Leptospira spp.

This is from a presentation. The pictures were my slides. Feel free to download them if you wish.

Leptospirosis, a zoonosis, is caused by a pathogenic Spirochaeta of the genus Leptospira.
The name is derived from the Greek leptos (thin) and the Latin spira (coiled).

Leptospirosis is a multisystem disease first described by Albert Weil in 1986 (in Heidelberg). It was called infectious jaundice and was often confused with yellow fever.

Leptospira was 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 Bacteria

1. Leptospira spp, is a Spirochaeta, has two methods of classification.

Older serological method:
Leptospira was divided into two species – L interrogans (pathogenic) and L biflexa (non-pathogenic). There were many serovars of L interogans based on somatic O antigen. Related serovars were grouped into serogroups.

Genetic classification: Classification is based on the genetic similarity supported by the 16S RNA sequence. The species are classified as pathogenic, non-pathogenic and pathogenicity uncertain.

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

https://www.youtube.com/embed/BMo7cOvJxYc?feature=oembedThe mechanism of two-phase motility in the spirochete Leptospira: Swimming and crawling

3. Leptospira has a worldwide distribution.

4. Host and carriers:

The 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 by these carriers.
Human-to-human transmission has not been reported.

It is transmitted to humans by direct or indirect contact with animal urine. Professions like abattoirs, and vets, may acquire the infection through direct contact. Indirect contact may occur with farmers (contaminated soil/ water), sewage workers, and firefighters (during a flood). Leptospirosis has also been reported after recreational activities.

Portal of entry and Incubation period

Leptospira can enter humans through the mucous membrane (mouth, gut), conjunctiva, cuts, 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 10 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

Leptospirosis – Signs and symptoms:

Most Leptospira infections are subclinical and self-limiting.

The disease often follows two phases (although it may not occur in all patients). In a septicaemic phase, the bacteria could be found in the blood and then an immune phase. In the immune phase, Leptospira disappears from the blood, and IgM appears. This phase shows signs and symptoms of organ involvement.

Aseptic meningitis

• In the immune phase (80% cases).
• Headache (frontal, bi-temporal), photophobia.
• Lymphocytic pleocytosis, Protein – mild elevation, glucose – normal.

Weil’s disease: 

• In some cases, the severe form of Leptospira infection may start immediately after the acute phase.
• High fever and rapid onset of organ failure.
•  Liver failure- conjugated bilirubinaemia, ALT usually <200 IU/L.
• Renal impairment – non-oliguric hypokalaemia, impaired sodium reabsorption.
• Thrombocytopenia; no DIC.
• Severe pulmonary haemorrhage syndrome.

Mortality rate: 

• Up to 50% of 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 have 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 made using – 16S ribosomal RNA PCR, PFGE etc.

The methods used in National Leptospirosis service are –

PCR – in the acute stage of infection (within 5 days of symptoms onset).
Serological assays (ELISA or MAT) later in the illness.  
Microscopic agglutination test (MAT) – gold standard (see image) and the confirmatory test. Agglutinating antibodies are usually present 5 days after the onset of the disease. It is necessary to examine at least 2 serum specimens taken at least 7 days apart.
Typing – MLST

Treatment