Future Direction in Small Animal Leptospirosis
ACVIM 2008
Jane Sykes, BVSc (Hons), PhD, DACVIM
Davis, CA, USA

Introduction

Leptospirosis is considered a globally re-emerging disease. Increasing case numbers have been recognized in humans in developing countries, especially in association with flooding and natural disasters. Frequent outbreaks have been reported in South East Asia and Central and South America, although many outbreaks probably go unrecognized, as the disease is likely underdiagnosed.1 Increasing case numbers have also been identified in developed countries, especially in association with recreational activities involving freshwater exposure.2 It is generally accepted that the leptospirosis is a re-emerging disease in dogs, and current cases in developed countries appear to be associated with serovars other than Icterohemorrhagiae and Canicola. The International Leptospirosis Society (ILS) is promoting increased awareness and surveillance of leptospirosis through the availability of LeptoNet, an online database that aims to provide epidemiological information about the worldwide occurrence of leptospirosis. In conjunction with ILS, in 2003, the World Health Organization published guidelines for diagnosis, surveillance, and control of human leptospirosis.3 It is critical that veterinarians worldwide be aware of these efforts as they clearly play an important role in the detection and prevention of this zoonosis, and in increasing awareness of the general public regarding the disease.

Future Challenges in Small Animal Leptospirosis

Diagnosis

Rapid in-house serologic assays are being developed and evaluated for diagnosis of leptospirosis in dogs. It is important that these assays be adequately validated for use in dogs in the geographic areas they are being used. Practitioners must also understand how to interpret these assays, given that the majority of cases with peracute disease may initially test negative, and vaccination and previous exposure may cause positive test results, even using assays for IgM. Antigen assays are also being developed, which will require validation. There is also a need for better understanding of the variation in MAT results between veterinary diagnostic laboratories, and diagnostic laboratories should encouraged to either include serovars representing more serogroups, or at least to consider offering initial screening using a genus-specific screening test such as an ELISA using a broadly reactive antigen. This will help prevent false negative results for dogs infected with serogroups other than those included in the MAT, and in some situations may be positive before the MAT. Positive ELISA results should be confirmed using the MAT, because some ELISA assays are less specific for leptospirosis than the MAT. More information is required regarding the value of PCR for diagnosis of canine leptospirosis. Currently there is a lack of validated assays for canine leptospiral serovars. Practitioners should be encouraged to use fluorgenic (real-time) PCR rather than conventional PCR because of its lower rate of contamination. Practitioners should also be encouraged to submit heparinized blood for leptospiral culture at an appropriate laboratory prior to initiating antimicrobial therapy, such that a bank of canine isolates can be accrued for future epidemiologic studies, which in turn will promote optimal prevention and control in the future. For each submission, data should be collected regarding exposure history, including contact with possible contaminated water or mud, freshwater exposures, date(s) and location(s) of exposure, exposure to animals, list of animals concerned and whether they were ill or died, presence of skin wounds during the 4 weeks before infection, and source(s) of drinking-water. Blood should be collected for culture within the first 10 days of illness, and ideally no more than a few drops of blood should be inoculated into 5 mL of leptospiral culture medium. Because leptospires die quickly in urine, urine is a less valuable fluid for culture purposes. Culture is also useful for diagnosis in animals that die early in the course of illness, before antibodies can be detected. The zoonotic concerns associated with shipment of samples potentially containing pathogenic leptospires must also be considered.

Epidemiology

There is a need for molecular typing studies using canine leptospiral isolates to allow an improved understanding of the epidemiology of leptospirosis in dogs, and to determine the relatedness of isolates from canine cases and human cases of leptospirosis. Continued surveillance of the pet dog population based on the results of the MAT at a single laboratory, as performed previously,4 is encouraged. There is also a need for more prevalence studies aimed at farm and wildlife species, using both serological and isolation/genotyping studies. More sensitive molecular methods are required for detection and characterization of pathogenic leptospires from environmental reservoirs.

Treatment

The optimum treatment for canine leptospirosis is unknown. In human patients, severe leptospirosis is treated with high dose intravenous penicillin, although the use of once daily ceftriaxone has recently been suggested as a safer and less labor-intensive alternative.5 Intravenous penicillin derivatives appear to be safe and efficacious in dogs. The efficacy of fluoroquinolones for treatment of leptospirosis has been controversial, but a recent study in hamsters suggested that ciprofloxacin and levofloxacin, when administered at very high doses, may have efficacy similar to that of doxycycline.6 The need for specific antimicrobials to eliminate renal carriage is not clearly understood, and more studies need to be performed to determine whether penicillin derivatives alone can eliminate renal carriage of leptospires. Veterinarians should be encouraged to offer referral of cases with severe renal failure to veterinary hemodialysis centers wherever feasible, because as few as 1 or 2 hemodialysis treatments can offer the opportunity for recovery of renal function during antimicrobial therapy.

Zoonotic Implications

It has been reported that approximately 10% of human cases of leptospirosis in California result from contact with pets.2 However, it is likely that the number of cases of leptospirosis in people associated with pet contact is underreported. The extent of leptospiral shedding by dogs infected with current serovars is largely unknown, as is the impact of antimicrobial therapy on shedding. The development and application of novel quantitative real-time PCR assays should help to answer such questions. Guidelines for handling dogs suspected to have leptospirosis should also be developed and endorsed by veterinary infectious disease societies. Issues such as whether or not prophylactic doxycycline treatment should be recommended for humans in contact with pet dogs diagnosed with leptospirosis prior to initiating antimicrobial therapy should be discussed with human health care professionals.

Prevention

The introduction of vaccines containing serovars Pomona and Grippotyphosa was based on increasing reports of canine disease in North America associated with seroconversion to these serovars, together with the fact that immunity following vaccination is serovar specific. Disease caused by serovars other than Icterohemorrhagiae and Canicola also appears to be prevalent in Europe, where additional serovars have not yet been incorporated into vaccines.7 Until broadly protective vaccines are available for dogs, improved understanding of the geographic variation in disease caused by various leptospiral serovars and strains is required to determine the optimum constituent antigens for inclusion in canine leptospiral vaccines.

In recent years, more information has become available regarding the degree of protection induced by leptospiral vaccines and duration of immunity following vaccination, but more studies are needed. Challenge studies show protection following vaccination and challenge a few weeks later with a homologous serovar. One recent study showed that vaccination with a bivalent inactivated bacterin completed protected against leptospiremia, leptospiruria, and renal carriage.8 Another study showed marked reduction in the degree of leptospiremia and leptospiruria following challenge at 56 weeks, although the degree of protection was not quite as strong as following challenge at 5 weeks.9 Vaccination should be recommended for at risk dogs just prior to the peak seasonal incidence of leptospirosis for a particular geographic area. More information is required on the duration of immunity associated with vaccines containing serovars Pomona and Grippotyphosa, and the prevalence of vaccine breakthroughs. There is a need for safe vaccines that provide cross-protection against a variety of serovars and that prevent development of the carrier state. Recently there has been rapid progress made in the development of cross-reactive recombinant DNA vaccines for control of leptospirosis.10,11

References

1.  Hartskeerl RA. Indian J Med Microbiol 2006;24:309.

2.  Meites E, et al. Emerg Infect Dis 2004;10:406.

3.  Terpstra WJ, World Health Organization, International Leptospirosis Society. 2003; http://www.med.monash.edu.au/microbiology/staff/adler/ils.html.

4.  Moore GE, et al. Emerg Infect Dis 2006;12:501.

5.  Panaphut T, et al. Clin Infect Dis 2003;36:1507.

6.  Griffith ME, et al. Antimicrob Agents Chemother 2007;51:2615.

7.  Geisen V, et al. J Small Anim Pract 2007;48:324.

8.  Schreiber P, et al. Vet Microbiol 2005;108:113.

9.  Klaasen HL, et al. Vet Microbiol 2003;95:121.

10. Faisal SM, et al. Vaccine 2008;26:277.

11. Palaniappan RU, et al. Infect Immun 2006;74:1745.

Speaker Information
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Jane Sykes, BVSc (Hons), PhD, DACVIM
University of California, Davis
Davis, CA


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