Gender Differences in Survival among Adult Patients Starting Antiretroviral Therapy in South Africa: A Multicentre Cohort Study

Background

Increased mortality among men on antiretroviral therapy (ART) has been documented but remains poorly understood. We examined the magnitude of and risk factors for gender differences in mortality on ART.

Methods and Findings

Analyses included 46,201 ART-naïve adults starting ART between January 2002 and December 2009 in eight ART programmes across South Africa (SA). Patients were followed from initiation of ART to outcome or analysis closure. The primary outcome was mortality; secondary outcomes were loss to follow-up (LTF), virologic suppression, and CD4+ cell count responses. Survival analyses were used to examine the hazard of death on ART by gender. Sensitivity analyses were limited to patients who were virologically suppressed and patients whose CD4+ cell count reached >200 cells/µl. We compared gender differences in mortality among HIV+ patients on ART with mortality in an age-standardised HIV-negative population.Among 46,201 adults (65% female, median age 35 years), during 77,578 person-years of follow-up, men had lower median CD4+ cell counts than women (85 versus 110 cells/µl, p<0.001), were more likely to be classified WHO stage III/IV (86 versus 77%, p<0.001), and had higher mortality in crude (8.5 versus 5.7 deaths/100 person-years, p<0.001) and adjusted analyses (adjusted hazard ratio [AHR] 1.31, 95% CI 1.22–1.41). After 36 months on ART, men were more likely than women to be truly LTF (AHR 1.20, 95% CI 1.12–1.28) but not to die after LTF (AHR 1.04, 95% CI 0.86–1.25). Findings were consistent across all eight programmes. Virologic suppression was similar by gender; women had slightly better immunologic responses than men. Notably, the observed gender differences in mortality on ART were smaller than gender differences in age-standardised death rates in the HIV-negative South African population. Over time, non-HIV mortality appeared to account for an increasing proportion of observed mortality. The analysis was limited by missing data on baseline HIV disease characteristics, and we did not observe directly mortality in HIV-negative populations where the participating cohorts were located.

Conclusions

HIV-infected men have higher mortality on ART than women in South African programmes, but these differences are only partly explained by more advanced HIV disease at the time of ART initiation, differential LTF and subsequent mortality, and differences in responses to treatment. The observed differences in mortality on ART may be best explained by background differences in mortality between men and women in the South African population unrelated to the HIV/AIDS epidemic. Please see later in the article for the Editors'' Summary.     

Diapausing egg banks,lake size,and genetic diversity in the rotifer <Emphasis Type="Italic">Brachionus plicatilis</Emphasis> Müller (Rotifera,Monogononta)

The fish from the family Anostomidae represent one of the most important groups of freshwater ichthyofauna from South America, with species of high economical value. The migratory characteristic of some species, through the several Amazonian environments, takes them into waters with different physico-chemical characteristics. Cytogenetic studies on the Anostomidae demonstrate that these fishes have a conserved diploid number and karyotype macrostructure. So, to verify if this conservation occurs also in the genomic level, the current study aimed at a chromosomal comparative physical mapping, using 45S and 5S rDNA, of seven species of anostomids: Leporinus fasciatus, L. agassizi, L. friderici, L. trifasciatus, Rhytiodus macrolepis, Laemolyta taeniata, and Schizodon fasciatus, collected in different Amazonian environments. The results obtained corroborate the conservation of the karyotype macrostructure. However, significant differences were found in the distribution of heterochromatin and on the pair bearing the nucleolus organizer region. The staining of 45S and 5S rDNA by FISH highlighted, for four of the seven species, more than one chromosome pair bearing the site 45S. The 5S rDNA, although present in only one chromosome pair, varied in its chromosome and karyotype position. Thus, although the Anostomidae family has a conserved chromosomic macrostructure the use of molecular techniques revealed the presence of chromosomic translocation during the evolution of these fishes.     

Reduction in Malaria Incidence following Indoor Residual Spraying with Actellic 300 CS in a Setting with Pyrethroid Resistance: Mutasa District,Zimbabwe

Background

More than half of malaria cases in Zimbabwe are concentrated in Manicaland Province, where seasonal malaria epidemics occur despite intensified control strategies. Recently, high levels of pyrethroid and carbamate resistance were detected in Anopheles funestus, the major malaria vector in eastern Zimbabwe. In response, a single round of indoor residual spraying (IRS) using pirimiphos-methyl (an organophosphate) was implemented in four high burden districts of Manicaland Province from November 1, 2014 to December 19, 2014. The objective of this study was to evaluate the effect of this programmatic switch in insecticides on malaria morbidity reported from health care facilities in Mutasa District, one of the worst affected districts in Manicaland Province.

Methods

The number of weekly malaria cases for each health facility 24 months prior to the 2014 IRS campaign and in the subsequent high transmission season were obtained from passive case surveillance. Environmental variables were extracted from remote-sensing data sources and linked to each health care facility. Negative binomial regression was used to model the weekly number of malaria cases, adjusted for seasonality and environmental variables.

Results

From December 2012 to May 2015, 124,206 malaria cases were reported from 42 health care facilities in Mutasa District. Based on a higher burden of malaria, 20 out of 31 municipal wards were sprayed in the district. Overall, 87.3% of target structures were sprayed and 92.1% of the target population protected. During the 6 months after the 2014 IRS campaign, a period when transmission would have otherwise peaked, the incidence of malaria was 38% lower than the preceding 24 months at health facilities in the sprayed wards.

Conclusions

Pirimiphos-methyl had a measurable impact on malaria incidence and is an effective insecticide for the control of An. funestus in eastern Zimbabwe.     

Macronuclear Molecules Encoding Actins in Spirotrichs

Abstract The nucleotide sequences of 16 newly reported and 8 previously reported actin-encoding macronuclear DNA molecules in spirotrichs have been compared. As described for the eight previously reported molecules, the first 50 bases (noncoding) inside the telomere at both 5′ strands in additional actin molecules are purine-rich. This anomalous base composition might serve as a signal to identify macronuclear molecules in micronuclear DNA during development. The 50-base segment upstream of the ATG in the 5′ leaders of the actin molecules contains extensive, conserved sequence motifs that are possibly promoter elements. The 3′ noncoding trailers contain virtually no conserved sequence motifs. With one exception, the 3′ trailers contain a second stop codon (TGA) 36 bases on average downstream of the primary stop codon. Excluding Moneuplotes crassus, amino acid identities in actin I range from 78 to 100%, with variations distributed nonrandomly along the sequence. Phylogenetic trees based on the actin nucleotide sequences of 22 spirotrichs define the evolutionary relationships of their actin-encoding molecules. The actin phylogeny, while well supported by posterior probabilities, does not always coincide with the phylogeny defined in rDNA analyses or classical taxonomic classifications.     

Molecular, anatomical, and functional organization of the Drosophila olfactory system

BACKGROUND: Olfactory receptor neurons (ORNs) convey chemical information into the brain, producing internal representations of odors detected in the periphery. A comprehensive understanding of the molecular and neural mechanisms of odor detection and processing requires complete maps of odorant receptor (Or) expression and ORN connectivity, preferably at single-cell resolution. RESULTS: We have constructed near-complete maps of Or expression and ORN targeting in the Drosophila olfactory system. These maps confirm the general validity of the "one neuron--one receptor" and "one glomerulus--one receptor" principles and reveal several additional features of olfactory organization. ORNs in distinct sensilla types project to distinct regions of the antennal lobe, but neighbor relations are not preserved. ORNs grouped in the same sensilla do not express similar receptors, but similar receptors tend to map to closely appositioned glomeruli in the antennal lobe. This organization may serve to ensure that odor representations are dispersed in the periphery but clustered centrally. Integrated with electrophysiological data, these maps also predict glomerular representations of specific odorants. Representations of aliphatic and aromatic compounds are spatially segregated, with those of aliphatic compounds arranged topographically according to carbon chain length. CONCLUSIONS: These Or expression and ORN connectivity maps provide further insight into the molecular, anatomical, and functional organization of the Drosophila olfactory system. Our maps also provide an essential resource for investigating how internal odor representations are generated and how they are further processed and transmitted to higher brain centers.     

Mitochondrial DNA phylogeography of the Mesoamerican spiny-tailed lizards (Ctenosaura quinquecarinata complex): historical biogeography, species status and conservation

Through the examination of past and present distributions of plants and animals, historical biogeographers have provided many insights on the dynamics of the massive organismal exchange between North and South America. However, relatively few phylogeographic studies have been attempted in the land bridge of Mesoamerica despite its importance to better understand the evolutionary forces influencing this biodiversity 'hotspot'. Here we use mitochondrial DNA sequence data from fresh samples and formalin-fixed museum specimens to investigate the genetic and biogeographic diversity of the threatened Mesoamerican spiny-tailed lizards of the Ctenosaura quinquecarinata complex. Species boundaries and their phylogeographic patterns are examined to better understand their disjunct distribution. Three monophyletic, allopatric lineages are established using mtDNA phylogenetic and nested clade analyses in (i) northern: México, (ii) central: Guatemala, El Salvador and Honduras, and (iii) southern: Nicaragua and Costa Rica. The average sequence divergence observed between lineages varied between 2.0% and 3.7% indicating that they do not represent a very recent split and the patterns of divergence support the recently established nomenclature of C. quinquecarinata, Ctenosaura flavidorsalis and Ctenosaura oaxacana. Considering the geological history of Mesoamerica and the observed phylogeographic patterns of these lizards, major evolutionary episodes of their radiation in Mesoamerica are postulated and are indicative of the regions' geological complexity. The implications of these findings for the historical biogeography, taxonomy and conservation of these lizards are discussed.     

A Polymer/Oil Based Nanovaccine as a Single-Dose Immunization Approach

The recognized necessity for new antigen delivery carriers with the capacity to boost, modulate and prolong neutralizing immune responses prompted our approach, in which we describe a multifunctional nanocarrier consisting of an oily nanocontainer protected by a polymeric shell made of chitosan (CS), named CS nanocapsules (CSNC). The CS shell can associate the antigen on its surface, whereas the oily core might provide additional immunostimulating properties. In this first characterization of the system, we intended to study the influence of different antigen organizations on the nanocarrier''s surface (using the recombinant hepatitis B surface antigen –rHBsAg– as a model antigen) on their long-term immunopotentiating effect, without any additional immunostimulant. Thus, two prototypes of antigen-loaded CSNC (CSNC+ and CSNC−), exhibiting similar particle size (200 nm) and high antigen association efficiency (>80%), were developed with different surface composition (polymer/antigen ratios) and surface charge (positive/negative, respectively). The biological evaluation of these nanovaccines evidenced the superiority of the CSNC+ as compared to CSNC- and alum-rHBsAg in terms of neutralizing antibody responses, following intramuscular vaccination. Moreover, a single dose of CSNC+ led to similar IgG levels to the positive control. The IgG1/IgG2a ratio suggested a mixed Th1/Th2 response elicited by CSNC+, in contrast to the typical Th2-biased response of alum. Finally, CSNC+ could be freeze-dried without altering its physicochemical properties and adjuvant effect in vivo. In conclusion, the evaluation of CSNC+ confirms its interesting features for enhancing, prolonging and modulating the type of immune response against subunit antigens, such as rHBsAg.