Characterization and in vitro evaluation of a vaginal gel containing Lactobacillus crispatus for the prevention of gonorrhea.

The increasing resistance of Neisseria gonorrhoeae to any current antibiotic treatment and the difficulties associated with the use of prevention means such as condom urge the need for alternative methods to prevent this sexually transmitted infection. In this work, a prevention strategy based on the use of a vaginal gel containing Lactobacilli was assessed in vitro. A Lactobacillus crispatus strain (ATCC 33197) was selected based on the published data on its ability to inhibit Neisseria gonorrhoeae. Its probiotic properties were first characterized. Then, a thermo-sensitive hydrogel containing 21.5% of poloxamer 407, 1% of sodium alginate and 9log10 CFU of Lactobacillus crispatus per gel sample (5 g) was developed. The gelation temperature and the rheological characteristics of this formulation appeared suitable for a vaginal administration. Lactobacillus crispatus was viable in the gel for six months although a large amount of the bacteria was not culturable. The ability of Lactobacillus crispatus to inhibit Neisseria gonorrhoeae was still observed with the gel. Such system, thus, appeared promising for the prevention of gonorrhea.

[Descriptive study of the regulation N°06/2010/CM/UEMOA on procedures followed for registration of pharmacticals for human use in UEMOA member states]. / Etude descriptive du reglement N°06/2010/CM/UEMOA relatif aux procedures d'homologation des produits pharmaceutiques a usage humain dans les etats membres de l'UEMOA.

PURPOSE: The purpose of this study was to describe Regulation No 06/2010/CM/UEMOA on procedures for Registration of Pharmaceuticals for human use in UEMOA member states to facilitate their implementation in the national legislation of each Member State. METHODS: Our study material was composed of the national laws of member states of UEMOA, the texts adopted at Community level relating to community management mechanisms of the drug in West Africa, and in particular regulations No 02/2005/CM/UEMAO on the harmonization of drug regulation in the member states of the UEMOA and No. 06/2010/CM/UEMOA. These texts were analyzed, their scope appreciated, and their origin studied. RESULT: The Regulation No 06/2010/CM/UEMOA describes all the procedures for obtaining a marketing authorization for a medicinal product in the Member States of the UEMOA. This regulation establishes a committee in charge of the technical evaluation of dossiers of application for approval and a national committee in charge of the drug definitive opinion on the request for approval, where the Minister of Health is the administrative authority issuing the marketing authorization. CONCLUSION: The regulation makes a great UEMOA standardization of procedures for drug approval and guarantees the safety and quality of medicines circulating in the UEMOA.

BUT: L'objectif de ce travail est de décrire le règlement n°06/2010/CM/UEMOA relatif aux procédures d'homologation des produits pharmaceutiques à usage humain dans les Etats membres de l'UEMOA en vue de faciliter son application dans chacun des Etats membres. MATÉRIEL ET MÉTHODE: Notre matériel d'étude a été constitué des législations nationales des Etats membres de l'UEMOA d'une part et par les textes adoptés au plan communautaire relatifs aux mécanismes communautaires de gestion du médicament en Afrique de l'Ouest d'autre part en particulier les règlements n°02/2005/CM/UEMAO relatif à l'harmonisation de la réglementation pharmaceutique dans les Etats membres de l'UEMOA et n°06/2010/CM/UEMOA. Ces textes ont été analysés, leur champ d'application apprécié, leur fondement étudié. RÉSULTAT: Le règlement n°06/2010/CM/UEMOA décrit l'ensemble des procédures pour l'obtention d'une AMM d'un médicament à usage humain dans les Etats membres de l'UEMOA. Ce règlement institue un comité technique pour l'évaluation technique des dossiers de demande d'homologation et un comité national du médicament chargé de l'avis définitif sur la demande d'homologation, le ministre de la santé étant l'autorité administrative qui délivre l'AMM. CONCLUSION: Le règlement UEMOA réalise une formidable standardisation des procédures d'homologation des médicaments et garantit la sécurité et la qualité des médicaments qui circulent dans l'espace UEMOA.

In vitro and in vivo characteristics of a thermogelling and bioadhesive delivery system intended for rectal administration of quinine in children.

The aim of this work was to improve the rectal bioavailability of quinine hydrochloride by designing thermosensitive and mucoadhesive gels intended for rectal delivery. The rheological and mucoadhesive properties of poloxamer 407 solutions have been modulated by addition of hydroxypropylmethycellulose (HPMC) and propanediol-1,2. In vitro release and rectal absorption of quinine have been highlighted by a dialysis dissolution testing method and by the determination of bioavailability of the different formulations in rabbits. Increasing the proportions of HPMC and poloxamer in the formulations resulted in a prolonged release of quinine. Indeed, compared to the DT 50% of a rectal solution and a simple HPMC gel (27 and 65 min, respectively) the DT 50% of thermosensitive ternary systems was increased and ranged between 80 and 138 min, depending on the system composition. The release rate depended strongly on the elasticity of the gels after thermogelation. The absolute rectal bioavailability of quinine determined in rabbits was significantly improved with these thermosensitive and adhesive systems. It increased from 62% for the rectal solution to 98% for a ternary system 16/0.5/30 (poloxamer (16%)/HPMC (0.5%)/propanediol-1,2 (30%)). As a result of combined bioadhesion and prolonged release of quinine in vivo, higher average values of MRT and t(max) (9.1+/-0.2h and 30 min, respectively) were obtained compared to the rectal solution (6.9+/-0.9h and 15 min, respectively). Moreover, these formulations presented a very good rectal tolerance. Modulation by HPMC of the viscoelastic and mucoadhesive properties of poloxamer 407 thermogelling solutions allowed a prolonged release of quinine hydrochloride and an improvement of bioavailability in rabbit.

Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine.

The aim of this work was to formulate and characterize thermosensitive gels based on poloxamer 407, a thermosensitive polymer, and hydroxypropylmethylcellulose (HPMC), a bioadhesive polymer, intended for the rectal delivery of quinine in children. In order to avoid the macroscopic phase separation between the two polymers it was necessary to add propanediol-1,2. After the formulation of stable ternary systems, their rheological properties were studied as a function of temperature. It was thus possible to obtained the gelation temperature of the systems as well as their elastic modulus, G', at 37 degrees C. It appeared that HPMC in the presence of propanediol-1,2 had a synergistic effect on the gelation of poloxamer 407. Tests on the rabbit rectal mucous membrane, founded on a technique of traction of the adhesive/adhered joint, made it possible to characterize the bioadhesive properties of the gels by measuring the work of adhesion, W, and the maximum detachment force, F(max). Over small concentration ranges of poloxamer and HPMC, very important variations of the viscoelastic and mucoadhesives properties were observed. It was shown that the viscoelastic and the bioadhesive properties were tightly correlated. Indeed, an empirical equivalence relation was established between the shear frequency and the rate of deformation in traction and allowed to describe all our samples by a master curve. This master curve would make it possible to predict the values of W at various rates of traction by the simple non-destructive measurement of the elastic modulus, G', at an equivalent shear frequency.

[Vectorial transmission of malaria in shrubby Savannah area at Ganse, Ivory Coast]. / Transmission vectorielle du paludisme en savane arborée a Ganse en Côte d'Ivoire.

A longitudinal entomologic study was carried out in the village of Ganse located in the Northeastern Ivory Coast from July 2000 to July 2001. The threefold purpose of the study was to index Plasmodium-carrying Anopheles species by capturing mosquitoes on human volunteers, collecting larvae in different dwelling types, and evaluating the involvement each species in the malaria transmission. A total of 4 species belonging to the Anopheles genus were collected in the village. Identification of circumsporozoite protein using the ELISA technique demonstrated that three species were plasmodium vectors. These species belonged to the An. gambiae complex (An. gambiae s.s. 100%), to the An. funestus group (An. funestus s.s. 95.6%) and to the An. nill group (An. nili s.s. 100%). The estimated mean sporozoite index was 5.9% for An. gambiae s.l., 4.3% for the An. funestus group and 2.6% for the An. nili group. The main larva breeding sites were standing water such as puddles for An. gambiae s.l., streams with tall plants for the An. funestus group and the Comoe River for An. nili group. Because peak breeding of these three species occurs at three successive times; i.e., in May, September and July respectively, transmission of P. falciparum is continuous throughout the year. The transmission rate is high since we recorded up to up to 410 infected bites per person per year. In addition to showing the presence of An. rivulorum-like, our findings in the area demonstrates the important role of An. nili s.s. in the transmission and the complexity of the vectorial system.

Transmission vectorielle du paludisme en savane arborée à Gansé en Cote d'Ivoire

Un suivi entomologique longitudinal a ete realise a Ganse; un village du Nord-Est de la Cote d'Ivoire; entre juillet 2000 et juillet 2001. L'objectif de cette etude etait de repertorier les especes vectrices des Plasmodium par capture des moustiques sur des volontaires; recolter des larves dans diff e rents types de gites et evaluer l'implication de ces especes dans la transmission du paludisme. Quatre especes appartenant au genre Anopheles ont ete recoltees dans le village. La technique ELISA d'identification des antigenes CSP de Plasmodium a montre que trois de ces especes etaient ve c t rices. Ces especes appartenaient au complexe An. gambiae (An. gambiae s.s. a 100); au groupe An. funestus (An. funestus s.s. a 95;6) et au groupe An. nili (An. nili s.s. a 100). Les indices sporozoitiques moyen etaient de 5;9pour An. gambiae s.l.; 4;3pour les Anopheles du groupe funestus et 2;6pour les Anopheles du groupe nili. Les principaux gites larvaires etaient des points d'eau temporai es tels que des flaques pour An. gambiae s.l.; des cours d'eau a vegetation dressee pour les Anopheles du groupe funestus et le fleuve Comoe pour les Anopheles du groupe nili. La presence de ces trois especes avec des pics d'abondance observes respectivement en mai; en septembre et en juillet; assure une transmission quasi permanente de P. falciparum. Cette transmission est importante car on a pu enregistrer jusqu'a 410 piqures infectees par homme et par an. Dans cette localite; nous avons montre la presence d'An. rivulorum-like mais surtout le role important d'An. nili s.s. dans la transmission et la complexite du systeme vectoriel dans la region

[Resistance of Culex quinquefasciatus (Say, 1823) to deltamethrin and the use of impregnated mosquito nets in an urban area of Bouaké, Côte d'Ivoire]. / Résistance de Culex quinquefasciatus (Say, 1823) à la deltaméthrine et l'utilisation de la moustiquaire imprégnée en milieu urbain de Bouaké, Côte d'Ivoire.

The efficacy of pieces of nets treated with two formulations of deltamethrin (concentrated suspension at 1% and tablets at 25%) against two strains of Culex quinquefasciatus ("S-Lab", sensitive strain and "Bouaké", local strain) has been evaluated at the laboratory by experimental tunnels tests. The observed mortality of the sensitive strain has been 2-3 time more important than that of local strain. This observation seems to be linked to Culex quinquefasciatus of Bouaké pyrethrinoids-resistance. The excito-repellency effect of the two formulations has been lower for the local strain than for the sensitive strain. It has also been more important with the tablet at 25% than with concentrated suspension at 1%. The blood feeding rate has been more important for the local strain than for sensitive strain and it has been lower with the tablet at 25% than with the concentrated suspension at 1%.

Resistance to carbosulfan in Anopheles gambiae from Ivory Coast, based on reduced sensitivity of acetylcholinesterase.

Resistance to carbosulfan, a carbamate insecticide, was detected in field populations of the malaria vector mosquito Anopheles gambiae Giles (Diptera: Culicidae) from two ecologically contrasted localities near Bouaké, Ivory Coast: rural M'bé with predominantly M form of An. gambiae susceptible to pyrethroids; suburban Yaokoffikro with predominantly S form of An. gambiae highly resistant to pyrethroids (96% kdr). The discriminating concentration of 0.4% carbosulfan (i.e. double the LC100) was determined from bioassays with the susceptible An. gambiae Kisumu strain. Following exposure to the diagnostic dosage (0.4% carbosulfan for 1 h), mortality rates of female An. gambiae adults (reared from larvae collected from ricefields) were 62% and 29% of those from M'bé and Yaokoffikro, respectively, 24 h post-exposure. Exposure for 3 min to netting impregnated with the operational dosage of carbosulfan 200 mg/m2 gave mortality rates of 88% of those from M'bé and only 12.2% for Yaokoffikro. In each case the control untreated mortality rate was insignificant. Biochemical assays to detect possible resistance mechanism(s) revealed the presence of insensitive AChE in populations of An. gambiae at both localities, more prevalent in the S form at Yaokoffikro than in M form at M'bé, as expected from bioassays results. Our study demonstrates the need to monitor carbamate resistance among populations of the An. gambiae complex in Africa, to determine its spread and anticipate vector control failure if these insecticides are employed.

[Impact of pyrethrin resistance on the efficacity of impregnated mosquito nets in the prevention of malaria: results of tests in experimental cases with deltamethrin SC]. / Impact de la résistance aux pyréthrinoïdes sur l'efficacité des moustiquaires imprégnées dans la prévention du paludisme: résultats des essais en cases expérimentales avec la deltaméthrine SC.

The effects of impregnated bednets treated with deltamethrin at a dosage of 25 mg a.i./m2 were evaluated at two testing stations in Côte d'Ivoire. The first one was located in Yaokoffikro, where Anopheles gambiae s.s. are resistant to pyrethroids (including deltamethrin), and the second in M'be, close to a large rice-growing area where An. gambiae s.s. are susceptible pyrethroids. In both situations, treating bednets with deltamethrin was very effective in limiting contact between man and vector. 72% fewer female An. gambiae entered the huts in the susceptible area, whereas a decrease of 43% was recorded in the resistant area, indicating that deltamethrin still has a certain repellent effect on resistant populations of An. gambiae s.s. Overall mortality induced by bednets treated with insecticide was significantly higher in the resistant area (56.4% as versus 44.3%). An explanation for this apparent paradox is that the mosquitoes being less repelled by the insecticide remain on the treated material for longer periods of time and most of them eventually die. The results of this study indicate that bednets treated with deltamethrin are an effective prophylactic measure even in areas where An. gambiae s.s. are resistant to pyrethroids and should still be considered as a practical means of personal protection against malaria even in pyrethroid resistance areas with high frequency of kdr resistance genes.

[Laboratory evaluation of alpha-cypermethrin insecticide efficacy on Anopheles gambiae populations of Côte d'Ivoire resistant to permethrin and deltamethrin]. / Evaluation au laboratoire de l'efficacité insecticide de l'alpha-cyperméthrine sur les populations d'Anopheles gambiae de Côte d'Ivoire résistantes à la perméthrine et à la deltaméthrine.

Susceptibility tests were carried out in laboratory conditions to evaluate the efficacy of alpha-cypermethrin (a synthetic pyrethroid never used in Côte d'Ivoire) for malaria vector control. Five wild populations of Anopheles gambiae originating from M'bé, Yaokoffikro, Korhogo, Kafiné and Daola and two laboratory reared strains (Kisumu susceptible and Kou permethrin resistant selected strain) were tested. The diagnostic dosage of alpha-cypermethrin for the sensitive strain Kisumu was 2.5 x 10(-3)%. A comparative study of the susceptibility of samples of wild populations of An. gambiae was carried out according to the WHO standard susceptibility test. Impregnated papers with 4% DDT, 0.25% permethrin, 0.025% deltamethrin and 0.0025% alpha-cypermethrin were used. The results showed that except for mosquitoes from M'bé, all the other populations were resistant to these insecticides. Bioassays were carried out with alpha-cypermethrin at the operational dosage of 20 mg a.i./m2 on the same population and laboratory reared strains. The results showed the efficacy of this insecticide on both the Kisumu strain and the population from M'bé, a maintained efficacy for the Daloa, Kafiné and Korhogo mosquito populations, but the wild anopheline population from Yaokoffikro clearly appeared fully resistant.

[Stegomyian indices and epidemiological status of yellow fever in a rural area of the Ivory Coast]. / Indices stégomyiens et situation épidémiologique de la fièvre jaune en zone rurale de Cote d'Ivoire.

The M'bahiakro region, located in the center of Ivory Coast and inhabited by the N'gain, has been the scene of a yellow fever epidemic since 1982. This region reunites all the conditions for cyclic emergence of the flavivirus given the current epidemiologic pattern of yellow fever in Africa. In view of this situation ORSTOM, in collaboration with the Pasteur Institute of Ivory Coast, has created a pilot zone for epidemiologic surveillance of yellow fever in this region. The N'gain region which has a total population of 12,000 living in 20 villages with between 100 and 2000 inhabitants is located in a preforest area with an attenuated transitional climate characterized by a dry season and a rainy season with two peak periods of precipitation (May and October) but a low mean annual rainfall (1172 mm). There are few springs, wells and rivers and maintaining water supplies is difficult. As a result villagers stockpile rainwater in various types of containers. Inspections were carried out from February to July in the 20 villages of the region. Each room of every dwelling was registered and visited. Water reserves were inspected and those containing pre-imaginal stage Culicidae were counted as positive. Nymphs and larva were sometimes collected. Nymphs were raised and larva preserved. Species identification by the laboratory was based on these larva and imagos obtained by raising the nymphs. Correspondence tables established by the World Health Organization between stegomiyan indices (dwelling), container, BRETEAU) and flavivirus in the population were used to exploit the results.(ABSTRACT TRUNCATED AT 250 WORDS)