Biomedical subjects

W O Johnson

Publications and source records attributed to W O Johnson.

At least 19 recordsLinked to original sources

PubMed2001

Screening without a "gold standard": the Hui-Walter paradigm revisited.

The authors consider screening populations with two screening tests but where a definitive "gold standard" is not readily available. They discuss a recent article in which a Bayesian approach to this problem is developed based on data that are sampled from a single population. It was subsequently pointed out that such inferences will not necessarily be accurate in the sense that standard errors for parameters may not decrease as n increases. This problem will generally occur when the data are insufficient to estimate all of the parameters as is the case when screening a single population with two tests. If both tests are applied to units sampled from two populations, however, this particular difficulty disappears. In this article the authors further examine this issue and develop an approach based on sampling two populations that yields increasingly accurate inferences as the sample size increases.

Bayes Theorem↗

PubMed2001

Selection bias in epidemiological studies of infectious disease using Escherichia coli and avian cellulitis as an example.

In epidemiological studies of infectious disease, researchers often rely on specific cues of the host, such as clinical signs, as surrogate indicators of pathogen presence. A selection bias would manifest if the specific visual cues used in sampling for the pathogen were not representative of the full range of signs caused by the strains of that pathogen. In our molecular epidemiological studies of Escherichia coli associated with avian cellulitis in broilers, we collect carcasses at the processing plant based on visual cues of lesion morphology. Therefore, the objectives of this study were to: (1) explore the potential impacts of selection bias in an application of infectious disease epidemiology, and (2) utilize a validation protocol to assess the potential for selection bias in our molecular epidemiological studies of E. coli and avian cellulitis. In two different trials, E. coli DNA fingerprints were compared between birds that our observers collected and the birds that the observers missed. Using Fisher's exact tests and simulation models, we determined that the isolates collected by the observers were not significantly different from the isolates missed by the observers (P > 0.60 in both trials). Our method of selecting birds suspected of having cellulitis did not significantly bias our inferences about the population of E. coli associated with cellulitis in the flock. We encourage more investigators to critically assess the relationship of the sample to the target population in epidemiological studies of infectious disease.

Animals↗

PubMed2000

Persistence of cellulitis-associated Escherichia coli DNA fingerprints in successive broiler chicken flocks.

Avian cellulitis in broiler chickens is primarily caused by Escherichia coli. Previous research found that the E. coli isolates of cellulitis origin were unique to each ranch, suggesting that these E. coli were endemic within the ranch environment. To test the hypothesis that the E. coli associated with cellulitis are endemic in the litter of the broiler house, we designed a study to determine whether E. coli DNA fingerprints associated with cellulitis persist over successive flocks that are grown in the same house. In addition, we assessed the impact of different cleaning and disinfection strategies on this persistence. Two broiler houses were followed on each of five farms over 3-4 flocks. A total of 353 E. coli isolates from cellulitis lesions were analyzed in this study, and 314 of these isolates (89%) were DNA fingerprinted by PFGE. In each ranch, there were several DNA fingerprint patterns that were present over successive flocks, regardless of the cleaning and disinfection strategy utilized. Isolates persisted as long as 191 days, implying that these E. coli are capable of persisting in the broiler house environment for long periods of time. In addition, these E. coli isolates were associated with cellulitis lesions in successive flocks. Thus, the isolates of E. coli that are associated with cellulitis in broiler chickens appear to be endemic in the litter environment of the broiler house.

Animal Husbandry↗

PubMed2000

Estimation of sensitivity and specificity of diagnostic tests and disease prevalence when the true disease state is unknown.

The performance of a new diagnostic test is frequently evaluated by comparison to a perfect reference test (i.e. a gold standard). In many instances, however, a reference test is less than perfect. In this paper, we review methods for estimation of the accuracy of a diagnostic test when an imperfect reference test with known classification errors is available. Furthermore, we focus our presentation on available methods of estimation of test characteristics when the sensitivity and specificity of both tests are unknown. We present some of the available statistical methods for estimation of the accuracy of diagnostic tests when a reference test does not exist (including maximum likelihood estimation and Bayesian inference). We illustrate the application of the described methods using data from an evaluation of a nested polymerase chain reaction and microscopic examination of kidney imprints for detection of Nucleospora salmonis in rainbow trout.

Algorithms↗

PubMed2000

Log-linear and logistic modeling of dependence among diagnostic tests.

We developed log-linear and logistic-modeling approaches to investigate dependence among diagnostic tests. To illustrate the approaches, we used published data for swine toxoplasmosis, bovine paratuberculosis, and swine brucellosis. These diseases were selected because each animal's true disease status was known, at least five tests were used, and the serologic tests had been previously shown to have moderate-to-high pairwise dependence in test sensitivities (and sometimes in test specificities). Log-linear and logistic modeling yielded similar results for swine toxoplasmosis and swine brucellosis. However, logistic modeling could not be used to investigate test dependence for bovine paratuberculosis because of quasi-separation in the data attributable to two fecal-based tests having specificities of 100%. Findings from our modeling indicated that 3 (modified agglutination, enzyme-linked immunosorbent assay (ELISA), latex agglutination) of 5 serologic tests for toxoplasmosis and 2 (rivanol and particle concentration fluorescence immunoassay) of 6 serologic tests for brucellosis were adequate for diagnosis. For bovine paratuberculosis, both fecal-based tests (Herrold's egg-yolk culture and radiometric culture) and 1 (ELISA) of 3 serologic tests were necessary in serial and parallel testing schemes.

Animals↗

PubMed2000

Mortality and recovery of runt white sturgeon (Acipenser transmontanus) in a commercial farm in California, USA.

We investigated the effect of raising runt white sturgeon (Acipenser transmontanus) separately from dominant fish during the initial stages of grow-out in a commercial farm. Runt fish are poor-growers, have underdeveloped muscle mass, swim slowly and are more-frequently found at the top of the water column. The objective of the study was to describe the mortality and recovery rates (and their determinants) of white-sturgeon runts after separating them from dominant fish. Runt white sturgeon were stocked into twelve 2 m x 2 m rectangular tanks and graded periodically during a follow-up of 46-102 days. Overall mortality rates ranged from 0.3 to 7 dead fish per 1000 sturgeon-days at risk and overall recovery rates from 3.9 to 13.5 recovered fish per 1000 sturgeon-days at risk. Period-specific mortality and recovery rates increased over time. The period-specific mortality rates for all three periods were significantly higher for tanks of runts originating from grow-out tanks with high mortality (p-values: first period = 0.06; second period = 0.09; third period = 0.03), but were similar for tanks of runts of high- and low-mean initial weight. The period-specific recovery rates were significantly higher in runts originating from high-mortality grow-out tanks only for the third period (p = 0.05) but not the first and second periods (p-values = 0.33 and 0.25, respectively). Recovery rates were significantly higher in the higher-mean-weight runts tanks for the first and third period but not for the second (p-values: first period = 0.02; second period = 0.65; third period = 0.06). We concluded that the proportion of runts that recover during a 46-89 day period is substantial (16-58%); therefore, it might be worthwhile growing such fish separately in a fish farm for about three months. Financial analysis showed that this practice was profitable, if the value of white sturgeon fish for the farm exceeded $2.05 per kg.

Animal Diseases↗

PubMed2000

Growth of white sturgeon (Acipenser transmontanus) following recovery from the stunted stage in a commercial farm in California, USA.

Runt white sturgeon (Acipenser transmontanus) develop during grow-out and are characterized by atrophied muscles and decreased growth. Our first objective was to compare the growth (and body condition) of previously-runt white sturgeon after they recovered from the runt state and sturgeon that had never been runts. On 12 occasions, recovered runts and age- and size-matched controls that had never been runts were tagged and put in a tank that already contained fish of similar age and size. Tagged groups were followed for 119-134 days. Median relative growth rates (RGRs) of the recovered runts were significantly (p < or = 0.05) higher than those of the controls in three tanks. Multiple linear regression was used to model final weight as a function of initial weight and status (recovered runt or control). Status was not significantly related (p = 0.71) to final weight, after adjusting for initial weight, "tank" and time of follow-up. Our second objective was to determine factors that influenced the loss of tags by white sturgeon during the follow-up period. Logistic regression analysis indicated that higher initial weight and being a control fish might have been associated with losing both tags. We concluded that once white sturgeon runts recovered and started growing, they grew at least as well as fish that had never been runts.

Animals↗

PubMed2000

Bayesian accelerated failure time analysis with application to veterinary epidemiology.

Standard methods for analysing survival data with covariates rely on asymptotic inferences. Bayesian methods can be performed using simple computations and are applicable for any sample size. We propose a practical method for making prior specifications and discuss a complete Bayesian analysis for parametric accelerated failure time regression models. We emphasize inferences for the survival curve rather than regression coefficients. A key feature of the Bayesian framework is that model comparisons for various choices of baseline distribution are easily handled by the calculation of Bayes factors. Such comparisons between non-nested models are difficult in the frequentist setting. We illustrate diagnostic tools and examine the sensitivity of the Bayesian methods.

Abortion, Veterinary↗

PubMed2000

A statistical model for assessing sample size for bacterial colony selection: a case study of Escherichia coli and avian cellulitis.

A general problem for microbiologists is determining the number of phenotypically similar colonies growing on an agar plate that must be analyzed in order to be confident of identifying all of the different strains present in the sample. If a specified number of colonies is picked from a plate on which the number of unique strains of bacteria is unknown, assigning a probability of correctly identifying all of the strains present on the plate is not a simple task. With Escherichia coli of avian cellulitis origin as a case study, a statistical model was designed that would delineate sample sizes for efficient and consistent identification of all the strains of phenotypically similar bacteria in a clinical sample. This model enables the microbiologist to calculate the probability that all of the strains contained within the sample are correctly identified and to generate probability-based sample sizes for colony identification. The probability of cellulitis lesions containing a single strain of E. coli was 95.4%. If one E. coli strain is observed out of three colonies randomly selected from a future agar plate, the probability is 98.8% that only one strain is on the plate. These results are specific for this cellulitis E. coli scenario. For systems in which the number of bacterial strains per sample is variable, this model provides a quantitative means by which sample sizes can be determined.

Animals↗

PubMed2000

Pooled-sample testing as a herd-screening tool for detection of bovine viral diarrhea virus persistently infected cattle.

The study was conducted to develop methodology for least-cost strategies for using polymerase chain reaction (PCR)/probe testing of pooled blood samples to identify animals in a herd persistently infected with bovine viral diarrhea virus (BVDV). Cost was estimated for 5 protocols using Monte Carlo simulations for herd prevalences of BVDV persistent infection (BVDV-PI) ranging from 0.5% to 3%, assuming a cost for a PCR/probe test of $20. The protocol associated with the least cost per cow involved an initial testing of pools followed by repooling and testing of positive pools. For a herd prevalence of 1%, the least cost per cow was $2.64 (95% prediction interval = $1.72, $3.68), where pool sizes for the initial and repooled testing were 20 and 5 blood samples per pool, respectively. Optimization of the least cost for pooled-sample testing depended on how well a presumed prevalence of BVDV-PI approximated the true prevalence of BVDV infection in the herd. As prevalence increased beyond 3%, the least cost increased, thereby diminishing the competitive benefit of pooled testing. The protocols presented for sample pooling have general application to screening or surveillance using a sensitive diagnostic test to detect very low prevalence diseases or pathogens in flocks or herds.

Animals↗

PubMed2000

Risk factors for outbreaks of disease attributable to white sturgeon iridovirus and white sturgeon herpesvirus-2 at a commercial sturgeon farm.

OBJECTIVE: To determine management, fish, and environmental risk factors for increased mortality and an increased proportion of runts for white sturgeon exposed to white sturgeon iridovirus (WSIV) and white sturgeon herpesvirus-2 (WSHV-2). ANIMALS: White sturgeon in 57 tanks at 1 farm and observations made for fish at another farm. PROCEDURE: A prospective cohort study was conducted. Data on mortality, proportion of runts, and potential risk factors were collected. Five fish from each tank were examined for WSIV and WSHV-2 via inoculation of susceptible cell lines and microscopic examination of stained tissue sections. An ANCOVA was used to evaluate effects of risk factors on mortality and proportion of runts. RESULTS: Major determinants of number of dead fish (natural logarithm [In]-transformed) were spawn, source (90% confidence interval [CI] for regression coefficient, 0.62 to 2.21), and stocking density (90% CI, 0.003 to 0.03). Main predictors of proportion of runts (In-transformed) were spawn, mortality incidence density (90% CI, 0.004 to 0.03), age (90% CI, -0.012 to -0.004), and the difference in weight between the largest and smallest nonrunt fish (90% CI, 0.0002 to 1.24). Additional observations indicated a possible protective effect attributable to previous exposure to the viruses. CONCLUSIONS AND CLINICAL RELEVANCE: Mortality and proportion of runts for white sturgeon after exposure to WSIV and WSHV-2 may be reduced for a farm at which the viruses are endemic by selection of specific broodstock, stocking with fish that survived outbreaks of viral disease, using all-in, all-out production, and decreasing stocking densities.

Animals↗

PubMed1999

Comparison of methods for estimation of individual-level prevalence based on pooled samples.

We review frequentist and Bayesian approaches for estimating animal-level disease prevalence using pooled samples obtained by simple random sampling. We determine the preferred approach for different prevalence scenarios and with varying knowledge about sensitivity and specificity values. When sensitivity and specificity are perfect or known, we can choose between the large-sample theory estimates and the one-to-one relationship exact estimates. When sensitivity and specificity are unknown, we must use large-sample theory estimates or Bayesian methodology (which gives exact estimates). However, when the large-sample theory produces a negative lower confidence limit, we must use one of the exact methods. We compare estimates from each approach using culture results from pools of 20 eggs from three flocks on a California ranch that were producing eggs that were contaminated with Salmonella enteritidis phage type 4.

Animal Diseases↗

PubMed1999

Dual screening.

We discuss the problem of screening a general population for characteristics such as HIV or drug use. Our main approach is Bayesian, which allows for the incorporation of prior information about parameters. In the particular problem we consider, there is currently no information in the data for estimating the sensitivity of the screening test, and consequently, the prevalence of the characteristic among screened negatives cannot be estimated from the collected data alone. Our inferences are straightforward to obtain using Gibbs sampling techniques, and they are valid for large or small samples and for arbitrary prevalence or accuracy of screening tests. We also develop the maximum-likelihood approach using the EM algorithm.

AIDS Serodiagnosis↗

PubMed1998

Evaluation of bluetongue virus diagnostic tests in free-ranging bighorn sheep.

Five bluetongue virus (BTV) diagnostic tests were evaluated for use in free-ranging bighorn sheep. We sampled one bighorn sheep population four times between 1989 and 1995. The tests evaluated included virus isolation (VI), polymerase-chain reaction (PCR), serum neutralization (SN), agar-gel immunodiffusion (AGID), and competitive enzyme-linked immunosorbent assay (c-ELISA). The c-ELISA, AGID and SN tests had high levels of agreement in determining serogroup exposure in bighorn sheep. We used maximum-likelihood algorithms to estimate the parameters of each diagnostic test used. Although the c-ELISA and AGID had high sensitivity and specificity, the SN had perfect specificity but lower apparent sensitivity. Due to the potential of cross-reactions among multiple serotypes, results of the SN must be interpreted with caution when assessing serotype exposure in an area where multiple serotypes are endemic. The PCR assay delineated convalescent antibody titers from more-recent infections, and consequently, was pivotal in distinguishing a different exposure pattern between the bighorn sheep and cattle in an adjacent herd. Based on an increasing seroprevalence (50% to 100%), BTV circulated through this bighorn sheep population between 1989 and 1993. This increase in seroprevalence coincided with a bighorn die-off due to BTV infection in June, 1991. An adjacent cattle herd was sampled in 1995 for comparison. The bighorn sheep and adjacent cattle had different patterns of exposure to BTV between 1994 and 1995. There was no evidence that BTV circulated through the bighorn sheep population from 1994 to 1995. In 1995, seroprevalence to BTV decreased to 72%, none of yearling bighorn was seropositive, and all of the 39 bighorn sheep were PCR-negative. In contrast, all adult cattle were seropositive to BTV by c-ELISA and SN, and 4 of the calves were seropositive; 11 of the 24 cattle were PCR-positive, including all five calves. Overall, the pattern of temporal herd immunity in the bighorn sheep appeared to follow a classic epidemic curve, with the appearance and subsequent disappearance of herd immunity coinciding with the 1991 die-off in this population. As low levels of herd immunity and high proportions of susceptible animals are key factors in the development of epidemics, this population of bighorn sheep may be at increased risk for a BTV epidemic in the future.

Animals↗

PubMed1991

Factors associated with transmission of bovine leukemia virus by contact in cows on a California dairy.

A prospective study was undertaken on a California dairy from 1984 to 1987 to examine factors associated with contact transmission of bovine leukemia virus in cows. Two approaches were used to model the probability of infection. First, the expected number of new infections per pen-month was assumed to follow a binomial distribution. The probability of infection was modeled, using logistic regression, as a function of prevalence of infection in pen, presence of lactating cows, proportion of pregnant cows, presence of an infected bull, and proportion of infected cows with a lymphocyte count above 10,000 cells/microliters of blood and/or with Mr 24,000 protein (p24) antibodies. The probability of infection was significantly associated with the prevalence of infection and at the limit of significance for presence of lactating cows in pen. Second, the Cox model with time-dependent covariates was used to analyze time from first parturition or from the beginning of the study to infection. Factors examined were age, breed, lactation number, whether the cow was pregnant and/or lactating, prevalence of infection, presence of an infected bull, and density of cattle in the pen holding the cow. Non-pregnant cows were 2.9 times more at risk of infection than were pregnant cows, and risk of infection significantly increased as prevalence of infection in a pen increased.

Animals↗

PubMed1991

Factors associated with in utero or periparturient transmission of bovine leukemia virus in calves on a California dairy.

A three-year prospective study involving 143 calves born from infected cows was undertaken on a California dairy to evaluate possible factors of the dam associated with bovine leukemia virus infection in utero or during the periparturient period. In utero or periparturient infection occurred at a rate of 4.8% and was more likely in calves born to cows with an average peripheral blood lymphocyte count during pregnancy greater than 12,000 cells/microL (p = 0.043) or in calves born to cows that developed malignant lymphoma (p = 0.00004), but not in calves born to cows with p-24 antibodies (p = 0.675).

Animals↗

PubMed1990

Effect of brucellosis vaccination and dehorning on transmission of bovine leukemia virus in heifers on a California dairy.

Brucellosis vaccination and dehorning were examined for an association with bovine leukemia virus (BLV) infection in heifers on a California dairy between April 1984 and June 1987. Between December 1985 and June 1986, weaned heifers were dehorned using the gouge method at the time of brucellosis vaccination. Using logistic regression, the estimated probability for a nondehorned heifer to seroconvert within three months after brucellosis vaccination (0.08) was significantly less than that for heifers dehorned after a noninfected heifer (0.46) or than that for heifers dehorned after an infected heifer (0.85) (p = 0.039 and p less than 0.001, respectively). To evaluate risk of transmission by brucellosis vaccination, which was usually done within one month postweaning, cumulative proportions of heifers remaining uninfected were computed among heifers that did not seroconvert three months after dehorning. Because results of a Cox model analysis indicated that groups of heifers were 6.6 times more at risk of becoming infected if placed in pens holding gouge-dehorned heifers (where prevalence varied between 50 and 70%) (p less than 0.001) than other groups placed in pens without gouge-dehorned heifers (where prevalence varied between 10 and 30%), cumulative proportions of heifers remaining uninfected were computed for each type of group. The cumulative proportion of heifers remaining uninfected from weaning to first calving was 0.60 for the high prevalence group and 0.96 for the low prevalence group. No change in slope of cumulative proportions was observed before and after one month postweaning, suggesting that brucellosis vaccination was not an effective means of transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Regression models for time to seroconversion following experimental bovine leukaemia virus infection.

This paper develops a parametric model for time to seroconversion after experimental bovine leukaemia virus (BLV) infection, and examines the effects of inoculation route, volume of inoculum, type of inoculation material, and antigen status of donor on seroconversion time. We used parametric and nonparametric statistical methodology to analyse interval data on 150 animals from 13 published reports. The log-logistic model fitted the observed times to seroconversion better than the log-normal or Weibull models, which were the considered alternatives.

Animals↗