Advances in the Prevention of Leptospirosis
ACVIM 2008
Richard E. Goldstein, DVM, DACVIM, DECVIM (CA)
Ithaca, NY, USA

Introduction

Leptospirosis is an important world-wide zoonosis, caused by an infection with a pathogenic species of the genus Leptospira. These are highly motile obligate aerobic spirochetes that share features of both gram-negative and gram-positive bacteria.1 This short presentation will concentrate on methods of prevention of canine leptospirosis. Prevention is of the utmost importance in this disease because of a combination of factors including the difficulty in diagnosing the disease, especially early on, the relatively high mortality rate (around 20-25%) even with very aggressive therapy and the human health risk. Prevention of the canine disease includes minimizing exposure of dogs to the bacteria and vaccination. Different types of vaccination s, those currently available and those likely to be available in the future will be discussed.

Minimizing Dogs' Exposure to the Bacteria

This includes minimizing the dogs' contact with reservoir hosts and their excretions. Reservoir hosts vary from serovar to serovar and not all are definitively characterized (table 1)

Table 1. Reservoir hosts for the common serovars.1

Serovar

Reservoir host

Canicola

Dog

Icterohaemorrhagiae

Rat

Grippotyphosa

Raccoon, Marsupials

Pomona

Cow, Pig

Hardjo

Cow

Bratislava

Horse

Autumnalis

Mouse

The ideal conditions for the bacteria to survive after being excreted in the host's urine are a warm and moist environment. Hence there is seasonality to canine leptospirosis cases with the typical highest number of cases being in the late summer and fall. The number of cases in a specific year has been correlated to the amount of rainfall the previous spring.2 Outbreaks in humans and likely animals often occur after flooding when water sources are contaminated, including a recent outbreak among triathlon participants in the US.3 Minimizing exposure of dogs to standing water or moist areas where hosts resides is the first step in prevention. In a kennel situation of there is a concern of leptospirosis dogs should be kept on a dry clean (any detergent is fine, bleach is often used) surface such as concrete thus eliminating the chance of survival of the bacteria and infection of the dogs.

Currently Available Vaccines

Currently all commercially available vaccines against Leptospira organisms are based on bacterins, or killed bacteria. Each vaccines contain killed bacteria from 2 or 4 serovars with what is thought to be little cross protection between serovars, meaning to protect again serovar Grippotyphosa one needs to vaccinate with the same serovar. The Leptospira serovars currently available in most US approved vaccines are serovars Icterohaemorrhagiae and Canicola. These are the two serovars that have been available for many years. More recently two commercially available vaccines came on the market that include 4 serovars; the 2 previous ones as well as serovars Pomona and Grippotyphosa. These 2 additional serovars are among the most commonly reported serovars in canine disease (based on MAT titers) in recent reports from the eastern and central US.4,5 These vaccines include a modified sub-unit and a purified whole cell bacterin. Some concern has been expressed by breeders and veterinarians about the safety of Leptospira vaccines, and some breed related questions have been raised especially about the sub-unit vaccine. There is little published data to confirm this, as there is no independent mechanism to report vaccine reactions in the US. The largest study on acute vaccine reactions recently published did not show an increased risk of reactions with a multi-valent vaccine that included Leptospira sub units.6 These vaccines do appear to be efficacious and should be strongly considered in dogs at risk of contracting the disease. One question that has been raised in the literature is do the vaccines prevent a carrier state or chronic shedding state in addition to preventing disease in the dog. Data recently published,7 as well as data from a study we performed will be presented that clearly shows that at least with the vaccines and challenge serovars tested, they do prevent renal colonization and shedding as well as protecting the dog from disease. If there is a question of a carrier state it is most likely to with occur serovar Canicola, since the dog is the definitive host for this serovar. This serovar is not seen often in today's pet population. With all commercially available vaccines today annual boosters are most likely necessary as these vaccines are unlikely protect for 3 years.

The Future of Leptospira Vaccines

Two main avenues of development are currently underway:

 Adding additional serovars in bacterin type vaccines to broaden the coverage.

 Sub-unit non serovar-specific vaccines. The "holy grail" of Leptospirosis prevention for animals as well as humans.

Understanding the molecular basis for Leptospiral virulence is crucial in the effort to produce more effective vaccines. A lot of effort in recent years has been placed in to identifying surface antigens that are expressed during active infection, that appear to be part of the pathogenic mechanism of the bacteria, and are common to all pathogenic serovars. Once identified these proteins can then be investigated as possible targets for vaccine development. For example, Leptospira immunoglobulin-like protein A (LigA) contains domains homologous to proteins with attachment and invasion functions and is expressed in vivo after the bacteria sense the salinity of the host.2 Somewhat encouraging data from multiple studies will be presented demonstrating partial protection from challenge in ligA vaccinated rodents.8,9 We are not there yet, but hopefully within a reasonable amount of time we will have non-serovar specific vaccine based on one or more of these surface antigens. This hopefully will enable better protection by potentially less reactive vaccines against all Leptospira pathogens for humans in endemic areas as well as domestic animals.

References

1.  Levett PN, et al. Clin Inf Dis 2003;36(4):447.

2.  Bharti AR, et al. Lancet Infect Dis 2003 ;3 :757.

3.  Morgan J, et al. Clin Inf Dis 2002 ;34 :1593-9.

4.  Goldstein RE, et al. J Vet Intern Med 2006;20(3):489-94.

5.  Moore GE, et al. Emerg Infect Dis 2006;12(3):501-3.

6.  Moore GE, et al. J Am Vet Med Assoc 2005;227(7):1102-1108.

7.  Schreiber P, et al. Vet Micro 2005;108:113-118.

8.  Faisal SM, et al. Vaccine 2008;26:277-287.

9.  Silva EF, et al. Vaccine 2007 ;25 :6277-6286.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Richard Goldstein, DVM, DACVIM, DECVIM-CA
Cornell University
Ithaca, NY


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