Leptospirosis is a globally important zoonotic disease caused by spirochetes of the genus Leptospira (Fig. 171-1). In 1885, Adolf Weil described the clinical hallmarks of this disease as an acute process characterized by splenomegaly, jaundice, and nephritis. With time, the designation Weil's disease came to signify severe leptospirosis characterized by diverse clinical findings, particularly fever, jaundice, acute renal injury, refractory shock, and hemorrhage (especially pulmonary hemorrhage). The global burden of leptospirosis is hard to quantify because of the difficulties encountered in its clinical diagnosis and the lack of efficient confirmatory laboratory testing, which limits public health reporting.
Transmission electron micrograph of Leptospira interrogans serovar Icterohaemorrhagiae.
The genus Leptospira (order Spirochetales, family Leptospiraceae) constitutes the most ancient lineage of spirochetes pathogenic for humans and the only spirochetes that can live both in animals and free in the environment. This genus includes 20 named species, 9 of which are classified as pathogenic, 5 as intermediately pathogenic, and 6 as nonpathogenic (saprophytic) based on molecular phylogenetic analysis (Fig. 171-2). Of the pathogenic and intermediate Leptospira species, more than 250 serovars—classified on the basis of agglutination testing with specific antisera—cause disease in humans and animals. New species and serovars continue to be discovered. Although all species, serovars, and strains are morphologically identical, leptospires are described by serovar for clinical and epidemiologic reasons.
Differentiation of pathogenic, intermediately pathogenic, and nonpathogenic (saprophytic) Leptospira species based on molecular phylogenetic analysis using the 16S rRNA gene. Scale bar indicates rate of nucleotide substitution per base pair.
The dimensions and motility of leptospires (~0.1 × 6–20 μm) allow them to pass through filters used to sterilize culture medium. Leptospires are tightly and regularly coiled, with characteristic hooked ends (hence the species name interrogans), and are highly motile, spinning around their longitudinal axis and darting back and forth. The organisms cannot be seen by direct light microscopy. To visualize the spirochetes directly in culture or in clinical specimens, dark-field or phase-contrast microscopy must be used. Small protein strands that appear motile by Brownian movement can easily be confused with leptospires. In tissues, leptospires can be visualized by silver impregnation (i.e., Warthin-Starry staining), immunohistochemistry, or immunofluorescence microscopy.
Leptospires are difficult to isolate in pure culture from clinical specimens such as blood, urine, and cerebrospinal fluid (CSF), although certain species and serovars (e.g., L. interrogans serovar Copenhageni) are grown more easily than others. The organisms have peculiar nutritional requirements, particularly their inability to ferment glucose and their apparently exclusive use of long-chain fatty acids to generate energy and metabolites for cell division and growth. Standard leptospiral culture medium [Ellinghausen–McCullough–Johnson–Harris (EMJH)] contains oleic acid polymers (Tween60 and Tween40) as fatty acid sources. These spirochetes do not grow in medium typically used in automated blood culture systems but can be recovered if specimens are subcultured within~1 week onto EMJH, Stuart, Fletcher's, or Korthoff's medium. EMJH, the standard for isolation of Leptospira from clinical specimens, is a liquid polysorbate-Tween medium to which 0.1% agar is added (sometimes supplemented with antibiotics to prevent growth of contaminants). The primary isolation of Leptospira requires the presence of a solid phase in the medium, which is provided by the agar particles. Cultures are maintained in the dark at 28–30°C and are examined at weekly intervals by dark-field microscopy for up to 3 months. After some weeks, florid growth sometimes produces a dense ring of organisms—Dinger's ring—just under the surface of the medium.
Leptospirosis is a zoonotic disease. Human-to-human transmission does not occur. Although more than 100 different mammals can be infected, the most important sources of transmission to humans are rats, dogs, cattle, and pigs. Rats do not become ill from leptospiral infection, but dogs often develop severe disease similar to that in humans; infection can cause reproductive failure in cattle and pigs. Even when vaccinated, asymptomatic dogs, cattle, and pigs can be leptospiruric and thus transmit infection to humans. Classic (but not exclusive) serovar-animal associations include Icterohaemorrhagiae and Copenhageni in domestic rats (Rattus norvegicus, R. rattus), Grippotyphosa in opossums and raccoons (emerging in the United States and Canada in the absence of a vaccine that covers this serovar), Canicola in dogs, Hardjo in cattle and buffalo, and Pomona in pigs.
Patterns of leptospirosis transmission are characterized as epidemic, endemic, and sporadic. Factors that facilitate human infection are those that bring susceptible persons into indirect contact with contaminated animal urine through surface waters, moist soil, or other wet environments or into direct contact with urine and other excreta (e.g., products of parturition, placenta) of infected animals. In recent years, fewer occupation-related cases and more cases related to environmental exposure have been seen. Seasonal rains and seasonal flooding are the most important factors in the occurrence of epidemic leptospirosis. Tropical humid environments, poor sanitation leading to rodent infestation, and uncontrolled dog populations are important for endemic transmission. Sporadic leptospirosis is associated with human contact with contaminated environments in various settings: on the job (veterinary, sewer, and slaughterhouse workers), in poorly hygienic inner-city alleys and slums, during adventure travel and other non-work-related outdoor activities, and during military training exercises in endemic regions.
Reliable data on the incidence of leptospirosis and on rates of associated morbidity and mortality remain scant and are generally drawn from biased hospital-based series or from governmental registries including passively reported serologic results. In the United States, leptospirosis was removed from the list of notifiable diseases in the 1990s. The ~50–100 cases passively reported annually to the Centers for Disease Control and Prevention (CDC) clearly represent an underestimate; the majority of these cases are from Hawaii, and others are sporadically acquired in inner-city settings or ...