The Zoonotic Aspect Leptospirosis
ACVIM 2008
Robyn A. Stoddard, DVM, PhD
Atlanta, GA, USA

Introduction

Leptospirosis is one of the main causes of acute febrile illness along with dengue, malaria, and influenza and is presumed to be the most widespread zoonoses in the world.1 Leptospirosis has been considered to be an emerging infectious disease, however, it was removed from the list of reportable diseases in the United States in 1994. Historically, identification of Leptospira spp. has been based on serologic classification (serovar) which does not always coincide well with genotypic classification. There are 17 different Leptospira species including more than 250 serovars, not all are considered to be pathogenic. Disease caused by pathogenic Leptospira spp. can cause a widespread spectrum of disease in humans which ranges from no symptoms to a severe disease which can cause rapid mortality.

Epidemiology

Leptospires have been detected in more than 180 animal species but only mammals excrete the bacteria in their urine. Certain Leptospira serovars have adapted to specific mammal species that serve as a maintenance host for the bacteria. Rodents are common maintenance hosts for serovars in the serogroups Icterohaemorrhagiae and Ballum. Domestic animals may also serve as maintenance hosts. Dairy cattle are associated with the serovars Hardjo, Pomona, and Grippotyphosa; pigs may carry Pomona, Tarassovi, and Bratislava; sheep may harbor Hardjo and Pomona; and dogs have been associated with serovar Canicola. More than 10 serogroups have been cultured from humans, domestic animals, and wild animals in the United States (Table 1).2-11 Animals are vaccinated for the serogroups that cause disease in the U.S., but not for all serogroups that are known to be present (Table 1).

Transmission of leptospires in urine or contaminated water to humans mainly occurs through entry into abrasions or cuts in the skin or via the conjunctiva. Infection may also occur through ingestion of water or inhalation of aerosols. Infection rarely occurs due to animal bites. There are few reports in the literature that demonstrate the direct transmission of leptospirosis from domestic animals to humans. Several reports in the literature discuss the possible infection of humans and their pets from the same source.4,12 Humans are infected through occupational, recreational, or avocational exposures with occupational exposures being a significant risk factor. Occupational exposure can occur through direct contact with infected tissues (veterinarians, farmers, meat inspectors) or through indirect animal contact (sewer workers, miners, fish farmers, rice field workers). Recreational exposures are generally associated with water sports. Avocational exposure often occurs in tropical regions through normal daily activities such as walking barefoot in damp conditions.

There are three known epidemiologic patterns of leptospirosis which were defined by Faine in 1999.13 The first pattern is due to infection through farming of pigs and cattle in temperate locations. Few serovars are seen and control involves vaccination of carrier animals. The second pattern occurs in wet tropical areas where there are many more reservoir species and a larger number of serovars are present. Increased environmental contamination occurs in this pattern, especially during the rainy season. Prevention of the disease in these locations are more complicated and involves controlling the rodent population, draining wet areas, and occupational hygiene. The last pattern is due to rodent populations in urban areas, especially in less developed countries and prevention in this pattern is through rodent control.

Clinical Signs

The clinical presentation of leptospirosis in humans is biphasic with the acute phase having symptoms associated with septicemia. Once the immune system begins to produce antibodies in the second week, the patient then moves into the second phase in which leptospires are then excreted in the urine. During this phase the bacteria will move into tissues causing most of the complications associated with the disease. Most people who are infected with leptospires either experience subclinical or very mild disease. The most common symptom associated with leptospirosis is acute febrile illness. Other symptoms which may be seen include: chills, headache, myalgia, abdominal pain, and skin rash. Icteric leptospirosis, or Weil's disease, is much more severe and commonly is associated with acute renal failure. Pulmonary symptoms and ocular manifestations, such as conjunctival suffusion, have also been seen in leptospirosis.

Diagnosis

Differential diagnoses for human leptospirosis are influenza, HIV, dengue, typhoid, encephalitis, poliomyelitis, rickettsiosis, glandular fever, brucellosis, malaria, hepatitis, and pneumonitis. Definitive diagnosis of leptospirosis in humans is made by isolation of the bacteria from tissue or body fluids, but leptospires grow slowly on initial isolation and culture is therefore often not useful in patient management. The bacteremic phase lasts for only about 7 days whereas antibodies are detectable in blood about 5 to 7 days after onset of symptoms making diagnosis more likely by serology. At the Centers for Disease Control and Prevention (CDC) the Leptospira Dip-S-Tick (Panbio Inc., Columbia, MD), a qualitative IgM enzyme immunoassay, is initially run. If a specimen is found to be positive the microscopic agglutination test (MAT), the reference method for serologic diagnosis, is performed. Paired sera are always tested with MAT. The current CDC panel tests 20 serovars representing 17 serogroups whereas routine testing in veterinary medicine generally tests for 7 (Table 1).

Interpretation of the results of MAT in humans can be difficult due to the fact that antibody levels detectable by MAT usually do not appear before day 6 or 7 after development of symptoms and usually peak by the fourth week. MAT is relatively insensitive when acute phase samples are tested and the use of paired sera collected at the appropriate times can make interpretation easier. When only one specimen is received, a titer equal to or greater than 100 is considered positive and when paired specimen are received a fourfold rise in titer is positive. Determining the infecting serovar through the use of MAT may not always be predictive. The antibodies in serum may cross-react with several different serovars in the MAT (paradoxical reaction), particularly in acute specimens. Paradoxical reactions are an issue when interpreting results in vaccinated animals due to the fact that animals may also have positive titers to serovars other than those that they were vaccinated with.14 A false-positive reaction can occur due to cross reactions (sometimes with significant seroconversion) in serum of patients with syphilis, relapsing fever, Lyme disease, Legionella, viral hepatitis, and Epstein Barr virus.

Treatment

In humans treatment depends on severity of the disease. In patients with mild diseases treatment is based on symptoms but in patients with more severe disease treatment is more aggressive. Doxycycline is the standard treatment but intravenous penicillin along with supportive therapies are given to patients with more severe disease.

Control and Prevention

Vaccination of animals and control measures to prevent contact with wildlife is important for decreasing the disease in animals. The incidence of leptospirosis in dogs presenting to teaching hospitals has been on the increase.15 Care should be taken when dealing with pets that show signs consistent with leptospirosis. Veterinarians, their staff, and persons which may have contact with infected animals must follow proper protocol to decrease likelihood of exposure. Animals should be kept in isolation and persons in contact should wear a gown, gloves, and protective eyewear if there is a potential for splashing of materials. Hands should be washed thoroughly after working with the animal and surfaces should be treated with 10% bleach. Blood, urine, and tissue from an infected animal should be treated as hazardous waste. Animals should still be isolated once they are sent home with the owner since the bacteria can be shed for up to 3 months in the urine, even with treatment. Animals should urinate in locations away from water and locations where humans and other animals have access.

Table 1. Leptospira serogroups identified in species in the United States, those serogroups vaccinated and tested for.

Serogroup

Found in:

Vaccine

Testing:

Humans

Dogs

Large
animals

Wild
animals

Humans

Animals1

Australis

X

X

 

X

 

CDC

A,I

Autumnalis

X

   

X

 

CDC

A,I

Ballum

X

   

X

 

CDC

 

Bataviae

X

   

X

 

CDC

 

Canicola

X

X

Pigs

X

Dogs, cattle

CDC

A,I

Celledoni3

         

CDC

 

Cynopteri3

         

CDC

 

Djasiman3

         

CDC

 

Grippotyphosa

X

 

Cattle, horses, pigs

X

Dogs, cattle

CDC

A,I

Hebdomadis

X

       

CDC

 

Icterohaemorrhagiae

X

X

Cattle, pigs

X

Dogs, cattle

CDC

A,I

Javanica

X

       

CDC

 

Louisiana

     

X

     

Mini

X

 

Cattle, pigs

X

 

CDC

 

Pomona

X

X

Cattle, goats, horses, pigs

X

Dogs, cattle

CDC

A,I

Pyrogenes

     

X

 

CDC

 

Ranarum

     

X

     

Sejroe

X

 

Cattle

 

Cattle

CDC

A,I2

Tarassovi

     

X

 

CDC

 

1A=Antech, I=IDEXX
2By request
3People traveling outside the United States may be infected with these serogroups

References

1.  Levett PN, Clin Microbiol Rev 2001;14(2): 296.

2.  Sulzer CR, 1975. Leptospiral Serotype Distribution Lists According to Host and Geographic Area 1996; U.S. Department of Health, Education, and Welfare.

3.  Katz AR, et al. Am J Trop Med Hyg 2002;66(1):61.

4.  Barkin RM, et al. Am J Epidemiol 1973;98(3):184.

5.  Campagnolo ER, et al. J Am Vet Med Assoc 2000;16(5): 676.

6.  Donahue JM, et al. J Vet Diagn Invest 1992;4(3):279.

7.  Meites E, et al. Emerg Infect Dis 2004;10(3):406.

8.  Morgan J, et al. Clin Infect Dis 2002;34(12): 1593-9.

9.  Nielsen JN, et al. J Am Vet Med Assoc 1991;199(3):351.

10. Vinetz JM, et al. Ann Intern Med 1996;125(10):794.

11. Kmety E, et al. Classification of the species Leptospira interrogans and history of its serovars 1993; University Press.

12. Venkataraman KS, et al. Comp Immunol Microbiol Infect Dis 1992;15(4):243.

13. Faine S, et al. Leptospira and leptospirosis 1999;MediSci.

14. Barr SC, et al. Am J Vet Res 2005;66(10):1780.

15. Ward MP, et al. J Am Vet Med Assoc 2002;220(1):53.

Speaker Information
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Robyn Stoddard, DVM, PhD
Centers for Disease Control & Prevention
Atlanta, GA


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