Biomedical subjects

Ian A Gardner

Publications and source records attributed to Ian A Gardner.

At least 19 recordsLinked to original sources

PubMed2006

Sample size calculations for disease freedom and prevalence estimation surveys.

We developed a Bayesian approach to sample size calculations for studies designed to estimate disease prevalence that uses a hierarchical model for estimating the proportion of infected clusters (cluster-level prevalence) within a country or region. The clusters may, for instance, be villages within a region, cities within a state, or herds within a country. Our model allows for clusters with zero prevalence and for variability in prevalences among infected clusters. Moreover, uncertainty about diagnostic test accuracy and within-cluster prevalences is accounted for in the model. A predictive approach is used to address the issue of sample size selection in human and animal health surveys. We present sample size calculations for surveys designed to substantiate freedom of a region from an infectious agent (disease freedom surveys) and for surveys designed to estimate cluster-level prevalence of an endemic disease (prevalence estimation surveys). In disease freedom surveys, for instance, assuming the cluster-level prevalence for a particular infectious agent in the region is greater than a maximum acceptable threshold, a sample size combination consisting of the number of clusters sampled and number of subjects sampled per cluster can be determined for which authorities conducting the survey detect this excessive cluster-level prevalence with high predictive probability. The method is straightforward to implement using the Splus/R library emBedBUGS together with WinBUGS.

Animals↗

PubMed2006

Sensitivity and specificity of the agar-gel-immunodiffusion test, ELISA and the skin test for detection of paratuberculosis in United States Midwest sheep populations.

Our objective was to estimate the sensitivity and specificity of the agar-gel-immunodiffusion test (AGID), the ELISA, and the skin test for the detection of Mycobacterium avium subspecies paratuberculosis (MAP) in sheep using Bayesian methods without a gold standard. Fourteen flocks (2 465 sheep) were used. Five flocks (450 sheep) were considered MAP non-infected and 9 flocks (2 015 sheep) had sheep infected with MAP. Sheep were skin tested and blood was collected for AGID and ELISA testing. Results were analyzed using a Bayesian 3-test in 1-population model fitted in WinBUGS. The model allowed for dependence (correlation) between the two serologic tests, but these two tests were assumed to be conditionally independent of the skin test. The estimated specificity was 99.5% (95% PI of 98.9-99.9%) for the AGID; 99.3% (98.4-99.8%) for the ELISA using an optical density measured cutoff of 0.20; 99.2% (98.1-99.8%) using a cutoff of 0.15; 97.5% (95.8-98.7%) using a cutoff of 0.10; and 98.7% (97.3-99.5%) for the skin test. The estimated sensitivities were 8.3% (6.2-10.7%) for the AGID; 8.0% (6.0-10.4%), 10.6% (8.3-13.1%), and 16.3% (13.5-19.4%) for the ELISA using the cutoffs 0.20, 0.15, and 0.10 respectively; and 73.3% (62.3-85.8%) for the skin test. The skin test was specific in non-infected populations and sensitive in infected populations, although in some cases a positive skin test might represent MAP exposure rather than infection. The AGID and ELISA were specific but lacked sensitivity. The AGID and ELISA consistently identified two different populations of infected sheep with only moderate overlap between positive test results.

Animals↗

PubMed2006

Receiver-operating characteristic curves and likelihood ratios: improvements over traditional methods for the evaluation and application of veterinary clinical pathology tests.

Receiver-operating characteristic (ROC) curves provide a cutoff-independent method for the evaluation of continuous or ordinal tests used in clinical pathology laboratories. The area under the curve is a useful overall measure of test accuracy and can be used to compare different tests (or different equipment) used by the same tester, as well as the accuracy of different diagnosticians that use the same test material. To date, ROC analysis has not been widely used in veterinary clinical pathology studies, although it should be considered a useful complement to estimates of sensitivity and specificity in test evaluation studies. In addition, calculation of likelihood ratios can potentially improve the clinical utility of such studies because likelihood ratios provide an indication of how the post-test probability changes as a function of the magnitude of the test results. For ordinal test results, likelihood ratios can be calculated on a category-specific basis from the empirical data or by using the slope of the line joining adjacent category limits on the ROC curve. For continuous test results, data need to be categorized into intervals for estimation of likelihood ratios, or they can be calculated as the slope (tangent) to the ROC curve at a unique test value. We use ROC analysis and calculate likelihood ratios to evaluate the performance of tests reported in 2 articles previously published in this journal.

Animal Diseases↗

PubMed2006

Evaluation of cost-effectiveness of targeted sampling methods for detection of Mycobacterium avium subsp paratuberculosis infection in dairy herds.

OBJECTIVE: To investigate the epidemiologic and financial impacts of targeted sampling of subpopulations of cows, compared with random sampling of all cows, for classification of dairy herd infection status for paratuberculosis. ANIMALS: All cows from 4 infected herds with a low-to-moderate prevalence of paratuberculosis and from 1 noninfected herd in California. PROCEDURE: The infection status of each cow was classified on the basis of results of an ELISA or combined ELISA and fecal culture results. Thirteen sampling schemes designed to randomly sample cows on the basis of lactation number, stage of lactation, and milk production were evaluated. Sampling without replacement was used to obtain a probability of herd detection of paratuberculosis for each evaluated sampling method and for simulated sample sizes between 30 and 150 cows. Marginal cost-effectiveness analysis was used to determine the cost increase relative to the increase in detection probability. RESULTS: Sampling cows in the third or higher lactation and > or = 200 days into lactation yielded the highest detection probability in most instances, resulting in a detection probability that was 1.4 to 2.5 times that obtained by sampling 30 cows in the second or higher lactation. Costs of testing via the alternative method with a 95% detection probability were approximately dollar 300 lower in a high-prevalence herd (31%) and dollar 800 lower in a low-prevalence herd (9%), compared with use of the reference method. CONCLUSIONS AND CLINICAL RELEVANCE: Detection of herds with paratuberculosis could be improved, and costs of testing substantially reduced by sampling targeted groups of cows.

Animals↗

PubMed2006

Association between findings on palmarodorsal radiographic images and detection of a fracture in the proximal sesamoid bones of forelimbs obtained from cadavers of racing Thoroughbreds.

OBJECTIVE: To determine the distribution for limbs and bones in horses with fractures of the proximal sesamoid bones and relationships with findings on palmarodorsal radiographic images. SAMPLE POPULATION: Proximal sesamoid bones obtained from both forelimbs of cadavers of 328 racing Thoroughbreds. PROCEDURE: Osteophytes; large vascular channels; and fracture location, orientation, configuration, and margin distinctness were categorized by use of high-detail contact palmarodorsal radiographs. Distributions of findings were determined. Relationships between radiographic findings and fracture characteristics were examined by use of chi2 and logistic regression techniques. RESULTS: Fractures were detected in 136 (41.5%) horses. Biaxial fractures were evident in 109 (80%) horses with a fracture. Osteophytes and large vascular channels were evident in 266 (81%) and 325 (99%) horses, respectively. Medial bones typically had complete transverse or split transverse simple fractures, indistinct fracture margins, > 1 vascular channel that was > 1 mm in width, and osteophytes in abaxial wing and basilar middle or basilar abaxial locations. Lateral bones typically had an oblique fracture and distinct fracture margins. Odds of proximal sesamoid bone fracture were approximately 2 to 5 times higher in bones without radiographic evidence of osteophytes or large vascular channels, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Biaxial fractures of proximal sesamoid bones were common in cadavers of racing Thoroughbreds. Differences between medial and lateral bones for characteristics associated with fracture may relate to differences in fracture pathogeneses for these bones. Osteophytes and vascular channels were common findings; however, fractures were less likely to occur in bones with these features.

Age Distribution↗

PubMed2006

Indirect fluorescent antibody testing of cerebrospinal fluid for diagnosis of equine protozoal myeloencephalitis.

OBJECTIVE: To assess the use of CSF testing with an indirect fluorescent antibody test (IFAT) for diagnosis of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona. SAMPLE POPULATION: Test results of 428 serum and 355 CSF samples from 182 naturally exposed, experimentally infected, or vaccinated horses. PROCEDURE: EPM was diagnosed on the basis of histologic examination of the CNS. Probability distributions were fitted to serum IFAT results in the EPM+ and EPM-horses, and correlation between serum and CSF results was modeled. Pairs of serum-CSF titers were generated by simulation, and titer-specific likelihood ratios and post-test probabilities of EPM at various pretest probability values were estimated. Post-test probabilities were compared for use of a serum-CSF test combination, a serum test only, and a CSF test only. RESULTS: Post-test probabilities of EPM increased as IFAT serum and CSF titers increased. Post-test probability differences for use of a serum-CSF combination and a serum test only were < or = 19% in 95% of simulations. The largest increases occurred when serum titers were from 40 to 160 and pre-test probabilities were from 5% to 60%. In all simulations, the difference between pre- and post-test probabilities was greater for a CSF test only, compared with a serum test only. CONCLUSIONS AND CLINICAL RELEVANCE: CSF testing after a serum test has limited usefulness in the diagnosis of EPM. A CSF test alone might be used when CSF is required for other procedures. Ruling out other causes of neurologic disease reduces the necessity of additional EPM testing.

Animals↗

PubMed2005

Sample size determination for estimation of the accuracy of two conditionally independent tests in the absence of a gold standard.

We developed an Excel spreadsheet template (available at http://www.epi.ucdavis.edu/diagnostictests/) to calculate sample sizes to estimate sensitivity and specificity with desired precision in the absence of a gold standard. Calculations are predicated on the use of two conditionally independent tests for screening animals from two populations and are based on the methods of Hui and Walter(1980). Sample size calculations rely on asymptotic normality of maximum likelihood (ML) estimates of parameters. Spreadsheets for calculating standard errors for the parameter estimates and for providing ML estimates using cross-tabulated data also are included. An example of application of the methods to bovine paratuberculosis is presented.

Animals↗

PubMed2005

Evaluation of methods for improved detection of Cryptosporidium spp. in mussels (Mytilus californianus).

Bivalve molluscs concentrate Cryptosporidium oocysts from fecal-contaminated aquatic environments and are therefore useful in monitoring water quality. A real-time TaqMan polymerase chain reaction (PCR) system was developed to allow for large scale quantitative detection of Cryptosporidium spp. in mussels (Mytilus californianus). The TaqMan sensitivity and specificity were compared to conventional PCR and direct immunofluorescent antibody (DFA) assays, with and without immunomagnetic separation (IMS), to identify the best method for parasite detection in mussel hemolymph, gill washings and digestive glands. TaqMan PCR and two conventional PCR systems all detected 1 or more oocysts spiked into 1 ml hemolymph samples. The minimum oocyst detection limit in spiked 5 ml gill wash and 1 g digestive gland samples tested by TaqMan PCR and DFA was 100 oocysts, with a 1 log(10) improvement when samples were first processed by IMS. For tank exposed mussels, TaqMan and conventional PCR methods detected C. parvum in <5% of hemolymph samples. No gill washings from these same mussels tested positive by TaqMan PCR or DFA analysis even with IMS concentration. All methods detected the highest prevalence of C. parvum-positive samples in digestive gland tissues of exposed mussels. In conclusion, the most sensitive method for the detection of C. parvum in oocyst-exposed mussels was IMS concentration with DFA detection: 80% of individual and 100% of pooled digestive gland samples tested positive. TaqMan PCR was comparable to conventional PCR for detection of C. parvum oocysts in mussels and additionally allowed for automated testing, high throughput, and semi-quantitative results.

Animals↗

PubMed2005

Factor analysis of a Johne's disease risk assessment questionnaire with evaluation of factor scores and a subset of original questions as predictors of observed clinical paratuberculosis.

Factor analysis was used to examine the interrelationships among 38 variables collected as part of a Johne's disease risk assessment questionnaire completed in 2002 on 815 U.S. dairy operations. Eleven factors were extracted, accounting for two-thirds of the variance encountered in the original variables. Responses to many of the risk assessment questions were closely related. Standardized scores on the 11 factors were calculated for operations providing complete information, and were evaluated as predictors in a model-based logistic regression analysis with the outcome being whether operations had observed one or more cows with clinical signs suggestive of paratuberculosis during the previous year. A logistic regression model was also used to evaluate the predictive ability of a reduced subset of approximately one-third of the original variables that was selected to represent the derived factors. The performance of both sets of predictors was comparable with respect to goodness-of-fit and predictive ability. In conclusion, the length of the current risk assessment instrument could be reduced considerably without a substantial loss of information by removing or combining questions that are strongly correlated.

Animals↗

PubMed2005

Fecal shedding of Mycobacterium avium subsp. paratuberculosis by dairy cows.

Between 1982 and 2000, fecal samples were obtained from 786 cows that were shedding Mycobacterium avium subsp. paratuberculosis (Map). These cows were resident on 93 Pennsylvania dairies (mean herd size, 64 milk cows) that had no or minimal previous testing for Map. Feces were cultured on four tubes of Herrold's egg yolk medium and the distribution of mean Map colony forming units (CFU) was evaluated. Most cows were light (< 10 CFU/tube, 51.4%) or high (> 50 CFU/tube, 30.8%) fecal shedders with fewer cows in the moderate category (10-50 CFU/tube). Of the 786 cows, 192 (24.4%) had colonies in only one of four tubes. In the multivariable negative binomial model, there were significant associations between mean CFU/tube and prevalence, herd size, and season and an interaction between herd size and season. The linear mixed model of continuous tube counts with a random herd effect yielded similar findings with associations with herd size as a continuous variable, season, and an interaction between categorized prevalence and continuous herd size. Variability in CFU/tube was greatest among cows in the same herd, intermediate for replicate tubes from the same cow, and smallest among cows in different herds. Reduction in the number of replicate tubes from four would have reduced the sensitivity of fecal culture for Map by approximately 6% (for three tubes) to 12% (for two tubes).

Animals↗

PubMed2005

Immune responses during pregnancy in heifers naturally infected with Neospora caninum with and without immunization.

This study was designed to identify changes in parasite-specific immune responses that occur during vertical transmission of Neospora caninum and can be used as indicators of parasite reactivation in naturally infected heifers. Ten heifers were unimmunized and 11 immunized with killed tachyzoites. One unimmunized heifer, which aborted at week 19 of gestation, had an increase in parasite-specific antibodies, mainly IgG(2), from week 15 to week 19 and a concomitant decline in parasite-specific cell-mediated immune (CMI) responses. Eight unimmunized heifers, which had live full-term congenitally infected calves, had an increase in antibodies, mainly IgG(2), from week 21 onwards. All immunized heifers delivered live full-term congenitally infected calves, and had a bimodal increase in antibodies; primarily IgG(1) following immunization and predominantly IgG(2) from week 17 onwards. Immunized heifers had significantly greater overall mean humoral and CMI responses than unimmunized heifers. Nine uninfected control heifers and their calves were seronegative. These results indicate that reactivation of a latent infection occurred in the naturally infected heifers, regardless of their immunization status, and was associated with increased parasite-specific antibodies, mainly IgG(2).

Abortion, Veterinary↗

PubMed2005

Clams (Corbicula fluminea) as bioindicators of fecal contamination with Cryptosporidium and Giardia spp. in freshwater ecosystems in California.

This study evaluated clams as bioindicators of fecal protozoan contamination using three approaches: (i) clam tissue spiking experiments to compare several detection techniques; (ii) clam tank exposure experiments to evaluate clams that had filtered Cryptosporidium oocysts from inoculated water under a range of simulated environmental conditions; (iii) sentinel clam outplanting to assess the distribution and magnitude of fecal contamination in three riverine systems in California. Our spiking and tank experiments showed that direct fluorescent antibody (DFA), immunomagnetic separation (IMS) in combination with DFA, and PCR techniques could be used to detect Cryptosporidium in clam tissues. The most analytically sensitive technique was IMS concentration with DFA detection of oocysts in clam digestive gland tissues, which detected 10 oocysts spiked into a clam digestive gland 83% of the time. In the tank experiment, oocyst dose and clam collection time were significant predictors for detecting Cryptosporidium parvum oocysts in clams. In the wild clam study, Cryptosporidium and Giardia were detected in clams from all three study regions by IMS-DFA analysis of clam digestive glands, with significant variation by sampling year and season. The presence of C. parvum DNA in clams from riverine ecosystems was confirmed with PCR and DNA sequence analysis.

Animals↗

PubMed2004

Probability of introduction of exotic strains of bluetongue virus into the US and into California through importation of infected cattle.

Strategies designed to minimize the probability of bluetongue virus (BTV) introduction to new areas should be based on a quantitative assessment of the probability of actually establishing the virus once it is introduced. The risk of introducing a new strain of bluetongue virus into a region depends on the number of viremic animals that enter and the competency of local vectors to transmit the virus. We used Monte Carlo simulation to model the probability of introducing BTV into California, USA, and the US through importation of cattle. Records of cattle and calf imports into California and the US were obtained, as was seroprevalence information from the exporting countries. A simulation model was constructed to evaluate the probability of importing either a viremic PCR-negative animal after 14-day quarantine, a c-ELISA BTV-antibody-negative animal after 28-day quarantine, or an untested viremic animal after 100-day quarantine into California and into the US. We found that for animals imported to the US, the simulated (best to worst scenarios) median percentage that tested positive for BTV-antibody ranged from 5.4 to 7.2%, while for the subset imported to California, the simulated median percentage that tested positive for BTV-antibody ranged from 20.9 to 78.9%. Using PCR, for animals imported to the US these values were 71.8-85.3%, and for those imported to California, the simulated median that test positive ranged from 74.3 to 92.4%. The probability that an imported animal was BTV-viremic is very low regardless of the scenario selected (median probability=0.0%). The probability of introducing an exotic strain of BTV into California or the US by importing infected cattle was remote, and the current Office International des Epizooties (OIE) recommendation of either a final PCR test performed 14 days after entry into quarantine, a c-ELISA performed 28 days after entry into quarantine or a 100-day quarantine with no testing requirement was adequate to protect cattle in the US and California from an exotic strain of BTV.

Animals↗

PubMed2004

Diagnostic test accuracy and prevalence inferences based on joint and sequential testing with finite population sampling.

The two-test two-population model, originally formulated by Hui and Walter, for estimation of test accuracy and prevalence estimation assumes conditionally independent tests, constant accuracy across populations and binomial sampling. The binomial assumption is incorrect if all individuals in a population e.g. child-care centre, village in Africa, or a cattle herd are sampled or if the sample size is large relative to population size. In this paper, we develop statistical methods for evaluating diagnostic test accuracy and prevalence estimation based on finite sample data in the absence of a gold standard. Moreover, two tests are often applied simultaneously for the purpose of obtaining a 'joint' testing strategy that has either higher overall sensitivity or specificity than either of the two tests considered singly. Sequential versions of such strategies are often applied in order to reduce the cost of testing. We thus discuss joint (simultaneous and sequential) testing strategies and inference for them. Using the developed methods, we analyse two real and one simulated data sets, and we compare 'hypergeometric' and 'binomial-based' inferences. Our findings indicate that the posterior standard deviations for prevalence (but not sensitivity and specificity) based on finite population sampling tend to be smaller than their counterparts for infinite population sampling. Finally, we make recommendations about how small the sample size should be relative to the population size to warrant use of the binomial model for prevalence estimation.

Agglutination Tests↗

PubMed2004

Modelling risk when binary outcomes are subject to error.

We present methods for binomial regression when the outcome is determined using the results of a single diagnostic test with imperfect sensitivity and specificity. We present our model, illustrate it with the analysis of real data, and provide an example of WinBUGS program code for performing such an analysis. Conditional means priors are used in order to allow for inclusion of prior data and expert opinion in the estimation of odds ratios, probabilities, risk ratios, risk differences, and diagnostic test sensitivity and specificity. A simple method of obtaining Bayes factors for link selection is presented. Methods are illustrated and compared with Bayesian ordinary binary regression using data from a study of the effectiveness of a smoking cessation program among pregnant women. Regression coefficient estimates are shown to change noticeably when expert prior knowledge and imperfect sensitivity and specificity are incorporated into the model.

Adult↗

PubMed2004

Prevalence of antibodies against Saint Louis encephalitis and Jamestown Canyon viruses in California horses.

Jamestown Canyon (JC) and Saint Louis encephalitis (SLE) viruses are mosquito-transmitted viruses that have long been present in California. The objective of this study was to determine the seroprevalence of these two viruses in horses prior to the introduction of West Nile (WN) virus. Approximately 15% of serum samples collected in 1998 from 425 horses on 44 equine operations horses throughout California had serum antibodies to JC virus, whereas antibodies were not detected to SLE virus. The results indicate that horses in California were commonly infected prior to 1998 with mosquito-transmitted Bunyaviruses that are identical or closely related to JC virus, but not with SLE virus. The different seroprevalence of SLE and JC viruses in horses likely reflects the unique ecology of each virus, and it is predicted that WN virus will have a wider distribution in California than closely related SLE virus.

Animals↗

PubMed2004

Sample size calculations for surveys to substantiate freedom of populations from infectious agents.

We develop a Bayesian approach to sample size computations for surveys designed to provide evidence of freedom from a disease or from an infectious agent. A population is considered "disease-free" when the prevalence or probability of disease is less than some threshold value. Prior distributions are specified for diagnostic test sensitivity and specificity and we test the null hypothesis that the prevalence is below the threshold. Sample size computations are developed using hypergeometric sampling for finite populations and binomial sampling for infinite populations. A normal approximation is also developed. Our procedures are compared with the frequentist methods of Cameron and Baldock (1998a, Preventive Veterinary Medicine34, 1-17.) using an example of foot-and-mouth disease. User-friendly programs for sample size calculation and analysis of survey data are available at http://www.epi.ucdavis.edu/diagnostictests/.

Animals↗

PubMed2004

Effects of prevalence and testing by enzyme-linked immunosorbent assay and fecal culture on the risk of introduction of Mycobacterium avium subsp. paratuberculosis-infected cows into dairy herds.

A stochastic simulation model was developed to assess the risk of introduction of Mycobacterium avium subsp. paratuberculosis infection into a dairy herd through purchase of female replacement cattle. The effects of infection prevalence in the source herd(s), number of females purchased, and testing by enzyme-linked immunosorbent assay (ELISA) alone or ELISA and fecal culture as risk mitigation strategies were evaluated. Decisions about negative test results were made on a lot and individual basis. A hypothetical dairy herd, free from M. a. paratuberculosis, which replaced 1 lot (10, 30, or 100) of cows per year, was considered. Probability distributions were specified for the sensitivities and specificities of ELISA and fecal culture, the proportion of infected herds and within-herd prevalence for randomly selected replacement source herds (high prevalence) and herds in level 2 (medium prevalence) and level 3 (low prevalence) of the Voluntary Johne's Disease Herd Status Program (VJDHSP). Simulation results predicted that 1-56% of the lots had at least 1 M. a. paratuberculosis-infected cow. Assuming that ELISA sensitivity was 25%, simulation results showed on a lot basis that between 0.4% and 18% and between 0.1% and 9% were predicted to have at least 1 infected cow not detected by ELISA and by a combination of ELISA and fecal culture, respectively. On an individual cow basis, between 0.1% and 8.3% of ELISA-negative cattle in ELISA-positive lots were estimated to be infected. In both the lot and individual analyses, the probability of nondetection increased with larger lot sizes and greater prevalence. Sensitivity analysis indicated that the effect of a lower ELISA sensitivity (10%) was a variable decrease in mean detection probabilities for all combinations of prevalence and lot size. The benefit of testing introduced cattle with ELISA alone or in combination with fecal culture was found to be minimal if cows were purchased from known, low-prevalence (level 3) herds. The value of testing by ELISA alone or in combination with fecal culture was greatest in high-prevalence herds for all lot sizes. Testing of random-source cattle, bought as herd replacements, can partially mitigate the risk of introduction of M. a. paratuberculosis but not as well as by using low-prevalence source herds (level-3 VJDHSP), with or without testing.

Animals↗