Leptospirosis

Hospitalist Conference
17 y.o. male
CC: Fever and rash
PMHx:
 RLL Pneumonia 1998
 Mononucleosis 2005
MEDs:
 None
Allergies:
 Penicillins - rash
Social Hx:
 Lives with parents
 Junior in High School
 Works on family farm
 Alcohol: None
 Tobacco: 1 pack/wk
Family Hx:
 Hypertension: Father
 Colon Cancer: PGF
Case Conference
17 y.o. male
CC: Fever and rash
PMHx:
 RLL Pneumonia 1998
 Mononucleosis 2005
MEDs:
 None
Allergies:
 Penicillins - rash
Social Hx:
 Lives with parents
 Junior in High School
 Works on family farm
 Alcohol: None
 Tobacco: 1 pack/wk
Family Hx:
 Hypertension: Father
 Colon Cancer: PGF
HPI:
 Felt well until 1 week ago
 Developed headache and neck pain
 No vision changes, mild sore throat
 After 3 days, noted fevers to 100.6
 Seen in New Ulm ED
Case Conference
17 y.o. male
CC: Fever and rash
PMHx:
 RLL Pneumonia 1998
 Mononucleosis 2005
MEDs:
 None
Allergies:
 Penicillins - rash
Social Hx:
 Lives with parents
 Junior in High School
 Works on family farm
 Alcohol: None
 Tobacco: 1 pack/wk
Family Hx:
 Hypertension: Father
 Colon Cancer: PGF
HPI:
 Felt well until 1 week ago
 Developed headache and neck pain
 No vision changes, mild sore throat
 After 3 days, noted fevers to 100.6
 Seen in New Ulm ED
HPI Continued:
 Throat culture and mono spot negative
 LP not done
 Discharged with Tylenol and Advil
 3 days later, fever to 102 with nausea
 Diffuse, non-pruritic rash “blotches”
 no raised lesions or blisters
 Rash involved trunk, back and thighs
 Recurrent fever to 102.7 – returned to ED
Labs:
3.0
14.2
46
Neut: 69% Lymph 23%
West Nile IgG, IgM sent
CXR: No acute disease
17 y.o. male
CC: Fever and rash
Case Conference
HPI Continued:
 Discharged from ED
 Thought to be viral etiology
 Slept 20 hours next day
 Fevers to 104.4
 PMD referred pt to ANW ED
ROS:
 Positive for fatigue, fevers and chills, decreased
appetite, nausea, vomiting and diarrhea
 No cough or sputum, no SOB
 No recent sick contacts
 No recent tick bites or travel
Exam:
Vitals: HR 105 BP 124/58 T 102.8 RR 16 O2 97%
HEENT: no scleral icterus, injected bilaterally
Resp: CTA
CV: Tachycardic, regular
Abdomen: soft, non-tender, bowel sounds present
Neuro: Alert and oriented x3, CN II-XII intact, strength
5/5 bilaterally, reflexes 2+
Skin: Diffuse erythematous rash on chest, back, abdomen
with reticular appearing rash on arms
17 y.o. male
CC: Fever and rash
Case Conference
Labs:
Alk Phos: 214 Hepatitis Serology: Negative
135
97
20
34
2.8
96 AST: 305
HIV: Negative
22
3.8
1.3
Blood Cultures: No Growth
ALT: 277
HPI Continued:
13.8
Ehrlichia: Negative
T. bili: 2.0
 Seen by ID
West Nile IgM, IgG: Negative
 Additional History:
 Assisted on a pig farm during the summer
 Bitten by a pig 2 months prior – resolved
 850 pigs died during heat wave when fan in barn malfunctioned
 patient assisted with disposing of dead pigs – did not use gloves or mask
 Empirically started on Doxycycline for presumed Leptospirosis
 IgG and IgM serology, Lepto urine and blood cultures
17 y.o. male
CC: Fever and rash
Case Conference
Labs:
2.8
13.8
Alk Phos: 214 Hepatitis Serology: Negative
135
97
20
34
96 AST: 305
HIV: Negative
22
3.8
1.3
Blood Cultures: No Growth
ALT: 277
T. bili: 2.0
Ehrlichia: Negative
West Nile IgM, IgG: Negative
LEPTOSPIROSIS
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
Epidemiology

Worldwide distribution


Most cases occur in tropics
Thailand: 30-fold increased in cases from 1995-2000


In US, most cases are in southern and Pacific coastal states


Hawaii has most cases of any state in US
Outbreaks can occur


Hypothesis: increased rat population and seasonal flooding
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
At Risk Populations

Occupational Exposure:


Recreational Activities:


Farmers, veterinarians, sewer workers, rice field workers
Fresh water swimming, canoeing, kayaking
Household Exposures:

Domesticated livestock, infestation by infected rodents
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
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

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

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%
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
CDC Diagnostic Criteria
Diagnosis

Culture:

Blood



CSF


Positive in 1st 10 days of illness
Isolation successful in only 50% of cases
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
Diagnosis

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
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