20 research outputs found
Effect of isoniazid preventive therapy on risk of death in west African, HIV-infected adults with high CD4 cell counts: long-term follow-up of the Temprano ANRS 12136 trial
Temprano ANRS 12136 was a factorial 2âĂâ2 trial that assessed the benefits of early antiretroviral therapy (ART; ie, in patients who had not reached the CD4 cell count threshold used to recommend starting ART, as per the WHO guidelines that were the standard during the study period) and 6-month isoniazid preventive therapy (IPT) in HIV-infected adults in CĂŽte d'Ivoire. Early ART and IPT were shown to independently reduce the risk of severe morbidity at 30 months. Here, we present the efficacy of IPT in reducing mortality from the long-term follow-up of Temprano.
Methods
For Temprano, participants were randomly assigned to four groups (deferred ART, deferred ART plus IPT, early ART, or early ART plus IPT). Participants who completed the trial follow-up were invited to participate in a post-trial phase. The primary post-trial phase endpoint was death, as analysed by the intention-to-treat principle. We used Cox proportional models to compare all-cause mortality between the IPT and no IPT strategies from inclusion in Temprano to the end of the follow-up period.
Findings
Between March 18, 2008, and Jan 5, 2015, 2056 patients (mean baseline CD4 count 477 cells per ÎŒL) were followed up for 9404 patient-years (Temprano 4757; post-trial phase 4647). The median follow-up time was 4·9 years (IQR 3·3â5·8). 86 deaths were recorded (Temprano 47 deaths; post-trial phase 39 deaths), of which 34 were in patients randomly assigned IPT (6-year probability 4·1%, 95% CI 2·9â5·7) and 52 were in those randomly assigned no IPT (6·9%, 5·1â9·2). The hazard ratio of death in patients who had IPT compared with those who did not have IPT was 0·63 (95% CI, 0·41 to 0·97) after adjusting for the ART strategy (early vs deferred), and 0·61 (0·39â0·94) after adjustment for the ART strategy, baseline CD4 cell count, and other key characteristics. There was no evidence for statistical interaction between IPT and ART (pinteraction=0·77) or between IPT and time (pinteraction=0·94) on mortality.
Interpretation
In CĂŽte d'Ivoire, where the incidence of tuberculosis was last reported as 159 per 100â000 people, 6 months of IPT has a durable protective effect in reducing mortality in HIV-infected people, even in people with high CD4 cell counts and who have started ART
Alternative Splicing Regulates Targeting of Malate Dehydrogenase in Yarrowia lipolytica
Alternative pre-mRNA splicing is a major mechanism contributing to the proteome complexity of most eukaryotes, especially mammals. In less complex organisms, such as yeasts, the numbers of genes that contain introns are low and cases of alternative splicing (AS) with functional implications are rare. We report the first case of AS with functional consequences in the yeast Yarrowia lipolytica. The splicing pattern was found to govern the cellular localization of malate dehydrogenase, an enzyme of the central carbon metabolism. This ubiquitous enzyme is involved in the tricarboxylic acid cycle in mitochondria and in the glyoxylate cycle, which takes place in peroxisomes and the cytosol. In Saccharomyces cerevisiae, three genes encode three compartment-specific enzymes. In contrast, only two genes exist in Y. lipolytica. One gene (YlMDH1, YALI0D16753g) encodes a predicted mitochondrial protein, whereas the second gene (YlMDH2, YALI0E14190g) generates the cytosolic and peroxisomal forms through the alternative use of two 3âČ-splice sites in the second intron. Both splicing variants were detected in cDNA libraries obtained from cells grown under different conditions. Mutants expressing the individual YlMdh2p isoforms tagged with fluorescent proteins confirmed that they localized to either the cytosolic or the peroxisomal compartment
An integrated approach to control soil-transmitted helminthiasis, schistosomiasis, intestinal protozoa infection, and diarrhea : protocol for a cluster randomized trial
Background: The global strategy to control helminthiases (schistosomiasis and soil-transmitted helminthiasis) emphasizes preventive chemotherapy. However, in the absence of access to clean water, improved sanitation, and adequate hygiene, reinfection after treatment can occur rapidly. Integrated approaches might be necessary to sustain the benefits of preventive chemotherapy and make progress toward interruption of helminthiases transmission.
Objective: The aim of this study was to assess and quantify the effect of an integrated control package that consists of preventive chemotherapy, community-led total sanitation, and health education on soil-transmitted helminthiasis, schistosomiasis, intestinal protozoa infection, and diarrhea in rural CĂŽte dâIvoire.
Methods: In a first step, a community health education program was developed that includes an animated cartoon to promote improved hygiene and health targeting school-aged children, coupled with a health education theater for the entire community. In a second step, a cluster randomized trial was implemented in 56 communities of south-central CĂŽte dâIvoire with 4 intervention arms: (1) preventive chemotherapy; (2) preventive chemotherapy plus community-led total sanitation; (3) preventive chemotherapy plus health education; and (4) all 3 interventions combined. Before implementation of the aforementioned interventions, a baseline parasitologic, anthropometric, and hygiene-related knowledge, attitudes, practices, and beliefs survey was conducted. These surveys were repeated 18 and 39 months after the baseline cross-sectional survey to determine the effect of different interventions on helminth and intestinal protozoa infection, nutritional indicators, and knowledge, attitudes, practices, and beliefs. Monitoring of diarrhea was done over a 24-month period at 2-week intervals, starting right after the baseline survey.
Results: Key results from this cluster randomized trial will shed light on the effect of integrated approaches consisting of preventive chemotherapy, community-led total sanitation, and health education against infections with soil-transmitted helminths, schistosomes, an intestinal protozoa and prevention of diarrhea in a rural part of CĂŽte dâIvoire.
Conclusions: The research provided new insights into the acceptability, strengths, and limitations of an integrated community-based control package targeting helminthiases, intestinal protozoa infections, and diarrhea in rural communities of CĂŽte dâIvoire. In the longer term, the study will allow determining the effect of the integrated control approach on infection patterns with parasitic worms and intestinal protozoa, diarrheal incidence, anthropometric measures, and hygiene-related knowledge, attitudes, practices, and beliefs
Evaluation du test rapide oral awareâą omt HIV 1/2 pour le depistage de lâinfection a vih en Cote dâIvoire
Introduction : le test rapide oral est une alternative moins invasive du test sanguin pour le dĂ©pistage du VIH Ă©liminant ainsi le risque dâexposition au sang des professionnels de la santĂ©. Lâobjectif Ă©tait dâĂ©valuer la sensibilitĂ©, la spĂ©cificitĂ© et la facilitĂ© dâutilisation du test rapide oral AwareTM HIV-1/2 OMT dans le contexte ivoirien.MĂ©thodes : LâĂ©tude a portĂ© sur 450 participants venus pour un dĂ©pistage volontaire ou un bilan initial dans 4 diffĂ©rents sites dâAbidjan ayant donnĂ© un consentement Ă©crit. Chaque participant a fourni un Ă©chantillon de fluide oral pour la rĂ©alisation du test AwareâąÂ OMT HIV-1/2 et du sang testĂ© suivant lâalgorithme sĂ©quentiel de tests ELISAs MurexÂź HIV-1.2.0 (Laboratoires Abbott, Japon) et Test ELISA peptidique maison du CeDReS.RĂ©sultats : la sensibilitĂ©, la spĂ©cificitĂ©, la Valeur PrĂ©dictive Positive et la Valeur PrĂ©dictive NĂ©gative du test rapide oral Ă©taient de 99,5 % [IC 95%: 98,6 Ă 100], 100 % [IC 95%: 96,1 Ă 100], 100 % et de 99,5 % respectivement. Selon les critĂšres de lâOMS, le test Awareâą OMT HIV 1/2 est dâune praticabilitĂ© trĂšs simple et dâune utilisation aisĂ©e dans les laboratoires pĂ©riphĂ©riques.Conclusion : Le test Aware OMT HIV 1/2 prĂ©sente d'excellentes performances techniques permettant son utilisation dans lâalgorithme national de dĂ©pistage du VIH aprĂšs une validation en phase II et dans le cadre de stratĂ©gies avancĂ©es de dĂ©pistage en CĂŽte dâIvoire. Toutefois, la confirmation des rĂ©sultats positifs par les tests sanguins est une nĂ©cessitĂ© en raison de lâinstabilitĂ© du fluide oral.Mots clĂ©s : VIH -sensibilitĂ©-spĂ©cificitĂ©-fluide oral- CĂŽte dâIvoire