LEPTOSPIROSIS

EPIDEMIOLOGY

Endemic zoonosis caused by pathogenic Leptospira species

Worldwide distribution
More common in tropics and subtropics
Men>Women
In the Philippines:
680 leptospirosis cases and 40 deaths from the disease reported every year
Prevalence of 10/100,000
Peak incidence in July to October
ETIOLOGIC AGENT

Order Spirochaetales, family Leptospiraceae

22 leptospiral species
10 are pathogenic
5 are intermediate
7 are non pathogenic
TRANSMISSION

Affects almost all mammalian species

RODENTS most important reservoir
WATER most important vehicle (survive a humid environment for
months)
Direct contact with urine, blood, or tissue from an infected animal
Exposure to environmental contamination
Human-human transmission is very rare
EPIDEMICS

Not well understood

Outbreaks
may result form exposure to flood waters contaminated by urine from
infected animals
May occur without floods
Flood may occur without outbreaks
RISK FACTORS

Direct/indirect contact with animals

Occupation
Veterinarians, agricultural workers, slaughterhouse employees, fishing
industry workers

Recreational activities
Canoieng, windsurfing swimming, waterskiing
PATHOGENESIS
Transmission through cuts, abraded skin, or mucous
membrane especially conjunctival and oral mucosa.

Leptospiremic phase
Organisms proliferate, cross tissue barriers,
disseminate hematogenously to all organs

Initial incubation period isolated from the

blood stream
Evade complement-mediated killing by Pathogenic leptospires resist ingestion and
binding factor H strong inhibitor of killing by neutrophils, monocytes, and
complement system macrophages.

Immune phase
appearance of antibodies coincides with
the disappearance of leptospires from the
blood.

Bacteria persist in various organs, including liver, lung,

kidney, heart, and brain
PATHOGENESIS

Renal
acute tubular damage and interstitial nephritis
Acute tubular lesions progress in time to interstitial edema and acute
tubular necrosis
Severe nephritis is observed in patients who survive long enough to
develop it and seems to be a secondary response to acute epithelial
damage

Liver
focal necrosis, foci of inflammation, and plugging of bile canaliculi
Widespread hepatocellular necrosis is not found.
PATHOGENESIS

Petechiae and hemorrhages

heart, lungs, kidneys (and adrenals), pancreas, liver, gastrointestinal
tract (including retroperitoneal fat, mesentery, and omentum),
muscles, prostate, testis, and brain (subarachnoid bleeding)

Platelet consumption may play a role

Consumptive coagulopathy
elevated markers of coagulation activation (thrombinantithrombin
complexes, prothrombin fragments 1 and 2, d-dimer)
diminished anticoagulant markers (antithrombin, protein C)
deregulated fibrinolytic activity.
CLINICAL MANIFESTATIONS

Incubation period - 12 weeks but ranges from 1 to 30 days.

Biphasic
Acute leptospiremic phase
characterized by fever of 310 days duration
Organism can be cultured from blood.
Immune phase
Resolution of symptoms may coincide with the appearance of antibodies
Leptospires can be cultured from the urine.
The distinction between the first and second phases is not always
clear
Milder cases do not always include the second phase
Severe disease may be monophasic and fulminant
BIPHASIC NATURE OF LEPTOSPIROSIS AND RELEVANT
INVESTIGATIONS AT DIFFERENT STAGES OF DISEASE.
MILD LEPTOSPIROSIS
Asymptomatic
Serologic evidence of past inapparent infection is frequently found in
persons who have been exposed but have not become ill
HISTORY
Flu-like illness of sudden onset
fever, chills, headache, nausea, vomiting, abdominal pain,
conjunctival suffusion (redness without exudate), and myalgia.
Muscle pain is intense and especially affects the calves, back, and
abdomen.
The headache is intense, localized to the frontal or retroorbital
region (resembling that occurring in dengue), and sometimes
accompanied by photophobia.
Aseptic meningitis may be present and is more common among
children than among adults
MILD LEPTOSPIROSIS
Physical Examination
Fever
conjunctival suffusion
pharyngeal injection
muscle tenderness
Lymphadenopathy
Rash
Meningismus
Hepatomegaly
Splenomegaly
MILD LEPTOSPIROSIS

Natural course
Spontaneous resolution within 710 days
Persistent symptoms have been documented
Mortality rate in mild leptospirosis is low.
SEVERE LEPTOSPIROSIS
Often rapidly progressive
Casefatality rate ranging from 1 to 50%
Higher mortality rates
age >40
altered mental status
Acute renal failure
Respiratory insufficiency
Hypotension
Arrhythmias.
The classic presentation, often referred to as Weil's
syndrome
triad of hemorrhage, jaundice, and acute kidney
SEVERE LEPTOSPIROSIS
Jaundice 5-10%
Acute kidney injury common
Electrolyte abnormalities hypokalemia, hypocalcemia
Leptospiral nephropathy hypomagnesemia
Hypotension is associated with acute tubular necrosis, oliguria, or anuria
*requiring fluid resuscitation and sometimes vasopressor therapy.

Cardiac involvement
nonspecific ST and T wave changes
Repolarization abnormalities and arrhythmias - poor prognostic factors.
Myocarditis
Rare hemolysis, thrombotic thrombocytopenic purpura, and hemolytic-
uremic syndrome.
SEVERE LEPTOSPIROSIS

Septic shock with multiorgan failure and/or severe

bleeding complications
lungs (pulmonary hemorrhage)
gastrointestinal tract (melena, hemoptysis)
urogenital tract (hematuria)
skin (petechiae, ecchymosis, and bleeding from
venipuncture sites).
Pulmonary hemorrhage (with or without jaundice
presenting with cough, chest pain, respiratory distress, and
hemoptysis that may not be apparent until patients are
intubated.
SEVERE LEPTOSPIROSIS

Long-term symptoms
fatigue, myalgia, malaise, and headach
may persist for years

Sequelae Autoimmune-associated uveitis

DIAGNOSIS

Based on appropriate exposure history combined with

any of the protean manifestations of the disease
Signs of a bacterial infection
leukocytosis with a left shift
elevated markers of inflammation (C-reactive protein level and
erythrocyte sedimentation rate)
Thrombocytopenia (platelet count 100 109/L)
Urinalysis
Urinary sediment changes (leukocytes, erythrocytes, and hyaline
or granular casts)
mild proteinuria in mild disease
renal failure and azotemia in severe leptospirosis.
DIAGNOSIS

Blood Chemistry
Serum bilirubin levels may be high
Aminotransferase and alkaline phosphatase moderate levels
Amylase levels are often elevated.
Aseptic meningitis (CSF Findings)
Pleocytosis - few cells to >1000 cells/L
Polymorphonuclear cell predominance.
Protein Concentration may be elevated
CSF glucose levels are normal.
DIAGNOSIS

Pulmonary radiographic abnormalities

Patchy bilateral alveolar pattern that corresponds to
scattered alveolar hemorrhage.
Affect the lower lobes
Other findings
pleura-based densities (representing areas of hemorrhage)
diffuse ground-glass attenuation typical of acute respiratory
distress syndrome (ARDS).
DIAGNOSIS

Definitive diagnosis
based on isolation of the organism from the patient
positive result in the polymerase chain reaction (PCR)
seroconversion or a rise in antibody titer.

Standard serologic procedures

Microscopic agglutination test (MAT)
single antibody titer of 1:2001:800
fourfold or greater rise in titer in acute- and convalescent-phase serum
specimens.
Enzyme-linked immunosorbent assay (ELISA)
TREATMENT
TREATMENT
Nonoliguric renal dysfunction
aggressive fluid and electrolyte resuscitation to prevent
dehydration and precipitation of oliguric renal failure.
Oliguric renal failure
Peritoneal dialysis or hemodialysis should be provided.
Rapid initiation of hemodialysis has been shown to reduce
mortality risk and typically is necessary only for short periods.
Pulmonary hemorrhage
reduced pulmonary compliance (as seen in ARDS)
mechanical ventilation with low tidal volumes to avoid high
ventilation pressures.
use of glucocorticoids and desmopressin are contradictory
PROGNOSIS

Most patients recover

High mortality
Elderly
Has severe disease (pulmonary hemorrhage, Weils syndrome)

High fetal mortality rates for Leptospirosis in pregnancy

Long-term follow-up of patients with renal failure and hepatic
dysfunction has documented good recovery of renal and
hepatic function.