Efficacy of non-artemisinin- and artemisinin-based combination therapies for uncomplicated falciparum malaria in Cameroon

<p>Abstract</p> <p>Background</p> <p>The use of drug combinations, including non-artemisinin-based and artemisinin-based combination therapy (ACT), is a novel strategy that enhances therapeutic efficacy and delays the emergence of multidrug-resistant <it>Plasmodium falciparum</it>. Its use is strongly recommended in most sub-Saharan African countries, namely Cameroon, where resistance to chloroquine is widespread and antifolate resistance is emerging.</p> <p>Methods</p> <p>Studies were conducted in Cameroonian children with acute uncomplicated <it>P. falciparum </it>malaria according to the standard World Health Organization protocol at four sentinel sites between 2003 and 2007. A total of 1,401 children were enrolled, of whom 1,337 were assigned to randomized studies and 64 were included in a single non-randomized study. The proportions of adequate clinical and parasitological response (PCR-uncorrected on day 14 and PCR-corrected on day 28) were the primary endpoints to evaluate treatment efficacy on day 14 and day 28. The relative effectiveness of drug combinations was compared by a multi-treatment Bayesian random-effect meta-analysis.</p> <p>Findings</p> <p>The results based on the meta-analysis suggested that artesunate-amodiaquine (AS-AQ) is as effective as other drugs (artesunate-sulphadoxine-pyrimethamine [AS-SP], artesunate-chlorproguanil-dapsone [AS-CD], artesunate-mefloquine [AS-MQ], dihydroartemisinin-piperaquine [DH-PP], artemether-lumefantrine [AM-LM], amodiaquine, and amodiaquine-sulphadoxine-pyrimethamine [AQ-SP]). AM-LM appeared to be the most effective with no treatment failure due to recrudescence, closely followed by DH-PP.</p> <p>Conclusion</p> <p>Although AM-LM requires six doses, rather than three doses for other artemisinin-based combinations, it has potential advantages over other forms of ACT. Further studies are needed to evaluate the clinical efficacy and tolerance of these combinations in different epidemiological context.</p

Ecological characterization of the Subterraneum Clover (Trifolium subterraneum L., Fabaceae) natural habitat in Northeastern Algeria

Within the framework of the evaluation and valorization of the plant genetic resources bearing a fodder and pastoral interest in Algeria, a study was carried out about the ecological characterization of the Subterraneum Clover natural habitat. Following a prospecting and collecting mission conducted in the northeastern part of the country, thirty nine (39) Subterraneum Clover sites were identified. For each site, three soil samples were taken randomly (117 samples). Sixteen (16) physical and chemical parameters of soils (pH, electric conductivity, total limestone, total nitrogen, potassium, phosphorus, carbon, organic matter, C/N ratio, particle composition) were analysed. Two (02) additional variables, linked to the topography (altitude) and to the climate (rainfall) of the natural habitat of the species were as well taken into account. The variance analysis showed highly significant results for the whole physical and chemical characteristics of the soils taken into consideration. Thus, the Subterraneum Clover seems to be adapted to unsalted and calcareous soils, characterized by rather diverse textures (clay, clayey loam, loamy sand, sandy clay loam, loam) and a pH varying from 6.46 to 8.64 (slightly acid, neutral, slightly alkaline, alkaline). The record of Algerian populations of Subterranean Clover on frankly alkaline soils appears as the first one for some subspecies and/or varieties of the species T. subterraneum. The Subterraneum Clover seems as well to tolerate soils whose phosphorus and potassium content are variable and the C/N ratio relatively high. Significant relations were noticed between altitude and rainfall, on the one hand and some soil physical and chemical parameters on the other, with a relatively stronger influence of the first factor (altitude). The pH seems to vary with the natural habitat altitude of the different populations of Subterraneum Clover. The use and valorization of this clover, in different edaphical and climatic conditions, would permit the development of marginal regions, mainly the ones located in mountainous regions to which the species seems to be well adapted.Dans le cadre de l’évaluation et de la valorisation des ressources phytogénétiques d’intérêt fourrager et pastoral en Algérie, une étude portant sur la caractérisation écologique de l’habitat naturel du Trèfle souterrain (Trifolium subterraneum L. ; Fabaceae), a été réalisée. Suite à une mission de prospection et de collecte menée dans le Nord-Est du pays, trente-neuf (39) sites de Trèfle souterrain ont été identifiés. Pour chaque site, trois échantillons de sol ont été prélevés de façon aléatoire (117 échantillons). Seize (16) paramètres physico-chimiques des sols (pH, conductivité électrique, calcaire total, azote total, potassium, phosphore, carbone, matière organique, rapport C/N, composition de la texture du sol) ont été analysés. Deux (02) variables supplémentaires liées à la topographie (altitude) et au climat (pluviométrie) de l’habitat naturel de l’espèce ont également été considérées. L’analyse de variance a montré des résultats très hautement significatifs pour l’ensemble des variables physico-chimiques considérées. Le Trèfle souterrain semble ainsi adapté aux sols non salins, franchement calcaires, caractérisés par des textures assez diverses (argileux, argileux francs, sableux francs, argilo-sableux francs, équilibrés) et un pH variable (légèrement acide, neutre, légèrement alcalin, alcalin) allant de 6,46 à 8,64. La présence de plusieurs populations Algériennes de Trèfle souterrain sur des sols franchement alcalins est signalée pour la première fois pour certaines sous-espèces et /ou variétés appartenant à T. subterraneum. Le Trèfle souterrain semble également tolérer des sols dont les teneurs en phosphore et en potassium sont variables et le rapport C/N relativement élevé. Des relations significatives ont été mises en relief entre l’altitude et la pluviométrie, d’une part, et certains paramètres physico-chimiques des sols d’autre part, avec une influence relativement plus prononcée du premier facteur (altitude). Le pH semble varier avec l’altitude de l’habitat naturel des différentes populations de Trèfle souterrain. L’utilisation et la valorisation du trèfle souterrain, dans des conditions édapho-climatiques différentes, permettraient la mise en valeur des régions marginales, notamment celles localisées dans les zones montagneuses, au niveau desquelles l’espèce semble bien adaptée

Evolution of the levels of human leukocyte antigen G (HLA-G) in Beninese infant during the first year of life in a malaria endemic area : using latent class analysis

Background: HLA-G, a non-classical HLA class I antigen, is of crucial interest during pregnancy by inhibiting maternal immune response. Its role during infections is discussed, and it has been described that high levels of soluble HLA-G during childhood increase the risk of malaria. To explore more precisely interactions between soluble HLA-G and malaria, latent class analysis was used to test whether distinct sub-populations of children, each with distinctive soluble HLA-G evolutions may suggest the existence of groups presenting variable malaria susceptibility. Method: A study was conducted in Benin from 2010 to 2013 and 165 children were followed from birth to 12 months. Evolution of soluble HLA-G was studied by the latent class method. Results: Three groups of children were identified: one with consistently low levels of soluble HLA-G during follow-up, a second with very high levels and a last intermediate group. In all groups, low birth weight, high number of malaria infections and high exposure to malaria transmission were associated with high level of soluble HLA-G. Placental malaria was not. Presence of soluble HLA-G in cord blood increased the probability of belonging to the highest trajectory. Conclusion: These results, together with previous ones, confirm the important role of HLA-G in the individual susceptibility to malaria. Assaying soluble HLA-G at birth could be a good indicator of newborns more fragile and at risk of infections during childhood

Molecular monitoring of plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future

<p>Abstract</p> <p>Background</p> <p>Regular monitoring of the levels of anti-malarial resistance of <it>Plasmodium falciparum </it>is an essential policy to adapt therapy and improve malaria control. This monitoring can be facilitated by using molecular tools, which are easier to implement than the classical determination of the resistance phenotype. In Cameroon, chloroquine (CQ), previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ) monotherapy. Then, artemisinin-based combination therapy (ACT), notably artesunate-amodiaquine (AS-AQ) or artemether-lumefantrine (AL), was gradually introduced in 2004. This situation raised the question of the evolution of <it>P. falciparum </it>resistance molecular markers in Yaoundé, a highly urbanized Cameroonian city.</p> <p>Methods</p> <p>The genotype of <it>pfcrt </it>72 and 76 and <it>pfmdr1 </it>86 alleles and <it>pfmdr1 </it>copy number were determined using real-time PCR in 447 <it>P. falciparum </it>samples collected between 2005 and 2009.</p> <p>Results</p> <p>This study showed a high prevalence of parasites with mutant <it>pfcrt </it>76 (83%) and <it>pfmdr1 </it>86 (93%) codons. On the contrary, no mutations in the <it>pfcrt </it>72 codon and no samples with duplication of the <it>pfmdr1 </it>gene were observed.</p> <p>Conclusion</p> <p>The high prevalence of mutant <it>pfcrt </it>76T and <it>pfmdr1 </it>86Y alleles might be due to the choice of alternative drugs (AQ and AS-AQ) known to select such genotypes. Mutant <it>pfcrt </it>72 codon was not detected despite the prolonged use of AQ either as monotherapy or combined with artesunate. The absence of <it>pfmdr1 </it>multicopies suggests that AL would still remain efficient. The limited use of mefloquine or the predominance of mutant <it>pfmdr1 </it>86Y codon could explain the lack of <it>pfmdr1 </it>amplification. Indeed, this mutant codon is rarely associated with duplication of <it>pfmdr1 </it>gene. In Cameroon, the changes of therapeutic strategies and the simultaneous use of several formulations of ACT or other anti-malarials that are not officially recommended result in a complex selective pressure, rendering the prediction of the evolution of <it>P. falciparum </it>resistance difficult. This public health problem should lead to increased vigilance and regular monitoring.</p

Ecological characterization of the natural habitat of Sulla (Fabaceae) in Northeastern Algeria

As part of the evaluation and enhancement of plant genetic resources of fodder and pastoral interest in Algeria, a study of the ecological characterization of the natural habitat of Sulla coronaria (L.) Medik. (Syn. Hedysarum coronarium L., Fabaceae) was carried out in Northeastern Algeria. Following a collecting mission, 36 sites of Sulla were randomly selected. In each site, three soil samples were randomly collected. Sixteen soil parameters (soil pH, electrical conductivity, total limestone, total nitrogen, potassium, phosphorus, carbon, organic matter, the C/N ratio and particle composition) were analysed. Two factors related to topography (altitude) and climate (rainfall) of the natural habitat of S. coronaria were also considered. Variance analyses (univariate and multivariate) showed a high variation of the physical and chemical characteristics between the different sites. The pH varies between 8.1 and 8.94. In most cases, soils were characterized by a clayey texture, but the species may also adapt to other types of texture (clayey loam, silty clay loam, silty clay, silty). Cluster analysis highlighted five groups of sites. The altitude and rainfall seem to play a prominent part in the formation of these groups. Relations have also been found between certain characteristics of the soil and between altitude and rainfall in the natural habitat of the species. The effect of altitude seems to be more pronounced. This study will contribute to valorize and develop S. coronaria in the marginal, isolated and deprived areas where fertilizers are not economically advisableDans le cadre de l'évaluation et de la valorisation des ressources phytogénétiques d'intérêt fourrager et pastoral en Algérie, une étude portant sur la caractérisation écologique de l'habitat naturel de Sulla coronaria (L.) Medik. (Syn. Hedysarum coronarium L., Fabaceae) à été réalisée. Suite à une mission de prospection et de collecte menée dans le Nord-Est de l'Algérie, 36 sites spontanés de Sulla ont été choisis au hasard. Pour chaque site, trois échantillons de sol ont été prélevés de façon aléatoire. Seize paramètres ont été analysés (pH du sol, conductivité électrique, calcaire total, azote total, potassium, phosphore, carbone, matière organique, rapport C/N, composition de la texture du sol). Deux facteurs liés à la topographie (altitude) et au climat (pluviométrie) de l'habitat naturel de l'espèce ont également été considérés. Les analyses de variance, appliquées aux caractéristiques physiques et chimiques du sol, ont indiqué une importante variation entre les différents sites. Le pH du sol varie entre 8,1 et 8,94. Dans la majorité des cas, les sols sont caractérisés par une texture argileuse, mais l'espèce semble s'adapter à d'autre types de texture (argileux franc, argilo-limoneux franc, argilo-limoneux, limoneux). L'analyse hiérarchique à mis en relief cinq groupes de sites. L'altitude et la pluviométrie semblent jouer un rôle prépondérant dans la formation de ces groupes. Des relations ont également été établies entre certaines caractéristiques du sol, d'une part et entre l'altitude et la pluviométrie de l'habitat naturel de l'espèce d'autre part. L'effet de l'altitude semble cependant plus prononcé. Cette étude contribuera à la valorisation et au développement de S. coronaria dans les régions marginales, isolées et déshéritées du pays ou l'apport d'engrais n'est pas économiquement recommandable

Evolution of the levels of human leukocyte antigen G (HLA-G) in Beninese infant during the first year of life in a malaria endemic area: using latent class analysis

Abstract Background: HLA-G, a non-classical HLA class I antigen, is of crucial interest during pregnancy by inhibiting maternal immune response. Its role during infections is discussed, and it has been described that high levels of soluble HLA-G during childhood increase the risk of malaria. To explore more precisely interactions between soluble HLA-G and malaria, latent class analysis was used to test whether distinct sub-populations of children, each with distinctive soluble HLA-G evolutions may suggest the existence of groups presenting variable malaria susceptibility. Method: A study was conducted in Benin from 2010 to 2013 and 165 children were followed from birth to 12 months. Evolution of soluble HLA-G was studied by the latent class method. Results: Three groups of children were identified: one with consistently low levels of soluble HLA-G during follow-up, a second with very high levels and a last intermediate group. In all groups, low birth weight, high number of malaria infections and high exposure to malaria transmission were associated with high level of soluble HLA-G. Placental malaria was not. Presence of soluble HLA-G in cord blood increased the probability of belonging to the highest trajectory. Conclusion: These results, together with previous ones, confirm the important role of HLA-G in the individual susceptibility to malaria. Assaying soluble HLA-G at birth could be a good indicator of newborns more fragile and at risk of infections during childhood

Synthesis and Antiplasmodial Activity of New IndoloneN-Oxide Derivatives

Synthesis and Antiplasmodial Activity of New IndoloneN-Oxide Derivative