1. Internal Medicine Workshop Series Laos September /October 2009
Leptospirosis
Internal Medicine Workshop Series Laos
September /October 2009

2. What do you know about leptospirosis?
Write down …
2 animals that can be infected with leptospirosis
2 ways the bacteria can enter the human body
2 complaints the patient may have (history)
2 examination findings (physical)
2 organs that may be involved and how the organ damage can be shown
2 antibiotics to treat leptospirosis

3. Background Caused by gram negative spirochetes: Genus Leptospira
Most common zoonosis (disease from animals) in the world
Humans and animals (mammals, birds, amphibians and reptiles) can develop Leptospira infection
Humans are rarely chronic carriers (they are accidental hosts)
Animals are often chronic carriers

4. A scanning electron micrograph depicting Leptospira on a 0
A scanning electron micrograph depicting Leptospira on a 0.1-µm polycarbonate filter

5. How does infection happen?
Direct contact with
the body fluid of an acutely infected animal
exposure to soil or fresh water contaminated with the urine of an animal that is infected or a chronic carrier

6. How does infection happen?
Leptospires enter host through…
abrasions in healthy skin
waterlogged , wet skin
intact mucus membranes or conjunctiva, nasal mucosa
lungs (aerosolized body fluid)
placenta (during pregnancy)
Then through the lymphatics, causing septicemia and spread to all organs
Host develops immunoglobulin to clear bacteria

7. Two stages Acute Delayed septicemic stage of acute febrile illness
lasts 5-7 days
Delayed
immune phase
lasts 4-30 days

8. Two presentations Anicteric leptospirosis
self limited disease, flu like illness
septicemic phase (acute)
immune phase (delayed)
Icteric leptospirosis (Weil disease)
severe illness with multi-organ involvement and failure
septicemic and immune phase are mixed together

9. Morbidity/mortality Mild forms are rarely fatal
90% of cases are mild
In severe forms, mortality is 5-40%
Elderly and immunocompromised are at highest risk for severe cases
Working aged-males have more exposure

10. How quickly and for how long?
Incubation period usually 5-14 days (3-30)
Leptospires remain in renal tubules, brain anterior chamber of eye for 60 days (longer in animals)

11. Leptospirosis is an infective systemic vasculitis
Leptospires multiply in the small blood vessel endothelium resulting in vasculitis

12. Leptospirosis is an infective systemic vasculitis
Kidneys
interstitial nephritis and tubular necrosis
Liver
centrilobular necrosis and hepatocyte dysfunction
Pulmonary
alveoloar and interstitial vascular damage with hemorrhage ( MAJOR CAUSE OF LEPTOSPIROSIS ASSOCIATED DEATH )

13. Silver stain, liver, fatal human leptospirosis

14. Leptospirosis is an infective systemic vasculitis
Skin
epithelial blood vessels leak (rash, purpura)
Skeletal muscle
edema
Capillary leakage
hypovolemia, shock
Coagulation abnormalities
disseminated intravascular coagulation (DIC)
hemolytic uremic syndrome (HUS)
thrombotic thrombocytopenic purpura (TTP)

15. Up to 80% of people in the tropics have evidence of past infection

16. History
Exposure
Urine, kidneys, or conception products of infected animals.
Rodents, dogs, cattle and pigs
Direct infection (body fluids, organs of infected animals)
Indirect infection (inoculated soil and water)

17. Acute phase 5-7 days High temperature Rigors Sudden headache
Nausea and vomiting
Anorexia
Diarrhea
Cough, pharyngitis
Non pruritic skin rash
Muscle pains (calf and lumbar area)

18. Physical Fever (about 7 days) Signs of volume depletion tachycardia
hypotension
oliguria
Abnormal chest exam
Skin
transient petechial eruption (palate)
Jaundice
purpura
Eyes
conjuctival suffusion (like conjunctivitis but no exudates)
uveitis

19. Physical Muscle tenderness Lung exam Myocarditis Abdomen
paraspinal and calf muscles
Lung exam
crackles or consolidation from alveoloar hemorrhage
Myocarditis
signs of heart failure
Abdomen
liver enlargement and tenderness from acalculous cholecystitis
Meningeal signs
neck stiffness
rigidity
photophobia
delerium
In severe disease, may have prolonged mental symptoms like depression, anxiety, irritability, psychosis, dementia

20. Clinical Diagnosis Fever > 38. 0°C (100
Clinical Diagnosis Fever > 38.0°C (100.4 °F) AND at least TWO from COLUMN A or ONE from COLUMN B
COLUMN A
Headache
Myalgias
Jaundice
Chills/Rigors
Skin rash
Conjunctival suffusion without purulent discharge
COLUMN B
Aseptic meningitis
Acute renal failure
Hemorrhagic pneumonitis
Cardiac arrhythmias, EKG abnormalities
Liver failure
Jaundice with acute renal failure (Weil’s disease)

21. Differential diagnosis
Influenza Enteric fever Hantavirus Rickettsial disease Encephalitis Primary HIV infection

22. Laboratory: confirm diagnosis
Isolate the leptospires from human tissue or body fluids (urine)
Paired acute and convalescent serum specimens using microscopic agglutination test (MAT) 4X rise in antibody titre
Singly MAT titer of 1:800
Identification of spirochetes on dark-field microscopy

23. Laboratory: organ involvement
CBC (hemorrhage, platelets from DIC)
Creatinine and BUN (renal failure, shock)
Magnesium and potassium (wasting)
Bilirubin, (capillaritis in the liver). Alkaline phosphatase AST, ALT
INR PTT (DIC, liver disease)

24. Diagnostic imaging Chest Xray Abdominal ultrasound
bilateral diffuse airspace disease
cardiomegaly, pulmonary edema
patchy infiltrates
Abdominal ultrasound
acalculous cholecystitis

25. Treatment: antimicrobial
Outpatient treatment
Oral doxycycline
Decreases duration of fever and most symptoms
100 mg PO bid for 7 days
Hospitalized patient
Intravenous penicillin G
20-24 million U/d IV divided q4-6h for 7 days
Intravenous doxycycline
100 mg IV q12h for 7 days

26. Other antimicrobials Amoxicillin Cefotaxime Ceftriaxone
g PO q8h
Cefotaxime
1 g IV q6h
Ceftriaxone
1 g IV q24h
Erythromycin (pregnant, penicillin allergy)
500 mg IV q6h
500 mg PO qid

27. Treatment: supportive
Monitor and treat patient for
Shock
Renal failure (usually always reversible)
Respiratory failure (mechanical ventilation)
Cardiac monitoring (arrhythmias)
Plasma exchange, corticosteroids, IV immunoglobulin

28. Prevention
Avoid or reduce contact with animals, contaminated soil or water
Wear protective garments including footwear, gloves and eye protection
Attention to hygiene and sanitation

29. What new knowledge do you have?
Write down different information!
2 animals that can be infected with leptospirosis
2 ways the bacteria can enter the human body
2 complaints the patient may have (history)
2 examination findings (physical)
2 organs that may be involved and how the organ damage can be shown
2 antibiotics to treat leptospirosis