Efficacy of sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in southern Mauritania.

BACKGROUND: Until 2006, the Mauritanian Ministry of Health recommended chloroquine and sulfadoxine-pyrimethamine for first- and second-line treatment of uncomplicated malaria, respectively. This study assessed the clinical efficacy of sulfadoxine-pyrimethamine in Kobeni as first-line treatment. MATERIALS AND METHODS: This study included 55 patients with Plasmodium falciparum infections, who were treated with sulfadoxine-pyrimethamine and followed up for 28 days. Isolates were genotyped to distinguish between recrudescence and reinfection. Treatment success rates and survival were analysed per protocol to evaluate drug efficacy. RESULTS: After inclusion, 2 patients were excluded for protocol violations, and 3 patients were lost to follow-up. Of the remaining 50 patients (per protocol population), 43 (86%) had adequate clinical and parasitological responses. Of the 7 patients with treatment failure, 5 (10%) were early failures, while 2 (4%) had initially responded and had late clinical failure on day 7, associated with recrudescence. With the exception of one adult weighing 91 kg, all treatment failures occurred in children aged from 7 to 12 years. CONCLUSIONS: Sulfadoxine-pyrimethamine monotherapy was moderately effective but insufficiently reliable in view of the relatively high rate of early treatment failure. The high prevalence of chloroquine resistance found in earlier studies and the results of the present study on sulfadoxine-pyrimethamine justify the change in national policy and systematic use of artemisinin-based combination therapy for first-line treatment of P. falciparum malaria in Mauritania.

Prenatal exposure to maternal low or high protein diets induces modest changes in the adipose tissue proteome of newborn piglets.

The possibility that maternal diets during gestation could affect growth and tissue development of offspring and program their later phenotype is an emerging challenge in pig production. The objective of the current study was to investigate the effects of contrasted protein levels in diets of pregnant sows on the proteomic features of subcutaneous adipose tissue (SCAT) of the offspring at birth and its possible persistence later in age. Sows were fed control (Con), low (LP), or high protein (HP) diets throughout gestation. A subset of piglets was killed at 1 d of age for SCAT sampling. The remaining piglets were cross-fostered to nonexperimental sows during lactation. They were fed standard diets during postweaning and fattening periods until 186 d of age. Modifications in SCAT protein abundance shortly after birth were investigated by 2-dimensional gel electrophoresis followed by mass spectrometry. A total of 65 spots were found differentially expressed (P 0.10) in the 3 groups at d 186 of age. Enolase 1 has less abundance (P < 0.05) in LP pigs compared with Con pigs at this stage. In conclusion, the proteomics tool has allowed the identification of early changes in various molecular pathways of SCAT in response to the levels of maternal protein supply during gestation.

Erythrocyte invasion profiles are associated with a common invasion ligand polymorphism in Senegalese isolates of Plasmodium falciparum.

Plasmodium falciparum parasites use multiple ligand-receptor interactions to invade human erythrocytes. Variant expression levels of members of the PfRh and PfEBA ligand families are associated with the use of different erythrocyte receptors, defining invasion pathways. Here we analyse a major polymorphism, a large sequence deletion in the PfRh2b ligand, and erythrocyte invasion profiles in uncultured Senegalese isolates. Parasites vary considerably in their use of sialic acid-containing and protease-sensitive erythrocyte receptors for invasion. The erythrocyte selectivity index was not related to invasion pathway usage, while parasite multiplication rate was associated with enhanced use of a trypsin-resistant invasion pathway. PfRh2b protein was expressed in all parasite isolates, although the PfRh2b deletion was present in a subset (approximately 68%). Parasites with the PfRh2b deletion were found to preferentially utilize protease-resistant pathways for erythrocyte invasion. Sialic acid-independent invasion is reduced in parasites with the PfRh2b deletion, but only in isolates derived from blood group O patients. Our results suggest a significant role for PfRh2b sequence polymorphism in discriminating between alternative erythrocyte receptors for invasion and as a possible determinant of virulence.

Distinct physiological states of Plasmodium falciparum in malaria-infected patients.

Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in children, ranging from mild flu-like symptoms to coma and death. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown. Studies of in vitro gene expression have found few transcriptional differences between different parasite strains. Here we present a large study of in vivo expression profiles of parasites derived directly from blood samples from infected patients. The in vivo expression profiles define three distinct transcriptional states. The biological basis of these states can be interpreted by comparison with an extensive compendium of expression data in the yeast Saccharomyces cerevisiae. The three states in vivo closely resemble, first, active growth based on glycolytic metabolism, second, a starvation response accompanied by metabolism of alternative carbon sources, and third, an environmental stress response. The glycolytic state is highly similar to the known profile of the ring stage in vitro, but the other states have not been observed in vitro. The results reveal a previously unknown physiological diversity in the in vivo biology of the malaria parasite, in particular evidence for a functional mitochondrion in the asexual-stage parasite, and indicate in vivo and in vitro studies to determine how this variation may affect disease manifestations and treatment.

[Clinical and psychopathological postpartum depression: eleven Senegalese cases report]. / Aspects cliniques et psychopathologiques de la dépression du postpartum: rapport d'une série de onze cas sénégalais.

INTRODUCTION: The postpartum depression is a frequent puerperium psychiatric disorder. The authors study the clinical, therapeutic and evolutionary aspects of the postpartum depression among eleven Senegalese women. MATERIAL AND METHOD: They examined the medical reports and hospital registers of eleven patients belonging to a sample of 52 women presenting psychic disorders of the puerperality. The diagnosis was made by using the International Classification of the Diseases. RESULTS: The symptoms of depression were irritability, bad concentration, multiple somatic complaints, of insomnia of drowsiness, loss of the usual interests. All the patients profited from psychotherapy and have received chemotherapy with antidepressant treatment associated tranquillizing in six cases. They improved from 29 to 43 days after their admission. CONCLUSION: The pregnancy and the childbirth, the parity, personal history of the patient, their social environment and the cultural representations of maternity are factors of depression of the postpartum. The antidepressant is always essential in the treatment.

Aspects cliniques et psychopathologiques de la depression du postpartum : rapport d'une serie de onze cas senegalais

Introduction : La depression du post-partum occupe une place importante parmi les accidents psychiatriques de la puerperalite. Les auteurs rapportent les differents aspects cliniques; therapeutiques et evolutifs de la depression du post-partum dans une serie de onze cas senegalais. Materiel et methode : Il s'agit d'un travail mene a partir des observations medicales et des registres d'hospitalisation d'une serie de 11 patientes appartenant a un echantillon de 52 femmes presentant des troubles psychiques de la puerperalite. Le diagnostic a ete fait en utilisant la classification internationale des maladies. Resultats : Sur le plan clinique les symptomes de depression etaient constitues principalement d'irritabilite; de troubles de la concentration; de plaintes somatiques multiples; d'insomnie d'endormissement; de perte des interets habituels. Pour la prise en charge; toutes nos patientes ont beneficie d'une psychotherapie de soutien et d'un traitement antidepresseur; associes a un traitement tranquillisant dans six cas. L'evolution a ete favorable au bout de 29 a 43 jours d'hospitalisation. Conclusion : Le vecu de la grossesse et de l'accouchement; la parite; l'histoire personnelle de la patiente; son environnement et les representations culturelles de la maternite sont des facteurs de depression du postpartum. Le traitement antidepresseur est dans tous les cas indispensable

Defining the origin of Plasmodium falciparum resistant dhfr isolates in Senegal.

We previously reported a high baseline prevalence of mutations in the dhfr and dhps genes of Plasmodium falciparum throughout Senegal. The highest prevalence of the triple dhfr pyrimethamine associated mutations were found in isolates obtained in the western part of the country near the capital city of Dakar. In this study, we sought out to determine the relatedness of dhfr wild type and mutated strains by analyzing three microsatellite regions upstream of the dhfr locus. Twenty-six of the 31 wild type strains had a unique microsatellite pattern. In contrast, of the 17 isolates containing the triple mutation in dhfr, 11 had an identical microsatellite pattern. Diverse geographical isolates in Senegal containing the triple dhfr mutation have arisen from a limited number of ancestral strains. In addition, we demonstrate that these isolates have shared ancestry with the previously reported triple mutation haplotype found in Tanzania, South Africa, and southeast Asia. This common ancestry may have implications for the malaria control strategy for reducing the spread of sulfadoxine-pyrimethamine resistance in Senegal and elsewhere in Africa.

Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase genes in Senegal.

Senegal recently (2004) switched to sulfadoxine-pyrimethamine (SP) with amodiaquine as first line therapy for malaria in response to increasing chloroquine resistance. In anticipation of emerging resistance to SP as a result of this change in drug pressure, we set out to define the baseline prevalence of SP-associated mutations in the dhfr and dhps genes in Plasmodium falciparum using geographically diverse and longitudinally collected samples. A total of 153 blood samples were analysed from patients (5 years or older) with mild malaria after informed consent was obtained. Longitudinal samples were collected between 2000 and 2003 in Pikine, a suburb of Dakar. Geographically diverse site sampling was carried out in 2003. The mutation prevalence in DHFR codons 51, 59 and 108 is 65%, 61% and 78% in Pikine, 2003. The overall prevalence of the triple mutation that is associated with high-level pyrimethamine resistance is 61%. The mutation prevalence rate in DHPS codons 436 and 437 is 21% and 40%, respectively. There is significant geographic variation in genotypic resistance, as samples from Pikine in 2003 had higher mutation prevalence in the pfdhfr and pfdhps genes compared to samples from Tambacounda (P < 0.015). In summary, this study demonstrates a high background prevalence of SP resistance mutations already present in P. falciparum in Senegal.

Bayesian analysis of an epidemiologic model of Plasmodium falciparum malaria infection in Ndiop, Senegal.

Plasmodium falciparum has a complex transmission cycle. Public health planning and research would benefit from the ability of a calibrated model to predict the epidemiologic characteristics of populations living in areas of malaria endemicity. This paper describes the application of Bayesian calibration to a malaria transmission model using longitudinal data gathered from 176 subjects in Ndiop, Senegal, from July 1, 1993, to July 31, 1994. The model was able to adequately predict P. falciparum parasitemia prevalence in the study population. Further insight into the dynamics of malaria in Ndiop was provided. During the dry season, the estimated fraction of nonimmune subjects goes down to 20% and then increases up to 80%. The model-predicted time-weighted average incidences contributed by nonimmune and immune individuals are 0.52 cases per day and 0.47 cases per day, respectively. The median times needed to acquire infection (conversion delay) for nonimmune and immune individuals are estimated at 39 days and 285 days, respectively.

[A baobab solution for the prevention and treatment of acute dehydration in infantile diarrhea]. / Une solution de pain de singe pour la prévention et le traitement de la déshydratation aiguë due aux diarrhées infantiles.

OBJECTIVE: The purpose of this study was to compare the clinical efficacy of a local solution based on "pain de singe", fruit of baobab (Adansonia digitata), and the WHO standard solution in the treatment of children with acute diarrhea and resulting mild to moderate dehydration. METHODOLOGY: A prospective clinical trial comparing the local solution to the standard WHO solution was conducted; in children of 6 months or older (mean age = 16.6 +/- 8.8 months), 79 received the WHO solution and 82 the local solution, and were followed for a period ranging from 4 to 48 hours. Evolution of diarrhea and weight gain were evaluated as variables of interest. RESULTS: WHO solution was found to be superior, but not statistically significant in term of duration of diarrhea and weight gain. DISCUSSION: The pain de singe based solution presents additional advantages: nutritional, economic and cultural; we recommend it to promote use of TRO at home.

Une solution de pain de singe pour la prevention et le traitement de la deshydratation aigue due aux diarrhees infantiles

L'objectif de cette etude etait d'evaluer de maniere comparative; les resultats de la therapie de rehydratation par voie orale (TRO) avec la solution standard obtenue avec les sachets de l'OMS et une solution a base de pulpe de fruit de baobab (Adansonia digitata); pain de singe; chez les enfants presentant une diarrhee aigue. Un essai clinique de TRO a ete mene chez des enfants diarrheiques; ages de 6 mois a 57 mois et presentant une diarrhee ou une deshydratation moyenne ; 79 enfants ont recu la solution OMS et 82 la solution de pain de singe ; l'evolution de la diarrhee et le gain de poids ont ete evalues. La solution OMS a eu des resultats legerement superieurs a ceux de la solution a base de pain de singe; quant a l'amelioration de la diarrhee et au gain de poids aux 4eme et 48eme heures; mais cette difference etait statistiquement non significative. La solution a base de pain de singe presente en outre des avantages sur le plan nutritif; economique et socio-culturel ; les auteurs la recommandent; en vue d'une utilisation plus etendue de la TRO a domicile