Read the French translation: La Leptospirose Canine--Nouveaux Défis

The infection of dogs with leptospires causes a wide spectrum of organ manifestations with injury to the kidney, liver, vasculature, blood, and lung. The resulting clinical picture can vary markedly between affected individuals and it tends to shift over time depending on prevailing leptospiral serovars or strains. The goal of this lecture is to review some of the clinical characteristics of canine leptospirosis, with particular emphasis on recent observations made in Europe and in Switzerland.

Leptospirosis: A Worldwide Zoonosis with a Local Significance

Leptospirosis is considered one of the most important zoonoses worldwide with tens of millions of human cases estimated to occur each year. As such, humans with direct and indirect contact with animals are likely to be exposed to and infected with this potentially life-threatening bacterial infection. The introduction of bivalent canine vaccines against Leptospira icterohaemorrhagiae and L. canicola four decades ago and their worldwide inclusion in the routine core vaccination programs of dogs has drastically reduced the number of canine cases diagnosed in most countries. In the last decade however, an increased number of canine cases has been reported, first in North America and now in some European countries. This increase seems to be linked to the emergence of "newer" non-vaccinal serovars in this species including L. bratislava, L. pomona, L. grippotyphosa, and L. australis. However, the resurgence of the disease and the observed serovar shift are likely to be associated with other predisposing parameters than only the lack of vaccinal protection to explain the re-emergence of the canine leptospirosis in developed countries. Climate changes, ease of rapid and extensive traveling, increased popularity of outdoor water sport activities, and expansion of the living habitat of humans and pet dogs are just a few examples of factors resulting in changes in our direct and indirect contact with potential carrier wildlife and the environment. Even the urban environment is changing and some studies in Brazil have demonstrated differences in the human manifestation of acute leptospirosis between cities and villages, including a higher prevalence of the severe pulmonary form in urban centers.¹ Recent studies have shown a high prevalence of leptospirosis infection (12.6%, PCR) in small rodents of the inner-city of Zurich (Switzerland) and a high seroprevalence in urban wild boars in Berlin (Germany), supporting a common exposure of dogs even when confined to an urban environment.^2,3 The interplay of these parameters is certainly very complex and dynamic. The study of their individual role in the resultant disease prevalence and manifestation in small animals will hopefully gain support from our better understanding of the biology of leptospires and from the development of more recent investigational technologies including newer PCR protocols and epidemiological modeling systems.

Considering the close contact of humans and dogs, canines are likely to represent not only a direct source of infection for humans, but being exposed to many similar environmental risk factors, dogs should probably be viewed as a sentinel species for humans. It would therefore seem reasonable to regard the currently observed increase in prevalence of canine leptospirosis as a warning for humans with potential similar exposure. This is even more important considering that human leptospirosis is not an infectious disease under official control and mandatory declaration in most countries. Prevalence of human cases is therefore difficult to assess and the disease is often considered to be underdiagnosed in western countries. Despite these difficulties, a reported increase in the incidence of human cases in Germany in recent years with a possible link to dogs seems to justify the view of canines as both a potential health risk and an important sentinel role for human leptospirosis.⁴

Being exposed to a large number of diseased dogs and a likely even larger number of carriers, veterinarians and their technical staff represent a typical population at risk for leptospirosis, together with sewer workers, farmers, slaughterhouse workers, gardeners, and military personnel. Dogs with acute kidney injury as a classical manifestation of leptospirosis are commonly shedding large numbers of infectious organisms in their urine, blood, and other body secretions. Such dogs should therefore always be considered infectious and preventive measures should be applied. It should however not be forgotten that clinically healthy dogs or dogs presented for other conditions can be chronic asymptomatic carriers shedding leptospires in their urine. Despite the lower number of excreted infectious organisms, the risk of such dogs may be even larger due to the lack of suspicion when collecting and handling samples. In endemic areas, depending on the prevalence rate of clinical cases, protective measures may have to be extended to these less suspicious groups of patients and incorporated in the routine hygiene guidelines of clinical practice. In our hospital we consider every dog with acute kidney injury to be suspicious for leptospirosis until proven otherwise. These dogs are always tested for leptospirosis, they are treated accordingly with immediate antibiotic therapy (already while waiting for test results), they are labeled as leptospirosis-suspect for increased awareness, and they are always handled with exam gloves. Regular training of the medical and technical personnel is important in order to keep a high index of suspicion and to avoid neglecting preventive measures against this potentially life-threatening zoonosis, especially during peak months in endemic areas. In fall, we commonly have 3-5 dogs simultaneously with leptospirosis in our intensive care unit and this tends to result in a feeling of routine with progressive negligence of personnel protection measures. A recently performed cross-sectional seroepidemiologic survey of our medical and technical staff indicated the adequacy of our protection protocols and no need for additional protective measures.⁵ The zoonotic risk is however well documented in the literature and it should therefore not be underestimated.

Canine Leptospirosis in Europe and in Switzerland

Following closely the re-emergence of canine leptospirosis observed in North America during the last decade, an increasing number of cases has been observed similarly in some European countries including France, Germany, and Switzerland. From the same referral basis, the teaching hospital of the University of Berne has diagnosed an average of 1-3 cases per year in the late 1990s and over 25 confirmed cases 10 years later.⁶ This increase was observed in other areas of the country as well and it has led to some alarming media reports. Almost all affected dogs were current on their vaccination according to recommended protocols, with more than half of them being infected within less than 6 months of vaccination. Serovars identified (seroconversion) seem to vary somehow geographically, but most cases were seroconverting for L. australis and L. bratislava, followed by L. grippotyphosa, L. pomona, and L. autumnalis. The disease seems to present similarly in most European countries with some geographical differences.

The clinical manifestation of canine leptospirosis is very variable and it is likely to be influenced by host, pathogen, and environmental factors. The wide spectrum of organ involvement with the various combinations of renal, liver, systemic (sepsis, DIC), and pulmonary injury seems to be changing continuously. Temporal or geographical clusters of similar cases may indicate a role of specific pathogen strains with defined virulence or of environmental factors in the specific clinical manifestation of affected dogs. The serological pathogen classification (serovars) is very likely insufficient to differentiate various strains and thus to analyze the relationship of the affecting strain with the clinical picture. The use of molecular biological techniques is likely to help in this regard and the information gained from a better understanding of the pathogen characteristics may result in more efficient preventive and therapeutic strategies in the future. Similar to a shift observed in the past from a predominantly ictero-hemorrhagic form to a renal manifestation, the clinical picture of most dogs diagnosed at the University of Berne and in some other areas tends to be dominated now by severe pulmonary hemorrhages.^7,8

Leptospirosis-Associated Pulmonary Hemorrhages (LAPH)

Dogs with LAPH are suffering from a very acute manifestation of leptospirosis, with severe and commonly fatal respiratory failure caused by bleeding in the pulmonary interstitium and in the alveolar space. A prospective evaluation of this manifestation indicated a very high prevalence with over 80% of dogs affected clinically or radiologically at the time of presentation to a referral hospital.⁷ The concurrent acute kidney injury tended to no longer be the limiting factor for recovery with over 40% of the affected dogs being euthanized for respiratory failure. The exact mechanism of pulmonary injury is largely unclear at this state, but the most likely explanation is a combination of specific virulence factors of the involved leptospiral strains with factors of the host response to the infection indicating immune-mediated mechanisms.⁹ The dog seems to be a naturally-occurring model for the human LAPH which is a similarly devastating very severe form of leptospirosis associated with 30-60% mortality rates.

Management of dogs with LAPH remains challenging and requires typically intensive care facilities equipped for renal replacement and respiratory support. Milder cases may be treated with appropriate conventional fluid and medical therapy, with careful attention to avoid overly aggressive fluid therapy and secondary pulmonary complications. Treatment goals should aim at correcting fluid, electrolyte, and acid-base disturbances, supporting the gastro-intestinal tract (nausea, vomiting, diarrhea), and treating the infection with appropriate antibiotic therapy. A global approach to all expected problems of acute kidney injury with realistic goals and expectations is central to a successful therapy and special care should be taken to avoid compensating for the inherent limitations of treatment with over-treatment, since this can only lead to additional complications. Treatment limitations can only be overcome with renal replacement therapies (intermittent or continuous hemodialysis, peritoneal dialysis) or with respiratory support (mechanical ventilation), when appropriate.

Treatment and prevention of pulmonary hemorrhages in dogs with leptospirosis requires a high index of suspicion and cautious intervention. Considering our limited understanding of the pathogenesis of the pulmonary injury at this stage, specifically targeted treatment is not possible and therapy remains limited to avoid worsening existing bleeding by keeping the animals very quiet (sedated if necessary), paying extremely close attention to fluid balance and blood pressure control, and providing early oxygen therapy. Additional uremic pulmonary injury should be avoided by controlling the azotemia with renal replacement if necessary. More specific therapies including use of desmopressin (DDAVP) and corticosteroids (dexamethasone) have been used with variable success in humans but they have not been successful in dogs.^10,11,12

References

1.  Ganoza CA, et al. PLoS Med 2006;3(8):e308.

2.  Hadler H, et al. Epidemiol Infect 2002;128(1):107.

3.  Jansen A, et al. Emerg Infect Dis 2007;13(5):739.

4.  Jansen A, et al. Emerg Infect Dis 2005;11(7):1048.

5.  Barmettler R, et al. JAVMA [in press].

6.  Francey T. (abs) JVIM 2006.

7.  Schweighauser A, et al. (abs) JVIM 2008.

8.  Radeke K, et al. (abs) JVIM 2009.

9.  Medeiros, et al. Acta Tropica 2010 [epub];

10. Schweighauser A, et al. (abs) JVIM 2008.

11. Pea L, et al. Am J Respir Crit Care Med 2003;167(5):726.

12. Niwattayakul K, et al. Clin Microbiol Infect 2009 [epub].