Uptake of Home-Based HIV Testing,Linkage to Care,and Community Attitudes about ART in Rural KwaZulu-Natal,South Africa: Descriptive Results from the First Phase of the ANRS 12249 TasP Cluster-Randomised Trial

BackgroundThe 2015 WHO recommendation of antiretroviral therapy (ART) for all immediately following HIV diagnosis is partially based on the anticipated impact on HIV incidence in the surrounding population. We investigated this approach in a cluster-randomised trial in a high HIV prevalence setting in rural KwaZulu-Natal. We present findings from the first phase of the trial and report on uptake of home-based HIV testing, linkage to care, uptake of ART, and community attitudes about ART.ConclusionsHome-based HIV testing was well received in this rural population, although men were less easily contactable at home; immediate ART was acceptable, with good viral suppression and retention. However, only about half of HIV-positive people accessed care within 6 mo of being identified, with nearly two-thirds accessing care by 12 mo. The observed delay in linkage to care would limit the individual and public health ART benefits of universal testing and treatment in this population.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01509508","term_id":"NCT01509508"}}NCT01509508     

Space Use and Movement Patterns in a Semi-Free-Ranging Herd of European Bison (Bison bonasus)

The successful reintroduction and restocking of the European Bison demands a reliable knowledge of the biology of this species. Yet little is known to date about the European bison, and empirical data remains insufficient to set up a reliable plan ensuring the reintroduction, maintenance and survival of populations in habitats that have been largely modified by human activity. Studies of the ecology, social behaviour and management of bison are therefore crucial to the conservation of this species and its cohabitation with humans. To meet these challenges, we focused on movement patterns and space use in a semi-free-ranging herd of European bison living in the Réserve Biologique des Monts-d’Azur (France). Bison spend over 80% of their time foraging and resting; foraging mainly occurs around the artificial feeding sites (i.e., hay racks) or in meadows. The time of day and the presence of snow have no influence on the time budget allocated to each activity. Animals, however, spend more time at the food racks in winter. Bison also spend most of their time in small groups of individuals, confirming the occurrence of both fission-fusion dynamics and sexual segregation in this species. Bison seem to follow a Lévy walk pattern of movement, which is probably related to the geographical distribution and size of food patches in the reserve. The conclusions of this study provide a better understanding of the sociality, life habits and habitat use of bison, and also describe how the provision of hay affects all these behaviours. These results could be useful in the development of tools to select the most suitable habitats for the reintroduction, management and conservation of bison populations.     

Single Low Dose Primaquine (0.25mg/kg) Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects

Background

Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75mg/kg (adult dose 45mg) but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15–20%) in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25mg/kg (adult dose 15mg) to Artemisinin-based Combination Therapies (ACTs) without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant) approximates 15%.

Methods and Findings

The tolerability and safety of primaquine (single dose 0.25 mg base/kg) combined with dihydroartemisinin-piperaquine (DHA-PPQ) given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4.7%) were greater than in G6PD normal subjects (0.3%, -0.8 and -1.7%) but were clinically insignificant. Fractional drops in haemoglobin concentration larger than 25% following single dose primaquine were observed in 1.8% of the population but were asymptomatic.

Conclusions

The single low dose (0.25mg/kg) of primaquine is clinically well tolerated and can be used safely without prior G6PD testing in populations with high prevalence of G6PD deficiency. The present evidence supports a broader use of low dose primaquine without G6PD testing for the treatment and elimination of falciparum malaria.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01872702","term_id":"NCT01872702"}}NCT01872702     

Surface polysaccharides and quorum sensing are involved in the attachment and survival of Xanthomonas albilineans on sugarcane leaves

Xanthomonas albilineans, the causal agent of sugarcane leaf scald, is a bacterial plant pathogen that is mainly spread by infected cuttings and contaminated harvesting tools. However, some strains of this pathogen are known to be spread by aerial means and are able to colonize the phyllosphere of sugarcane before entering the host plant and causing disease. The objective of this study was to identify the molecular factors involved in the survival or growth of X. albilineans on sugarcane leaves. We developed a bioassay to test for the attachment of X. albilineans on sugarcane leaves using tissue‐cultured plantlets grown in vitro. Six mutants of strain XaFL07‐1 affected in surface polysaccharide production completely lost their capacity to survive on the sugarcane leaf surface. These mutants produced more biofilm in vitro and accumulated more cellular poly‐β‐hydroxybutyrate than the wild‐type strain. A mutant affected in the production of small molecules (including potential biosurfactants) synthesized by non‐ribosomal peptide synthetases (NRPSs) attached to the sugarcane leaves as well as the wild‐type strain. Surprisingly, the attachment of bacteria on sugarcane leaves varied among mutants of the rpf gene cluster involved in bacterial quorum sensing. Therefore, quorum sensing may affect polysaccharide production, or both polysaccharides and quorum sensing may be involved in the survival or growth of X. albilineans on sugarcane leaves.     

Historical and contemporary determinants of global phylogenetic structure in tropical reef fish faunas

Identifying the main determinants of tropical marine biodiversity is essential for devising appropriate conservation measures mitigating the ongoing degradation of coral reef habitats. Based on a gridded distribution database and phylogenetic information, we compared the phylogenetic structure of assemblages for three tropical reef fish families (Labridae: wrasses, Pomacentridae: damselfishes and Chaetodontidae: butterflyfishes) using the net relatedness (NRI) and nearest taxon (NTI) indices. We then related these indices to contemporary and historical environmental conditions of coral reefs using spatial regression analyses. Higher levels of phylogenetic clustering were found for fish assemblages in the Indo‐Australian Archipelago (IAA), and more particularly when considering the NTI index. The phylogenetic structure of the Pomacentridae, and to a lower extent of the Chaeotodontidae and Labridae, was primarily associated with the location of refugia during the Quaternary period. Phylogenetic clustering in the IAA may partly result from vicariance events associated with coral reef fragmentation during the glacial periods of the Quaternary. Variation in the patterns among fish families further suggest that dispersal abilities may have interacted with past habitat availability in shaping the phylogenetic structure of tropical reef fish assemblages.     

Centrosome centering and decentering by microtubule network rearrangement

The centrosome is positioned at the cell center by pushing and pulling forces transmitted by microtubules (MTs). Centrosome decentering is often considered to result from asymmetric, cortical pulling forces exerted in particular by molecular motors on MTs and controlled by external cues affecting the cell cortex locally. Here we used numerical simulations to investigate the possibility that it could equally result from the redistribution of pushing forces due to a reorientation of MTs. We first showed that MT gliding along cell edges and pivoting around the centrosome regulate MT rearrangement and thereby direct the spatial distribution of pushing forces, whereas the number, dynamics, and stiffness of MTs determine the magnitude of these forces. By modulating these parameters, we identified different regimes, involving both pushing and pulling forces, characterized by robust centrosome centering, robust off-centering, or “reactive” positioning. In the last-named conditions, weak asymmetric cues can induce a misbalance of pushing and pulling forces, resulting in an abrupt transition from a centered to an off-centered position. Taken together, these results point to the central role played by the configuration of the MTs on the distribution of pushing forces that position the centrosome. We suggest that asymmetric external cues should not be seen as direct driver of centrosome decentering and cell polarization but instead as inducers of an effective reorganization of the MT network, fostering centrosome motion to the cell periphery.     

A laboratory approach for characterizing chronic fatigue: what does metabolomics tell us?

Metabolomics - Pre-eclampsia is a hypertensive gestational disorder that affects approximately 5% of all pregnancies. As the pathophysiological processes of pre-eclampsia are still uncertain, the...     

Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons

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No correlation between inbreeding depression and delayed selfing in the freshwater snail Physa acuta

Inbreeding depression, one of the main factors driving mating system evolution, can itself evolve as a function of the mating system (the genetic purging hypothesis). Classical models of coevolution between mating system and inbreeding depression predict negative associations between inbreeding depression and selfing rate, but more recent approaches suggest that negative correlations should usually be too weak or transient to be detected within populations. Empirical results remain unclear and restricted to plants. Here, we evaluate, for the first time, the within-population genetic correlation between inbreeding depression and a trait that controls the amount of self-fertilization (the waiting time) in a self-fertile hermaphroditic animal, the freshwater snail Physa acuta. Using a large quantitative-genetic design (36 grand-families and 348 families), we observe abundant within-population family-level genetic variation for both inbreeding depression (estimated for survival, fecundity, and size) and the degree of behavioral selfing avoidance. However, we detected no correlation between waiting time and inbreeding depression across families. In agreement with recent models, this result shows that mutational variance rather than differential purging accounts for most of the genetic variance in inbreeding depression within a population.     

Speech and non-speech audio-visual illusions: a developmental study

It is well known that simultaneous presentation of incongruent audio and visual stimuli can lead to illusory percepts. Recent data suggest that distinct processes underlie non-specific intersensory speech as opposed to non-speech perception. However, the development of both speech and non-speech intersensory perception across childhood and adolescence remains poorly defined. Thirty-eight observers aged 5 to 19 were tested on the McGurk effect (an audio-visual illusion involving speech), the Illusory Flash effect and the Fusion effect (two audio-visual illusions not involving speech) to investigate the development of audio-visual interactions and contrast speech vs. non-speech developmental patterns. Whereas the strength of audio-visual speech illusions varied as a direct function of maturational level, performance on non-speech illusory tasks appeared to be homogeneous across all ages. These data support the existence of independent maturational processes underlying speech and non-speech audio-visual illusory effects.