Albert Weil described the multisystem disease in 1886.

It was called infectious jaundice and often confused with diseases like yellow fever.

 

First isolated from an autopsy specimen – the patient was suspected of having yellow fever.

Many scientists, like stokes and Noguchi, died trying to isolate the organism.

The name is derived from Greek leptos (thin) and Latin spira (coiled).

Leptospira is motile using two axial flagella underlying the membrane sheath.

Classification:

Leptospira was previously classified into pathogenic and non-pathogenic species.

The Leptospira interrogans, the pathogenic species had many serovers.

The current classification is done based on genetic relatedness.

In tropical countries the disease is most common in rainy season.

Host and carriers:

Most important carrier of this infection is rodents and other small animals. Leptospira causes chronic renal infection in these animals, causing prolonged shedding of the bacteria in the urine, often lifelong.
Other domestic and wild animals could get infected from these carriers.

Humans are the dead-end host. Human to human transmission has not been reported.
Humans can get infected from contact with contaminated water or animal products/urine.

Portal of entry:

Leptospira can enter humans through the mucous membrane (mouth, gut), conjunctiva, cuts and abrasions and aerosol.

After entering the blood, it causes systemic vasculitis, which facilitates the entry of the bacteria into various tissues. The incubation period is approx ten days (range 2-26 days)

Virulence & pathogenicity:

Leptospira pathogenicity is poorly understood, but some mechanisms are as follows.
1. Ability to evade TLR4 (innate immune system).
2. Toxin mediated damage of tissues
3. Ability to produce superantigen in some individuals (HLA- DQ6 positive)
4. Immune-mediated damage.

Sign and symptoms:

Most Leptospira infections are subclinical and self-limiting.
The mean incubation period is approx ten days.

The disease often follows two phases (although it may not occur in all patients). A septicaemic phase, in which the bacteria could be found in the blood, usually manifests with

  • Fever and flu-like illness
  • Myalgia (calf, lumber)
  • Conjunctival suffusion
  • Upper respiratory tract symptoms
  • Gastrointestinal symptoms
  • Pretibial maculopapular rash
  • Lymphadenopathy, and
  • Hepatosplenomegaly.

    This phase is followed by a remission of fever before the immune phase starts.

In the immune phase Leptospira disappears from the blood and IgM appears.
This phase shows signs and symptoms of organ involvement –

  • Renal impairment/failure,
  • Hepatic impairment/failure,
  • Cardiac arrhythmia,
  • Pancreatitis,
  • Pulmonary manifestation (could be haemorrhagic),
  • Meningitis (aseptic),
  • Eye involvement (photophobia, pain, uveitis),
  • Lymphadenopathy and
  • Hepatosplenomegaly.
Aseptic meningitis
  • In immune phase (80% cases).
  • Headache (frontal, bi-temporal), photophobia.
  • Lymphocytic pleocytosis, Protein – mild elevation, glucose – normal.
Weil’s disease: 
  • The severe form of Leptospira infection may start immediately after the acute phase in some cases.
  • High fever and rapid onset of organ failure.
  •  Liver failure- conjugated bilirubinaemia, ALT usually <200 IU/L.
  • Renal impairment – nonolguric hypokalaemia, impaired sodum reabsorption.
  • Thrombocytopenia; no DIC.
  • Severe pulmonary haemorrhage syndrome.
Mortality rate: 
  • Up to 50% in hospitalised patients. 
  • The adverse outcome is associated with – older age, CNS involvement, jaundice and renal failure.

 

Laboratory diagnosis:

Leptospira can be isolated from blood, CSF, Peritoneal fluid etc for up to 10 days (longer from urine). However, culture and microscopy has low sensitivity. Dark ground microscopy was used to look for Leptospira.
Culture media- EMJH media
Stain – Immunofluorescence stain (see image, from CDC, PHIL), silver stain etc.
Identification can also be done using – 16S ribosomal RNA PCR, PFGE etc.

The methods used are –
PCR (during early phases).
Serology
   ELISA – confirmed by MAT
   Microscopic agglutination test (MAT) – gold standard (see image).
    Latex agglutination etc.
Typing – MLST

In the UK, sample should be sent to Porton Down for PCR/IgM. Positive samples are sent to Colindale from RIPL for MAT and typing.

Antibiotic

Mild cases:

  • Doxycycline
  • Amoxicillin
  • Azithromycin

Severe cases:

  • Doxycycline
  • Ceftriaxone
  • Penicillin

Other supportive measures

  • Ventilation
  • renal suppport
  • Fluids
  • Correcting electrolyte imbalance etc

Prophylaxis

  • Avoid high risk exposure
    Rodent control
  • Animal immunisation
  • Human immunisation (less common)
  • Weekly doxycycline (200 mg) Prophylaxis
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