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Laboratory-based surveillance for meningococcal disease in selected areas, United States, 1989-1991.

PROBLEM/CONDITION: Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in the United States. Accurate surveillance for meningococcal disease is required to detect trends in patient characteristics, antibiotic resistance, and serogroup-specific incidence of disease. REPORTING PERIOD COVERED: January 1989 through December 1991. DESCRIPTION OF SYSTEM: A case of meningococcal disease was defined by the isolation of N. meningitidis from a normally sterile site, such as blood or cerebrospinal fluid, in a resident of a surveillance area. Cases were reported by personnel in each hospital laboratory in the surveillance areas. The surveillance areas consisted of three counties in the San Francisco metropolitan area, eight counties in the Atlanta metropolitan area, four counties in Tennessee, and the entire state of Oklahoma. RESULTS: Age- and race-adjusted projections of the U.S. population suggest that approximately 2,600 cases of meningococcal disease occurred annually in the United States. The case-fatality rate was 12%. Incidence declined from 1.3/100,000 in 1989 to 0.9/100,000 in 1991. Seasonal variation occurred, with the highest attack rates in February and March and the lowest in September. The highest rates of disease were among infants, with 46% of cases affecting those < or = 2 years of age. Males accounted for 55% of total cases, with an incidence of 1.2/100,000, compared with 1.0/100,000 among females (relative risk (RR) = 1.3, 95% confidence interval (CI) 1.0-1.6). The incidence was significantly higher among blacks (1.5/100,000) than whites (1.1/100,000) (RR = 1.4 [95% CI 1.1-1.8]). Serogroup B caused 46% of cases and serogroup C, 45% Thirty-eight percent of isolates were reported to be resistant to sulfa; none were reported to be resistant to rifampin. INTERPRETATION: The decline in incidence of meningococcal disease from 1989 through 1991 cannot be explained by any change in public health control measures; this trend should be monitored by continued surveillance. The age, sex, and race distribution and seasonality of cases are consistent with previous reports. The proportion of N. meningitidis isolates resistant to sulfa continues to be substantial. A relatively small proportion of cases is potentially preventable by the use of the currently available polysaccharide vaccine, which induces protection against serogroups, A, C, Y, and W135 and is effective only for persons > 2 years of age. ACTIONS TAKEN: Current recommendations against the use of sulfa drugs for treatment or prophylaxis of meningococcal disease unless the organism is known to be sensitive to sulfa should be continued. Since resistance to rifampin is rarely reported, it continues to be the drug of choice for prophylaxis. The development of vaccines effective for infants and vaccines inducing protection against serogroup B would be expected to have a substantial impact on disease.

Adolescent↗

Medical genetic test reporting for cystic fibrosis (deltaF508) and factor V Leiden in North American laboratories.

PURPOSE: Physicians are ordering an increasing number of genetic tests. Results and additional information provided in the test result report are vital to the physician in making appropriate patient management decisions. Because variability in test result reports can impact patient care, we sought to determine whether variations exist in test reports for cystic fibrosis (CF) and factor V Leiden (fVL) with specific comparison to professional guidelines and recommendations. METHODS: A cross-sectional study design analyzing for the presence of 16 critical elements in CF reports and 12 critical elements in fVL reports solicited from United States and Canadian laboratories. RESULTS: Of 44 laboratories performing CF testing and 72 laboratories performing fVL testing, 64% responded. For CF reports, 21% included ethnicity, 64% described methodology, and 61% discussed genetic counseling. For fVL reports, 80% described methodology and 52% discussed the need for genetic counseling in mutation-positive reports. CONCLUSIONS: Variability exists in report content among North American laboratories performing CF and fVL testing. Many reports lack information deemed critical by professional guidelines and recommendations.

Cross-Sectional Studies↗

Large epidemic of adenovirus type 4 infection among military trainees: epidemiological, clinical, and laboratory studies.

Outbreaks of adenovirus type 4 (Ad4) acute respiratory disease (ARD) have reemerged among US military personnel during the past decade. A prospective epidemiological investigation of 678 military recruits was conducted at Fort Jackson, South Carolina, in the fall of 1998; 115 (17%) of the recruits were hospitalized for febrile ARD. Adenovirus types 4, 3, and 21 were recovered from the cultures of 70 (72%), 7 (7%), and 2 (2%) of 97 recruits, respectively. In addition, 69 (83%) of the 83 hospitalized and 82 (49%) of the 166 nonhospitalized unit contacts had seroconversion to Ad4, which indicates the very high susceptibility and communicability of Ad4 among military recruits. Young age (<20 years) and male sex increased the risk for anti-Ad4 seroconversion. Recruits from tropical areas had higher preexisting immunity than did recruits from temperate regions. Military recruits are highly susceptible to Ad4 infections. Prompt reinstitution of an adenovirus vaccination program in this high-risk population is urgently needed.

Adenoviridae↗

Isoprostanes and related products of lipid peroxidation in neurodegenerative diseases.

Lipid peroxidation is a major outcome of free radical-mediated injury to brain, where it directly damages membranes and generates a number of oxidized products. Some of the chemically and metabolically stable oxidation products are useful in vivo biomarkers of lipid peroxidation. These include the isoprostanes (IsoPs) and isofurans (IsoFs), derived from arachidonic acid (AA), and neuroprostanes (NeuroPs), derived from docosahexaenoic acid (DHA). We have shown increased levels of IsoPs, NeuroPs, and IsoFs in diseased regions of brain from patients who died from advanced Alzheimer's disease (AD) or Parkinson's disease (PD). Increased cerebrospinal fluid (CSF) levels of IsoPs are present in patients with AD or Huntington's disease (HD) early in the course of their illness, and CSF IsoPs may improve the laboratory diagnostic accuracy for AD. In contrast, quantification of IsoPs in plasma and urine of AD patients has yielded inconsistent results. These results indicate that brain lipid peroxidation is a potential therapeutic target early in the course of AD and HD, that CSF IsoPs may aid in the assessment of anti-oxidant experimental therapeutics and laboratory diagnosis of AD.

Alzheimer Disease↗

Practical diagnostic testing for human immunodeficiency virus.

Since the discovery of human immunodeficiency virus (HIV) as the causative agent of acquired immunodeficiency syndrome in 1983, there has been a proliferation of diagnostic tests. These assays can be used to detect the presence of HIV antibody, HIV antigen, HIV ribonucleic and deoxyribonucleic acids, and HIV reverse transcriptase. Enzyme-linked immunosorbent assays, Western blot, radioimmunoprecipitation assays, indirect immunofluorescence assays, reverse transcriptase assays, and several molecular hybridization techniques are currently available. Enzyme-linked immunosorbent, Western blot, and indirect immunofluorescence assays for HIV antibody are very sensitive, specific, and adaptable to most laboratories. An enzyme-linked immunosorbent assay for HIV antigen is also readily adaptable to most laboratories and will be commercially available soon. While the other assays are more tedious, they are valuable confirmatory tests and are suitable for reference laboratories. The biohazards of performing HIV testing can be minimized with proper biosafety measures.

Acquired Immunodeficiency Syndrome↗

Management of complex multi-space odontogenic infections.

The successful management of multi-space orofacial odontogenic infections involves identification of the source of the infection, the anatomical spaces encountered, the predominant microorganisms that are found during the various stages of odontogenic fascial space infection, the impact of the infectious process on defense systems, the ability to use and interpret laboratory data and imaging studies, and a thorough understanding of contemporary antibiotic and supportive care. The therapeutic goals, when managing multi-space odontogenic infections, are to restore form and/or function while limiting patient disability and preventing recurrence. Odontogenic infections are commonly the result of pericoronitis, carious teeth with pulpal exposure, periodontitis, or complications of dental procedures. The second and third molars are frequently the etiology of these multi-space odontogenic infections. Of the two teeth, the third molar is the more frequent source of infection. Diagnostic imaging modalities are selected based on the patient's history, clinical presentation, physical findings and laboratory results. Periapical and panoramic x-rays are reliable initial screening instruments used in determining etiology. Magnetic resonance imaging and computed tomography are ideal imaging studies that permit assessment of the soft tissue involvement to include determining fluid collections, distinguishing abscess from cellulitis, and offering insight as to airway patency. Antibiotics are administered to assist the host immune system's effort to control and eliminate invading microorganisms. Early infections, first three (3) days of symptoms, are primarily caused by aerobic streptococci which are sensitive to penicillin. Amoxicillin is classified as an extended spectrum penicillin. The addition of clavulanic acid to amoxicillin (Augmentin) increases the spectrum to staphylococcus and other anaerobes by conferring beta-lactamase resistance. In late infections, more than three (3) days of symptoms, the predominant microorganisms are anaerobes, predominantly Peptostreptococcus, Fusobacterium, or Bacteroides, that are resistant to penicillin. Clindamycin is an attractive alternative drug for first line therapy in the treatment of these infections. The addition of metronidazole to penicillin is also an excellent treatment choice. Alternatively, Unasyn (Ampicillin/Sublactam), should be considered. The mainstay of management of these infections remains appropriate culture for bacterial identification, timely and aggressive incision and drainage, and removal of the etiology. It is usually preferable to drain multi-space infections involving the submandibular, submental, masseteric, pterygomandibular, temporal, and/or lateral pharyngeal masticator spaces, as early as possible from an extraoral approach. Trismus and airway management are important considerations and may preclude the selection of other surgical approaches. The patients with multi-space infections should be hospitalized and patient care provided by experienced clinicians capable of management of airway problems, in administration of parenteral antibiotics and fluids, utilization of interpretation of laboratory and diagnostic imaging studies, and control of possible surgical complications.

Abscess↗

Screening for diabetes mellitus in general practice using a reflectance meter system. The Islington Diabetes Survey.

The feasibility of using a blood-glucose reflectance meter to identify subjects with abnormal glucose tolerance in a community-based screening programme for diabetes mellitus has been assessed. 530 (51.0%) of 1,040 screened subjects had a finger-prick capillary blood-glucose level estimated 2 h after a 75 g oral glucose load. Blood-glucose estimations were performed on this sample by an automated glucose-oxidase method and by a reflectance meter system (Reflocheck, BCL (London) Ltd., Lewes, East Sussex, UK). Blood-glucose values measured by the meter were found to be higher than those assayed by the glucose-oxidase method by a mean ratio of 1.16:1. This overestimation could not wholly be explained by the meter being calibrated to measure plasma- rather than whole blood-glucose. This ratio was constant in specimens assayed by the glucose-oxidase method within 24 h of sampling or within 7 days of sampling. The meter system gave a good approximation of the prevalence of DM in the sample (14 "diabetics" identified by the meter, 15 by the glucose-oxidase 2hBG). The optimal test characteristics of the meter 2hBG as a screening test for DM were at a cut-off level of 9.7 mmol/l (sensitivity and specificity 98.4%, CI 85.8-100%, for sensitivity, 97.3-99.5% for specificity). However, in order to be 100% sensitive for DM, confirmatory GTTs would be necessary on all subjects with meter 2hBG greater than 9.5 mmol/l, providing a specificity of 98.2% (CI 97.0-99.7%). The unit cost of detecting 1 case of DM using a single meter became cheaper than using the laboratory glucose-oxidase method when 143 subjects had been screened.

Autoanalysis↗

Accuracy, reproducibility and clinical utility of the CoaguChek S portable international normalized ratio monitor in an outpatient anticoagulation clinic.

The accuracy and reproducibility of the CoaguChek S, and its clinical agreement with conventional laboratory international normalized ratio (INR) determination, were evaluated in an outpatient anticoagulation clinic setting. Forty-three patients provided 248 paired INR measurements for analysis. The paired results were highly correlated (r = 0.90). The mean coefficient of variation for the CoaguChek S for a random sample of 21 patients with three repeated tests each, was 4%. Clinical applicability was also measured by discrepant INR values, as defined in the literature by expanded and narrow agreement, and by INR values resulting in a different clinical decision by a blinded haematology registrar. Expanded agreement and narrow agreement between the two INR values occurred 90 and 88% of the time, respectively. The stricter criteria set down by the clinician resulted in 73% of paired results producing the same dosage decision. The CoaguChek S displayed good correlation with laboratory determination of INR and compared relatively well with expanded and narrow clinical agreement criteria.

Ambulatory Care Facilities↗

Comparison of biomarkers in exhaled breath condensate and bronchoalveolar lavage.

RATIONALE: Exhaled breath condensate (EBC) is increasingly studied as a noninvasive research method of sampling the lungs, measuring several biomarkers. The exact site of origin of substances measured in EBC is unknown, as is the clinical applicability of the technique. Special techniques might be needed to measure EBC biomarkers. OBJECTIVES: To assess biomarker concentrations in clinical disease and investigate the site of origin of EBC, we compared EBC and bronchoalveolar lavage (BAL) biomarkers in 49 patients undergoing bronchoscopy for clinical indications. MEASUREMENTS: We measured exhaled nitric oxide, 8-isoprostane, hydrogen peroxide, total nitrogen oxides, pH, total protein, and phospholipid (n = 33) and keratin (n = 15) to assess alveolar and mucinous compartments, respectively. EBC was collected over 10 min using a refrigerated condenser according to European Respiratory Society/American Thoracic Society recommendations, and BAL performed immediately thereafter. RESULTS: 8-Isoprostane, nitrogen oxides, and pH were significantly higher in EBC than in BAL (3.845 vs. 0.027 ng/ml, 28.4 vs. 3.8 microM, and 7.35 vs. 6.4, respectively; p < 0.001). Hydrogen peroxide showed no difference between EBC and BAL (17.5 vs. 20.6 microM, p = not significant), whereas protein was significantly higher in BAL (33.8 vs. 183.2 microg/ml, p < 0.001). Total phospholipid was also higher in EBC, but keratin showed no difference. No significant correlation was found between EBC and BAL for any of the biomarkers evaluated either before or after correction for dilution. CONCLUSIONS: In clinical disease, markers of inflammation and oxidative stress are easily measurable in EBC using standard laboratory techniques and EBC is readily obtained. However, EBC and BAL markers do not correlate.

Biomarkers↗

The link between providers and patients: how laboratories can ensure quality results with genetic testing.

Advances in genetic testing technology can provide important opportunities for health improvement. Simultaneously, they entail complexity in laboratory analysis and interpretation. The nature of genetic testing may engender implications distinct from other diagnostic tests. In this article, we summarize these implications, including the role of informed consent; quality assurance in diagnostic testing services; interpretation of the test results; patient support; appropriate disclosure; and regulations relevant for laboratories involved with genetic tests. Research and clinical laboratories need to stay abreast of these advancing technologies and their implications for health-care patients and providers. Collaboration between testing personnel, geneticists, and other health-care providers is necessary to ensure that patients receive the full benefits from testing, including a clear understanding of their genetic test information.

Adult↗

Use of PRZM-3 to validate a laboratory to field degradation conceptual model.

The test substance, boscalid, was applied at two field sites, but, depending on how kinetic calculations were performed, the time required for 50% of the initial compound concentration to dissipate (half-life) ranged from 27 to 200 days. Laboratory aerobic soil studies indicated that the DT50 for the compound was about 108 days, and since compound dissipation rates are typically shorter in the field than those observed in the laboratory, confidence in the field half-life calculations was questioned. Researchers have asked whether exposure models might be useful for relating laboratory to field behavior, especially when results are difficult to reconcile between the two systems. In order to determine how realistic field dissipation-time kinetic calculations were, a 60-day DT50 (some masked data), 150-day DT50 and a 196-day rate constant (t1/2) kinetic result were entered into the Pesticide Root Zone Model (PRZM-3) for a California site. A 27-day DT50, and a 200 day t1/2 kinetic result were also entered into the model for a Florida site. Results indicate that using the shortest DT50 solution in PRZM-3 provided the best fit to actual field data. Results from this study suggest that PRZM-3 can be used successfully to address uncertainty between a laboratory conceptual understanding of a compound's behavior and the actual behavior observed in the field.

Biphenyl Compounds↗

Evaluation of the Graseby PCAS. A clinical and laboratory study.

The Graseby patient-controlled analgesia system was evaluated in the laboratory and in clinical use. The problems encountered with eight examples used to treat 510 patients are reported. Laboratory performance revealed the unit to be accurate at infusion volumes of 1 and 2 ml.

Analgesia, Patient-Controlled↗

Hepatitis B surface antigen and e antigen in pleural effusion: a case report.

Hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) were demonstrated in pleural fluid obtained from a 40-year-old dialysis patient who had HBSAg and HBeAg in her serum. The titers of HBsAg and HBeAg were similar in serum and pleural fluid. Examination of the pleural fluid by electron microscopy revealed the presence of intact hepatitis B virus particles. These findings underline the potential hepatitis B virus infectivity of other body fluids besides blood, especially for medical and laboratory personnel.

Adult↗

Differentiation latency and dormancy signatures define fetal liver hematopoietic stem cells at single-cell resolution.

Decoding the mechanisms governing the self-renewal of hematopoietic stem cells (HSCs) during their expansion in the fetal liver (FL) could unlock novel therapeutic strategies to expand transplantable HSCs, a long-standing challenge. To explore intrinsic and extrinsic regulation of FL-HSC self-renewal at single-cell resolution, we engineered a culture platform replicating the FL endothelial niche that supports the amplification of serially engraftable HSCs. Leveraging this platform together with single-cell index flow cytometry, live imaging, transplantation assays, and single-cell RNA sequencing, we demonstrate that differentiation latency, cell-division symmetry, and transcriptional signatures of biosynthetic dormancy are distinguishing properties of rare FL-HSCs capable of serial multilineage hematopoietic reconstitution. Our findings support a paradigm in which intrinsic programs and niche-derived signals together facilitate the symmetric self-renewal of FL-HSCs while delaying their active participation in hematopoiesis. Our study also provides a resource for future investigations into intrinsic and extrinsic signaling pathways governing FL-HSC self-renewal.

Hematopoietic Stem Cells↗

A major trio.

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Academic Medical Centers↗

Evaluating sampling strategies for the detection of avian influenza viruses in the environment.

Highly pathogenic avian influenza (HPAI) viruses pose an increasing threat to wildlife, livestock and human health, underscoring the need for scalable and early-warning surveillance systems. Environmental RNA (eRNA) monitoring offers a non-invasive, cost-effective alternative to traditional host-based sampling by detecting viral genetic material shed into the environment. Despite its utility, the relative performance of different environmental sampling approaches for avian influenza virus (AIV) detection remains poorly resolved. Here, we conducted a longitudinal study with monthly sampling over approximately one year across two urban waterfowl ponds in Aotearoa New Zealand to evaluate four eRNA sampling strategies - fresh faeces, sediment, active-filtered water and passive-filtered water - for their ability to detect AIV. Using a combination of metagenomic sequencing and RT-qPCR, we show that all sample types can detect AIV, although detections were highly inconsistent across sampling methods, locations and time points. While metagenomic sequencing provided valuable genomic data, including subtype identification and phylogenetic context, RT-qPCR exhibited greater sensitivity, with active-filtered water yielding the highest detection rates, and is currently the more cost-effective approach for large-scale surveillance. Notably, AIV detections were asynchronous among sample types and frequently lacked temporal concordance, suggesting that environmental heterogeneity, RNA persistence, and methodological detection limits strongly influence surveillance outcomes. Despite these inconsistencies, phylogenetic analyses revealed that detected viruses belong to established Australasian lineages, highlighting the ability of environmental surveillance to capture ecologically relevant viral diversity. Our findings demonstrate that while eRNA-based surveillance holds substantial promise as a complementary tool for AIV monitoring, its effectiveness is highly dependent on the environmental sampling strategies and laboratory detection methods used.

Ducks↗

Multicenter clinical trial and laboratory utilization of an enzymatic detection method for gonococcal antigens.

Seven institutions participated in a comparative study evaluating standard culture method and a new enzyme immunoassay (EIA, Gonozyme, Abbott Diagnostics) for the detection of Neisseria gonorrhoeae. Five hundred twenty-three patients were entered from hospitals of various sizes representing different population densities, ethnic and economic sectors, and gonococcal prevalence. Statistical analysis showed sensitivity, specificity, and positive and negative predictive values of 80.3%, 94.6%, 66.2%, and 97.3% for the total population tested. For the high-prevalence (greater than 15%) population the respective values were as follows: 78.6%, 91.5%, 68.8%, and 94.7%. Specimens from females had a lower sensitivity than those from males. In the low-prevalence population (less than 10%) results were as follows: 100%, 97.8%, 50%, and 100%. A cost comparison emphasized the benefit of the Gram's stain and culture. It also indicated that, unless batched or assayed at high volume, Gonozyme is not cost competitive for laboratories using standard culture methods. The impact of the EIA method, in general, and Gonozyme, specifically, on the microbiology section also was investigated. Integration would require altering of established work patterns and loss of flexibility and freedom of standard plating technics. The fact that Gonozyme is a "presumptive" test limits it to being a complementary assay, not an alternative. The authors conclude that Gonozyme is optimally suited to a high-volume laboratory, screening a low-prevalence female outpatient population, where specimen transport is a problem and gonococcal resistance to penicillin has not been demonstrated. This would include sexually transmitted disease clinics, reference laboratories, and state health departments.

Antigens, Bacterial↗