Synthesis and anthelmintic activity of some hybrid Benzimidazolyl-chalcone derivatives

Purpose: To synthesize hybrid benzimidazolyl-chalcone derivatives, evaluate their anthelmintic activity, and establish some structural elements which could lead to induction and enhancement of this activity.Methods: A series of 1-(1H-benzimidazol-2-yl)-3-aryl-2-propen-1-one compounds (6a-z) was synthesized by condensation reaction of 2-acetylbenzimidazole with aryl and heteroaryl aldehyde derivatives. The physicochemical characterization of these benzimidazolyl-chalcones was carried out by nuclear magnetic resonance spectroscopy (1H and 13C NMR) and mass spectroscopy (MS). All compounds were screened in vitro for their nematicidal activity against Haemonchus contortus in larval development assay. The anthelmintic activities obtained were compared with those of anthelmintic reference drugs (fenbendazole and ivermectin); 1,3-diphenyl-2-propen-1-one also used as reference for chalcone.Results: Compounds 6a, 6g, 6w and 6y showed good nematicidal activity (LC100) at 0.002 and 0.0092 μg/ml. The activity of these four benzimidazolyl-chalcones is nearly equal to that of fenbendazole. It is also interesting to know that these compounds have anti-haemonchus activity which is equal or more efficient than ivermectin. Four other compounds (6d, 6h, 6o and 6t) possess interesting anthelmintic activities at 0.68 and 0.16 μg/ml.Conclusion: Preliminary structure-activity relationship studies revealed that arylpropenone group in position 2 of the benzimidazole ring can be considered as new pharmacophore for nematicidal activity.Keywords: Benzimidazole, Chalcone, Anthelmintic activity, Haemonchus contortu

Study of water pollution by agricultural inputs: case of five intensive agriculture areas in Burkina Faso

Pour optimiser les rendements (agricoles), l’agriculture intensive nécessite une utilisation massive d’intrants agricoles dont les engrais chimiques, potentiellement sources de pollution des ressources en eau. La région du Sud - Ouest du Burkina, dont font partie les zones concernées par la présente étude, connaît une agriculture intensive du coton. Il est fait usage dans les champs de coton, d’engrais à base essentiellement d’azote, de phosphate, de potassium, mais également d’urée, de chlorure de potassium et de nitrate d’ammonium. Un total de 42 échantillons d’eau de surface, de puits et de forages ont fait l’objet d’analyses, afin d’évaluer l’impact de ces engrais sur la qualité des ressources en eau de consommation des populations sur une année. Eu égard à la nature des fertilisants utilisés, les paramètres essentiels suivants ont été ciblés : Nitrates, nitrites, ortho-phosphates, ammonium, potassium, conductivité électrique et dureté totale. Il ressort de ces investigations que les eaux de puits, pendant la saison hivernale, présentent des teneurs plus importantes en nitrates et potassium avec des valeurs maximales respectives de 178 mg/L (plus de 3 fois la valeur limite admise par l’OMS pour les eaux de consommation) et 55 mg/L pour une norme admise par l’OMS de 10 mg/L en potassium. Les ortho-phosphates, forme soluble du phosphore et les nitrites, présentent des teneurs inférieures aux normes admises. S’agissant des ions ammonium, un seul puits par sa position en aval d’un WC et d’un parc d’animaux, a donné des valeurs supérieures à la norme qui est fixée à 1,5 mg/L, atteignant ainsi 20 mg/L de N-NH+4. Les échantillons d’eau de forages sont exempts de toute contamination, alors que 33% des prélèvements d’eau de surface ont donné des teneurs dépassant la valeur limite admise seulement en potassium. Globalement, 61% des échantillons d’eau de puits sont contaminés par les nitrates, 67% par le potassium et 17% donnent des teneurs supérieures à la norme en ammonium. Ce qui permet d’en déduire qu’il y a une infiltration de pollution dans la nappe superficielle qui alimente les puits. La conductivité électrique et la dureté totale sans être excessives présentent les valeurs les plus importantes pour les mêmes sites que sont les puits, avec des valeurs maximales respectives de 1252 μS/cm et 202 mg/L de CaCO3

Evaluating Short-Term Patient Outcomes after HIV Care Interventions in a Low Resource Setting: Preparing for an HIV Vaccine Trial Site in Bamako, Mali

Poster Presentation From AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 201

Abcès post-traumatique du psoas compliqué d’une hydronéphrose: à propos d’un cas et revue de littérature

L’abcès du psoas est une entité clinique relativement rare, en général secondaire à un foyer infectieux de voisinage (gastro-intestinal, génito-urinaire ou ostéo-articulaires). L’abcès post traumatique est rare. La clinique est complexe en l’absence de tableau clinique typique. Le diagnostique est basé sur la clinique et les données radiologiques. Le traitement associe le drainage percutané et l’antibiothérapie. Nous rapportons un cas d’abcès post traumatique du psoas compliqué d’hydronéphrose et traité par abord chirurgical

Enhanced ocean carbon storage from anaerobic alkalinity generation in coastal sediments

The coastal ocean is a crucial link between land, the open ocean and the atmosphere. The shallowness of the water column permits close interactions between the sedimentary, aquatic and atmospheric compartments, which otherwise are decoupled at long time scales (≅ 1000 yr) in the open oceans. Despite the prominent role of the coastal oceans in absorbing atmospheric CO2 and transferring it into the deep oceans via the continental shelf pump, the underlying mechanisms remain only partly understood. Evaluating observations from the North Sea, a NW European shelf sea, we provide evidence that anaerobic degradation of organic matter, fuelled from land and ocean, generates total alkalinity (AT) and increases the CO2 buffer capacity of seawater. At both the basin wide and annual scales anaerobic AT generation in the North Sea's tidal mud flat area irreversibly facilitates 7–10%, or taking into consideration benthic denitrification in the North Sea, 20–25% of the North Sea's overall CO2 uptake. At the global scale, anaerobic AT generation could be accountable for as much as 60% of the uptake of CO2 in shelf and marginal seas, making this process, the anaerobic pump, a key player in the biological carbon pump. Under future high CO2 conditions oceanic CO2 storage via the anaerobic pump may even gain further relevance because of stimulated ocean productivity

Small-scale field evaluation of PermaNet® Dual (a long-lasting net coated with a mixture of chlorfenapyr and deltamethrin) against pyrethroid-resistant Anopheles gambiae mosquitoes from Tiassalé, Côte d'Ivoire

BACKGROUND: Due to the rapid expansion of pyrethroid-resistance in malaria vectors in Africa, Global Plan for Insecticide Resistance Management (GPIRM) has recommended the development of long-lasting insecticidal nets (LLINs), containing insecticide mixtures of active ingredients with different modes of action to mitigate resistance and improve LLIN efficacy. This good laboratory practice (GLP) study evaluated the efficacy of the chlorfenapyr and deltamethrin-coated PermaNet((R)) Dual, in comparison with the deltamethrin and synergist piperonyl butoxide (PBO)-treated PermaNet((R)) 3.0 and the deltamethrin-coated PermaNet((R)) 2.0, against wild free-flying pyrethroid-resistant Anopheles gambiae sensu lato (s.l.), in experimental huts in Tiassale, Cote d'Ivoire (West Africa). METHODS: PermaNet((R)) Dual, PermaNet((R)) 3.0 and PermaNet((R)) 2.0, unwashed and washed (20 washes), were tested against free-flying pyrethroid-resistant An. gambiae s.l. in the experimental huts in Tiassale, Cote d'Ivoire from March to August 2020. Complementary laboratory cone bioassays (daytime and 3-min exposure) and tunnel tests (nightly and 15-h exposure) were performed against pyrethroid-susceptible An. gambiae sensu stricto (s.s.) (Kisumu strain) and pyrethroid-resistant An. gambiae s.l. (Tiassale strain). RESULTS: PermaNet((R)) Dual demonstrated significantly improved efficacy, compared to PermaNet((R)) 3.0 and PermaNet((R)) 2.0, against the pyrethroid-resistant An. gambiae s.l. Indeed, the experimental hut trial data showed that the mortality and blood-feeding inhibition in the wild pyrethroid-resistant An. gambiae s.l. were overall significantly higher with PermaNet((R)) Dual compared with PermaNet((R)) 3.0 and PermaNet((R)) 2.0, for both unwashed and washed samples. The mortality with unwashed and washed samples were 93.6 +/- 0.2% and 83.2 +/- 0.9% for PermaNet((R)) Dual, 37.5 +/- 2.9% and 14.4 +/- 3.9% for PermaNet((R)) 3.0, and 7.4 +/- 5.1% and 11.7 +/- 3.4% for PermaNet((R)) 2.0, respectively. Moreover, unwashed and washed samples produced the respective percentage blood-feeding inhibition of 41.4 +/- 6.9% and 43.7 +/- 4.8% with PermaNet((R)) Dual, 51.0 +/- 5.7% and 9.8 +/- 3.6% with PermaNet((R)) 3.0, and 12.8 +/- 4.3% and - 13.0 +/- 3.6% with PermaNet((R)) 2.0. Overall, PermaNet((R)) Dual also induced higher or similar deterrence, exophily and personal protection when compared with the standard PermaNet((R)) 3.0 and PermaNet((R)) 2.0 reference nets, with both unwashed and washed net samples. In contrast to cone bioassays, tunnel tests predicted the efficacy of PermaNet((R)) Dual seen in the current experimental hut trial. CONCLUSION: The deltamethrin-chlorfenapyr-coated PermaNet((R)) Dual induced a high efficacy and performed better than the deltamethrin-PBO PermaNet((R)) 3.0 and the deltamethrin-only PermaNet((R)) 2.0, testing both unwashed and 20 times washed samples against the pyrethroid-susceptible and resistant strains of An. gambiae s.l. The inclusion of chlorfenapyr with deltamethrin in PermaNet((R)) Dual net greatly improved protection and control of pyrethroid-resistant An. gambiae populations. PermaNet((R)) Dual thus represents a promising tool, with a high potential to reduce malaria transmission and provide community protection in areas compromised by mosquito vector resistance to pyrethroids

Entomological investigations carried out from 2002 to 2010 into the involvement of water bugs (Heteroptera - Hemiptera) in transmission of Mycobacterium ulcerans to humans in Côte d’Ivoire (West Africa)

Ulcer is a disease caused by a mycobacterium present in the environment: Mycobacterium ulcerans.This communicable disease occurs essentially in wet tropical regions, and in particular in west Africa where it is endemic. It is the third most common mycobacterial disease affecting humans after leprosy and tuberculosis, although it is more prevalent than either leprosy or tuberculosis in some rural areas of several countries (Benin, Côte d’Ivoire and Ghana). This has led WHO to act, and in 1998 to declare Buruli ulcer an « emerging disease » and to recognize it as a neglected tropical disease. Its development is a source of concern in Côte d’Ivoire, the country most affected in the world, with an aggregate number of 30 000 cases and more than 2000 cases detected each year. It particularly affects children living in isolated rural areas around bodies of stagnant or slowly flowing water.  In order to control the disease, it is essential fully to understand its epidemiology. In this connection, there are several hypotheses on the mode of transmission of M. ulcerans to humans. Since 1999, the involvement of water bugs belonging to the order of the hemiptera has been invoked by Portaels. In 2002, this hypothesis was confirmed by Marsollier et al. for water bugs of the genus Naucoris taken from the region of Daloa in Côte d’Ivoire, where the disease is endemic. In 2008, Portaels also found M. ulcerans in samples taken from the environment (Gerridae) in Ghana. In 2007, studies began in Côte d’Ivoire into the specific diversity, biology, ecology, ethology and role of aquatic heteroptera in the transmission of M. ulcerans to humans. Samples of aquatic heteroptera were collected each month from different aquatic environments in endemic areas of Côte d’Ivoire. The insects were identified by family, genus and occasionally species. Their distribution, population dynamics and ecological distribution in the water points investigated were correlated with human activities. Monospecific batches of water bugs were regularly composed in order to identify the molecular signatures of M. ulcerans using PCR at the bacteriology laboratory of the Institut Pasteur in Côte d’Ivoire and at the bacteriology laboratory of the Groupe d’Etudes des Interactions Hôtes-Pathogènes (Host-Pathogen Study Group) at the University Teaching hospital in Angers, France. Eighteen (18) species belonging to 8 families were identified. After the aquatic insects collected had been identified, 283 monospecific batches were composed and sent to the Institut Pasteur in Côte d’Ivoire (IPCI) for PCR. Twenty four (24) of the 283 batches i.e. 8,5% containing the following, 14 Diplonychus sp, 2 Naucoris sp, 3 Micronecta sp, 2 Ranatra fusca, 2 Anisops sp and 1 Laccotrephes ater, respectively belonging to the families Belostomatidae, Naucoridae, Corixidae, Ranatridae and Nepidae tested positive under PCR. Thirty five (35) samples of saliva were collected from specimens of the genus Diplonychus. Six of the samples (i.e. 17%) tested positive under PCR. Out of 109 other monospecific batches sent to the laboratory in Angers, France, 33 (i.e. 30%) tested positive under PCR. They comprised 11 batches of Diplonychus sp (Belostomatidae), 8 batches of Micronecta sp (Corixidae), 2 batches of Laccocoris sp (Naucoridae), 4 batches of Ranatra fusca (Ranatridae), 3 batches of Anisops sp, 1 lot de Anisops sardea et 1 lot de Enithares sp (Notonectidae), 2 batches of Plea pullula (Pleidae) and 1 batch of de Laccotrephes sp (Nepidae). Clearly, not only is Diplonychus sp the genus most commonly found, it is also that most affected by M. ulcerans. This justifies the decision to breed this genus in the laboratory since 2008, in order to improve our understanding of its biology and ethology and to standardize physical and chemical parameters so as to determine the best conditions for breeding the insect which would provide an animal model for experimental infections. We have now bred six successive generations in the laboratory. To conclude, although some aquatic heteroptera that host M. ulcerans are strictly phytophagous, (e.g. the Corixidae), the great majority of water bugs are carnivorous predators that are hosts and vectors of M. ulcerans. The absence of a reliable key for determining the family, genus and species in central and west Africa has led us to draw up an iconographic catalogue to determine the taxonomy of these insects

Livestock keepers’ attitudes: Keystone of effective community-based breeding programs

Livestock keepers in southwestern Burkina Faso hold the local Lobi taurine breed, local Zebu cattle, and their crosses. Some communities in the region have begun to implement community-based cattle breeding programs (CBBPs), which involve animal tagging and recording and, potentially, also bull sharing. Based on the hypothesis that the participation of livestock keepers in CBBPs depends on their attitudes towards these programs, we used questionnaires to survey the attitudes of 125 farmers towards cattle breeding strategies and tools. Results were analyzed using principal component analysis. Farmers showed a highly positive attitude towards maintaining the features of their preferred cattle breed, but their attitudes varied substantially towards crossbreeding for breed improvement. Farmers generally agreed that performance was more important than animal appearance, and most of them were willing to cooperate with breeders’ associations but were skeptical about sharing their bulls with other farmers. The majority was reluctant to record performance data, which may be due to a capacity deficit and their confidence in being able to select the best animals based purely on phenotype. Our analysis suggests that breeders’ associations, as a key component of CBBPs, should lay down clear rules and obligations for their members from the outset. Timely consideration of farmers’ attitudes towards different breeding tools may improve their uptake and guarantee the sustainability of CBBPs

Rapid and Sustained Long-Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin-Associated Periodic Syndrome Ages Five Years and Younger.

To assess long-term efficacy and safety of canakinumab and the response to vaccination in children ages ≤5 years with cryopyrin-associated periodic syndrome (CAPS). CAPS patients (ages ≤5 years) received 2 mg/kg canakinumab subcutaneously every 8 weeks; patients with neonatal-onset multisystem inflammatory disease (NOMID) received a starting dose of 4 mg/kg in this open-label trial. Efficacy was evaluated using physician global assessment of disease activity and serum levels of C-reactive protein (CRP) and amyloid A (SAA). Adverse events (AEs) were recorded. Vaccination response was evaluated using postvaccination antibody titers at 4 and 8 weeks after immunization. Of the 17 patients enrolled, 12 (71%) had Muckle-Wells syndrome, 4 (24%) had NOMID, and 1 (6%) had familial cold autoinflammatory syndrome. All 17 patients had a complete response to canakinumab. Disease activity improved according to the physician global assessment, and for 65% of the patients autoinflammatory disease was characterized as "absent" at the end of the study. Median CRP levels decreased over time. No such change was evident in SAA levels. During the extension study, postvaccination antibody titers increased above protective levels in 16 (94%) of 17 assessable vaccinations. Ten of the patients (59%) had AEs suspected to be related to canakinumab; 8 (47%) experienced at least 1 serious AE (SAE). None of the AEs or SAEs required interruption of canakinumab therapy. Our findings indicate that canakinumab effectively maintains efficacy through 152 weeks and appears to have no effect on the ability to produce antibodies against standard childhood non-live vaccines. The safety profile of canakinumab was consistent with previous studies, supporting long-term use of canakinumab for CAPS in children ≤5 years of age