Symptoms

Fever Weakness Vomiting Anorexia Cough/cold Epistaxis Jaundice dyspnea Abdominal pain Diarrhea Tea colored urine

Physical examination
Weak looking Gasping respiration Hypotension Bradycardia Generalized Jaundice Cool, blotchy,congested skin Pale palpebral conjunctivae Icteric Sclerae Circumoral cyanosis Palpable Cervical lymph node Decreased vocal and tactile fremitus Hepatosplenomegaly Pale nailbeds Rapid and weak pulses Prolonged CRT

Neurologic examination Lethargic anisocoria (+) left lateral gaze (+) weak gag reflex Sluggish reaction to painful stimulus No clonus No nuchal rigidity

Laboratory results
Leukopenia Thrombocytopenia Prolonged APTT, PT Hyperkalamia Metabolic Acidosis

Social History

Salient Features
DIC
Weak looking Gasping respiration Hypotension Bradycardia Cool, blotchy,congested skin Pale palpebral conjunctivae Circumoral cyanosis

FEVER

JAUNDICE

HEPATOMEGALY
Chronic

Acute

Hepatitis A

Hemolytic Uremic Syndrome

Malaria

Dengue Hemorrhagic Fever

Typhoid Fever Leptospirosis

Fever
Incubation Period 28 days
Range 2 weeks- 6 months

Nausea Vomiting Anorexia

Abdominal Pain
Diarrhea

Direct Cell Injury

Cholestasis Jaundice Prolonged Coagulation Parameters

Inadequate Liver function

LIVER NECROSIS

FEVER

JAUNDICE

HEPATOMEGALY

Acute

Hepatitis A

Hemolytic Uremic Syndrome

Malaria

Dengue Hemorrhagic Fever

Typhoid Fever Leptospirosis

Ingestion of bacteria

BLOODY DIARRHEA
Flu-like symptoms Endothelial cell injury

Inflammation/ ulceration of colon Hemolysis

LEUKOCYTOSIS
Thrombocytopenia

Hepato splenomegaly

NOMAL COAGULATION PARAMETERS

Thrombosis/ischemia

Platelet aggregation

Anemia Pallor

FEVER

JAUNDICE

HEPATOMEGALY

Acute

Hemolytic Uremic Syndrome

Malaria

Dengue Hemorrhagic Fever

Typhoid Fever Leptospirosis

Fever Anorexia Weakness Cough & Cold Abdominal Pain

NO SEVERE ANEMIA
Anemia

Generalized Jaundice Hepatosplenomegaly

Leukopenia

Thrombocytopenia

FEVER

JAUNDICE

HEPATOMEGALY

Acute

Malaria

Dengue Hemorrhagic Fever

Typhoid Fever Leptospirosis

Incubation Period 2-7 days

Fever Vomiting Anorexia Weakness Abdominal Pain Cough Leukopenia

Liver Injury

Disorder in Hemostasis

Platelet DURATION Dysfunction

Coagulopathy Thrombocytopenia

NO HEMOCONCENTRATION
Bleeding

FEVER

JAUNDICE

HEPATOMEGALY

Acute

Dengue Hemorrhagic Fever

Typhoid Fever Leptospirosis

1st Week
10-14 Days
Fever Malaise Anorexia Cough Abdominal Pain

2nd Week Cholestasis & Hepatitis Nephritis Renal Failure Hyperkalemia

Splenomegaly Respiratory Distress

Genealized Jaundice

Tea colored Urine

Hepatomegaly

FEVER

JAUNDICE

HEPATOMEGALY

Acute

Typhoid Fever Leptospirosis

LEPTOSPIROSIS

Anicteric Form

Icteric Form * 5-10%

Septicemic Phase

Immune Phase

Septicemic Phase

Immune Phase

(3 - 7 Days)

(3 - 7 Days)

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

*18th Ed Nelson Textbook of Pediatrics

Part A ,
or

Part A + Part B together Score

26 or more or

PART A + B + C
25 or more

score between 20 and 25

Part A Fever? If Yes is the temp 39C or more Jaundice?

Yes=2 No= 0 Yes=2 No= 0 Yes=1 No= 0 Total Score Yes=10

Score 2 2 1 5 Score 10

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

TotalScore A+B

15

Part A Has the patient Headache of sudden onset Fever?

If Yes is the temp 39C or more

Conjuntival Suffusion?

Meningism
Are all three features (conjuntival suffusion,muscle pains and meningism present together? Jaundice? Albuminuria or Nitrogen retention

Yes=2 No= 0 Yes=2 No= 0 Yes=2 No= 0 Yes=4 No= 0 Yes=4 No= 0 Yes=10

Score 2 2

2
4

0
0

Yes=1 No= 0 Yes=2 No= 0 Total Score

1 2 13

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

Yes=10

Score 10

TotalScore A+B

23

Part C

Bacteriologicallaboratory findings?
Positive serology-leptospirosis endemic

DiagnosisCriteria Yes=2 No=0

Yes=10 No=0 Yes=25 No=0

Single positive, low titer

Single positive, high titer Paired Sera,rising Titer

Positive serology,leptospirosis not endemic

Single positive, low titer Single positive, high titer Paired Sera,rising Titer Yes=5 No=0 Yes=15 No=0 Yes=25 No=0 Total Score A+B+C

PATHOGENESIS

Infected Urine & Excreta

Endotoxin
Flu-like symptoms
Hemorrhagic Diasthesis (fever,cough &colds,diarrhea leukopenia thrombocytopenia) Endothelial damage to the different organ system of the body Multiorgan Dysfunction Septicemic Phase

Immune Phase

Pulmonary

Liver

Renal

Cardiac

RENAL FAILURE

HEPATIC FAILURE

HEMORRHAGIC DIASTHESIS

Hypovolemia & Hypotension

Dehydration

Circulatory Collapse

Multiple Organ Failure

DEATH

MULTIPLE ORGAN FAILURE SECONDARY TO WEILS DISEASE

THANK YOU !

PULMONARY
20-70%
Acute Inflammation Pneumonia

Parenchymal Cells

Endothelial damage to capillaries

Interstitial and Alveolar Hemorrhage

Necrosis

Respiratory Distress

Decreased Vocal & Tactile Fremitus

5th edition Textbook of Infectious Diseases by Feigin

LIVER
Centrilobular Necrosis with Kupffer Proliferation

Hepatic Dysfunction

HEMOLYSIS

HEPATOCELLULAR INJURY

Jaundice

Anemia

Hemoglobin 104

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

Thrombocytopenia

Hepatomegaly

Hypovolemia
Tachycardia Hypotension

Electrolyte Imbalance
Hyperkalemia

Cardiac Dysfunction

Hypoperfusion

Prolonged Capillary Time

Rapid & Weak Pulses

RENAL
Tubular necrosis Interstitial Nephritis

tea colored urine

Renal Failure
Dehydration
Hyperkalemia

Widespread damage of capillary endothelium

Primary Hemostasis
Bone marrow supression Thrombocytopenia

Secondary Hemostasis
Fibrinolysis

Prolonged APTT/PT

Hemorrhagic Diasthesis

GI Bleeding

Pulmonary Hemorrhage

Intracranial Bleed
Uncal herniation

Blood streaked Vomitus

Cough Dyspnea

lethargy lateral gaze

anisocoria

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 Transmission
Animal 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

Serological Classification & Groupings

Hosts
RATS MICE DAIRY CATTLES DOGS SHEEP PIGS HUMANS

Serogroups
L. Icterohaemorrhagiae L. Ballum L. Hardjo, Pomona L. Canicola L. Hardjo L. Pomona, Tarassovi L. Icterohaemorrhagiae

Recreational
water sports, swimming, canoeing, water rafting, potholing, caving

Avocational exposures
barefoot walking, flood swimming

Adhesion to Cell Surfaces and Cellular Toxicity

LEPTOSPIRES
PORT OF ENTRY

Small Blood Vessel vasculitis Kidney interstitial nephritis & tubular necrosis Liver centrilubular necrosis Skeletal Muscles swelling, focal necrosis

Conjunctiva Mucous Membrane Mouth Abraded Skin Open wounds

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 FEATURES
Severe Leptospirosis (Weils 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 ESR
- urine sediments changes leokocytes, erythrocytes, hyaline or granular

casts, with mild proteinuria

- elevated (anicteric leptospirosis) peripheral leukocyte count range from 3,000 to 26,000/Ul with left shift; (Weils Syndrome) marked leukocytosis

THROMBOCYTOPENIA LIVER ENZYMES

- in about 50% of patients implying renal failure

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

and aminotransferase)

PROTHROMBINE TIME

- is prolonged in Weils 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 - Weils syndrome may require dialysis for renal failure, may need transfusion of whole blood/or platelets

Hepa A