Application opportunities of geographic information systems analysis to support achievement of the UNAIDS 90-90-90 targets in South Africa

In an effort to achieve control of the HIV epidemic, 90-90-90 targets have been proposed whereby 90% of the HIV-infected population should know their status, 90% of those diagnosed should be receiving antiretroviral therapy, and 90% of those on treatment should be virologically suppressed. In this article we present approaches for using relatively simple geographic information systems (GIS) analyses of routinely available data to support HIV programme management towards achieving the 90-90-90 targets, with a focus on South Africa (SA) and other high-prevalence settings in low- and middle-income countries. We present programme-level GIS applications to map aggregated health data and individual-level applications to track distinct patients. We illustrate these applications using data from City of Johannesburg Region D, demonstrating that GIS has great potential to guide HIV programme operations and assist in achieving the 90-90-90 targets in SA

Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a growing threat to global health, with recent efforts towards its eradication being reversed in the wake of the COVID-19 pandemic. Increasing resistance to gyrase-targeting second-line fluoroquinolone antibiotics indicates the necessity to develop both novel therapeutics and our understanding of M. tuberculosis growth during infection. ParDE toxin–antitoxin systems also target gyrase and are regulated in response to both host-associated and drug-induced stress during infection. Here, we present microbiological, biochemical, structural, and biophysical analyses exploring the ParDE1 and ParDE2 systems of M. tuberculosis H37Rv. The structures reveal conserved modes of toxin–antitoxin recognition, with complex-specific interactions. ParDE1 forms a novel heterohexameric ParDE complex, supported by antitoxin chains taking on two distinct folds. Curiously, ParDE1 exists in solution as a dynamic equilibrium between heterotetrameric and heterohexameric complexes. Conditional remodelling into higher order complexes can be thermally driven in vitro. Remodelling induces toxin release, tracked through concomitant inhibition and poisoning of gyrase activity. Our work aids our understanding of gyrase inhibition, allowing wider exploration of toxin–antitoxin systems as inspiration for potential therapeutic agents

Implementing 'universal' access to antiretroviral treatment in South Africa:a scoping review on research priorities

‘Universal’ access to antiretroviral treatment (ART) has become the global standard for treating people living with HIV and achieving epidemic control; yet, findings from numerous ‘test and treat’ trials and implementation studies in sub-Saharan Africa suggest that bringing ‘universal' access to ART to scale is more complex than anticipated. Using South Africa as a case example, we describe the research priorities and foci in the literature on expanded ART access. To do so, we adapted Arksey and O’Malley’s six-stage scoping review framework to describe the peer-reviewed literature and opinion pieces on expanding access to ART in South Africa between 2000 and 2017. Data collection included systematic searches of two databases and hand-searching of a sub-sample of reference lists. We used an adapted socio-ecological thematic framework to categorize data according to where it located the challenges and opportunities of expanded ART eligibility: individual/client, health worker–client relationship, clinic/community context, health systems infrastructure and/or policy context. We included 194 research articles and 23 opinion pieces, of 1512 identified, addressing expanded ART access in South Africa. The peer-reviewed literature focused on the individual and health systems infrastructure; opinion pieces focused on changing roles of individuals, communities and health services implementers. We contextualized our findings through a consultative process with a group of researchers, HIV clinicians and programme managers to consider critical knowledge gaps. Unlike the published literature, the consultative process offered particular insights into the importance of researching and intervening in the relational aspects of HIV service delivery as South Africa’s HIV programme expands. An overwhelming focus on individual and health systems infrastructure factors in the published literature on expanded ART access in South Africa may skew understanding of HIV programme shortfalls away from the relational aspects of HIV services delivery and delay progress with finding ways to leverage non-medical modalities for achieving HIV epidemic control

Yellow Fever Outbreak, Southern Sudan, 2003

In May 2003, an outbreak of fatal hemorrhagic fever, caused by yellow fever virus, occurred in southern Sudan. Phylogenetic analysis showed that the virus belonged to the East African genotype, which supports the contention that yellow fever is endemic in East Africa with the potential to cause large outbreaks in humans

PAPER-64 Constraints On Reionization II: The Temperature Of The z=8.4 Intergalactic Medium

We present constraints on both the kinetic temperature of the intergalactic medium (IGM) at z=8.4, and on models for heating the IGM at high-redshift with X-ray emission from the first collapsed objects. These constraints are derived using a semi-analytic method to explore the new measurements of the 21 cm power spectrum from the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER), which were presented in a companion paper, Ali et al. (2015). Twenty-one cm power spectra with amplitudes of hundreds of mK^2 can be generically produced if the kinetic temperature of the IGM is significantly below the temperature of the Cosmic Microwave Background (CMB); as such, the new results from PAPER place lower limits on the IGM temperature at z=8.4. Allowing for the unknown ionization state of the IGM, our measurements find the IGM temperature to be above ~5 K for neutral fractions between 10% and 85%, above ~7 K for neutral fractions between 15% and 80%, or above ~10 K for neutral fractions between 30% and 70%. We also calculate the heating of the IGM that would be provided by the observed high redshift galaxy population, and find that for most models, these galaxies are sufficient to bring the IGM temperature above our lower limits. However, there are significant ranges of parameter space that could produce a signal ruled out by the PAPER measurements; models with a steep drop-off in the star formation rate density at high redshifts or with relatively low values for the X-ray to star formation rate efficiency of high redshift galaxies are generally disfavored. The PAPER measurements are consistent with (but do not constrain) a hydrogen spin temperature above the CMB temperature, a situation which we find to be generally predicted if galaxies fainter than the current detection limits of optical/NIR surveys are included in calculations of X-ray heating.Comment: companion paper to Ali et al. (2015), ApJ 809, 61; matches version accepted to ApJ; 11 pages, 7 figure

Hydrogen Epoch of Reionization Array (HERA)

The Hydrogen Epoch of Reionization Array (HERA) is a staged experiment to measure 21 cm emission from the primordial intergalactic medium (IGM) throughout cosmic reionization ($z=6-12$), and to explore earlier epochs of our Cosmic Dawn ($z\sim30$). During these epochs, early stars and black holes heated and ionized the IGM, introducing fluctuations in 21 cm emission. HERA is designed to characterize the evolution of the 21 cm power spectrum to constrain the timing and morphology of reionization, the properties of the first galaxies, the evolution of large-scale structure, and the early sources of heating. The full HERA instrument will be a 350-element interferometer in South Africa consisting of 14-m parabolic dishes observing from 50 to 250 MHz. Currently, 19 dishes have been deployed on site and the next 18 are under construction. HERA has been designated as an SKA Precursor instrument. In this paper, we summarize HERA's scientific context and provide forecasts for its key science results. After reviewing the current state of the art in foreground mitigation, we use the delay-spectrum technique to motivate high-level performance requirements for the HERA instrument. Next, we present the HERA instrument design, along with the subsystem specifications that ensure that HERA meets its performance requirements. Finally, we summarize the schedule and status of the project. We conclude by suggesting that, given the realities of foreground contamination, current-generation 21 cm instruments are approaching their sensitivity limits. HERA is designed to bring both the sensitivity and the precision to deliver its primary science on the basis of proven foreground filtering techniques, while developing new subtraction techniques to unlock new capabilities. The result will be a major step toward realizing the widely recognized scientific potential of 21 cm cosmology.Comment: 26 pages, 24 figures, 2 table

Incidence of Tuberculosis amongst HIV positive individuals initiating antiretroviral treatment at higher CD4 counts in the HPTN 071 (PopART) trial in South Africa.

INTRODUCTION: Antiretroviral treatment (ART) guidelines recommend lifelong ART for all HIV positive individuals. This study evaluated TB incidence on ART in a cohort of HIV positive individuals starting ART regardless of CD4 count in a programmatic setting at three clinics included in the HPTN 071 (PopART) trial in South Africa. METHODS: A retrospective cohort analysis of HIV-positive individuals aged ≥18 years starting ART, between January 2014 and November 2015, was conducted. Follow up was continued until 30 May 2016 or censored on the date of i) incident TB ii) loss to follow up from HIV care or death or iii) elective transfer out; whichever occurred first. RESULTS: The study included 2423 individuals. Median baseline CD4 count was 328 cells/µL (IQR 195-468), TB incidence rate was 4.41/100 PY (95% CI 3.62-5.39). The adjusted hazard ratio of incident TB was 0.27 (95% CI 0.12 - 0.62) when comparing individuals with baseline CD4 > 500cells/µL and ≤ 500cells/µL. Amongst individuals with baseline CD4 count > 500cells/µL there were no incident TB cases in the first three months of follow up. Adjusted hazard of incident TB was also higher amongst men (aHR 2.16; 95% CI: 1.41 - 3.30). CONCLUSION: TB incidence after ART initiation was significantly lower amongst individuals starting ART at CD4 counts above 500cells/µL. Scale up of ART, regardless of CD4 count, has the potential to significantly reduce TB incidence amongst HIV-positive individuals. However, this needs to be combined with strengthening of other TB prevention strategies that target both HIV positive and HIV negative individuals

PAPER-64 CONSTRAINTS ON REIONIZATION: THE 21 cm POWER SPECTRUM AT z = 8.4

In this paper, we report new limits on 21 cm emission from cosmic reionization based on a 135 day observing campaign with a 64-element deployment of the Donald C. Backer Precision Array for Probing the Epoch of Reionization in South Africa. This work extends the work presented in Parsons et al. with more collecting area, a longer observing period, improved redundancy-based calibration, improved fringe-rate filtering, and updated power-spectral analysis using optimal quadratic estimators. The result is a new 2σ upper limit on Δ[superscript 2](k) of (22.4 mK)[superscript 2] in the range 0.15 < k < 0.5h Mpc[superscript -1] at z = 8.4. This represents a three-fold improvement over the previous best upper limit. As we discuss in more depth in a forthcoming paper, this upper limit supports and extends previous evidence against extremely cold reionization scenarios. We conclude with a discussion of implications for future 21 cm reionization experiments, including the newly funded Hydrogen Epoch of Reionization Array