Leptospirosis: Practice Essentials, Background, Pathophysiology http://emedicine.medscape.

com/article/220563-overview#a4

Leptospirosis
Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD more...
Pathophysiology
Updated: Apr 14, 2015
Leptospires are thin, coiled, gram-negative, aerobic organisms 6-20 m in length (see the image below). They are
motile, with hooked ends and paired axial flagella (one on each end), enabling them to burrow into tissue. Motion is
marked by continual spinning on the long axis. They are unique among the spirochetes in that they can be isolated
on artificial media.

A scanning electron micrograph depicting Leptospira atop a 0.1-m polycarbonate filter. (This image is in the public domain and
thus free of any copyright restrictions. Courtesy of the Centers for Disease Control/Rob Weyant)

Leptospires belong to the order Spirochaetales and the family Leptospiraceae. Traditionally, the organisms are
classified based on antigenic differences in the lipopolysaccharide envelopes that surround the cell wall. Serologic
detection of these differences, therefore, is based on identifying serovars within each species. Based on this system,
the genus Leptospira contains two species: the pathogenic Leptospira interrogans, with at least 218 serovars; and
the nonpathogenic, free-living, saprophytic Leptospira biflexa, which has at least 60 serovars.

Current studies that classify the organisms based on DNA relatedness identify at least 7 pathogenic species of
leptospires. However, organisms that are identical serologically may be different genetically, and organisms with the
same genetic makeup may differ serologically. Therefore, some authors feel that the traditional serologic system is
the most useful from a diagnostic and epidemiologic standpoint.

Animal reservoirs

Most leptospiral serovars have their primary reservoir in wild mammals, which continually reinfect domestic
populations. The organism affects at least 160 mammalian species and has been recovered from rats, swine, dogs,
cats, raccoons, cattle, mongooses, and bandicoots.[14, 15] The most important reservoirs are rodents, and rats are
the most common source worldwide. In the United States, important leptospiral sources include dogs, livestock,
rodents, wild animals, and cats.

Many serovars are associated with particular animals. For example, L pomona and L interrogans are seen in cattle
and pigs; L grippotyphosa is seen in cattle, sheep, goats, and voles; L ballum and L icterohaemorrhagiae are
associated with rats and mice; and L canicola is associated with dogs. Other important serotypes include
Lautumnalis, Lhebdomidis, and Laustralis. Leptospiral species' and serogroups' host animals vary from region to
region. Individual animals may carry several serovars.

Leptospirosis in animals is often subclinical. Leptospires may persist for long periods in the renal tubules of animals
by establishing a symbiotic relationship with no evidence of disease or pathological changes in the kidney. As a
result, animals that serve as reservoirs of host-adapted serovars can shed high concentrations of the organism in
their urine without showing clinical evidence of disease.

This leptospiruria in animals often occurs for months after the initial infection. Leptospiruria also has been found to
occur in healthy immunized dogs. Leptospiruria in humans is more transient, rarely lasting more than 60 days.
Humans and nonadapted animals are incidental hosts. With rare exceptions, man represents a dead end in the
chain of infection because person-to-person spread of the disease is rare.

Transmission and incubation

Urinary shedding of organisms from infected animals is the most important source of these bacterial pathogens.
Contact with the organism via infected urine or urine-contaminated media results in human infection. Such media
include contaminated water and food, as well as animal bedding, soil, mud, and aborted tissue. Under favorable
conditions, leptospires can survive in fresh water for as many as 16 days and in soil for as many as 24 days. [16]

Leptospires are believed to enter the host through the following:

Abrasions in healthy skin

Animal and rodent bites
Sodden and waterlogged skin
Mucous membranes or conjunctiva
Lungs (after inhalation of aerosolized body fluid) [17]
The placenta during pregnancy

Virulent organisms in a susceptible host gain rapid access to the bloodstream through the lymphatics, resulting in
leptospiremia and spread to all organs, but particularly the liver and kidney. The incubation period is usually 5-14

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days but has been described from 72 hours to a month or more.

Leptospirosis
Pathologic effects

Although directSandra
Author: invasion
G of tissueMD,
Gompf, mayFACP,
causeFIDSA;
some pathologic effects,
Chief Editor: researchers
Michael note that
Stuart Bronze, MDthe marked degree of
more...
multiorgan tissue injury appears inconsistent with the number of leptospires found on microscopic examination of
tissue. Other
Updated: mediators
Apr 14, 2015 induced by the leptospire are the suspected causes of the disease's various manifestations.
Research has suggested endotoxin, hemolysin, and lipase as possible sources of pathogenicity. However, the true
mechanism of host tissue injury remains unclear and likely involves a complex set of interactions.

The most consistent pathologic finding in leptospirosis is vasculitis of capillaries, manifested by endothelial edema,
necrosis, and lymphocytic infiltration. Capillary vasculitis is found in every affected organ system. The resulting loss
of red blood cells and fluid through enlarged junctions and fenestrae, which cause secondary tissue injury, probably
accounts for many of the clinical findings.

In the kidneys, leptospires migrate to the interstitium, renal tubules, and tubular lumen, causing interstitial nephritis
and tubular necrosis. Capillary vasculitis is readily identified. Although the glomeruli are spared, the progression from
normal renal function to decreased glomerular filtration rate to renal failure requiring dialysis can be rapid. Renal
failure is usually due to tubular damage, but hypovolemia from dehydration and from altered capillary permeability
can also contribute to renal failure.

Liver involvement is marked by centrilobular necrosis and Kupffer cell proliferation. Jaundice may occur as a result of
hepatocellular dysfunction.

Pulmonary involvement is secondary to alveolar and interstitial vascular damage resulting in hemorrhage. This
complication is considered to be the major cause of leptospirosis-associated death.

Cardiac lesions have been identified in postmortem examinations. In an autopsy series of fatal cases of leptospirosis
in Mumbai, India in 2005, involvement of the cardiovascular system was found in 41 of 44 cases. Interstitial
myocarditis was the predominant feature on histopathological examination. These authors suggested that
leptospirosis be viewed as an infective systemic vasculitis.[18]

Hemorrhage, focal necrosis, and inflammatory infiltration have been documented within the adrenal gland. Although
these complications do not appear clinically, some researchers speculate that adrenal insufficiency may mediate, in
part, the final vascular collapse associated with fatal leptospirosis.

The skin is affected by epithelial vascular insult. Skeletal muscle involvement is secondary to edema, myofibril
vacuolization, and vessel damage. Muscular microcirculation is impaired and capillary permeability is increased, with
resultant fluid leakage and circulatory hypovolemia.

The damage to the vascular system as a whole can result in capillary leakage, hypovolemia, and shock. Patients
with leptospirosis may develop disseminated intravascular coagulation (DIC), hemolytic uremic syndrome (HUS), or
thrombotic thrombocytopenic purpura (TTP). Thrombocytopenia indicates severe disease and should raise suspicion
for a risk of bleeding.[19, 20]

If the host survives the acute infection, septicemia and multiplication of the organism persist until the development of
opsonizing immunoglobulin in the plasma, followed by rapid immune clearance. Although the systemic immune
response may eliminate the organism from the body, it may also lead to a symptomatic inflammatory reaction that
can produce secondary end-organ injury.

Despite clearance from the blood, leptospires may remain in immunologically privileged sites, including the renal
tubules, brain, and aqueous humor of the eye, for weeks to months. Persistent leptospires in the eye occasionally
lead to chronic or recurrent uveitis. In humans, leptospires in the renal tubules and resulting leptospiruria rarely
persist longer than 60 days.

Contributor Information and Disclosures

Author
Sandra G Gompf, MD, FACP, FIDSA Associate Professor of Infectious Diseases and International Medicine,
University of South Florida College of Medicine; Chief, Infectious Diseases Section, Director, Occupational Health
and Infection Control Programs, James A Haley Veterans Hospital

Sandra G Gompf, MD, FACP, FIDSA is a member of the following medical societies: American College of
Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)
Judith Green-McKenzie, MD, MPH FACP, FACOEM, Associate Professor, Director of Clinical Practice,
Occupational Medicine Residency Director, University of Pennsylvania School of Medicine

Judith Green-McKenzie, MD, MPH is a member of the following medical societies: American College of
Physicians, American College of Preventive Medicine, National Medical Association, American College of
Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Ana Paula Velez, MD Assistant Professor of Medicine, Division of Infectious Disease and International Medicine,
University of South Florida College of Medicine and James A Haley Veterans Affairs Medical Center; Attending
Physician, Moffitt Cancer Center

Ana Paula Velez, MD is a member of the following medical societies: American College of Physicians-American
Society of Internal Medicine, American Medical Association, Infectious Diseases Society of America

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Leptospirosis: Practice Essentials, Background, Pathophysiology http://emedicine.medscape.com/article/220563-overview#a4

Disclosure: Nothing to disclose.

Leptospirosis
Chief Editor
Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf
Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center;
Author: Sandra G Gompf, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD more...
Master of the American College of Physicians; Fellow, Infectious Diseases Society of America
Updated: Apr 14, 2015
Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American
Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association
of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements
Denise Demers, MD, FAAP Assistant Professor of Pediatrics, Uniformed Services University of the Health
Sciences; Attending Physician, Division of Pediatric Infectious Diseases, Department of Pediatrics, Tripler Army
Medical Center

Disclosure: Nothing to disclose.

Juan D Diaz, DO Fellow in Infectious Diseases, University of South Florida College of Medicine, Tampa General
Hospital, and James A Haley Veterans Hospital

Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics,

Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American
Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric
Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Patrick W Hickey, MD, FAAP Assistant Professor of Pediatrics and Preventive Medicine, Uniformed Services
University of the Health Sciences; Consulting Staff, Department of Pediatrics, Division of Pediatric Infectious
Disease, Walter Reed Army Medical Center

Patrick W Hickey, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American
Academy of Pediatrics, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of
America, International Society of Travel Medicine, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Edmond A Hooker II, MD, DrPH, FAAEM Assistant Professor, Department of Emergency Medicine, University of
Cincinnati College of Medicine; Associate Professor, Department of Health Services Administration, Xavier
University

Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of
Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and
Southern Medical Association

Disclosure: Nothing to disclose.

Matthew R Jezior, MD Fellow, Department of Cardiology, Walter Reed Medical Center

Disclosure: Nothing to disclose.

Maria D Mileno, MD Associate Professor of Medicine, Division of Infectious Diseases, The Warren Alpert Medical
School of Brown University

Maria D Mileno, MD is a member of the following medical societies: Alpha Omega Alpha, American College of
Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America,
International Society of Travel Medicine, and Sigma Xi

Disclosure: Nothing to disclose.

Joseph T Morris, MD Chief of Infectious Disease Service, Madigan Army Medical Center; Assistant Professor,
Department of Internal Medicine, Uniformed Services University of the Health Sciences

Disclosure: Nothing to disclose.

Gary J Noel, MD Professor, Department of Pediatrics, Weill Cornell Medical College; Attending Pediatrician, New
York-Presbyterian Hospital

Gary J Noel, MD is a member of the following medical societies: Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Cecily K Peterson, MD Program Director, Clinical Faculty, Department of Medicine, Madigan Army Medical
Center

Disclosure: Nothing to disclose.

Charles V Sanders, MD Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of
Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans;
Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans;
Consulting Staff, Ochsner Medical Center

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Leptospirosis: Practice Essentials, Background, Pathophysiology http://emedicine.medscape.com/article/220563-overview#a4

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics,
Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University
Leptospirosis
Professors, American Clinical and Climatological Association, American College of Physician Executives,
American College of Physicians, American Federation for Medical Research, American Foundation for AIDS
Research, AmericanGeriatricsSociety,
Author: Sandra G Gompf, MD, FACP, American
FIDSA;Lung Association,
Chief American
Editor: Michael StuartMedical
Bronze,Association,
MD more...American
Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for
Professionals
Updated: Apr 14,in2015
Infection Control and Epidemiology, Association of American Medical Colleges, Association of
American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and
Gynecology, InfectiousDiseases Societyof America, Louisiana State Medical Society, Orleans Parish Medical
Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club,
Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of
Clinical Microbiology

Disclosure: Nothing to disclose.

William H Shoff, MD, DTM&H Director, PENN Travel Medicine; Associate Professor, Department of Emergency
Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine

William H Shoff, MD, DTM&H is a member of the following medical societies: American College of Physicians,
American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for
Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical
Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American
Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases
Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric
Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Jeter (Jay) Pritchard Taylor III, MD Compliance Officer, Attending Physician, Emergency Medicine Residency,
Department of Emergency Medicine, Palmetto Health Richland, University of South Carolina School of Medicine;
Medical Director, Department of Emergency Medicine, Palmetto Health Baptist

Jeter (Jay) Pritchard Taylor III, MD is a member of the following medical societies: American Academy of
Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Society for
Academic Emergency Medicine

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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