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Contribution of serological tests and blood culture to the early diagnosis of systemic candidiasis.

The isolation of Candida species from a single blood culture is considered sufficient evidence for the initiation of systemic antifungal therapy. However, blood cultures still lack sensitivity. Previous reports have suggested that the combined serological detection of mannanemia and anti-mannan antibodies may be useful for the diagnosis of systemic candidiasis caused by Candida albicans (specificity and sensitivity 93% and 80%, respectively). In this study, serological tests to detect Candida albicans mannan and Candida albicans antibodies (Platelia Candida Antigen and Antibody tests; Bio-Rad, France) were applied retrospectively to a series of patients with at least one Candida-positive blood culture and from whom at least one serum sample, taken before or on the day of blood culture, was available. Forty-five patients were selected, including 23 infected by Candida albicans, 4 by Candida glabrata, 9 by Candida tropicalis, 5 by Candida parapsilosis, and 4 by Candida krusei. Serological tests were positive in 73% of patients at least 2 days, and in some patients, up to 15 days before blood cultures became positive. These data suggest that serological surveillance of at-risk patients using the Platelia Candida tests could result in earlier initiation of antifungal therapy, especially when used in conjunction with blood cultures. In this way, more efficient management of nosocomial infections caused by Candida species can be achieved.

Candidiasis↗

Diagnostic utility of invasive tests and serology for the diagnosis of Helicobacter pylori infection in different clinical presentations.

BACKGROUND: Invasive and noninvasive tests are used for the diagnosis of Helicobacter pylori infection. The aim of this study was to determine the diagnostic utility of rapid urease test (RUT), culture, histology and serology for the diagnosis of H. pylori in patients with different clinical presentations. METHODS: We studied 527 consecutive patients (mean age, 52.5 years; F:M, 1.3; age range 15-89 years) enrolled at the Hospital Universitario, Universidad Autónoma de Nuevo León. Patients had gastric cancer (GC, 9.1%), non-ulcer dyspepsia (NUD, 81.4%), or peptic ulcer disease (PUD, 9.1%). The infection by H. pylori was determined by histology, rapid urease test, culture, and serology. Patients were determined as infected with H. pylori if at least a) two invasive tests were positive and b) two tests were positive (invasive or non-invasive). Diagnostic utility was calculated for each assay. RESULTS: Prevalence of infection in the whole studied population was 50.9%. In NUD patients the prevalence was 51.3%, in PUD patients 58.3%, and in GC patients 39.6%. When we used the first diagnostic criteria, for the whole studied population, the RUT was the most reliable test, followed by the culture. Histology had the best sensitivity for the whole studied population and NUD patients and RUT had the best sensitivity value for the GC patients. In the whole studied population, NUD and GC patients, RUT and culture had the best specificity, accuracy and PPV. For PUD patients, serology had the best performance. When we used the second diagnostic criteria, histology and serology had a better performance compared with the results obtained with the first diagnostic criteria. CONCLUSIONS: Diagnostic utility of the tests varies according to the clinical presentations, which should be considered in the selection of the diagnostic test for the detection of H. pylori.

Adolescent↗

The use of serologic tests for the diagnosis of chlamydial infections.

Serology is commonly used for the diagnosis of acute Chlamydia pneumoniae infections and also for the diagnosis of complicated Chlamydia trachomatis infections. Furthermore, recent sero-epidemiological studies have linked C. pneumoniae infection with several diseases traditionally considered non-infectious. The objectives of this mini-review are to critically review and discuss some selected analytical and methodological aspects, controversies and current problems in chlamydial serodiagnosis. To illustrate our views we present some original data of the comparison of current technologies. The review of the literature revealed high variability in methodologies applied to different studies. This observation was supported by our own data, which explains occasional conflicting clinical interpretation. Although the microimmunofluorescence (MIF) technique is generally considered as the gold standard for serodiagnosis of chlamydial infections, assay conditions are highly variable and hence pose a major problem in the interpretation of the results. For instance, many recent studies linking C. pneumoniae and atherosclerosis have utilized MIF techniques with variable threshold criteria for the positivity, in combination with selection bias of cases and controls possibly leading to conflicting results. Variability of assay conditions is also a common problem with Western blots, and interpretation is problematic when both anti-C. pneumoniae and anti-C. trachomatis antibodies are present. Furthermore, there is a lot of disagreement in serological criteria applied to recently emerged enzyme immunoassay (EIA) techniques when these assays are used for acute and non-acute clinical conditions and their association with Chlamydiae. In conclusion, standardization of serological techniques and the development of uniform criteria for interpretation of serologic findings is necessary to increase our knowledge of the biology of Chlamydiae, pathogenesis of any chlamydial infection and chronic infections in particular.

Antibodies, Bacterial↗

A practical guide for serologic evaluation of autoimmune connective tissue diseases.

UNLABELLED: Serologic testing is important in the evaluation of patients with autoimmune connective tissue diseases (CTD). There are many techniques. Each of the tests has different sensitivity and specificity with varying diagnostic value. These serologic tests detect antibodies to numerous cellular components. The diagnostic significance and specificity of each antibody vary. Choosing the appropriate test and understanding its clinical utility is an important aspect in the diagnostic evaluation of patients with CTD. (J Am Acad Dermatol 2000;42:159-74.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the various serologic tests for CTD, should understand the associations of specific antibodies with individual CTD, and should identify the factors that influence the predictive value of these serologic tests.

Autoimmune Diseases↗

Comparison of serological and DNA PCR-SSP typing results for HLA-A and HLA-B in 421 Black individuals: a Collaborative Transplant Study report.

In a recent study, we observed a discrepancy rate of 8.5% between the results of molecular and serological HLA class I typing in Caucasian kidney donors and recipients. In the present study we addressed the question how often black individuals are mistyped using the serological technique. 421 Blacks whose HLA typing results were reported to the Collaborative Transplant Study (CTS) were typed retrospectively for HLA-A and -B using a PCR-SSP method. 78 of the 421 individuals (18.5%) showed a discrepancy for HLA-A and 107 individuals (25.4%) for HLA-B. 36.3% of all individuals tested showed either an HLA-A or an HLA-B discrepancy. 13.1% of the discrepancies at the HLA-A locus were due to antigen misassignments and 4.8% were due to missed antigens. HLA-B discrepancies were caused in 15.7% by antigen misassignments and in 10.5% by missed antigens. These results demonstrate an impressive advantage of the PCR-SSP method for HLA-A and HLA-B locus typing over serological typing in black individuals. The high typing discrepancy rate observed in Blacks provides a strong argument for replacing serological typing by the DNA method. It is likely that this will improve the HLA matching correlation in clinical transplantation in Blacks.

Black People↗

The utility of serologic testing for varicella in an adolescent population.

The purpose of this study was to determine what proportion of adolescents without a history of varicella are seropositive, and if serologic testing of this adolescent subpopulation is cost-effective. We identified 122 patients with 'no' or 'unknown' histories of chicken pox from our adolescent clinic. Of these, 58 (48%) were found to be Varicella Zoster Virus (VZV) seropositive. Cost to the government for batched serologic testing of all unknowns was $682.65, while each adolescent vaccinated cost $59.60. Serologic testing prior to routine immunization of adolescents with unclear varicella histories saved $2774.15 (38% of routine immunization costs). In this population, serologic testing is more cost effective than routinely immunizing all unknowns.

Adolescent↗

Evaluation of two serological tests for the diagnosis of chlamydial respiratory disease.

Serological tests for chlamydial infection are one of the most frequently used methods in the diagnosis of atypical respiratory infections. Use of serological tests has implicated chlamydial infections in asthma, arthritis and coronary heart disease, but the specificity of chlamydial serology tests has been questioned. The immunofluorescence test is the most sensitive and specific serological test available for detection of chlamydial antibodies. This study compares two commercially available immunofluorescent antibody tests. The SeroFIA test using purified elementary bodies of Chlamydia pneumoniae, C. psittaci and C. trachomatis, detected 24 cases of acute C. pneumoniae infection, whereas the Spot IF test using whole cell antigen of C. psittaci and C. trachomatis, misdiagnosed 20 of these as psittacosis and missed four cases.

Antibodies, Bacterial↗

Microbiological and serological diagnosis of pertussis.

Swedish vaccine trials have been used to examine sensitivity and specificity of diagnostic procedures for Bordetella pertussis infection. The proportions of cases diagnosed by culture and serology were 55% and 45%, respectively, when both methods were optimized. The culture method included nasopharyngeal aspiration, direct inoculation on plates, enrichment, and repeated collection of samples. An enzyme-linked immunosorbent assay for IgG antibodies to pertussis toxin (PT) and to filamentous hemagglutinin, with paired sera, was used for serology. Preexposure sera other than the acute serum increased the sensitivity of serology by 10%. A serology quality-assurance program to control imprecision and allow comparability over time and between laboratories is described. The direct fluorescent antibody technique had a sensitivity of 38% and a specificity of 99.6% in comparison with culture. A nested polymerase chain reaction (PCR) with the PT promoter region as target was 95% sensitive in comparison with culture if a cation-exchange resin was used to reduce inhibition. PCR enabled us to identify 83 positive samples in addition to 215 culture-positive ones-an increase of 38%--all with other indicators of pertussis infection.

Bordetella pertussis↗

Use caution with serologic testing for Helicobacter pylori infection in children.

Commercial serologic assays accurately detect adult Helicobacter pylori infection. Their use in children remains controversial. An ELISA to detect H. pylori IgG in children was developed and compared with three commercial assays. ELISA standardization was done with sera from all ages and validation was done with another cohort of sera with known H. pylori status. Three commercial serologic assays were subsequently compared against this pediatric ELISA at independent sites, at which 142 pediatric serum samples from different countries were evaluated. The pediatric ELISA was 91.4% sensitive. Assay 3 demonstrated a sensitivity of 78%. Less sensitivity was observed for assay 1 (70%) and assay 2 (63%). Accuracy of commercial assays was greatly reduced when sera from developing countries and younger ages were evaluated. Results of serologic tests used to diagnose H. pylori should be interpreted with caution when evaluating children with abdominal pain. Accurate serologic assays in children may be more important for epidemiologic research than for clinical decision making.

Adolescent↗

Cadaver donor discards secondary to serology.

The use of cadaveric skin has made a major impact in the survival of patients experiencing major thermal injury. However, the availability of cadaveric skin is often limited by potentially pathogenic organisms. Very little data exists as to why cadaveric skin from donors who have been previously screened was discarded. From March 1994 to March 1996, 813 donors were referred to our tissue bank. All donors were reviewed for the cause of death, history and physical, and social history. One hundred fifty-three donors screened were discarded. Sixty-one donors of this group were discarded because of positive serologies. The following are the percentages of the specific positive serologies: hepatitis B core antibody, 52.3%; hepatitis B surface antigen, 18.1%; hepatitis C virus antibody, 14.3%; human immunodeficiency virus antibody, 4.9%; human T lymphocyte virus antibody, 4.9% and syphilis, 5.5%. Retrospectively, all donor screening questionnaires were reviewed for possible indicators in relation to positive serologic testing. Current screening methods, although excellent in social screening, still fail to identify a significant number of donors who may have positive serologies because of hepatitis, human immunodeficiency virus, human T lymphocyte virus, or syphilis. As the field of tissue banking continues to evolve, the focus will need to be directed toward better screening mechanisms in order to decrease our current discard rates after donors have been approved through the screening process.

Algorithms↗

Hepatitis B virus serology in pregnant women: transmittal of results from obstetricians to pediatricians in California.

From late 1992 to early 1993, in order to assess the knowledge, attitudes and practice patterns of California obstetricians regarding hepatitis B virus screening of pregnant women and how maternal hepatitis B virus serologies are communicated by obstetricians to pediatricians, we mailed questionnaires to a random sample of 801 California obstetricians and 1030 California pediatricians. Response rates were 65.7% (526) for obstetricians and 71% (732) for pediatricians. Although 99.8% of the surveyed obstetricians indicated that they routinely screened all pregnant women for hepatitis B virus, their knowledge of the correct screening tests to order and their interpretation was mixed. Only 56.3% (95% confidence interval, 51.2 to 61.2) were aware of the California law and approximately 12% did not understand that it mandated universal screening of pregnant women. There was a great difference of opinion between obstetricians and pediatricians regarding how to communicate hepatitis B virus serology results on the mother. Forty-nine percent of obstetricians report that they always request the nurse to inform the pediatrician (48.6%), 51.2% always verbally inform the pediatrician, 39.1% always place an order in the mother's chart and 5.7% always send a letter to the pediatrician. In contrast only 12.9% of pediatricians responded that they always received maternal hepatitis B virus serology results from the obstetrical or nursery nurse, only 2.6% always received a verbal communication from the obstetrician, 14.1% always retrieved it from a written report in the mother's chart and 4.2% reported that they always received a letter from the obstetrician. A uniform system should be adopted to ensure efficient transmission of maternal hepatitis B serology results from obstetricians to pediatricians to ensure prompt treatment to prevent vertical transmission of hepatitis B.

Adult↗

Pretransplant herpesvirus serology and acute graft-versus-host disease.

Logistic regression was used to analyze the influence of pretransplant herpesvirus antibodies, in both patients and donors, on the development of acute graft-versus-host disease in 111 consecutive HLA-identical bone marrow recipients. In bivariate analysis, recipient seropositivity for cytomegalovirus (P = 0.01), donor seropositivity for herpes simplex virus (P = 0.02), and low bone marrow cell dosage (P less than 0.05) were associated with a high incidence of grade II-IV acute GVHD. In multivariate analysis the P values were P less than 0.05 for a positive recipient CMV serology and P = 0.07 for a positive donor HSV serology. Positive serology for 1-2 herpes-viruses among recipients or donors both resulted in a 12% incidence of grade II-IV acute GVHD. Positive serology for 3-4 herpesviruses among patients or donors resulted in an incidence of 32% and 38% of acute GVHD, respectively (P less than 0.05). It is concluded that recipient and donor pretransplant herpesvirus immunity can be used to calculate the risk of moderate-to-severe acute GVHD.

Acute Disease↗

Comparative study of cytomegalovirus (CMV) antigenemia assay, polymerase chain reaction, serology, and shell vial assay in the early diagnosis and monitoring of CMV infection after renal transplantation.

BACKGROUND: Early diagnosis of cytomegalovirus (CMV) infection, which is an important cause of morbidity and mortality in renal transplant recipients, remains of great importance. This prospective study was performed in kidney transplant recipients to determine the diagnostic value of the CMV antigenemia assay in comparison with polymerase chain reaction (PCR), serology, and shell vial assay. METHODS: Seventy-five consecutive renal transplant recipients were enrolled in this study and monitored by both antigenemia assay and serology. The initial 34 of the 75 patients were subjected to PCR and shell vial assay. RESULTS: Antigenemia, PCR, and shell vial assay became positive before the onset of CMV-related symptoms in 31/34 (89%), 13/16 (81%), and 2/16 (13%), respectively. None of the 34 patients who had symptomatic CMV disease showed a significant increase in IgG or IgM before the onset of symptoms. Antigenemia and PCR assays turned positive, 7 and 11 days (median), respectively, before the onset of clinical symptoms. Serology and shell vial assay became positive 21 and 25 days (median), respectively, after the onset of CMV-related clinical symptoms. To examine the clinical value of these assays, "good correlation" was defined based on the correlation between the clinical course and the results of the assays. Good correlation with the antigenemia assay was observed in 33 (96%) out of 34 renal transplant recipients who recovered from their CMV disease after ganciclovir therapy. Only one of 16 (7%) patients showed good correlation by shell vial assay, whereas PCR and serology did not show a good correlation. Consequently, antigenemia was considered the best way to monitor CMV infections after kidney transplantation. CONCLUSIONS: Only the CMV antigenemia assay can be successfully employed after renal transplantation for the early diagnosis and extensive monitoring of active CMV infection.

Adolescent↗

Evaluation of serological markers to differentiate between ulcerative colitis and Crohn's disease: pANCA, ASCA and agglutinating antibodies to anaerobic coccoid rods.

BACKGROUND: Accurate diagnosis of inflammatory bowel disease, in particular the differentiation between ulcerative colitis and Crohn's disease, is important for treatment and prognosis. Several serological markers have been used as non-invasive diagnostic tools in inflammatory bowel disease patients both to differentiate ulcerative colitis from Crohn's disease and to define patient subgroups. AIM: To evaluate the diagnostic accuracy of three serological tests in differentiating ulcerative colitis from Crohn's disease by single or combined use. METHODS: Sera from 51 patients with clinically well-defined ulcerative colitis and 50 patients with clinically well-defined Crohn's disease were analysed. Detection assays for the presence of perinuclear anti-neutrophil cytoplasmatic antibodies (pANCA), antibodies against (ASCA) and serum agglutinating antibodies to anaerobic coccoid rods were studied. Sensitivity, specificity, predictive values and likelihood ratios of each of these serological tests were determined. RESULTS: In supporting the diagnosis of ulcerative colitis, the sensitivity and specificity of the pANCA test were 63% and 86%, respectively. The ASCA test (immunoglobulin A or immunoglobulin G positive) for diagnosing Crohn's disease had a sensitivity of 72% and a specificity of 82%. The sensitivity of antibodies to anaerobic coccoid rods in diagnosing Crohn's disease was 52%, whereas specificity was 90%. A combination of pANCA-positive and ASCA-negative results in the case of ulcerative colitis showed a sensitivity and specificity of 51% and 94%, respectively. However, for ASCA-positive and pANCA-negative results in the case of Crohn's disease, sensitivity was 64% and specificity was 94%. The combination of all three tests increased positive predictive value and specificity to 100% for both ulcerative colitis and Crohn's disease. In Crohn's disease patients, positive pANCA was correlated with colonic involvement. No correlation was found between the presence of any of these antibodies and disease activity, duration and behaviour or medical treatment. CONCLUSIONS: The value of these serological tests in differentiating ulcerative colitis from Crohn's disease is limited when used separately but, by combining two or more tests, the positive predictive value and specificity can be improved substantially. These tests might be of help in studying disease heterogeneity, and may contribute to defining various subgroups of patients with different pathogeneses.

Adolescent↗

Changing serological status and low vaccination-induced protection rates against hepatitis B characterize chronic hepatitis C virus-infected injecting drug users in Greece: need for immunization policy.

OBJECTIVE: To evaluate the serological status of hepatitis B virus infection among Greek injecting drug users with chronic hepatitis C virus infection; to correlate hepatitis B virus infection status with the possible time of infection and the principal genotype of hepatitis C virus infection. METHODS: Two hundred and thirty consecutive injecting drug users with chronic hepatitis C virus infection were evaluated for serological markers of hepatitis B virus infection. One hundred and three of them (44.8%) reported intravenous drug use beginning before 1992 (group A) and 127/230 (55.2%) after 1992 (group B). Statistical analysis of data was based on Student's t-test and chi analyses. RESULTS: Eighty-five of 103 patients from group A (82.5%) and 28/127 (22%) from group B had serological markers of previous hepatitis B virus infection (P<0.001). Eleven patients from group A (10.6%) and 78 (61.4%) from group B were seronegative for all hepatitis B virus markers (P<0.001). Only 3.8% (4/103) of group A patients and 16.5% (21/127) of group B had vaccination-induced protective antibody levels (anti-HBs) against hepatitis B (P=0.02). The majority of patients were infected with hepatitis C virus genotype-3 (64.7% from group A vs 56.7% from group B, P=0.42). The percentages of patients infected with genotype-1 were also comparable in both groups (15.5% from group A vs 30.8% from group B, P=0.09). A significantly higher percentage of group A patients were infected with genotype-4 (19.7%) than those in group B (4.9%, P=0.02). CONCLUSION: The serological profile of hepatitis B virus infection among Greek hepatitis C virus-infected injecting drug users is changing. The proportion of successfully vaccinated hepatitis B virus injecting drug users, although significantly higher than the previous decades, is still relatively low. Vaccination policy in this high-risk group for viral hepatitis is urgently needed.

Adult↗

Serologic and genetic markers of celiac disease: a sequential study in the screening of first degree relatives.

OBJECTIVES: The prevalence of celiac disease (CD) among the relatives and the complications of an undiagnosed CD prompted us to identify a useful disease screening strategy. METHODS: We studied 441 first degree relatives of 208 CD patients by immunoglobulin (Ig)A antiendomysium antibodies (EMA) and radioimmunoprecipitation assay (RIA) IgA antitransglutaminase autoantibodies (TGAA). Of these, 364 were typed for human leukocyte antigen-DRB1, -DQA1, and -DQB1 genes by the polymerase chain reaction sequence specific primers method. It was suggested to the autoantibody-positive subjects that they should undergo intestinal biopsy. RESULTS: TGAA were positive in 46 of 439 relatives, EMA in 38; intestinal lesions related to CD were present in 40 subjects. We also found two immunodeficient fathers with duodenal villous atrophy. In three serology-positive subjects, permission for intestinal biopsy was refused; for another three serology-positive cases, duodenal mucosa was normal. Thus, the strict CD prevalence resulted 9.5%, the enlarged prevalence 10.9%. The DQ2/DQ8 heterodimers were carried in 231 of 364 subjects and in 38 of 40 biopsy-proven celiac patients. Three DQ2-positive parents became positive to the serology during a long-lasting follow-up. CONCLUSIONS: On the basis of a carefully conducted study, CD prevalence in our series was seen as very high. These data suggest an accurate algorithm to select candidates for intestinal biopsy among CD high-risk subjects. First, an evaluation of the sensitive RIA TGAA and of total IgA (in IgA deficiency RIA IgG anti-tissue transglutaminase assay) should be performed. Then, an evaluation of the TGAA and the genetic study would be advisable 2 to 3 years later in negative subjects. Those carrying the DQ2/DQ8 heterodimers should continue the serologic follow-up; the others need a clinical follow-up.

Adolescent↗

Management of neonates born to mothers with reactive serologic tests for syphilis.

PURPOSE OF REVIEW: The dramatic resurgence of maternal and congenital syphilis in the United States highlights the need for their optimal management as syphilis in pregnancy can result in substantial neonatal morbidity and mortality. This review summarizes current epidemiology and discusses guidance on the management of neonates born to mothers with reactive serologic tests for syphilis. RECENT FINDINGS: Timely communication with local health department professionals is essential for optimal management of mothers with reactive serologic tests for syphilis and their neonates. Knowledge of maternal syphilis treatment history by partnering with local jurisdictions can circumvent much of the incertitude surrounding neonatal management. All neonates born to mothers with reactive serologic tests for syphilis should be tested using a nontreponemal ('lipoidal antigen') test. However, a reactive test may only indicate maternal nontreponemal IgG antibodies that are transferred transplacentally to the fetus. Therefore, neonatal management depends on maternal history and treatment for syphilis as well as clinical, laboratory, and radiographic findings in the neonatal evaluation. Existing management algorithms are complex, highlighting the need for a more practical, yet safe, approach. SUMMARY: A neonatal management guideline is proposed that may simplify the management of neonates born to mothers with reactive serologic tests for syphilis while advocating for expanded use of single-dose benzathine penicillin G therapy.

Humans↗

Allelic frequencies of the HLA-B17 antigen group: comparative analysis by serology, IEF and PCR-SSOP typing.

Current typing technology for class I HLA antigens uses serological and/or isoelectric focusing gel electrophoresis. DNA typing for the HLA class I antigens can accurately identify the class I genotype of individuals and cell lines. Here, we report correlation of DNA typing results with serological and IEF results for the B17 group. The B17 antigens are relatively common, being carried by almost 9% of Caucasians and 28% of blacks. In this study, five 10th International Histocompatibility Workshop cell lines carrying B17 and 106 individuals in 61 families carrying B17 were DNA typed for B17 using B17-allele-specific amplification and sequence specific oligonucleotide probe hybridization pattern analysis. 38 (55.07%) out of 69 unrelated haplotypes had B*5701, 23 (33.33%) had B*5801, 6 (8.70%) had B*5702, and 2 (2.90%) had B*5802. DNA typing results correlated well with serological and isoelectric focusing results. In general, there was high degree of agreement between all three methods, although heterozygosity for B17 poses a particular problem for serological and IEF methodology. Both B*5701 and B*5801 have the same electrophoretic mobility on IEF gel, corresponding to B17.2, B*5702 corresponds to B17.1, while B*5802 corresponds to B17.3.

Amino Acid Sequence↗