A host signature based on TRAIL,IP-10, and CRP for reducing antibiotic overuse in children by differentiating bacterial from viral infections: a prospective,multicentre cohort study

ObjectivesIdentifying infection aetiology is essential for appropriate antibiotic use. Previous studies have shown that a host-protein signature consisting of TNF-related apoptosis-induced ligand (TRAIL), interferon-γ-induced protein-10 (IP-10), and C-reactive protein (CRP) can accurately differentiate bacterial from viral infections.MethodsThis prospective, multicentre cohort study, entitled AutoPilot-Dx, aimed to validate signature performance and to estimate its potential impact on antibiotic use across a broad paediatric population (>90 days to 18 years) with respiratory tract infections, or fever without source, at emergency departments and wards in Italy and Germany. Infection aetiology was adjudicated by experts based on clinical and laboratory investigations, including multiplex PCR and follow-up data.ResultsIn total, 1140 patients were recruited (February 2017–December 2018), of which 1008 met the eligibility criteria (mean age 3.5 years, 41.9% female). Viral and bacterial infections were adjudicated for 628 (85.8%) and 104 (14.2%) children, respectively; 276 patients were assigned an indeterminate reference standard outcome. For the 732 children with reference standard aetiology, the signature discriminated bacterial from viral infections with a sensitivity of 93.7% (95%CI 88.7–98.7), a specificity of 94.2% (92.2–96.1), positive predictive value of 73.0% (65.0–81.0), and negative predictive value of 98.9% (98.0–99.8); in 9.8% the test results were equivocal. The signature performed consistently across different patient subgroups and detected bacterial immune responses in viral PCR-positive patients.ConclusionsThe findings validate the high diagnostic performance of the TRAIL/IP-10/CRP signature in a broad paediatric cohort, and support its potential to reduce antibiotic overuse in children with viral infections.     

Limited value of chest radiography in predicting aetiology of lower respiratory tract infection in general practice.

BACKGROUND: In patients with lower respiratory tract infection (LRTI), changes on chest radiography are rare but poorly characterised, especially in general practice. AIM: To describe the range of findings on chest radiographs and the associations between these findings and the aetiology of LRTI. DESIGN OF STUDY: A prospective observational study. SETTING: General practices in the Leiden region, The Netherlands. METHOD: Adult patients with a defined LRTI were included. Standard medical history and physical examination were performed. Sputum, blood, and throat swabs were collected for diagnostic tests. Chest X-ray findings were assessed in relation to the aetiology. RESULTS: An abnormality on the chest X-ray was observed in 72 (55%) patients. Forty-five patients (35%) had changes due to infection, and 26 (20%) due to pneumonia. Pathogens were detected in 84 patients (33 single bacterial, 43 single viral, and 8 dual). Twelve (29%) patients with a bacterial infection (including dual infections) compared to four (9%) patients with viral infection had pneumonia on the chest X-ray (odds ratio [OR] = 4.0; 95% confidence interval [CI] = 1.2 to 13.8). Using the presence of pneumonia on chest X-ray as a test to predict a bacterial infection, the positive predictive value and the negative predictive value were 75% (CI = 48 to 93%) and 57% (CI = 45 to 69%), respectively. CONCLUSION: Pneumonia on the chest X-ray was found more frequently in patients with a bacterial infection than in patients with a viral infection. However, the sensitivity and the specificity are such that pneumonia on the chest X-ray is not a reliable test to discriminate between bacterial and non-bacterial LRTI in the general practice setting.     

Validation of a Diagnosis Model for Differentiating Bacterial from Viral Meningitis in Infants and Children under 3.5 Years of Age

 The aim of this study was to validate, in a population of infants and children under 3.5 years of age, a diagnosis model that provides a figure for the probability of bacterial meningitis (pABM), based on four parameters collected at the time of the first lumbar tap: the cerebrospinal fluid (CSF) protein level, CSF polymorphonuclear cell count, blood glucose level, and leucocyte count. The best cut-off value for distinguishing between bacterial and viral meningitis was previously found to be 0.1, since 99% of meningitides associated with pABM<0.1 were viral. The charts of 103 consecutive children aged 0.1–3.5 years who had been hospitalised for acute meningitis were reviewed. Each case was sorted into the following three categories for aetiology: bacterial (positive CSF culture, n=48); viral (negative CSF culture and no other aetiology, and no antibiotic treatment after diagnosis, n=36); and undetermined (fitting neither of the first two definitions, n=19). After computation of pABM values in each case, the predictive values of the model were calculated for different pABM cut-off values. The results confirmed that the best cut-off pABM value was 0.1, for which the positive and negative predictive values in this model were 96% and 97%, respectively. Only one case of bacterial meningitis (lumbar tap performed early in an infant with meningococcal purpura fulminans with negative CSF culture) was associated with a pABM value of <0.1. This model is quite reliable for differentiating between bacterial and viral meningitis in children under 3.5 years of age, and it may enable physicians to withhold antibiotics in cases of meningitis of uncertain aetiology.     

Prospective Validation of a Diagnosis Model as an Aid to Therapeutic Decision-Making in Acute Meningitis

 The aim of this study was to validate a diagnosis model that provides pABM, the probability of bacterial versus viral meningitis, based on four parameters collected at the time of first lumbar tap: cerebrospinal fluid protein level, cerebrospinal fluid polymorphonuclear cell count, blood glucose level, and leucocyte count. The model was evaluated prospectively as an aid to therapeutic decision-making in 109 consecutive patients with acute meningitis and negative cerebrospinal fluid Gram stain. In each case pABM was computed before a therapeutic decision and three diagnoses were established successively: (i) clinical evaluation, i.e. before pABM computation (bacterial meningitis, viral meningitis, or meningitis of undetermined origin); (ii) computation of pABM (viral meningitis if pABM<0.1, bacterial meningitis otherwise); and (iii) determination of definitive diagnosis (bacterial meningitis: positive cerebrospinal fluid culture; viral meningitis: negative cerebrospinal fluid culture, no other aetiology and no treatment; meningitis of undetermined origin: cases fitting neither of the first two diagnoses). The computed diagnosis was viral meningitis in 78 of the 80 cases diagnosed definitively as viral meningitis, and bacterial meningitis in four of the five cases diagnosed definitively as bacterial meningitis. Negative and positive predictive values and accuracy of the model were 98.7%, 66.7%, and 96.5%, respectively. The clinical diagnosis was undetermined in 22 cases, 15 of which were diagnosed definitively as viral cases; in all of these 15 cases, the computed diagnosis was viral meningitis, leading the physician to refrain from starting antibiotics in all of them. The results confirm that the model evaluated is reliable and aids in the identification of patients in whom antibiotics can be safely avoided.     

Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children – The TREND study

ObjectiveDiscriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses.MethodsChildren with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls.ResultsMxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p <0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 μg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78–99%) sensitivity and 100% (95% CI: 51–100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 μg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 μg/l, interquartile range: 679 to 2489).DiscussionMxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.     

Atypical glandular cells of undetermined significance. Outcome predictions based on human papillomavirus testing

Cases of atypical glandular cells (AGC) diagnosed on liquid-based preparations were culled from a 3-year period. When available, residual cellular material was analyzed for human papillomavirus (HPV) by polymerase chain reaction and correlated with cytologic and histologic (biopsy) outcome. Of 178,994 cytologic cases, 187 (0.1045%) contained AGC compared with 8,740 (4.8828%) atypical squamous cells (ASC) for an AGC/ASC ratio of 0.021. HPV results and follow-up were available for 108 specimens from 106 patients. Depending on the end-point (histologic/cyto-logic), the sensitivity range of HPV testing for significant cervical disease (high-grade squamous intraepithelial lesion [SIL], adenocarcinoma in situ [ACIS], invasive carcinoma) was 83% with a specificity range of 78% to 82%, a positive predictive value of 57% to 61%, and a negative predictive value of 91% to 95%. Fifteen false-positive results included concurrent ASC or low-grade SIL, ASC on follow-up cytology, and previous ACIS with a negative follow-up cone biopsy result. Noncervical glandular neoplasia (including atypical endometrial hyperplasia) was confirmed in 13 cases (1 recurrent), only 2 of which scored positive for HPV. HPV-positive AGC has a substantially higher positive predictive value for significant disease than ASC (61% vs historic 20%) and merits consideration in the triage of patients with atypical endocervical cells not otherwise specified. However, noncervical or other HPV-negative glandular neoplasia must be considered in all patients with AGC, particularly older patients.     

降钙素原在病毒性脑膜炎和细菌性脑膜炎鉴别诊断中的应用

目的探讨降钙素原（PCT）在病毒性脑膜炎和细菌性脑膜炎鉴别诊断中的应用价值。方法通过对27例细菌性脑膜炎和32例病毒性脑膜炎患者血清PCT值的检测和比较,从而分析降钙素原在其鉴别诊断中的临床意义。结果细菌性脑膜炎患者血中的PCT平均浓度为37.84 ng/ml,病毒性脑膜炎患者的PCT平均浓度为0.41 ng/ml,两者相比差异有统计学意义（χ2=28.45,P〈0.01）,特异性分别为100%和96.9%。结论降钙素原对病毒性脑膜炎和细菌性脑膜炎的鉴别诊断具有临床应用价值。     

Aetiology and Clinical Presentation of Mild Community-Acquired Bacterial Pneumonia

A prospective study was initiated to analyse the bacterial aetiology and clinical picture of mild community-acquired pneumonia in Slovenia using the previously described Pneumonia Severity Index. Radiographically confirmed cases of pneumonia in patients treated with oral antibiotics in seven study centres were included. An aetiological diagnosis was attempted using culture of blood and sputum, urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila, and antibody testing for Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila in paired serum samples. One hundred thirteen patients were evaluable for clinical presentation and 109 for aetiological diagnosis. At least one pathogen was detected in 62.4% patients. The most common causative agents were Mycoplasma pneumoniae in 24.8%, Chlamydia pneumoniae in 21.1%, and Streptococcus pneumoniae in 13.8% of patients. Dual infection was detected in 8.3% of patients. Most patients suffered from cough, fatigue, and fever. Patients with atypical aetiology of pneumonia differed from those with typical bacterial pneumonia or pneumonia of unknown aetiology in age, presence of dyspnea, and bronchial breathing on lung auscultation. Patients with pneumococcal, chlamydial, and mycoplasmal infections differed in age, risk class, presence of dyspnea, bronchial breathing, and proteinuria. There was an overlap of other clinical symptoms, underlying conditions, and laboratory and radiographic findings among the groups of patients classified by aetiology. Since patients with mild community-acquired pneumonia exhibit similar clinical characteristics and, moreover, since a substantial proportion of cases are attributable to atypical bacteria, broad-spectrum antibiotic treatment seems to be recommended.     

Human papillomavirus viral load expressed as relative light units (RLU) correlates with the presence and grade of preneoplastic lesions of the uterine cervix in atypical squamous cells of undetermined significance (ASCUS) cytology

Human papillomavirus (HPV) testing is more sensitive and has higher negative predictive value (NPV) than the Pap test for the detection of cervical intraepithelial neoplasia (CIN) in patients with atypical squamous cells of undetermined significance (ASCUS) cytology, but has low specificity, leading to high referral rates to second-level triage. Our goal was to identify the prognostic significance of HPV viral load figures. We evaluated whether a correlation between viral load, expressed as relative light units/cutoff (RLU/CO), and the severity of cervical lesions existed in 614 ASCUS cases. Hybrid Capture 2 (HC2?) RLU/CO values, categorised into five classes, were correlated to clinical outcomes and statistically analysed. A significant correlation (p?1,000 (p?相似文献   

Quantification of Epstein-Barr virus load in Argentinean transplant recipients using real-time PCR.

BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a frequent and severe Epstein-Barr virus (EBV)-associated complication in transplant recipients that is caused by suppression of T-cell function. OBJECTIVE: Evaluation of the diagnostic value of EBV DNA load in non-fractionated whole blood samples (n = 297) from 110 pediatric transplant patients by real-time PCR. RESULTS AND CONCLUSIONS: Patients with PTLD had a median viral load of 1.08 x 10(5) copies/ml blood (n = 24), which was significantly higher compared with patients without PTLD (median: 50 copies/ml blood, n = 273, P < 0.0001). From receiver operating characteristic (ROC) curve analysis we obtained a cut-off value of 6215 copies/ml blood with a sensitivity of 95.8%, specificity of 71.4%, negative predictive value (NPV) of 99.5% and positive predictive value (PPV) of 22.8%. Thus, real-time PCR proved to be more useful in ruling out than in indicating the presence of PTLD. Further analysis showed that patients without PTLD but developing a post-transplant EBV-primary infection had associated high viral loads that were indistinguishable from those of the PTLD group (statistically not significant). Similarly, the presence of clinical symptoms of disease in patients without PTLD was associated with higher viral loads than in patients that were asymptomatic (P < 0.0001), but the difference was much less significant when compared with the PTLD group of patients (P = 0.0391). These patients who had a high viral load may benefit from a close follow-up of the viral burden.     

Alpha-interferon responses in cerebrospinal fluid of patients with suspected meningitis.

Cerebrospinal fluid from 100 patients with clinically diagnosed meningitis was examined for alpha-interferon. In the laboratory four patient groups were identified: bacterial meningitis (n = 12), viral meningitis (n = 15), normal cerebrospinal fluid (n = 57) and abnormal cerebrospinal fluid (n = 16). A further 14 patients with cerebrospinal fluid shunts but no abnormality in the cerebrospinal fluid provided a control group for alpha-interferon determinations. The group with viral meningitis and the group with abnormal cerebrospinal fluid had significantly higher alpha-interferon concentrations (p less than 0.001) when compared with those of the three other groups. This assay had great predictive value in determining those patients with abnormal cerebrospinal fluid who did not have a bacterial cause of meningitis. As the groups with abnormal cerebrospinal fluid and viral meningitis had a similar spread in alpha-interferon values it is likely that both reflect viral infection of the central nervous system.     

Development and evaluation of a multiplex test for the detection of atypical bacterial DNA in community-acquired pneumonia during childhood

An incorrect or late diagnosis can lead to an increase in the morbidity and mortality caused by pneumonia, and the availability of a rapid and accurate microbiological test to verify the aetiology is imperative. This study evaluated a molecular test for the identification of the bacterial cause of atypical community-acquired pneumonia (ACAP). Fifty-four children with pneumonia were studied using bacteriological cultures, Mycoplasma pneumoniae , Coxiella burnetii , Chlamydophila pneumoniae and Legionella spp. serology, and Streptococcus pneumoniae and Legionella antigens. Simultaneously, the presence of bacterial and fungal DNA was tested for in respiratory secretion samples using the Vircell SL kit, including multiplex PCR and amplicon detection by means of line blots. There were 14 cases of ACAP caused by M. pneumoniae , with positive kit results for 13 of them, and two cases of Q-fever, with negative kit results for Coxiella burnetii . The test was negative in the remaining 38 cases (one staphylococcal pneumonia, 20 Streptococcus pneumoniae pneumonias, and 17 probable viral pneumonias). The sensitivity of the test for the detection of M. pneumoniae was 92.8% and the specificity was 100%. The Vircell SL kit allows detection of M. pneumoniae DNA in respiratory secretion samples from children with ACAP.     

Baseline factors and early viral response (week 4) to antiviral therapy with peginterferon and ribavirin for predicting sustained virologic response in patients infected with hepatitis C virus genotype 1: A multicenter study

Both baseline predictive factors and viral response at week 4 of therapy are reported to have high predictive ability for sustained virologic response to peginterferon and ribavirin combination therapy in patients with hepatitis C virus (HCV) genotype 1. However, it is not clear how these baseline variables and week 4 response should be combined to predict sustained virologic response. In this multicenter study, the authors investigated the impact of baseline predictive factors on the predictive value of week 4 viral response. Receiver‐operating characteristic curve analyses were performed to evaluate the ability of week 4 reduction in HCV RNA levels to predict sustained virologic response in 293 Japanese patients infected with HCV genotype 1b. Analyses were performed in all patients and in patient subgroups stratified according to baseline variables. Overall, week 4 viral reduction demonstrates a high predictive ability for sustained virologic response. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy were higher than those of viral reduction at week 12. However, the best cut‐off levels differ depending on the baseline factors and they were lower in patients with unfavorable baseline predictors. When patients had the TG/GG rs8099917 genotype, the best cut‐off was markedly low with low PPV. Week 4 viral response can be a predictor of sustained virologic response in patients with HCV genotype 1 and is better than week 12 viral response. However, the cut‐off levels should be modified based on the baseline predictive variables. J. Med. Virol. 85:65–70, 2012. © 2012 Wiley Periodicals, Inc.     

Novel point-of-care biomarker combination tests to differentiate acute bacterial from viral respiratory tract infections to guide antibiotic prescribing: a systematic review

BackgroundAcute respiratory tract infections (RTIs) are the most common reason to seek medical care, with many patients receiving inappropriate antibiotics. Novel testing approaches to identify aetiology at the point-of-care are required to accurately guide antibiotic treatment.ObjectiveTo assess the diagnostic accuracy of biomarker combinations to rapidly differentiate between acute bacterial or viral RTI aetiology.Data sourcesMEDLINE, Embase and Web of Science databases were searched to February 2021.Study eligibility criteriaDiagnostic accuracy studies comparing accuracy of point-of-care and rapid diagnostic tests in primary or secondary care, consisting of biomarker combinations, to identify bacterial or viral aetiology of RTI.MethodsRisk of bias was assessed using the QUADAS-2 tool. Sensitivity and specificity of tests reported by more than one study were meta-analysed using a random effects model.ResultsTwenty observational studies (3514 patients) were identified. Eighteen were judged at high risk of bias. For bacterial aetiologies, sensitivity ranged from 61% to 100% and specificity from 18% to 96%. For viral aetiologies, sensitivity ranged from 59% to 97% and specificity from 74% to 100%. Studies evaluating two commercial tests were meta-analysed. For ImmunoXpert, the summary sensitivity and specificity were 85% (95% CI 75%–91%, k = 4) and 86% (95% CI 73%–93%, k = 4) for bacterial infections, and 90% (95% CI 79%–96%, k = 3) and 92% (95% CI 83%–96%, k = 3) for viral infections, respectively. FebriDx had pooled sensitivity and specificity of 84% (95% CI 75%–90%, k = 4) and 93% (95% CI 90%–95%, k = 4) for bacterial infections, and 87% (95% CI 72%–95%; k = 4) and 82% (95% CI 66%–86%, k = 4) for viral infections, respectively.ConclusionCombinations of biomarkers show potential clinical utility in discriminating the aetiology of RTIs. However, the limitations in the evidence base, due to a high proportion of studies with high risk of bias, preclude firm conclusions. Future research should be in primary care and evaluate patient outcomes and cost-effectiveness with experimental study designs.Clinical trialPROSPERO registration number: CRD42020178973.     

Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa

The purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with symptoms of infectious keratitis (n?=?46) at the ophthalmology outpatient department of three hospitals in rural South Africa. Corneal swabs were tested for herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus DNA by real-time polymerase chain reaction (PCR) and for bacteria and fungi by culture. Based on clinical history, disease characteristics and laboratory results, 29 (63 %) patients were diagnosed as viral keratitis, including 14 (48 %) viral keratitis cases complicated by bacterial superinfection, and 17 (37 %) as bacterial keratitis. VZV and HSV-1 DNA was detected in 11 (24 %) and 5 (11 %) corneal swabs, respectively. Among clinically defined viral keratitis cases, a negative viral swab was predominantly (93 %) observed in cases with subepithelial inflammation and was significantly associated with an increased duration of symptoms (p?=?0.003). The majority of bacteria cultured were Gram-positive (24/35), including Staphylococcus epidermidis and S. aureus. Viral aetiology was significantly associated with a history of herpes zoster ophthalmicus (p?<?0.001) and a trend was observed between viral aetiology and HIV infection (p?=?0.06). Twenty-one (47 %) keratitis cases were complicated by anterior uveitis, of which 18 (86 %) were HIV-infected cases with viral keratitis. The data implicate a high prevalence of herpetic keratitis, in part complicated by bacterial superinfection and/or uveitis, in HIV-infected individuals presenting with infectious keratitis in rural South Africa.     

A diagnostic rule for the aetiology of lower respiratory tract infections as guidance for antimicrobial treatment.

BACKGROUND: The majority of patients with lower respiratory tract infections (LRTIs) are treated with antibiotics; some of them are unnecessary because of a viral cause. Information on prediction of the aetiology, especially in a general practice setting, is missing. AIM: To differentiate between viral and bacterial LRTI on simple clinical criteria, easily obtained at the bedside. DESIGN OF STUDY: Prospective observational study. SETTING: General practices in the Leiden region of The Netherlands. METHOD: Adult patients with LRTI were included. Standard medical history and physical examination were performed. Sputum, blood and throat swabs were collected for diagnostic tests. According to microbiological findings, patients were classified as bacterial, viral, dual infection and unknown cause. In a logistic regression model independent predictors were determined. Scoring systems were developed. The accuracies of the diagnostic rules were tested by using receiver operating characteristic (ROC) curves. RESULTS: One-hundred and forty-five patients were classified as having bacterial (n = 35), viral (n = 49), or dual infection (n = 8), or infection of unknown cause (n = 53), respectively. Independent predictors for bacterial infection were fever (odds ratio [OR] = 8.0; 95% confidence interval [CI] = 0.9 to 71.0), headache (OR = 4.3; 95% CI = 1.0 to 19.1) cervical painful lymph nodes (OR = 8.7; 95% CI = 1.1 to 68.0), diarrhoea (OR = 0.3; 95% CI = 0.1 to 1.0) and rhinitis (OR = 0.3; 95% CI = 0.1 to 0.9). As an additional independent predictor, an infiltrate on chest X-ray (OR = 5.0; 95% CI = 1.2 to 20.5) was found. The diagnostic rules developed from these variables classified the aetiology of LRTI with a ROC curve area of 0.79 (clinical score), 0.77 (simplified score) and 0.83 (extended score). CONCLUSIONS: A diagnostic rule was developed, based on information that is easy to obtain at the bedside, to predict a bacterial infection. This diagnostic rule may be a tool for general practitioners in their management of patients with LRTI.     

Bacterial and viral agents associated with tenosynovitis in broiler breeders in Western Australia

The pathology and infectious agents associated with several outbreaks of clinical tenosynovitis in poultry were investigated. Staphylococcus aureus were recovered from tendon tissue of from 51.9% to 97.8% of affected chickens in different outbreaks of the disease. S. aureus were also present in the liver and heart blood and were considered to contribute to the high mortality observed following occurrence of clinical tenosynovitis in individual chickens. Bacteria other than S. aureus were also recovered but in a much lower proportion of chickens than was S. aureus. Adenoviruses and reoviruses were also recovered from tendon tissue of chickens with a concurrent bacterial infection. Although the pathology observed in clinically affected chickens was suggestive of a bacterial aetiology it is hypothesised that the tenosynovitis outbreaks investigated were due to an early viral infection which normally remained subclinical and that secondary infection with bacteria, particularly S. aureus, was responsible for the development of clinical signs.