Current Issues on Infection and Vaccination Leptospirosis, a contagious disease affecting both animals and humans and spread by infection with a bacterial pathogen called Leptospira, may result in chronic liver and kidney disease and fatality in the dog. Over the past 30 years, preventative vaccination against two of the most common Leptospires, L. canicola and L. icterohaemorrhagiae, have nearly eradicated clinical disease associated with these strains among the inoculated population. Though not without potential side effects associated with allergic reactions to inoculant in a small number of dogs, the risks of not vaccinating for Leptospirosis once far outweighed risks of vaccine-reaction. In recent years, however, new outbreaks of Leptospirosis have been reported in the population of vaccinated dogs. Clinical evidence now suggests that these new cases are associated with the once, less-common Leptospires for which current vaccines do not protect against. In light of these findings, the process of vaccinating dogs with the current Leptospirosis vaccines is being seriously questioned. The following article provides a detailed examination of infectious Leptospirosis in the canine and the recent clinical findings and misconceptions surrounding the controversy of using current vaccines to immunize dogs. Infectious Leptospirosis The Leptospira Organism. Leptospires are known as "aquatic spirochetes": they thrive in water and appear long and helical with a characteristic hook on one or both ends. These organisms are divided into two species, Leptospira biflexa and Leptospira interogans, the latter of which is pathogenic in animals and humans. L. interogans is divided into strains, or serovars, based upon the types of antigens (cell-surface markers against which the infected host will make antibodies) on their surface. These cell surface antigens provide little cross-immunity against one serovar and the next; that is, a dog that has developed immunity to one strain by either previous infection or vaccination will not be able to immunologically fend-off an infection of a different, subsequent strain. Despite this, however, these antigens may be cross-reactive in serological testing; that is, diagnostic testing to differentiate one serovar infection from another may lead to false-positive results because some antigens from one strain may have similarities to antigens from another strain. Serovar prevalence. As recent as the 1980s, L. icterohaemorrhagiae and L. canicola were identified as the most prevalent serovars causing Leptospirosis in the canine. By the 1990s, however, an increased incidence of L. grippotyphosa and L. pomona was observed in conjunction with a resurgence of Leptospirosis disease suggesting a changing trend in the epidemiology of this disease. It is speculated that these changes in serovar prevalence are related to two primary factors that may strongly influence the epizootiology of Leptospira serovars. These factors are: 1) preventative vaccination has all but eradicated clinical disease in the domestic dog and 2) there has been an increased migration of wildlife, for which serovar infections with L. grippotyphosa and L. pomona are most prevalent, into suburban areas. Modes of Disease Transmission. Leptospira thrive in spring and autumn when wet soil conditions and moderate temperatures support their otherwise poor environmental survivability. Infection by contact with infected urine or ingestion of urine-contaminated water is the most common means of transmission of the disease. Less common modes of infection include transmittance of the organisms during breeding, gestation, or through the membranes of the eyes, abrasions or bite wounds, or ingestion of the flesh from infected animals such as rats, raccoons, skunks or opossums. A serovar infects the dog as a maintenance host, using the dog to carry out most, if not all of the organism's life cycle. Under these conditions, the kidneys of the infected dog become the "breeding" grounds for the serovar, some of which will be shed in the urine where they may gain access to other dogs and continue the infectious cycle. Symptoms of disease. During the first 4-12 days following infection with Leptospira, the dog may experience sudden symptoms of fever (103-105oF), depression, vomiting, loss of appetite, conjunctivitis, and generalized pain. Within 2 days of the onset of these primary symptoms, body temperature may drop suddenly and there may be a noticeable increase in thirst. A definite change in the color of the dog's urine and/or jaundice (icterus) is often noticed and may be the only indication of disease. Color intensity of the urine may vary from lemon to deep orange. Additionally, frequent urination and subsequent dehydration (uremia) are consistent with invasion of the kidney tubule cells by the Leptospira organism and usually present within a few days of the primary symptoms. In advanced cases of infection, profound depression, difficulty breathing, muscular tremors, bloody vomitus and feces are often observed as the infection progresses to include the liver, gastrointestinal system and other organs. Course and severity of the disease is often dependent upon the serovar responsible for the infection. Serovars associated with liver infection and symptoms of urine discoloration and/or jaundice (icterus), elevation of liver enzymes, and gastrointestinal symptoms include L. icterohaemorrhagiae and grippotyphosa. The serovar grippotyphosa is also associated with symptoms of renal failure as is the serovar pomona. Diagnosis. Given the nonspecific symptoms often associated with Leptospira infection, definitive diagnosis must be based on the combination of symptoms and results from laboratory and serologic tests. Despite this, however, Leptospirosis should be among the primary suspected causes of illness in dogs presenting with sudden-onset kidney dysfunction. Laboratory testing of blood chemistry and urine provide evidence of abnormalities of components of the blood, elevation in liver enzymes, electrolyte imbalances, and active urinary sediments all consistent with vascular, liver, and kidney disease associated with Leptospira infection. The most commonly used serologic test includes the microscopic agglutination test (MAT), which titrates reactivity of antibodies in the patient's serum with live leptospires. Limitations to MAT include false-negative results early in the course of the disease, reduced positive response in vaccinated dogs that may be harboring chronic infection, and cross-reactivity excluding the ability to distinguish between serovars. Other serological tests including the enzyme-linked immunosorbent assay (ELISA) and microcapsular agglutination test (MCAT) are more specific, reducing false-positives associated with vaccinal responses and providing earlier detection by monitoring immunoglobulins specific for immune response to infection (IgM), respectively. Treatment. Antibiotic therapy in the early course of Leptospirosis infection is efficient in shortening duration of the disease, reducing the time period for risks of contagion, and decreasing the severity of liver and kidney damage. In advanced cases, supportive therapy to compensate for abnormal blood, kidney and liver function may be required. Therapy to restore urine production, kidney filtration and blood flow are essential to reversing kidney failure. In cases of severe liver disease, a decrease in clotting factors in the blood may lead to bleeding disorders requiring treatment by transfusion. Since Leptospirosis poses a risk of contagion to other animals and to humans, special precautions must be taken to prevent transmission of Leptospira from the dog to other animals and human companions or caretakers. All blood, urine, and tissues from a dog suspected or determined to have Leptospirosis must be handled as biologically hazardous waste. Infected dogs should be quarantined and areas of contamination should be washed and disinfected with an iodine-based solution. It is important to note that even after treatment and control of the active disease state, dogs continue to shed serovar in their urine and therefore, may pose an infectious risk to other animals and to humans up to 3 months following infection. Prognosis. Fatalities as a direct result of Leptospirosis do not usually exceed 10% and usually occur 5-10 days after initial onset of the disease. Death arising from secondary complications associated with progressive kidney and liver damage are common but may not occur for long periods following the initial disease. Prevention. Commercial vaccines are available and protect against clinical disease associated with the L. icterohaemorrhagiae and L. canicola serovars. Inoculation does not, however, prevent infection and development of a carrier state whereby the dog will be clinically asymptomatic for disease yet provide a source of contagion through the shedding of serovars in its urine. Additionally, vaccinating against these specific serovars does not afford protection against other serovars. Current Issues Relating to Leptospirosis and Vaccination Annual Revaccination and Leptospirosis Current concerns in canine immunology have addressed issues related to overuse of vaccines in dogs and cats. General consensus among specialists in the field is that yearly vaccination against viral infections associated with canine distemper virus, canine parvovirus and canine adenovirus are generally unnecessary since active immunity induced by these vaccines provide at least several years of protection. This consensus, however, does not apply and should not be generalized to bacterin vaccines, which immunize against diseases associated with bacterial organisms. In fact, clinical evidence suggests that bacterin-derived vaccines including those which protect against Bordetella bronchiseptica (kennel cough), Leptospira (Leptospirosis), and Borrelia burgdoferi (Lyme disease) probably don't even provide protective immunity for 12 months suggesting that more frequent vaccination for these diseases are required. It is perhaps the common use of combination (all-in-one) vaccines containing bacterins, which immunize against bacterial infections such as Leptospirosis and/or kennel cough in addition to common viral infections, that gave rise to the practice of frequent vaccine administration. Indeed the incorrect generalization of long-term immunity, associated with vaccination against viral immunogens, to bacterin-based vaccines may lead to a decrease in annual vaccination for bacterial-based diseases and subsequently give rise to a resurgence of outbreaks of bacterial disease in the coming years. In light of this, annual re-boostering against bacterial diseases should continue despite discontinuation of yearly vaccination against viral diseases. The Current Leptospirosis Vaccine Recent serological studies on wildlife and domestic dogs suggests that L. grippotyphosa and L. pomona have replaced L. icterohaemorrhagiae and L. canicola as the prevalent serovars responsible for Leptospirosis in the United States today. As such, current commercial vaccines, which protect against the formerly prevalent serovars, would not be effective at providing immunity against Leptospirosis caused by L. grippotyphosa and L. pomona. For this reason, there has been some conjecture that current commercial vaccines should be considered obsolete for protecting against Leptospirosis. There are several factors that should be considered prior to drawing this conclusion. First, Leptospirosis vaccines, as mentioned above, protect against clinical disease but do not prevent subclinical infection to a "carrier" state. That is, a dog that is annually vaccinated may harbor infectious organisms of L. icterohaemorrhagiae or L. canicola which will pose a risk of contagion to dogs that are not vaccinated or in which vaccination for these serovars has been discontinued. Without serological testing, low clinical incidence of these formerly prevalent serovars may be a result of the currently large population of vaccinated dogs. If this is the case, discontinuing administration of the current Leptospirosis vaccine may result in a resurgence of clinical disease. Furthermore, it is important to note that samples from these studies are not necessarily representative of all regions of the US. When all the facts are considered, these findings do not necessarily suggest that L. icterohaemorrhagiae and L. canicola no longer pose a threat to dogs. Rather, this information should be taken into consideration when determining potential risk of infection in dogs that may be candidates for side effects associated with vaccine-reaction. Leptospirosis-containing vaccines are associated with a higher risk for side effects, particularly, anaphylactic reactions (see Canine Anaphylaxis). Taken together, benefits of vaccinating dogs, who live in areas where icterohaemorrhagiae and canicola incidence is low and who may have a higher predisposition for vaccine side effects with current Leptospirosis inoculants (see Vaccines, Infectious Diseases and the Canine Immune System), may not outweigh risks of vaccine reaction. New Leptospirosis Vaccine Immunizes Against L. grippotyphosa and L. pomona Fort Dodge now offers the Duramune Leptospirosis vaccine that immunizes against L. grippotyphosa and L. pomona serovars as well as L. icterohaemorrhagiae and L. canicola . This vaccine has been formulated through the new subunit technology that uses only the antigen component of the organism (that will produce an immune response) instead of the entire organism. As such, subunit vaccines greatly reduce vaccine side-effects that occur with higher incidence with bacterin-based vaccines while providing durable protection from the disease. More Information on Leptospirosis Visit the Leptospirosis Links Page References: Ford, RB and Schultz, RD. Vaccines and Vaccinations: Issues for the 21st Century. In: JD Bonagura, ed., Kirk's Current Veterinary Therapy XIII, W.B. Saunders, Philadelphia, 1999. pp. 250-253. Rentko, VT and Ross, LA. Canine Leptospirosis. In: JD Bonagura, ed., Kirk's Current Veterinary Therapy XI, W.B. Saunders, Philadelphia, 1992. pp. 260-263. Ribotta MJ, et al. Development of an indirect enzyme-linked immunosorbent assay for the detection of leptospiral antibodies in dogs. Can J Vet Res. 2000 Jan; 64(1):32-7. Mitchell MA, et al. Serologic survey for selected infectious disease agents in raccoons from Illinois. J Wildl Dis. 1999 Apr;35(2):347-55. Carmichael LE. Canine viral vaccines at a turning point--a personal perspective. Adv Vet Med. 1999;41:289-307. Gese EM, et al. Serological survey for diseases in free-ranging coyotes (Canis latrans) in Yellowstone National Park, Wyoming. J Wildl Dis. 1997 Jan;33(1) :47-56. Harkin KR, et al. Canine leptospirosis in New Jersey and Michigan: 17 cases (1990-1995). J Am Anim Hosp Assoc. 1996 Nov-Dec;32(6):495-501. Rentko VT, et al. Canine leptospirosis. A retrospective study of 17 cases. J Vet Intern Med. 1992 Jul-Aug;6(4):235-44. Copyright © 2001, 2000. Pamela A. Davol. All rights reserved.