Detection of in vivo hepatitis B virus surface antigen mutations-A comparison of four routine screening assays.

An important requirement for a state-of-the-art hepatitis B surface antigen (HBsAg) screening assay is reliable detection of mutated HBsAg. Currently, there is a striking shortage of data regarding the detection rates of in vivo HBsAg mutations for these clinically important assays. Therefore, we compared the detection rates of four commercial HBsAg screening assays using a global cohort of 1553 patients from four continents with known HBV genotypes. These samples, which represent the broadest spectrum of known and novel HBsAg major hydrophilic region (MHR) mutations to date, were analyzed for the presence of HBsAg using the Roche Elecsys® HBsAg II Qualitative, Siemens ADVIA Centaur XP HBsAg II, Abbott Architect HBsAg Qualitative II and DiaSorin Liaison® HBsAg Qualitative assays, respectively. Of the 1553 samples, 1391 samples could be sequenced; of these, 1013 (72.8%) carried at least one of the 345 currently known amino acid substitutions (distinct HBsAg mutation) in the HBsAg MHR. All 1553 patient samples were positive for HBsAg using the Elecsys® HBsAg II Qual assay, with a sensitivity (95% confidence interval) of 99.94% (99.64%-100%), followed by the Abbott Architect 99.81% (99.44%-99.96%), Siemens ADVIA 99.81% (99.44%-99.96%) and DiaSorin Liaison® 99.36% (98.82%-99.69%) assays, respectively. Our results indicate that the Elecsys® HBsAg II Qual assay exhibits the highest sensitivity among the commercial HBsAg screening assays, and demonstrate that its capacity to detect HBV infection is not compromised by HBsAg MHR mutants.

Racial differences in healthcare utilization among patients with suspected or diagnosed preeclampsia: A retrospective cohort study.

OBJECTIVES: To analyze healthcare resource utilization and severe maternal morbidity (SMM) in Black and White patients with preeclampsia diagnosis versus signs/symptoms. STUDY DESIGN: This was a retrospective cohort study analyzing data from the IBM® Explorys Database between 7/31/2012-12/31/2020. Demographic, clinical, and laboratory data were extracted. Healthcare utilization and SMM were analyzed during the antepartum period (20 weeks of gestation until delivery) among Black and White patients with signs/symptoms of preeclampsia, with a diagnosis of preeclampsia, or neither (control). MAIN OUTCOME MEASURES: Healthcare utilization and SMM in those with a preeclampsia diagnosis or signs/symptoms of preeclampsia only were compared with a control group (White patients with no preeclampsia diagnosis or signs/symptoms). RESULTS: Data from 38,190 Black and 248,568 White patients were analyzed. Patients with preeclampsia diagnosis or signs/symptoms were more likely to visit the emergency room compared to those without diagnosis or signs/symptoms. Black patients with signs/symptoms of preeclampsia had the highest elevated risk (odds ratio [OR] = 3.4), followed by Black patients with a preeclampsia diagnosis (OR = 3.2), White patients with signs/symptoms (OR = 2.2), and White patients with a preeclampsia diagnosis (OR = 1.8). More Black patients experienced SMM (SMM rate 6.1% [Black with preeclampsia diagnosis] and 2.6% [Black with signs/symptoms]) than White patients (5.0% [White with preeclampsia diagnosis] and 2.0% [White with signs/symptoms]). SMM rates were higher for Black preeclampsia patients with severe features than for White preeclampsia patients with severe features (8.9% vs 7.3%). CONCLUSIONS: Compared with White patients, Black patients had higher rates of antepartum emergency care and antepartum SMM.

Airway epithelium-derived transforming growth factor-beta is a regulator of fibroblast proliferation in both fibrotic and normal subjects.

BACKGROUND: In the healthy lung, airway epithelial cells (AEC) regulate fibroblast proliferation through release of soluble factors, such as prostaglandins and proteins. Fibroproliferative diseases and airway remodelling may result from an inadequate generation of suppressive factors by AEC or the inability of fibroblasts to respond to them appropriately. OBJECTIVE: The aim of this study was to study the effect of primary human AEC on the proliferation of fibroblasts obtained from healthy and fibrotic lungs in an interactive cell culture model. RESULTS: Conditioned medium (CM) from 14 out of 16 AEC lines significantly inhibited proliferation of normal human lung fibroblasts by 51.2+/-6.0%. The proliferation of fibroblasts derived from patients with lung fibrosis was equally inhibited by CM of AEC. The inhibitory effect of AEC-CM was completely reversed when fibroblasts were pre-incubated with 2.5 microm indomethacin. Furthermore, primary human AEC, but not fibroblasts, secrete TGF-beta, and the inhibitory effect of the AEC-CM was blocked by neutralizing anti-TGF-beta antibodies. CONCLUSION: These results demonstrate that AEC actively inhibit the proliferation of both normal and fibrotic fibroblasts via TGF-beta, which induces the prostaglandin E(2) synthesis in fibroblasts. The data indicate that proliferative lung diseases may be treated using the epithelial cell as the target of medication.

A comparison of the diagnostic utility of the sFlt-1/PlGF ratio versus PlGF alone for the detection of preeclampsia/HELLP syndrome.

OBJECTIVE: The Elecsys(®) immunoassay sFlt-1/PlGF ratio and the Triage(®) PlGF assay were compared (in a prospective, multicenter, case-control study) for diagnosis of preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. METHODS: Women in European perinatal care centers with singleton pregnancies were enrolled: 178 cases had confirmed preeclampsia and 391 controls had normal outcome. Patients in the preeclampsia/HELLP syndrome group were matched pairwise by gestational week to healthy controls (1:2). Maternal blood samples were analyzed using (a) fully automated Elecsys PlGF and Elecsys sFlt-1 immunoassays with two cutoffs (early-onset [<34 weeks] ≤33, ≥85; late-onset [≥34 weeks] ≤33, ≥110), and (b) Triage PlGF immunoassay (single cutoff). Diagnostic performance and utility were assessed. RESULTS: Respectively, 83 and 95 women had early-onset or late-onset preeclampsia/HELLP syndrome. The overall diagnostic performance of the Elecsys immunoassay sFlt-1/PlGF ratio (area under the curve [AUC] 0.941) was higher than for Triage PlGF (AUC 0.917). The Elecsys immunoassay sFlt-1/PlGF ratio sensitivity and specificity was: 94.0% (95% confidence interval [CI] 86.5-98.0) and 99.4% (95% CI: 96.8-99.9) for early-onset preeclampsia; and 89.5% (95% CI: 81.5-94.8) and 95.4% (95% CI: 91.7-97.8) for late-onset preeclampsia. The Triage assay sensitivity and specificity was: 96.4% (95% CI: 89.8-99.3) and 88.5% (95% CI: 82.8-92.8) (early-onset); and 90.5% (95% CI: 83-96) and 64.5% (95% CI: 57.8-70.9) (late onset). CONCLUSIONS: The fully automated Elecsys immunoassay sFlt-1/PlGF ratio provides improved diagnostic utility over the Triage PlGF assay with improved specificity for the clinical management of pregnant women with suspected preeclampsia/HELLP syndrome.

Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery.

The cause of stillbirth and preterm delivery is often unknown. We studied the prevalence of Chlamydia trachomatis antibodies in mothers with stillbirth and preterm labor. Serum specimens from 72 mothers with stillbirth after the 21st gestational week, and from 48 mothers with preterm delivery between gestational weeks 23 and 29, both from the greater Helsinki area, and cord blood from 96 consecutive liveborn deliveries at the Department of Obstetrics and Gynecology, the University of Helsinki, were studied for antibodies to C. trachomatis immunotypes CJHI, GFK and BED by microimmunofluorescence test. The prevalence of C. trachomatis antibodies was highest, 33.3%, in mothers with stillbirth, 18.8% in mothers with preterm delivery, and 10.4% in cord blood. The IgM seropositivity rate was high among mothers with preterm delivery (8.3%). We conclude that C. trachomatis IgG antibodies are frequently detected in sera from mothers with stillbirth, suggesting past infection, while mothers with preterm delivery often have serum IgM antibodies, suggesting of acute infection.

Chlamydia trachomatis infection in mothers with preterm delivery and in their newborn infants.

We studied Chlamydia trachomatis infection in mothers with preterm delivery and intrauterine transmission of the infection to their offspring. Forty-one mothers with preterm labour and their newborn infants (n=50) were studied for the presence of C. trachomatis infection using microimmunofluorescence test for detection of serum antibodies against C trachomatis and polymerase chain reaction for detection of C. trachomatis-specific DNA in mucosal swabs. Antibodies to C trachomatis were found in serum of 12 mothers (29%). Five of fourteen mothers had C. trachomatis DNA in cervical specimens. Eighteen neonates were born to the 14 mothers with positive serology and/or C. trachomatis DNA. C. trachomatis DNA was detected in specimens from 10 of the 18 neonates (55.5%). Three of the available cord blood samples contained C trachomatis IgM antibodies. Our results strongly suggest that mothers and their preterm babies may benefit from screening for active C. trachomatis infection.

Chlamydia trachomatis detected in human placenta.

AIMS: To evaluate the relation between Chlamydia trachomatis infection and stillbirth, placental tissue was studied for the presence of C trachomatis. METHODS: Paraffin wax embedded placental tissue of a stillbirth fetus, born at the 36th week of gestation to a 21 year old mother with high serum antibody titres to C trachomatis immunotypes during pregnancy and who was culture positive to C trachomatis three years previously, was studied by in situ hybridisation, polymerase chain reaction, and immunohistochemistry for the presence of C trachomatis. RESULTS: C trachomatis was detected in placental specimens by in situ hybridisation and alkaline phosphatase antialkaline phosphatase staining in several sections, whereas control tissues were uniformly negative, indicating the presence of C trachomatis nucleic acid and antigen in the placenta. CONCLUSION: This is the first reported case in which C trachomatis has been demonstrated in the human placenta.

Chlamydia trachomatis seropositivity during pregnancy is associated with perinatal complications.

Sera from the mothers of all children from the greater Helsinki area who were treated in the Neonatal Intensive Care Unit (NICU) of Children's Hospital (University of Helsinki) during a 22-month period were studied serologically, and antibody levels for mothers were compared with those for matched controls. IgM to Chlamydia trachomatis serotype GFK was detected more often in sera from mothers with children in the NICU than in that from controls; IgM was detected in sera from 39 of 264 mothers vs. 15 of 274 controls (P < .001; two-tailed test). The gestational age of children born to mothers in the IgM-seropositive group was 32.4 weeks whereas that of children born to mothers in the IgG/IgM-seronegative group was 34.3 weeks (all children were treated in the NICU). The frequency of signs of maternal infection (i.e., fever and vaginal discharge), the frequency of meconium-stained amniotic fluid, the frequency of chorioamnionitis, and the mortality rate were higher in the IgM-seropositive group than in the IgM-seronegative group; pneumonia, atelectasis, and pneumothorax occurred more frequently in the seronegative group. Thus, in terms of birth weight and perinatal infections, the outcome was better for children whose mothers did not have antibodies to C. trachomatis.

Chlamydia pneumoniae associated with central nervous system infections.

We identified 15 patients with serological evidence of current Chlamydia pneumoniae infection when we studied 263 patients with central nervous system infections among an adult population of 3 million in 1993. In 9 of the 15 patients no other associated or etiological agents were found. One patient died. Sequelae appeared in 7 patients. In neurological infections, C. pneumoniae may be more prevalent as an associated agent than appreciated, and adequate antibiotic therapy may be life-saving.

Increased frequency of Chlamydia pneumoniae antibodies in patients with asthma.

The worldwide increase in asthma incidences and the impact of the disease on public health care have led to new investigations of the cause of the disease. Besides well-defined environmental causes, accumulating evidence suggests that respiratory tract infections play an important role in the pathogenesis of asthma. Among these microorganisms Chlamydia pneumoniae is an intracellular pathogen causing persistent infection. Chlamydia pneumoniae infection has been discussed as possibly inducing the development of asthma. This study was designed to investigate the presence of C. pneumoniae-specific IgG, IgA, and IgM antibodies in serum samples of 33 adults with a clinical history of asthma, positive methacholine test, and reduced FEV(1). Patients with asthma were compared with age-, sex-, and locality-matched control subjects (n = 33). We observed no acute infection either in patients with asthma or in control subjects, but 63% of all investigated individuals had signs of past infection. Chlamydia pneumoniae-specific IgA was detected in 52% of the patients with asthma and in 15% of the healthy control subjects (p < 0.01). Serological evidence of chronic infection with C. pneumoniae (high IgG [> pr = 1:512] and high IgA [> or = 1:40]) was more frequent in patients with asthma (18.2%) compared with control subjects (3.0%) (p < 0.01). Our results provide further evidence that chronic infection with C. pneumoniae is linked to asthma.

Prevalence of Chlamydia pneumoniae specific antibodies in different clinical situations and healthy subjects in Izmir, Turkey.

Serological markers for Chlamydia pneumoniae were investigated by using the microimmunofluorescence (MIF) test in various age and patient groups in a specific area in Turkey. IgG seropositivity to C. pneumoniae was 64.3% and 18.7% in healthy adults and children, respectively. The highest positivity rate (77%) was in the 15-19 age group. Among the groups investigated, serological findings revealed a possible etiological association between C. pneumoniae and the clinical condition in the groups with acute myocardial infarction, atypical pneumoniae and chronic obstructive pulmonary disease.