Pathophysiology, clinical and lab features, management of leptospirosis

1. Leptospirosis
DR. ANKIT RAIYANI
LTMGH

2. Introduction
 Most common, underreported and under
diagnosed zoonosis.
 India - Cases reported from Maharashtra,
Gujarat , Kerala, Tamil Nadu, Karnataka,
Andaman.
 Source –Animals ( rodents and domestic
animals) or an environment contaminated by
their urine
 Causative org. can survive for months in water
& damp soil

3. Organism
 Order-Spirochaetales
 Family-Leptospiraceae
 Genus-Leptospira
 Species-17(11 pathogenic-L. interrogans sensu lato)
& (6 non-pathogenic-L. biflexa sensu lato)
 Pathogenic leptospira divided into ›26 serogroups & ›250
serovars.
 Leptospires are coiled thin highly motile organisms, 6-
20µm long and ~0.1µm wide, obligate aerobes
 Stain poorly… but seen by dark-field microscopy & by
silver impregnation tech.
 Culture media- EMJH, Fletcher, Korthof

4. Leptospira interrogans
L. Interrogans scanning electron microscope
L. Interrogans Silver impregnation
L. Interrogans Dark-field microscopy

5. Epidemiology
 Etiology: L interrogans
 Most widespread zoonosis in the world
 Peak incidence during rainy season
 Occupational & recreational exposures
 Source of infection in humans: direct or
indirect contact with the urine of an infected
animal
 Portal of entry: abrasions or cuts on skin,
conjunctiva & other mucous membranes.
 Inc. period: 2-30 days(commonly 5-14 days)

6. Epidemiology
 Rainfall
 Contaminated environment
 Poor Sanitation
 Inadequate drainage facilities
 Presence of Rodents, cattle& stray dogs
 Walking bare foot
 Specific source of infection cannot be
pinpointed with certainty.
 Males>Females… more chance of exposure

7. Transmission
Rodents
(Urine)
Humans
Domestic Contaminated
animals environment

8. PATHOGENESIS
Pathogenesis not completely understood
1. Leptospiremia...multiplication in blood, tissues.
2. Vasculitis– responsible for most of the
manifestations… LOS TNF-α
3. Kidneys- interstitial nephritis, tubular injury
4. Liver- centrilobular necrosis(usually not
extensive)
5. Lungs- involvement due to hemorrhage, not to
inflammation
6. Microcirculation damage, increased vascular
permeability….hypovolemia
7. Skeletal muscles-necrosis

9. Clinical Features
 Biphasic clinical presentation
 Acute or bacteremic phase lasting ~1 week
 Immune phase, characterized by antibody production and
leptospiruria
 Anicteric Leptospirosis
 Abrupt onset of fever, chills, headache, myalgia,
abdominal pain, conjunctival suffusion, transient
skin rash, Aseptic Meningoencephalitis
 Icteric Leptospirosis (Weil’s disease) 5-10%
 Occurs in 5-15% of patients
 Jaundice, Proteinuria, hematuria, oliguria and/or anuria
 Pulmonary hemorrhages, ARDS
 Myocarditis
 Aseptic Meningoencephalitis

10. Icteric Leptospirosis- LIVER
 Jaundice -Occurs 4-6 days (2 - 9 days)
 Sr.Bilirubin –Markedly increased- (20-40
mg/dl) Conjugated bilirubin rise
 SGOT / SGPT -Mild elevation
 ALP- moderately elevated
 Hepatocellular necrosis / Intra hepatic
cholestasis
 Death - Not due to Liver Disease…if no
predisposing factors present

11. Icteric Leptospirosis- G. I. tract
 Massive spontaneous G. I.
bleeding(major cause of death)
 Pancreatitis
 Severe abdominal wall tenderness
mimicking acute abdomen

12. Icteric Leptospirosis- Lungs
 Frequently involved with varying
severity
 Cough, dyspnoea, chest pain, blood
stained sputum, hemoptysis
 Severe pulmonary hemorrhage causing
Acute Respiratory Distress Syndrome
 May cause diffuse or focal interstitial
pneumonitis and pneumonia
 CXR- lesions seen are more extensive
than clinical findings, develop ›3-9 days

13. Microscopy

14. Hematological disturbances
 Severe thrombocytopenia…bleeding
 Anemia- d/t bloodloss, &/or hemolysis
 Petechiae, purpura, ecchymoses
common
 PT & PTTK time may be normal to
moderately elevated…can be corrected
with Vit K supplementation.
 D.I.C.-rare as compared to Gm(-) sepsis
 Jarisch-Herxheimer reaction- rare

15. Icteric Leptospirosis- Kidneys
 Invariably involved --Mild to Severe
 Urinalysis : Hematuria / Pyuria /Proteinuria
 Renal Failure: initially non-oliguric with K+
wasting….may become oliguric
Prerenal ATN
Hypotension
Endotoxins
Fluid loss/ Fluid shift
Toxic Metabolites
Myocarditis

16. Icteric Leptospirosis- Heart
Hemorrhagic Myocarditis- Arrhythmias
,Cardiac failure, Hypotension / Death
Arrhythmias- Atrial fibrillation / Conduction
defects (seen in 20-40%)
ECG changes- Non Specific ST-T changes, Low
voltage complexes

17. Icteric Leptospirosis- CNS
 Aseptic MeningoEncephalitis-
Occurs in the Immune phase
CSF – raised proteins , -
lymphocytes
 Rare-
Convulsions, Encephalitis
Myelitis & Polyneuropathy.

18. Other manifestations
 Skeletal Ms involvement- myalgia,
raised CPK levels
 Conjunctival suffusion
(pathognomic)
 Anterior uveal tract inflammation
Iritis / Iridocyclitis / chorioretinitis
 Occurs 2 weeks – 1 yr (6 months)

19. Modified Faine’s criteria

20. Diff. Diagnosis
 Fever-Viral fever/Malaria/Typhoid /
UTI
 Jaundice-Malaria, Viral hepatitis,
Sepsis
 Renal failure-Malaria, Hanta Virus,
Sepsis
 Meningitis-Bacterial / Viral
 Hemorrhagic Fever-Dengue, Hanta
virus, Typhus

21. Investigations- Routine
 CBC- low Hb, thrombocytopenia, leucocytosis
 LFTs- conjugated bilirubinemia, raised ALP,
mild elevation of AST/ALT
 RFTs- raised BUN/Creat…Ratio
 SE- hypokalemia, hypocalcemia,
hypomagnesaemia
 CPK- elevated
 PT/PTTK-mild elevation
 Pl. fibrinogen- normal
 Urine(R/M)- active sediments, proteinuria,
hematuria, Hb/Mb-uria.
 ECG- conduction defects, non-specific ST changes

22. Chest radiograph
 Three radiographic patterns:
1.small nodular densities (50-60%);
2.confluent areas of consolidation (10-20%); and
3.diffuse, ill-defined, ground-glass density (20-
30%).
 Serial radiographs may show a tendency for the
nodular pattern to be followed by confluent
consolidation and/or ground-glass density.
 Abnormalities are bilateral, non-lobar in all
cases, and have a marked tendency toward
peripheral predominance

23. Chest radiograph
Pulmonary hemorrhage in Leptospirosis

24. Specific investigations
 Dark-field microscopy –blood, CSF,
urine(Low Sensitivity & Specificity)
 Culture- blood, CSF, urine…takes up
to 4 weeks for diagnosis
 Serological tests- MAT, ELISA
 Rapid tests- latex agglutination,
ELISA
 Polymerase Chain Reaction Test

25. Microscopic Agglutination Test(MAT)
 Gold Standard, Complicated
 Titres rise late, but persist longer
 Valuable in epidemiologic studies
 Less sensitive for current diagnosis
 Positive- Seroconversion / 4 fold rise
in the titre, High titre(>1:100).
 Will stay positive for long time after
recovery

26. IgM ELISA and other rapid
Tests
 Useful for providing presumptive diagnosis in current
infection
 Sensitivity is low- 39-72% during acute phase illness
 Repeat sample after 3-4 days.

27. Polymerase Chain Reaction Test
 Highly valuable during acute illness(<7
days)
 Sensitivity decreases as bacteria is cleared
from blood
 Can detect even <10 bacteria in any given
sample
 Primers should cover all prevalent species
in given area
 Recent data - urine sample has more
sensitivity then blood sample after 7 days
 Use limited by less availability

28. Approach to Diagnosis
Clinical features suggestive of current leptospirosis
Leptospiremic phase < Immune phase > 7 days
7days
Blood culture ELISA / Rapid IgM
PCR Positive Negative
MAT(if Repeat >3-4
available) days

29. Biphasic nature of leptospirosis and relevant investigations
at different stages of disease
Clin Microbiol Rev. 2001 Apr;14(2):296-326

30. Management(severe
leptospirosis)
 Prompt triage of high-risk patients and
early supportive treatment
 General management and supportive
therapy
 Specific treatment of various organ
system failure
 Hemat
 RS
 Renal
 Liver

31. Contd…
Antibiotic therapy
 Shortens fever clearance time,
leptospiruria
 mortality
Antibiotic regimes
 Inj. Penicillin G 1.5 million U Q6H (iv) x 7
days(used to be DOC)
 Inj. Ceftriaxone 1 Gm OD (iv) x 7 days
 Inj. Cefotaxime 1 Gm Q6H (iv) x 7 days
 Other agents- Macrolides,
fluoroquinolones

32. Mild Leptospirosis
 Doxycycline 100 mg BD (po) x 7 days
 Amoxicillin 500 mg qid (po) x 7days

33. Prognosis
 Mortality is high in patients with
severe disease
 Weil’s disease- 5 to 40%
 Severe pulmonary hemorrhage->
50%
 Poor prognostic indicators- age>40
yrs, oliguria, respiratory distress,
pulmonary hemorrhage, arrhythmias,
altered sensorium, alcoholic patients

34. Prevention
 Controlling animal reservoirs,
interrupting transmission routes
 Protective clothing, chemical pesticides..
 Chemoprophylaxis-
Doxycycline (200 mg po /wk)
Doxycycline (100 mg bd ) x 7 days—for
postexposure prophylaxis(? Efficacy)
 Vaccine- Bacterin based vaccine(??efficacy,
?safety)

35. Thank you!!