Insights into perceptions, responses, and challenges experienced by women and girls' survivors of sexual violence and their communities in rural Guinea, 2020.

Introduction: Gender-based violence (GBV), particularly sexual violence, is a significant global public health issue with severe physical, psychological, and social consequences for survivors and their communities, especially among women and girls. In Guinea, limited data exist on the frequency and management of sexual violence in rural areas. This study aimed to analyze the perceptions, responses, and challenges faced by women and girls' survivors of sexual violence and their communities in two rural districts of Guinea in 2020.

Diabetes prevalence and risk factors, underestimated without oral glucose tolerance test, in rural Gombe-Matadi Adults, Democratic Republic of Congo, 2019.

An increase in the diabetes prevalence is reported worldwide. We aimed to determine the diabetes prevalence and its risk factors among adults in a rural area of the Democratic Republic of Congo. A cross-sectional study was conducted in 1531 inhabitants, selected by five stages, in the Health Zone of Gombe-Matadi.

Leishmania RNA virus-1 is similarly detected among metastatic and non-metastatic phenotypes in a prospective cohort of American Tegumentary Leishmaniasis.

American Tegumentary Leishmaniasis (ATL) is an endemic and neglected disease of South America. Here, mucosal leishmaniasis (ML) disproportionately affects up to 20% of subjects with current or previous localised cutaneous leishmaniasis (LCL). Preclinical and clinical reports have implicated the Leishmania RNA virus-1 (LRV1) as a possible determinant of progression to ML and other severe manifestations such as extensive cutaneous and mucosal disease and treatment failure and relapse.

Retention of healthcare workers 1 year after recruitment and deployment in rural settings: an experience post-Ebola in five health districts in Guinea.

Background: Guinea undertook health workforce reform in 2016 following the Ebola outbreak to overcome decades-long shortages and maldistribution of healthcare workers (HCWs). Specifically, over 5000 HCWs were recruited and deployed to rural health districts and with a signed 5-year commitment for rural medical practice. Governance structures were also established to improve the supervision of these HCWs.

Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix.

Therapeutic vaccinations aim to re-educate human immunodeficiency virus (HIV)-1-specific immune responses to achieve durable control of HIV-1 replication in virally suppressed infected individuals after antiretroviral therapy (ART) is interrupted. In a double blinded, placebo-controlled phase IIa multicenter study, we investigated the safety and immunogenicity of intranodal administration of the HIVACAT T cell Immunogen (HTI)-TriMix vaccine. It consists of naked mRNA based on cytotoxic T lymphocyte (CTL) targets of subdominant and conserved HIV-1 regions (HTI), in combination with mRNAs encoding constitutively active TLR4, the ligand for CD40 and CD70 as adjuvants (TriMix).

The impact of reimbursed user fee exemption of health centre outpatient consultations for the poor in pluralistic health systems: lessons from a quasi-experiment in two rural health districts in Cambodia.

Fees charged at the point of use are a barrier to the health services' users, especially for the poorest. Two decades ago, Cambodia introduced the so-called health equity fund (HEF) strategy, a waiver scheme which enhances access to public health services for the poor without undermining the economic situation of facilities. Evidence suggests that hospital-based HEF effectively removed financial barriers and reduced out-of-pocket expenditures.

Development of a clinical prediction rule for tuberculous meningitis in adults in Lima, Peru.

Objectives: Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic.

Methods: We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru.

The need for European OneHealth/EcoHealth networks.

Elaborating from the European One Health/Ecohealth (OH/EH) workshop that took place in fall 2016 and aimed to bring together different communities and explore collaborative potential, the creation of European networks focusing on the development of important OH/EH perspectives was a direct output from discussions at the end of some sessions, in particular: - A network on transdisciplinary One Health education. - A network integrating inputs from social sciences in One Health/EcoHealth actions and networks. - A network aiming at translating research findings on the Environment-Microbiome-Health axis into policy making, with a view to make healthy ecosystems a cost-effective disease prevention healthcare strategy.

Performance of clinical prediction rules for diagnosis of pleural tuberculosis in a high-incidence setting.

Objectives: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru.

Building a middle-range theory of free public healthcare seeking in sub-Saharan Africa: a realist review.

Realist reviews are a new form of knowledge synthesis aimed at providing middle-range theories (MRTs) that specify how interventions work, for which populations, and under what circumstances. This approach opens the 'black box' of an intervention by showing how it triggers mechanisms in specific contexts to produce outcomes. We conducted a realist review of health user fee exemption policies (UFEPs) in sub-Saharan Africa (SSA).

Evolutionary Dynamics and Complicated Genetic Transmission Network Patterns of HIV-1 CRF01_AE among MSM in Shanghai, China.

To explore the evolutionary dynamics and molecular transmission patterns of HIV-1 CRF01_AE in depth among men who have sex with men (MSM) in Shanghai, we constructed phylogenetic tree and genetic transmission networks based on 1, 152 pol sequences from MSM, 282 from other risk groups and 795 references. Phylogenetic analyses identified two distinct major CRF01_AE lineages and a Shanghai-based sub-lineage. The estimated tMRCAs for lineage 1 and 2 were 1996.

[Detection of Leishmania spp. based on the gene encoding HSP20].

Objectives: Explore a new target for molecular diagnosis of Leishmania.

Materials And Methods: We evaluated the utility of the gene that encodes the heat shock protein 20-kDa (Hsp20) for detecting Leishmania by polymerase chain reaction (PCR). PCR was normalized and analytical parameters were determined, as well as the validity and diagnostic accuracy, and concordance with the PCR - 18S.

A phase III trial to evaluate the efficacy, fabric integrity and community acceptance of Netprotect using a recommended long-lasting insecticidal net as positive control.

Background: The evaluation of new long-lasting insecticidal bed nets (LLINs) is coordinated by the WHO Pesticide Evaluation Scheme (WHOPES). In 2007, Netprotect® was granted WHOPES interim recommendation after Phase I and II evaluations. Present study evaluates Netprotect in a Phase III trial in rural Cambodia.

Changes in immunological profile as a function of urbanization and lifestyle.

Differences in lifestyle and break with natural environment appear to be associated with changes in the immune system resulting in various adverse health effects. Although genetics can have a major impact on the immune system and disease susceptibility, the contribution of environmental factors is thought to be substantial. Here, we investigated the immunological profile of healthy volunteers living in a rural and an urban area of a developing African country (Senegal), and in a European country (the Netherlands).

The validity of cerebrospinal fluid parameters for the diagnosis of tuberculous meningitis.

Objectives: To assess the diagnostic validity of laboratory cerebrospinal fluid (CSF) parameters for discriminating between tuberculous meningitis (TBM) and other causes of meningeal syndrome in high tuberculosis incidence settings.

Methods: From November 2009 to November 2011, we included patients with a clinical suspicion of meningitis attending two hospitals in Lima, Peru. Using a composite reference standard, we classified them as definite TBM, probable TBM, and non-TBM cases.

Can immunotherapy be useful as a "functional cure" for infection with Human Immunodeficiency Virus-1?

Immunotherapy aims to assist the natural immune system in achieving control over viral infection. Various immunotherapy formats have been evaluated in either therapy-naive or therapy-experienced HIV-infected patients over the last 20 years. These formats included non-antigen specific strategies such as cytokines that stimulate immunity or suppress the viral replication, as well as antibodies that block negative regulatory pathways.

Internalization of mRNA lipoplexes by dendritic cells.

Lipoplexes, composed of Lipofectamine and mRNA encoding HIV Gag protein, were shown to be internalized by dendritic cells (DCs) and promote antigen presentation to stimulate HIV-specific T cell responses. Using confocal microscopy, we showed that one-third of fluorescently labeled mRNA containing lipoplexes are colocalized with late endosomes. We further investigated the effect of inhibitors, blocking phagocytosis, macropinocytosis, and clathrin- and caveolae-mediated endocytosis, on both the internalization of the lipoplexes by DCs and the transfection efficiency.

Lipoplexes carrying mRNA encoding Gag protein modulate dendritic cells to stimulate HIV-specific immune responses.

Aim: Cationic lipids (Lipofectamine™ [Invitrogen, Merelbeke, Belgium] and 1,2-dioleoyl-3-trimethylammonium-propane/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and polymers (jetPEI™ and in vivo-jetPEI™ [Polyplus-transfection, Illkirch, France]) were evaluated for their potential to deliver mRNA to monocyte-derived dendritic cells.

Materials & Methods: Lipoplexes and polyplexes, containing mRNA encoding GFP or Gag protein, were incubated with human monocyte-derived dendritic cells and transfection efficiencies were assessed by flow cytometry.

Results: Lipofectamine was by far the most efficient in mRNA delivery, therefore it was used in further experiments.

MiniCD4 protein resistance mutations affect binding to the HIV-1 gp120 CD4 binding site and decrease entry efficiency.

Background: Binding of the viral envelope protein (Env), and particularly of its gp120 subunit, to the cellular CD4 receptor is the first essential step of the HIV-1 entry process. The CD4 binding site (CD4bs) of gp120, and especially a recessed cavity occupied by the CD4 Phe43 residue, are known to be highly conserved among the different circulating subtypes and therefore constitute particularly interesting targets for vaccine and drug design. The miniCD4 proteins are a promising class of CD4bs inhibitors.

Polyelectrolyte capsules-containing HIV-1 p24 and poly I:C modulate dendritic cells to stimulate HIV-1-specific immune responses.

Polyelectrolyte microcapsules (MCs) are potent protein delivery vehicles which can be tailored with ligands to stimulate maturation of dendritic cells (DCs). We investigated the immune stimulatory capacity of monocyte-derived DC (Mo-DC) loaded with these MCs, containing p24 antigen from human immunodeficiency virus type 1 (HIV-1) alone [p24-containing MC (MCp24)] or with the Toll-like receptor ligand 3 (TLR3) ligand poly I:C (MCp24pIC) as a maturation factor. MO-DC, loaded with MCp24pIC, upregulated CCR7, CD80, CD83, and CD86 and produced high amounts of interleukin-12 (IL-12) cytokine, to a similar extent as MCp24 in the presence of an optimized cytokine cocktail.

Efficient in vitro expansion of human immunodeficiency virus (HIV)-specific T-cell responses by gag mRNA-electroporated dendritic cells from treated and untreated HIV type 1-infected individuals.

Developing an immunotherapy to keep human immunodeficiency virus type 1 (HIV-1) replication suppressed while discontinuing highly active antiretroviral therapy (HAART) is an important challenge. In the present work, we evaluated in vitro whether dendritic cells (DC) electroporated with gag mRNA can induce HIV-specific responses in T cells from chronically infected subjects. Monocyte-derived DC, from therapy-naïve and HAART-treated HIV-1-seropositive subjects, that were electroporated with consensus codon-optimized HxB2 gag mRNA efficiently expanded T cells, secreting gamma interferon (IFN-gamma) and interleukin 2 (IL-2), as well as other cytokines and perforin, upon restimulation with a pool of overlapping Gag peptides.

Efficient stimulation of HIV-1-specific T cells using dendritic cells electroporated with mRNA encoding autologous HIV-1 Gag and Env proteins.

Infection with human immunodeficiency virus type 1 (HIV-1) is characterized by dysfunction of HIV-1-specific T cells. To control the virus, antigen-loaded dendritic cells (DCs) might be useful to boost and broaden HIV-specific T-cell responses. In the present study, monocyte-derived DCs from nontreated HIV-1-seropositive patients were electroporated with codon-optimized ("humanized") mRNA encoding consensus HxB-2 (hHXB-2) Gag protein.