Tissue distribution, shedding and environmental detection of infectious bursal disease virus genome following infection of meat chickens at two ages.

OBJECTIVE: To compare the effects of infectious bursal disease virus (IBDV) infection of commercial meat chickens at 0 and 16 days old (d.o.) and determine if IBDV vRNA is quantifiable in litter and dust samples. METHODS: Ross meat chickens (n = 60) were orally infected or not with IBDV at 0 or 16 d.o. Blood and faecal samples were collected longitudinally to 28 days post infection (dpi) from six chickens and tissues collected weekly from three euthanased chickens. Relative bursal weight was recorded postmortem. IBDV antibody titres in sera were measured using ELISA and VCN was determined in tissues, faeces, litter and dust using qRT-PCR. RESULTS: Chickens infected at 16 d.o. had earlier and more severe bursal atrophy, earlier and higher IBDV vRNA load in lymphoid organs and an earlier and greater antibody response to infection than those infected at 0 d.o. Faecal shedding of IBDV between 2 and 6 dpi was observed in both groups followed by cessation with the 0 d.o. group and re-initiation of shedding at 28 dpi. IBDV was readily detected and quantified in litter and dust samples. CONCLUSIONS: The presence of significant maternal antibody (MAb) titres in 0 d.o. chickens provided protection against IBDV replication and bursal atrophy at 7 and 14 days post infection. The reduced titres of MAb present at 16 d.o. did not prevent rapid IBDV replication and early marked bursal atrophy. The observed resistance of 0 d.o. chickens is likely to be a combination of MAb inhibition of IBDV and true age resistance of neonatal chicks. Measurement of IBDV in litter and dust may have research or diagnostic application.

Pathogenicity, tissue distribution, shedding and environmental detection of two strains of IBDV following infection of chickens at 0 and 14 days of age.

Infectious bursal disease virus (IBDV) is endemic to most poultry-producing countries worldwide. Immunosuppressive classical and variant IBDV strains endemic to Australia are genetically distinct from other international strains. We report the results of infection experiments with Australian classical strain 06/95 and variant strain 02/95 in SPF chickens. We tested the effects of strain and age of infection on bursal atrophy, viral RNA (vRNA) load in bursa of Fabricius (bursa), spleen, thymus, caecal tonsils, faeces, litter and exhaust dust as determined by real-time reverse transcriptase polymerase chain reaction. The two IBDV strains did not differ in the degree of bursal atrophy induced, lymphoid organ distribution and faecal shedding but variant strain 02/95 induced a greater antibody response to the infection than classical strain 06/95 which was associated with a more rapid decline in IBDV vRNA genome copy number (VCN) in lymphoid organs and faeces. Infection at 14 days of age induced greater bursal atrophy and higher vRNA copy number in lymphoid tissues than infection on the day of hatching, indicating true age susceptibility independent of maternal antibody (Mab) status. The direction of the association between rankings for IBDV vRNA load in bursa and relative bursal weight changed from positive at 3 and 6 days post-infection to negative at 28 days post-infection. Intra-tracheal administration of dust collected from chickens infected with IBDV resulted in successful transmission of IBDV. IBDV vRNA was detected successfully at high levels in the environmental litter and dust samples.

Field studies of the detection, persistence and spread of the Rispens CVI988 vaccine virus and the extent of co-infection with Marek's disease virus.

OBJECTIVE: To use specific real-time qPCR to determine (1) the vaccination success of Rispens CVI988 vaccine in feathers and dust; (2) persistence of Rispens infection in vaccinated layer chickens; (3) extent of co-infection with wild-type Marek's disease virus (MDV) in vaccinated layers; and (4) presence of Rispens virus in unvaccinated broiler flocks. METHODS: Feather, dust and serum samples were collected from birds aged 3 days to 91 weeks from three layer farms. qPCR was used to detect MDV and Rispens in DNA extracted from dust and feathers. Previously tested MDV-positive dust samples from 100 broiler flocks were tested for the presence of Rispens using qPCR, while serum samples were used to detect anti-MDV antibody using ELISA. RESULTS: Overall, 66% and 93% of feather and dust samples, respectively, from Rispens-vaccinated layers were Rispens-positive. Viral load in these samples varied between farms during early life, reaching readily detectable levels at 2-3 weeks of age. Vaccinated chickens maintained a high Rispens load in feathers and dust and high MDV antibody levels until 91 weeks of age. MDV infection was detected in 6.7% of feather samples from vaccinated chickens. Rispens virus was detected in 7% of samples from unvaccinated broiler flocks. CONCLUSION: Vaccine take can be measured effectively by Rispens-specific qPCR of feathers or dust from approximately 3 weeks post vaccination. Infection with Rispens is persistent, with lifelong shedding and serological response. The detectable infection rate of vaccinated chickens with MDV is low and there is preliminary evidence of escape of Rispens virus to unvaccinated flocks.

In vivo characterisation of two Australian isolates of Marek's disease virus including pathology, viral load and neuropathotyping based on clinical signs.

OBJECTIVE: To evaluate the pathogenicity of Australian Marek's disease virus (MDV) isolate MPF23 (1985) against the reference strain MPF57 based on pathology, viral load and neuropathotyping on the basis of clinical signs. PROCEDURE: Two MDV challenge isolates (MPF57 or MPF23) were administered to unvaccinated specific-pathogen free (SPF) layer chicks on day 5 after hatch at three challenge doses (500, 2000 or 8000 plaque-forming units (pfu)/chick). Mortality, body weight, immune organ weights, MDV load in peripheral blood lymphocytes (PBL) and clinical signs were measured to 56 days post challenge (dpc). RESULTS: MPF23 was the more pathogenic of the two viruses, inducing higher mortality (81% vs 62%) and incidence of MD lesions (100% vs 76%). MPF23 induced earlier, more sustained and more severe neurological signs in the period 26-56 dpc. However, there were few differences during the 0-23 dpc used in the neuropathotyping classification under test. The observed pattern during this earlier period classified both viruses as neuropathotype B, consistent with a very virulent pathotype. MDV load in PBL at 7 and 44 dpc did not differ between virus isolates, but the load at 7 dpc was significantly and negatively associated with time to euthanasia or death. CONCLUSION: MPF23 appears to be as, or more, virulent than the MDV strains isolated over the subsequent two decades. The neuropathotyping system developed in the USA did not clearly differentiate between the two isolates under test; however, extension of the period of assessment of clinical signs beyond 26 dpc did reveal clear differences.

Differentiation between pathogenic serotype 1 isolates of Marek's disease virus and the Rispens CVI988 vaccine in Australia using real-time PCR and high resolution melt curve analysis.

Two real-time PCR assays were developed which enable quantitation and differentiation between pathogenic Australian isolates of Marek's disease virus (MDV) serotype 1 and the serotype 1 vaccine strain Rispens CVI988. The assays are based on a DNA sequence variation in the meq gene between pathogenic and vaccinal MDV1 which has been confirmed by sequencing of 20 Australian field strains of MDV. Complete specificity has been demonstrated in samples containing pathogenic MDV (n=20), Rispens (3 commercial vaccine strains), or both. The limit of detection of both the Rispens-specific and the pathogenic MDV1-specific assays was 10 viral copies/reaction. The tests successfully differentiated and quantified MDV in mixtures of pathogenic and vaccinal Rispens virus. A high resolution melt curve analysis targeting the same SNP used for the real-time PCR assays was also developed which successfully detected sequence variation between Md5, six Australian MDV1 isolates and the three Rispens vaccines. However it was ineffective at differentiating mixtures of pathogenic and vaccinal MDV1. The real-time PCR assays have both diagnostic and epidemiological applications as they enable differentiation and quantitation of Rispens CVI988 and pathogenic MDV1 in co-infected chickens in Australia.

Effect of training on the incidence of nerve damage in thyroid surgery.

BACKGROUND: In thyroid surgery early postoperative recurrent laryngeal nerve (RLN) dysfunction offers a sensitive measure of the quality of the operation. The aim of this study was to analyse the effect of training in thyroid surgery on the rate of early functional disturbances of the RLN after thyroid resection. METHODS: In 617 patients (median age 48 years, female to male ratio 2.8:1) who underwent unilateral or bilateral thyroid resection, 1059 RLNs were subjected to operative risk. Laryngoscopy was performed before and after operation. The 45 surgeons were divided into three groups: group 1, specialist thyroid surgeons; group 2, experienced surgeons; and group 3, residents. Personal gain of experience was defined by the preceding number of thyroid operations. Within each group the complication profile was determined by adding the personal complication profiles of each surgeon. RESULTS: The complication rates were low during surgical residency (group 3). In group 2 complication rates increased up to the 50th operation. Group 1 showed the expected exponential decrease to under per cent after another 130 operations. CONCLUSION: Complication rates are affected considerably by the extent of surgical experience in a non-linear and complex logarithmic manner, starting with low rates in the beginner group, peaking after further experience and then decreasing exponentially.

Linking environmental and health care databases: assessing the health effects of environmental pollutants.

The assessment of pollutant effects on health status requires the mergence and analysis of two different databases: pollution measurements and health care information. This paper compares two subsets of these data: Ohio Environmental Protection Agency data on ambient air pollutants and Ohio Medicare data on respiratory diseases. Small area analysis was performed to assess statewide variations in hospital admission rates for respiratory diseases. The ambient air pollutant levels for each small area were compared to the variations in respiratory disease rates. Five groups of diseases correlated with pollutant levels. In addition, pollutant levels were significantly associated with medical complications. This study demonstrates the feasibility and benefit of linking environmental and health care databases and suggests the need for a more comprehensive, automated analysis of more pollutants and diseases.

Research review: pattern analysis for quality problems in medicine.

In conclusion, these results suggest that pattern analysis may provide a flexible and dynamic tool with which to sort cases prior to review, and evaluate changing medical practice patterns. Patterns analysis may also provide a way to avoid spending time and resources on cases with a low probability of quality problems. Lastly, pattern analysis promises to increase timely information and feedback to health care professionals and organizations.

Health care quality problems in Ohio: analysis by diagnosis related groups.

Quality problems occur throughout the health care system, regardless of the disease or diagnosis. Peer review groups and health care organizations can take advantage of this finding to design quality improvement programs that will have a greater impact on health care quality than traditional quality assurance programs. Problems associated with high volume diagnoses or high risk procedures can be analyzed with the understanding that lessons learned in those examinations can be applied to many other aspects of health care. Continuous quality improvement can be implemented, using specific indicators and criteria as models for the overall factors contributing to quality in the health care system. Quality improvement experts estimate that the majority of all quality problems originate in the system, rather than in the performance of individuals. An in-depth analysis of our hospital and health care systems, complementing the performance-based quality assurance programs already in place, will facilitate the comprehensive improvement of quality throughout our health care institutions.

Systems versus performance problems: a peer review organization's perspective.

An analysis of Ohio's Medicare data base by the state's Peer Review Organization, using the most common diagnosis-related group in the Medicare population (heart failure and shock), from January 1, 1989 to January 1, 1991, identified 72 cases with confirmed quality-of-care problems. The analysis was performed to determine whether the majority of quality-of-care problems are related to systems or performance deficiencies. Study results indicated that health care workers are being inappropriately blamed for problems that are inherent in the health care system--74% of problems were related to inefficiencies in the health care delivery system, and 26% were determined to reflect performance problems.

Unnecessary hospitalization of Medicare patients in Ohio. A preliminary profile.

Peer review organizations (PRO) review the health care given to Medicare beneficiaries. If a PRO determines that a hospital admission was unnecessary, the hospital is not reimbursed for the medical care and the case is "denied." The average hospital denial rate on Ohio is 2%; however, the denial rate for hospital admissions of one day or less is 7.5%. An analysis of hospitals and diagnoses for one-day hospital admission denials was performed, showing that urban hospitals and disorders of the circulatory and digestive systems predominate. The inappropriate utilization of health care resources costs millions of dollars per year in Ohio and could be costing the nation billions of dollars. There is an urgent need to research why resources are used less effectively by some hospitals and for some diseases.

Small area analysis shows differences in utilization.

Adjusted admission rates for respiratory distress (COPD, asthma, bronchitis, and pneumonia) varied up to 3.09-fold between the highest and lowest hospital market areas in 1986 for the state of Ohio. Reasons for the variability can be determined through small area analysis techniques with the help of area physicians. Substantial improvements in the availability, delivery, and cost of respiratory care would reasonably be anticipated as a result of such analysis and feedback.

Recidivism in the management of medical back pain.

One Ohio hospital underwent three years of 100% focused review of admissions for medical back problems (DRG 243) due to excessive numbers of admissions previously noted. On cessation of the focused review, the volume of admissions rose at this hospital, and the admission denial rate increased. Reinstitution of focused review appeared to decrease the number of admissions, but did not affect the rate of admission denials.

[Prospective observation study on the clinical course of chronic juvenile arthritis (JCA)]. / Prospektive Beobachtungsstudie zum klinischen Verlauf der juvenilen chronischen Arthritis (JCA).

A non-randomized follow-up study of 106 children with juvenile chronic arthritis was conducted for two years starting from the onset of the disease. All subgroups - with the exception of seropositive polyarthritis - showed a decrease in the number of joints affected, and activity of the disease in a number of patients. Instant remission and therapeutic effects cannot distinctly be differentiated. Radiological changes are proper criteria for early diagnosis in children with intense progressive joint-findings. X-ray examinations of the joints affected are therefore indicated at regular intervals especially, in the seropositive, occasionally in the seronegative polyarthritic subgroup.

[Differentiation of juvenile chronic arthritis--diagnostic significance of HLA associations]. / Differenzierung der Juvenilen Chronischen Arthritis (JCA)--Diagnostische Bedeutung der HLA-Assoziationen.

From January 1980 to June 1982, 150 children with primary onset of a joint disease during the previous 6 months were entered into a prospective non-randomized observation study. 106 of the 150 children were diagnosed as juvenile chronic arthritis cases according to the EULAR-criteria. Nine children of this group belonged to the systemic subgroup (7 girls, 2 boys). HLA-typing was performed in 100 of the 106 children: HLA-B27 was evident in the total patient group with significantly increased 41% versus 8.9% of the control group. This antigen is significantly evident in all subgroups with variously increased frequency, except in the systemic and early-onset (pauciarticular) subgroups; the frequency in the rheumatoid-factor-negative polyarticular type of juvenile chronic arthritis (JCA) was 37.9%, in the rheumatoid-factor-positive polyarticular form 33.3%, and in the oligoarthritis/sacroiliitis-group 72.2%. DR5 was significantly present in the total patient group with 32% (control group 13.4%) and in the early-onset oligoarthritis group (43.7%). The rheumatoid-factor-positive (50%) and negative polyarticular group (31%) showed a pronounced slightly significant increase.

[Chronic juvenile arthritis--difficult early diagnosis--differentiation of arthropathies in the patient case load of a juvenile arthritis hospital]. / Juvenile chronische Arthritis (JCA)--eine schwierige Frühdiagnose--Differenzierung der Gelenkserkrankungen im Krankengut einer Rheuma-Kinderklinik.

Among 2369 children who had been admitted and treated in the Rheumatic Children's Hospital Garmisch-Partenkirchen between 1952 and 1979 under the diagnosis "juvenile chronic arthritis (JCA)" or, "collagenosis", there were 244 patients (= 10.3%) for whom in the end a different diagnosis was set. The major part of these children suffered from arthritides where there was proof of a direct or an indirect connection with bacterial infections or where there existed a corresponding suspected diagnosis (altogether 162 out of these 244 children, = 66.4%). The remaining 82 cases differentiated into 26 further diagnoses with various frequencies. Our examinations show that six criteria are found relatively frequently in arthropathies not caused by juvenile chronic arthritis. These require special consideration in the differential diagnosis: oligoarthritic onset of the disease, high fever - especially septic intermittent fever, erythema nodosum, endomyocarditis, no (or only very slight) functional resp. morphological changes of the joints.

[Rheumatic iridocyclitis in childhood--differentiation on the basis of clinical and immunological parameters (author's transl)]. / Die rheumatische Iridocyclitis im Kindesalter--Differenzierung nach klinischen und immunologischen Gesichtspunkten.

In approximately 10% of the children suffering from juvenile chronic arthritis (JCA), rheumatic iridocyclitis was also diagnosed. In 90 JCA and iridocyclitis patients we studied relative risk, clinical course and prognosis by means of several clinical and immunological parameters. Antinuclear antibodies (ANA), selective IgA-deficiency, oligoarthritis type of onset of the disease and manifestation of JCA during infancy--predominantly in girls--were quite often accompanied by a pronounced susceptibility to rheumatic iridocyclitis, while seropositivity (RF-positivity) and systemic onset of juvenile chronic arthritis normally rule out rheumatic iridocyclitis. Among HLA-B27-positive boys of school age, the acute course of rheumatic iridocyclitis, which rarely results in serious and lasting complications, is more frequent; in some cases juvenile sacroiliitis or ankylosing spondylitis are evident. The evaluation of the risk factors makes it possible to systematically define subgroups likely to develop chronic iridocyclitis and less susceptible groups of patients, thus facilitating early diagnosis and treatment as well as clinical observation of the development of chronic iridocyclitis.