Is the HCV-HIV co-infection prevalence amongst injecting drug users a marker for the level of sexual and injection related HIV transmission?

BACKGROUND: Amongst injecting drug users (IDUs), HIV is transmitted sexually and parenterally, but HCV is transmitted primarily parenterally. We assess and model the antibody prevalence of HCV amongst HIV-infected IDUs (denoted as HCV-HIV co-infection prevalence) and consider whether it proxies the degree of sexual HIV transmission amongst IDUs. METHODS: HIV, HCV and HCV-HIV co-infection prevalence data amongst IDU was reviewed. An HIV/HCV transmission model was adapted. Multivariate model uncertainty analyses determined whether the model's ability to replicate observed data trends required the inclusion of sexual HIV transmission. The correlation between the model's HCV-HIV co-infection prevalence and estimated proportion of HIV infections due to injecting was evaluated. RESULTS: The median HCV-HIV co-infection prevalence (prevalence of HCV amongst HIV-infected IDUs) was 90% across 195 estimates from 43 countries. High HCV-HIV co-infection prevalences (>80%) occur in most (75%) settings, but can be lower in settings with low HIV prevalence (0.75). The model without sexual HIV transmission reproduced some data trends but could not reproduce any epidemics with high HIV/HCV prevalence ratios (>0.85) or low HCV-HIV co-infection prevalence (10%. The model with sexual HIV transmission reproduced data trends more closely. The proportion of HIV infections due to injecting correlated with HCV-HIV co-infection prevalence; suggesting that up to 80/60/90%. CONCLUSION: Substantial sexual HIV transmission may occur in many IDU populations; HCV-HIV co-infection prevalence could signify its importance

The Enlightenment: A Beginner's Guide

Blamed for the bloody disasters of the 20th century: Auschwitz, the Gulags, globalisation, Islamic terrorism; heralded as the harbinger of reason, equality, and the end of arbitrary rule, the Enlightenment has been nothing if not divisive. To this day historians disagree over when it was, where it was, and what it was (and sometimes, still is). Kieron O’Hara deftly traverses these conflicts, presenting the history, politics, science, religion, arts, and social life of the Enlightenment not as a simple set of easily enumerated ideas, but an evolving conglomerate that spawned a very diverse set of thinkers, from the radical Rousseau to the conservative Burke

Transcription of TP0126, Treponema pallidum Putative OmpW Homolog, Is Regulated by the Length of a Homopolymeric Guanosine Repeat

An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis

Introduction of syphilis point-of-care tests, from pilot study to national programme implementation in Zambia: A qualitative study of healthcare workers' perspectives on testing, training and quality assurance

Syphilis affects 1.4 million pregnant women globally each year. Maternal syphilis causes congenital syphilis in over half of affected pregnancies, leading to early foetal loss, pregnancy complications, stillbirth and neonatal death. Syphilis is under-diagnosed in pregnant women. Point-of-care rapid syphilis tests (RST) allow for same-day treatment and address logistical barriers to testing encountered with standard Rapid Plasma Reagin testing. Recent literature emphasises successful introduction of new health technologies requires healthcare worker (HCW) acceptance, effective training, quality monitoring and robust health systems. Following a successful pilot, the Zambian Ministry of Health (MoH) adopted RST into policy, integrating them into prevention of mother-to-child transmission of HIV clinics in four underserved Zambian districts. We compare HCW experiences, including challenges encountered in scaling up from a highly supported NGO-led pilot to a large-scale MoH-led national programme. Questionnaires were administered through structured interviews of 16 HCWs in two pilot districts and 24 HCWs in two different rollout districts. Supplementary data were gathered via stakeholder interviews, clinic registers and supervisory visits. Using a conceptual framework adapted from health technology literature, we explored RST acceptance and usability. Quantitative data were analysed using descriptive statistics. Key themes in qualitative data were explored using template analysis. Overall, HCWs accepted RST as learnable, suitable, effective tools to improve antenatal services, which were usable in diverse clinical settings. Changes in training, supervision and quality monitoring models between pilot and rollout may have influenced rollout HCW acceptance and compromised testing quality. While quality monitoring was integrated into national policy and training, implementation was limited during rollout despite financial support and mentorship. We illustrate that new health technology pilot research can rapidly translate into policy change and scale-up. However, training, supervision and quality assurance models should be reviewed and strengthened as rollout of the Zambian RST programme continues. © 2015, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Remembering Roy

'Wellcome History' is an easy and regular channel of communication between all Wellcome historians. It aims to be an informal, user-friendly centre of debate

William John Adie: the man behind the syndrome

William John Adie was an Australian neurologist in the early 20th century responsible for extensively describing the tonically dilated pupil associated with absent deep tendon reflexes – both features of a syndrome that now bears his name. In addition to other neurological syndromes, he was also significant in delineating narcolepsy through his clinical essays and case series. His ophthalmic and neurologic contributions have served the test of time and played an important role in the modern understanding of Adie syndrome and narcolepsy. This report reviews Adie's medical contributions, extensive descriptions of Adie syndrome, and provides a brief biographical account of his life