Overview
- Definition
One of the most common zoonotic infections in the world, caused by gram-negative helical spirochete Leptospira interrogans
Infection occurs via direct contact with animal blood or urine (farmers and abattoir workers, veterinarians, laboratory workers), or more commonly via indirect contact with contaminated water (farmers, sewer workers, freshwater swimmers/boaters); there is a higher incidence after heavy rainfall and flooding in temperate and tropical climates
Panuveitis is by far the most common ocular presentation
- Symptoms
Conjunctival redness
Photophobia
Blurry vision
Floaters
- Laterality
More commonly bilateral
- Course
Systemic disease presents acutely, typically 2 days to 4 weeks after exposure
Uveitis tends to occur in the late immune phase (see below), which can be months after acute systemic illness
- Age of onset
Young to middle-age adults
- Gender/race
Males are more often affected due to occupational exposures
Central and South America, the Caribbean, Southeast Asia, and the Pacific Islands
- Systemic association
Extremely wide spectrum of presentations, as the spirochete can invade any organ. Disease severity depends on serovar of the infecting organism and host’s immune response
- In general, leptospirosis is biphasic
Spirochetemic phase: abrupt headache, fever, vomiting, myalgia following the incubation period of 2–26 days; spirochete is found in blood, cerebrospinal fluid (CSF), and kidneys
Spirocheturic (immune) phase: recurrence of fever, development of complications, including meningitis, leptospiruria, nerve palsies, jaundice, renal failure, pulmonary hemorrhage, ocular symptoms, etc.; 90% of patients have mild, anicteric disease that gets resolved without treatment; the other 10% can have severe icteric disease with jaundice and azotemia, with up to 30% mortality rate
Weil’s syndrome: a particularly serious presentation of leptospirosis in which jaundice and renal failure occur; the biphasic nature is often obscured by rapid deterioration to multi-organ failure and death
Exam: Ocular
Anterior Segment
Conjunctival hyperemia and subconjunctival hemorrhage
Non-granulomatous anterior uveitis with diffuse Keratic Precipitates
Posterior synechiae
Hypopyon
Rapid cataract formation (but may resorb in some cases)
Posterior Segment
- Frequently severe vitritis with large clumps and membranes
Vitreous membranes are highly suggestive of diagnosis in the right clinical setting, after toxoplasmosis and infectious endophthalmitis are ruled out
Non-occlusive periphlebitis
Papillitis with optic nerve head hyperemia and edema
Cystoid Macular Edema (CME) is very rare
Exam: Systemic
Fever
Jaundice
Aseptic meningitis
Respiratory symptoms
Neuropathy
Imaging
- FA
Vascular staining
Late optic disc hyperfluorescence
Laboratory and Radiographic Testing
Testing is imperfect; if there is high clinical suspicion, empiric treatment may be appropriate
Culture of body fluids (blood and CSF during the first week of infection, and urine after the first week of infection, can remain positive for up to 30 days after symptoms resolve) with Ellinghausen-McCullough-Johnson-Harris (EMJH) medium: growth can take several weeks but can be negative if antibiotics are given prior to collection of samples
- Leptospiral antibody detection (serology) by Enzyme-Linked Immunosorbent Assay (ELISA) antibodies can be found after 5–7 days of illness in naïve patients
Background seropositivity in endemic areas makes this strategy challenging for diagnosis of acute infection
Paired serum (acute/convalescent samples) are preferred
Polymerase Chain Reaction (PCR) for leptospiral DNA: test blood during bacteremic phase, CSF, and urine a few days after onset of symptoms, aqueous and vitreous fluids
Microscopic agglutination test (MAT) is the reference standard for testing and may be requested through the Center for Disease Control and Prevention if ELISA or PCR is positive
Differential Diagnosis
HLA-B27 uveitis
Pars planitis
Behcet’s disease
Eales disease
Lyme disease
Tuberculosis
Treatment
Observation may be appropriate for mild cases
Doxycycline, azithromycin, or amoxicillin for mild disease
Intravenous (IV) penicillin, doxycycline, or third-generation cephalosporin (ceftriaxone, cefotaxime) for severe cases; systemic corticosteroid is controversial
Treatment should be promptly started within the first 4 days of illness
Doxycycline is preferred when differential diagnosis includes rickettsial infection, which can be clinically similar to leptospirosis
Because ocular compartments can harbor live leptospira long after acute systemic disease, we recommend systemic antibiotic treatment, along with judicious use of topical and periocular steroids, for uveitis
Jarisch–Herxheimer reaction can occur following therapy
Prevention
Vaccination of domestic/farm animals
Avoiding exposure to stagnant water, rodents, contaminated food
Prophylactic antibiotics for patients at high risk of exposure (e.g., during outbreaks or flooding in endemic areas): doxycycline—200 mg weekly
Referral/Comanagement
Infectious disease