CHAPTER 80: LEPTOSPIROSIS

Rudy A. Hartskeerl; Jiři F. P. Wagenaar

INTRODUCTION

Leptospirosis is a globally important zoonotic disease whose apparent reemergence is illustrated by recent outbreaks on virtually all continents. The disease is caused by pathogenic Leptospira species and is characterized by a broad spectrum of clinical manifestations, varying from asymptomatic infection to fulminant, fatal disease. In its mild form, leptospirosis may present as nonspecific symptoms such as fever, headache, and myalgia. Severe leptospirosis, characterized by jaundice, renal dysfunction, and hemorrhagic diathesis, is often referred to as Weil’s syndrome. With or without jaundice, severe pulmonary hemorrhage is increasingly recognized as an important presentation of severe disease.

ETIOLOGIC AGENT

Leptospira species are spirochetes belonging to the order Spirochaetales and the family Leptospiraceae. Traditionally, the genus Leptospira comprised two species: the pathogenic L. interrogans and the free-living L. biflexa, now designated L. interrogans sensu lato and L. biflexa sensu lato, respectively. Twenty-two Leptospira species with pathogenic (10 species), intermediate (5 species), and nonpathogenic (7 species) status have now been described on the basis of phylogenetic and virulence analyses (Fig. 80-1). Genome sequences of five Leptospira species (L. biflexa, L. interrogans, L. santarosai, L. borgpetersenii, and L. licerasiae) have been published, and the availability of genome sequences of a wide variety of Leptospira strains will undoubtedly lead to a better understanding of the pathogenesis of leptospirosis. However, classification based on serologic differences better serves clinical, diagnostic, and epidemiologic purposes. Pathogenic Leptospira species are divided into serovars according to their antigenic composition. More than 250 serovars make up the 26 serogroups.

FIGURE 80-1

Differentiation of pathogenic, intermediate, and nonpathogenic (saprophytic) Leptospira species by molecular phylogenetic analysis using the rrs gene and including the potentially new pathogenic species Leptospira borgpetersenii group B and the saprophytic species Leptospira idonii. Scale bar indicates the rate of nucleotide substitutions per base pair. (Figure prepared and provided by Dr. A. Ahmed, KIT Biomedical Research, Amsterdam, The Netherlands.)

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Leptospires are coiled, thin, highly motile organisms that have hooked ends and two periplasmic flagella, with polar extrusions from the cytoplasmic membrane that are responsible for motility (Fig. 80-2). These organisms are 6–20 μm long and ~0.1 μm wide; they stain poorly but can be seen microscopically by dark-field examination and after silver impregnation staining of tissues. Leptospires require special media and conditions for growth; it may take weeks to months for cultures to become positive.

FIGURE 80-2

Transmission electron microscopic image of Leptospira interrogans invading equine conjunctival tissue. (Image kindly provided by Dr. JE Nally, National Animal Disease Center, U.S. Department of Agriculture, Ames, IA. This image appears on the homepage of the European Leptospirosis Society website [http://eurolepto.ucd.ie/].)