The evolution of a neglected disease: tuberculosis discoveries in the centuries.

Tuberculosis (TB) and humans have coexisted for more than 40,000 years. The word "tuberculosis" derives from "tubercle", the histological lesion which appears in the organs, described by Pott in the late Eighteenth century and found, by molecular biology, in human skeletons dating back to 5000 BC. Early description of TB can be found in the writings of ancient India and China and in the Bible. In ancient Greece tuberculosis was not considered contagious, but Aristotle recognized the contagious nature of the pig's and ox's scrofula. The suspicion that phthisis is a contagious disease and that isolation can reduce the risk of transmission was expressed for the first time by the Arabian Avicenna, in his work "The canon of medicine". In 1699, the Health Council of the Republic of Lucca founded the "sanatorium" concept as place of care and isolation. In 1865 Villemain inoculated tubercular material from a human lymph node into a rabbit, obtaining for the first time the typical tubercular lesions. Some years later, on March 24, 1882, Robert Koch announced to the Berlin Society of Physiology the discovery of Mycobacterium tuberculosis. In the same period Virchow improved awareness of risk factors and correct behaviours among the general population. In 1952 Waksman won the Nobel Prize for the discovery of the first active drug against TB: streptomycin. Nevertheless, drug resistance appeared rapidly some years later and it is still a great challenge in TB fight nowadays.

Equine blastocyst production under different incubation temperatures and different CO2 concentrations during early cleavage.

Some basic parameters for equine invitro embryo production have not yet been established, including the optimum temperature for maturation and embryo culture, and the optimum CO2 concentration and pH during early embryo development. To explore this, we first performed cultures in incubators set at 37.2°C, 37.7°C or 38.2°C. At these temperatures, the corresponding maturation rates were 33%, 38% and 42%; cleavage rates were 84%, 86% and 88%; and blastocyst rates were 35%, 44% and 44% per injected oocyte. These rates did not differ significantly (P>0.2). We then evaluated three different CO2 concentrations (6%, 6.5% or 7% CO2) in 5% O2 for culture over Days 0-5 after intracytoplasmic sperm injection, using a commercial human embryo medium with added serum, at 38.2°C. The pH values of these media were 7.36, 7.33 and 7.29 respectively. In the presence of 6%, 6.5% or 7% CO2, cleavage rates were 68%, 80% and 70% respectively, and blastocyst rates per injected oocyte were 42%, 54% and 27% respectively. The blastocyst rate for the 7% CO2 treatment was significantly lower than that for the 6.5% CO2 treatment (P<0.05). We conclude that equine invitro embryo production is equally effective within the range of 37.2-38.2°C, but that equine early cleavage stage development is sensitive to small changes in CO2 atmosphere and/or medium pH.

[Prescription And Delivery's Survey Of Benzodiazepines In The Occurrence Of Addictions At Mbour's District]. / Evaluation De La Prescription Et De La Delivrance Des Benzodiazepines Dans La Survenue Des Addictions Dans Le District Sanitaire De Mbour.

Impact of the prescription and delivery of benzodiazepines in the occurrence of addictions in the district of Mbour. INTRODUCTION: Benzodiazepines (BZD) are widely used nowadays and are at the origin of an addiction. OBJECTIVES: The objective was to evaluate the quality of benzodiazepine prescribing and delivery in the Mbour department of Senegal and subsequently to implement an addictovigilance strategy. Thus, we studied the prescribing habits, the quality of delivery and identified the consumption habits of these drugs. MATERIALS AND METHODS: It was a cross-sectional, prospective study with two questionnaires: addressed to patients and prescribers, conducted in pharmacies, hospitals, districts and Mbour health posts. RESULTS: 44% of BZD prescriptions were prescribed by doctors and especially general practitioner. 31.1% did not comply with the rules of prescription (marketing authorization). As for the dispensing rules, (85.3%) were dispensed without a prescription. The level of consumption was high in the 30-40 age group (43.95%) predominantly female (59%). Insomnia predominated as a reason for prescription (16.4%) on anxiety (11.94%) with (65.5%) dependence. CONCLUSION: The abuses observed in the prescription, the delivery and consumption of BZD, constitutes a real health problem. Half of the consumers become addicted, hence the need for a national addictovigilance program.

INTRODUCTION: Les benzodiazépines (BZD) sont très utilisées de nos jours et sont à l'origine d'une addiction. OBJECTIFS: L'objectif était d'évaluer la qualité de la prescription et de la délivrance des benzodiazépines dans le département de Mbour au Sénégal et ultérieurement mettre en place une stratégie d'addictovigilance. Ainsi, nous avons étudié les habitudes de prescription, la qualité de délivrance et identifié les habitudes de consommation de ces médicaments. MATÉRIELS ET MÉTHODES: Il s'agissait d'une étude transversale, prospective avec deux questionnaires : adressé aux patients et prescripteurs, menée dans des pharmacies, hôpital, district et postes de santé de Mbour. RÉSULTATS: 44% des ordonnances de BZD étaient prescrites par des médecins et particulièrement des généralistes. 31,1% ne respectaient pas les règles de prescriptions (hors AMM). Quant aux règles de délivrance, 85,3% étaient délivrées sans ordonnance. Le niveau de consommation était élevé dans la tranche d'âge 30-40 ans (43,95%) avec une prédominance féminine (59%). L'insomnie prédominait comme motif de prescription (16,4%) sur l'anxiété (11,94%) avec (65,5%) de dépendance. CONCLUSION: Les abus observés dans la prescription, la délivrance et la consommation des BZD, constitue un véritable problème de santé. La moitié des consommateurs deviennent addictes, d'où la nécessité de mettre en place un programme d'addictovigilance à l'échelon national.

[Impact of sickle cell trait on arterial stiffness in African subjects]. / Impact du trait drépanocytaire sur la rigidité artérielle des sujets africains.

Sickle cell trait (SCT) is the benign condition of sickle cell disease. Often asymptomatic, the carriers of the sickle cell trait have hemorheological disturbances with increased oxidative stress compared to healthy subjects. These disturbances can lead to structural and functional changes in large vessels. The aim of the study was to measure arterial stiffness, an independent marker of subclinical atherosclerosis, SCT carriers compared to sickle cell anemia (SCA) subjects. Nine SCT carriers aged 32±9 years (7 men) were compared to 14 SCA subjects aged 29±9 years (2 men) and 22 control subjects aged 34±9 years (11 men) recruited by the National blood transfusion center (CNTS) in Dakar (Senegal). Arterial stiffness was assessed by measurement of the finger-toe pulse wave velocity (PWVft) using pOpmètre® (Axelife SAS-France). The cardiovascular risk (CVR) was assessed according to the Framingham Laurier score. The SCT carriers had a higher PWVft (m/s) than SCA subjects (8.2±2.2 vs 6.1±0.9m/s, P=0.004) but not different from that of healthy controls (8.2±2.2 vs 7.4±1.8m/s, P=0.33). Linear regression showed a positive relationship between PWVft and the pulse pressure (PP) (P˂0.001; r2=0.39; F=13.20). The results show that the SCT carriers have stiffer arteries than SCA subjects. Linear regressions adjusted for age, mean arterial pressure (MAP) and PP, showed that only age and PP were independently correlated with arterial stiffness in the entire population.

Vaginal prolapse in a pregnant Maine coon cat: a case report.

Vaginal prolapse is a condition characterised by excessive accumulation of mucosal oedema and protrusion of hyperplastic tissue through the vulva. It has been reported in ruminants and canines, but has not been characterised in felines. This report describes the history, clinical signs and treatment of a pregnant Maine coon cat with a Type III vaginal prolapse diagnosed approximately 54 days after the first day of mating. Prior to queening, the prolapse was reduced and retained using a vulvar cruciate suture. Due to the risk of dystocia and recurrence, a caesarean section with ovariohysterectomy was performed. Postoperatively, a stay suture was maintained in the vulva for 2 weeks, resulting in permanent reduction of the vaginal prolapse. To the authors' knowledge, this case represents the first report of the successful management of vaginal prolapse in a pregnant cat.

[Evaluation of erythrocyte deformability in subjects with sickle cell trait during a soccer game: effect of hydration ad libitum]. / Évaluation de la déformabilité érythrocytaire des sujets porteurs de trait drépanocytaire au cours d'un match de football : effet de l'hydratation ad libitum.

This study compared erythrocyte changes between a group of subjects with sickle cell trait (SCT) and controls (subjects without hemoglobinopathy) during a soccer game in two conditions: with and without hydration. Erythrocyte deformability of subjects was assessed by the coefficient of erythrocyte rigidity (Tk) which was calculated before and after football match. Our results showed a significant increase in erythrocyte rigidity (Tk) in SCT at the end of physical activities without hydration; however when water was provided ad libitum their Tk decreased significantly, reaching values of controls. And adequate hydration is recommended in subjects with sickle cell trait during and after exercise.

Disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (CCFA) to pony mares with placentitis.

The objective of this study was to determine the pharmacokinetics of CCFA in mares with placentitis and evaluate the disposition of the drug in fetal fluids, fetal membranes, colostrum, and serum of foals. A secondary objective was to obtain pilot data regarding the efficacy of CCFA for improving foal survival in mares with placentitis. Twelve pregnant pony mares were enrolled in the study, inoculated with Streptococcus zooepidemicus, intracervically and assigned to one of three groups: CEFT (n = 3; administered CCFA only; 6.6 mg/kg, i.m., q96h); COMBO (n = 6; administered combination therapy of CCFA, altrenogest, and pentoxifylline); UNTREAT (n = 3, no treatment). Treatment was initiated at the onset of clinical signs. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur metabolites, were measured using high-performance liquid chromatography. Maximum and minimum serum concentrations of DCA at steady state in treated mares were 2.40±0.40 µg/mL and 1.06±0.29 µg/mL, respectively. Concentration of DCA in colostrum was 1.51±0.60 µg/mL. DCA concentrations in placenta and fetal tissues were very low (median = 0.03 µg/mL) and below the minimum inhibitory concentration of relevant pathogens. DCA was not detected in amniotic fluid or foal serum. Treatment did not appear to improve foal survival (CEFT: 0/3; COMBO: 2/6; UNTREAT: 2/3). Bacteria were recovered from the uterus of most mares postpartum and from blood cultures of most foals regardless of treatment.

Serological HLA class I alleles in Senegalese blood donors detected HBs Ag positive.

We analysed the HLA class I alleles in 96 blood donors HBs Ag positive compared with 93 healthy control individuals (HBs negative). The most frequent HLA-A, -B, -C alleles found were, A23 (33.6%); A2 (25%); A30 (25%); B8 (31.5%); B7 (16.3%); B58 (11.9%); B35 (11.9%); B49 (11.9%); B53 (10.8%); Cw7 (39.1%); Cw3 (36.9%); Cw4 (36.9%). Significant differences (P<0.001) were found between the blood donors and the controls for the following HLA alleles, A1; A23; B8 and Cw3. The detection of HBe antigen was positive in 26/84 blood donors. It was observed a significant difference (P<0.01; odds ratios (OR)=6.25) between positive and negative HBe antigens blood donors for HLA-A1 allele.

[Association between Class I HLA alleles and HBs antigen carrier status among blood donors in Senegal]. / Association entre allèles HLA de classe I et portage de l'antigene HBs chez des donneurs de sang au Sénégal.

The course of hepatitis B virus (HBV) infection may be influenced by the host immune response. A prospective study was carried out in ninety-eight subjects (mean age = 23 years) HBs antigens carriers of hepatitis B and living in Dakar, Senegal. We analysed the HLA-A, -B, and C antigens distribution compared to that one of a control (HBs negative) healthy senegalese population (n = 96) living in Dielmo village where a longitudinal study was set-up since 1990. The HLA class I typing was performed by microlymphocytotoxicity assays. The most frequent HLA-A, -B, -C antigens found were: locus A: A23 (33.6%), A2 (25%), A30 (25%), locus B: B8 (31%), B7 (16.3%), B58 (11.9%), B35 (11%), B49 (11%), B53 (10.8%) and locus C: Cw7 (39.1%), Cw17 (39.1%), Cw3 (36.9%), Cw4 (36.6%). Significant differences (P < 0.001) were found between the donors and the control group for the following HLA antigens: A1, A23, B8 and Cw3. The detection of HBe antigen was positive in 26/84 blood donors. It was observed a significant difference (p < 0.01) between positive and negative HBe donors for HLA-A1 allele with an odds ratio of 6.25. All the donors carrying the HLA haplotype: A1-B8-Cw7 (11.5%) were positive in HBe antigen. HLA: B8-Cw7 haplotype (detected in 8.5% of positive donors) seems to be likely associated with a liver cancer according to many reports. An adequate follow-up should be set-up for positive HBe subjects carrying a susceptible HLA type.

[HLA-DQ allele typing in a Senegalese population: comparative study of serology and PCR-SSP]. / Typage des allèles HLA-DQ dans une population sénégalaise: étude comparative de la sérologie et de la PCR-SSP.

In this study, we compared the serological standard typing method and the DNA genotyping PCR-SSP for the characterization of HLA-DQ alleles in a senegalese population. For this purpose, 120 individuals leaving in Dielmo were typed using the microlymphocytotoxicity assay and the PCR-SSP DQ low Resolution method. A discordance of 42.5% (51/120) was found between these two methods. Thirty % (36/120) of serological typed persons failed to be typed by PCR-SSP method whereas 1% (1/120) assigned by PCR-SSP failed to be characterized by serology. Advantages and limits of these two typing methods and also the genetic background of our study population were valid arguments to comment our findings. The PCR-SSP, as suggested by several authors, is reliable, accurate and fast for HLA class II alleles characterization. Nevertheless, it needs, to become an alternative HLA typing method, available primers adapted to genetic background of study population.

[Prognostic value of cytokines and HLA markers in patients with cerebral malaria in Senegal]. / Valeurs pronostiques des cytokines et marqueurs HLA chez des patients atteints de neuropaludisme au Sénégal.

41 patients senegalese patients suffering from clinically defined severe malaria were studied in the intensive medical care unit of the Hôpital Principal in Dakar, Senegal. All of these individuals lived in Dakar, an area of low and seasonal Plasmodium falciparum transmission. In this study, we aim to determine in one hand, the cytokine levels of TNF-alpha, TNF-alpha sRI, TNF-alpha sRII, IL-2 sR, IL-6, IL-6 sR, and IL-10 to evaluate their prognostic value in the course of the disease; in the other hand, the influence of the HLA-DR alleles in the susceptibility to get severe malaria. At the day of admission (day 0) and 3 days later, one or two blood samples were collected for each patient to assess different biological parameters. Plasma samples were tested for cytokines cited above by ELISA (Medegenix EASIA kits) and DNA samples for HLA-DR by PCR-SSP genotyping. The concentrations of all the cytokines and/or their receptors were significantly increased at day 0 in the patients who died (TNF-alpha = 455 +/- 480 pg/ml, IL6 = 511 +/- 396 pg/ml) and decreased rapidly in the patients who survived from the disease (TNF-alpha = 354 +/- 629 pg/ml, IL6 = 453 +/- 706 pg/ml). A fatal issue seems likely related to the age of patients (20 +/- 12 years for surviving patients and 31 +/- 16 years for patients who died) and the kinetic of the cytokines. Significant differences were observed (pc < 0.001) between patients with severe malaria and a control group for the following HLA alleles: DR3, DR10 and DR13. The HLA-DR13 allele was found positively and highly associated with severe malaria.

HLA-A, -B, -C, -DR, -DQ typing in a population group of Senegal: distribution of HLA antigens and HLA-DRB1*13 and DRB1*11 subtyping by PCR using sequence-specific primers (PCR-SSP).

One-hundred-and sixteen Senegalese Serere were typed for HLA antigens and compared with other ethnic groups in Gambia. We did not find significant differences (Fisher's exact test; P < 0.01) in the HLA antigens distribution between the Serere and Mandinka groups in Senegal and the Serere, Mandinka and Wolof in The Gambia. The most common HLA haplotypes found (P < 0.01; Chi square with Yates' correction) were: A1, B8; A2, B51; A32, B44; A33, B58; A2, Cw2; A2, Cw4; A33, Cw3; A2, DR17; A10, DR10; B35, Cw4; B53, Cw6; B57, Cw3; B65, Cw8; B50, DR15; B52, DR4; Cw2, DR17; DR7, DQ2; DR18, DQ4. The HLA-DRB1*13 and DRB1*11 alleles were subtyped by PCR-SSP and the frequencies of these alleles in the studied population given. HLA-DRB1*1304 and DRB1102 were the most common alleles found respectively 15.0 and 18.5%.

[HLA class II typing: determination of the allelic subtypes of HLA-DR*13 and DRB1*11 using PCR-SSP]. / Typage HLA classe II: détermination des sous-types des allèles HLA-DRB1*13 et DRB1*11 par PCR-SSP.

In this study, we reported the HLA-class II genotyping by PCR-SSP (PCR-Sequence Specific Primers). This method was used to subtype the HLA-DRB1*13 and 11 alleles in Dielmo population. The most frequent DRB1*11 subtypes were 1101, 1102 et 1104; the frequency of 1102 was the highest (18.5%). The DRB1*13 subtypes were more polymorphic in the population and DRB*1304 was the most common subtype (15%). There were significant differences between the ethnic groups for some subtypes of DRB1*11 and 13 alleles.

Immuno-epidemiology of Schistosoma mansoni infections in a recently exposed community in Senegal.

Schistosoma mansoni was introduced in the Senegal basin around 1988, due to man-made ecological changes. Since 1991, we investigate a recent but very intense focus, Ndombo, a village near the city of Richard Toll where the outbreak was first described. Four cohorts, each a random sample (+/- 400 subjects each) from this community, were examined and followed up after treatment, starting at 8 month intervals over a 2-year period. Each cohort is examined parasitologically (Kato-Katz), clinically, serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; followed up 6-10 weeks, one and two years after treatment; and monitored for water contact patterns and local snail densities. In the first cohort, the prevalence was 91%, with a mean egg count of 663 epg. Prevalences are near 100% in all age groups, but egg counts decline strongly in adults. Antigen detection in serum and urine confirmed that the egg counts genuinely reflect variations of worm burdens, not e.g. of worm fecundity. This is surprising, as in this focus acquired immunity in adults should not have yet developed according to current hypothesis. The antigen detection assays (CAA/CCA) showed high sensitivity and quantitative power, and promising perspectives as a research tool and possibly as a method for non-invasive diagnosis and screening in urine. Epidemiological in subsequent cohorts were highly similar, although seasonal variations were observed possibly due to transmission fluctuations. Anti-AWA and anti-SEA IgE levels increased with age, while IgG4 peaked in the age-group 10 years and correlated well with egg counts.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: A cohort analysis was performed in Ndombo, Senegal, a community of about 4000, in the epicenter of the schistosomiasis outbreak. Four randomly selected cohorts of +or- 400 subjects were surveyed. Each cohort was examined parasitologically, clinically, and serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; and followed up at 6-12 weeks and at 1 and 2 years after treatment. The first cohort numbered 422 individuals, of which 91% had positive egg counts, with a mean egg count of 663 eggs per gram feces (epg). Quantitative egg counts in those aged 10-14 were 1409 epg and then declined to 632 epg in the age group 20-29 and to 266 epg in the age group over 40. In cohorts 2 and 3, examined in the spring and autumn, egg counts were substantially lower, particularly in adults, as compared with cohorts 1 and 4, which were both examined in the summer season. 94% of the subjects were positive in the serum circulating anodic antigen (CAA) ELISA, 83% in the serum CAA ELISA, and 95% in the urine circulating cathodic antigen (CCA) ELISA; CAA in urine was less sensitive, and was negative in half of the urine samples. Positivity rates for all assays increased with rising egg counts, and circulating antigen concentrations in both serum and urine correlated well with egg counts. IgE showed a significant increase with age, while IgG4 peaked in the age groups 10-15 and/or 15-19 years. A strong correlation between IgG, IgGl, and IgG4 against both crude antigens with pretreatment egg load was observed. Of the subjects in the first cohort, 61% reported abdominal pain, 33% diarrhea; only 16% showed mild hepatomegaly and only a few children had mild splenomegaly. In the first cohort, 82% of 298 reexamined subjects were still positive for S. mansoni 12 weeks after treatment with praziquantel 40 mg/kg. One year after treatment, cohort 1 showed mean egg counts in children (5-19 years) at 358 epg as compared with 1188 epg pretreatment.

Epidemiology, immunology and chemotherapy of Schistosoma mansoni infections in a recently exposed community in Senegal.

Schistosoma mansoni was introduced in the Richard Toll area (Senegal) around 1988, probably due to man-made ecological changes in the Senegal river basin. Since 1991, we investigate the community of Ndombo, close to Richard Toll. Four random population samples of approximately 400 subjects are surveyed, starting at 8 months intervals. Each cohort is examined parasitologically (Kato-Katz), clinically, serologically (circulating antigen and antibody profiles); treated with praziquantel 40 mg/kg; and followed up 6-12 weeks, 1 and 2 years after treatment. Water contact patterns and snail densities are longitudinally surveyed. In the first cohort, prevalence of infection was 91%, with 41% excreting over 1000 eggs per gram (epg); the mean egg count was 646 epg, individual counts up to 24,000 epg. Prevalences remained almost 100%, but egg counts declined strongly in adults, in spite of continued exposure and the supposed lack of acquired immunity. Antigen detection in serum and urine confirmed that the egg counts genuinely reflect variations of worm burdens. Serum circulating anodic antigen (CAA) provided intriguing epidemiological information on worm burdens, while circulating cathodic antigen (CCA) showed promise for non-invasive diagnosis and screening. So far, similar epidemiological results were found in subsequent cohorts, although some variations were observed, possibly due to seasonal transmission fluctuations. IgE levels increased with age, while IgG4 peaked in the age-group 10-19 years. IgE and IgG4-levels against adult worm antigen (AWA) and soluble egg antigen (SEA) increased between cohort 1 and cohort 3 in almost all age-groups. In all 3 cohorts examined so far a strong correlation between IgG4 and pre-treatment egg-load was observed. Further follow-up and analysis, and comparison with chronically infected populations will provide insight in the development of acquired immunity. Abdominal discomfort was reported by 61% and diarrhoea by 33% of the subjects in the first cohort; mild hepatomegaly was found in 16%, splenomegaly in 0.5%. There was no correlation between frequency of symptoms and egg counts. This low morbidity, in spite of intense infections, was confirmed by ultrasound, and may be due to the recent nature of the focus. In the first cohort, 82% of treated subjects still excreted eggs 12 weeks after treatment, though egg counts declined strongly. Antigen detection confirmed these results. Parasitological negativation rates in subsequent cohorts, followed up sooner after treatment, improved but remained remarkably low. The low drug efficacy may be due to very rapid reinfection (though further reinfection after one year was limited), and/or to the lack of immunity in the population. Reduced susceptibility of the local schistosome strain can not be excluded, however. Praziquantel treatment provoked impressive but transient side effects (colics, vomiting, urticaria, oedema), the frequency of which correlated with intensity of infection.