Debating Africa : BBC's documentary "Heart & soul - return to Zanzibar"

This issue of ISJ carried another article in the irregular series "Debating and Documenting Africa", the first one having been published in volume 1, number 2 (June 2008). This issue carries a discussion between Katy Hickman, Senior Producer at BBC World Service Religion and Ethics and Prof. Abdul Sheriff, formerly Professor of History at the University of Dar es Salaam and Director of Zanzibar Museums and the author of forthcoming titles, Dhow Cultures of the Indian Ocean: Cosmopolitanism, Commerce and Islam and The Early Dhow Culture in the Indian Ocean: From the Periplus to the Portuguese. The context of this debate is BBC Radio’s "Return to Zanzibar" programme in their series, Heart & Soul. Setting the scene is Katy Hickman’s contact with Prof. Sheriff in which she enclosed an early outline of the programme. This is followed by Prof. Sheriff’s response which raises various key issue of relevance to the study of Africa. This is followed by Katy Hickman’s response which explains how the final version was influenced by points raised by Prof. Sheriff. Also included is a later piece by the presenter of the programme, Yasmin Alibhai-Brown. While not part of this discussion, the latter is included to provide the presenter’s perspective. All these provide a look behind the scene on debates that take place before programmes are made and bring out the key role that historians, researchers and academicians can, and need to play, in social communications. ISJ’s Editorial Board re-presents this debate to stimulate further discussion

The impact of direct-acting antivirals on hepatitis C viraemia among people who inject drugs in England; real-world data 2011–2018

Direct‐acting antiviral (DAA) therapy for anybody with viraemic HCV infection has been scaled‐up in England since 2017. To assess early impacts, we investigated trends in, and factors associated with, HCV viraemia among people who inject drugs (PWID). We also examined trends in self‐reported treatment access. Bio‐behavioural data from an annual, national surveillance survey of PWID (2011–2018) estimated trends in viraemic prevalence among HCV antibody‐positive PWID. Multivariable logistic regression identified characteristics independently associated with viraemia. Trends in treatment access were examined for PWID with known infection. Between 2011 and 2016, viraemic prevalence among antibody‐positive PWID remained stable (2011, 57.7%; 2016, 55.8%) but decreased in 2017 (49.4%) and 2018 (50.4%) (both p < 0.001). After adjustment for demographic and behavioural characteristics, there remained significant reduction in viraemia in 2017 (adjusted odds ratio [aOR] 0.79, 95% CI 0.65–0.94) and 2018 (aOR 0.79, 95% CI 0.66–0.93) compared to 2016. Other factors associated with viraemia were male gender (aOR 1.68, 95% CI 1.53–1.86), geographical region, injecting in past year (aOR 1.26, 95% CI 1.13–1.41), imprisonment (aOR 1.14, 95% CI 1.04–1.31) and homelessness (aOR 1.17, 95% CI 1.04–1.31). Among non‐viraemic PWID with known infection, the proportion reporting ever receiving treatment increased in 2017 (28.7%, p < 0.001) and 2018 (38.9%, p < 0.001) compared to 2016 (14.5%). In conclusion, there has been a small reduction in HCV viraemia among antibody‐positive PWID in England since 2016, alongside DAA scale‐up, and some indication that treatment access has improved in the same period. Population‐level monitoring and focus on harm reduction is critical for achieving and evaluating elimination

Impact of opioid substitution therapy on antiretroviral therapy outcomes:a systematic review and meta-analysis

BACKGROUND: Human immunodeficiency virus (HIV)-infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. METHODS: We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I2 statistic. RESULTS: We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32-2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17-2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41-3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63-.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21-1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65-1.25). CONCLUSIONS: These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID

Childhood tuberculosis is associated with decreased abundance of T cell gene transcripts and impaired T cell function

The WHO estimates around a million children contract tuberculosis (TB) annually with over 80 000 deaths from dissemination of infection outside of the lungs. The insidious onset and association with skin test anergy suggests failure of the immune system to both recognise and respond to infection. To understand the immune mechanisms, we studied genome-wide whole blood RNA expression in children with TB meningitis (TBM). Findings were validated in a second cohort of children with TBM and pulmonary TB (PTB), and functional T-cell responses studied in a third cohort of children with TBM, other extrapulmonary TB (EPTB) and PTB. The predominant RNA transcriptional response in children with TBM was decreased abundance of multiple genes, with 140/204 (68%) of all differentially regulated genes showing reduced abundance compared to healthy controls. Findings were validated in a second cohort with concordance of the direction of differential expression in both TBM (r2 = 0.78 p = 2x10-16) and PTB patients (r2 = 0.71 p = 2x10-16) when compared to a second group of healthy controls. Although the direction of expression of these significant genes was similar in the PTB patients, the magnitude of differential transcript abundance was less in PTB than in TBM. The majority of genes were involved in activation of leucocytes (p = 2.67E-11) and T-cell receptor signalling (p = 6.56E-07). Less abundant gene expression in immune cells was associated with a functional defect in T-cell proliferation that recovered after full TB treatment (p<0.0003). Multiple genes involved in T-cell activation show decreased abundance in children with acute TB, who also have impaired functional T-cell responses. Our data suggest that childhood TB is associated with an acquired immune defect, potentially resulting in failure to contain the pathogen. Elucidation of the mechanism causing the immune paresis may identify new treatment and prevention strategies

Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)

Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies comine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV ‘Treatment as Prevention’ (TasP) in PWID

The political economy of streetspace reallocation projects: Aldgate Square and Bank Junction, London

Streetspace reallocation projects are often difficult to plan and implement, attracting great controversy with residents and other actors. This paper considers two streetspace reallocation projects, in Aldgate Square and Bank Junction, London. 15 in-depth interviews are used to explore the competing discourses on each project. The analysis covers the different viewpoints on perceived problems and opportunities, project impacts and effectiveness, distribution of benefits, technical assessment, participatory processes and the resulting sanctioned discourse. Using NVivo software, it examines the language used by the different actors in the process

Confirmation of significantly differentially expressed genes from Cohort 1 in Cohort 2.

<p><b>A</b>. Average log fold change in the SDE transcripts identified in the time-course study (cohort 1) and their corresponding log fold change in the single time-point study (cohort 2). 140/262 transcripts identified in cohort 1 were measured in cohort 2. 129 transcripts followed the same regulation pattern (purple crosses); and 11 showed opposite regulation (represented by red crosses, annotated by gene symbol). Correlation coefficient was r2 = 0.78, 95% CI = [0.71, 0.82] p<2x10-16. The y-axis shows log fold change of SDE gene transcripts in cohort 1 relative to cohort 1 Healthy Controls (HC), and the x-axis shows their log fold change in cohort 2 relative to cohort 2 HC. <b>B</b>. Average log fold change in TBM patients relative to cohort 2 HC (x-axis) plotted against average log fold change in PTB patients relative to cohort 2 HC (y-axis) of the significant transcripts (140) that were identified in cohort 1 and common to both cohorts. Least-squares fitted line is shown in dashes. Correlation coefficient was <i>r</i>^<i>2</i> = 0.71, 95% CI = [0.62, 0.79] <i>p</i><2x10^-16. <b>C.</b> Heat map showing almost complete discrimination between TBM cases from cohort 1 and cohort 2 and healthy controls (cohort 2) using 129 transcripts significantly differentially expressed in both cohorts. Gene list is provided in Table C in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185973#pone.0185973.s002" target="_blank">S1 File</a>. Hierarchical clustering was performed by the complete linkage method to identify similar clusters. Solid red bar (top) shows cases, green bar shows controls. Intensity of colour indicates degree of reduced (green) or elevated (red) abundance of each transcript relative to healthy controls. White indicates no expression.</p

Functional T-cell responses in cohort 3.

<p><b>A.</b> Adjusted T-cell proliferative responses (cpm) to PHA in acute TB (TBM n = 19, EPTB n = 29, PTB n = 27) and healthy Mantoux positive controls n = 26. Normalised proliferative responses were determined by deducting the value for the unstimulated well from that of the PHA well. Means are shown by horizontal bars together with standard error of the mean. Asterisk denotes significant differences in corrected p values. PTB vs HC * <i>p</i> = 0.018, TBM vs HC ** <i>p</i> = 0.001, EPTB vs HC *** <i>p<</i>0.0003. <b>B.</b> IFNγ production in response to PHA in acute TB (TBM n = 36, other EPTB n = 57, PTB n = 55) and healthy Mantoux positive controls (HC) n = 75. Medians are shown by horizontal bars together with their interquartile ranges. Asterisk denotes significant difference in corrected p value between TBM and controls * <i>p</i><0.0003.</p

Modelled temporal changes in gene expression.

<p><b>A</b>. Heat map showing modelled changes in expression of the significant gene transcripts in TBM patients from the time of diagnosis (0) to 180 days. Green represents lower transcript abundance, red represents higher transcript abundance and black represents no difference in expression as compared to healthy children with a past history of TB sampled at least one year after diagnosis and treatment. The relative degree of transcript abundance is indicated by the colour intensity derived from the fitted mean expression levels over time (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185973#sec002" target="_blank">methods</a>). Genes showing similar temporal patterns of expression have been clustered together. The apparent linear change in colour is derived from the statistical model that interpolates the observed time points and can therefore be represented as a continuum. <b>B and C</b>. Example plots of two significantly differentially expressed gene transcripts. Expression levels for each TBM patient (red circles n = 9) are shown from diagnosis (time 0) to day 180. Blue circles are expression levels for healthy children (n = 9) with a past history of TB sampled at least one year after diagnosis and treatment. M = “minus” and denotes the log₂ ratio of the red and green channels. The line represents the fitted mean gene expression level over time, from linear mixed-effects model (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0185973#sec002" target="_blank">methods</a>). 1b = <i>TARP</i>; 1c = <i>IL1R2</i>.</p