Use of machine-learning algorithms to aid in the early detection of leptospirosis in dogs

Leptospirosis is a life-threatening, zoonotic disease with various clinical presentations, including renal injury, hepatic injury, pancreatitis, and pulmonary hemorrhage. With prompt recognition of the disease and treatment, 90% of infected dogs have a positive outcome. Therefore, rapid, early diagnosis of leptospirosis is crucial. Testing for Leptospira-specific serum antibodies using the microscopic agglutination test (MAT) lacks sensitivity early in the disease process, and diagnosis can take >2 wk because of the need to demonstrate a rise in titer. We applied machine-learning algorithms to clinical variables from the first day of hospitalization to create machine-learning prediction models (MLMs). The models incorporated patient signalment, clinicopathologic data (CBC, serum chemistry profile, and urinalysis = blood work [BW] model), with or without a MAT titer obtained at patient intake (=BW + MAT model). The models were trained with data from 91 dogs with confirmed leptospirosis and 322 dogs without leptospirosis. Once trained, the models were tested with a cohort of dogs not included in the model training (9 leptospirosis-positive and 44 leptospirosis-negative dogs), and performance was assessed. Both models predicted leptospirosis in the test set with 100% sensitivity (95% CI: 70.1–100%). Specificity was 90.9% (95% CI: 78.8–96.4%) and 93.2% (95% CI: 81.8–97.7%) for the BW and BW + MAT models, respectively. Our MLMs outperformed traditional acute serologic screening and can provide accurate early screening for the probable diagnosis of leptospirosis in dogs.

[1]  C. Levy,et al.  Clinical, diagnostic, and epidemiological features of a community-wide outbreak of canine leptospirosis in a low-prevalence region (Maricopa County, Arizona). , 2021, Journal of the American Veterinary Medical Association.

[2]  J. Wagenaar,et al.  Leptospira infection and shedding in dogs in Thailand , 2020, BMC Veterinary Research.

[3]  K. Gruszynski,et al.  Leptospiral shedding and seropositivity in shelter dogs in the Cumberland Gap Region of Southeastern Appalachia , 2020, PloS one.

[4]  J. Weese,et al.  A cross-sectional study of environmental, dog, and human-related risk factors for positive canine leptospirosis PCR test results in the United States, 2009 to 2016 , 2019, BMC Veterinary Research.

[5]  A. Hoffmaster,et al.  Rapid, actionable diagnosis of urban epidemic leptospirosis using a pathogenic Leptospira lipL32-based real-time PCR assay , 2017, PLoS neglected tropical diseases.

[6]  R. Klopfleisch,et al.  Evaluation of clinical, laboratory, imaging findings and outcome in 99 dogs with leptospirosis , 2017, The Journal of small animal practice.

[7]  P. Kass,et al.  Validation of a Clinical Scoring System for Outcome Prediction in Dogs with Acute Kidney Injury Managed by Hemodialysis , 2016, Journal of veterinary internal medicine.

[8]  K. Hartmann,et al.  Urinary shedding of leptospires and presence of Leptospira antibodies in healthy dogs from Upper Bavaria. , 2016, Berliner und Munchener tierarztliche Wochenschrift.

[9]  C. Goarant,et al.  Though not Reservoirs, Dogs might Transmit Leptospira in New Caledonia , 2014, International journal of environmental research and public health.

[10]  M. Lappin,et al.  Vaccine‐Associated Leptospira Antibodies in Client‐Owned Dogs , 2014, Journal of veterinary internal medicine.

[11]  G. Moore,et al.  Regional and Temporal Variations of Leptospira Seropositivity in Dogs in the United States, 2000–2010 , 2014, Journal of veterinary internal medicine.

[12]  M. Littman,et al.  Clinicopathologic and atypical features of naturally occurring leptospirosis in dogs: 51 cases (2000-2010). , 2013, Journal of the American Veterinary Medical Association.

[13]  T. Francey,et al.  Evaluation of the diagnostic value of serologic microagglutination testing and a polymerase chain reaction assay for diagnosis of acute leptospirosis in dogs in a referral center. , 2013, Journal of the American Veterinary Medical Association.

[14]  D. Philpott,et al.  Downregulation of the Na/K-ATPase Pump by Leptospiral Glycolipoprotein Activates the NLRP3 Inflammasome , 2012, The Journal of Immunology.

[15]  T. Seemann,et al.  Pathogenesis of leptospirosis: the influence of genomics. , 2011, Veterinary microbiology.

[16]  K. Hartmann,et al.  2010 ACVIM Small Animal Consensus Statement on Leptospirosis: Diagnosis, Epidemiology, Treatment, and Prevention , 2011, Journal of veterinary internal medicine.

[17]  G. Moore,et al.  Detection of antibodies against Leptospira serovars via microscopic agglutination tests in dogs in the United States, 2000-2007. , 2010, Journal of the American Veterinary Medical Association.

[18]  J. Nally,et al.  Detection and quantification of leptospires in urine of dogs: a maintenance host for the zoonotic disease leptospirosis , 2010, European Journal of Clinical Microbiology & Infectious Diseases.

[19]  M. Picardeau,et al.  A century of Leptospira strain typing. , 2009, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[20]  P. Kass,et al.  A novel clinical scoring system for outcome prediction in dogs with acute kidney injury managed by hemodialysis. , 2008, Journal of veterinary internal medicine.

[21]  J. Kaneene,et al.  Prevalence of serum antibodies against six Leptospira serovars in healthy dogs. , 2007, Journal of the American Veterinary Medical Association.

[22]  C. Greene,et al.  Canine leptospirosis infections - clinical signs and outcome with different suspected Leptospira serogroups (42 cases). , 2007, The Journal of small animal practice.

[23]  F. Dondi,et al.  Clinicopathologic features and outcome predictors of Leptospira interrogans Australis serogroup infection in dogs: a retrospective study of 20 cases (2001-2004). , 2007, Journal of veterinary internal medicine.

[24]  H. Erb,et al.  Influence of infecting serogroup on clinical features of leptospirosis in dogs. , 2006, Journal of veterinary internal medicine.

[25]  D. Aucoin,et al.  Canine Leptospirosis, United States, 2002–2004 , 2006, Emerging infectious diseases.

[26]  M. Chengappa,et al.  Comparison of polymerase chain reaction assay, bacteriologic culture, and serologic testing in assessment of prevalence of urinary shedding of leptospires in dogs. , 2003, Journal of the American Veterinary Medical Association.

[27]  L. Cowgill,et al.  Treatment and outcome of dogs with leptospirosis: 36 cases (1990-1998). , 2000, Journal of the American Veterinary Medical Association.

[28]  J. Randolph,et al.  Naturally acquired leptospirosis in 36 dogs: serological and clinicopathological features. , 1998, The Journal of small animal practice.

[29]  P. Brown,et al.  Evaluation of the polymerase chain reaction for early diagnosis of leptospirosis. , 1995, Journal of medical microbiology.

[30]  A. Doucet,et al.  Inhibition of Na,K-ATPase by an endotoxin extracted from Leptospira interrogans: a possible mechanism for the physiopathology of leptospirosis. , 1995, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[31]  Bernhard E. Boser,et al.  A training algorithm for optimal margin classifiers , 1992, COLT '92.

[32]  A. Thiermann Incidence of leptospirosis in the detroit rat population. , 1977, The American journal of tropical medicine and hygiene.

[33]  W. Schulze The Diagnosis of Leptospirosis in Dogs. , 1951 .

[34]  B. Eddie,et al.  Canine Leptospirosis in the United States. , 1939 .