Роль «национальной» политики центра в разногласиях в руководстве Азербайджана (вторая половина - 20-х – 30-е годы ХХ века)

International audienc

The macrofilaricidal efficacy of repeated doses of ivermectin for the treatment of river blindness

Background: Mass drug administration (MDA) with ivermectin is the cornerstone of efforts to eliminate human onchocerciasis by 2020 or 2025. The feasibility of elimination crucially depends on the effects of multiple ivermectin doses on Onchocerca volvulus. A single ivermectin (standard) dose clears the skin-dwelling microfilarial progeny of adult worms (macrofilariae) and temporarily impedes the release of such progeny by female macrofilariae, but a macrofilaricidal effect has been deemed minimal. Multiple doses of ivermectin may cumulatively and permanently reduce the fertility and shorten the lifespan of adult females. However, rigorous quantification of these effects necessitates interrogating longitudinal data on macrofilariae with suitably powerful analytical techniques. Methods: Using a novel mathematical modeling approach, we analyzed, at an individual participant level, longitudinal data on viability and fertility of female worms from the single most comprehensive multiple-dose clinical trial of ivermectin, comparing 3-monthly with annual treatments administered for 3 years in Cameroon

Statistical problems encountered in the study of antiretroviral treatment of adults infected with HIV in sub-Saharan Africa

Partant de problématiques statistiques rencontrées dans l'étude du traitement antirétroviral des adultes infectés par le virus de l'immunodéficience humaine (VIH) en Afrique subsaharienne, cette thèse cherche, d'une part, à favoriser la vulgarisation d'outils méthodologiques relativement récents auprès d'un public d'utilisateurs moins avertis et, d'autre part, à participer au développement de nouveaux outils. Le premier chapitre présente différentes méthodes de modélisation des données longitudinales dont des méthodes d'analyse de l'évolution d'un critère au cours du temps (les modèles linéaires mixtes généralisés et les modèles d'équations d'estimation généralisées) ou de la survenue d'un évènement au cours du temps (le modèle semi-paramétrique de Cox et ses extensions à la prise en compte des covariables dépendantes du temps et de la censure informative). Le deuxième chapitre s'intéresse aux tests de non-infériorité et propose deux développements de la procédure classique de ces tests pour les cas où la marge de non-infériorité est relative. Enfin, le troisième chapitre aborde la question des données manquantes et propose une extension de la méthode d'imputation multiple par les distributions conditionnelles univariées qui consiste à prendre en compte des effets non-linéaires des covariables dans les modèles d'imputation par des fonctions B-splines. Ces méthodes sont illustrées par des études sur le VIH au Cameroun et au Sénégal.On the basis of statistical challenges encountered in study of antiretroviral treatment of adults infected with human immunodeficiency virus (HIV) in sub-Saharan Africa, this thesis aims to promote the dissemination of relatively recent methodological tools of less aware audience of users on one hand and to participate to development of new tools on the other hand. The first chapter presents various methods for modeling longitudinal data of which analysis methods for changing of a criterion over time (the generalized linear mixed models and models of generalized estimating equations) or the occurrence of an event over time (the semi-parametric Cox model and its extensions to take into account time-dependent covariates and informative censoring). The second chapter focuses on non-inferiority test and provides two developments of the classical procedure of these tests in cases where the non-inferiority margin is relative. The third chapter addresses the question of missing data and proposes an extension of the multiple imputation method based on fully conditional specification, to take into account nonlinear effects of covariates in the imputation models using B-splines functions. These methods are illustrated by studies on HIV in Cameroon and Senegal

Problématiques statistiques rencontrées dans l'étude du traitement antirétroviral des adultes infectés par le VIH en Afrique subsaharienne

Partant de problématiques statistiques rencontrées dans l'étude du traitement antirétroviral des adultes infectés par le virus de l'immunodéficience humaine (VIH) en Afrique subsaharienne, cette thèse cherche, d'une part, à favoriser la vulgarisation d'outils méthodologiques relativement récents auprès d'un public d'utilisateurs moins avertis et, d'autre part, à participer au développement de nouveaux outils. Le premier chapitre présente différentes méthodes de modélisation des données longitudinales dont des méthodes d'analyse de l'évolution d'un critère au cours du temps (les modèles linéaires mixtes généralisés et les modèles d'équations d'estimation généralisées) ou de la survenue d'un évènement au cours du temps (le modèle semi-paramétrique de Cox et ses extensions à la prise en compte des covariables dépendantes du temps et de la censure informative). Le deuxième chapitre s'intéresse aux tests de non-infériorité et propose deux développements de la procédure classique de ces tests pour les cas où la marge de non-infériorité est relative. Enfin, le troisième chapitre aborde la question des données manquantes et propose une extension de la méthode d'imputation multiple par les distributions conditionnelles univariées qui consiste à prendre en compte des effets non-linéaires des covariables dans les modèles d'imputation par des fonctions B-splines. Ces méthodes sont illustrées par des études sur le VIH au Cameroun et au Sénégal.On the basis of statistical challenges encountered in study of antiretroviral treatment of adults infected with human immunodeficiency virus (HIV) in sub-Saharan Africa, this thesis aims to promote the dissemination of relatively recent methodological tools of less aware audience of users on one hand and to participate to development of new tools on the other hand. The first chapter presents various methods for modeling longitudinal data of which analysis methods for changing of a criterion over time (the generalized linear mixed models and models of generalized estimating equations) or the occurrence of an event over time (the semi-parametric Cox model and its extensions to take into account time-dependent covariates and informative censoring). The second chapter focuses on non-inferiority test and provides two developments of the classical procedure of these tests in cases where the non-inferiority margin is relative. The third chapter addresses the question of missing data and proposes an extension of the multiple imputation method based on fully conditional specification, to take into account nonlinear effects of covariates in the imputation models using B-splines functions. These methods are illustrated by studies on HIV in Cameroon and Senegal.MONTPELLIER-BU Médecine UPM (341722108) / SudocSudocFranceF

Effect of a Single Standard Dose (150–200 μg/kg) of Ivermectin on Loa loa Microfilaremia: Systematic Review and Meta-analysis

International audienceBackground: In central Africa, millions of individuals infected with Loa loa have received the anthelminthic drug ivermectin (IVM) as part of mass drug administration (MDA) campaigns targeting onchocerciasis control or elimination. Nonetheless, the parasitological surveys that are occasionally conducted to evaluate the impact of IVM treatments on Onchocerca volvulus do not include an assessment of the extra benefits of those MDA campaigns on L. loa.Methods: We conducted a systematic review of trials on the effect of a single standard (150-200 μg/kg) dose of IVM on L. loa microfilarial density (MFD). The dynamics of MFD over 365 days of treatment were described using multilevel regression and latent class modeling.Results: IVM brings about a rapid, dramatic, and sustained decrease, with reduction rates of 60%, 75%, 85%, and 90% on day 1 (D1), D2, D7, and D365, respectively. At D365, no participants (0/238) with an initial MFD of <20 000 microfilariae (mf)/mL were at risk of postivermectin severe adverse events, and only 1/57 individuals with an initial MFD of ≥20 000 mf/mL presented with an MFD above this value. The main predictor of post-treatment MFD was the pretreatment value, but this post-treatment value varied little between D8 and D365 regardless of the pretreatment level.Conclusions: A single dose of IVM is very effective at substantially reducing L. loa MFD for at least a year, irrespective of the initial level of parasitemia. Individuals treated with IVM are probably not any more at risk of severe adverse events when retreated 1 year later

Long-term effectiveness and safety of didanosine combined with lamivudine and efavirenz or nevirapine in antiretroviral-naive patients : a 9-year cohort study in Senegal

OBJECTIVE The use of didanosine (ddI) in first-line antiretroviral therapy has been recently promoted for resource-limited settings. We therefore compared the long-term effectiveness and safety of the regimen combining ddI, lamivudine, and efavirenz or nevirapine with that of the WHO-recommended regimen of zidovudine (ZDV), lamivudine, and efavirenz or nevirapine in antiretroviral-naive patients in Senegal. METHODS Observational cohort study of patients enrolled between January 2000 and April 2002 in the Senegalese antiretroviral drug access initiative. Multivariate analyses were performed to compare, between the ddI and ZDV groups, the proportion of patients with a viral load 0.3). The rate of death tended to be higher in the ddI group (P = 0.06). ddI was less commonly discontinued than ZDV (P = 0.03). CONCLUSION The combination of ddI, lamivudine, and efavirenz or nevirapine resulted in sustained viral suppression and immunological recovery

Improving the management and security of COVID 19 diagnostic test data with a digital platform in resource-limited settings: The case of PlaCARD in Cameroon

During the COVID 19 pandemic, round-the-clock demand for COVID -19 laboratory tests exceeded capacity, placing a significant burden on laboratory staff and infrastructure. The use of laboratory information management systems (LIMS) to streamline all phases of laboratory testing (preanalytical, analytical, and postanalytical) has become inevitable. The objective of this study is to describe the architecture, implementation, and requirements of PlaCARD, a software platform for managing patient registration, medical specimens, and diagnostic data flow, as well as reporting and authentication of diagnostic results during the 2019 coronavirus pandemic (COVID -19) in Cameroon. Building on its experience with biosurveillance, CPC developed an open-source, real-time digital health platform with web and mobile applications called PlaCARD to improve the efficiency and timing of disease-related interventions. PlaCARD was quickly adapted to the decentralization strategy of the COVID 19 testing in Cameroon and, after specific user training, was deployed in all COVID 19 diagnostic laboratories and the regional emergency operations center. Overall, 71% of samples tested for COVID 19 by molecular diagnostics in Cameroon from 05 March 2020 to 31 October 2021 were entered into PlaCARD. The median turnaround time for providing results was 2 days [0–2.3] before April 2021 and decreased to 1 day [1– 1] after the introduction of SMS result notification in PlaCARD. The integration of LIMS and workflow management into a single comprehensive software platform (PlaCARD) has strengthened COVID 19 surveillance capabilities in Cameroon. PlaCARD has demonstrated that it can be used as a LIMS for managing and securing test data during an outbreak. Author summary Following the emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China, in December 2019 and its global spread, the number of tests conducted by laboratories COVID 19 increased rapidly, placing a significant burden on laboratory staff and infrastructure. This resulted in long turnaround times for laboratory results, which in turn led to delays in immediate follow-up and strategic decision making. The use of laboratory information management systems (LIMS) to streamline all phases of laboratory testing (preanalytical, analytical, and postanalytical) has therefore become essential. The objective of this study was to describe thearchitecture requirements of the PlaCARD (Platform for Collecting, Analyzing, and Reporting Data) digital platform and its implementation for decentralization of COVID 19 diagnostics in a resource-constrained environment. The results of this study showed that integrating of the LIMS and workflow management into a comprehensive software platform improved COVID 19 surveillance capabilities in Cameroon. The PlaCARD platform demonstrated that it could be used as a LIMS for managing and storing test data during an outbreak

Improving the management and security of COVID 19 diagnostic test data with a digital platform in resource-limited settings: The case of PlaCARD in Cameroon.

During the COVID 19 pandemic, round-the-clock demand for COVID -19 laboratory tests exceeded capacity, placing a significant burden on laboratory staff and infrastructure. The use of laboratory information management systems (LIMS) to streamline all phases of laboratory testing (preanalytical, analytical, and postanalytical) has become inevitable. The objective of this study is to describe the architecture, implementation, and requirements of PlaCARD, a software platform for managing patient registration, medical specimens, and diagnostic data flow, as well as reporting and authentication of diagnostic results during the 2019 coronavirus pandemic (COVID -19) in Cameroon. Building on its experience with biosurveillance, CPC developed an open-source, real-time digital health platform with web and mobile applications called PlaCARD to improve the efficiency and timing of disease-related interventions. PlaCARD was quickly adapted to the decentralization strategy of the COVID 19 testing in Cameroon and, after specific user training, was deployed in all COVID 19 diagnostic laboratories and the regional emergency operations center. Overall, 71% of samples tested for COVID 19 by molecular diagnostics in Cameroon from 05 March 2020 to 31 October 2021 were entered into PlaCARD. The median turnaround time for providing results was 2 days [0-2.3] before April 2021 and decreased to 1 day [1- 1] after the introduction of SMS result notification in PlaCARD. The integration of LIMS and workflow management into a single comprehensive software platform (PlaCARD) has strengthened COVID 19 surveillance capabilities in Cameroon. PlaCARD has demonstrated that it can be used as a LIMS for managing and securing test data during an outbreak

Virological failure and antiretroviral resistance among HIV-infected children after five years follow-up in the ANRS 12225-PEDIACAM cohort in Cameroon

International audienceObjective In the present study, we aimed to evaluate the virological failure (VF) and drug resistance among treated HIV-infected children after five years follow-up in the ANRS-Pediacam cohort in Cameroon. Methods From November 2007 to October 2011, HIV-infected children born to HIV-infected mothers were included in the ANRS-PEDIACAM study and followed-up for more than 5 years. Plasma viral load (VL) was measured at each visit (every three months until month 24 and every 6 months thereafter). VF was the main outcome and HIV drug resistance test was performed using the ANRS procedures and algorithm. Results Data from 155 children were analyzed. The median age at combination antiretroviral therapy (cART) initiation was 4.2 months (interquartile range (IQR): 3.2–5.8), with 103 (66.5%) children taking LPV/r-containing regimen and 51 (32.9%) children taking NVP. After five years follow-up, 63 (40.6%; CI: 32.9–48.8) children experienced VF. The median duration between cART initiation and VF was 22.1 months (IQR: 11.9–37.1) with a median VL of 4.8 log10 (IQR: 4.0–5.5). Among the 57 children with HIV drug resistance results, 40 (70.2%) had at least one drug resistance mutation. The highest resistance rates (30.4–66.1%) were obtained with Lamivudine; Efavirenz; Nevirapine and Rilpivirine. Conclusions These results show high resistance to NNRTI and emphasize the need of VL and resistance tests for optimal follow-up of HIV-infected people especially children