Determinants of the generic's prescription among general practitioners in Casablanca, Morocco: A cross-sectional study.

Background: Prescription of generic drugs is a public health policy challenge with a very high economic potential worldwide, particularly in the Kingdom of Morocco. Generic drug prescriptions seem to be an effective measure to decrease the cost of drugs and improve affordability. The purpose of this study was to determine the factors related to the prescription of generic drugs among general practitioners.

Marked heterogeneity in malaria infection rate in a Malian longitudinal cohort.

Variation in malaria infection risk, a product of disease exposure and immunity, is poorly understood. We genotypically profiled over 13,000 blood samples from a six-year longitudinal cohort in Mali to characterize malaria infection dynamics with detail. We generated Plasmodium falciparum amplicon sequencing data from 464 participants (aged 3 months - 25 years) across the six-month 2011 transmission season and profiled a subset of 120 participants across the subsequent five annual transmission seasons.

Plasmodium falciparum expresses fewer var genes at lower levels during asymptomatic dry season infections than clinical malaria cases.

In seasonal transmission areas, clinical malaria occurs during the wet season when mosquitoes are present, while in the dry season, malaria transmission is interrupted and clinical cases are rare. In Mali, Plasmodium falciparum can persist in low parasitaemic asymptomatic individuals through the six-month dry season and shows circulation of more developed parasite stages compared to clinical malaria cases, indicative of reduced cytoadhesion of infected erythrocytes. How prolonged circulation of infected erythrocytes is achieved remains unknown.

Anti-sporozoite monoclonal antibody for malaria prevention: secondary efficacy outcome of a phase 2 randomized trial.

CIS43LS is a long-acting monoclonal antibody specific for the Plasmodium falciparum circumsporozoite protein expressed on sporozoites. We previously reported that CIS43LS is protective against P. falciparum infection as detected by thick blood smear (TBS; primary endpoint) in a phase 2 double-blind randomized trial involving 330 healthy Malian adults receiving placebo or a single intravenous infusion of 10 mg kg or 40 mg kg of CIS43LS (1:1:1).

Protocol for affinity enrichment of polyclonal autoantibodies from human plasma.

Autoantibodies (AAbs) contribute to various immune-mediated diseases and are valuable biomarkers for diagnosis, classification, and disease activity. Here, we present a protocol for the affinity enrichment of AAbs from human plasma samples. We describe steps to generate a human cell line lysate, which is immobilized on Sepharose beads for affinity enrichment of AAbs.

A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade.

Plasmodium falciparum apical membrane antigen 1 (AMA1) binds a loop in rhoptry neck protein 2 (RON2L) during red cell invasion and is a target for vaccines and therapeutic antibodies against malaria. Here, we report a panel of AMA1-specific naturally acquired human monoclonal antibodies (hmAbs) derived from individuals living in malaria-endemic regions. Two neutralizing hmAbs engage AMA1 independent of the RON2L-binding site.

Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

The gut microbiome is associated with susceptibility to febrile malaria in Malian children.

Malaria is a major public health problem, but many of the factors underlying the pathogenesis of this disease are not well understood, including protection from the development of febrile symptoms, which is observed in individuals residing in areas with moderate-to-high transmission by early adolescence. Here, we demonstrate that susceptibility to febrile malaria following Plasmodium falciparum infection is associated with the composition of the gut microbiome prior to the malaria season in 10-year-old Malian children, but not in younger children. Gnotobiotic mice colonized with the fecal samples of malaria-susceptible children were shown to have a significantly higher parasite burden following Plasmodium infection compared to gnotobiotic mice colonized with the fecal samples of malaria-resistant children.

Infection length and host environment influence on Plasmodium falciparum dry season reservoir.

Persistence of malaria parasites in asymptomatic hosts is crucial in areas of seasonally-interrupted transmission, where P. falciparum bridges wet seasons months apart. During the dry season, infected erythrocytes exhibit extended circulation with reduced cytoadherence, increasing the risk of splenic clearance of infected cells and hindering parasitaemia increase.

Autoantibodies inhibit Plasmodium falciparum growth and are associated with protection from clinical malaria.

Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (n = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season.

Prevalence and associated factors of psychiatric comorbidities in epilepsy in the Casablanca-Settat region of Morocco: A cross-sectional study.

Objective: To determine the estimated prevalence of anxiety, depression, and anxiety-depression syndrome (ADS) and to identify the associated factors in Moroccan people with epilepsy (PWE).

Method: A cross-sectional study was conducted among adult PWE (June 2021-December 2022) in the Casablanca-Settat region. PWE were interviewed by completing a questionnaire collecting sociodemographic and clinical data.

Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

Background: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from infection in a region where this organism is endemic is unclear.

Methods: We conducted a phase 2 trial in Mali to assess the safety and efficacy of subcutaneous administration of L9LS in children 6 to 10 years of age over a 6-month malaria season.

Susceptibility to febrile malaria is associated with an inflammatory gut microbiome.

Malaria is a major public health problem, but many of the factors underlying the pathogenesis of this disease are not well understood. Here, we demonstrate in Malian children that susceptibility to febrile malaria following infection with is associated with the composition of the gut microbiome prior to the malaria season. Gnotobiotic mice colonized with the fecal samples of malaria-susceptible children had a significantly higher parasite burden following infection compared to gnotobiotic mice colonized with the fecal samples of malaria-resistant children.

Normal Clinical Laboratory Ranges by Age and Sex, and Impact on Study Screening Outcomes in Rural Mali.

The interpretation of a laboratory test result requires an appropriate reference range established in healthy subjects, and normal ranges may vary by factors such as geographic region, sex, and age. We examined hematological and clinical chemistry parameters in healthy residents at two rural vaccine trial sites: Bancoumana and Doneguebougou in Mali, West Africa. During screening of clinical studies in 2018 and 2019, peripheral blood samples from 1,192 apparently healthy individuals age 6 months to 82 years were analyzed at a laboratory accredited by the College of American Pathologists for a complete blood count, and creatinine and/or alanine aminotransferase levels.

Knowledge, attitudes and practices towards epilepsy in morocco: A cross-sectional study.

Background: This study aims to assess knowledge, practices and attitudes of the general Moroccan population towards epilepsy and to highlight predictive factors.

Method: A cross-sectional study was conducted in the Casablanca-Settat Moroccan region. A questionnaire was used to collect sociodemographic data and item answers from 400 people with epilepsy (PWE) and without epilepsy caregivers on dependent variables: knowledge, attitudes, and practices towards epilepsy.

NK cell-induced damage to P.falciparum-infected erythrocytes requires ligand-specific recognition and releases parasitophorous vacuoles that are phagocytosed by monocytes in the presence of immune IgG.

Natural killer (NK) cells lyse virus-infected cells and transformed cells through polarized delivery of lytic effector molecules into target cells. We have shown that NK cells lyse Plasmodium falciparum-infected red blood cells (iRBC) via antibody-dependent cellular cytotoxicity (ADCC). A high frequency of adaptive NK cells, with elevated intrinsic ADCC activity, in people chronically exposed to malaria transmission is associated with reduced parasitemia and resistance to disease.

Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota.

There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease.

Interfacial engineering to modulate surface dipoles, work functions and dielectric confinement of halide perovskites.

The interfacial properties between perovskite photoactive and charge transport layers are critical for device performance and operational stability. Therefore, an accurate theoretical description of the link between surface dipoles and work functions is of scientific and practical interest. We show that for a CsPbBr perovskite surface functionalized by dipolar ligand molecules, the interplay between surface dipoles, charge transfers, and local strain effects leads to upward or downward shifts of the valence level.

Accumulation of Neutrophil Phagocytic Antibody Features Tracks With Naturally Acquired Immunity Against Malaria in Children.

Background: Studies have demonstrated the protective role of antibodies against malaria. Young children are known to be particularly vulnerable to malaria, pointing to the evolution of naturally acquired clinical immunity over time. However, whether changes in antibody functionality track with the acquisition of naturally acquired malaria immunity remains incompletely understood.

Neither the African-Centric S47 Nor P72 Variant of TP53 Is Associated With Reduced Risk of Febrile Malaria in a Malian Cohort Study.

Background: TP53 has been shown to play a role in inflammatory processes, including malaria. We previously found that p53 attenuates parasite-induced inflammation and predicts clinical protection to Plasmodium falciparum infection in Malian children. Here, we investigated whether p53 codon 47 and 72 polymorphisms are associated with differential risk of P.

Evidence for exposure dependent carriage of malaria parasites across the dry season: modelling analysis of longitudinal data.

Background: In malaria endemic regions, transmission of Plasmodium falciparum parasites is often seasonal with very low transmission during the dry season and high transmission in the wet season. Parasites survive the dry season within some individuals who experience prolonged carriage of parasites and are thought to 'seed' infection in the next transmission season.

Methods: Dry season carriers and their role in the subsequent transmission season are characterized using a combination of mathematical simulations and data analysis of previously described data from a longitudinal study in Mali of individuals aged 3 months-12 years (n = 579).