Leptospira spp.
Leptospirosis, a zoonosis, is caused by a pathogenic Spirochaeta of genus Leptospira. The name is derived from Greek leptos (thin) and Latin spira (coiled).
Leptospirosis is a multisystem disease, first described by Albert Weil in 1986 (in Heidelberg). It was called infectious jaundice and 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
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 groups into serogroups.
Genetic classification:
Classification is now based on the genetic similarity supported by the 16S RNA sequence. The species are classified as pathogenic, non-pathogenic and pathogenicity uncertain.
Leptospira is motile using two axial flagella underlying the membrane sheath
Cross-section of leptospira showing sheath and the axial flagella
The mechanism of two-phase motility in the spirochete Leptospira: Swimming and crawling
Leptospira has a worldwide distribution
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 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, vets, may acquire the infection by direct contact.
Indirect contact may occur in
farmers (contaminated soil/ water), sewage workers,
firefighters (during a flood).
Leptospirosis has also been reported after recreational water activities.
Portal of entry and Incubation period
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 approximately 10 days (range 2-26 days).
Virulence & pathogenicity
Leptospira pathogenicity is poorly understood, but some mechanisms are as follows.
Ability to evade Toll-like receptor - TLR4 (innate immune system).
Toxin mediated damage to tissues.
Ability to produce superantigen in some individuals (HLA- DQ6 positive).
Immune-mediated damage.
Leptospirosis – Signs and symptoms
Most (up to 90%) Leptospira infections are subclinical and self-limiting.
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 and followed by 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
Common in the 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 – non-oliguric hypokalaemia, impaired sodium 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 have low sensitivity. Dark ground microscopy was used for Leptospira (see image).
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
Dark ground microscopy
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 from 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
MAT
Treatment
