In vitro susceptibility of Candida albicans clinical isolates to eight antifungal agents in Ouagadougou (Burkina Faso).

INTRODUCTION: In recent years, the infection Candida albicans infection worldwide has risen, and the incidence of resistance to traditional antifungal therapies is also increasing. The aim of this study was to evaluate in vitro susceptibility of C. albicans clinical isolates to eight antifungal agents in Ouagadougou. MATERIALS AND METHODS: A cross-sectional study was conducted from January 2013 to December 2015 at Yalgado Ouédraogo University Teaching Hospital. Two hundred seven strains have been isolated from 347 symptomatic patients received in different clinical services. Samples were cultured on Sabouraud Dextrose Agar supplemented with Cloramphenicol. Isolates were diagnosed as C. albicans using germ tube test, chlamydospore formation on Corn Meal Agar, and Api-Candida test (Biomérieux). Antifungal susceptibility testing was performed by disk diffusion method and isolates classified as susceptible, susceptible dose-dependent and resistant. RESULTS: Three hundred forty-seven (347) patients are included in this study. Two hundred and six (206) out of 347 collected samples (59.36%) were found positive for C. albicans. The strains were mostly isolated from vulvovaginal (49%) and oral infections (40.3%). The highest resistance rates of azoles were obtained with fluconazole (66.5%), itraconazole (52.3%) and ketoconazole (22.9%) when all clinical isolates were included. The resistance rates of fluconazole, itraconazole and ketoconazole remain highest for vulvovaginal and oral isolates. The rate of resistance to the polyene amphotericin B was 32.0% for all clinical isolates and was 56.4% for vulvovaginal strains. Resistance rate to nystatin was 6.3% for all clinical isolates. Cross-resistance analysis with data of all clinical strains revealed that the incidence of resistance to ketoconazole and itraconazole in fluconazole-resistant isolates was significantly higher than recorded for fluconazole-susceptible isolates. CONCLUSION: In vitro C. albicans antifungal susceptibility test in this study showed relatively high resistance to commonly and widely used azoles (fluconazole, ketoconazole). Most C. albicans clinical isolates were susceptible to nystatin.

Facteurs associés à la qualité de vie de patients souffrant du diabète de type 2 au Burkina Faso

Le diabète est une maladie responsable de complications qui aggravent le risque de mortalité chez les malades. au Burkina Faso, très peu de données existent sur la qualité de vie des patients souffrant du diabète de type 2. l'objectif de l'étude est de decrire la qualité de vie des patients diabétiques de type 2 dans les deux principales villes du pays. il s'agit d'une étude transversale descriptive qui a inclus des patients de Ouagadougou et Bobo-dioulasso souffrant de diabète de type 2 et suivis par un spécialiste dans les hôpitaux publiques et les cliniques privées. au total cent 100 (patients) ont été inclus dans l'étude. les informations sociodémographiques et cliniques ont été collectées à partir de questionnaires adminitrés en vis-à-vis par des enquêteurs formés. la perception de la qualité de vie a été mesurée sur une échelle de 10 (10/10 = vit parfaitement avec sa maladie ; 0/10 = ne vit pas du tout parfaitement avec sa maladie). le patient était considéré comme mécontent de sa qualité de vie si le score était < 5. une analyse descriptive pour explorer l'échantillon a été réalisée. ensuite, une analyse factorielle des correspondances multiples a été effectuée pour analyser la relation entre les caractéristiques des patients et la qualité de vie perçue. dans l'échantillon, il y avait 52 % (52) d'hommes et 61 % (61) des patients avaient plus de 50 ans. la plupart des patients étaient mariés, chefs de ménage, et avaient un travail. au total, 39 % (39) des patients ne vivaient pas du tout parfaitement avec leur maladie. les facteurs qui contribuent à la première dimension (65,2 % de l'inertie) appelée « répercussions de la maladie » étaient celle décrivant l'impact du diabète sur la vie professionnelle (12,2 %), économique (11,2 %), sociale (9,4 %) et familiale (3,8 %) du patient. les facteurs qui contribuent à la deuxième dimension (27,37 % de l'inertie) appelée « complications de la maladie » étaient les complications cardiovasculaires (16,6 %), nerveuses (12,5 %, rénales (11,2 %), et oculaires (9,2 %), et le fait d'avoir une durée de la maladie d'au moins 5 ans (7,5 %). l'étude a montré que le diabète de type 2, a non seulement des répercussions sur la vie professionnelle, économique, sociale et familiale, mais aussi des repercussions en termes de complications cliniques qui impactent négativement sur la qualité de vie des malades. une stratégie de promotion de santé centrée sur la sensibilisation de l'entourage des malades et l'accessibilité aux soins permettraient d'améliorer la santé des patients souffrant de diabète de type 2

Effect of increased ART-CPT uptake on tuberculosis outcomes and associated factors, Burundi, 2009-2013.

We retrospectively examined 3579 records of human immunodeficiency virus infected tuberculosis (TB) patients diagnosed from January 2009 to June 2013 in 55 TB treatment facilities in Burundi, to demonstrate whether improvement of combined cotrimoxazole preventive therapy and antiretroviral therapy (ART) uptake was accompanied by improvement of treatment outcomes, and to describe associated factors. Treatment success rates increased from 71% to 80% (P < 0.001). While loss to follow-up and transfer-out rates declined significantly, death rates decreased modestly, and remained high, at 14%. ART uptake was worse in suburban areas and private for-profit institutions. World Health Organization targets could be achieved if peripheral health facilities were prioritised.

Une étude rétrospective conduite de janvier 2009 à juin 2013 au Burundi chez 3579 patients co-infectées par la tuberculose (TB) et le virus de l'immunodéficience humaine dans 55 centres de diagnostic et de traitement de la TB, décrit l'évolution des résultats de traitement antirétroviral (ART) et cotrimoxazole et apprécie les facteurs liés à l'ART. La proportion des succès au traitement a augmenté de 71% à 80% (P < 0,001). Tandis que les taux de perdus de vue et de transferts ont baissé significativement, celui des décès n'a baissé que modestement, tout en restant élevée, à 14%. La couverture en ART est plus faible dans les centres de santé périphériques et dans ceux relevant du privé non lucratif. Les objectifs de l'Organisation Mondiale de la Santé pourraient être atteints si les districts sanitaires ruraux étaient inclus dans la fourniture des soins.

En el presente estudio se analizaron 3579 registros de pacientes aquejados de coinfección por el virus de la inmunodeficiencia humana (VIH) y la tuberculosis (TB) en Burundi de enero del 2009 a junio del 2013, provenientes de 55 establecimientos de tratamiento de la TB, con el objeto de investigar si al aumentar la aceptación del tratamiento preventivo con cotrimoxazol en asociación con el tratamiento antirretrovírico (ART) se mejoraban los desenlaces terapéuticos y también se describieron los factores que se asociaban con esta situación. Las tasas de éxito terapéutico aumentaron de un 71% a un 80% (P < 0,001). Aunque las tasas de pérdida durante el seguimiento y de remisión a otros establecimientos disminuyeron de manera significativa, la disminución de las tasas de mortalidad fue leve y permanecieron en un nivel alto de 14%. La aceptación del ART fue más deficiente en las zonas suburbanas y en los establecimientos privados con ánimo de lucro. Sería posible cumplir con las metas de la Organización Mundial de la Salud si se da prioridad a los establecimientos sanitarios periféricos.

Treatment of nonunion in neglected long bone shaft fractures by osteoperiosteal decortication.

UNLABELLED: In emerging countries, nonunion in the shaft of fractured long bones is common. PATIENTS AND METHODS: In a 3-year long prospective study, 50 patients (38 men, 12 women) with an average age of 40.9 years (range 17-60) were treated for neglected diaphyseal nonunion an average of 11 months (range 6-48) after the fracture event. The femur was involved 14 times, tibia 22 times, humerus eight times and forearm bones six times. All of these patients had consulted initially with a traditional bone setter at the time of fracture. The surgical procedure consisted of osteoperiosteal decortication followed by repermeabilization of the medullary canal and then internal fixation. Compression plating was used for the humerus, radius and ulna. Nonunion of the middle-third of the femur and tibia was treated by intramedullary nailing and nonunion of the proximal third of the femur with an inverted DCS screw-plate. Patients were reviewed clinically and with X-rays on postoperative days 21, 45, 90 and 120. RESULTS: Bone union was obtained in under 90 days in the upper limb and under 120 days in the lower limb. No additional grafting was needed. There were only two cases of leg length differences. DISCUSSION: Osteoperiosteal decortication is a reliable technique that leads to predictable, satisfactory results, given the limited materials required to treat long bone nonunion in emerging countries.

User fees and access to ARV treatment for persons living with HIV/AIDS: implementation and challenges in Burkina Faso, a limited-resource country.

Access to antiretroviral (ARV) treatment remains a crucial problem for patients living with HIV/AIDS (PLWHA) in limited-resources countries. Some African countries have adopted the principle of providing ARV free of charge, but Burkina Faso opted for a direct out-of-pocket payment at the point of care delivery, with subsidized payments and mechanisms for the poorest populations to receive these services free of charge. Our objectives were to determine the proportion of PLWHA who pay for ARV and to identify the factors associated with ARV access in Burkina Faso. A cross-sectional study was performed in 13 public health facilities, 10 Nongovernmental Organizations and association health facilities, and three faith-based health facilities. In each facility, 20 outpatients receiving ARV were interviewed during a routine clinic visit. A multivariate analysis by logistic regression was performed. Among the expected 520 patients receiving ARV, 499 (96.0%) were surveyed. The majority of patients (79%) did not pay for their ARV treatment, thereby limiting cost recovery from patient payments. In a multivariate analysis, level of education and income were associated with free access to ARV. Patients with no education more frequently received free ARV than those who had received some level of education (OR 2.7, 95% CI [1.3-5.6]). Patients without any income or with less than US$10 per month were more likely to receive free ARV (OR 2.6 [95% CI 1.3-5.2]) than those who earned more than US$10 per month. However, 16% of patients without any income and 21% of those without employment paid for ARV, and the costs of drugs for opportunistic infections, food, and transport remained a burden for 85%, 91%, and 74%, respectively, of those who did not pay for ARV. Free access to a minimum care package for every PLWHA would enhance access to ARV.

Neonatal haemoglobinopathy screening in Burkina Faso.

AIMS: To report our experience of neonatal screening for sickle cell disease in Ouagadougou (Burkina Faso) and to discuss the feasibility of neonatal screening in this country. METHODS: Between the years 2000 and 2004, there were about 2,341 births in five maternity services in Ouagadougou. These babies were screened for sickle cell disease in a universal screening pilot programme. In 2006, 53 babies born to selected couples were screened. The specimens were collected either by cord blood sampling or from a dried blood spot on filter paper. The screening was performed using an isoelectric focusing technique. RESULTS: In the first stage (2000-4), the incidence of sickle cell disease was 1:57. In the second stage, six of 53 babies of selected couples were found to have major haemoglobinopathies: one was homozygous for haemoglobin S and five were compound heterozygotes for haemoglobins S and C. CONCLUSIONS: The results suggest that a national screening programme should be implemented in Burkina Faso with effective newborn and subsequent follow-up, but a methodology needs to be developed.

Neonatal screening and clinical care programmes for sickle cell disorders in sub-Saharan Africa: lessons from pilot studies.

OBJECTIVES: Despite the widespread use of neonatal screening programmes for sickle cell disease in Western regions, few studies have focused on the special healthcare needs in sub-Saharan African countries. The purpose of this review is to evaluate the need for a neonatal screening programme for sickle cell disease, and if justified, to propose a realistic healthcare programme for sickle cell newborns in those countries based on personal experiences in Kinshasa (Democratic Republic of the Congo) and Ouagadougou (Burkina Faso) as well as from a review of the literature. REVIEW: There are well-established criteria for the development of neonatal screening programmes for sickle cell disease in sub-Saharan African countries. In particular, in regions where incidence of the disease is 0.5 per 1000 or higher, a sickle cell screening programme can be proposed that includes the systematic screening of all newborns, or the targeted screening of those newborns who have a mother with a sickle cell or haemoglobin C trait. Screening should be preferentially organized using cord blood, with a simple, effective and affordable screening method such as isoelectric focusing. If necessary, confirmation of results should be performed using another cost-effective technique such as citrate agar electrophoresis at an acidic pH. There is also a need for a sickle cell disease clinical care programme which should include: infection prophylaxis with penicillin and malarial prophylaxis; family training to identify early severe or persistent symptoms and the gravity of malarial crises; the evaluation of nutritional status and adequate fluid intake; and the importance of regular medical visits. Improved knowledge of the diagnosis was found to reduce the need for unnecessary and unsafe blood transfusions. CONCLUSIONS: This paper provides an overview of practices employed in neonatal screening and clinical care programmes for sickle cell disease in sub-Saharan African countries. The development of these programmes is pivotal to improving the health care of those affected by haemoglobin disorders. However, such programmes require major economic and organizational resources, which must taken into account and balanced against other local health priorities.

Satisfaction with health services for STIs, HIV, AIDS among a high-risk population in West Africa.

The goal of this study was to develop an instrument and assess the degree of satisfaction regarding HIV/STIs services for women working in, associated with, or living in or nearby, prostitution environments. This study took place in seven West-African countries (Benin, Burkina Faso, Ghana, Mali, Niger, Senegal, Togo) participating in the West Africa Aids Program (AIDS3). A validated six-dimension questionnaire was used to interview 698 women. The main inclusion criterion was having had recourse to adapted services offered through the AIDS3 program in the last six months. Results showed that women surveyed are satisfied overall. Two dimensions scored low: 'Technical skills perceived' and 'Accessibility'. Regression analyses showed that those most satisfied were women who had used the adapted services many times and women connected with community groups. Although these results are consistent with results published previously in other contexts, they now allow the AIDS3 program to consider the voices of women rarely listened to: West-African women living and working in prostitution environments.

[Genetic diversity of P. falciparum and pathogenesis of the severe malarial anaemia in children under 5 years old in the province of Boulgou, Burkina Faso]. / Diversité génétique de Plasmodium falciparum et pathogénie de l'anémie palustre sévere chez des enfants de moins de 5 ans de la province du Boulgou, Burkina Faso.

The clinical presentation of malaria mainly the severe form may be related to Plasmodium falciparum msp-2 (merozoite surface protein 2) specific family To verify this hypothesis, during the high malaria transmission season in 2001; we analyzed the allelic polymorphism of the msp-2 gene of P. falciparum in children under 5 years old with different presentation of malaria in the regional Hospital and at community level in the Boulgou Province (Burkina Faso). A total of 405 children (107 severe malarial anaemia cases, 102 severe malaria cases without severe anaemia and 196 non severe malaria cases) were enrolled in the study. The frequencies of the FC27 were 89.2% in severe malarial anaemia children group, then 89.7% and 86.9% respectively in severe malaria non anaemic children cases and non severe malaria cases (P = 0.4). The frequencies of the 3D7 were 72.5%; 84.1% and 77% respectively severe malaria non anaemic children, severe malarial anaemia cases and non severe malaria cases (P = 0.7). The complexity of the FC27 genotypes was significantly higher in children with severe malaria (with and without severe anaemia) compared to the non severe malarial children (P << 0.001). No significant difference was pointed up in the complexity of the 3D7 genotypes.

Tumor-suppression function of transcription factor USF2 in prostate carcinogenesis.

Although the transcription factor USF2 has been implicated in the regulation of cellular growth and proliferation, it is unknown whether alterations in USF2 contribute to tumorigenesis and tumor development. We examined the role of USF2 in prostate tumorigenesis. Western blot analysis revealed markedly decreased USF2 levels in three androgen-independent prostate cancer cell lines, PC-3, DU145, and M12, as compared to nontumorigenic prostate epithelial cells or the androgen-dependent cell line, LNCaP. Ectopic expression of USF2 in PC-3 cells did not affect the cell proliferation rate of PC-3 cells on plastic surfaces. However, it dramatically decreased anchorage-independent growth of PC-3 cells in soft agar (90-98% inhibition) and the invasion capability (80% inhibition) of PC-3 cells in matrix gel assay. Importantly, expression of USF2 in PC-3 cells inhibited the tumorigenicity of PC-3 cells in an in vivo nude mice xenograft model (80-90% inhibition). These results suggest that USF2 has tumor-suppression function. Consistent with its function in tumor suppression, we found that the USF2 protein is present in normal prostate epithelial cells but absent in 18 of 42 (43%) human prostate cancer tissues (P = 0.015). To further examine the functional role of USF2 in vivo, we generated mice with genetic deletion of USF2 gene. We found that USF2-null mice displayed marked prostate hyperplasia at a young age, suggesting that USF2 is involved in the normal growth and differentiation of prostate. Together, these studies demonstrate that USF2 has tumor-suppressor function and plays a role in prostate carcinogenesis.

[Plasma lipids profile of non treated HIV infected adults in Ouagadougou (Burkina Faso)]. / Profil lipidique au cours de l'infection par le VIH à Ouagadougou - Burkina Faso: intérêt des marqueurs lipidiques dans le suivi de l'évolution de l'infection à VIH.

Many authors reported metabolic perturbations in connection with HIV infection. The aim of this studies was to determinate plasma lipids profile in non treated HIV infected adults in Ouagadougou (Burkina Faso). The results obtain with 187 HIV infected patients showed a significative (p < 10(-6)) high level of LDL, triglycerid, atherogenic indice; HDL was decreased. The atherogenic risk is increased with lymphocytes CD4 depletion. Plasma lipids levels must be consider in the choice of antiretroviral treatment.

[Neonatal screening of glucose-6-phosphate dehydrogenase deficiency in umbilical cord blood]. / Dépistage néonatal du déficit en glucose-6-phosphate déshydrogénase (G6PD) sur sang de cordon.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most frequent enzyme deficiency. It is a sex-linked genetic disease concerning mostly african, mediterranean and far-eastern populations. The main clinical expression is a hemolytic anemia which can be acute or chronic. During the neonatal period the disease may manifest as neonatal jaundice. We have been asked by the neonate department to set up a blood screening test for this deficiency. We have therefore developed a test using umbilical cord blood. The assay of G6PD has been automatised and red blood cell aspartate-amino-transferase (ASAT) chosen as a reference enzyme to evaluate the age of red blood cells. Normal values of G6PD, ASAT and G6PD/ASAT ratio have been calculated from 235 cord samples. Genetic frequency of this deficiency in 2002 was 6% in male and 1% in female newborns.

The transcription factors MTF-1 and USF1 cooperate to regulate mouse metallothionein-I expression in response to the essential metal zinc in visceral endoderm cells during early development.

During early development of the mouse embryo, expression of the metallothionein-I (MT-I) gene is heightened specifically in the endoderm cells of the visceral yolk sac. The mechanisms of regulation of this cell-specific pattern of expression of metallothionein-I are unknown. However, it has recently been shown that MTF-1, functioning as a metalloregulatory transcription factor, activates metallothionein genes in response to the essential metal zinc. In contrast with the metallothionein genes, MTF-1 is essential for development; null mutant embryos die due to liver degeneration. We report here that MTF-1 is absolutely essential for upregulation of MT-I gene expression in visceral endoderm cells and that optimal expression also involves interactions of the basic helix-loop-helix upstream stimulatory factor-1 (USF1) with an E-box1-containing sequence at -223 bp in the MT-I promoter. Expression of MT-I in visceral endoderm cells was dependent on maternal dietary zinc. Thus, the essential metal, zinc, apparently provides the signaling ligand that activates cell-specific MT-I expression in visceral endoderm cells.

The USF proteins regulate transcription of the follicle-stimulating hormone receptor but are insufficient for cell-specific expression.

Expression of the FSH receptor (FSHR) is limited to granulosa cells of the ovary and Sertoli cells of the testis. Previous studies showed that an E box in the proximal promoter of the FSHR gene is required for transcription and that the predominant E box binding proteins are the ubiquitous transcription factors, upstream stimulatory factor 1 (USF1) and USF2. Through cotransfection analysis, we have shown that both wild-type and dominant negative forms of the USF proteins regulate the rat FSHR promoter and that transcriptional activation of FSHR required several domains within the amino-terminal portion of the USF proteins. Analysis of the FSHR promoter region using in vivo genomic footprinting indicated that the E box is occupied by proteins in Sertoli cells but not in cells that fail to express the receptor, despite the presence of the USF proteins. To help delineate the regions of the rat FSHR gene required for correct spatial and temporal expression, transgenic mice harboring two constructs containing variable amounts of 5'-flanking sequence (5,000 bp and 100 bp) were generated. Examination of 16 different transgenic lines revealed varied transgene expression profiles with multiple lines having different amounts of ectopic expression and two lines failing to express the transgene. In addition, little or no expression was observed in Sertoli cells. These studies indicate that additional regulatory sequences outside the region from -5,000 to +123 bp are needed for proper expression in Sertoli cells.

Spatial organization of RNA polymerase II transcription in the nucleus.

In eukaryotic cells, mRNA synthesis is carried out by large, multifunctional complexes that are also involved in coordinating transcription with other nuclear processes. This survey focuses on the distribution and structural arrangement of these complexes within the nucleus, in relationship with the discrete positioning of particular chromosomal loci. To better understand the link between the spatial organization of the nucleus and the regulation of gene expression, it is necessary to combine information from biochemical studies with results from microscopic observations of preserved nuclear structures. Recent experimental approaches have made this possible. The subnuclear locations of specific chromosome loci, RNA transcripts, RNA polymerases, and transcription and pre-mRNA-processing factors can now be observed with computer-assisted microscopy and specific molecular probes. The results indicate that RNA polymerase II (RNAPII) transcription takes place at discrete sites scattered throughout the nucleoplasm, and that these sites are also the locations of pre-mRNA processing. Transcribing polymerases appear to be grouped into clusters at each transcription site. Cell cycle-dependent zones of transcription and processing factors have been identified, and certain subnuclear domains appear specialized for expression or silencing of particular genes. The arrangement of transcription in the nucleus is dynamic and depends on its transcriptional activity, with the RNAPII itself playing a central role in marshalling the large complexes involved in gene expression.

Loss of USF transcriptional activity in breast cancer cell lines.

USF is a family of transcription factors that are structurally related to the Myc oncoproteins and also share with Myc a common DNA-binding specificity. USF overexpression can prevent c-Myc-dependent cellular transformation and also inhibit the proliferation of certain transformed cells. These antiproliferative activities suggest that USF inactivation could be implicated in carcinogenesis. To explore this possibility, we compared the activities of the ubiquitous USF1 and USF2 proteins in several cell lines derived from either normal breast epithelium or breast tumors. The DNA-binding activities of USF1 and USF2 were present at similar levels in all cell lines. In the non-tumorigenic MCF-10A cells, USF in general, and USF2 in particular, exhibited strong transcriptional activities. In contrast, USF1 and USF2 were completely inactive in three out of six transformed breast cell lines investigated, while the other three transformed cell lines exhibited loss of USF2 activity. Analyses in cells cultured from healthy tissue confirmed the transcriptional activity of USF in normal human mammary epithelial cells. These results demonstrate that a partial or complete loss of USF function is a common event in breast cancer cell lines, perhaps because, like Myc overexpression, it favors rapid proliferation.

Upstream stimulatory factor regulates major histocompatibility complex class I gene expression: the U2DeltaE4 splice variant abrogates E-box activity.

The tissue-specific expression of major histocompatibility complex class I genes is determined by a series of upstream regulatory elements, many of which remain ill defined. We now report that a distal E-box element, located between bp -309 and -314 upstream of transcription initiation, acts as a cell type-specific enhancer of class I promoter activity. The class I E box is very active in a neuroblastoma cell line, CHP-126, but is relatively inactive in the HeLa epithelial cell line. The basic helix-loop-helix leucine zipper proteins upstream stimulatory factor 1 (USF1) and USF2 were shown to specifically recognize the class I E box, resulting in the activation of the downstream promoter. Fine mapping of USF1 and USF2 amino-terminal functional domains revealed differences in their abilities to activate the class I E box. Whereas USF1 contained only an extended activation domain, USF2 contained both an activation domain and a negative regulatory region. Surprisingly, the naturally occurring splice variant of USF2 lacking the exon 4 domain, U2DeltaE4, acted as a dominant-negative regulator of USF-mediated activation of the class I promoter. This latter activity is in sharp contrast to the known ability of U2DeltaE4 to activate the adenovirus major late promoter. Class I E-box function is correlated with the relative amount of U2DeltaE4 in a cell, leading to the proposal that U2DeltaE4 modulates class I E-box activity and may represent one mechanism to fine-tune class I expression in various tissues.