Chapter 171

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.

###### Figure 171-1

Transmission electron micrograph of Leptospira interrogans serovar Icterohaemorrhagiae.

### Etiologic Agent

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.

###### Figure 171-2

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 ...

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