Valeur diagnostique de deux tests rapides utilisés dans le diagnostic du VIH-2 au Mali : Diagnosis value of two HIV-2 rapid diagnostic tests used in Mali

Context and objective. In sub-Saharan Africa, the epicenter of HIV infection, rapid tests are proposed in first line, but diagnosis value of these tests is rarely performed. The goal of the present study was to evaluate the performance of 2 rapid tests used for the diagnosis of HIV-2 infection compared to a baseline test in order to propose in algorithm for HIV infection diagnosis in health care system. Methods. A cross-sectional study was carried out in three treatment centers in Mali (Bamako, Segou and Sikasso). The tests evaluated were: Genie® II HIV-1/HIV-2 (Sanofi Diagnostic Pasteur, France) and ImmunoComb® II HIV 1&2 BiSpot (Organics, Strasbourg, France). The study involved 34 sera collected consecutively. The l’INNO-LIA HIV I/II Score confirmatory test was used as a reference test in Belgium. Performance of tests were assessed using sensibility, specificity, positive predictive value, negative predictive value and kappa concordance. Results. Patients’ ages ranged from 12 years to 78 years, 19 patients were women (55.8%) and 28 patients had HIV-2 infection. The sensitivity of the rapid tests was 96.4%. The kappa concordance coefficient was 0.85. We found 28 HIV-2 positive patients out of 34 patients. Conclusions. The two rapid tests used in Mali yielded satisfactory results, but the quality of HIV-1 and 2 discrimination serology could be improved. Contexte et objectif. Dans les pays d’Afrique subsaharienne épicentre de l’infection à VIH, les tests rapides sont proposés en première intention, mais la valeur diagnostique de ces tests est rarement réalisée. L’objectif du présent travail était d’évaluer la performance de 2 tests rapides utilisés pour le diagnostic de l’infection à VIH-2 par rapport un test de référence afin de proposer des algorithmes de tests simples et rapides utilisables dans les structures sanitaires. Méthodes.Une étude transversale a été réalisée, dans trois centres de prise en charge au Mali (Bamako, Ségou et Sikasso). Les tests évalués étaient le Genie® II HIV-1/HIV-2 (Sanofi Diagnostic Pasteur, France) et l’ImmunoComb® II HIV 1&2 BiSpot (Organics, Strasbourg, France). L’étude a porté sur 34 sérums collectés consécutivement. Le test de confirmation l’INNO-LIA HIV I/II Score a été utilisé comme test de référence en Belgique. La performance de deux tests précités a été évaluée en recherchant la sensibilité, la spécificité, la valeur prédictive positive (VPP), la valeur prédictive négative (VPN) et la concordance. Résultats. L’âge des patients variait de 12 ans à 78 ans, 19 patients étaient des femmes (55,8%) et 28 patients avaient le VIH-2. La sensibilité des tests rapides était de 96,4%. Le coefficient de concordance kappa était de 0,85. Conclusions. Les deux tests rapides utilisés au Mali ont donné des résultats satisfaisants, et peuvent être proposés en première intention dans l’algorithme national du diagnostic de l’infection à VIH-2 au Mali

Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir

<p>Abstract</p> <p>Background</p> <p>Human Immunodeficiency Virus type 2 is naturally resistant to some antiretroviral drugs, restricting therapeutic options for patients infected with HIV-2. Regimens including integrase inhibitors (INI) seem to be effective, but little data on HIV-2 integrase (IN) polymorphisms and resistance pathways are available.</p> <p>Materials and methods</p> <p>The <it>integrase </it>coding sequence from 45 HIV-2-infected, INI-naïve, patients was sequenced and aligned against the ROD (group A) or EHO (group B) reference strains and polymorphic or conserved positions were analyzed.</p> <p>To select for raltegravir (RAL)-resistant variants <it>in vitro</it>, the ROD strain was cultured under increasing sub-optimal RAL concentrations for successive rounds. The phenotype of the selected variants was assessed using an MTT assay.</p> <p>Results</p> <p>We describe <it>integrase </it>gene polymorphisms in HIV-2 clinical isolates from 45 patients. Sixty-seven percent of the integrase residues were conserved. The HHCC Zinc coordination motif, the catalytic triad DDE motif, and AA involved in IN-DNA binding and correct positioning were highly conserved and unchanged with respect to HIV-1 whereas the connecting residues of the N-terminal domain, the dimer interface and C-terminal LEDGF binding domain were highly conserved but differed from HIV-1. The N155 H INI resistance-associated mutation (RAM) was detected in the virus population from one ARV-treated, INI-naïve patient, and the 72I and 201I polymorphisms were detected in samples from 36 and 38 patients respectively. No other known INI RAM was detected.</p> <p>Under RAL selective pressure <it>in vitro</it>, a ROD variant carrying the Q91R+I175M mutations was selected. The Q91R and I175M mutations emerged simultaneously and conferred phenotypic resistance (13-fold increase in IC₅₀). The Q91R+I175M combination was absent from all clinical isolates. Three-dimensional modeling indicated that residue 91 lies on the enzyme surface, at the entry of a pocket containing the DDE catalytic triad and that adding a positive charge (Gln to Arg) might compromise IN-RAL affinity.</p> <p>Conclusions</p> <p>HIV-2 polymorphisms from 45 INI-naïve patients are described. Conserved regions as well as frequencies of HIV-2 IN polymorphisms were comparable to HIV-1. Two new mutations (Q91R and I175M) that conferred high resistance to RAL were selected <it>in vitro</it>, which might affect therapeutic outcome.</p

Antiretroviral-induced adverse drug reactions in HIV-infected patients in Mali: a resource-limited setting experience

Background: There are few reports in the literature from sub-Saharan Africa (SSA) regarding antiretroviral-induced adverse drug reactions (ADRs). Antiretroviral therapy (ART) is now widely available in SSA, and ADRs during HIV infection are also frequent. In this study, we reported the frequency and risk factors of ART-induced ADRs in a Malian population.Methods: This prospective cohort study was performed in the HIV Care and Counseling Centre (CESAC) of Mali from 2011 to 2012. Adult patients infected with HIV and who had recently started ART were included and followed-up clinically Were included in this study, adult patients living with HIV and had recently started ART who were followed up for at least 6 months to determine the incidence of ADRs using Naranjo’s classification scale.Results: During this study, 357 (42.3%) patients presented ADRs (40.1% of our patients (n=338) experienced at least one ADR, and 2.2% (n=19) experienced at least two ADRs). The prevalence of ADRs by organ system was: 45.9% neurological (n=164); 29.4% metabolic (blood chemistry) (n=105); 15.4% hematological (n=55). High probable rate of ADR was observed as indicated by the Naranjo score in 83.7% of the cases. Zidovudine (AZT) and stavudine (d4T) use was identified as a risk factor for either anaemia or peripheral neuropathy whereas nevirapine (NVP) and female gender were risk factors for skin reactions. Patients with advance disease had the highest rate of ADRs compared to the others.Conclusions: Based on the Naranjo probability scale, our data show that ADRs such as peripheral neuropathy and anemia are very frequent. These ADR was linked to AZT and D4T. Our findings highlight the need for active monitoring, continuous pharmacovigilance of ART and change of some ART drug in this population

Peoples’ attitude toward COVID-19 vaccine, acceptance, and social trust among African and Middle East countries

Background: To end the COVID-19 pandemic, a large part of the world must be immune to the virus by vaccination. Therefore, this study aimed to gauge intent to be vaccinated against COVID-19 among ordinary people and to identify attitudes towards vaccines and barriers for vaccine acceptance. Methods: The study population comprises 1880 people residing in different countries that answer a prepared questionnaire. The questionnaire topics are demographics, historical issues, participants’ attitudes and beliefs regarding vaccines, concerns, and vaccine hesitancy. Results: Attitudes and beliefs relating to vaccines in general, and the COVID-19 vaccine, were ascertained. Overall, 66.81% of the contributors would like to be vaccinated against COVID-19, while %33.19 did not intend to be vaccinated. Reasons for COVID-19 vaccine hesitancy included concern regarding vaccine side effects, fear of getting sick from the uptake of the vaccine, and the absence of accurate vaccine promotion news. Individuals with higher education believe that India (68.6%) produces the best vaccine (P&lt;0.001), while healthcare workers think the Chinese vaccine (44.2%) is the best (P=0.020). Individuals with higher education have not been vaccinated, not be healthcare workers, and females were the most contributors to effective of the vaccine in reducing mortality from COVID-19 disease. Conclusion: Given the degree of hesitancy against COVID-19 vaccination, a multifaceted approach to facilitate vaccine uptake that includes vaccine education, behavioral change strategies, and health promotion, is paramount

Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection

BACKGROUND: For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are 500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Transcriptome Analysis Methods: From the Serial Analysis of Gene Expression and Microarray to Sequencing new Generation Methods

Up-to-date research in biology, biotechnology, and medicine requires fast genome and transcriptome analysis technologies to investigate cellular state, physiology, and activity. Gene expression is the process of generating messenger RNA copies of a gene. The transcriptome, which contains the mRNA of the cell, reflects the cell's overall gene expression pattern. Understanding the nature and frequency of each RNA molecule in a given cell under certain circumstances is necessary to examine the transcriptome. Microarray and serial analysis of gene expression are two primary techniques researchers use in transcriptome studies. Here, microarray technology and next-generation sequencing of transcripts are states of the art. Since microarray technology is limited to RNA, quantifying transcript levels and sequence information, RNA-Seq provides nearly unlimited possibilities in modern bioanalysis. Sequencing of RNA, or RNA-Seq, is now a standard method to analyze gene expression and uncover novel RNA species. In addition, aspects of RNA biogenesis and metabolism can be interrogated with specialized techniques for cDNA library preparation. The present study will introduce and compare new high-performance methods used in examining the transcriptome. This also presents a detailed description of next-generation sequencing, describes the impact of this technology on transcriptome analysis, and explains its possibilities to explore the modern RNA world

Gut Microbiota and Human Body Interactions; Its Impact on Health: A Review

Gut microbiota (GM), as an organ of the human body, has a particular and autonomous function that is related to it. This review aims to investigate human intestinal and gut microbiota interaction and its impact on health. As a creation referable database about this dynamic and complex organ, several comprehensive projects are implemented by using culture-dependent (culturomics), culture-independent methods ( e.g., metagenomics, mathematics model), and Gnotobiological together. This study was done by searching PubMed, Scopus and Google scholar database in the gut, health microbiota, and interaction keywords. The first acquired microbiota during pregnancy or childbirth is colonized in the gut by using specific and non-specific mechanisms. Its structure and shape reach relative stability with selection pressure along with host development until adulthood and keeps its resilience against external or internal variables depending on the host's genetics and negative feedback. According to research, individuals have 2 functional group microbiotas, including the core (common between vast majorities human) and flexible (transient population) microbiome. The most important role of the GM in the human body can be summarized in three basic landscapes: metabolic, immune system, and gut-brain axis interaction. So, the loss of microbial population balance will lead to disorder and disease