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. However, what determines parasite persistence for long periods of time remains unknown. Here, we investigated whether seasonality affects plasma composition so that P. falciparum can detect and adjust to changing serological cues; or if alternatively, parasite infection length dictates clinical presentation and persistency. Data from Malian children exposed to alternating ~6-month wet and dry seasons show that plasma composition is unrelated to time of year in non-infected children, and that carrying P. falciparum only minimally affects plasma constitution in asymptomatic hosts. Parasites persisting in the blood of asymptomatic children from the dry into the ensuing wet season rarely if ever appeared to cause malaria in their hosts as seasons changed. In vitro culture in the presence of plasma collected in the dry or the wet seasons did not affect parasite development, replication or host-cell remodelling. The absence of a parasite-encoded sensing mechanism was further supported by the observation of similar features in P. falciparum persisting asymptomatically in the dry season and parasites in age- and sex-matched asymptomatic children in the wet season. Conversely, we show that P. falciparum clones transmitted early in the wet season had lower chance of surviving until the end of the following dry season, contrasting with a higher likelihood of survival of clones transmitted towards the end of the wet season, allowing for the re-initiation of transmission. We propose that the decreased virulence observed in persisting parasites during the dry season is not due to the parasites sensing ability, nor is it linked to a decreased capacity for parasite replication but rather a consequence decreased cytoadhesion associated with infection length.

Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.

[Dermatoses of elderly inpatients in Casablanca: epidemiology and factors associated with length of stay]. / Dermatoses du sujet âgé en hospitalisation à Casablanca : épidémiologie et facteurs associés à la durée de séjour.

Geriatric in-patient dermatoses are diverse. Few data in Morocco describe the epidemiological profile and factors associated with average length of stay (LOS). Our aim was to identify these dermatoses and determine the factors associated with LOS.

Drug-resistant epilepsy in Morocco: description, prevalence and predictive factors in Casablanca-Settat region.

Drug-resistant epilepsy (DRE) affects about one-third of people with epilepsy (PWE). Our study aims to estimate the DRE prevalence and its predictive factors in Morocco. A cross-sectional study was conducted over 18 months. PWE with clinical diagnosis of epilepsy, and with an antiseizure treatment duration >12 months were examined in the neurology, neurosurgery, psychiatry, and pediatrics departments, of different sampled clinical sectors for the Casablanca-Settat region. Sociodemographic and clinical data were collected using a questionnaire during consultations. Antiseizure multi-therapy, a seizure freedom duration <12 months, compliance, and adequate posology were the determining factors for classifying DRE. Data were analyzed using Statistical Package for Social Sciences (SPSS) software, version 21.0. Statistical significance was set at p < 0.05 and logistic regression was performed to determine the predictive factors. In our sample of 446 PWE, the median age is 25 years (IQR: 11.75-44.00). The DRE estimated prevalence was 29.4 %. Pseudo-resistant epilepsy (PRE) was 18.0 %. Multivariate logistic regression analysis reports that single marital status (ORa = 1.94; CI95%: 1.02-3.71), comorbidities and concomitant affections (ORa = 2.14; CI95%: 1.27-3.59), structural etiology (ORa = 1.96; CI95%: 1.16-3.30), pre-ictal aura (ORa = 1.90; CI95%: 1.09-3.29), inter-ictal EEG abnormalities (ORa = 2.45; CI95%: 1.24-4.84) and allopathic treatment use (ORa = 2.10; CI95%: 1.30-3.39) are the predictive factors for DRE. We report an alarming DRE prevalence. Associated factors found may contribute to the prognosis and early management. PWE awareness, facilitating healthcare access and the development of epilepsy surgery are the key points to limit DRE in Morocco and prevent its various complications, especially for the pediatric population.

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. Baseline AAb seroprevalence increased with age and asymptomatic Plasmodium falciparum infection. We found that AAbs purified from the plasma of protected individuals inhibit the growth of blood-stage parasites and bind P. falciparum proteins that mediate parasite invasion. Protected individuals had higher plasma immunoglobulin G (IgG) reactivity against 33 of the 123 antigens assessed in an autoantigen microarray. This study provides evidence in support of the hypothesis that a propensity toward autoimmunity offers a survival advantage against malaria.

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. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Out of 21 points, a score ≥8 is in favor of considerable anxiety/depression symptoms and a sum of the two scores ≥15 indicates the presence of ADS. Data were analyzed using Statistical Package for Social Sciences (SPSS) 21.0. p-values ≤0.05 were considered statistically significant and logistic regression was performed to determine the associated factors. RESULTS: Among 294 PWE, the median age was 39 years (interquartile range [IQR]: 25.75-54.00). The median anxiety, depression, and ADS scores were 8 (IQR: 5.00-10.00), 7 (IQR: 4.00-10.00), and 15 (IQR: 10.00-20.00), respectively. Anxiety, depression, and ADS were revealed in 51.4%, 44.9%, and 51.0% of PWE, respectively. Depression was the only predictor for anxiety (aOR = 24.20; 95%CI: 12.45-47.01). Antiseizure polytherapy (aOR = 3.35; 95%CI: 1.72-6.54) and anxiety (aOR = 24.04; 95%CI: 12.12-47.67) were the factors associated with depression. The risk of ADS was increased by female gender (aOR = 2.83; 95%CI: 1.68-4.78), antiseizure polytherapy (aOR = 2.75; 95%CI: 1.62-4.65), structural epilepsy (aOR = 1.73; 95%CI: 1.01-2.94), and the presence of concomitant conditions with epilepsy (aOR = 1.96; 95%CI: 1.16-3.31). SIGNIFICANCE: Our study reports high psychiatric comorbidity prevalence in epilepsy, which supports the bidirectional link hypothesis. Associated factors found are important in the prognosis and prevention. PLAIN LANGUAGE SUMMARY: The neural mechanisms underlying epilepsy tend to expose PWE to psychiatric disorders. Our study aims to quantify the rate of psychiatric comorbidities and their predictive factors in Moroccan PWE. The estimated prevalences of significant symptoms of anxiety, depression, and ADS were 51.4%, 44.9%, and 51.0%, respectively. Depression was the predictor of anxiety. Antiseizure polymedication and anxiety were the associated factors with depression. The risk of SAD was increased by female gender, antiseizure polymedication, structural epilepsy, and concomitant diseases with epilepsy. Our results are important for considering the psychiatric aspect of PWE and improving their care and quality of life.

Antiseizure medication adherence and epilepsy surgery attitude in people with epilepsy in Morocco: A cross-sectional study.

We determine the proportion of non-Antiseizure Medication Adherence (non-AMA) and refusal attitude towards Epilepsy Surgery (ES) and their associated factors in Moroccan People With Epilepsy (PWE). A cross-sectional study was conducted (December 2021-December 2022) among adult Moroccan PWE. PWE were interviewed for their reactions to AMA and the ES attitude. Their medical files were processed to complete their sociodemographic and clinical data. Data were analyzed by the Statistical Package for Social Sciences (SPSS) software 21.0. A Chi-square test was performed to compare variables and multivariate logistic regression was used to highlight associations. Statistical tests were considered significant at a p-value ≤ 0.05 for a Confidence Interval (CI) of 95 %. The median age of our sample (n = 294) was 38 years (IQR: 25.00-55.00). Non-AMA was noted in 24.5 % with indifference as the main reason (55.6 %). ES refusal was found in 33.3 %, attributed mostly to apprehension (61.2 %). In the multivariate analysis, male sex (aOR = 1.94; 95 %CI: 1.03-3.64) and the existence of a family history of epilepsy (aOR = 1.96; 95 %CI: 1.02-3.75) were the factors associated with the non-AMA, whereas the use of allopathic treatments (aOR = 2.32; 95 %CI: 1.20-4.51), exclusively focal or generalized (not combined) seizures (aOR = 2.66; 95 %CI: 1.36-5.21) and the combination of a generic with the originator ASM (aOR = 2.64; 95 %CI: 1.12-6.18) were the predictive factors with the ES refusal attitude. The proportions found of non-AMA and ES refusal were relatively low compared to other studies, which may indicate the effort that medical staff have devoted recently to raising awareness of the importance of PWE's therapeutic involvement.

Subcutaneous Administration of a Monoclonal Antibody to Prevent Malaria.

BACKGROUND: Subcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether a monoclonal antibody administered subcutaneously can protect children from P. falciparum 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. In part A of the trial, safety was assessed at three dose levels in adults, followed by assessment at two dose levels in children. In part B of the trial, children were randomly assigned, in a 1:1:1 ratio, to receive 150 mg of L9LS, 300 mg of L9LS, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection, as detected on blood smear performed at least every 2 weeks for 24 weeks. A secondary efficacy end point was the first episode of clinical malaria, as assessed in a time-to-event analysis. RESULTS: No safety concerns were identified in the dose-escalation part of the trial (part A). In part B, 225 children underwent randomization, with 75 children assigned to each group. No safety concerns were identified in part B. P. falciparum infection occurred in 36 participants (48%) in the 150-mg group, in 30 (40%) in the 300-mg group, and in 61 (81%) in the placebo group. The efficacy of L9LS against P. falciparum infection, as compared with placebo, was 66% (adjusted confidence interval [95% CI], 45 to 79) with the 150-mg dose and 70% (adjusted 95% CI, 50 to 82) with the 300-mg dose (P<0.001 for both comparisons). Efficacy against clinical malaria was 67% (adjusted 95% CI, 39 to 82) with the 150-mg dose and 77% (adjusted 95% CI, 55 to 89) with the 300-mg dose (P<0.001 for both comparisons). CONCLUSIONS: Subcutaneous administration of L9LS to children was protective against P. falciparum infection and clinical malaria over a period of 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT05304611.).

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 Plasmodium falciparum 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 Plasmodium infection compared to gnotobiotic mice colonized with the fecal samples of malaria-resistant children. The fecal microbiome of the susceptible children was enriched for bacteria associated with inflammation, mucin degradation, gut permeability and inflammatory bowel disorders (e.g., Ruminococcus gauvreauii, Ruminococcus torques, Dorea formicigenerans, Dorea longicatena, Lachnoclostridium phocaeense and Lachnoclostridium sp. YL32). However, the susceptible children also had a greater abundance of bacteria known to produce anti-inflammatory short-chain fatty acids and those associated with favorable prognosis and remission following dysbiotic intestinal events (e.g., Anaerobutyricum hallii, Blautia producta and Sellimonas intestinalis). Metabolomics analysis of the human fecal samples corroborated the existence of inflammatory and recovery-associated features within the gut microbiome of the susceptible children. There was an enrichment of nitric oxide-derived DNA adducts (deoxyinosine and deoxyuridine) and long-chain fatty acids, the absorption of which has been shown to be inhibited by inflamed intestinal epithelial cells, and a decrease in the abundance of mucus phospholipids. Nevertheless, there were also increased levels of pseudouridine and hypoxanthine, which have been shown to be regulated in response to cellular stress and to promote recovery following injury or hypoxia. Overall, these results indicate that the gut microbiome may contribute malaria pathogenesis and suggest that therapies targeting intestinal inflammation could decrease malaria susceptibility.

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. Based on manufacturers' reference range values, which are currently used in Malian clinical laboratories, abnormal values were common in this healthy population. In fact, 30.4% of adult participants had abnormal neutrophil levels and 19.8% had abnormal hemoglobin levels. Differences by sex were observed in those who were older, but not in those younger than 10 years, for several parameters, including hemoglobin, platelet, and absolute neutrophil counts in hematology, and creatinine in biochemistry. The site-specific reference intervals we report can be used in malaria vaccine clinical trials and other interventional studies, as well as in routine clinical care, to identify abnormalities in hematological and biochemical parameters among healthy Malian trial participants.

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. Bivariate and logistic regression analyses were performed using IBM SPSS Statistics 21.0. Statistical significance was set when P value < 0.05. RESULTS: The rates of poor knowledge, practices, and attitudes toward epilepsy were 11.5 %, 41 %, and 66.6 %, respectively. In the multivariate analysis, the risk of having poor knowledge about epilepsy was favored by lack of education (ORa = 4.31;CI95%:1.83-10.13;p = 0.001) and the absence of familiarity with epilepsy (ORa = 4.05;CI95%:1.92-8.54;p < 0.001). The risk of preferring allopathic practices to treat epilepsy was associated with lack of education (ORa = 2.21;CI95%:1.01-4.82;p = 0.046), residence in a city outside Casablanca (ORa = 2.33;CI95%:1.06-5.15;p = 0.035), age over 59 years (ORa = 2.50;CI95%:1.26-4.95; p = 0.008), residence in a rural areas (ORa = 4.41;CI95%:2.61-7.47;p < 0.001) and absence of familiarity with epilepsy (ORa = 4.08;CI95%:2.33-7.15;p < 0.001). Predictors of stigma towards epilepsy were female sex (ORa = 3.05;CI95%:2.04-4.56;p < 0.001) and the tendency to abandon anti-seizure medication for allopathic alternatives (ORa = 3.98;CI95%:2.21-7.17;p < 0.001), whereas advanced age was a protective factor (ORa = 0.57;CI95%:0.36-0.89;p = 0.014[39-59 years vs 18-29 years];ORa = 0.44;CI95%:0.23-0.82;p = 0.011[>59 years vs 18-29 years]). CONCLUSIONS: The rate of poor attitudes and treatment-seeking behavior was high. This socio-cultural context certainly impacts the quality of life and care of Moroccan PWE. These results should be considered to raise awareness in the Moroccan population.

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. How NK cells bind to iRBC and the outcome of iRBC lysis by NK cells has not been investigated. We applied gene ablation in inducible erythrocyte precursors and antibody-blocking experiments with iRBC to demonstrate a central role of CD58 and ICAM-4 as ligands for adhesion by NK cells via CD2 and integrin αMß2, respectively. Adhesion was dependent on opsonization of iRBC by IgG. Live imaging and quantitative flow cytometry of NK-mediated ADCC toward iRBC revealed that damage to the iRBC plasma membrane preceded damage to P. falciparum within parasitophorous vacuoles (PV). PV were identified and tracked with a P.falciparum strain that expresses the PV membrane-associated protein EXP2 tagged with GFP. After NK-mediated ADCC, PV were either found inside iRBC ghosts or released intact and devoid of RBC plasma membrane. Electron microscopy images of ADCC cultures revealed tight NK-iRBC synapses and free vesicles similar in size to GFP+ PV isolated from iRBC lysates by cell sorting. The titer of IgG in plasma of malaria-exposed individuals that bound PV was two orders of magnitude higher than IgG that bound iRBC. This immune IgG stimulated efficient phagocytosis of PV by primary monocytes. The selective NK-mediated damage to iRBC, resulting in release of PV, and subsequent phagocytosis of PV by monocytes may combine for efficient killing and removal of intra-erythrocytic P.falciparum parasite. This mechanism may mitigate the inflammation and malaria symptoms during blood-stage P. falciparum infection.

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

IMPORTANCE: 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. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children.

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 CsPbBr3 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. We further demonstrate that the contribution of individual molecular entities to the surface dipoles and electric susceptibilities are essentially additive. Finally, we compare our results to those predicted from conventional classical approaches based on a capacitor model that links the induced vacuum level shift and the molecular dipole moment. Our findings identify recipes to fine-tune materials work functions that provide valuable insights into the interfacial engineering of this family of semiconductors.

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. METHODS: Using systems serology, we characterized sporozoite- and merozoite-specific antibody profiles of uninfected Malian children before the malaria season who differed in their ability to control parasitemia and fever following Plasmodium falciparum (Pf) infection. We then assessed the contributions of individual traits to overall clinical outcomes, focusing on the immunodominant sporozoite CSP and merozoite AMA1 and MSP1 antigens. RESULTS: Humoral immunity evolved with age, with an expansion of both magnitude and functional quality, particularly within blood-stage phagocytic antibody activity. Moreover, concerning clinical outcomes postinfection, protected children had higher antibody-dependent neutrophil activity along with higher levels of MSP1-specific IgG3 and IgA and CSP-specific IgG3 and IgG4 prior to the malaria season. CONCLUSIONS: These data point to the natural evolution of functional humoral immunity to Pf with age and highlight particular antibody Fc-effector profiles associated with the control of malaria in children, providing clues for the design of next-generation vaccines or therapeutics.

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. falciparum infection and uncomplicated malaria in a prospective cohort study of malaria immunity. METHODS: p53 codon 47 and 72 polymorphisms were determined by sequencing TP53 exon 4 in 631 Malian children and adults enrolled in the Kalifabougou cohort study. The effects of these polymorphisms on the prospective risk of febrile malaria, incident parasitemia, and time to fever after incident parasitemia over 6 months of intense malaria transmission were assessed using Cox proportional hazards models. RESULTS: Confounders of malaria risk, including age and hemoglobin S or C, were similar between individuals with or without p53 S47 and R72 polymorphisms. Relative to their respective common variants, neither S47 nor R72 was associated with differences in prospective risk of febrile malaria, incident parasitemia, or febrile malaria after parasitemia. CONCLUSIONS: These findings indicate that p53 codon 47 and 72 polymorphisms are not associated with protection against incident P. falciparum parasitemia or uncomplicated febrile malaria.

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). RESULTS: Simulating the life-history of individuals experiencing repeated exposure to infection predicts that dry season carriage is more likely in the oldest, most exposed and most immune individuals. This hypothesis is supported by the data from Mali, which shows that carriers are significantly older, experience a higher biting rate at the beginning of the transmission season and develop clinical malaria later than non-carriers. Further, since the most exposed individuals in a community are most likely to be dry season carriers, this is predicted to enable a more than twofold faster spread of parasites into the mosquito population at the start of the subsequent wet season. CONCLUSIONS: Carriage of malaria parasites over the months-long dry season in Mali is most likely in the older, more exposed and more immune children. These children may act as super-spreaders facilitating the fast spread of parasites at the beginning of the next transmission season.

The estimated burden of fungal diseases in Mali.

Mali is a developing country facing several health challenges with a high rate of tuberculosis (TB) and a moderate HIV infection burden. Little is known or done about fungal diseases, yet they represent a significant public health problem in certain populations. The aim of this study was to estimate the national burden of fungal disease, and summarize data, diagnostic and treatment gaps. We used national demographics and PubMed searches to retrieve articles on published data on these infections and at-risk populations (pulmonary TB, HIV/AIDS patients, patients receiving critical care etc.) in Mali. The estimated Malian population was 21,251,000 in 2020 (UN), of which 45% were children <14 years. Among HIV patients, we estimate an annual incidence of 611 cryptococcosis, 1393 Pneumocystis pneumonia, 180 histoplasmosis and >5,700 esophageal candidiasis and some microsporidiosis cases. Our prevalence estimates for tinea capitis are 2.3 million, for recurrent vulvovaginal candidiasis 272,460, ∼60,000 fungal asthma and 7,290 cases of chronic pulmonary aspergillosis (often mistaken for TB). Less common acute fungal infections are probably invasive aspergillosis (n=1230), fungal keratitis (n=2820), candidaemia (>1,060) and mucormycosis (n=43). Histoplasmin was found in 6% in general population. A few cases of mycetoma are described in Mali. Many WHO Essential medicines and Diagnostics are not available in Mali. This shows a marked disparity in documented and estimated cases of fungal diseases in Mali. These infections are underestimated due to the lack of accurate diagnosis tools and lack of support for fungal diseases diagnosis and management.

Safety and Efficacy of a Monoclonal Antibody against Malaria in Mali.

BACKGROUND: CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in a phase 1 clinical trial. Whether a monoclonal antibody can prevent P. falciparum infection in a region in which the infection is endemic is unknown. METHODS: We conducted a phase 2 trial to assess the safety and efficacy of a single intravenous infusion of CIS43LS against P. falciparum infection in healthy adults in Mali over a 6-month malaria season. In Part A, safety was assessed at three escalating dose levels. In Part B, participants were randomly assigned (in a 1:1:1 ratio) to receive 10 mg of CIS43LS per kilogram of body weight, 40 mg of CIS43LS per kilogram, or placebo. The primary efficacy end point, assessed in a time-to-event analysis, was the first P. falciparum infection detected on blood-smear examination, which was performed at least every 2 weeks for 24 weeks. At enrollment, all the participants received artemether-lumefantrine to clear possible P. falciparum infection. RESULTS: In Part B, 330 adults underwent randomization; 110 were assigned to each trial group. The risk of moderate headache was 3.3 times as high with 40 mg of CIS43LS per kilogram as with placebo. P. falciparum infections were detected on blood-smear examination in 39 participants (35.5%) who received 10 mg of CIS43LS per kilogram, 20 (18.2%) who received 40 mg of CIS43LS per kilogram, and 86 (78.2%) who received placebo. At 6 months, the efficacy of 40 mg of CIS43LS per kilogram as compared with placebo was 88.2% (adjusted 95% confidence interval [CI], 79.3 to 93.3; P<0.001), and the efficacy of 10 mg of CIS43LS per kilogram as compared with placebo was 75.0% (adjusted 95% CI, 61.0 to 84.0; P<0.001). CONCLUSIONS: CIS43LS was protective against P. falciparum infection over a 6-month malaria season in Mali without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04329104.).

Cystic lymphangioma of the upper limb: Clinical case and literature review.

We report an observation of a macro- and microcystic lymphatic malformation located in the right upper limb. This was a 5-year-old girl with no previous pathological history, followed since the age of 11 months for a congenital subcutaneous, painless and soft swelling of the right upper limb. Ultrasound of the soft tissue and magnetic resonance imaging (MRI) allowed the diagnosis of macro- and microcystic lymphatic malformation of the right upper limb. There is little epidemiological data on cystic lymphatic malformations (CLM). Superficial MLKs are more numerous than deep MLKs; of the superficial MLKs, nearly 75% are located in the head and neck, with an estimated incidence of 1.2 to 2.8 per 1000 births, and in the axillary hollows in 20% of cases. They affect equally males and females and different ethnic backgrounds. Involvement of the upper limb and particularly the arm is very rare. MRI plays an important role in the diagnosis and assessment of the tumor's boundaries. Treatment can be difficult because of the location of the tumor and its extension into the surrounding tissue.