Variation in the assessment of adequacy in cervical smears

OBJECTIVE: To assess the interobserver reproducibility of the diagnosis of 'adequacy' of cervical smears according to the Bethesda System criteria in cervical smears. STUDY DESIGN: 358 cervical smears were obtained from three Italian cytopathological centres in 1998-99. All centres provided consecutively collected smears. The cervical smears were independently and blindly assessed by four cytologists.The screening was performed using a 10x objective and an additional evaluation of the percentage of cellularity was performed using a 4x objective. RESULTS: The proportion of smears assessed by the four cytologists as 'adequate' ranged from 60% to 70%, the proportion of 'satisfactory for evaluation but limited by' ranged from 27% to 38%, and the proportion of 'inadequate smears' ranged from 2% to 4%. Full agreement in the assessment of smear adequacy was observed in 311 slides and disagreement was observed only in 47. The category 'inadequate smear' was less reliable than the other two; however, the kappa value observed was acceptable. CONCLUSION: The present study shows that it is possible to achieve a high reproducibility in the assessment of smear adequacy, at least among expert cytologists who follow the Bethesda System criteria strictly.     

Evolutionary analysis of inter-farm transmission dynamics in a highly pathogenic avian influenza epidemic

Phylogenetic studies have largely contributed to better understand the emergence, spread and evolution of highly pathogenic avian influenza during epidemics, but sampling of genetic data has never been detailed enough to allow mapping of the spatiotemporal spread of avian influenza viruses during a single epidemic. Here, we present genetic data of H7N7 viruses produced from 72% of the poultry farms infected during the 2003 epidemic in the Netherlands. We use phylogenetic analyses to unravel the pathways of virus transmission between farms and between infected areas. In addition, we investigated the evolutionary processes shaping viral genetic diversity, and assess how they could have affected our phylogenetic analyses. Our results show that the H7N7 virus was characterized by a high level of genetic diversity driven mainly by a high neutral substitution rate, purifying selection and limited positive selection. We also identified potential reassortment in the three genes that we have tested, but they had only a limited effect on the resolution of the inter-farm transmission network. Clonal sequencing analyses performed on six farm samples showed that at least one farm sample presented very complex virus diversity and was probably at the origin of chronological anomalies in the transmission network. However, most virus sequences could be grouped within clearly defined and chronologically sound clusters of infection and some likely transmission events between farms located 0.8-13 Km apart were identified. In addition, three farms were found as most likely source of virus introduction in distantly located new areas. These long distance transmission events were likely facilitated by human-mediated transport, underlining the need for strict enforcement of biosafety measures during outbreaks. This study shows that in-depth genetic analysis of virus outbreaks at multiple scales can provide critical information on virus transmission dynamics and can be used to increase our capacity to efficiently control epidemics.     

The EAR Motif Controls the Early Flowering and Senescence Phenotype Mediated by Over-Expression of SlERF36 and Is Partly Responsible for Changes in Stomatal Density and Photosynthesis

The EAR motif is a small seven amino acid motif associated with active repression of several target genes. We had previously identified SlERF36 as an EAR motif containing gene from tomato and shown that its over-expression results in early flowering and senescence and a 25–35% reduction of stomatal density, photosynthesis and stomatal conductance in transgenic tobacco. In order to understand the role of the EAR motif in governing the phenotypes, we have expressed the full-length SlERF36 and a truncated form, lacking the EAR motif under the CaMV35S promoter, in transgenic Arabidopsis. Plants over-expressing the full-length SlERF36 show prominent early flowering under long day as well as short day conditions. The early flowering leads to an earlier onset of senescence in these transgenic plants which in turn reduces vegetative growth, affecting rosette, flower and silique sizes. Stomatal number is reduced by 38–39% while photosynthesis and stomatal conductance decrease by about 30–40%. Transgenic plants over-expressing the truncated version of SlERF36 (lacking the C-terminal EAR motif), show phenotypes largely matching the control with normal flowering and senescence indicating that the early flowering and senescence is governed by the EAR motif. On the other hand, photosynthetic rates and stomatal number were also reduced in plants expressing SlERF36ΔEAR although to a lesser degree compared to the full- length version indicating that these are partly controlled by the EAR motif. These studies show that the major phenotypic changes in plant growth caused by over-expression of SlERF36 are actually mediated by the EAR motif.     

Aboveground nitrogen and phosphorus use by five plantation-grown trees with different leaf longevities

Aboveground nitrogen (N) and phosphorus (P) requirement, retranslocation and use efficiency were determined for 28-year-old red oak (Quercus rubra L.), European larch (Larix decidua Miller), white pine (Pinus strobes L.), red pine (Pinus resinosa Ait.) and Norway spruce (Picea abies (L) Karst.) plantations on a similar soil in southwestern Wisconsin. Annual aboveground N and P requirements (kg/ha/yr) totaled 126 and 13 for red oak, 86 and 9 for European larch, 80 and 9 for white pine, 38 and 6 for red pine, and 81 and 13 for Norway spruce, respectively. Nitrogen and P retranslocation from current foliage ranged from 81 and 72%, respectively, for European larch, whereas red pine retranslocated the smallest amount of N (13%) and Norway spruce retranslocated the smallest amount of P (18%). In three evergreen species, uptake accounted for 72 to 74% of annual N requirement whereas for two deciduous species retranslocation accounted for 76 to 77% of the annual N requirement. Nitrogen and P use (ANPP/uptake) was more efficient in deciduous species than evergreen species. The results from this common garden experiment demonstrate that differences in N and P cycling among species may result from intrinsic characteristics (e.g. leaf longevity) rather than environmental conditions.     

A method for determining weights for excess relative risk and excess absolute risk when applied in the calculation of lifetime risk of cancer from radiation exposure

Radiation-related risks of cancer can be transported from one population to another population at risk, for the purpose of calculating lifetime risks from radiation exposure. Transfer via excess relative risks (ERR) or excess absolute risks (EAR) or a mixture of both (i.e., from the life span study (LSS) of Japanese atomic bomb survivors) has been done in the past based on qualitative weighting. Consequently, the values of the weights applied and the method of application of the weights (i.e., as additive or geometric weighted means) have varied both between reports produced at different times by the same regulatory body and also between reports produced at similar times by different regulatory bodies. Since the gender and age patterns are often markedly different between EAR and ERR models, it is useful to have an evidence-based method for determining the relative goodness of fit of such models to the data. This paper identifies a method, using Akaike model weights, which could aid expert judgment and be applied to help to achieve consistency of approach and quantitative evidence-based results in future health risk assessments. The results of applying this method to recent LSS cancer incidence models are that the relative EAR weighting by cancer solid cancer site, on a scale of 0–1, is zero for breast and colon, 0.02 for all solid, 0.03 for lung, 0.08 for liver, 0.15 for thyroid, 0.18 for bladder and 0.93 for stomach. The EAR weighting for female breast cancer increases from 0 to 0.3, if a generally observed change in the trend between female age-specific breast cancer incidence rates and attained age, associated with menopause, is accounted for in the EAR model. Application of this method to preferred models from a study of multi-model inference from many models fitted to the LSS leukemia mortality data, results in an EAR weighting of 0. From these results it can be seen that lifetime risk transfer is most highly weighted by EAR only for stomach cancer. However, the generalization and interpretation of radiation effect estimates based on the LSS cancer data, when projected to other populations, are particularly uncertain if considerable differences exist between site-specific baseline rates in the LSS and the other populations of interest. Definitive conclusions, regarding the appropriate method for transporting cancer risks, are limited by a lack of knowledge in several areas including unknown factors and uncertainties in biological mechanisms and genetic and environmental risk factors for carcinogenesis; uncertainties in radiation dosimetry; and insufficient statistical power and/or incomplete follow-up in data from radio-epidemiological studies.     

Combining Surveillance Systems: Effective Merging of U.S. Veteran and Military Health Data

Background

The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) had more than 18 million healthcare beneficiaries in 2011. Both Departments conduct individual surveillance for disease events and health threats.

Methods

We performed joint and separate analyses of VA and DoD outpatient visit data from October 2006 through September 2010 to demonstrate geographic and demographic coverage, timeliness of influenza epidemic awareness, and impact on spatial cluster detection achieved from a joint VA and DoD biosurveillance platform.

Results

Although VA coverage is greater, DoD visit volume is comparable or greater. Detection of outbreaks was better in DoD data for 58% and 75% of geographic areas surveyed for seasonal and pandemic influenza, respectively, and better in VA data for 34% and 15%. The VA system tended to alert earlier with a typical H3N2 seasonal influenza affecting older patients, and the DoD performed better during the H1N1 pandemic which affected younger patients more than normal influenza seasons. Retrospective analysis of known outbreaks demonstrated clustering evidence found in separate DoD and VA runs, which persisted with combined data sets.

Conclusion

The analyses demonstrate two complementary surveillance systems with evident benefits for the national health picture. Relative timeliness of reporting could be improved in 92% of geographic areas with access to both systems, and more information provided in areas where only one type of facility exists. Combining DoD and VA data enhances geographic cluster detection capability without loss of sensitivity to events isolated in either population and has a manageable effect on customary alert rates.     

Storage and Flux of Nutrients in a Dry Tropical Forest in India

Storage and flux of N, P, Ca, K and Na were studied in a drytropical forest The nutrient concentrations in different growthforms were in the order herb > shrub > tree, whereas thestanding state of nutrients followed the order tree > shrub> herb The total storage (kg ha^–1) in vegetation amountedto 567 N, 37 P, 278 Ca, 256 K and 46 Na The share of above-groundparts in vegetation storage was 82 % for N, 83 % for P, 76 %for Ca, 85 % for K and 79 % for Na From 56 to 71 % of foliarN, P and K was withdrawn during senescence Nutrient input (kgha^–1 year^–1) from the vegetation (above-ground +below-ground) to forest floor amounted to 115 N, 8 P, 62 Ca,38 K and 10 Na compared to total net annual uptake (kg ha^–1)of 143 N, 10 P, 78 Ca, 52 K and 12 Na, indicating marginal accumulationin the system Fine roots were as important a pathway of nutrientreturn as leaf litter Turnover rate and turnover time for differentnutrients on the forest floor ranged, respectively, between72 and 83 % and 12 and 1 39 years Dry tropical forest, nutnent concentration, standing state, uptake, internal cycling, turnover     

Estimating the disease burden of 2009 pandemic influenza A(H1N1) from surveillance and household surveys in Greece

Background

The aim of this study was to assess the disease burden of the 2009 pandemic influenza A(H1N1) in Greece.

Methodology/Principal Findings

Data on influenza-like illness (ILI), collected through cross-sectional nationwide telephone surveys of 1,000 households in Greece repeated for 25 consecutive weeks, were combined with data from H1N1 virologic surveillance to estimate the incidence and the clinical attack rate (CAR) of influenza A(H1N1). Alternative definitions of ILI (cough or sore throat and fever>38°C [ILI-38] or fever 37.1–38°C [ILI-37]) were used to estimate the number of symptomatic infections. The infection attack rate (IAR) was approximated using estimates from published studies on the frequency of fever in infected individuals. Data on H1N1 morbidity and mortality were used to estimate ICU admission and case fatality (CFR) rates. The epidemic peaked on week 48/2009 with approximately 750–1,500 new cases/100,000 population per week, depending on ILI-38 or ILI-37 case definition, respectively. By week 6/2010, 7.1%–15.6% of the population in Greece was estimated to be symptomatically infected with H1N1. Children 5–19 years represented the most affected population group (CAR:27%–54%), whereas individuals older than 64 years were the least affected (CAR:0.6%–2.2%). The IAR (95% CI) of influenza A(H1N1) was estimated to be 19.7% (13.3%, 26.1%). Per 1,000 symptomatic cases, based on ILI-38 case definition, 416 attended health services, 108 visited hospital emergency departments and 15 were admitted to hospitals. ICU admission rate and CFR were 37 and 17.5 per 100,000 symptomatic cases or 13.4 and 6.3 per 100,000 infections, respectively.

Conclusions/Significance

Influenza A(H1N1) infected one fifth and caused symptomatic infection in up to 15% of the Greek population. Although individuals older than 65 years were the least affected age group in terms of attack rate, they had 55 and 185 times higher risk of ICU admission and CFR, respectively.     

Recent emergence of serogroup C meningococcal disease in Greece

The number of cases of meningococcal disease reported to the Meningitis Reference Laboratory in Athens rose dramatically in 1996-1997. The aims were (1) to determine if the increase was due to introduction of new strains, (2) to assess the geographic and age distribution of the cases, (3) to compare antibiotic sensitivity patterns of the current isolates with strains from the early 1990s. In 1993-1994, 15/19 (74%) of the cases for which information on age was available were in children < or = 5 years; in 1995-1997, 80/179 (45%) of cases were in children < or = 5 years and 99 (55%) in the older age range (P < 0.02). From 593 cases in 1993 1997, 214 (36%) isolates were available for characterisation. Serogroup B was predominant in the early 1990s, but by 1997, serogroup C accounted for 46/72 (64%) of isolates and serogroup B for 25/72 (35%). Serogroup B was predominant in children < or = 5 years (44/78, 56%) but only 19/99 (18%) of older children and adults (P=0.0000005). Sulfonamide resistance decreased from 10/22 (45%) in 1993-1994 to 27/192 (14%) in 1995-1997 (P<0.01). Multilocus enzyme electrophoresis of 70 strains obtained during this period identified the epidemic ET-15 clone in 24 (34.3)%. The profiles of the Greek ET-15 isolates were identical to C:2a:P1.2(P1.5) strains responsible for the epidemic in the Czech Republic which began in 1993. This genotype was not found in Greek strains isolated prior to 1993. We conclude that the increase in meningococcal disease is due to introduction of the epidemic serogroup C:2a:P1.2(P1.5) strain responsible for disease in the Czech Republic and Canada.     

Double-antibody solid-phase enzyme immunoassay for the detection of staphylococcal enterotoxin A.

A simple double-antibody enzyme immunoassay that uses a microtechnique was developed for detecting staphylococcal enterotoxin A in food products. Sample preparation can be completed in less than 15 min. Assay sensitivity ranges from 0.4 ng (20-h test time) to 3.2 ng (1- to 3-h test time) of toxin per ml of prepared sample. Separation and detection of enterotoxin from spiked food products ranged between 72 and 98% of the amount added.     

Double-antibody solid-phase enzyme immunoassay for the detection of staphylococcal enterotoxin A.

A simple double-antibody enzyme immunoassay that uses a microtechnique was developed for detecting staphylococcal enterotoxin A in food products. Sample preparation can be completed in less than 15 min. Assay sensitivity ranges from 0.4 ng (20-h test time) to 3.2 ng (1- to 3-h test time) of toxin per ml of prepared sample. Separation and detection of enterotoxin from spiked food products ranged between 72 and 98% of the amount added.     

A Review of Evaluations of Electronic Event-Based Biosurveillance Systems

Electronic event-based biosurveillance systems (EEBS’s) that use near real-time information from the internet are an increasingly important source of epidemiologic intelligence. However, there has not been a systematic assessment of EEBS evaluations, which could identify key uncertainties about current systems and guide EEBS development to most effectively exploit web-based information for biosurveillance. To conduct this assessment, we searched PubMed and Google Scholar to identify peer-reviewed evaluations of EEBS’s. We included EEBS’s that use publicly available internet information sources, cover events that are relevant to human health, and have global scope. To assess the publications using a common framework, we constructed a list of 17 EEBS attributes from published guidelines for evaluating health surveillance systems. We identified 11 EEBS’s and 20 evaluations of these EEBS’s. The number of published evaluations per EEBS ranged from 1 (Gen-Db, GODsN, MiTAP) to 8 (GPHIN, HealthMap). The median number of evaluation variables assessed per EEBS was 8 (range, 3–15). Ten published evaluations contained quantitative assessments of at least one key variable. No evaluations examined usefulness by identifying specific public health decisions, actions, or outcomes resulting from EEBS outputs. Future EEBS assessments should identify and discuss critical indicators of public health utility, especially the impact of EEBS’s on public health response.     

Hybrid Closed-Loop Insulin Pump Technology Can Be Safely Used in the Inpatient Setting

BackgroundHybrid closed-loop (HCL) systems, also known as automated insulin delivery systems, are a rapidly growing technology in diabetes management. Because more patients are using these systems in the outpatient setting, it is important to also assess inpatient safety to determine whether HCL use can be continued when those patients become hospitalized.MethodsThe records of patients using HCL technology on admission to our hospital between June 1, 2020, and June 30, 2021, were analyzed.ResultsThe final analysis included 71 patients divided into 3 categories based on their pump use as an inpatient: (1) HCL users; (2) manual pump users; and (3) pump removed. All cohorts were similar in age, sex, race, hemoglobin A1C at admission, and in Medicare Severity Diagnosis Related Group. Pairwise comparisons indicated that patient-stay mean glucose levels, frequency of patient-specific hyperglycemic measurements, and frequency of hypoglycemic events were similar between all groups. No adverse events, particularly occurrences of diabetic ketoacidosis, pump site complications or infection, or equipment malfunction, were reported.ConclusionThis preliminary case series review indicates that continued use of HCL technology in the hospital is safe. Moreover, glycemic control in HCL users was comparable with that in those using insulin pump with manual settings and those converted to basal-bolus insulin therapy.     

Ex vivo measurement of lumbar intervertebral disc pressure using fibre-Bragg gratings

Methods were developed to measure intervertebral disc pressure using optical fibre-Bragg gratings (FBGs). The FBG sensor was calibrated for hydrostatic pressure in a purpose-built apparatus and the average sensitivity was determined to be -5.7 +/- 0.085 pm/MPa (mean +/- SD). The average coefficient of determination (r(2)) for the calibration data was 0.99, and the average hysteresis of the sensor was 2.13% of full scale. The FBG was used to measure intradiscal pressure response to compressive load in five lumbar functional spine units. The pressure measured by the FBG sensor varied linearly with applied compressive load with coefficients of determination ranging from 0.84 to 0.97. The FBG sensor's sensitivity to compressive load ranged from 0.702 +/- 0.043 kPa/N (mean +/- SD) in a L1-L2 specimen, to 1.07 +/- 0.069 kPa/N in a L4-L5 specimen. These measurements agree with those of previous studies in lumbar spines. Two strain gauge pressure sensors were also used to measure intradiscal pressure response to compressive load. The measured pressure sensitivity to load ranged from 0.251 kPa/N (L4-L5) to 0.850 kPa/N (L2-L3). The average difference in pressure sensitivity to load between Sensors 1 and 2 was 12.9% of the value for Sensor 1, with a range from 1.1% to 20.4%, which suggests that disc pressure was not purely hydrostatic. This may have contributed to the difference between the responses of the FBG and strain gauge sensors.     

Use of purified tachyzoite surface antigen p38 in an ELISA to diagnose bovine neosporosis

Affinity-purified 38 kDa surface antigen of Neospora caninum tachyzoites was used to develop an enzyme-linked immunosorbent assay (ELISA) to diagnose N. caninum-associated abortion in cattle. The specificity of this antigen was demonstrated by using sera from cattle experimentally infected with other apicomplexan parasites. In a panel of field sera, serological differences could be demonstrated between herds with epidemic and endemic abortions. Optimal ELISA cut-offs were determined for the detection of association between seropositivity and abortion in herds with N. caninum-associated abortions. These optimal cut-offs differed markedly when only sera from either endemic or epidemic cases were used for cut-off determination. It may thus be appropriate to apply different cut-offs in serological tests depending on the abortion pattern to be analysed.     

Potential to improve transfer of N in intercropped systems by optimising host-endophyte combinations

Possibilities for improving N transfer from N2-fixing plants to non-N2-fixing plants by mycorrhiza have been investigated. Initially, the genetic variability with respect to N uptake was assessed by screening five varieties of chicory (Cichorium intybus L.), four of peas (Pisum sativum L.) and three of red clover (Trifolium pratense L.) in combination with eight isolates of arbuscular mycorrhizal fungi. The most promising plant - fungi combinations identified through the cultivar screening were used to optimise conditions for N transfer between intercropped N2-fixing plants (peas and clover) and non-N2-fixing chicory. In the first experiment, the recovery of fixed legume N was investigated using three cultivars, of chicory intercropped with pea variety, and inoculated with one of four mycorrhizal isolates. Roots of the N2-fixing pea and the non-N2-fixing chicory were separated by a root-free soil layer in a three-compartment container. A section of the legume roots was forced to grow into a separate compartment which received four split applications of ¹⁵N. The percentage of N in the chicory derived from transfer ranged between 3% and 50%. In a second experiment one chicory variety was intercropped with one red clover variety and inoculated with four mycorrhizal isolates respecetively. A harvest regime was chosen in which the shoots were harvested from intercropped plants at 3,4.5 and 6 months of age. At three months the percentage of N in the chicory derived from transfer ranged between 15% and 18% and at a plant age of 4.5 months from 46 to 77%. At six months the percentage of N in the chicory roots derived from transfer of legume N ranged from 20 to 34% and varied with fungal isolate. Our results show that there is potential for improving N transfer in intercropped plant systems through the methodological selection of suitable plant and mycorrhizal partners.     

Crowdsourcing as a Screening Tool to Detect Clinical Features of Glaucomatous Optic Neuropathy from Digital Photography

AimCrowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images.MethodsOptic disc images (N = 127) with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs) from a crowdsourcing platform (Amazon MTurk) classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC).ResultsOverall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83–88% across both trials and study designs, however the specificity was poor, ranging between 35–43%. In trial 1, the highest AUC (95%CI) was 0.64(0.62–0.66) and in trial 2 it was 0.63(0.61–0.65). There were no significant differences between study design or trials conducted.ConclusionsCrowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis.     

Epitope Predictions Indicate the Presence of Two Distinct Types of Epitope-Antibody-Reactivities Determined by Epitope Profiling of Intravenous Immunoglobulins

Epitope-antibody-reactivities (EAR) of intravenous immunoglobulins (IVIGs) determined for 75,534 peptides by microarray analysis demonstrate that roughly 9% of peptides derived from 870 different human protein sequences react with antibodies present in IVIG. Computational prediction of linear B cell epitopes was conducted using machine learning with an ensemble of classifiers in combination with position weight matrix (PWM) analysis. Machine learning slightly outperformed PWM with area under the curve (AUC) of 0.884 vs. 0.849. Two different types of epitope-antibody recognition-modes (Type I EAR and Type II EAR) were found. Peptides of Type I EAR are high in tyrosine, tryptophan and phenylalanine, and low in asparagine, glutamine and glutamic acid residues, whereas for peptides of Type II EAR it is the other way around. Representative crystal structures present in the Protein Data Bank (PDB) of Type I EAR are PDB 1TZI and PDB 2DD8, while PDB 2FD6 and 2J4W are typical for Type II EAR. Type I EAR peptides share predicted propensities for being presented by MHC class I and class II complexes. The latter interaction possibly favors T cell-dependent antibody responses including IgG class switching. Peptides of Type II EAR are predicted not to be preferentially presented by MHC complexes, thus implying the involvement of T cell-independent IgG class switch mechanisms. The high extent of IgG immunoglobulin reactivity with human peptides implies that circulating IgG molecules are prone to bind to human protein/peptide structures under non-pathological, non-inflammatory conditions. A webserver for predicting EAR of peptide sequences is available at www.sysmed-immun.eu/EAR.     

Serological differences in Neospora caninum-associated epidemic and endemic abortions.

A sandwich enzyme-linked immunosorbent assay (ELISA) for the sensitive and specific detection of bovine antibodies to Neospora caninum was developed and evaluated using sera from cattle experimentally infected with N. caninum, Toxoplasma gondii, Sarcocystis cruzi, Sarcocystis hominis, Sarcocystis hirsuta, Eimeria bovis, Cryptosporidium parvum, Babesia divergens, and field sera from naturally exposed animals. Field sera were classified using a gold standard that included the results from an indirect fluorescent antibody test (IFAT) and an immunoblot (IB). Based on these gold standard results, i.e., IFAT-IB results, an equal relative sensitivity and specificity of 94.2%(theta0) was reached when a cutoff of 0.034 (d0) was employed. The analysis of IFAT-IB-positive field sera showed that within groups of aborting and nonaborting dams, the animals from herds with endemic N. caninum-associated abortions had significantly higher ELISA indices than animals from herds with N. caninum-associated epidemic abortions. By contrast, IFAT-IB-positive aborting dams from herds with endemic N. caninum-associated abortions had significantly lower IFAT titers than IFAT-IB-positive aborting dams from herds with epidemic N. caninum-associated abortions. This is the first time that statistically significant serological differences between herds exhibiting epidemic and endemic N. caninum-associated abortions are described.