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

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

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

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

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

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

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

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

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

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)

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

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 )

Silver stain, liver, fatal human leptospirosis

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)

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

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)

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)

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

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

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)

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

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

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)

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

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

Other antimicrobials Amoxicillin Cefotaxime Ceftriaxone 0.5-1.0 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

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

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

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