Syndromic surveillance using veterinary laboratory data: algorithm combination and customization of alerts.

BACKGROUND: Syndromic surveillance research has focused on two main themes: the search for data sources that can provide early disease detection; and the development of efficient algorithms that can detect potential outbreak signals. METHODS: This work combines three algorithms that have demonstrated solid performance in detecting simulated outbreak signals of varying shapes in time series of laboratory submissions counts. These are: the Shewhart control charts designed to detect sudden spikes in counts; the EWMA control charts developed to detect slow increasing outbreaks; and the Holt-Winters exponential smoothing, which can explicitly account for temporal effects in the data stream monitored. A scoring system to detect and report alarms using these algorithms in a complementary way is proposed. RESULTS: The use of multiple algorithms in parallel resulted in increased system sensitivity. Specificity was decreased in simulated data, but the number of false alarms per year when the approach was applied to real data was considered manageable (between 1 and 3 per year for each of ten syndromic groups monitored). The automated implementation of this approach, including a method for on-line filtering of potential outbreak signals is described. CONCLUSION: The developed system provides high sensitivity for detection of potential outbreak signals while also providing robustness and flexibility in establishing what signals constitute an alarm. This flexibility allows an analyst to customize the system for different syndromes.

Syndromic surveillance using veterinary laboratory data: data pre-processing and algorithm performance evaluation.

Diagnostic test orders to an animal laboratory were explored as a data source for monitoring trends in the incidence of clinical syndromes in cattle. Four years of real data and over 200 simulated outbreak signals were used to compare pre-processing methods that could remove temporal effects in the data, as well as temporal aberration detection algorithms that provided high sensitivity and specificity. Weekly differencing demonstrated solid performance in removing day-of-week effects, even in series with low daily counts. For aberration detection, the results indicated that no single algorithm showed performance superior to all others across the range of outbreak scenarios simulated. Exponentially weighted moving average charts and Holt-Winters exponential smoothing demonstrated complementary performance, with the latter offering an automated method to adjust to changes in the time series that will likely occur in the future. Shewhart charts provided lower sensitivity but earlier detection in some scenarios. Cumulative sum charts did not appear to add value to the system; however, the poor performance of this algorithm was attributed to characteristics of the data monitored. These findings indicate that automated monitoring aimed at early detection of temporal aberrations will likely be most effective when a range of algorithms are implemented in parallel.

Exploratory analysis of methods for automated classification of laboratory test orders into syndromic groups in veterinary medicine.

BACKGROUND: Recent focus on earlier detection of pathogen introduction in human and animal populations has led to the development of surveillance systems based on automated monitoring of health data. Real- or near real-time monitoring of pre-diagnostic data requires automated classification of records into syndromes--syndromic surveillance--using algorithms that incorporate medical knowledge in a reliable and efficient way, while remaining comprehensible to end users. METHODS: This paper describes the application of two of machine learning (Naïve Bayes and Decision Trees) and rule-based methods to extract syndromic information from laboratory test requests submitted to a veterinary diagnostic laboratory. RESULTS: High performance (F1-macro = 0.9995) was achieved through the use of a rule-based syndrome classifier, based on rule induction followed by manual modification during the construction phase, which also resulted in clear interpretability of the resulting classification process. An unmodified rule induction algorithm achieved an F(1-micro) score of 0.979 though this fell to 0.677 when performance for individual classes was averaged in an unweighted manner (F(1-macro)), due to the fact that the algorithm failed to learn 3 of the 16 classes from the training set. Decision Trees showed equal interpretability to the rule-based approaches, but achieved an F(1-micro) score of 0.923 (falling to 0.311 when classes are given equal weight). A Naïve Bayes classifier learned all classes and achieved high performance (F(1-micro)= 0.994 and F(1-macro) = .955), however the classification process is not transparent to the domain experts. CONCLUSION: The use of a manually customised rule set allowed for the development of a system for classification of laboratory tests into syndromic groups with very high performance, and high interpretability by the domain experts. Further research is required to develop internal validation rules in order to establish automated methods to update model rules without user input.

Retrospective time series analysis of veterinary laboratory data: preparing a historical baseline for cluster detection in syndromic surveillance.

The practice of disease surveillance has shifted in the last two decades towards the introduction of systems capable of early detection of disease. Modern biosurveillance systems explore different sources of pre-diagnostic data, such as patient's chief complaint upon emergency visit or laboratory test orders. These sources of data can provide more rapid detection than traditional surveillance based on case confirmation, but are less specific, and therefore their use poses challenges related to the presence of background noise and unlabelled temporal aberrations in historical data. The overall goal of this study was to carry out retrospective analysis using three years of laboratory test submissions to the Animal Health Laboratory in the province of Ontario, Canada, in order to prepare the data for use in syndromic surveillance. Daily cases were grouped into syndromes and counts for each syndrome were monitored on a daily basis when medians were higher than one case per day, and weekly otherwise. Poisson regression accounting for day-of-week and month was able to capture the day-of-week effect with minimal influence from temporal aberrations. Applying Poisson regression in an iterative manner, that removed data points above the predicted 95th percentile of daily counts, allowed for the removal of these aberrations in the absence of labelled outbreaks, while maintaining the day-of-week effect that was present in the original data. This resulted in the construction of time series that represent the baseline patterns over the past three years, free of temporal aberrations. The final method was thus able to remove temporal aberrations while keeping the original explainable effects in the data, did not need a training period free of aberrations, had minimal adjustment to the aberrations present in the raw data, and did not require labelled outbreaks. Moreover, it was readily applicable to the weekly data by substituting Poisson regression with moving 95th percentiles.

Evaluation of experimental impact injury for inducing post-traumatic osteoarthritis in the metacarpophalangeal joints of horses.

OBJECTIVE: To determine whether a single contusive impact injury to the palmar aspect of the metacarpus would progress to post-traumatic osteoarthritis or palmar osteochondral disease in horses. ANIMALS: 12 horses. PROCEDURES: In each horse, an impact injury was created on the palmar aspect of the medial metacarpal condyle of 1 randomly chosen limb with an impactor device under arthroscopic and fluoroscopic guidance. The opposite limb was sham operated as a control. A low to moderate amount of forced exercise was instituted, and horses were evaluated clinically via lameness examinations weekly for 5 months, then biweekly until endpoint, with synovial fluid analysis performed at 0, 1, 2, 3, 4, 6, 8, and 10 months and radiography at baseline and endpoint. Macroscopic examination, micro-CT, and sample collection for cartilage viability and sulfated glycosaminoglycan content, histologic evaluation, immunohistochemical analysis, and fluorochrome analysis were performed following euthanasia at 1 (3 horses), 4 (4), and 8 to 10 (5) months after surgery. RESULTS: There was variability in impact lesion location, depth, and area on macroscopic inspection, but on histologic evaluation, cartilage defects were less variable. Mean sulfated glycosaminoglycan concentration from cartilage at the impact site was significantly lower than that at a similar site in control limbs. Higher concentrations of cartilage oligomeric matrix protein were observed in synovial fluid from impact-injured joints. CONCLUSIONS AND CLINICAL RELEVANCE: The impact injury method caused mild focal osteoarthritic lesions in the metacarpophalangeal joint, but did not progress to palmar osteochondral disease at this site. Repeated injury is probably required for the development of palmar osteochondral disease.

Trends in domestic animal medico-legal pathology cases submitted to a veterinary diagnostic laboratory 1998-2010.

Pathologists at veterinary diagnostic laboratories receive medico-legal cases from a variety of animal species for postmortem examination. A search of computerized records of the Animal Health Laboratory, University of Guelph, Guelph, Ontario, Canada from 1998 to 2010 identified 1706 medicolegal cases. These were categorized according to the history as criminal investigations, anesthetic-related deaths, insurance, litigation, malpractice cases, and regulatory cases. Statistically significant linear trends in the proportion of medicolegal cases for all animals and criminal cases for companion animals were identified over the 12 year period. Companion animals had significantly greater odds of being a medicolegal case in all categories except for insurance and regulatory cases, compared to noncompanion animals. Based on pathology reports for the 271 criminal cases, 43.1% were consistent with neglect, 29.2% were compatible with non-accidental injury, 4.80% were poisonings, 10.7% were deemed to be due to natural disease, and 11.43% were inconclusive.

The emergence of a new strain of porcine circovirus-2 in Ontario and Quebec swine and its association with severe porcine circovirus associated disease--2004-2006.

In the late fall of 2004 more severe lesions of porcine circovirus-2 associated disease (PCVAD) than usual occurred during an outbreak of porcine circovirus-2 (PCV-2) infection in Ontario nursery and grower/finisher pigs. The lesions were of unprecedented severity and included diffuse bronchointerstitial pneumonia, granulomatous enteritis, vasculitis, interstitial nephritis, and new lesions of splenic infarction. Some affected herds had up to 50% mortality. The outbreak correlated with the sudden emergence of a variant PCV-2, with PCR restriction fragment length polymorphism (RFLP) type 321. Phylogenetic comparison of ORF2 sequences and full genome sequences showed the new variant to be different from the previously dominant RFLP type 422 viruses, and similar to viruses that had occurred in France and other European and Asian countries. A subsequent retrospective study showed a statistically significant increase in the frequency of histological lesions in lymph node, spleen, lung, small intestine, colon and kidney, for pigs spontaneously infected with RFLP type 321, compared with the older RFLP type 422 strain. Viral burden, based on IHC staining in lymph node, also showed a statistically significant increase in pigs infected with the newer variant RFLP type 321, compared with the older RFLP type 422 strain. This enhanced virulence in pigs infected with PCV-2 RFLP type 321 strain may be related to the genetic differences in this new strain of PCV-2. This virus is now the dominant strain of PCV-2 virus found in Ontario and Quebec swine.

Diseases and pathogens associated with mortality in Ontario beef feedlots.

This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots.

Naturally occurring Mycoplasma bovis-associated pneumonia and polyarthritis in feedlot beef calves.

Mycoplasma bovis is perceived as an emerging cause of mortality in feedlot beef cattle. This study examined the lesions and infectious agents in naturally occurring M. bovis-associated bronchopneumonia and arthritis and the relationship of this condition with bovine viral diarrhea virus (BVDV) infection. Standardized pathologic, immunohistochemical, and microbiologic investigations were conducted on 99 calves that died or were euthanized within 60 days after arrival in 72 feedlots. Cranioventral bronchopneumonia with multiple foci of caseous necrosis was identified in 54 of 99 calves, including 30 with concurrent fibrinosuppurative bronchopneumonia typical of pneumonic pasteurellosis. Mycoplasma bovis was consistently identified in these lesions by culture and immunohistochemistry, but also commonly in healthy lungs and those with pneumonia of other causes. Focal lesions of coagulation necrosis, typical of pneumonic pasteurellosis, were often infected with both Mannheimia haemolytica and M. bovis. Arthritis was present in 25 of 54 (46%) calves with M. bovis pneumonia, and all calves with arthritis had pneumonia. BVDV infection was more common in calves with lesions of bacterial pneumonia than in those dying of other causes, but BVDV infection was not more common in calves with caseonecrotic bronchopneumonia than those with fibrinosuppurative bronchopneumonia. Retrospective analysis identified cases of M. bovis pneumonia in the early 1980s that had milder lesions than the current cases. The findings suggest that, in at least some calves, M. bovis induces caseonecrotic bronchopneumonia within the lesions of pneumonic pasteurellosis.

Characterization of experimentally induced post-traumatic osteoarthritis in the medial femorotibial joint of horses.

OBJECTIVE: To study osteoarthritis in the equine medial femorotibial (MFT) joint after a single traumatic injury. ANIMALS: 10 mature horses. PROCEDURE: In vitro explant cultures were used to determine injury threshold for stifle joint cartilage. Contusive impacts were applied to the medial femoral condyle (MFC), and horses were followed for 84 (n = 5) and 180 days (5). Synovial fluid samples were collected every 14 days for determination of sulphated glycosaminoglycan (sGAG) concentrations. Radiographic and lameness evaluations were performed. Gross and histologic descriptions, and immunohistochemistry, cartilage sGAG content determination, and cartilage aggregate modulus determination were performed at the MFC impact site (MFCi), MFC nonimpact site (MFCn), and medial tibial plateau (MTP). RESULTS: Synovial fluid sGAG concentration decreased significantly on days 14, 28, 42, and 56 in all horses. Macroscopic and microscopic articular lesions developed within all MFT joints. No radiographic abnormalities were observed. Mild lameness was evident in several horses. No significant differences were found between short-term and longterm cohorts of horses with respect to histologic scores and TUNEL results. On immunohistochemistry, MFCi was positive for COL2-(3/4)C(short). International Cartilage Repair Society scores differed significantly between short-term and long-term cohorts of horses. In all horses, sGAG concentrations were significantly decreased at the MFCi, compared with the MFCn. CONCLUSIONS AND CLINICAL RELEVANCE: Use of contusive impacts on the MFC of horses results in cartilage lesions that are similar to those described clinically, supporting trauma as a contributing factor in the natural pathogenesis of osteoarthritis.