In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(03)00830-2.pdf

Leptospirosis: a zoonotic disease of global importance

Leptospirosis is a widespread and potentially fatal zoonosis that is endemic in many tropical regions and causes large epidemics after heavy rainfall and flooding. Infection results from direct or indirect exposure to infected reservoir host animals that carry the pathogen in their renal tubules and shed pathogenic leptospires in their urine. Although many wild and domestic animals can serve as reservoir hosts , the brown rat (Rattus norvegicus) is the most important source of human infections. Individuals living in urban slum environments characterized by inadequate sanitation and poor housing are at high risk of rat exposure and leptospirosis. The global burden of leptospirosis is expected to rise with demographic shifts that favor increases in the number of urban poor in tropical regions subject to worsening storms and urban flooding due to climate change. Data emerging from prospective surveillance studies suggest that most human leptospiral infections in endemic areas are mild or asymptomatic. Development of more severe outcomes likely depends on three factors: epidemiological conditions, host susceptibility, and pathogen virulence (Fig. 1). Mortality increases with age, particularly in patients older than 60 years of age. High levels of bacteremia are associated with poor clinical outcomes and, based on animal model and in vitro studies, are related in part to poor recognition of leptospiral LPS by human TLR4. Patients with severe leptospirosis experience a cytokine storm characterized by high levels of IL-6, TNF-alpha, and IL-10. Patients with the HLA DQ6 allele are at higher risk of disease, suggesting a role for lymphocyte stimulation by a leptospiral superantigen. Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever. Newer diagnostic methods facilitate early diagnosis and antibiotic treatment. Patients progressing to multisystem organ failure have widespread hematogenous dissemination of pathogens. Nonoliguric (high output) renal dysfunction should be supported with fluids and electrolytes. When oliguric renal failure occurs, prompt initiation of dialysis can be life saving. Elevated bilirubin levels are due to hepatocellular damage and disruption of intercellular junctions between hepatocytes, resulting in leaking of bilirubin out of bile caniliculi. Hemorrhagic complications are common and are associated with coagulation abnormalities. Severe pulmonary hemorrhage syndrome due to extensive alveolar hemorrhage has a fatality rate of >50 %. Readers are referred to earlier, excellent summaries related to this subject (Adler and de la Pena-Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et al. 2005).

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Leptospirosis in Humans

Detection of pathogenic Leptospira spp. through TaqMan polymerase chain reaction targeting the LipL32 gene

SUMMARY: Two sets of primers derived from genomic DNA libraries of Leptospira serovars icterohaemorrhagiae (strain RGA) and bim (strain 1051) enabled the amplification by PCR of target DNA fragments from leptospiral reference strains belonging to all presently described pathogenic Leptospira species. The icterohaemoirhagiae-derived primers (G1/G2) enabled amplification of DNA from L. interrogans, L. borgpetersenii, L. weilii, L. noguchii, L. santarosai and L. meyeri, whereas the bim-derived primers (B64-I/B64-II) enabled the amplification of L. kirschneri. Southern blot and DNA sequence analysis revealed inter-species DNA polymorphism within the region spanned by primers G1 and G2 between L. interrogans and various other Leptospira species. Using a mixture of primer sets G1/G2 and B64-I/B64-II, leptospires of serovars icterohaemorrhagiae, copenhageni, hardjo, pomona, grippotyphosa and bim were detected in serum samples collected from patients during the first 10 days after the onset of illness.

Detection of seven species of pathogenic leptospires by PCR using two sets of primers

Deoxyribonucleic acid hybridization (hydroxyapatite method, 55 and 70°C) was used to characterize 38 serovars from 22 named serogroups of Leptospira interrogans and Leptospira biflexa, 6 serovars from 4 new unnamed serogroups of Leptospira interrogans, and single serovars of the proposed species Leptospira parva and Leptonema illini. Deoxyribonucleic acid relatedness confirmed the validity of Leptospira parva and Leptonema illini. The well-accepted species Leptospira interrogans and Leptospira biflexa, as currently defined, were extremely heterogeneous. Relatedness results revealed at least five new species among the parasitic serovars formerly included in Leptospira interrogans and two new species among the saprophytic serovars formerly included in Leptospira biflexa. Serogrouping did not equate with species identification, as serovars from several different subserogroups belonged to different species. The new species named in this paper are Leptospira, noguchii, Leptospira weilii, Leptospira santarosai, Leptospira borgpetersenii, Leptospira meyeri, Leptospira wolbachii, and Leptospira inadai.

Deoxyribonucleic Acid Relatedness between Serogroups and Serovars in the Family Leptospiraceae with Proposals for Seven New Leptospira Species

Publisher Summary This chapter discusses the serological typing methods of Leptospires . They are the members of the Treponemataceae family. The genus includes strains which are parasitic or free living. Some strains may be pathogenic for man or various other animal species. When leptospira strains are classified, first the serogroup to which a strain belongs has to be determined by the microscopic agglutination test using selected rabbit group sera. The procedures used for the determination of the serotype status of a strain are derived from the definition of serotypes. Serotypes should be subdivided into varieties based on the presence of a thermolabile antigen. The relatively high specificity of host-serotype relationships means that accurate typing of isolated strains is one of the basic methods for epidemiological investigations. In studies dealing with pathogenic properties of strains-production of hemolysis, and lipases, knowledge of the serotype status is also essential.

H. Dikken

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Chapter VIII Serological Typing Methods of Leptospires