Cerebral venous thrombosis in a sub-saharan African country: A preliminary monocentric study of a 70 case series at the neurology department of Fann teaching hospital in Dakar - Senegal.

INTRODUCTION: Cerebral venous thrombosis (CVT) are underdiagnosed in sub-saharan Africa where publications are uncommon. Our study aim was to describe the CVT diagnostic and therapeutic features through a senegalese case series. PATIENTS AND METHOD: A monocentric retrospective and prospective study was conducted at the adult Neurology department of Fann Teaching Hospital in Dakar (Senegal), between January 01, 2013 and April 30, 2020. It had included all CVT cases diagnosed by neurovascular imaging. RESULTS: Seventy CVT cases were collected including 48 women (68.6%). The average age of the patients was 35.2±14 years. The main neurological signs were headache (92.8%) and motor deficit (41.4%), with subacute onset in 67.2% of cases. The superior sagittal sinus (54.3%) and the transverse sinus (38.6%) were the most affected with multiple involvements in 27 patients (38.6%). Thirty patients (42.8%) had indirect parenchymal signs such as venous infarction (15.7%), cerebral edema (11.4%) or intracerebral hemorrhage (12.8%). The etiological factors were mostly infectious (41.4%) with meningoencephalitis (12.8%) and otorhinolaryngological infection (10%). Gyneco-obstetric factors (27%) and Behçet's disease (7%) were the main aseptic factors. In the short-term clinical course, curative anticoagulation (98.6%) had enabled a favourable outcome (mRS 0-1) in half of the patients. CONCLUSION: Our study, the largest series in sub-saharan Africa to this date, confirms that CVT is a young women disease. Infectious etiology is the most frequent at the Fann national teaching hospital (41.4% in Dakar against 6.5% in Germaine Bousser's series) even if the etiological assessment is limited by financial constraints (no coagulopathy/thrombophilia check-up).

[Neuro-Behçet in a Sub-Saharan Africa Country: a Series of Sixteen Patients in Fann Teaching Hospital, Dakar, Senegal]. / Neuro-Behçet dans un pays d'Afrique subsaharienne : une série de 16 patients au centre hospitalier national universitaire de Fann de Dakar, Sénégal.

Neuro-Behçet (NB) African studies are mainly North African, but Sub-Saharan Africa is not to be outdone. Our aim was to describe diagnostic and therapeutic features of NB in a Senegalese series collected in Dakar. This was a descriptive and retrospective study conducted at the Neurology department of Fann Teaching Hospital in Dakar, Senegal. All patients who met the NB's diagnostic criteria were included. Sixteen patients were collected, 14 males and 2 females with an average age of 40 years [18-71]. The main neurological signs were motor deficit (13 cases), headache (10 cases), and language disorders (4 cases). Extra-neurological signs were dermatological (14 cases), ocular (2 cases), and articular (2 cases) with aseptic unilateral gonarthritis. Fever was present in 9 patients. Neurological involvement was mostly isolated parenchymal (8 cases) or mixed (6 cases). The main clinical forms of NB were rhombencephalitis (8 cases) and retrobulbar optic neuritis (4 cases). Seven patients had a cerebral angio-Behçet with cerebral venous thrombosis (3 cases), ischemic stroke (2 cases), and intracerebral hematoma (2 cases). Under prednisone (16 cases) and azathioprine (3 cases), the short-term clinical outcome was mostly favorable (14 cases) with a modified Rankin scale at 2. NB is an under-diagnosed adult male disease in Sub-Saharan Africa and further studies are needed.

Les études africaines sur le neuro-Behçet (NB) sont majoritairement maghrébines, mais l'Afrique noire n'est pas en reste. L'objectif de l'étude était de décrire les particularités diagnostiques et thérapeutiques du NB dans une série sénégalaise colligée à Dakar. Il s'agit d'une étude rétrospective à visée descriptive menée à la clinique de neurologie du centre hospitalier universitaire de Fann de Dakar, au Sénégal. Tous les patients répondant aux critères diagnostiques de NB ont été inclus. Seize patients ont été colligés, 14 hommes et deux femmes avec un âge moyen de 40 ans [18­71]. Les principaux signes neurologiques étaient un déficit moteur (13 cas), des céphalées (10 cas) et un trouble du langage (4 cas). Les signes extraneurologiques étaient dermatologiques (14 cas), oculaires (2 cas) et articulaires (2 cas) à type de gonarthrite unilatérale aseptique. Une fièvre était présente chez neuf patients. L'atteinte neurologique était majoritairement parenchymateuse isolée (8 cas) ou mixte (6 cas). Les principales formes cliniques de NB étaient la rhombencéphalite (8 cas) et la névrite optique rétrobulbaire (4 cas). Sept patients avaient un angio-Behçet cérébral à type de thromboses veineuses cérébrales (3 cas), d'infarctus cérébraux (2 cas) et d'hématomes intracérébraux (2 cas). Sous prednisone (16 cas) et azathioprine (3 cas), l'évolution clinique à court terme était majoritairement favorable (14 cas) avec un score de Rankin modifié de 2 au moment de l'exeat. Le NB est une maladie de l'homme adulte sous-diagnostiquée en Afrique noire. Des études ultérieures multicentriques nationales et sous-régionales sont souhaitables.

Functional and Expression Analyses of the Pneumocystis MAT Genes Suggest Obligate Sexuality through Primary Homothallism within Host Lungs.

Fungi of the genus Pneumocystis are obligate parasites that colonize mammals' lungs and are host species specific. Pneumocystis jirovecii and Pneumocystis carinii infect, respectively, humans and rats. They can turn into opportunistic pathogens in immunosuppressed hosts, causing severe pneumonia. Their cell cycle is poorly known, mainly because of the absence of an established method of culture in vitro It is thought to include both asexual and sexual phases. Comparative genomic analysis suggested that their mode of sexual reproduction is primary homothallism involving a single mating type (MAT) locus encompassing plus and minus genes (matMc, matMi, and matPi; Almeida et al., mBio 6:e02250-14, 2015). Thus, each strain would be capable of sexual reproduction alone (self-fertility). However, this is a working hypothesis derived from computational analyses that is, in addition, based on the genome sequences of single isolates. Here, we tested this hypothesis in the wet laboratory. The function of the P. jirovecii and P. carinii matMc genes was ascertained by restoration of sporulation in the corresponding mutant of fission yeast. Using PCR, we found the same single MAT locus in all P. jirovecii isolates and showed that all three MAT genes are often concomitantly expressed during pneumonia. Extensive homology searches did not identify other types of MAT transcription factors in the genomes or cis-acting motifs flanking the MAT locus that could have been involved in MAT switching or silencing. Our observations suggest that Pneumocystis sexuality through primary homothallism is obligate within host lungs to complete the cell cycle, i.e., produce asci necessary for airborne transmission to new hosts.IMPORTANCE Fungi of the genus Pneumocystis colonize the lungs of mammals. In immunosuppressed human hosts, Pneumocystis jirovecii may cause severe pneumonia that can be fatal. This disease is one of the most frequent life-threatening invasive fungal infections in humans. The analysis of the genome sequences of these uncultivable pathogens suggested that their sexual reproduction involves a single partner (self-fertilization). Here, we report laboratory experiments that support this hypothesis. The function of the three genes responsible for sexual differentiation was ascertained by the restoration of sexual reproduction in the corresponding mutant of another fungus. As predicted by self-fertilization, all P. jirovecii isolates harbored the same three genes that were often concomitantly expressed within human lungs during infection. Our observations suggest that the sexuality of these pathogens relies on the self-fertility of each isolate and is obligate within host lungs to complete the cell cycle and allow dissemination of the fungus to new hosts.

Comorbidities and Neuromyelitis Optica - Spectrum Diseases : What are the current Data ?

Neuromyelitis optica (NMO-SD) or Devic disease is an acute transverse myelitis associated with an optic neuritis united -or bilateral. It is an inflammatory disease very disabling evolving by thrust. The long-term prognosis is also difficult to predict due to comorbidities which determine the evolution and the quality of life of patients. The objective of our study was to determine the different types of co-morbidities found in patients with NMO -SD.Methods: It was a descriptive study through a review of the literature on PubMed with the combination (Neuromyelitis optica, comorbidity). The data analysis was made on the software SPSS 23 Results: Total 27 articles were published and available on PubMed (June 2017). Among these 27 work we included ten (10) specific studies of co-morbidities in the NMO-SD. Three categories of illnesses have been reported in these 10 articles including coexisting diseases with the NMO-SD without any risk factor common or similar

Functional characterization of the Pneumocystis jirovecii potential drug targets dhfs and abz2 involved in folate biosynthesis.

Pneumocystis species are fungal parasites colonizing mammal lungs with strict host specificity. Pneumocystis jirovecii is the human-specific species and can turn into an opportunistic pathogen causing severe pneumonia in immunocompromised individuals. This disease is currently the second most frequent life-threatening invasive fungal infection worldwide. The most efficient drug, cotrimoxazole, presents serious side effects, and resistance to this drug is emerging. The search for new targets for the development of new drugs is thus of utmost importance. The recent release of the P. jirovecii genome sequence opens a new era for this task. It can now be carried out on the actual targets to be inhibited instead of on those of the relatively distant model Pneumocystis carinii, the species infecting rats. We focused on the folic acid biosynthesis pathway because (i) it is widely used for efficient therapeutic intervention, and (ii) it involves several enzymes that are essential for the pathogen and have no human counterparts. In this study, we report the identification of two such potential targets within the genome of P. jirovecii, the dihydrofolate synthase (dhfs) and the aminodeoxychorismate lyase (abz2). The function of these enzymes was demonstrated by the rescue of the null allele of the orthologous gene of Saccharomyces cerevisiae.

[Epilepsy and reproductive health: Senegalese cohort]. / Épilepsie et santé de la reproduction : cohorte sénégalaise.

INTRODUCTION: Epilepsy is a public health problem in Senegal and Africa because of its severity and its social importance. It occurs at any age sparing no sex. It can influence sexual life and reciprocally. Our aims were to study the effects of antiepileptic drugs on the sexual lives of women with epilepsy, the influence of these drugs on pregnancy and breastfeeding. METHODS: We conducted a prospective study from 1st March to 31st August 2011 in the neurological department of the Fann-Dakar teaching hospital Senegal. Only women with epilepsy were included. RESULTS: We collected 120 patients aged 16-64years with a mean age of 30.58years, 45% married, 44.16% were uneducated preponderant. All patients were taking antiepileptic drugs, 89.16% was alone. Fifty-five percent of our patients had epilepsy for at least 6years; 45.83% had generalized epilepsy; 44.17% of partial seizures. In our cohort, 64.16% were under phenobarbital, 69.16% had good adherence. As side effects of drugs, 90% had sexual problems. Seventy-five percent enjoyed an active sex life. A decrease in the number of sex per week for the disease [31/55=56.66%] was noted. In addition, 51.17% were using contraception, including 38.7% of oral kind and 64.86% had noticed an increase in seizure frequency during their pregnancies. Of the 74 women who had contracted a pregnancy, 41.89% had premature infants, 16.21% have made abortions and 61.17% had psychosocial life affected. DISCUSSION AND CONCLUSION: People with epilepsy often experience sexual problems that may be caused by epilepsy, antiepileptic and/or reactions of the partner and the other facing the diagnosis of epilepsy.

Placental expression of the obesity-associated gene FTO is reduced by fetal growth restriction but not by macrosomia in rats and humans.

Genetic variants in the FTO (fat mass- and obesity-associated) gene have the highest association of all obesity-associated genes. Its placental expression was shown to relate to birth weight, suggesting that it may participate in the control of fetal weight gain. To gain more insight into the implication of FTO in fetal growth, we measured its placental expression in samples including extremes of abnormal fetal growth, such as after intrauterine growth restriction (IUGR) or macrosomia in both rats and humans. In rats, fetal growth was modulated by maternal nutritional modifications. In humans, placental villi were collected from pathological pregnancies (i.e. with IUGR or fetal macrosomia). Placental FTO mRNA expression was reduced by IUGR but was not significantly affected by macrosomia in either rats or humans. Our data suggest that placental FTO may participate in interactions between the in utero environment and the control of fetal growth under IUGR conditions by modulating epigenetic processes.

Permissivity of Vero cells, human pneumocytes and human endometrial cells to Waddlia chondrophila.

Growing evidence suggests that the bacterium Waddlia chondrophila, a novel member of the Chlamydiales order, is an agent of miscarriage in humans and abortion in ruminants. We thus investigated the permissivity of three epithelial cell lines, primate Vero kidney cells, human A549 pneumocytes and human Ishikawa endometrial cells to this strict intracellular bacteria. Bacterial growth kinetics in these cell lines was assessed by quantitative PCR and immunofluorescence and our results demonstrated that W. chondrophila enters and efficiently multiplies in these epithelial cell lines. Additionally, confocal and electron microscopy indicated that the bacteria co-localize with host cell mitochondria. Within Vero and A549 cells, intracellular growth of W. chondrophila was associated with a significant decrease in host cell viability while no such cytophatic effect was detected in Ishikawa cells. Bacterial cell growth in this endometrial cell line stopped 48 h after infection. This stop in the replication of W. chondrophila coincided with the appearance of large aberrant bodies, a form of the bacteria also observed in Chlamydiaceae and associated with persistence. This persistent state of W. chondrophila may explain recurrent episodes of miscarriage in vivo, since the bacteria might reactivate within endometrial cells following hormonal changes that occur during pregnancy.

Gamma interferon-producing CD4 T-cells correlate with resistance to Mycoplasma mycoides subsp. mycoides S.C. infection in cattle.

Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides SC (MmmSC), is one of the most significant cattle disease in Africa. The control measures, which led to eradication from numerous countries are not feasible in Africa where the only prophylaxis relies on vaccination. However, the attenuated vaccines, used up to now in Africa, are of low efficiency. The development of an improved vaccine is, therefore, a necessity. The purpose of this study was to compare some immunological parameters in MmmSC-infected cattle (endobronchial versus natural in-contact infection) and assess the response in correlation with the clinical outcome (death versus recovery). Characterization of the immune parameters elicited in recovered animals, known to be refractory to new infection, will be an important step towards development of new vaccines against CBPP. A significant outcome of this study was the demonstration that all MmmSC-infected cattle developed a MmmSC-specific cell-mediated immune response. A kinetic analysis of the MmmSC responsiveness showed that the main difference between endobronchially- and in-contact infected animals was the delay before the onset of the MmmSC-specific immune response. The first MmmSC-responding PBMC sample was selected from each animal for cell phenotyping. The phenotypic analysis of this early MmmSC-induced response revealed the predominant contribution of the CD4 T-cells in all animals whereas IFNgamma was only constantly produced in recovered animals. Evolution of this early MmmSC-specific immune response was then followed by a kinetic analysis of the MmmSC-induced CD4 T-cell response and IFNgamma released. The results demonstrated that in recovered animals, the MmmSC-specific CD4 Th1-like T-cell response was maintained until slaughtering whereas in animals with acute disease, progression of CBPP was associated with a decreased ability of the PBMC to produce IFNgamma. The results led to the identification of immune parameters, which correlate with protection against CBPP and to a relevant strategy for the development of improved vaccines against this disease.

Effect of surface treatment of NiTi alloy on its corrosion behavior in Hanks' solution.

The effect of surface modification of NiTi shape memory alloy on its corrosion behavior in Hanks' solution was determined. The near-equi-atomic super elastic NiTi (Ni 55.8 wt %) alloy used for this study was provided by Memry USA. The surfaces of heat-treated samples were modified by mechanical polishing (MP), electropolishing (EP), and electropolishing followed by chemical passivation (CP). As-heat-treated samples with straw-colored oxide finishes (SCO) and blue-colored oxide finishes (BO) also were included in the study. Surface analysis was performed using auger electron spectroscopy (AES), atomic force microscopy (AFM), and contact angle measurements (CAM). It was shown that surface roughness increased in the order CP < EP < SCO < BO < MP. The nickel release within the five groups of NiTi samples, as determined by atomic absorption spectrophotometry, reduced in time over the measured period. The level of Ni ions released over a 25-day immersion period was highest in the SCO sample (0.002 microg/day). This Ni level is negligible compared with the daily intake of Ni in an ordinary diet. The auger electron spectroscopy (AES) analyses indicated that before immersion in Hanks' physiologic solution, the main surface composition of all the samples was titanium and nickel, with a small amount of oxygen, carbon, and sulphur as contaminants. And the surface oxide thickness of the different samples increased in the order CP < EP < MP < BO < SCO. On the other hand, for the electrodes treated under the same conditions, the mean breakdown potential value decreased in the order BO > MP > CP > EP > SCO while the corrosion current density and rate increased in the order CP < SCO < EP < BO < MP.

Diagnosis of malaria using thick bloodsmears: definition and evaluation of a faster protocol with improved readability.

The value of some inexpensive modifications to the standard method of preparing thick bloodsmears, involving rapid drying, an isotonic fixative and a haemolysing solution containing saponin, was evaluated. The drying, haemolysing, fixing and staining steps, together called the fast-thick-smear method (FTS), can be completed in < 10 min. The FTS and a more classical thick-smear method (CTS) were both used on each of 1185 samples of venous blood samples from 1034 cases of suspected malaria (all international travellers returning to France). The results indicated that there was no statistically significant differences between the two methods in terms of their sensitivity, specificity or predictive values for parasite detection. However, estimates of the intensities of the Plasmodium falciparum infections observed, based on counts of trophozoites against 200 leucocytes, were markedly higher (37.8% higher overall) with the FTS than with the CTS (P < 0.0001). Moreover, the concordance between results obtained by inexperienced and experienced microscopists was excellent when the FTS was used, with a kappa value of 0.96 (95% confidence interval = 0.93-0.98).

Evaluation of an immunofluorescent-antibody test using monoclonal antibodies directed against Enterocytozoon bieneusi and Encephalitozoon intestinalis for diagnosis of intestinal microsporidiosis in Bamako (Mali).

A 2-month study was carried out in Mali to evaluate an immunofluorescent-antibody test (IFAT) using monoclonal probes specific for Enterocytozoon bieneusi or Encephalitozoon intestinalis. Sixty-one human immunodeficiency virus (HIV)-seropositive adult patients and 71 immunocompetent children were enrolled. Microsporidia were detected in stools from 8 of 61 patients (13.1%) seropositive for HIV. A single species, E. bieneusi, was identified. All the children were negative for microsporidia. The sensitivity and specificity of IFAT were 100% compared with those of PCR, which was used as the "gold standard." Moreover, species identification by IFAT was more rapid and less expensive than that by PCR. These results show the suitability of IFAT for detection of microsporidia in developing countries.

[Antifungal drugs in the treatment of systemic candidiasis: susceptibility to antifungal drugs, drug resistance, pharmacological data]. / Utilisation des antifongiques dans le traitement des candidoses systémiques: antifongigramme, point sur les résistances, données pharmacologiques.

The available antifungal agents are amphotericin B (conventional or lipid formulation), flucytosin and azole derivatives (ketoconazole, fluconazole, itraconazole). The main target of these molecules are a specific compound of fungal membrane, ergosterol. Determination of the fungal sensitivity to antifungal drugs is difficult and no consensus has been achieved so far. Minimal inhibitory concentrations are poor predictors of clinical success or failure. A good correlation between in vitro and in vivo results has been observed only in patients with oropharyngeal candidiasis associated with HIV infection. Combinations of antifungal drugs are currently under study. The role of hemopoietic growth factors (G-CSF, GM-CSF) as an adjuvant has not been fully established. New antifungal drugs (triazole derivatives, echinocandins) should be available within months.