OS 217: Infectious Diseases
1
Lec 19: Leptospirosis
Dr. Evalyn A. Roxas, MD, FPCP. DPSMID
TOPIC OUTLINE
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
Introduction
Epidemiology
Causative Agent
Pathogenesis
Natural Course of the Disease and
Manifestations
A. Leptospiremic Phase
B. Leptospiruric Phase
Classification of Leptospirosis
A. Mild
B. Moderate to Severe
C. Weil’s Syndrome
Diagnosis
A. WHO Criteria for Definitive Leptospirosis
B. Laboratory Diagnosis
C. Faine’s Criteria
Treatment
Prophylaxis
Management of Complications
A. Acute Kidney Injury
B. Pulmonary Involvement
Prevention and Control
I. INTRODUCTION
1.
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Leptospirosis
infectious, zoonotic disease
asymptomatic infection to severe and fatal illness
usually peaks after periods of high rainfall storms
Most important reservoir are rats; Others: domestic/wild animals
(dogs, cats, swine, cattles, raccoons,)
Transmission – contact of mucous membranes or broken skin
with water, moist soil or vegetation contaminated with the urine of
infected animals
Incubation period - 10 days (2-30 days)
II. EPIDEMIOLOGY
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Actual incidence of leptospirosis in the Asia Pacific region is not
well-documented, similar to the situation in many regions worldwide
Aside from under reporting, incidence data are further compromised
by the unavailability of laboratory diagnosis
Within the Asia pacific region, Southeast Asia and Oceania have the
highest incidence of leptospirosis.
Philippines has moderate incidence of leptospirosis in the Asia
pacific Region (1 to 10 annual incidence per 100,000) along with
China, mainland India, Indonesia and Malaysia
Prevalent Leptospira serovars (1960-1970) Pyrogenes, Bataviae,
Pomona, Grippotyphosa, Manilae and Javanica
Outbreaks of leptospirosis due to flooding were reported in prisons,
penal farms, and in many parts of the country
DOH statistics after typhoon Ondoy (October 27, 2009)
o Total Leptospirosis Cases = 2,292
o Mortality = 178 (7.6%)
From 2016 trans:
Endemic throughout the world
May be the most common zoonosis
o Temperate zones: 0.1 to 1/100,000/year
o Tropics: >10/100,000/year
o Outbreaks: >100/100,000 may be affected
Peak incidences
o Tropics: Rainy season
o Temperate regions: Late summer to fall
Shen, Franz, Jerry
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Underdiagnosed due to wide range of presenting clinical pictures
Reasons for resurgence of leptospirosis
o Rapid urbanization
o Forested areas converted to residential or business zones
o Forested areas has decreased from 70% in 1900 to 18% in 1999
o Typhoons hit the country an average of 20x/yr with associated heavy
rainfall
o Flooded areas are expanding
o Drainage, creeks, esteros are clogged with garbage
o Poor waste disposal system
o Rat infestation
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Pathogenic Leptospires
o long corkscrew-shaped bacteria, too thin to be visible under the
ordinary microscope
o dark-field microscopy is required
Phenotypic classification
o Genus Leptospira
o Species L. interrogans (pathogenic)
o L. biflexa (saprophytic)
240 pathogenic serovars
Clinical
Legends:
From the Powerpoint presentation
From the lecturer
From other sources (textbook, Internet, etc.)
From 2016
September 10, 2014
III. CAUSATIVE AGENT
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Table 1. Prevailing Leptospira serovars in humans in the Philippines
Prevailing Serovars
Pyrogenes
Grippotyphosa
Autumnalis
Hardjo
Bataviae
Manilae
Icterohemorrhagiae
Poi
Pomona
Javanica
Hyos
Tarrasoni
1. Natural Habitat
o Leptospires can be:
o Free living in water, soil or sewage contaminated with the animal urine;
or
o Associated with renal infection with animals
o Incidence is high in warm climate countries because they survive longer in
humid condition.
o Saprophytic leptospires – free-living organisms found in wet or humid
environments ranging from surface waters and moist soil to tap water
o Saprophytic halophilic leptospires – found in seawater
2. Transmission
o Human become incidental/ accidental host:
o direct contact with infected animals, or
o indirectly through contact with water contaminated with excreta.
o Human infections can be acquired through occupational (rice field fever,
cane cutter’s disease, swineherd’s disease, dairy farm fever, mud fever)
and recreational exposures
o Human to human transmission is rare by sexual intercourse,
transplacentally from mother to fetus, via breast milk
3. Transmission Cycle
o Mammals are the maintenance host of leptospires
o an MH is a carrier animal/specie which becomes a reservoir of a distinct
serovar
o includes rodents, livestock, companion animals
o MH do not show signs of illness but once infected shed the organism in
their urine for life
o Pathogenic leptospires are maintained in the renal tubules
o Transmission of leptospires requires continuous circulation of the
pathogen among maintenance hosts
o Leptospires survive for weeks or months in moist soil and water after
excretion in the urine
o Cell aggregation and biofilm formation contribute to survival of leptospires
outside their hosts
o Knowledge on the prevalent serovars and their maintenance host
is essential for epidemiologic identification.
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Lec 15: Leptospirosis
4. Persistent Colonization
o Essential component of the life cycle of pathogenic leptospires is
persistent renal carriage in reservoir animals
o In rats, systemic infection occurs but is subsequently cleared from all
organs except the renal tubules
o Colonized tubules are densely populated with leptospires which aggregate
into an amorphous biofilm
o Expression of LPS O antigen facilitates carriage in the tubules
o Renal tubule is an immunopriviledged site, contributing to high-grade
persistence of the pathogen
Figure 1. The Cycle of Leptospiral Infection
IV. PATHOGENESIS
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Organism gains entry in the body through
o skin abrasions or cuts
o intact mucosa: conjunctiva, oro/nasopharynx, gut
o waterlogged skin
o inhalation of droplets of urine
o ingestion of contaminated water or food
After entry, it multiplies in the blood and tissues including CSF
Leptospires can damage the wall of small blood vessels causing
vasculitis
Vasculitis is responsible for the most important manifestations of
the disease.
The most important known pathogenic properties of leptospires are
adhesion to cell surfaces and cellular toxicity
Kidneys
o Leptospires migrate to the interstitium, renal tubules, and tubular
lumen, causing interstitial nephritis and tubular necrosis.
o Much recent work has focused on the role of surface lipoprotein
 The major surface lipoprotein seen among pathogenic
serovars, LipL32
 LipL32 is the major target of the human immune response
and is involved in pathogenesis of tubulointerstitial nephritis
Liver
o Centrilobular necrosis with proliferation of Kupffer cells
o Severe hepatocellular necrosis is not a feature of leptospirosis
o Liver involvement – not a feature of severe leptospirosis
Pulmonary
o Involvement is the result of hemorrhage and not of inflammation
o Pulmonary hemorrhage is secondary to vasculitis, not
thrombocytopenia
Skeletal Muscle
o Invasion of leptospires results in swelling, vacuolation of the
myofibrils and focal necrosis
o Skeletal muscle involvement – manifests as calf tenderness
Prolonged leptospiremia until the host mounts an effective immune
response
Leptospires evade the host innate immune response during the initial
stages of infection; resist the alternative pathway of complement
activation
Widespread hematogenous dissemination and penetration of tissue
barriers
o Facilitated by systemic vasculitis
 Pulmonary haemorrhage
 Acute tubular necrosis
 Destruction of hepatocytes
Shen, Franz, Jerry
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OS 213
Onset of disease correlates with appearance of agglutinating antibodies
and clearance of leptospires by antibody-mediated opsonization and lysis
Vascular endothelial damage – hallmark of severe leptospirosis causing
capillary leakage, hemorrhagic gastroenteritis, vasculitis
Activation of coagulation cascade causing DIC
Production of pro-inflammatory cytokines which mediate inflammation
and damage of end-organ tissues
1. Determinants of Disease
o Host susceptibility factors – HLA DQ6
o first genetic susceptibility factor identified
o synergism between HLA-DQ6 and environmental exposure found during
the triathlon outbreak is the first gene-envt interaction to be identified
for an infectious disease
o Dose of infecting inoculum
o Virulence characteristics of the infecting strain, which include:
o Surface proteins which mediate interaction between bacteria and host
tissues
o Loa22 – first virulence factor gene exposed on bacterial surface
o Motility of leptospira and its ability to swim through viscous media;
impt in the initial infection and dissemination of organisms from site of
entry to sites of end-organ
o Hemolysins, proteases, sphingomyelinase, microbial collagenase
o Leptospiral LPS is less toxic than the gram negative LPS, activates
macrophages via TLR2 instead of TLR4
2.
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Determinants of Disease
Incubation period : 5-14 d, range 2-30 d
Febrile illness which resolves after the first week of symptoms
5-15% develop severe leptospirosis
Severe late phase manifestations occur 4-6 days after onset of illness but
may vary depending on inoculum dose
Classic presentation
o Septicemic phase (5 to 7 days)
o Interphase (1 to 3 days)
o Immune phase (4 to 30 days)
In severe cases, no distinct phases
Some present only with immune phase
Figure 2. Disease Kinetics of Leptospirosis
V. NATURAL COURSE OF THE DISEASE AND CLINICAL
MANIFESTATIONS
1. Natural Course of the Disease (see Appendix 1)
A. Leptospiremic/Septicemic Phase
o first week after entry, proliferation of spirochetes, appearance of
systemic/non-specific manifestations (see manifestations in
accompanying slides/pictures)
o High remittent fever
o Headache, chills, rigors, myalgias
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Lec 15: Leptospirosis
o
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B.
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Conjunctival suffusion without discharge and calf tenderness are most
specific findings
Anorexia, nausea, vomiting
Abdominal pain
Cough, pharyngitis
Pretibial maculopapular eruption
U/A: mild proteinuria, pyuria, hematuria with or without
hyaline/granular casts
Death rare in this phase of illness
OS 213
Severe pulmonary hemorrhages
Cardiac involvement
Weil’s Syndrome
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Most severe form of leptospirosis
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Manifests as:
o
Profound jaundice
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Renal dysfunction
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Hepatic necrosis
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Pulmonary dysfunction
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Hemorrhagic diathesis
Leptospiruric/ Immune Phase
o Second week; immune phase or production of antibodies against the
spirochetes; appearance of more specific signs and symptoms
o Weil’s Disease - Impaired hepatic function
 Disturbance of liver function out of proportion to pathologic
findings (mild and nonspecific)
 Degenerative changes in hepatocytes
 Kupffer cells are hypertrophied
 Cholestasis, erythrophagocytosis
 Mononuclear cell infiltrates
 Necrosis almost absent
 Direct bilirubin > 80 mg/dL
 AST and ALT ≤ 200 U/L
 Jaundice is slow to resolve
 BUN usually < 100 mg/dL
 Crea 176 – 707 mg/dL
 Initially non-oliguric hypokalemic renal insufficiency
 Impaired sodium reabsorption (loss of ENaC channel in
proximal tubule)
 Increased distal sodium delivery
 Potassium wasting
 Progresses to oliguric renal failure if electrolyte and volume losses
are not replaced
3 most common manifestations: fever, headache, myalgia; however,
diarrhea is becoming a more common manifestation in a recent study
C. Clinical Manifestations
 Many Leptospira-infected persons remain asymptomatic
 Among the symptomatics, more than 90% have relatively mild and
usually anicteric form of leptospirosis
 Severe leptospirosis develops in only 5-10% of infected
individuals
D.
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When to Suspect Leptospirosis?
Any individual with acute febrile illness of at LEAST 2 days
Residing in a flooded area OR
High risk exposure (Wading in flood waters, contact with
contaminated animal fluids, swimming in or ingestion
ofcontaminated water )
At LEAST 2 of the following symptoms:
o Myalgia
o Calf tenderness
o Conjunctival suffusion
o Chills
o Abdominal Pain
o Headache
o Jaundice
o Oliguria
VI. CLASSIFICATION OF LEPTOSPIROSIS
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WHO NEEDS HOSPITAL ADMISSION?
A. Mild – outpatient management
 Stable vital signs
 Anicteric sclerae
 Good urine output
 (-) Meningismus
 (-) Sepsis/ Shock
 (-) Dyspnea
 (-) Jaundice
 Tolerates oral medications
B. Moderate to Severe – requires hospitalization
 Unstable vital signs
 Jaundice/ icteric sclerae
 Abdominal pain
 Nausea, vomiting, diarrhea
 Oliguria/ anuria
 Meningeal irritation
 Sepsis/ Shock
 Altered sensorium
 Difficulty breathing
 Hemoptysis
Figure 3. Common Presenting Features of Leptospirosis
Mild leptospirosis
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Fever
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Body aches (severe myalgia)
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Headache
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Conjunctival suffusion
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Diarrhea &/ or vomiting
Moderate to severe leptospirosis
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Jaundice
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Fever > 40 C
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Hypotension
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Active Bleeding
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Oligura/Anuria
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Sensorial changes
Shen, Franz, Jerry
Basis for determining management
E.
Weil’s Syndrome
VII. DIAGNOSIS
A. WHO Criteria for Definitive Leptospirosis
a. Positive leptospiral culture of the blood and/or urine
b. High positive single lepto Microagglutination Test (MAT) titer of
1:1600
c. Seroconversion from initial MAT negative to a positive antibody
titer
d. Fourfold rise in antibody titers by MAT from acute to
convalescent
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Lec 15: Leptospirosis
B. Laboratory Diagnosis
1. Direct Detection Method
 Gold standard is culture isolation of the organism
 Uses specialized culture media (EMJH or Fletcher’s)
 Additional/alternative test: Korthof Media; (+) Dinger’s Ring: whitish
aggregation indicative of growth of spirochetes
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2. Indirect Detection Method [Microagglutination Antibody
Test for Leptospirosis (MAT)]
Utilizes live antigens of leptospires (non-pathogenic) against
patient’s serum and examined under dark field for agglutination
Genus specific MAT
o Uses Leptospira biflexa as live antigen
o Available only in UP- PGH Medical Reseach Laboratory
o 10 to 12 leptospiral serovars prevalent in the country
MAT Postive – a single antibody titer of 1:200- 1:800 (locally,
1:1600)
Cross reactions: syphilis, relapsing fever, Lyme disease, viral
hepatits, HIV, legionellosis, autoimmune disease
Interpretation of MAT
o MAT Positive
 a single antibody titer of 1:200 to 1:800 (locally, the cut-off is
1:1600 because of the prevalence in the country)
 Preferably, a fourfold or greater rise in titer is detected
between acute- and convalescent-phase serum specimens.
 Initial high titer of 1:1600
 Seroconversion
Interpretation of MAT results:
o Probable Cases -– cases combining with epidemiologically
suggestive features with compatible clinical, laboratory, and
radiographic findings, with no other diagnosis envisioned
o Confirmed case -– finding microorganism on direct examination
or culture of blood or urine or seroconversion or by a significant
increase in the antibody titer between two samples
e. Faine’s Criteria (see Appendix 2)
 also used for prognostication; not definitive
 Based on WHO Faine’s Criteria
o Scoring system for diagnosis of Leptospirosis on the basis of
clinical, epidemiological and laboratory data (A+B+C).
o Current Leptospirosis :
 Score of ≥26 when using PART A, PART A+B
 Score of ≥ 25 using PART A+B+C
 Modified Faine’s Criteria
o Sensitivity – 58 %
o Specificity – 97 %
o Positive Predictive Value – 86 %
o Negative Predictive Value – 90 %
 Clinical Utility of Modified Faine’s Criteria in the Diagnosis of
Leptospirosis
o The sensitivity (Sn) of the Modified Faine’s Parts A+B (4%,
95% CI 1 to 8) increased with the addition of Part C (73%,
95% CI 64 to 81).
o Initial high titer MAT was most sensitive at a cut-off titer level
of 1:400 (57%, 95% CI 48 to 67).
o No significant correlation was found between disease severity
and either time to culture positivity (p=0.74) or initial MAT titer
levels (p=0.16).
 Clinical Diagnosis based on WHO Faine’s Criteria
o Inclusion of malaise, chills and oliguria, and revision of the
point allocation and the use of MAT titer level of 1:400
resulted in a criteria with a significantly higher Sn (95%, 95%
CI 92 to 99%)
o Conclusion: The Modified Faine’s Criteria did not reflect local
leptospirosis symptomatology.
 Taken singly, the diagnostic utility of Lepto IgM test, initial
high titer MAT and Modified Faine’s Criteria remained
poor.
 However, revision of the Modified Faine’s symptom
checklist and scoring based on local data plus reassessment of the cut-off values for MAT yielded a
criterion of greater clinical utility in the diagnosis of
leptospirosis.
Shen, Franz, Jerry
OS 213
VIII. TREATMENT
Table 2. Treatment of Mild and Moderate-Severe Leptospirosis
Primary Drug
Alternative Drug
Mild Leptospirosis
Doxycycline
 Amoxicillin 500 mg
100 mg BID PO x 7
q 6 hours PO or 1g
days
q8
 Azithromycin
Dihydrate
1g
initially then 500
mg OD PO x 2
more days
Moderate to Severe Penicillin G1.5
 Ceftriaxone 1gm
M IV q 6 hours x 7
IV q 24 hours
Leptospirosis
 Ampicillin 0.5-1gm
days
IV q 6 hours
 Azithromycin
dihydrate 500 mg
OD x 5 days
 Cefotaxime 1gm IV
q 6 hours
1. The Evidence
 Doxycycline for anicteric leptospirosis in Panama showed a
reduction in the duration of fever
 Randomized controlled trial involving 42 patients with severe
leptospirosis showed that length of febrile period, length of hospital
stay, creatinine level, and leptospiruria was significantly shorter in
the penicillin group compared to placebo
 Prospective, open-label, randomized trial in Thailand: ceftriaxone
and IV penicillin had comparable treatment outcomes in terms of
duration of fever, duration of organ dysfunction, and mortality rate in
severe leptospirosis.
2.
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Cost-effectiveness
Empiric treatment is potentially cost-effective
Early treatment resulted in fewer hospitalizations and complications
Cost per patient with doxycycline was low
3.
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Jarisch-Herxheimer Reactions
Systemic reaction resembling bacterial sepsis
Begins 6-8 hours after administration of penicillin
Sudden rise and gradual fall in body temperature and blood
pressure
Abrupt onset of chills, myalgia, headache, tachycardia,
hyperventilation, vasodilation with flushing, obtundation
Peripheral leukocytosis and lymphopenia
Postulated etiology - inflammatory process that results from
activation of the cytokine cascade (increase IL-1 and IL-6)
secondary to release of heat stable protein from degenerating
spirochetes. Patients receiving penicillin should be monitored for
these reactions
No report of a Jarisch-Herxheimer reaction in leptospirosis patients
given Penicillin
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IX. PROPHYLAXIS
1. Pre-exposure Prophylaxis
 Pre-exposure prophylaxis: NOT ROUTINE. However if you feel
that you are of high risk of acquiring leptospirosis such as that you
will be engaging in water-related recreational and occupational
activities, pre exposure prophylaxis can be taken
 Pre-exposure prophylaxis for high risk exposure (e.g. travelers,
soldiers, those engaged in water-related recreational and
occupational activities)
 Recommended: Doxycycline 200mg once weekly starting 1-2 days
pre-exposure continued throughout the period of exposure
o Contraindications
 Pregnant
 Breast feeding mother
 Children younger than 8 years, can cause permanent
yellowing or graying of teeth
 Allergic reaction
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Lec 15: Leptospirosis
o
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Doxycycline can make your skin more sensitive to sunlight and
sunburn as a result
o May also make birth control pills less effective
o Don’t lie down for an hour following doxycycline intake to prevent
pill esophagitis
o If 200 mg OD is not tolerated, take doxycycline 100 mg capsule
BID
Pregnant Patients: NO Recommendation
2. Post-exposure Prophylaxis
 Patients who actually waded in floodwater
 Risk exposure assessment
o LOW-RISK EXPOSURE- single history of wading in flood or
contaminated water without wounds, cuts or open lesions of the
skin
o MODERATE-RISK EXPOSURE- single history of wading in
flood or contaminated water with wounds, cuts, or open lesions
of the skin OR accidental ingestion of contaminated water
o HIGH-RISK EXPOSURE- individuals with continuous exposure
of wading in flood or contaminated water with or without wounds,
cuts or open lesions of the skin; Swimming in flooded waters
especially in urban areas
 Individuals should continue to monitor themselves for fever and
other flu-like symptoms and should continue to wear personal
protective measures since antibiotic prophylaxis is not 100%
effective.
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Wasting sodium and potassium defect has been consistently
documented
C. Management of ARF
 Indications for dialysis
o any of the ff: ARDS, ph <7.2, HCO3 <10, CrCl < 20 ml/min,
K> 5
o for hypovolemic patients, persistent oliguria despite hydration
and vasopressors
o for hypervolemic or euvolemic patients, persistent oliguria
despite furosemide
D. Prognosis of ARF
 Full renal recovery is the rule within two weeks after clinical
improvement
 Impaired capacity to concentrate urine osmolarity may last for up
to 6 months
D. Prognosis of ARF
 196 consecutive cases of lepto-associated AKI from 1985-2006
in Fortaleza, Brazil
 Crackles (OR 5.2, 95% CI 1.9 to 14.4)
 Elevated direct bilirubin levels (OR 1.05, 95% CI 1.001 to 1.093)
 See Appendix III for the algorithm for the management of oliguria
in leptospirosis
2. Pulmonary Involvement (see Appendix 4)
A. Clinical Features
 Tachypnea (RR >30) – First Sign
 New onset cough, dyspnea and hemoptysis
 Symptoms appear on the 4th to 6th day of disease
 chest pain, cough, dyspnea, hemoptysis, ARDS
 Occur in both anicteric and icteric leptospirosis
 Severity of pulmonary disease is unrelated to jaundice
 Smoking – risk factor for devt of pulmo manifestations
 See Appendix IV for the algorithm for the diagnosis and
management of leptospirosis with pulmonary complications.
B. Complications
 Acute Respiratory Distress Syndrome
 Pulmonary Hemorrhage
 usually associated with worse prognosis and high mortality
 In a multicenter retrospective analytical study of leptospirosis
patients after typhoon Ondoy last 2009, most of pulmonary
hemorrhage is the only significant complication and 71 % of
those who died had pulmonary hemorrhage
 In the same study, pulmonary hemorrhage is the only
significant predictor for mortality
 In a study done at National Kidney and Transpalnt Institute,
determing the predictors for dialysis, pulmonary hemorrhage
is also a significant predictor of mortality.
Figure
4.
Post-exposure
Prophylaxis
recommended by the Lepto Task Force
algorithm
as
X. MANAGEMENT OF COMPLICATIONS
1. Acute Kidney Injury (see Appendix 3)
a. Clinical Features
 Mild proteinuria to severe anuric acute renal failure
 COMMONLY – Non-oliguric renal failure with mild hypokalemia
 Poor Prognosis: Oliguria with hyperkalemia
B.
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Acute Renal Failure
Occurs in 16-40% of severe leptospirosis
May present as isolated proteinuria to severe anuric ARF
Non-oliguric forms have better prognosis
Oliguria and hyperkalemia identified as predictors of a lethal
outcome
Commonly presents as a non-oliguric and a hypokalemic state,
low potassium levels may be detected in 41%-45% of patients
Shen, Franz, Jerry
C. Management
 Leptospires = release of inflammatory mediators = vasculitis
= pulmonary involvement in leptospirosis; hence there is a
possible role for steroids in treatment
 Methylprednisolone (1 g IV bolus) preferably given within
12 hrs of onset of respiratory involvement
 Methylprednisolone should be given for 3 days
o Methylprednisolone with non-invasive ventilation is lifesaving in ARDS owing to leptospirosis -Abraham Ittyachen et
al. Methylprednisolone as an adjuvant treatment of ARDS
owing to Leptospirosis. Indian J Crit Care Med. July-Sept 2005.
o Corticosteroids reduce mortality and change outcome
significantly when used early in the management of
pulmonary leptospirosis – Shenoy, VV. Et. Al. Pulmonary
leptospirosis:
an
excellent
response
to
bolus
Methylprednisolone. Postgrad Med J 2006;82:602–606
o On the other hand, In a retrospective study on patients with
leptospirosis with pulmonary involvement admitted to PGH
from 2003 to 2006 comparing the mortality rates among
patients given adjunctive steroids, there was No reduction in
mortality and assisted ventilation were observed among
those given steroids. However, there was A trend towards a
reduction in dialysis rates, but it was not significant. –
Villanueva, R. Use of Steroids in Leptospirosis to Improve
Survival: An Exploratory Study.
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Lec 15: Leptospirosis
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Shift to oral Prednisone 1 mg/kg/day for 7 days
D. Steroids for Severe Leptospirosis
 Case reports on the use of glucocorticoids in severe cases
 24 patients successfully treated with 7-day course of
amoxicillin and steroids (prednisone 60 mg OD x 7 days,
MPPT x 3 days, or Hydrocortisone 200 mg LD then 100 mg
q6) in 1978 in Hungary
 1 patient treated successfully with Hydrocortisone 200 mg
LD then 100 mg q6, presenting with thrombocytopenia and
bleeding, in the US
 1 patient in France with multiple organ failure with
methyprednisolone 500 mg and IV immunoglobulin
XI. PREVENTION AND CONTROL
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Leptospirosis is a preventable disease
Control measures
o Risk communications - Leptospirosis has been considered an
occupational disease, thus control measures towards agriculture
and other at risk workers
o Improvement in sanitation and living conditions
o Rodent control
o Prophylactic and therapeutic medical
o Vaccination
 On going research into numerous vaccine preparations for
humans and animals is well documented
 The local variability in serovars of endemic leptospiral strains
complicates the development of vaccine that can be used
worldwide
 In the Region, human vaccines against Leptospira are
available in China, Japan, Korea and Vietnam
 Vaccine Development
o
Whole-leptospire based vaccines administered to
livestock & domestic animals associated with high rates
of adverse reactions; short-term serovar specific
immunity
o
Subunit vaccine candidates that will protect against
multiple Leptospira sp
o
Determine whether infection with leptospira protects
against reinfection in high-risk populations and identify
mechanisms of immunity
o
Protective Immunity
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Serovar-specific Abs against leptospiral LPS are
protective

Patient is immune to reinfection with the same
serovar as long as the Ab titer is high enough

mmunity is serovar-specific
1. Control of Infection Source
 Control of rodent population
 Separation of animal reservoirs from human habitations by fences or
screens
 Removal of rubbish, garbage disposal system
 Keep surroundings clean
 Sewerage, drainage system
 Do not leave food around especially in recreational areas where rats may
be present
2. Interruption of Transmission


Avoid high-risk exposure
o Immersion in freshwater
o Contact with animals and urine-contaminated soil, food and
water
Protective measures
o Boots, goggles, overalls, gloves
o Avoid walking barefoot
o Cover wounds with waterproof dressing
END
Shen, Franz, Jerry
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APPENDIX 1. Natural Course of Disease
Appendix B. Faine’s and Modified Faine’s Criteria
Shen, Franz, Jerry
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Lec 15: Leptospirosis
OS 213
Appendix 3. Algorithm for the Management of Oliguria in Leptospirosis
Appendix 4. Algorithm for the Diagnosis and Management of Leptospirosis with Pulmonary Involvement
Shen, Franz, Jerry
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