Haemoglobin C and S in natural selection against Plasmodium falciparum malaria: a plethora or a single shared adaptive mechanism?

Conclusive evidence exists on the protective role against clinical Plasmodium falciparum malaria of Haemoglobin S (beta 6Glu-->Val) and HbC (HbC; beta 6Glu-->Lys), both occurring in sub-Saharan Africa. However, the mechanism/s of the protection exerted remain/s debated for both haemoglobin variants, HbC and HbS. Recently, an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, was reported on HbAC and HbCC infected erythrocytes that showed reduced cytoadhesion and impaired rosetting in vitro. On this basis it has been proposed that HbC protection might be attributed to the reduced PfEMP1-mediated adherence of parasitized erythrocytes in the microvasculature. Furthermore, impaired cytoadherence was observed in HbS carriers suggesting for the first time a convergence in the protection mechanism of these two haemoglobin variants. We investigated the impact of this hypothesis on the development of acquired immunity against P. falciparum variant surface antigens (VSA) encoding PfEMP1 in HbC and HbS carriers in comparison with HbA of Burkina Faso. Higher immune response against a VSA panel and several malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. Thus, these findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. We reviewed the hypothesized mechanisms so far proposed in light of these recent results

Major enzymatic factors involved in bacterial penicillin resistance in Burkina Faso

peer reviewedMany clinical species of bacteria were isolated from biological samples such as urines, blood and wound in Saint Camille medical centre of Ouagadougou. Among the concerned species, the most important members were Escherichia coli and Klebsiella pneumoniae. These β-lactamases producing isolates were directly screened by PCR to identify the nature of the amplified genes responsible for penicillin destroying activity. Therefore specific TEM and SHV primers were used. The PCR products were sequenced. The sequencing results indicated that the parental forms blaTEM-1 and blaSHV-1 were the most common determinants of β-lactamase found, respectively in Escherichia species and Klebsiella pneumoniae. The bacterial susceptibility analysis by MICs measurement clearly correlated the presence of concerned β-lactamase determinants and their resistance patterns. This study is part of a set of investigations carried out by our laboratory to assess the β-lactamase incidence in the failure of β-lactam therapy. In particular, the purpose of this study was to determine the precise nature of β-lactamase supporting the low susceptibility of host bacteria towards penicillins. © 2007 Asian Network for Scientific Information

Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria.

Haemoglobin S (HbS; beta6Glu-->Val) and HbC (beta6Glu-->Lys) strongly protect against clinical Plasmodium falciparum malaria. HbS, which is lethal in homozygosity, has a multi-foci origin and a widespread geographic distribution in sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational load, occurs only in a small area of central West-Africa. To address this apparent paradox, we adopted two partially independent haplotypic approaches in the Mossi population of Burkina Faso where both the local S (S(Benin)) and the C alleles are common (0.05 and 0.13). Here we show that: both C and S(Benin) are monophyletic; C has accumulated a 4-fold higher recombinational and DNA slippage haplotypic variability than the S(Benin) allele (P = 0.003) implying higher antiquity; for a long initial lag period, the C alleles did apparently remain very few. These results, consistent with epidemiological evidences, imply that the C allele has been accumulated mainly through a recessive rather than a semidominant mechanism of selection. This evidence explains the apparent paradox of the uni-epicentric geographic distribution of HbC, representing a 'slow but gratis' genetic adaptation to malaria through a transient polymorphism, compared to the polycentric 'quick but costly' adaptation through balanced polymorphism of HbS

Haemoglobin S and haemoglobin C: 'quick but costly' versus 'slow but gratis' genetic adaptations to Plasmodium falciparum malaria.

Haemoglobin S (HbS; beta6Glu-->Val) and HbC (beta6Glu-->Lys) strongly protect against clinical Plasmodium falciparum malaria. HbS, which is lethal in homozygosity, has a multi-foci origin and a widespread geographic distribution in sub-Saharan Africa and Asia whereas HbC, which has no obvious CC segregational load, occurs only in a small area of central West-Africa. To address this apparent paradox, we adopted two partially independent haplotypic approaches in the Mossi population of Burkina Faso where both the local S (S(Benin)) and the C alleles are common (0.05 and 0.13). Here we show that: both C and S(Benin) are monophyletic; C has accumulated a 4-fold higher recombinational and DNA slippage haplotypic variability than the S(Benin) allele (P = 0.003) implying higher antiquity; for a long initial lag period, the C alleles did apparently remain very few. These results, consistent with epidemiological evidences, imply that the C allele has been accumulated mainly through a recessive rather than a semidominant mechanism of selection. This evidence explains the apparent paradox of the uni-epicentric geographic distribution of HbC, representing a 'slow but gratis' genetic adaptation to malaria through a transient polymorphism, compared to the polycentric 'quick but costly' adaptation through balanced polymorphism of HbS

Rice yellow mottle virus is a suitable amplicon vector for an efficient production of an anti-leishmianiasis vaccine in Nicotiana benthamiana leaves

International audienceBackground Since the 2000's, plants have been used as bioreactors for the transient production of molecules of interest such as vaccines. To improve protein yield, "amplicon" vectors based on plant viruses are used. These viral constructs, engineered to carry the gene of interest replicate strongly once introduced into the plant cell, allowing significant accumulation of the protein. Here, we evaluated the suitability of the monocot-infecting RNA virus Rice yellow mottle virus (RYMV) as an amplicon vector. The promastigote surface antigen (PSA) of the protozoan Leishmania was considered as a protein of interest due to its vaccine properties against canine leishmaniasis. Results Since P1 (ORF1) and CP (ORF3) proteins are not strictly necessary for viral replication, ORF1 was deleted and the PSA gene was substituted to ORF3 in the RYMV-based vector. We evaluated its expression in the best described plant bioreactor system, Nicotiana benthamiana which, unlike rice, allows transient transformation by Agrobacterium. Despite not being its natural host, we demonstrated a low level of RYMV-based vector replication in N. benthamiana leaves. Under optimized ratio, we showed that the P19 silencing suppressor in combination with the missing viral CP ORF significantly enhanced RYMV amplicon replication in N. benthamiana. Under these optimized CP/P19 conditions, we showed that the RYMV amplicon replicated autonomously in the infiltrated N. benthamiana cells, but was unable to move out of the infiltrated zones. Finally, we showed that when the RYMV amplicon was expressed under the optimized conditions we set up, it allowed enhanced PSA protein accumulation in N. benthamiana compared to the PSA coding sequence driven by the 35S promoter without amplicon background. Conclusion This work demonstrates that a non-dicot-infecting virus can be used as an amplicon vector for the efficient production of proteins of interest such as PSA in N. benthamiana leaves

Troubles du sommeil, symptômes anxio-dépressifs et risque cardio-vasculaire chez les hypertendus noirs africains: étude transversale de 414 hypertendus suivis en ambulatoire au CHU de Ouagadougou (Burkina Faso)

Introduction: Dans le but de déterminer la fréquence des troubles du sommeil, de l'anxiété et de la dépression, et de rechercher l'existence d'une relation entre ces troubles et le risque cardio-vasculaire global chez les hypertendus noirs africains, nous avons réalisé une étude transversale de mai 2010 à mars 2011 à l'unité de consultation externe du service de cardiologie du CHU-Yalgado Ouédraogo de Ouagadougou qui a inclut 414 hypertendus adultes suivis en ambulatoire. Après un examen clinique à la recherche des facteurs de risque cardio-vasculaire, deux auto-questionnaires ont été administrés. Méthodes: Le questionnaire de l'«European Sleep Center » pour la recherche des troubles du sommeil et, l'échelle «Hospital Anxiety and Depression Scale » de Zigmond et Snaith pour la recherche de l'anxiété et la dépression. Le diagnostic du syndrome d'apnée du sommeil était clinique et basé sur la présence des 4 symptômes principaux : hypersomnolence diurne, éveils nocturnes fréquents avec nycturie, asthénie matinale avec ou sans céphalées et ronflements importants. Le risque cardio-vasculaire global était calculé grâce à l'équation d'Anderson tirée de l'étude de Framingham. L'analyse des données a été réalisée par le logiciel SPSS version 17. La comparaison des variables a été effectuée grâce au test de Khi 2 pour les variables qualitatives et au test «t» de Student pour les variables quantitatives. Le seuil de signification a été fixé à 5%. Résultats: L'échantillon était composé de 414 patients dont 248 femmes (59,9%). L'âge moyen était de 54,6 ± 9,3 ans. Les troubles du sommeil étaient retrouvés dans 72,2 % des cas. Ils étaient dominés par l'insomnie (49,2%), le syndrome d'apnée du sommeil (33,5%) et le syndrome des jambes sans repos (25,8%). L'anxiété était retrouvée dans 37,1% des cas et la dépression dans 16,6% des cas. Le risque cardio-vasculaire global était faible dans 21,0 %, modéré dans 33,6 %, élevé dans 24,4 % et très élevé dans 21,0 % des cas. Le syndrome d'apnée du sommeil (p=0,033), le syndrome des jambes sans repos (p=0,005), l'anxiété (p=0,0021) et la dépression (p=0,0001) étaient significativement associés à un risque cardio-vasculaire élevé à très élevé. Conclusion: Les troubles du sommeil, l'anxiété et la dépression sont fréquents chez les hypertendus noirs africains. Ils sont liés à un niveau de risque cardio-vasculaire élevé. Leur dépistage devrait être intégré à la prise en charge des hypertendus

Prise en charge post exposition des victimes d’agression par un animal à Ouagadougou

Le nombre de victimes d’agression par un animal ne cessent de croître au Burkina Faso. Chaque année plus de 5 000 cas  d’agressions par un animal sont notifiés dans le pays par les centres nationaux de traitement anti rabiques (CNTAR) du pays. L’étude se propose de décrire la prise en charge post agression des victimes d’agression par un animal de la commune de  Ouagadougou. Il s’est agi d’une étude rétrospective descriptive des victimes d’agression par animal, reçues au CNTAR de Ouagadougou, entre le 1er janvier et le 31 décembre 2009. Les données ont été collectées à partir du registre de consultation des victimes. Les données ont été analysées avec Epi-info 2000 version 3.5.3. La plupart des victimes d’agression provenaient de la commune de Ouagadougou (98,5 %) et l’âge médian était de 15 ans à prédominance masculine. L’animal agresseur était un chien domestique non immunisé contre la rage. Les victimes dans 25,48 % ont bénéficié d’une prophylaxie vaccinale anti rabique ; 30,70 % étaient agressées par un chien errant ou enragé avec une prophylaxie antirabique incomplète dans 22,54 % des cas. La rage a une issue toujours fatale ; le seul traitement reste la prévention primaire et surtout secondaire qui doivent être  renforcées.Mots-cles : Morsure, chien, rage, prévention, Ouagadougou.The number of victims of aggression by an animal are growing in Burkina. Each year more than 5000 cases of attacks by animals are notified by the anti rabies  treatment centers in the country. The study is to describe the post aggression management of victims of the town of Ouagadougou. It is a retrospective descriptive study of attack victims by animal received at the anti-rabies national processing center in Ouagadougou between 01st January and 31st December 2009. Data were collected from the  victims consultation register. The data analysis were performed with Epi-Info version 2000 3.5.3. Most victims of aggression came from  Ouagadougou city (98.5%). The median age was 15 years predominantly male (60%); 95% of the animal were  domestic dog and unvaccinated against rabies. The most common form of aggression was the bite (99%). After exposure, 25.48 % of the victims have received anti rabies vaccine prophylaxis, of which 30.70 % were attacked by a rabid stray dog, whose rabies prophylaxis was incomplete in 22.54 % of cases. Rabies having always fatal issue, the only treatment is primary   prevention, specially secondary prevention which should be strengthened.Keywords: bite, dog, rabies, prevention, Ouagadougou