case scenario and overview on Leptospirosis

1. Dr. Chetan Chaudhari
DNB Resident
Department of Paediatrics
HINDUHRIDAYSAMRAT BALASAHEB THACKERAY
MEDICAL COLLEGE (HBTMC) & DR.R.N.COOPER
MUNICIPAL GENERAL HOSPITAL, MUMBAI
Date- 28st October 2020

2.  On 31st July 2020
 Roshani Gupta, 11 yrs old Female Child
 Admitted at Dr.R.N.Cooper Hospital for the first time
 Brought by : Mother (Informant Reliable)
 Chief complaints:
Fever since 4 days
Body ache, Headache since 3 days
Abdominal pain since 3 days
Decreased oral intake since 3 days
Difficulty in breathing since 1 day
Clinical Scenario

Short History

3.  Fever - 4 Days back, undocumented fever, insidious onset, mod-high grade,
intermittent, no diurnal variations, relieved on oral medications. No chills or
rigors. Normal inter febrile.
followed by myalgia, Headache
 Next day- persistence of above complaints +
Abdominal pain, Decreased oral intake
Decreased Urine Output
 Difficulty in breathing – 1 Day prior, fast and labored breathing,
progressive
 Relevant H/O wading in rain water a week ago,
 Normal Birth History, completely immunized, developmentally Normal,
averagely built well nourished child
History of present illness


4. DOA 1
Day 5 illness
Conscious, Alert, GCS 15, in cardiorespiratory distress
with vitals:
• Temp: 37 C HR: 120 bpm RR: 60 bpm
• SPO2: 90% off O2 BP: 110/70 mmHg (50th-90th)
RS:
• Tachypnea+, Symmetrical expansion
• B/L AE reduced, B/L crepts +
• +Intercostal retraction + Subcostal retraction
• no local tenderness,
• On O2 CPAP 96% with +RD +WOB
Course in Ward

On Examination

5. • CVS: Normal precordium,
Apex beat at left 5th ICS MCL, (-) murmur,
Tachycardia+
(-) thrills, (-) palpable P2; normally split S2;
• Abdo: no scars, soft, no guarding/rigidity
bowel sounds present,
Liver non palpable, span 8 cm, Non tender
Course in Ward

On Examination
CNS: Conscious, oriented, follows commands
GCS 15 (E4V5M6)
Rest neurologic exam were unremarkable

6. By 6 Hours
of
Admission
• Diagnostics sent:
ABG, CBC with DLC, PS, RMAT, CRP, BUN, S.Creat, S.
Electrolytes, AST, ALT, PT APTT, blood CS, U/RM,
Dengue test, Leptospira test, CXR PA, Covid-19 swab
• Tachypnea+, ++ WOB, Significant distress with
impending Respiratory failure,
• ARDS
• Hypotensive
• Intubated, inotropes added, Upgraded AB
• Pt. was Transferred to PICU
Course in Ward

Under Evaluation

7. Any thoughts ?? Any Questions ??


9. Any thoughts ?? Lab Reports!!

• Lepto IgM + Lepto ELISA +
• HB- 8.5, TLC- 8000, PLT- 91000, INR- 1.35
• BUN-17.8, Creat-0.9, SGOT-50,SGPT-36
• Na+135, K+3.8, Cl-99
• ABG-pH7.4, pO2-71 pCO2-29 HCO3-18.4
DOA 1
Day 5 illness

10. Any thoughts ?? Lab Reports!!

• Lepto IgM + Lepto ELISA +
• HB- 8.5, TLC- 8000, PLT- 91000, INR- 1.35
• BUN-17.8, Creat-0.9, SGOT-50,SGPT-36
• Na+135, K+3.8, Cl-99
• ABG-pH7.4, pO2-71 pCO2-29 HCO3-18.4
DOA 1
Day 5 illness
By 4-5 Days
of
Admission
On Mech. Ventilation,
Over next few days Child had developed
Oligouria, U/O ~ 0.7ml/kg/hr,
Profuse pulmonary bleed,
High grade Fever, continued RD+
GCS – 11/15

11. Any thoughts ?? Lab Reports!!

• HB- 5.7, TLC- 22400, PLT- 81000, INR- 2.38
• BUN-112, Creat- 4.9, SGOT-7210,SGPT-4894
• Na+ 158, K+ 4.3, Cl-120
• MRI Brain- fronto-parietal micro haemorrhages,
Chronic subdural hygroma
By
DOA 5
Day 10 illness

12. Any thoughts ?? Lab Reports!!

• Lepto IgM + Lepto ELISA +
• HB- 8.5, TLC- 8000, PLT- 91000, INR- 1.35
• BUN-17.8, Creat-0.9, SGOT-50,SGPT-36
• Na+135, K+3.8, Cl-99
• ABG-pH7.4, pO2-71 pCO2-29 HCO3-18.4
DOA 1
Day 5 illness
• HB- 5.7, TLC- 22400, PLT- 81000, INR- 2.38
• BUN-112, Creat- 4.9, SGOT-7210,SGPT-4894
• Na+ 158, K+ 4.3, Cl-120
• MRI Brain- fronto-parietal micro haemorrhages,
Chronic subdural hygroma
By
DOA 5
Day 10 illness

13. Diagnosis

Leptospirosis with Multi Organ Dysfunction
(ARDS with Pulmonary hemorrhage with Acute
Liver Failure, Acute Kidney Failure, Hypernatremia)
with Multiple intracranial hemorrhages with Bed sores
treated for above diagnosis (3 PRBC, 3FFP, 3PLT, Inotropes, IV
Steroids, Higher Antibiotics, Antifungal, Sedation,
Antiepileptic, Neurotropic Proteins)
25 Days of Hospitalization

14. Dr. Chetan Chaudhari
DNB Resident
Department of Paediatrics
HINDUHRIDAYSAMRAT BALASAHEB THACKERAY
MEDICAL COLLEGE (HBTMC) & DR.R.N.COOPER
MUNICIPAL GENERAL HOSPITAL, MUMBAI
Overview

15.  Common & widespread zoonotic disease in the world in
tropical and subtropical countries
 Historically known as Weil’sdisease
(Described in 1885 by Adolf Weil)
 One of the emerging infectious diseases since the late 1990s
Recent large outbreaks in Asia, Central & South America
 Hosts - rats, dogs, cattle and pigs. Reservoir: rodents
 Leptospires survive for days to weeks in water and moist soil
 Transmission:
Exposure to water or soil contaminated with rat urine
Exposure to contaminated floodwaters
High-risk occupations
EPIDEMIOLOGY


16.  Patterns of transmission Epidemic / Endemic / Sporadic
 In India, only sporadic cases being recorded.
 Urban leptospirosis - reported from Mumbai & Chennai
Last Outbreak reported was in Mumbai in 2015
 Rural leptospirosis - Gujarat, Kerala & Andaman
 Leptospirosis is endemic in
 Kerala
 Tamil Nadu
 Gujarat
 Karnataka
 Maharashtra
 Annual incidence (WHO) – 0.1 to 1 per 100 000 per year
 Estimated case-fatality rates ranges from <5% - 30%

17.  SpirocheteLeptospira –
22 species,
10 pathogenic species
L. interrogans,
L.icterohaemorrhagiae,
L.copenhageni
 All species are
morphologicallyidentical
Obligate
Aerobic
Motile
Tightly & regularly coiled,
MORPHOLOGY

Electron Microscopy

19. Infects mucosa (oral, nasal or conjunctival) or through
abraded skin or ingestion of contaminated water
Proliferate in bloodstream and disseminate
hematogenously
Development of antibodies(5-7 days)
Organisms disappear from blood & CSF but remain
localized in tissues, organs including kidneys, brain,
liver, lung, heart
Pathogenesis

20. Loss of fluids into the third space
Hypovolaemic shock and vascular collapse
Vascular Endothelial damage - produces endotoxin
Attach onto the endothelial cells
Capillary endothelial necrosis and lymphocytic infiltration
Vasculitis and leakage : petechiae, intra parenchymal
bleeding and bleeding along serosa and mucosa

21. Excreted in urine
Interstitial Nephiritis, Tubular Injury
Penetrate basement membrane of PCT
Adhere to proximal tubule epithelial cells
Traverse interstitial spaces of kidney

22. Brain – Aseptic meningitis, meningoencephalitis
Eyes - Uveitis
Lungs – involvement due to hemorrhage
(not inflammation)
Liver – Centrilobular Necrosis(usually not extensive)
Cholecystitis, Pancreatitis
Heart – Myocarditis, Skeletal Muscles – necrosis

23.  Incubation period - 2 to 30 days (mean: 15 days)
 Spectrum of disease - Asymptomatic (90%)
Severe disease - (10%) with MODS & Death
 Onset is abrupt & follows classically described biphasic course
 Initial or Septicemic phase : 3-7 days
leptospira in blood, CSF
 Immune or leptospiruric phase :
leptospira in urine
appearance of circulating IgM antibody,
disappearance of organisms from the blood and CSF
signs and symptoms with localization of leptospira in tissues
Clinical course


24. Clinical course & Clinical Menifestations

25.  fever - Abrupt onset with flulike signs with shaking chills, lethargy, severe
headache, malaise, generalized lymphadenopathy
 Myalgia - severe debilitating myalgia most prominent in the lower extremities,
lumbosacral spine, and abdomen (increase in Sr CPK level)
 Cunjunctival suffusion ( but no chemosis and purulent exudate)
 Rash - transient (<24 hr) erythematous maculopapular, urticarial, petechial,
purpuric or desquamating rash
 Aseptic meningitis - Immune phase
(80% of infected children -abnormal CSF profiles,
only 50% - clinical meningeal manifestations)
pleocytosis with polymorphonuclear leukocytosis,
normal or slightly elevated protein levels, and normal glucose
CNS symptoms resolve spontaneously within 1 wk
 Uveitis selflimited - unilateral or bilateral
Anicteric Leptospirosis

26. conjunctival suffusion
petechial rash

27.  Weil syndrome is a severe Severe form of leptospirosis
more common in adults (>30 yr)
 characterized by jaundice
 Initial phase manifestations are similar to anicteric leptospirosis
 Immune phase - Jaundice, Acute renal dysfunction & Thrombocytopenia
 Fulminant cases – menifest with
Pulmonary hemorrhage (morecommonly)
Cardiovascular collapse
Hepatic involvement
Renal dysfunction
Multisystem involvementoccurs
Icteric Leptospirosis
(Weil’s Syndrome)

28.  Jaundice 4 - 7 day (direct & indirect hyperbilirubinemia)
 right upper quadrant pain, tender hepatomegaly
 modestly elevated serum levels of hepatic enzymes
(<5 times the upper limit)
 cholestasis with hepatocellular necrosis
 Liver function usually returns to normal after recovery
 Hepatic encephalopathy or death due to hepatic failure is rare
 Splenomegaly in a minority of patients
Hepatic involvement


29.  Acute kidney failure occurs in 16–40% of cases (most severe complication)
 can occur after several days of illness (by 4th day or by 2nd wk)
 Urine analysis - hematuria, pyuria, proteinuria
 nonoliguric with K+ wasting, but may become oliguric
 acute tubular necrosis (ATN) and interstitial nephritis
 Azotemia - features of uremia like breathlessness, convulsion, delirium and
altered level of consciousness in very severe cases
 Severe acute failure cases- may require vasopressor support and hemodialysis,
complete recovery occurs by the end of the 4th week, usually no residual renal
dysfunction
Renal involvement


30. Immunohistochemical demonstration of leptospira in kidney tissue

31.  Mild illness - only cough, chest pain and blood tinged sputum
 Severe cases - hemoptysis, rapidly increasing breathlessness which may lead to
respiratory failure and death.
 toxin-mediated capillary vasculitis OR immune mediated
Capillary injury in the lungs >> leakage >> inflammatory reaction
Pulmonary oedema >> fibrin depositions and proliferative fibroblastic reactions
>> intra-alveolar haemorrhage >> acute respiratory distress syndrome (ARDS)
Severe Pulmonary Form of Leptospirosis (SPFL) –
intra-alveolar haemorrhage >> acute respiratory failure >> death
 Death - within hours to 2 days due to pulmonary hemorrhage and severe
respiratory distress.
 Pulmonary haemorrhage syndrome >50% mortality rate
Pulmonary involvement


32.  Hemorrhagic pneumonitis
with interstitial and
intra alveolar hemorrhage
surrounded by
focal capillary injury
are common pathologic changes.
 O/E – Tachypnea,
crepitation in the basal region,
which rapidly spread upwards
to middle and upper lobes.
Pulmonary involvement

Alveolar infiltrates are visible on CXR
(basal and mid zone)

33.  Abnormal ECG in 90% of cases. but congestive heart failure is uncommon
 Myocarditis - Segmental depression and T wave inversion may be present in
some patients.
 Shock – Echocardiography reveals normal systolic function of left ventricle
hypotension is due to either dehydration or peripheral vasodilatation
 Arrhythmias - palpitations, syncope and irregular pulse.
Supraventricular tachyarrhythmia
A.V. blocks of various degrees
Ventricular tachycardia infrequently
Cardiovascular system involvement


34.  CNS - commonly present as meningitis.
Aseptic Meningitis
Headache, irritability, seizures & coma can occur.
Encephalitis, focal deficits, spasticity, paralysis, nystagmus,
peripheral neuropathies, nerve palsies
 Transient thrombocytopenia in >50% of cases.
Rarely, hemorrhagic manifestations occur,
epistaxis, hemoptysis
gastrointestinal, and adrenal hemorrhage
bleeding manifestations in leptospirosis resolve in 2-3 days
 Anterior uveal tract inflammation - Uveitis , iridocyclitis & rarely
chorioretinitis
Other Menifestations


35.  Suspected: Acute febrile illness with headache, myalgia and prostration
associated with a history of exposure to infected animals or an environment
contaminated with animal urine with one or more of the following –
Calf muscle tenderness
Conjunctival suffusion
Anuria or oliguria and/or proteinuria
Jaundice
Hemorrhagic manifestations (intestines, lung)
Meningeal irritation
Nausea, Vomiting, Abdominal pain, Diarrhoea.
 Probable: Suspected case with positive presumptive laboratory diagnosis.
 Confirmed: Suspect/Probable case with confirmatory laboratory test.
Recommended case definition


36. Presumptive diagnosis
 A positive result in IgM based immune assays, slide agglutination test or latex
agglutination test or immuno-chromatographic test.
 A Microscopic Agglutination Test (MAT) titre of 100/200/400 or above in single
sample based on endemicity.
 Demonstration of leptospires directly or by staining methods
Confirmatory diagnosis
 Isolation of leptospires from clinical specimen
 Four fold or greater rise in the MAT titer between acute and convalescent
phase serum specimens run in parallel.
 Positive by any two different type of rapid test.
 PCR test.
Criteria for Diagnosis


37.  High index of suspicion - exposure history & manifestations
 “In endemic area all cases of fever with myalgia and conjunctival suffusion
should be considered as suspected cases of leptospirosis.”
 Biochemical, hematological and urinalysis may suggest
but are not specific for diagnosis
 The disease is usually diagnosed by –
Serological tests – MAT
Molecular- DNA PCR
Rapid tests – ELISA
Latex agglutination test
Dipstick tests ( Lepto dipstick, Lepto Tek)
Lepto Tek, Dri-Dot test
Indirect hemagglutination
Macroscopic slide agglutination test (MSAT)
Diagnosis


38. Gold standard diagnostic method is the Microscopic Agglutination Test
 Rapid tests - simple, more sensitive and become positive earlier than MAT
(5-6th day) as they detect specific IgM antibodies
 Culture - Leptospires can be cultured from blood and CSF during first 7-10
days, but takes 2-4 weeks to bepositive

39. Dark field microscopy showing Leptospira spp.

40. Microscopic Agglutination Test(MAT)
 Sensitivity 92% Specificity 95%
 MAT has a very limited availability
 Negative in the first 7–10 days of onset on infection

42. Treatment
 Prompt initiation of antibiotic therapy shortens the course
and prevents progression.
 Prompt triage of High risk patients & early supportive T/t
 Mild leptospirosis resolves without any treatment.
 Severe disease - empirically broad- spectrum antibiotics before
confirmation
 Hypotension to be managed by fluids and vasopressors
 Transfusion of blood and blood products
 Specific Treatment of various organ system failure – Cardiovascular
Pulmonary
Renal
Hepatic

43.  Mild disease - Oral Doxycycline, Amoxicillin, and Ampicillin
 Penicillin G
(Inj. Crystalline penicillin 2–4 lacs IU/kg/day divided every 4-6 hr IV for 7 days)
 Doxycycline (in children ≥8 yr of age)
a short (<2 wk) course of doxycycline may be safe in children >2 yr of age
Doxycycline 2 mg/kg/day divided in 2 doses (max 100 mg twice daily)
 Cefotaxime, Ceftriaxone, and Azithromycin
have demonstrated equivalent effectiveness with doxycycline
Children< 8 years:
 Amoxycillin/ Ampicillin 30-50 mg/kg/day in divided doses for 7 days
 Inj. Crystalline penicillin 2–4 lacs IU/kg/ day for 7 days.
 Ceftriaxone 50-75 IV mg/kg/day for 7 days
 Cefotaxime 50-100 IV mg/kg/day for 7 days
 Erythromycin OR Azithromycin may be given
Antibiotics


44.  Transfusion of blood and blood products
 Intensive immunosuppression - IV methylprednisolone
 IV Methylprednisone f/b oral prednisolone for 7 days
(Dose: 1 gram methylprednisone IV for first 3 days
f/b oral prednisolone 1 mg/kg for 7 days.)
reduced the need for ventilator support
Steroids effective if given within first 24 hours of onset of pulmonary symptoms
 Timely initiation of mechanical ventilation with PEEP and high FiO2
 Hypoxemia in leptospirosis with pulmonary hemorrhage - difficult to treat
inspite of maximal mechanical ventilation.
 ECMO - cardiopulmonary support
minimizes the damage by mechanical ventilation requiring high
FiO2, high tidal volumes and high airway pressures
Specific T/t of Organ System Failure

Pulmonary hemorrhage

45.  Management of fluids and electrolytes
 Management of AKI - Diuretic therapy
 Acute interstitial nephritis - short course corticosteroids
 Renal replacement therapy
 Indications for acute renal replacement therapy or dialysis -
Uremic Symptoms
encephalopathy
Serum creatinine > 3mg/dL
Severe hyperkalaemia unresponsive to traditional treatment
Serum K > 5.5 meqs/L in an oliguric patient
Severe volume overload
ARDS, Pulmonary hemorrhage pH <7.2
Fluid overload
 Hemodialysis is preferred over peritoneal dialysis
Specific T/t of Organ System Failure

Renal Dysfunction & Renal Replacement Therapy

46. Prognosis

 High mortality in severe disease,
 Pulmonary haemorrhage >50% mortality rate
 Poor prognostic indicators - pulmonary involvement, elevated
creatinine, oliguria and thrombocytopenia
 Liver dysfunction has not been confirmed to be an independent risk
factor for death
 No permanent sequelae or progressive organ dysfunction after
resolution
“Patients with multiple organ involvement to be referred to tertiary care centre”

47.  No vaccine availablecurrently
1. Personal protection
General sanitation measures, Rodents Control
Avoidance of swimming in contaminated places
Avoid of direct and indirect human contact with animal urine
Use rubber shoes and gloves in water logged areas
2. Chemoprophylaxis
During the peak transmission season
Doxycycline 200 mg, once a week, for six weeks
(never to be extended for more than eight weeks)
Alternative-Azithromycin 10 mg/kg single dose (max 500 mg)
PREVENTION


48.  Adequate history of exposure is most important in diagnosis
 Possibility of leptospirosis to be kept in d/d of
icteric illness
acute flulike febrile illnesses.
 Prompt treatment can prevent life threatening complications
 Dialysis for acute kidney injury (AKI) and ventilatory support for
respiratory failure would definitely reduce mortality.
 Health education, sanitation measures and awareness for prevention
Take Home Message
