LEptospirorsis

2. • GENERAL:
– To present a case and discuss about Leptospirosis
• SPECIFIC
– To discuss the incidence and epidemiology of the
disease
– To discuss the pathophysiology of Leptospirosis
– To discuss the complications of the disease
– To discuss the guidelines in management and
treatment of leptospirosis
– To discuss the prevention of the disease

3. This is a case of M.F. 59 y/o male, married,
Filipino, Roman Catholic, born on October 13,
1954, presently residing at 04 Capoas St.
Masambong Quezon City admitted at QCGH
on September 15,2014

4. DIFFICULTY OF BREATHING

5. • 3 months prior to admission patient had
history of flood wading.
• 2 months prior to admission patient had
febrile episodes associated with myalgia
• 1 week prior to admission he sought consult
at QCGH ER, was diagnosed with UTI and
given ceftriaxone

6. • 4 days prior to admission patient
experienced easy fatigability with
decreased urine output
• 1 day PTA patient sought consult again for
generalized body weakness, advised
admission but went HAMA
• On the day of consultation patient
developed difficulty of breathing

7. • Unremarkable
Comorbidities?
History of previous infection?

8. • Unremarkable
Family members with history of leptospirosis

9. • Smoker with 5 pack years
• Heavy alcoholic beverage drinker
Description of the patient’s residence
Environment and community?
Work of the patient?
Vectors in the area?
Incidence of floods?

10. • Head and Neck: No headache, injury,
neck stiffness
• Ears: No changes in hearing, otalgia,
tinnitus, ear discharge
• Nose: No colds/nasal stiffness, bleeding,
dryness, discharge, pain, sneezing
• Mouth/Throat no bleeding gums,
soreness, ulcer, hoarseness, pain, dryness,
difficulty in swallowing

11. • Hematology no bruises, pallor
• Endocrine no heat or cold intolerance,
polyphagia, polydypsia, polyuria

12. GENERAL:
Patient is, conscious, coherent, non ambulatory,in severe
Cardio Repiratory Distress with the following vital signs:
• BP: 130/80 mmHg, CR: 115 bpm RR:35 T: 37.4
SKIN: Brown in color, moist, warm to touch, good skin
turgor, no lesions, with healed wounds on the feet and
petichiae on the extremities
HEENT: Icteric sclerae, pinkpalpebral conjunctiva, no nasal
and aural discharge, no tonsillopharyngeal congestion, no
cervical lymphadenopathy, no bruit, no anterior neck
mass, no neck vein distension

13. CHEST and LUNGS: Symmetrical chest expansion, no
lagging, with retractions on the supraclavicular area, equal
vocal and tactile fremitus, bibasal crackels
HEART: Adyanamic precordium, Tachycardic, PMI at 5th ICS
LMCL, Normal rate , regular rhythm, no murmur
ABDOMEN: Flabby abdomen, normoactive bowel sound,
tympanitic, soft, non tender to light and deep palpation
EXTREMITIES: Grossly normal extremities, no deformities, no
external signs of cyanosis, with grade 1 pitting edema, with
calf tenderness, full and equal pulses on the brachial,
radial, and dorsalis pedis arteries

14. • 59 y/o male
• 3 months PTA
• (+) history of flood wading
• 2 months PTA
• (+) fever (undocumented)
• Associated with:
– Myalgia
• Not associated with:
– Difficulty of breathing
– Rashes
– Vomiting
– Calf pain
– Abdominal pain
– Redness of the eye
– Calf pain
• 1 week PTA
– Diagnosed with UTII
– Associated with urinary
symptoms
• 4 days PTA
– Easy Fatigability
– Decreased urine out put
– Not associated with:
– Fever, myalgia, bleeding,
rashes, yellowish skin or
sclera, difficulty of breathing
• 1 day PTA
– generalized body weakness,
• Few hour PTA
– difficulty of breathing
– Not associated with cough,
back pain, chest pain,
edema, dysphagia,

15. • Personal and Social
– Heavy alcohol beverage
drinker
– Smoker with 5 pack yers
• Physical Examination
Patient is, conscious, coherent,
non ambulatory,in severe
Cardio Repiratory Distress with
the following vital signs:
• BP: 130/80 mmHg,
• CR: 115 bpm
• RR:35
• T: 37.4
- Petichiae on extremities
- Icteric sclera
- Bi-basal crackles
- Tachycardic
- Grade 1 pitting edema

16. ACUTE KIDNEY INJURY SECONDARY TO
LEPTOSPIROSIS MODERATE-SEVERE

17. • FOR ADMISSION
• IV PNSS 1L X200CC/hr
• NPO temporary
• Diagnostics:
• CBC WITH PC
• Na, K, Cl
• BUN, Crea
• ABG
• PT, PTT, INR
• SGPT, SGOT
• UA
• Lepto MAT
• 12L ECG
• CXR-PA
Therapeutics:
– Cefrtiraxone 1mg TIV now
then OD
– Furosenide 80gm TIV
– Q8 with BP precaution
– Omeprazole 40mg TIV
now then OD in AM
– Vitamin K 30mg TIV now
then 10 mg TIV Q8

21. • “Weil’s disease”
• Severe
Leptospirosis
• Characterized by:
– Fever
– Jaundice
– Acute Renal failure
– Refractory shock
– Pulmonary
haemorrhage

25. Occupation: (Dairy/Rice field/Sugar/Slaughter House workers
Junkshop/Warehouse/Sewage/flood control workers,
Vet. Meds.)

26. Exposure to contaminated fresh pond/ flood waters
Wading/ swimming/ Water related sports activities

29. • 1. Direct bacterial invasion
• 2. Non specific inflammation
• 3. Immunological reaction
Journal Inf. Dis.

33. Leptospira
Endothelial injury
Plasma pooling
Immunologic injury
Toxin production
Surface lipoprotein
OMP,LPS
Renal Ischemia
IN,ATN
Hepatic injury w/
subcelullar necrosis
Alveolar hemorrhage
Interstitial
Myocarditis
vasculitis
IP 2-28 days Vasculitis
Dysregulation of
Na-K ATPase
Pulmonary
epithelial
channel
Mandel, Principle of Inf Dse,5th edition
Journal of Postgraduate Medicine, Vol. 51,
No. 3, July-September, 2005

35. Renal involvement:
1. sub-clinical- mild proteinuria and few urinary sedi-ments
2. Icteric
Weil’s Syndrome (jaundice, renal dysfunction, he-morrhagic
diathesis)
ARF (10% to > 60%)
virulence, bacterial load, host immunity
hyperbilirubinemia
hypercatabolic with cholestasis

36. Renal involvement is common.
1. bacterial invasion
2. inflammatory process
3. hemodynamic alteration
4. direct toxicity of bacterial product
Basic lesion is Interstitial Nephritis
Glomerular changes are not remarkable
Tubular Necrosis Acute Renal Failure
primarily involves the PT

37. Pathogenesis
BACTERIAL INVASION/INFLAMMATION:
Outer membrane protein-activates
monocytes-
release of pro-inflammatory cytokines-
vasoactive substances and adhesion
molecules
Humoral response (Th1 and Th2 lymphocytes)
deposition of IgM and C3
Cell mediated (cytokines and chemokines)

38. Hemodynamics:
Pattern 2 ( seen in pulmonary hemorrhage )
cardiac index/SVR normal
pulmonary vascular resistance increase
Pattern 3 ( seen in hyperbilirubinemia )
SVR slightly increase or normal
CI, mean arterial pressure decrease
pulm vascular resistance normal

39. HEMODYNAMIC CHANGES:
Pattern 1 ( similar to sepsis )
SVR is decreased by nitric oxide
CO, CI and blood volume increased
Renal vasculature resistance increased
Renal blood flow and GFR decreased
pulm vascular resistance normal
+ hypotension (60%)

40. DIRECT NEPHROTOXICITY
Fluctuating renal tissue pH: (virulence)
ammonia recycling
urinary acidification
Bacterial cell wall (LPS)
OMP –outer membrane proteins
OmpL1, LipL41, LipL36

41. HYPOTENSION
1. renal ischemia
2. inflammatory processes
Renal Ischemia:
dysregulation of lung salt and water channels
downregulate pulmo epithelial Na
channel(ENaC),
Na-K ATPase and aquaporin 5

42. Non-specific inflammatory factors:
hemolysis
myonecrosis
intravascular coagulation
free radicals
hyperbilirubinemia
increased blood viscosity

43. Renal injury- is compounded by concomittant
dehydration>>hypovolemia & hypotension,
development of anuria>> poor prognostic
sign.
In fatal cases- kidney are swollen & yellow w/
prominent cortical blood vessels.>>>focal
areas of tubular necrosis.
Severe hemorrhagic Pneumonitis & Acute pulm
distress syndrome- prominent manifestation of
infection & occur in the absence of hepatic &
renal failure.( CXR lower lobe evolve from
small nodular densities Snow flakes like)

44. Human leptospirosis
Kidneys:
swollen, bile stained
interstitial edema, infiltration of
mononuclear
cells and eosinophils
ATN:
Degeneration and necrosis of tubular epith
cells and disruption of basement membrane

45. Hemorrhagic Syndrome in Leptospirosis
The basic pathomorphological substrate
endothelial damage leading to generalized vasculitis.
studies have shown that capillary leakage and
hemorrhage result from the disruption of endothelial
cell membranes of small vessels via the intercalation
glycoprotein toxin w/c displaces the host long chain fatty
acids required to maintain vascular cell wall integrity.

46. and therefore: systemic vasculitides
pulmonary hemorrhage
ischemia to renal cortex
destruction to hepatic architectiure

49. Chest X-Ray Findings:
1. small, “snow-flakes like” nodular
density
2. large confluent consolidation
3. diffuse, ill-defined ground glass
appearance

52. Dark field microscopy – direct visualization of
leptospires in blood & urine.
ELISA- 75% + to the patient on the day of
admission to the hosp but not available
commercially.
PCR(Polymerase Chain Reaction)only
advantage is confirming the diagnosis during
early acute phase of illness before the
appearance of IgM ANTIBODIES.
In fulminating cases in which death occurs
before seroconversion this test maybe of
great value.

53. relied on silver impregnation staining, but
immunohistochemical staining offer greater
sensitivity & specificity.
Isolation and Identification
leptospires can be isolated from blood, CSF,&
peritoneal dialysate fluid during first 10 days of
illness. Specimen should be collected while the
patient is febrile & before antibiotic therapy is
initiated.
Urine can be cultured after the ist wk of illness.
Culture are performed in Albumin polysorbate
media – incubated 30C x sev wks- slow growth.

54. MAT- ( Microscopic Agglutination Test)
majority of leptospires cases are
diagnosed by Serology. Live antigen
representing different serogroups of
leptospires are reacted w/ serum
sample & examined under Darkfield
Microscopy fof Agglutination.

56. INDICATION DRUG DOSAGE
Chemo Doxycycline 200mg p.o. 1x/wk
Mild Lepto Doxycycline 100mg BID p.o.
Ampicillin 500mgQID p.o.
Amoxicillin 5oomg QID p.o.
Mod-
Severe PenG 1.5m IV QID
Ceftriaxone 1g IV OD
Ampi 0.5-1g IV QID

57. • Acute Kidney injury
– Plain NSS with potassium incoporation
– Renal replacement theraphy for patients
in uremia, increasing creatinine of K levels,
fluid overload, metabolic acidosis,

58. Methylprednisolone as Adjuvant in
treatment of ARDS owing to Leptospirosis
methylprednisolone 40mg iv q 6 hr
methylprednisolone 40mg iv q 8 hr
methylprednisolone 40mg iv q 12hr x 2
oral prednisone 1 mg/kg taper in one
week