Leptospira: Difference between revisions
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Leptospira
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== Background == |
== Background == |
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=== Microbiology === |
=== Microbiology === |
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− | * Thin, flagellated [[ |
+ | * Thin, flagellated [[Cellular shape::spirochete]] |
* Best viewed with darkfield microscopy |
* Best viewed with darkfield microscopy |
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* Species and serovars are divided into three broad categories within the genus ''Leptospira'' |
* Species and serovars are divided into three broad categories within the genus ''Leptospira'' |
Revision as of 16:17, 5 July 2020
Background
Microbiology
- Thin, flagellated spirochete
- Best viewed with darkfield microscopy
- Species and serovars are divided into three broad categories within the genus Leptospira
- Pathogens: L. interrogans (multiple serovars, most common), L. noguchii, L. borgpetersenii, L. santarosai, L. kirschneri, L. weilii, L. alexanderi, L. alstonii, L. meyeri, L. wolffi, and L. kmetyi
- Non-pathogenic saprophytes: L. biflexa, L. wolbachii, L. vanthielii, L. terpstrae, L. yanagawae, and L. idonii
- Species of indeterminate pathogenicity: L. inadai, L. fainei, L. broomii, and L. licerasiae
- Within each species, there may be multiple serovars that are defined based on lipopolysaccharide (LPS) O-antigens
- A single species may have pathogenic and non-pathogenic serovars
Epidemiology
- Endemic worldwide
- More common during rainy seasons in tropical regions and late summer to fall in temperate regions
- In US, more common in Hawaii
- Major reservoir is as a chronic kidney infection in animals, especially rodents
- Among livestock, may cause spontaneous abortions
- Most common risk factor is exposure to water or soil contaminated with rodent urine
- Includes occupational exposures and direct contact
- High-risk occupations include farmers, slaughterhouse workers, pet traders, veterinarians, rodent catchers and sewer workers
- Leptospires can survive in water or soil for months, depending on the conditions
Pathophysiology
- Bacteria enter through cuts and abrasions, mucous membranes, conjunctivae, and inhalation
- After entering, it disseminates hematogenously
- Human TLR4 cannot bind leptospiral LPS
- Virulence factors
- Sphingomyelinase and hemolysin
- Also spirochete motility
- Also hooked ends
Clinical Presentation
- Spectrum of severity, from asymptomatic seroconversion (most common) to nonspecific febrile illness to severe, life-threating multiorgan failure
- Asymptomatic disease is likely frequent, given high seroprevalence in some populations
- Incubation period 10 days (range 5 to 14)
- Acute febrile phase
- Acute phase lasts 5 to 7 days
- Starts with high fevers, headaches, chills, rigors, and myalgias
- Conjunctival injection is an identifying feature
- Muscle tenderness, especially in the calf and lumbar areas, is also characteristic
- Occasionally have a pretibial papular eruption
- Can also have lymphadenopathy, splenomegaly, and hepatomegaly
- Mild leukocytosis and neutrophilia, with thrombocytopenia and occasionally anemia
- Spirochetes detectable in blood and CSF, possibly urine
- Immune phase
- Lasts 4 to 30 days
- Corresponds with the appearance of IgM antibodies
- Spirochete is cleared from blood and CSF but detectable in other organs, including urine
- May develop jaundice, renal failure, arrhythmias, pulmonary symptoms, aseptic meningitis, non-purulent conjunctival injection, photophobia, eye pain, muscle tenderness, adenopathy, and hepaosplenomegaly
- Weil disease (liver and renal failure) may develop during or directly following the acute phase
- Liver injury is predominantly jaundice with only mild liver enzyme rise
- Renal failure
- Nonoliguric hypokalemia with impaired sodium reabsorption and increased distal sodium delivery
- Selective loss of ENaC channels in proximal ubule
- Biopsy shows AIN
- Severe pulmonary hemorrhage syndrome (SPHS)
- May have frank hemoptysis, but not always
- Can show up as CXR lower lobe "snowflake-like" densities
- Arrhythmias, including atrial fibrillation and ventricular tachycardia
- Circulatory shock
- Rarely, congestive heart failure from myocarditis
- Severe disease has high mortality from 5 to 40%
Diagnosis
- In general, use PCR if early in disease (<7 days) and ELISA IgM followed by confirmatory MAT if further in disease (≥7 days)
Method | Sens | Spec |
---|---|---|
Culture | 5-50% | 100% |
Darkfield microscopy | 40% | 60% |
Microscopic agglutination test (MAT) | 90% | >90% |
ELISA IgM | >90% | 88-95% |
Latex agglutination | 92% | 95% |
Lateral flow assay | 81% | 96% |
PCR | 100% | 93% |
Microscopy
- Leptospires can be seen directly under darkfield microscopy
- Low sensitivity and specificity of blood and urine samples, even if spirochetes are seen (as spirochetes can also be normal flora)
Culture
- Can get positive cultures from blood and CSF, ideally when collected while febrile and before antibiotics
- Can inoculate one to blood drops directly into culture at bedside
- Urine can be cultured after the first week of illness, but need to be processed quickly
- Use Fletcher's medium (commercial version)
- Not very sensitive, and cultures can take weeks
Serology
- Detects IgM antibodies, which appear around day 5 to 7
- Microscopic agglutination test (MAT) for antigen detection (Sn 90%, Sp 90%)
- Leptospira antigens are mixed with serum and monitored for agglutination
- Monitor for a four-fold rise in titres from acute-phase to convalescent phase (repeat 4 to 6 weeks), or a single titre of at least 1:800
- May cross-react with syphilis, relapsing fever, Lyme disease, viral hepatitis, HIV, Legionella, and autoimmune diseases
- Cross-reacts between different serogroups
- IgM ELISA, needs confirmation by MAT (Sn 90%, Sp 90%) (this is the test in Canada)
- Latex agglutination test, needs confirmation by MAT (Sn 80%, Sp 95%)
- Lateral flow test, needs confirmation by MAT (Sn 80%, Sp 95%)
PCR
- Loop-mediated isothermal amplification (LAMP) assays and other PCR assays exist
- Unclear sensitivity and specificity, but has the potential to diagnose disease before antibodies develop
- Usually done from blood, but can try in urine as well
Differential Diagnosis
- Early in disease, it is essentially a non-specific febrile syndrome
- Viral
- Influenza
- Acute HIV
- Infectious mononucleosis (EBV/CMV)
- Flaviviruses: dengue virus, yellow fever virus, West Nile virus
- Alphaviruses: Chikungunya virus
- Bunyaviruses: Hantavirus, Lassa fever virus
- Other viral hemorrhagic fever virus
- Viral hepatitis
- Measles virus, with cough and conjunctivitis
- Bacterial
- Parasitic
Management
- Treat early in disease course, usually before diagnosis
- Usual treatment is penicillin G 1.5 MU IV q6h, if severe, or doxycycline 100 mg po bid, if mild
- May be able to use amoxicillin, ampicillin, ceftriaxone, or azithromycin as alternatives
- May develop a Jarisch-Herxheimer reaction during treatment (only with beta-lactams)
- Duration is 5 to 7 days (except 3 days for azithromycin
- Close monitor and intensive supportive therapy required for severe patient
- May need hemodialysis, but usually recovers renal function
- SPHS is managed as ARDS with lung-protective ventilation
Prevention
- Mostly avoidance of high-risk exposures
- Immunization is possible but rarely done, and covers only specific serovars
- Even if immunizing animals, it prevents disease but not asymptomatic carriage
- Can do chemoprophylaxis of high risk occupations with doxycycline 200 mg PO once weekly