Search

Puccinia arachidiscauses rust, which is one of the most important peanut foliar diseases in the world, particularly in Burkina Faso. In favourable conditions, rust can cause serious damage, and lead to notable crop losses in fields. For sustainable peanut production, alternative control strategies including biological control methods for integrated disease management are needed to control rust. Thus, we investigated the effectiveness of Akanthomyces lecanii, hyperparasite of P. arachidisfor the biological control of peanut rust in Burkina Faso. Our results revealed that a conidial suspension of A. lecaniireduces the germination rate of P. arachidisurediniospores within the range of 55.67 to 59.34%, compared to the distilled water control. In addition, leaf treatments with the conidial suspension of A. lecaniisignificantly reduced the severity of rust on detached leaves and peanut plants compared to the distilled water control. We found that the rust severity on the treated leaves and plants were always lower than in the control, regardless of the pathogen isolate. These disease severities did not exceed 13% in the treated leaves and plants but could reach 45.5% in the control. From our findings, weight of pods was high in treated peanut plants compared to those of the control. The A. lecaniispores is promising tool in biocontrol of peanut rust, and could be used to promote organic farming in West Africa.

In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) is associated to misfolding and defective gating of the mutant channel. One of the most promising CF drug targets is the ubiquitin ligase RNF5, which promotes F508del-CFTR degradation. Recently, the first ever reported inhibitor of RNF5 was discovered, i.e., the 1,2,4-thiadiazol-5-ylidene inh-2. Here, we designed and synthesized a series of new analogues to explore the structure–activity relationships (SAR) of this class of compounds. SAR efforts ultimately led to compound 16, which showed a greater F508del-CFTR corrector activity than inh-2, good tolerability, and no toxic side effects. Analogue 16increased the basal level of autophagy similar to what has been described with RNF5 silencing. Furthermore, co-treatment with 16significantly improved the F508del-CFTR rescue induced by the triple combination elexacaftor/tezacaftor/ivacaftor in CFBE41o–cells. These findings validate the 1,2,4-thiadiazolylidene scaffold for the discovery of novel RNF5 inhibitors and provide evidence to pursue this unprecedented strategy for the treatment of CF.

Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine for pregnant women (IPTp-SP) coverage remains far below the desirable goal of at least three doses before delivery. This study evaluates an innovative intervention using mobile phones as a means of increasing coverage for the third dose of IPTp-SP.

In cystic fibrosis (CF), the deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) leads to misfolding and premature degradation of the mutant protein. These defects can be targeted with pharmacological agents named potentiators and correctors. During the past years, several efforts have been devoted to develop and approve new effective molecules. However, their clinical use remains limited, as they fail to fully restore F508del-CFTR biological function. Indeed, the search for CFTR correctors with different and additive mechanisms has recently increased. Among them, drugs that modulate the CFTR proteostasis environment are particularly attractive to enhance therapy effectiveness further. This Perspective focuses on reviewing the recent progress in discovering CFTR proteostasis regulators, mainly describing the design, chemical structure, and structure–activity relationships. The opportunities, challenges, and future directions in this emerging and promising field of research are discussed, as well.

Graphical abstract:

Cystic fibrosis (CF) is a life-threatening autosomal recessive disease, caused by mutations in the CF transmembrane conductance regulator (CFTR) chloride channel. CFTR modulators have been reported to address the basic defects associated with CF-causing mutations, partially restoring the CFTR function in terms of protein processing and/or channel gating. Small-molecule compounds, called potentiators, are known to ameliorate the gating defect. In this study, we describe the identification of the 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole core as a novel chemotype of potentiators. In-depth structure–activity relationship studies led to the discovery of enantiomerically pure 39endowed with a good efficacy in rescuing the gating defect of F508del- and G551D-CFTR and a promising in vitrodruglike profile. The in vivocharacterization of γ-carboline 39showed considerable exposure levels and good oral bioavailability, with detectable distribution to the lungs after oral administration to rats. Overall, these findings may represent an encouraging starting point to further expand this chemical class, adding a new chemotype to the existing classes of CFTR potentiators.

Nous avons mené cette étude dans le but de présenter la survie des patients atteints de pleurésie maligne et paramaligne dans un contexte de pays à ressources limitées. Il s’agit d’une étude rétrospective sur la base de dossiers de patients reçus pour pleurésie maligne et paramaligne dans trois formations sanitaires de la ville de Ouagadougou du 1er août 2009 au 30 juillet 2015. La survie a été analysée selon différentes caractéristiques liées aux patients et à la maladie. Quatre-vingts patients âgés en moyenne de 54 ans ont été retenus. Le sex-ratio était de 0,9. Seize patients avaient une comorbidité. La pleurésie était révélatrice, métachrone et synchrone dans respectivement 55 %, 26 % et 17,5 % des cas. Le cancer du poumon a été le plus souvent à l’origine des pleurésies néoplasiques (27,5 %) suivi du cancer du sein (19 %). La médiane de survie globale était de 3 mois ; elle variait selon les cancers primitifs : 5 mois pour les cancers primitifs inconnus, 4 mois pour les cancers pulmonaires et 2 mois pour les cancers du sein. Le sexe et la présence de comorbidité ont été les facteurs indépendants influençant la survie des patients. Dans cette étude, la durée de survie des patients est fortement compromise par les insuffisances du plateau médicotechnique.

Background: Deletion of phenylalanine 508 is the most frequent mutation causing cystic fibrosis. It causes multiple defects: 1) misfolding of the protein causing retention at the ER (processing defect); 2) reduced channel activity (gating defect); 3) reduced plasma membrane residency time due to increased internalization rate and defective recycling. Methods: Druggability of F508del-CFTR was demonstrated by several studies. Correctors are molecules able to improve maturation and trafficking to the membrane of F508del- CFTR. Correctors could act as pharmacological chaperones or as proteostasis regulators. Pharmacological chaperones act directly on mutant CFTR, while proteostasis regulators modify the proteostasis environment leading to beneficial effects on CFTR maturation. Results: The use of a single compound is not sufficient to promote a therapeutically relevant F508del-CFTR rescue. Drug therapy for CF will require combinations of correctors exploiting different mechanisms of action, i.e. pharmacological chaperones combined together or with a proteostasis regulator. Conclusion: Development of more effective CF drugs could therefore rely on a better understanding of the molecular events underlying CFTR processing/degradation. This review will focus on most promising pathways and related targets for the development of novel CF pharmacotherapies.

L’ecthyma gangreneux est une infection sévère de la peau le plus souvent due à Pseudomonas aeruginosa. Il est caractérisé par des ulcérations nécrotiques limitées par un halo inflammatoire. Les lésions siègent habituellement dans les régions péri-anale, péri-génitale ou axillaire. L’ecthyma gangreneux survient en général chez des sujets immunodéprimés : chimiothérapie aplasiante, infection par le VIH, neutropénie ou déficit fonctionnel des polynucléaires neutrophiles, agammaglobulinémie ; il a plus rarement été décrit comme compliquant une varicelle.

Background: Plasmodium falciparummalaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. Methods: This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3–59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. Conclusion: The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention.

ABSTRACTDeclining malaria transmission and known difficulties with current diagnostic tools for malaria, such as microscopy and rapid diagnostic tests (RDTs) in particular at low parasite densities, still warrant the search for sensitive diagnostic tests. Molecular tests need substantial simplification before implementation in clinical settings in countries where malaria is endemic. Direct blood PCR (db-PCR), circumventing DNA extraction, to detect Plasmodiumwas developed and adapted to be visualized by nucleic acid lateral flow immunoassay (NALFIA). The assay was evaluated in the laboratory against samples from confirmed Sudanese patients (n= 51), returning travelers (n= 214), samples from the Dutch Blood Bank (n= 100), and in the field in Burkina Faso (n= 283) and Thailand (n= 381) on suspected malaria cases and compared to RDT and microscopy. The sensitivity and specificity of db-PCR-NALFIA compared to the initial diagnosis in the laboratory were 94.4% (95% confidence interval [CI] = 0.909 to 0.969) and 97.4% (95% CI = 0.909 to 0.969), respectively. In Burkina Faso, the sensitivity was 94.8% (95% CI = 0.88.7 to 97.9%), and the specificity was 82.4% (95% CI = 75.4 to 87.7%) compared to microscopy and 93.3% (95% CI = 87.4 to 96.7%) and 91.4% (95% CI = 85.2 to 95.3%) compared to RDT. In Thailand, the sensitivity and specificity were 93.4% (CI = 86.4 to 97.1%) and 90.9 (95% CI = 86.7 to 93.9%), respectively, compared to microscopy and 95.6% (95% CI = 88.5 to 98.6%) and 87.1% (95% CI = 82.5 to 90.6) compared to RDT. db-PCR-NALFIA is highly sensitive and specific for easy and rapid detection of Plasmodiumparasites and can be easily used in countries where malaria is endemic. The inability of the device to discriminate Plasmodiumspecies requires further investigation.

Disclosure of HIV-serostatus remains a way to avoid sexual transmission of HIV because it allows partners to take the necessary protective measures, e.g. use of condoms. Disclosure is nevertheless difficult due to the discrimination associated with HIV. The objective of this study was to analyze factors leading to self-disclosure of HIV-positive status within a sample of persons of both sexes attending different healthcare services in Burkina Faso.

Arsenic levels in tube-wells water, food, residents' urine and the prevalence of skin lesions in Yatenga province, Burkina FasoThe aim of the present study was to evaluate the levels of arsenic in tube-well water, food and residents' urines samples in Yatenga province, Burkina Faso. The prevalence of skin lesions was evaluated as well. The study was cross-sectional in design. It was conducted during April 2009. Permanent residents of 20 villages were included in the study. Water samples were collected from 31 tube-wells located in the selected villages. Tomatoes, cabbages, and potatoes produced in the selected village were randomly sampled. Arsenic content in water, food, and residents' urine was determined by atomic absorption spectrophotometry using hydride generation method. Finally, 240 people were examined by a medical doctor for skin lesions. Arsenic concentrations from the tube-well water ranged from 1 to 124 μg/l. Arsenic concentrations of more than one-half (52%) of the water samples exceeded the WHO guideline value (10 μg/l). No trace of arsenic was found in the samples of tomatoes, cabbages, and potatoes. Variation in arsenic concentrations in the urines was correlated to arsenic concentrations in tube-well water. Clinical examinations revealed that melanosis and keratosis were respectively identified in 29.26% and 46.34% of the population. Both conditions were observed in 24.39% of the population. The frequency of skin lesions was positively associated with the arsenic concentration in tube-well water. A great majority (89.53%) of those who had skin lesions were at least 18 years old. In conclusion, chronic arsenic poisoning remains a major public health problem in the province of Yatenga (Burkina Faso).

L’apparition d’un syndrome de détresse respiratoire aiguë constitue une des formes graves de la COVID-19. Bien qu’il y ait eu plusieurs études sur les facteurs pronostiques de sa forme sévère, aucune étude de ce type n’a été menée au Burkina Faso.