FeverFeverWeaknessWeaknessVomitingVomitingAnorexiaAnorexiaCough/coldCough/cold

EpistaxisEpistaxisJaundiceJaundicedyspnea dyspnea Abdominal painAbdominal painDiarrheaDiarrheaTea colored urineTea colored urine

Symptoms

Physical Physical examinationexamination

Weak lookingWeak lookingGasping respirationGasping respirationHypotensionHypotensionBradycardiaBradycardiaGeneralized JaundiceGeneralized JaundiceCool, blotchy,congested Cool, blotchy,congested

skinskinPale palpebral conjunctivaePale palpebral conjunctivaeIcteric ScleraeIcteric ScleraeCircumoral cyanosisCircumoral cyanosisPalpable Cervical lymph Palpable Cervical lymph

nodenode

Decreased vocal and Decreased vocal and tactile fremitustactile fremitus

HepatosplenomegalyHepatosplenomegalyPale nailbedsPale nailbedsRapid and weak pulsesRapid and weak pulsesProlonged CRTProlonged CRT

LethargicLethargicanisocoriaanisocoria(+) left lateral gaze(+) left lateral gaze(+) weak gag reflex(+) weak gag reflexSluggish reaction toSluggish reaction topainful stimuluspainful stimulus

No clonusNo clonusNo nuchal rigidityNo nuchal rigidity

Neurologic examinationNeurologic examination

LeukopeniaLeukopeniaThrombocytopeniaThrombocytopeniaProlonged APTT, PTProlonged APTT, PTHyperkalamiaHyperkalamiaMetabolic AcidosisMetabolic Acidosis

Laboratory resultsLaboratory results

Social HistorySocial History

Salient FeaturesSalient Features

Weak lookingWeak lookingGasping respirationGasping respirationHypotensionHypotensionBradycardiaBradycardiaCool, blotchy,congested skinCool, blotchy,congested skinPale palpebral conjunctivaePale palpebral conjunctivaeCircumoral cyanosisCircumoral cyanosis

DIC

FEVER +JAUNDICE+ HEPATOMEGALY

Acute Chronic

Hepatitis A

Hemolytic Uremic Syndrome

Dengue Hemorrhagic Fever

Malaria

Typhoid Fever

Leptospirosis

Incubation Period 28 days

Range2 weeks- 6 months

FeverNausea

VomitingAnorexia

Abdominal PainDiarrhea

Direct Cell Injury

Cholestasis Jaundice

InadequateLiver function

Prolonged Coagulation Parameters

LIVER NECROSIS

FEVER +JAUNDICE+ HEPATOMEGALY

Acute

Hepatitis A

Hemolytic Uremic Syndrome

Dengue Hemorrhagic Fever

Malaria

Typhoid Fever

Leptospirosis

Ingestion of bacteria

Inflammation/ulceration of colon

Endothelial cell injury HemolysisFlu-like symptoms

Platelet aggregationThrombocytopenia Anemia Pallor

Hepatosplenomegaly Thrombosis/ischemia

BLOODY DIARRHEA

LEUKOCYTOSIS

NOMAL COAGULATION PARAMETERS

FEVER +JAUNDICE+ HEPATOMEGALY

Acute

Hemolytic Uremic Syndrome

Dengue Hemorrhagic Fever

Malaria

Typhoid Fever

Leptospirosis

Fever

Abdominal Pain

AnorexiaWeakness

Cough & Cold

Anemia

Thrombocytopenia

Leukopenia

HepatosplenomegalyGeneralized Jaundice

NO SEVERE ANEMIA

FEVER +JAUNDICE+ HEPATOMEGALY

Acute

Dengue Hemorrhagic Fever

Malaria

Typhoid Fever

Leptospirosis

Incubation Period 2-7 days

Fever

AnorexiaWeakness

Vomiting

Abdominal PainCough

Disorder in Hemostasis

Platelet Dysfunction

Coagulopathy

Bleeding

Thrombocytopenia

Leukopenia

DURATION

NO HEMOCONCENTRATION

Liver Injury

FEVER +JAUNDICE+ HEPATOMEGALY

Acute

Dengue Hemorrhagic Fever

Typhoid Fever

Leptospirosis

10-14 Days

Fever

MalaiseAnorexiaCough

Abdominal Pain

Cholestasis & Hepatitis

Nephritis Renal Failure

Genealized Jaundice

Hepatomegaly

Tea colored Urine

Hyperkalemia Splenomegaly

Respiratory Distress

1st Week

2nd Week

FEVER +JAUNDICE+ HEPATOMEGALY

Acute

Typhoid Fever

Leptospirosis

LEPTOSPIROSIS

Icteric Form

Septicemic Phase Immune

PhaseImmune Phase

Septicemic Phase

(3 - 7 Days) (0 - 1 Month)(3 - 7 Days) (10 - 30 Days)

Anicteric Form* 5-10%

*18th Ed Nelson Textbook of Pediatrics

Part A ,

Part A + Part B together Score26 or more

or

PART A + B + C

25 or more

or

score between score between 20 and 2520 and 25

Fever?Fever? Yes=2Yes=2No= 0No= 0

22

If “Yes” is the temp 39C or moreIf “Yes” is the temp 39C or more Yes=2Yes=2No= 0No= 0

22

Jaundice?Jaundice? Yes=1Yes=1No= 0No= 0

11

Total ScoreTotal Score 55

Part APart A ScoreScore

Part BPart B ScoreScoreEpidemilogigal Factors: contact with Epidemilogigal Factors: contact with animals at home,work travel or contact animals at home,work travel or contact with known contaminated waterwith known contaminated water

Yes=10Yes=10 1010

TotalScore A+BTotalScore A+B 1515

Has the patient Headache of sudden onset Has the patient Headache of sudden onset Yes=2Yes=2No= 0No= 0

22

Fever?Fever? Yes=2Yes=2No= 0No= 0

22

If “Yes” is the temp 39C or moreIf “Yes” is the temp 39C or more Yes=2Yes=2No= 0No= 0

22

Conjuntival Suffusion?Conjuntival Suffusion? Yes=4Yes=4No= 0No= 0

44

MeningismMeningism Yes=4Yes=4No= 0No= 0

00

Are all three features (conjuntival Are all three features (conjuntival suffusion,muscle pains and meningism suffusion,muscle pains and meningism present together?present together?

Yes=10Yes=10 00

Jaundice?Jaundice? Yes=1Yes=1No= 0No= 0

11

Albuminuria or Nitrogen retentionAlbuminuria or Nitrogen retention Yes=2Yes=2No= 0No= 0

22

Total ScoreTotal Score 1313

Part APart A ScoreScore

Part BPart B ScoreScoreEpidemilogigal Factors: contact with Epidemilogigal Factors: contact with animals at home,work travel or contact animals at home,work travel or contact with known contaminated waterwith known contaminated water

Yes=10Yes=10 1010

TotalScore A+BTotalScore A+B 2323

Part CPart CBacteriologicallaboratory findings?Bacteriologicallaboratory findings? DiagnosisCriteriaDiagnosisCriteriaPositive serology-leptospirosis endemicPositive serology-leptospirosis endemic Single positive, low titer Single positive, low titer Yes=2Yes=2

No=0No=0 Single positive, high titer Single positive, high titer Yes=10Yes=10

No=0No=0 Paired Sera,rising TiterPaired Sera,rising Titer Yes=25Yes=25

No=0No=0Positive serology,leptospirosis not Positive serology,leptospirosis not endemicendemic Single positive, low titer Single positive, low titer Yes=5Yes=5

No=0No=0 Single positive, high titer Single positive, high titer Yes=15Yes=15

No=0No=0 Paired Sera,rising TiterPaired Sera,rising Titer Yes=25Yes=25

No=0No=0Total ScoreTotal ScoreA+B+CA+B+C

Infected Urine & Excreta

PATHOGENESIS

Endotoxin

Flu-like symptoms(fever,cough &colds,diarrhea

leukopenia thrombocytopenia)

Hemorrhagic Diasthesis

Septicemic Phase

Endothelial damage to the different

organ system of the body

Multiorgan Dysfunction

Immune Phase

Pulmonary Liver CardiacRenal

RENAL FAILURE

HEPATICFAILURE

HEMORRHAGIC DIASTHESIS+ +

Hypovolemia

Circulatory CollapseCirculatory Collapse

Multiple Organ FailureMultiple Organ Failure

DEATHDEATH

Hypotension&

Dehydration

MULTIPLE ORGAN FAILURE MULTIPLE ORGAN FAILURE SECONDARY TO WEIL’S DISEASESECONDARY TO WEIL’S DISEASE

THANK YOU !THANK YOU !

PULMONARY20-70%

Endothelial damage to capillaries

Interstitial and Alveolar Hemorrhage

Parenchymal Cells

Necrosis

Decreased Vocal & Tactile Fremitus

Respiratory Distress

Acute Inflammation

Pneumonia

5th edition Textbook of Infectious Diseases by Feigin

LIVER

Centrilobular Necrosis with Kupffer Proliferation

Hepatic Dysfunction

HEPATOCELLULARHEPATOCELLULAR INJURYINJURY

Jaundice AnemiaHemoglobin 104

Prolonged APTT (62.5 sec)&PT(56.5 sec)

Thrombocytopenia

Hepatomegaly

HEMOLYSISHEMOLYSIS

Cardiac Dysfunction

Hypoperfusion

Prolonged Capillary Time

HypotensionTachycardia

Rapid & Weak Pulses

Hypovolemia Electrolyte Imbalance

Hyperkalemia

RENAL

TubularTubularnecrosisnecrosis

Interstitial Interstitial NephritisNephritis

tea colored tea colored urineurine

Renal FailureRenal Failure

DehydrationDehydration

HyperkalemiaHyperkalemia

Widespread damage of capillary endotheliumWidespread damage of capillary endothelium

Hemorrhagic DiasthesisHemorrhagic Diasthesis

GI BleedingGI Bleeding

Blood streaked Vomitus

PulmonaryPulmonaryHemorrhageHemorrhage

IntracranialIntracranial BleedBleed

Uncal Uncal herniationherniation

anisocoriaanisocoria

lethargylethargylateral lateral gazegaze

DyspneaDyspnea

Cough

Primary Hemostasis Secondary Hemostasis

Thrombocytopenia

Prolonged APTT/PT

FibrinolysisBone marrow supression

INCIDENCE Leptospirosis is a worldwide zoonotic infection and now identified as

one of the emerging infectious diseases

Endemic with estimated incidence of 25 clinical infection per 100,000 population

Significant outbreaks in Nicaragua, Brazil, India, Malaysia & USA

Large clusters of cases were noted following flooding as a result of excessive rainfall

Human infection is either direct or indirect contact with the urine of an infected animal, higher in warm-climate countries

Chain of TransmissionAnimal Species :

Rodents Cattles

Domestic animals

Human Infections: Occupational

Direct Contact• farmers• veterinarians• abattoir workers• meat inspectors Indirect• sewers • miners • soldiers• septic tank cleaners• canal workers

Recreational water sports, swimming,

canoeing, water rafting, potholing, caving

Avocational exposures barefoot walking ,

flood swimming

Serological Classification & Groupings Hosts Serogroups

RATS L. Icterohaemorrhagiae MICE L. Ballum

DAIRY CATTLES L. Hardjo, Pomona DOGS L. Canicola

SHEEP L. Hardjo PIGS L. Pomona, Tarassovi

HUMANS L. Icterohaemorrhagiae

PORTOF

ENTRY

LEPTOSPIRES

ConjunctivaMucous MembraneMouthAbraded SkinOpen wounds

Adhesion to Cell Surfacesand Cellular Toxicity

Small Blood Vessel –vasculitis

Kidney – interstitial nephritis&

tubular necrosis

Liver – centrilubular necrosis

Skeletal Muscles – swelling ,

focal necrosis

CLINICAL FEATURES

Incubation Period - 2 – 25 days after initial direct exposure

to the urine or tissue of an infected animal

Biphasic stages Anicteric Leptospirosis

1 .Acute leptospiremic phase - - Non-specific flu-like symptoms as fever and chills ,

severe headache usually frontal and retrobulbar w/photophobia nausea and vomiting

muscle pain affecting the calves, back and abdomen mental confusion pulmonary involvement as cough with some hemoptysis - Signs of conjunctival suffusion is evident less common are myalgias, lymphadenoathy, hepatosplenomegaly, rashes in any form

CLINICAL FEATURES

2. Immune leptospiremic phase

- asymptomatic for a week, and illness recur within a few days in some

- aseptic meningitis may develop in some patient for certain duration

- however, in a few cases complication such iritis, iridocyclitis and

chorioretinitis may occur.

CLINICAL FEATURESSevere Leptospirosis (Weil’s Syndrome)

1. Jaundice

2. Renal dysfunction

3. Hemorrhagic diasthesis

-Infection is associated with serovars L. icterohemorrhagiae and copenhagen

-Within 4 – 9 days, jaundice and vascular dysfunction generally develop.

-Renal failure within 2-3 weeks after, however, reversible if attended

-Pulmonary involvement with cough, dyspnea, chest pain and blood- stain sputum

-Hemorrhagic manifestations e.g. epistaxis, petechiae, purpura and eechymoses

GI bleeding, adrenal and subarachnoid hemorrhage are seen

-Rhabdomyolysis, myocarditis, CHF, cardiogenic shock, ARDS, and multi-organ failure are seen

LABORATORY & RADIOLOGIC FINDINGS

URINALYSIS - urine sediments changes leokocytes, erythrocytes, hyaline or granular

casts, with mild proteinuria

ESR - elevated (anicteric leptospirosis) peripheral leukocyte count range from 3,000 to

26,000/Ul with left shift; (Weil’s Syndrome) marked leukocytosis

THROMBOCYTOPENIA - in about 50% of patients implying renal failure

LIVER ENZYMES - are noted to be elevated up to up to 200U/L (alkaline phosphatase

and aminotransferase)

PROTHROMBINE TIME - is prolonged in Weil’s however can be corrected by Vit K

CSF - slightly elevated protein, normal glucose level but there is increase of polymorphs

followed by mononuclear cell increases

RADIOGRAPHIC FINDINGS - the affected lower lobes shows patchy alveolar pattern

that corresponds to alveolar hemorrhages

DIAGNOSIS

Definitive Diagnosis Isolation of the organism from the patient

Seroconversion or rise in antibody titer in MAT

Presumptive MAT with antibody titer of >1:100

Positive macroscopic slide agglutination test Presence of compatible clinical illness

DIAGNOSIS

ANTIGEN DETECTION

MICROSCOPIC AGGLUTINATION TEST ( MAT )

- reference method for serological diagnosis of leptospirosis

- patient sera is mixed with live antigen suspensions of leptospiral serovars

- after incubation, the serum-antigen mixture are examined microscopically for

agglutination and titers are determined

CDC case definition, a titer of >200 = probable case w/clinically compatible illness

Endemic Countries: a single titer of >800 in symptomatic patients is indicative of Lep

Acute Infection: may go as high as >25,600

DIAGNOSIS

ENZYME-LINK IMMUNOASSAY ( ELISA )

- use to detect IgM antibodies for diagnosis of human leptospira infection

- useful towards detection of serovar-specific antibodies for detection of infection

in food animals, detection of serovar pomona and hardjo infection in cattle

- IgM-specific dot-ELISA was developed and use to detect IgG and IgA anibodies

and shown to be sensitive

MACROSCOPIC SLIDE AGGLUTINATION TEST

-used for detection of 12 serovars for rapid screening of sera from humans & animals

- a new commercial slide agglutination assay was found to be as sensitive and

specific as an IgM-ELISA while remaining reactive for a shorter time after recovery

DIAGNOSIS

INDIRECT HEMAGGLUTINATION ASSAY ( IHA )

- use to detect both IgM and IgG antibodies

- it was developed at CDC and shown to have a sensitivity of 92% and a specificity

of 95% for serological diagnosis of leptospirosis

MICROCAPSULE AGGLUTINATION TEST (MCAT)

-using a synthetic polymer in place of RBC and has been extensively evaluated in

Japan and China

- more sensitive than MAT and IgM-ELISA in acute phase samples

- this is a direct agglutination method

POLYMERASE CHAIN REACTION ( PCR )

- use for detection of Leptospiral DNA, more sensitive than culture

- has been used to distinguish pathogenic from non-pathogenic serovars

DIAGNOSIS

CULTURE OF THE ORGANISM

- leptospire can be detected from blood and CSF during the first 10 days of illness

- while in urine for several weeks beginning within the 1st week

- cultures may become positive after 2 to 4 weeks ranging from 2 weeks to 4 months

- sometimes urine culture remain positive for months or years from the start of illness

-

TREATMENT

Mild Cases of Leptospirosis - Oral Tetracycline, Doxycycline, Ampicillin and Amoxycillin

Severe Leptospirosis - Intravenous Penicillin-G, Amoxycillin, Ampicillin or Erythromycin

- Weil’s syndrome may require dialysis for renal failure, may need

transfusion of whole blood/or platelets

Hepa AHepa A