Delta infection without increase in severity of hepatitis.

The findings of increased morbidity of HbsAG positive hepatitis with delta infection in a study by Dr. Smedile et al were contrary to those of studies performed by the authors. A group of 27 and a group of 41 drug abusers were examined serologically and had liver biopsies performed. There was no significant difference in histological findings between delta positive and delta negative patients in the 27 member group. None of the 41 member group showed any increase in severity of illness. Ethnic origin may be an important factor in the pathogenicity of the delta agent

Isolation and Characterization of Intestinal Epithelial Cells from Normal and SIV-Infected Rhesus Macaques

Impairment of intestinal epithelial barriers contributes to the progression of HIV/SIV infection and leads to generalized HIV-induced immune-cell activation during chronic infection. Rhesus macaques are the major animal model for studying HIV pathogenesis. However, detailed characterization of isolated rhesus epithelial cells (ECs) from intestinal tissues is not well defined. It is also not well documented whether isolated ECs had any other cell contaminants from intestinal tissues during the time of processing that might hamper interpretation of EC preparations or cultures. In this study, we identify and characterize ECs based on flow cytometry and immunohistochemistry methods using various enzymatic and mechanical isolation techniques to enrich ECs from intestinal tissues. This study shows that normal healthy ECs differentially express HLA-DR, CD23, CD27, CD90, CD95 and IL-10R markers. Early apoptosis and upregulation of ICAM-1 and HLA-DR in intestinal ECs are thought to be the key features in SIV mediated enteropathy. The data suggest that intestinal ECs might be playing an important role in mucosal immune responses by regulating the expression of different important regulatory and adhesion molecules and their function

First Phase 1 Double-Blind, Placebo-Controlled, Randomized Rectal Microbicide Trial Using UC781 Gel with a Novel Index of Ex Vivo Efficacy

Objectives: Successful control of the HIV/AIDS pandemic requires reduction of HIV-1 transmission at sexually-exposed mucosae. No prevention studies of the higher-risk rectal compartment exist. We report the first-in-field Phase 1 trial of a rectally-applied, vaginally-formulated microbicide gel with the RT-inhibitor UC781 measuring clinical and mucosal safety, acceptability and plasma drug levels. A first-in-Phase 1 assessment of preliminary pharmacodynamics was included by measuring changes in ex vivo HIV-1 suppression in rectal biopsy tissue after exposure to product in vivo. Methods: HIV-1 seronegative, sexually-abstinent men and women (N = 36) were randomized in a double-blind, placebo-controlled trial comparing UC781 gel at two concentrations (0.1%, 0.25%) with placebo gel (1:1:1). Baseline, single-dose exposure and a separate, 7-day at-home dosing were assessed. Safety and acceptability were primary endpoints. Changes in colorectal mucosal markers and UC781 plasma drug levels were secondary endpoints; ex vivo biopsy infectibility was an ancillary endpoint. Results: All 36 subjects enrolled completed the 7-14 week trial (100% retention) including 3 flexible sigmoidoscopies, each with 28 biopsies (14 at 10 cm; 14 at 30 cm). There were 81 Grade 1 adverse events (AEs) and 8 Grade 2; no Grade 3, 4 or procedure-related AEs were reported. Acceptability was high, including likelihood of future use. No changes in mucosal immunoinflammatory markers were identified. Plasma levels of UC781 were not detected. Ex vivo infection of biopsies using two titers of HIV-1 BaL showed marked suppression of p24 in tissues exposed in vivo to 0.25% UC781; strong trends of suppression were seen with the lower 0.1% UC781 concentration. Conclusions: Single and 7-day topical rectal exposure to both concentrations of UC781 were safe with no significant AEs, high acceptability, no detected plasma drug levels and no significant mucosal changes. Ex vivo biopsy infections demonstrated marked suppression of HIV infectibility, identifying a potential early biomarker of efficacy. (Registered at ClinicalTrials.gov; #NCT00408538). © 2011 Anton et al

Tuberculosis and HIV Co-Infection

Tuberculosis (TB) and HIV co-infections place an immense burden on health care systems and pose particular diagnostic and therapeutic challenges. Infection with HIV is the most powerful known risk factor predisposing for Mycobacterium tuberculosis infection and progression to active disease, which increases the risk of latent TB reactivation 20-fold. TB is also the most common cause of AIDS-related death. Thus, M. tuberculosis and HIV act in synergy, accelerating the decline of immunological functions and leading to subsequent death if untreated. The mechanisms behind the breakdown of the immune defense of the co-infected individual are not well known. The aim of this review is to highlight immunological events that may accelerate the development of one of the two diseases in the presence of the co-infecting organism. We also review possible animal models for studies of the interaction of the two pathogens, and describe gaps in knowledge and needs for future studies to develop preventive measures against the two diseases

Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways

Early events in the human airways determining whether exposure to Mycobacterium tuberculosis (Mtb) results in acquisition of infection are poorly understood. Epithelial cells are the dominant cell type in the lungs, but little is known about their role in tuberculosis. We hypothesised that human primary airway epithelial cells are part of the first line of defense against Mtb-infection and contribute to the protective host response in the human respiratory tract. We modelled these early airway-interactions with human primary bronchial epithelial cells (PBECs) and alveolar macrophages. By combining in vitro infection and transwell co-culture models with a global transcriptomic approach, we identified PBECs to be inert to direct Mtb-infection, yet to be potent responders within an Mtb-activated immune network, mediated by IL1β and type I interferon (IFN). Activation of PBECs by Mtb-infected alveolar macrophages and monocytes increased expression of known and novel antimycobacterial peptides, defensins and S100-family members and epithelial-myeloid interactions further shaped the immunological environment during Mtb-infection by promoting neutrophil influx. This is the first in depth analysis of the primary epithelial response to infection and offers new insights into their emerging role in tuberculosis through complementing and amplifying responses to Mtb

Changes in incidence of hepatitis B in Ireland from 1970-1987.

Routine tests for hepatitis B became available in Ireland in 1970. This paper analysed data on 2,226 cases of hepatitis B virus (HBV) infection detected during the years 1970 to 1987. Data from this study showed that the mean annual incidence of hepatitis B had quadrupled since 1980, compared with the 10 years before 1980. Although some of this increase was attributed to greater awareness, resulting in more testing, most of it was attributed to the 15-fold increase in hepatitis B infections in an expanded population of intravenous drug abusers

The serology of delta hepatitis and the detection of IgM anti-HD by EIA using serum derived delta antigen.

This article presented the findings of a study on the serology of delta hepatitis and the detection of IgM anti-hepatitis D by EIA using serum-derived delta antigen. Research was conducted by means of a retrospective and prospective study of an outbreak of hepatitis B. This study located 135 hepatitis B surface antigen (HBsAg)positive drug misusers with acute hepatitis, and 18 HBsAg carriers attending various hospitals and clinics in Dublin, who were found to be infected with hepatitis D. The authors concluded that the findings of their research suggested that HDAg was singly the best marker of hepatitis D co-infection and, where only late specimens were available, IgM anti-hepatitis D was also useful. IgM anti-hepatitis D was also found to distinguish between chronic hepatitis D virus infection and previous exposure

Chronic active hepatitis in intravenous drug abusers may be delta agent infection assoicated.

Twenty-seven parenteral drug users had serum tested for delta aintigen and antidelta antibody and had liver biopsies performed. All patients has been referred from the Drug Advisory and Treatment Centre by its Medical Director. Of the thirteen delta positive patients four had chronic active hepatitis. All four patients with chronic active hepatitis were delta positive. This study suggests that delta agent infection increases the risk of progression of intravenous drug abuse associated liver disease to chronic active hepatitis

Non-A non-B hepatitis in parenteral drug abusers.

This study suggested that vaccination of drug abusers with inactivated HBsAG will not prevent the development of chronic liver disease, but may slow the progression of the disease and lessen the risk of subsequent cirrhosis or hepatoma. Twenty-seven parenteral drug abusers admitted to hospital for liver biopsy between 1 January and 31 August 1981 made up the sample for this study. Twenty-two of these were male, aged between 12 and 29 years, with a mean duration of 33.6 months of intravenous drug misuse. Nearly 90% of the total sample showed evidence of non-A, non-B hepatitis. The findings suggested that a non-A, non-B vaccine will be needed

Drug induced liver disease.

This article examines the detection and treatment of drug abuse associated with liver disease, which the authors believe is a serious problem amongst adolescents using drugs. The rapid growth in the number of intravenous drug abusers carries with it a corresponding increase in the risk of liver disease among such drug-users. It was estimated that about six tenths of the users attending the National Drug Advisory and Treatment Centre will develop chronic active hepatitis. Added to this is the increased number of close contacts between drug users, who would also be at risk of contracting disease, including contacts not receiving treatment for drug misuse. The authors argue that the problem should be combated through preventative methods. Education and policy should aim to reduce and ideally eliminate intravenous drug misuse. In the meantime, they recommend that facilities should be made available for the management of these patients, and that a programme of vaccination should be introduced