17 y.o. male CC: Fever and rash PMHx: RLL Pneumonia 1998 Mononucleosis 2005 MEDs: None Allergies: Penicillins - rash

8. Leptospirosis

9. History A zoonosis caused by the spirochete leptospira interrogans 1883: First recognized as an occupational disease of sewer workers 1886: Weil’s disease Named after Adolph Weil who described the disease as: “an acute infectious disease with enlargement of spleen, jaundice, and nephritis” This is most severe form of leptospirosis 1907: Stimpson, first isolate

10. Epidemiology Worldwide distribution Most cases occur in tropics Thailand: 30-fold increased in cases from 1995-2000 Hypothesis: increased rat population and seasonal flooding In US, most cases are in southern and Pacific coastal states Hawaii has most cases of any state in US Outbreaks can occur 12% of athletes participating in Illinois triathlon after exposure to lake water in swimming phase Areas with high rat population and seasonal flooding have the highest incidence

11. At Risk Populations Occupational Exposure: Farmers, veterinarians, sewer workers, rice field workers Recreational Activities: Fresh water swimming, canoeing, kayaking Household Exposures: Domesticated livestock, infestation by infected rodents

12. Pathogenesis Humans become infected after exposure to environmental sources: Animal urine (wild and domestic mammals especially rodents, cattle, swine, dogs, horses, sheep, and goats) Contaminated soil or water Infected animal tissue Portals of entry: Abraded skin Mucous membranes Conjunctiva Incubation period 7-12 days

13. Clinical Course 90% of patients have mild symptoms while 5-10% have severe form with jaundice (Weil’s Disease) Natural course has 2 distinct phases: First Stage (Leptospiremic): Lasts 4-7 days Non-specific flu-like symptoms Fevers, chills, sore throat, headaches, myalgias, rash Second Stage (Immune or Leptospiruric): Lasts up to 30 days Circulating antibodies may be detected Organism may be isolated from urine Meningeal symptoms in 50% of patients Viral etiology may be suspected

14. Exam findings During First Stage: Fevers, pharyngeal injection, lymphadenopathy Conjunctival suffusion: Conjunctival redness due to increased blood flow During Second Stage: Adenopathy, rash, fever Jaundice, splenomegaly, abdominal tenderness

15. Advanced Disease – Weil’s Syndrome Severe form of leptospirosis characterized by profound jaundice, renal dysfunction, hepatic necrosis, and hemorrhagic diathesis Criteria for diagnosis are not well defined Complications include: Renal failure, uveitis, hemorrhage, ARDS, myocarditis, rhabdomyolysis, liver failure Mortality rate of 5-10% Some studies suggest case fatality rates of 20-40%

16. Laboratory Findings Thrombocytopenia Leukocytosis with left shift Elevations of transaminases (<200) in 40% of patients Elevated CK in up to 50% of patients UA with proteinuria CSF may show a neutrophilic or lymphocytic pleocytosis with normal protein and glucose

17. CDC Diagnostic Criteria

18. Diagnosis Culture: Blood Positive in 1st 10 days of illness Isolation successful in only 50% of cases CSF Positive in 1st 10 days of illness Urine Becomes positive in 2nd week of illness May remain positive for up to 30 days after resolution of symptoms

19. Serology: Microscopic agglutination test (MAT), macroscopic agglutination test, indirect hemagglutination, and ELISA Gold standard is MAT, but is not widely available Most common tests used in clinical practice: Microplate IgM ELISA IgM dot-ELISA dipstick If one of these is positive, sera for MAT can be sent to CDC PCR is being explored and showing some promise in diagnosis, but is not yet widely available Diagnosis

20. Treatment Antibiotic treatment for one week Doxycycline 100 mg IV or po q 12 hrs Ampicillin 500 - 1000 mg IV q 6 hrs Penicillin G 3-4 million units IV q 4 hrs Penicillin G 1.5 million units IV q 6 hrs Ceftriaxone 1 gram IV qd