Presence of hepatitis B virus markers in umbilical cord blood: Exposure to or infection with the virus?

BackgroundWe aimed to clarify whether presence of hepatitis B virus (HBV) markers in cord blood indicates exposure to or infection with HBV.MethodsWe prospectively recruited HBsAg-positive pregnant women and their neonates 2012 through 2015. All neonates received postnatal immunoprophylaxis. The infants were followed up at 7–14 months of age.ResultsTotally 329 HBsAg-positive pregnant women and 333 neonates were enrolled. No cord blood was anti-HBc IgM positive. A total of 290 (87.1%) neonates were followed up at 7–14 months of age and 6 (2.1%) of them were infected with HBV. Of 146 neonates born to HBeAg-negative mothers, 38 (26.0%) and 30 (20.5%) had detectable HBsAg and HBV DNA in cord blood respectively, but none of 126 infants followed up was infected. Of 187 neonates born to HBeAg-positive mothers, 92 (49.2%) and 79 (42.2%) had detectable HBsAg and HBV DNA in cord blood respectively; 6 (3.7%) of 164 infants followed up were infected. Of seven neonates with HBV DNA > 10⁵ IU/ml in cord blood, four had no infection and three others were infected.ConclusionPresence of HBsAg and/or HBV DNA, even at high levels, in cord blood just indicates exposure to, but not infection with HBV. Presence of HBV markers in cord blood cannot define intrauterine infection.     

Vav Proteins in Development of the Brain: A Potential Relationship to the Pathogenesis of Congenital Zika Syndrome?

Zika virus (ZIKV) infection during pregnancy can result in a significant impact on the brain and eye of the developing fetus, termed congenital zika syndrome (CZS). At a morphological level, the main serious presentations of CZS are microcephaly and retinal scarring. At a cellular level, many cell types of the brain may be involved, but primarily neuronal progenitor cells (NPC) and developing neurons. Vav proteins have guanine exchange activity in converting GDP to GTP on proteins such as Rac1, Cdc42 and RhoA to stimulate intracellular signaling pathways. These signaling pathways are known to play important roles in maintaining the polarity and self-renewal of NPC pools by coordinating the formation of adherens junctions with cytoskeletal rearrangements. In developing neurons, these same pathways are adopted to control the formation and growth of neurites and mediate axonal guidance and targeting in the brain and retina. This review describes the role of Vavs in these processes and highlights the points of potential ZIKV interaction, such as (i) the binding and entry of ZIKV in cells via TAM receptors, which may activate Vav/Rac/RhoA signaling; (ii) the functional convergence of ZIKV NS2A with Vav in modulating adherens junctions; (iii) ZIKV NS4A/4B protein effects on PI3K/AKT in a regulatory loop via PPI3 to influence Vav/Rac1 signaling in neurite outgrowth; and (iv) the induction of SOCS1 and USP9X following ZIKV infection to regulate Vav protein degradation or activation, respectively, and impact Vav/Rac/RhoA signaling in NPC and neurons. Experiments to define these interactions will further our understanding of the molecular basis of CZS and potentially other developmental disorders stemming from in utero infections. Additionally, Vav/Rac/RhoA signaling pathways may present tractable targets for therapeutic intervention or molecular rationale for disease severity in CZS.     

Human Cytomegalovirus Inhibits the PARsylation Activity of Tankyrase—A Potential Strategy for Suppression of the Wnt Pathway

Human cytomegalovirus (HCMV) was reported to downregulate the Wnt/β-catenin pathway. Induction of Axin1, the negative regulator of the Wnt pathway, has been reported as an important mechanism for inhibition of β-catenin. Since Tankyrase (TNKS) negatively regulates Axin1, we investigated the effect of HCMV on TNKS expression and poly-ADP ribose polymerase (PARsylation) activity, during virus replication. Starting at 24 h post infection, HCMV stabilized the expression of TNKS and reduced its PARsylation activity, resulting in accumulation of Axin1 and reduction in its PARsylation as well. General PARsylation was not changed in HCMV-infected cells, suggesting specific inhibition of TNKS PARsylation. Similarly, treatment with XAV939, a chemical inhibitor of TNKS’ activity, resulted in the accumulation of TNKS in both non-infected and HCMV-infected cell lines. Reduction of TNKS activity or knockdown of TNKS was beneficial for HCMV, evidenced by its improved growth in fibroblasts. Our results suggest that HCMV modulates the activity of TNKS to induce Axin1, resulting in inhibition of the β-catenin pathway. Since HCMV replication is facilitated by TNKS knockdown or inhibition of its activity, TNKS may serve as an important virus target for control of a variety of cellular processes.     

Interaction of hepatitis C virus with the type Ⅰ interferon system

Hepatitis C virus (HCV) needs to tightly manipulate host defences in order to establish infection. The innate immune response slows down viral replication by activating cytokines such as the type Ⅰ interferons (IFN-α/β), which trigger the synthesis of antiviral proteins and modulate the adaptive immune system. HCV has therefore developed a number of countermeasures to stay ahead of the IFN system. Here, I will attempt to summarize the current state of research regarding IFN responses against HCV and the viral escape strategies.Particular emphasis will be put on the newly discovered mechanisms HCV employs to avoid the induction of IFN in infected cells.     

Impact of human immunodeficiency virus infection on the course of hepatitis C virus infection： A meta-analysis

AIM： TO analyze the influence of human immunodeficiency virus （HIV） infection on the course of hepatitis C virus （HCV） infection. METHODS： We performed a meta-analysis to quantify the effect of HIV co-infection on progressive liver disease in patients with HCV infection. Published studies in the English or Chinese-language medical literature involving cohorts of HIV-negative and -positive patients coinfected with HCV were obtained by searching the PUBMED, EMBASE and CBM. Data were extracted independently from relevant studies by 2 investigators and used in a fixed-effect meta analysis to determine the difference in the course of HCV infection in the 2 groups. RESULTS： Twenty-nine trails involving 16750 patients were identified including the outcome of histological fibrosis or cirrhosis or de-compensated liver disease or hepatocellular carcinoma or death. These studies yielded a combined adjusted odds ratio （OR） of 3.40 [95% confidence interval （CI） = 2.45 and 4.73]. Of note, studies that examined histological fibrosis/ cirrhosis, decompensated liver disease, hepatocellular carcinoma or death had a pooled OR of 1.47 （95% CI = 1.27 and 1.70）, 5.45 （95% CI = 2.54 and 11.71）, 0.76 （95% CI = 0.50 and 1.14）, and 3.60 （95% CI = 3.12 and 4.15）, respectively. CONCLUSION： Without highly active antiretroviral therapies （HAART）, HIV accelerates HCV disease progression, including death, histological fibrosis/ cirrhosis and decompensated liver disease. However, the rate of hepatocellular carcinoma is similar in persons who had HCV infection and were positive for HIV or negative for HIV.     

Relationship of human leukocyte antigen class Ⅱ genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients. METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNa-lb for 24 wk. RESULTS: The frequencies of HLA-DRB1~*06, DRB1~*08 and DRB1~*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR=3.837, P=0.018; 11.11% vs 5.50%, OR=2.148, P=0.034; and 6.94% vs 3.00%, OR=0.625, P=0.049, respectively); whereas that of DRB1~*07 allele was lower (2.78% vs 7.75%, OR=0.340, P=0.046). The frequency of HLA-DRB1~*14 allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs 2.08%, OR=10.444, P=0.031), whereas that of DQB1*07 allele was inverse (9.09% vs 37.50%, OR=0.167, P=0.021). CONCLUSION: The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRB1~*06, DRB1~*08, and DRB1~*16 may be associated with chronicity of HBV infection, HLA-DRB1~*07 with protection against HBV infection, and HLA-DRB1~*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQB1~*07 may be associated with low response rate to IFN.     

What is the role of virus vaccination in patients with asthma?

It is estimated that viruses play a role in 30% to 80% of asthma exacerbations. Thus, virus vaccination in patients with asthma could play an important role in preventing asthma exacerbations and other complications. Influenza is the only agent for which a routine vaccine is currently available. This article discusses whether influenza vaccination in patients with asthma, based on the available evidence, is justified. Cost-effectiveness of (influenza) vaccination for patients with asthma is questionable. For the other major viruses involved, the present state of affairs is described. Although progress is being made, a vaccine may be available in the near future only for respiratory syncytial virus (RSV). Meanwhile, clinicians and patients should aim for an optimal treatment with the currently available asthma medication.     

Pericardial effusion with tamponade——an uncommon presentation leading to the diagnosis of eosinophilic granulomatosis polyangiitis: A case report

BACKGROUND Eosinophilic granulomatosis polyangiitis(EGPA) is a small vessel necrotizing vasculitis that commonly presents as peripheral eosinophilia and asthma; however, it can rarely manifest with cardiac involvement such as pericarditis and cardiac tamponade. Isolated pericardial tamponade presenting as the initial symptom of EGPA is exceedingly rare. Early diagnosis and appropriate treatment are crucial to prevent life-threatening outcomes.CASE SUMMARY 52-year-old woman with no past medical history presented with progressive dyspnea and dry cough. On physical exam she had a pericardial friction rub and bilateral rales. Vital signs were notable for tachycardia at 119 beats per minute and hypoxia with 89% oxygen saturation. On laboratory exam, she had 45% peripheral eosinophilia, troponin elevation of 1.1 ng/m L and N-terminal prohormone of brain natriuretic peptide of 2101 pg/m L. TTE confirmed a large pericardial effusion and tamponade physiology. She underwent urgent pericardial window procedure. Pericardial and lung biopsy demonstrated eosinophilic infiltration. Based on the American College of Radiology guidelines, the patient was diagnosed with EGPA which manifested in its rare form of cardiac tamponade. She was treated with steroid taper and mepolizumab.CONCLUSION This case highlights that when isolated pericardial involvement occurs in EGPA,diagnosis is recognized by performing pericardial biopsy demonstrating histopathologic evidence of eosinophilic infiltration.     

A meta-analysis of the relation of polymorphism at sites −1082 and −592 of the IL-10 gene promoter with susceptibility and clearance to persistent hepatitis B virus infection in the Chinese population

Background

Up to now, many publications about the Chinese population have evaluated the correlation between interleukin-10 (IL-10) ?1082 and ?592 polymorphisms and persistent hepatitis B virus (HBV) infection. However, the results remain inconclusive. In order to resolve this conflict, a meta-analysis was performed.

Methods

Seven studies were included and dichotomous data are presented as the odds ratio (OR) with a 95% confidence interval (CI).

Results

The results of our study suggest that carriers of the IL-10 ?592A allele were more likely to clear HBV spontaneously in the Chinese pooled population (A vs. C: OR = 0.799, 95% CI = 0.678–0.941, P = 0.007; AC vs. AA: OR = 1.343, 95% CI = 1.017–1.684, P = 0.011; AA vs. AC + CC: OR = 0.736, 95% CI = 0.594–0.912; AA + AC vs. CC: OR = 0.588, 95% CI = 0.408–0.848, P = 0.004) and the IL-10 ?1082A allele was associated with significantly reduced persistent HBV infection risk in Chinese (A vs. G: OR = 0.701, 95% CI = 0.494–0.996, P = 0.047; AA vs. GG + GA: OR = 0.684, 95% CI = 0.476–0.982, P = 0.040).

Conclusions

Persistent HBV infection susceptibility is associated with the gene polymorphism IL-10 ?1082GA in the Chinese population and the clearance of HBV is associated with the gene polymorphism IL-10 ?592CA in the Chinese population.     

Adverse reactions to the ivermectin treatment of onchocerciasis patients: does infection with the human immunodeficiency virus play a role?

To assess and compare the adverse effects resulting from ivermectin treatment of onchocerciasis patients with and without infection with human immunodeficiency virus (HIV-1), 1256 Ugandan cases of onchocerciasis were investigated as they were treated for the first time with the drug. Treatment followed the protocol of the Mectizan Expert Committee (i.e. a single dose of 150 mug/kg body weight). Adverse reactions to the ivermectin were determined, within 48 h of treatment, through questioning and clinical examinations during house-to-house visits. The HIV-1 status of each patient aged >15 years was initially determined using indirect ELISA, and any ELISA-positives were then confirmed in a western-blot assay.Among the cases aged >15 years, the frequency of adverse reactions to ivermectin was higher among those seropositive for HIV-1 (53.4%) than among the seronegative (45.7%) but the difference was not statistically significant (P = 0.25). The severity of the adverse reactions observed was, however, significantly lower in the HIV-1-positive patients than in the seronegative patients, with median scores of 1.37 and 1.68, respectively (P = 0.044). The conclusion is that ivermectin can be safely used for mass treatment in areas where the prevalences of onchocerciasis and HIV-1 infection are both high.     

When should the driver with a history of substance misuse be allowed to return to the wheel? A review of the substance misuse section of the Australian national guidelines

Assessing fitness to drive in applicants with a historical or current substance use disorder presents a specific clinical challenge. The Australian guidelines require evidence of remission and absence of cognitive change when considering applications for re‐licensing driver or individuals applying to reengage in safety‐sensitive work. This paper reviews some of the clinical and biochemical indicators that determine whether a particular person is in ‘remission’ and meets the criteria for return to driving or other safety‐sensitive occupation. It provides an overview of the challenges in establishing an evidence‐based approach to determining fitness for safety critical activities. There is no internationally accepted definition of ‘remission’. Review of the literature and examination of assessment protocols from other national jurisdictions are available for alcohol and the more important drugs of interest in road safety. Assessing fitness to drive when there is a history of substance misuse and/or substance use disorders is a complex issue that requires assessment of biomarkers, clinical findings and clinical assessment before the person returns to driving. We propose that hair testing provides a reliable and reproducible way to demonstrate remission and provide cost‐effective monitoring. Standardised psychological tests could provide a reproducible assessment of the cognitive effects of drug use and suitability to resume driving. We recommend that AustRoads amend the national guidelines to reflect an evidence‐based approach to assessing fitness to drive after conviction for offences related to alcohol and drug use.     

A unique insertion in the S gene of surface antigen—Negative hepatitis B virus chinese carriers

The presence of unique hepatitis B virus (HBV) variants has been investigated in two Chinese patients with chronic liver disease, whose sera were positive for HBV-DNA by dot blot hybridization or polymerase chain reaction (PCR) but hepatitis B surface antigen (HBsAg)-negative by conventional polyclonal antibody based immunoassays. PCR amplification of HBV-DNA followed by direct sequencing showed an insertion of six nucleotides, which introduced two additional amino acids between codons 122 and 123 in one patient (Isolate 1), whereas a nine nucleotide insertion in the other patient (Isolate 2) gave rise to three amino-acids between codons 123 and 124 immediately upstream from the ‘a’ determinant in the S gene. These insertions have not been described previously in any published sequences of the known subtypes and were absent from sequences of 30 HBsAg-positive Chinese patients from the same region. In the cases under study, the insertion is associated with four consecutive adenine molecules from nucleotides 516 to 519. It seems likely that this area is a hot spot for insertions in HBV. We found none of the previously described amino-acid deletions or substitutions in the pre-S1, pre-S2 and S genes, which are involved in unusual antigenic profiles. This finding suggests that genetic mutations in the S gene outside the ‘a’ determinant may be responsible for failure to detect HBsAg in some Chinese patients with chronic hepatitis caused by HBV infection.