Leptospira: Difference between revisions

From IDWiki
Leptospira
m (Aidan moved page Leptospirosis to Leptospira species)
(rearranged sections)
Line 1: Line 1:
== Microbiology ==
+
== Background ==
  +
=== Microbiology ===
 
 
* Thin, flagellated spirochetes
 
* Thin, flagellated spirochetes
 
* Best viewed with darkfield microscopy
 
* Best viewed with darkfield microscopy
Line 10: Line 10:
 
** A single species may have pathogenic and non-pathogenic serovars
 
** A single species may have pathogenic and non-pathogenic serovars
   
 
=== Epidemiology ===
== Differential Diagnosis ==
 
 
* Other infections, including influenza, hepatitis, dengue, Hantavirus infections or other viral haemorrhagic fevers, yellow fever, malaria, brucellosis, borreliosis, typhoid fever or other enteric diseases, and pneumonia.
 
** Think about measles, too, in febrile patients with conjunctivitis (can occur atypically without rash)
 
 
== Epidemiology ==
 
 
 
* Endemic worldwide
 
* Endemic worldwide
 
** More common during rainy seasons in tropical regions and late summer to fall in temperate regions
 
** More common during rainy seasons in tropical regions and late summer to fall in temperate regions
Line 27: Line 21:
 
* Leptospires can survive in water or soil for months, depending on the conditions
 
* Leptospires can survive in water or soil for months, depending on the conditions
   
== Pathophysiology ==
+
=== Pathophysiology ===
 
 
* Bacteria enter through cuts and abrasions, mucous membranes, conjunctivae, and inhalation
 
* Bacteria enter through cuts and abrasions, mucous membranes, conjunctivae, and inhalation
 
* After entering, it disseminates hematogenously
 
* After entering, it disseminates hematogenously
Line 37: Line 30:
 
** Also hooked ends
 
** Also hooked ends
   
== Presentation ==
+
== Clinical Presentation ==
 
 
* Spectrum of severity, from asymptomatic seroconversion (most common) to nonspecific febrile illnes to severe, lifethreating multiorgan failure
 
* Spectrum of severity, from asymptomatic seroconversion (most common) to nonspecific febrile illnes to severe, lifethreating multiorgan failure
 
* Incubaton period 10 days (range 5 to 14)
 
* Incubaton period 10 days (range 5 to 14)
Line 68: Line 60:
   
 
== Diagnosis ==
 
== Diagnosis ==
 
 
=== Microscopy ===
 
=== Microscopy ===
 
 
* Leptospires can be seen directly under darkfield 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)
 
* Low sensitivity and specificity of blood and urine samples, even if spirochetes are seen (as spirochetes can also be normal flora)
   
 
=== Culture ===
 
=== Culture ===
 
 
* Can get positive cultures from blood and CSF, ideally when collected while febrile and before antibiotics
 
* Can get positive cultures from blood and CSF, ideally when collected while febrile and before antibiotics
 
* Can innoculate one to blood drops directly into culture at bedside
 
* Can innoculate one to blood drops directly into culture at bedside
Line 83: Line 72:
   
 
=== PCR ===
 
=== PCR ===
 
 
* Loop-mediated isothermal amplification (LAMP) assays and other PCR assays exist
 
* 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
 
* Unclear sensitivity and specificity, but has the potential to diagnose disease before antibodies develop
Line 89: Line 77:
   
 
=== Serology ===
 
=== Serology ===
 
 
* Detects IgM antibodies, which appear around day 5
 
* Detects IgM antibodies, which appear around day 5
 
* Microscopic agglutination test (MAT) for antigen detection (Sn 90%, Sp 90%)
 
* Microscopic agglutination test (MAT) for antigen detection (Sn 90%, Sp 90%)
Line 100: Line 87:
 
* Lateral flow test, needs confirmation by MAT (Sn 80%, Sp 95%)
 
* Lateral flow test, needs confirmation by MAT (Sn 80%, Sp 95%)
   
== Management ==
+
== Differential Diagnosis ==
 
* Other infections, including influenza, hepatitis, dengue, Hantavirus infections or other viral haemorrhagic fevers, yellow fever, malaria, brucellosis, borreliosis, typhoid fever or other enteric diseases, and pneumonia.
 
** Think about measles, too, in febrile patients with conjunctivitis (can occur atypically without rash)
   
  +
== Management ==
 
* Treat early in disease course
 
* Treat early in disease course
 
* Usual treatment is penicillin 1.5 MU IV q6h, if severe, or doxycycline 100 mg po bid, if mild
 
* Usual treatment is penicillin 1.5 MU IV q6h, if severe, or doxycycline 100 mg po bid, if mild
Line 112: Line 102:
   
 
== Prevention ==
 
== Prevention ==
 
 
* Mostly avoidance of high-risk exposures
 
* Mostly avoidance of high-risk exposures
 
* Immunization is possible but rarely done, and covers only specific serovars
 
* Immunization is possible but rarely done, and covers only specific serovars
 
* Can do chemoprophylaxis of high risk occupations with doxycycline 200 mg po once weekly
 
* Can do chemoprophylaxis of high risk occupations with doxycycline 200 mg po once weekly
 
   
 
{{DISPLAYTITLE:''Leptospira'' species}}
 
{{DISPLAYTITLE:''Leptospira'' species}}

Revision as of 21:47, 29 November 2019

Background

Microbiology

  • Thin, flagellated spirochetes
  • 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 illnes to severe, lifethreating multiorgan failure
  • Incubaton 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
    • Can also have lymphadenopathy, splenomegaly, and hepatomegaly
    • Spirochetes in blood and CSF, possibly urine
  • Immune phase
    • Lasts 4 to 30 days
    • IgM antibodies appear
    • Spirochete is cleared from blood and CSF but detectable in other organs, including urine
    • May develop jaundice, renal failure, arrhythmias, pulmonary symptoms, aseptic meningitis, conjunctival injection, photophobia, eye pain, muscle tenderness, adenopathy, and hepaosplenomegaly
  • Weil disease may develop during or directly following the acute phase
    • Liver injury
    • Renal failure
      • Nonoliguric hypokalemia with impaired sodium reabsorption and increased distal sodium deliery
      • 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
    • High mortality from 5 to 40%

Diagnosis

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 innoculate 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

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

Serology

  • Detects IgM antibodies, which appear around day 5
  • 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, legionellosis, and autoimmune diseases
    • Cross-reacts between different serogroups
  • IgM ELISA, needs confirmation by MAT (Sn 90%, Sp 90%)
  • Latex agglutination test, needs confirmation by MAT (Sn 80%, Sp 95%)
  • Lateral flow test, needs confirmation by MAT (Sn 80%, Sp 95%)

Differential Diagnosis

  • Other infections, including influenza, hepatitis, dengue, Hantavirus infections or other viral haemorrhagic fevers, yellow fever, malaria, brucellosis, borreliosis, typhoid fever or other enteric diseases, and pneumonia.
    • Think about measles, too, in febrile patients with conjunctivitis (can occur atypically without rash)

Management

  • Treat early in disease course
  • Usual treatment is penicillin 1.5 MU IV q6h, if severe, or doxycycline 100 mg po bid, if mild
    • May be able to use amoxicillin, ampicillin, or ceftriaxone as alternatives
    • May develop a Jarisch-Herxheimer reaction during treatment (only with beta-lactams)
    • Duration about 7 days
  • 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
  • Can do chemoprophylaxis of high risk occupations with doxycycline 200 mg po once weekly