. The animal vaccine used in a given area should contain the
serovars known to be present in that area.
Control of Leptospirosis

Rodent control is most important.

Human’s should avoid contact with water contaminated with animal contact.

Vaccination of humans against a specific serovar prevalent in an area has

been undertaken in some European and Asian countries and has proved
effective.

Chemoprophylaxis with doxycycline (200 mg once a week)

DIALYSIS

To remove fluid and uremic waste products from the body when the kidneys
cannot do so
Used to treat patient with edema that does not responds to treatment,
hepatic coma, hyperkalemia, hypertension and uremia

Acute Dialysis:
indicated in high and rising level of serum potassium, fluid overload,
impending pulmonary edema, acidosis, pericarditis
Chronic or maintenance:
indicated in chronic renal failure,ESRD in presence of uremic
signs( nausea, vomiting, severe anorexia,increasing lethargy, mental
confusion) hyperkalemia, fluid overload not responsive to diuretics, fluid
restriction
HEMODIALYSIS
Most commonly used method
Favored in pts ( > 80kg) with no residual renal function.
For ill and requiring short term dialysis and in pt. with ESRD
3 x a wk for atleast 3-4 hrs

Components
DIALYZER: synthetic semipermeable membrane/ artificial kidney, replacing
glomerulus & tubules as the filter
Composition and delivery of dialysate- buffer is usually bicarbonate
Blood delivery system- composed of:
Dialysis machine- blood pump, dialysis solution delivery system
Dialysis access-fistula, graft or catheter through which blood is
obtained for hemodialysis
-complications include thrombosis due to intimal hyperplasia, which
results to stenosis 2 to 3cm proximal to the venous anastomosis
EQUIPMENT
Dialyzers/ artificial kidney
Flat-plate or hollow-fiber: contain thousands of tiny cellophane tubules that
acts as semipermeable membrane
Blood flow through the tubules while a solution(dialysate) circulate around
the tubules.
Exchange of wastes from the blood to the dialysate occurs through
semipermeable membrane tubules

Principles:

Extract toxic nitrogenous substances from the blood, remove excess water
Diffusion, osmosis and ultrafiltration are the principles
Toxin & waste are remove by diffusion using dialysate which is made up
of important electrolyte
Excess water is remove by osmosis

Vascular Access
Subclavian, internal jugular, femoral catheters
circulation for acute hemodialysis is achieved by inserting a double lumen
or multilumen catheter into the access
it can be used for several weeks
catheter are remove when no longer needed

Fistula
More permanent access
 Created surgically
Usually in the forearm, by joining an artery to a vein, either side to side
or end to side
Needles are inserted to the vessels to obtain a blood flow adequate to
pass through dialyser
Takes 4-6 wks to mature before it is ready to use

Graft
Arteriovenous
Created by subcutaneously interposing a biologic, semibiologic or
synthetic graft material between artery and vein
Used if patients vessels are not suitable for fistula, patient with
compromised vascular system
Usually placed in the fore artm, upper arm, or upper thigh.
Infection and thrombosis are the most common complication of
arteriovenous graft.

Complications during Hemodialysis

Common
Hypotension
Muscle cramps
Restless legs syndrome
Nausea & vomiting
Headache
Chest & back pain
Pruritus
Fever & chills

Uncommon
Dialysis dysequilibrium
Dialyzer reaction
Arrhythmia
Cardiac tamponade
Intracranial bleeding
Seizures
Hemolysis
Air embolism
Long-term Complications of Hemodialysis
Osteomalacia
Dialysis-induced beta-2 microglobulin
Myopathy
Accelerated atherosclerosis, vascular calcification
Hyperpigmentation
Hepatitis B/C, idiopathic ascites
Leukopenia, hypocomplementemia, bleeding diathesis
 PERITONEAL DIALYSIS
Remove toxic substances and metabolic waste and re establish normal fluid
and electrolyte balance
Treatment of choice for patients with renal failure who are unable or
unwilling to undergo hemodialysis or renal transplantation.

PRINCIPLES
Peritoneum a serous membrane that covers the abdominal organs and lines
the abdominal wall, serves as the semipermeable membrane
The of the peritoneum constitute a body surface area of about 22, 000 cm2
Sterile dialysate fluid is introduced into the peritoneal cavity through an
abdominal catheter at intervals.

Urea and creatinine metabolic end products normally excreted by the kidneys
are cleared from blood by diffusion and osmosis as waste products move
from an area of higher concentration to an area of lower concentration
across a semipermeable membrane
Urea is cleared at rate of 15-20mL/min, creatinine is remove at slower rate
Usually takes 36 to 48 hrs. to achieved peritoneal dialysis

PROCEDURE:

Preparing the patient

Explain the procedure and obtains sign consent
Assess anxiety, provide support and instruction

Preparing Equipment
cosult the Dr. to determine concentration of dialysate
dialysate warmed to body temperature
Assemble administration set and tubing

Inserting the catheter

ideally catheter is inserted in OR to maintain surgical asepsis

Performing the Exchange

series of cycles are involve
infusion, dwell, drainage of the dialysate
dialysate is infused by gravity into the peritoneal cavity
period of about 5 to 10 minutes is usually required infused 2L of fluid

diffusion of small molecules, urea, creatinine peaks in the 1st 5-10 minutes
of dwell time
Drainage is usually completed in 10 to 30 minutes
Removal of excess water is achieved by using hypertonic dialysate with high
dextrose concentration that creates an osmotic gradients.
Complications of Peritoneal Dialysis
Catheter
Pain
Bleeding
Leakage
Poor flowPeritonitis
flowPeritonitis
Leakage
Bleeding
Hypertriglyceridemia: long term complication

Acute perforation
Peritonitis
Nutrition
High glucose, protein loss
Hernia
Genital edema
Hydrothorax
Back Pain
Peritoneal fibrosis

Why pts don’t live on Dialysis?

*Dialysis does not replace ALL the functions of the kidneys especially those
with long-term significance such as erythropoietin production and Vitamin
D3 synthesis.