VETgirl Q4 2019 Beat e-Newsletter

LEPTOSPIROSIS GEORGE E. MOORE, DVM, MS, PHD, DACVPM, DACVIM College of Veterinary Medicine, Purdue University, West Lafayette, IN

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Bratislava has been associated with clinical disease in pigs (in the US and Europe) and in horses (in Europe), but Autumnalis has not been isolated from livestock or companion animals in the US. Positive titers to Autumnalis should be interpreted as a cross-reaction from another serovar. 3 Clinical signs in dogs are usually attributable to localization of infection to the renal, hepatic, or vascular system. Clinical findings can be quite varied in severity, ranging from acute oliguric renal failure, renal and hepatic disease, fever of unknown origin (FUO), or even no clinical signs (asymptomatic). A general classification of the frequency of organ involvement in canine leptospirosis, based on clinical and diagnostic findings, is: renal only: 30-50%, renal and hepatic: 25-35%, hepatic only: 10-20%, and other (uveitis, myalgia, FUO): 5-10%. A recently published report also documented fatal septicemia-like disease in dogs less than 1 year old; these dogs died before a positive- MAT response but were positive for Leptospira on special stains of kidney tissue. Some serovars may be more likely to cause disease in certain organs, but there is not consistent evidence to support this perception. 4 Determination of the infective serovar and even clinical diagnosis is hindered by lack of a sensitive, specific, low-cost, rapid and widely available diagnostic test for leptospirosis. Most cases of leptospirosis are diagnosed by serology, and the reference method is the microscopic agglutination test (MAT). The MAT is difficult

to standardize and requires live organisms for antigens. Cross- agglutination is also common. Despite these drawbacks, the MAT is still the diagnostic norm for many laboratories. Clinicians must presume that the serovar with the greatest antibody titer is the infective serovar, although paradoxical reactions to un-infective serovars have been noted. This is believed to occur most commonly early in infection, due to a non-specific IgM response; the MAT primarily measures IgM rather than IgG. Likewise, clinicians are in a quandary when 2 serovars have equal titers as dual infection is probably unlikely. The use of paired sera (2-4 weeks apart) is often required to confirm the diagnosis and clarify the infective serovar. Problematic however is the capability of leptospiral serovars to alter their outer membrane proteins. This is done in the natural host environment in order to reduce the host immune response to the invader. This transformational ability in laboratory-maintained serovars also could reduce the MAT correlation between laboratories and compared to the infective serovar. 5 Newer antibody-directed tests have been developed, including ELISA, immunoblot assay, a dipstick method, and a lateral flow assay. A new lateral flow assay (WITNESS® Lepto Antibody Test Kit by Zoetis), like some other new tests, is a semi-quantitative test using a color-change indicator for detecting a titer. These newer tests generally have higher sensitivity in detecting IgM in the first week of infection, but probably no difference by day 14. Advantage to the newer tests compared to MAT may be lower cost, more rapid test

results, and improved sensitivity early in infection; the disadvantages may include no numerical titer, no indication of infective serovar, and an increased risk of false-positive test results due to previous Leptospira exposures from environment or recent vaccination. 6 PCR of urine and/or blood is also used to diagnose leptospirosis before antibiotic administration (early in infection or hospitalization!), but its use and impact have raised new questions. Although PCR is increasingly available through many laboratories, controlled studies have not defined the correlation between PCR and MAT, using a true “gold standard” in a large number of cases. (continued)

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