Leptospirosis in Humans

Abstract

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 Peña-Moctezuma 2010; Bharti et al. 2003; Hartskeerl et al. 2011; Ko et al. 2009; Levett 2001; McBride et al. 2005).

A Review of Laboratory Diagnosis and Treatment of Leptospirosis

“…A limitation of PCR-based diagnosis of leptospirosis is the current inability of PCR assays to identify the infecting serovar, while this is not significant for individual patient management [34]. Real-time PCR, either using SYBR Green or Taqman technology has the advantage that it gives a result much faster than conventional PCR and is less prone to contamination [14].…”

“…Interpretation of the MAT is complicated by the high degree of crossreaction that occurs between different serogroups especially in acute-phase samples [34]. As well as the repeated weekly subculture of large numbers of strains presents hazards for laboratory workers and laboratory-acquired infections have been reported.…”

“…Usually, the saprophytic strain L. biflexa which shares several surface antigens with pathogenic strains and pathogenic species have also been used [34,44]. The specificity and the sensitivity of these Elisa are quite variable.…”

“…Specificity of Elisa is affected by the antigen used in the assay, by the presence of antibodies due to previous exposure (in endemic regions) and by the presence of other diseases [34]. A positive Elisa gives no indication on the infecting serovar/serogroup and is not sufficient to diagnose a case of leptospirosis, it must be confirmed by MAT, PCR or culture [15].…”

Seroprevalence of hantaviruses andLeptospirain muskrat and coypu trappers in the Netherlands, 2016

“…Ocular problems, renal and liver impairment, and haemorrhage can be seen in severe cases. Leptospirosis also manifests mostly subclinically or as a mild, self-limited illness [6,7]. Most common symptoms are fever, (severe) headache, muscle pain, cough, and gastrointestinal symptoms.…”