Craig E. Greene
Etiology and EPIDEMIOLOGY
Leptospirosis, a zoonotic disease of worldwide importance, is caused by infection with antigenically distinct serovars of the parasitic species Leptospira. Leptospires are thin filamentous motile bacteria made up of fine spirals. Their central core is a protoplasmic cylinder wound about an axial filament that produces their motion. The outer envelope is an antigenic mucopeptide, which is responsible for the immune response. Much confusion about the classification of leptospires is based upon the fact that serogrouping has been used in the past, while this overlaps with the newer classifications based upon genetic methodologies. Based upon genetic analysis, Leptospira interrogans sensu lato includes at least eight species. For those serovars of pathogenic importance, the species L. kirschneri contains serovar grippotyphosa, while species L. interrogans sensu stricto contains serovars hardjo, bataviae, canicola, pomona, icterohaemorrhagiae, autumnalis, and bratislava. Serovars are maintained in nature by numerous subclinically infected wild and domestic animal reservoir hosts that serve as a potential source of infection and illness for humans and other incidental animal hosts. The organism and its maintenance hosts appear to undergo adaptation to their environment, and these host preferences and pathogenicity can change with time and geographic region. Due to vaccination, the prevalence of disease caused by L .canicola and L. icterohaemorrhagiae has decreased, while there is increasing evidence that the other serovars are becoming more prevalent in producing disease. Encroachment of domestic dogs on the environment of wildlife reservoir hosts in rural or suburban environments is another factor increasing prevalence.
Leptospirosis was first recognized as a cause of acute fatal illness in dogs in Europe in the 1930's. Subsequent reports were confirmed in North America. Manifestations of both hepatic and renal failure were recognized and the disease was rapid and progressively fatal because of the lack of effective chemotherapeutic agents or vaccines. Since the advent of antibiotics and leptospiral vaccines, the disease became less common and severe, and many veterinarians have discontinued their use of the vaccines. In the last two decades, there have been increasing reports of leptospirosis in dogs caused by strains other than used in vaccines and the clinical syndrome is more of an insidious onset of chronic renal or hepatic failure. The disease caused by grippotyphosa has been present in kenneled hunting dogs in the southeastern United States. In the northeastern states, pomona has predominated and in the western coast bratislava and pomona. L. australis has been documented as the cause of chronic hepatitis in dogs in France. In Southern Germany, the predominant serovars in decreasing order have grippotyphosa, saxkoebing, bratislava, and seroje. The awareness of leptospirosis has expanded as the range of tested serovars has increased. Data gathered since the early 1980's suggests that this disease is not an expanding epidemic but an endemic problem that is now being recognized
Leptospires can potentially spread directly between hosts in close contact through urine, venereal routes, bites, or ingestion of infected tissues. Indirect transmission, involves exposure of susceptible animals to contaminated soil, food, or bedding. Water contact is the most prevalent means of spread, and habitats with stagnant warm water and alkaline pH favor leptospire survival. Ambient temperatures between 0 to 25 degrees C maintain the organism, and freezing decreases survival.
Clinical signs depend on the immunity of the host and virulence and quantity of the serovar to which they are exposed. Young animals are more severely affected. Acutely, elevated rectal temperature, stiffness and discomfort are noted. Subsequently, vomiting, dehydration, and shock may ensue. Coagulation defects have also been noted. In subacute cases, anorexia, dehydration, and thirst may be noted. Reluctance to move and paraspinal hyperesthesia can be noted. Respiratory signs of conjunctivitis, rhinitis, and tonsillitis may be observed. In more chronically infected animals, progressive deterioration in renal function may be manifest by weight loss, polyuria and polydipsia, anorexia, and vomiting. Signs of acute or chronic hepatic dysfunction also include icterus from acute necrosis or chronic fibrosis. Overt signs of liver failure such as inappetence, weight loss, ascites, icterus, or hepatoencephalopathy may also be observed. Signs in cats are often mild or inapparent despite histologic evidence of a chronic inflammatory process in renal and hepatic tissues.
Clinical laboratory abnormalities usually include leukocytosis, thrombocytopenia, high serum urea and creatinine, electrolyte disturbances. Dogs with hepatic dysfunction frequently have bilirubinemia, and high serum hepatic enzyme activities Urinalysis abnormalities are often glucosuria, proteinuria, and bilirubinuria with increased numbers of granular casts, leukocytes, and sometimes erythrocytes in the sediment. Coagulation parameters may be altered in severely affected animals.
Serologic testing usually involves the microscopic agglutination (MA) test, however other methods such as immunofluorescence (FA) or enzyme immunoassay (ELISA) have been used, especially in Europe. Dogs with positive titers generally have cross-reactive sera with a variety of serovars. The highest titer is generally interpreted as the infecting one, however this cross reaction may relate to differing genotypes that overlap. The pattern of serologic reactivity is generally variable to a given geographic area with adaptation of particular strains to reservoir and domestic hosts. With the MA test, titers greater than 1:800 are considered presumptive for recent or active infection with Leptospira. In animals that are seronegative or have lower titers, a four-fold or greater rising titer should be demonstrated with a follow-up in 2 to 3 weeks. Vaccine titers using bacterins do not usually increase above 1:400 titer range, and the duration of their increase is generally transient for not more than 1 to 2 months.
Organisms are difficult to isolate because of their fastidious growth requirements and susceptibility to pH and other environmental factors. Immunohistochemical methods are helpful in specific determination for tissue sections. Genetic detection using PCR has been helpful in determining specific leptospires in body fluids or tissues such as blood, CSF, aqueous humor, and urine. Genetic methods will likely improve our understanding of this disease in the future.
Supportive treatment depends on the severity of infection and whether renal or hepatic dysfunction exists. Antimicrobial therapy is essential in the treatment of leptospirosis to terminate the bacteremia. Penicillin and its derivatives are the treatment of choice, however, they do not eliminate the renal carrier state. Initially penicillin or ampicillin are given parenterally to animals with gastrointestinal disturbances from uremia or visceral inflammation. Amoxicillin is preferred for oral use in animals that are alimenting normally. Other drugs such as tetracyclines, aminoglycosides, or macrolides should be used to eliminate the carrier state. Doxycycline can be given regardless of the degree of renal dysfunction; however, aminoglycosides must be strictly avoided. Newer erythromycin derivatives can be used to clear the renal carrier state should doxycycline cause toxicity.
Prevention of leptospirosis involves clearing the renal carrier state of infected animals. This may prevent the risk of infecting people; however, it does nothing to eliminate the contamination of water from wildlife reservoirs. Prevention of contact of dogs and cats with wildlife reservoirs may help reduce the risk of contact but most infections are contracted from drinking or immersion in water rather than via direct urinary spread. Inactivated bacterins were developed against the serovars icterohemorrhagiae and canicola, and this strategy has reduced the prevalence of these highly virulent forms of illness in countries where vaccination is practiced. Bivalent bacterins have been available for many years that offer protection against L. canicola and
L. icterohemmorrhagiae. These are not cross protective against those serovars that are responsible for the majority of recent infections in dogs. A recent bacterin contains serovars grippotyphosa and pomona, either as a bivalent or quadrivalent product with the other two agents. As inactivated bacterins, leptospiral vaccines have always had the tendency to cause allergenic reactions, especially when they have been combined with other adjuvanted agents. Many manufacturers have improved and purified their leptospiral vaccines to allow them to put this product in combination with coronaviral vaccines.
Public Heath Risks
The majority of leptospiral infections in people are among those engaging in water-related activities, either in work or leisure. Contact with urine can produce disease when it contacts mucosal surfaces or a break in the epidermal barrier. Gloves should always be worn in cleaning kennels and when cleaning urine-contaminated areas. Facemasks and goggles are essential in people spraying down housing environments for animals. Disinfectants can be sprayed on the surface of areas before generating aerosols to reduce the chance of inadvertent transmission.