Mycobacterium tuberculosis Lineage 7 Strains Are Associated with Prolonged Patient Delay in Seeking Treatment for Pulmonary Tuberculosis in Amhara Region,Ethiopia

Recent genotyping studies of Mycobacterium tuberculosis in Ethiopia have reported the identification of a new phylogenetically distinct M. tuberculosis lineage, lineage 7. We therefore investigated the genetic diversity and association of specific M. tuberculosis lineages with sociodemographic and clinical parameters among pulmonary TB patients in the Amhara Region, Ethiopia. DNA was isolated from M. tuberculosis-positive sputum specimens (n = 240) and analyzed by PCR and 24-locus mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) analysis and spoligotyping. Bioinformatic analysis assigned the M. tuberculosis genotypes to global lineages, and associations between patient characteristics and genotype were evaluated using logistic regression analysis. The study revealed a high diversity of modern and premodern M. tuberculosis lineages, among which approximately 25% were not previously reported. Among the M. tuberculosis strains (n = 138) assigned to seven subgroups, the largest cluster belonged to the lineage Central Asian (CAS) (n = 60; 26.0%), the second largest to lineage 7 (n = 36; 15.6%), and the third largest to the lineage Haarlem (n = 35; 15.2%). Four sublineages were new in the MIRU-VNTRplus database, designated NW-ETH3, NW-ETH1, NW-ETH2, and NW-ETH4, which included 24 (10.4%), 18 (7.8%), 8 (3.5%), and 5 (2.2%) isolates, respectively. Notably, patient delay in seeking treatment was significantly longer among patients infected with lineage 7 strains (Mann-Whitney test, P < 0.008) than in patients infected with CAS strains (adjusted odds ratio [AOR], 4.7; 95% confidence interval [CI], 1.6 to 13.5). Lineage 7 strains also grew more slowly than other M. tuberculosis strains. Cases of Haarlem (OR, 2.8; 95% CI, 1.2 to 6.6) and NW-ETH3 (OR, 2.8; 95% CI, 1.0 to 7.3) infection appeared in defined clusters. Intensified active case finding and contact tracing activities in the study region are needed to expedite diagnosis and treatment of TB.     

Evaluation of the effects of 80% methanolic leaf extract of Caylusea abyssinica (fresen.) fisch. & Mey. On glucose handling in normal, glucose loaded and diabetic rodents

ABSTRACT: BACKGROUND: The leaves of Caylusea abyssinica (fresen.) Fisch. & Mey. (Resedaceae), a plant widely distributed in East African countries, have been used for management of diabetes mellitus in Ethiopian folklore medicine. However, its use has not been scientifically validated. The present study was undertaken to investigate antidiabetic effects of the hydroalcoholic leaf extract of C. abyssinica extract in rodents.Materials and methodMale Animals were randomly divided into five groups for each diabetic, normoglycemic and oral glucose tolerance test (OGTT) studies. Group 1 served as controls and administered 2% Tween-80 in distilled water, (TW80); Group 2 received 5 mg/kg glibenclamide (GL5); Groups 3, 4 and 5 were given 100 (CA100), 200 (CA200) and 300 (CA300) mg/kg, respectively, of the hydroalcoholic extract of C. abyssinica. Blood samples were then collected at different time points to determine blood glucose levels (BGL). Data were analyzed using one way ANOVA followed by Dunnet's post hoc test and p < 0.05was considered as statistically significant. RESULTS: In normal mice, CA200 and GL5 induced hypoglycemia starting from the 2nd h but the hypoglycemic effect of CA300 was delayed and appeared at the 4th h (p < 0.05 in all cases). In diabetic mice, BGL was significantly reduced by CA100 (p < 0.05) and CA300 (p < 0.01) starting from the 3rd h, whereas CA200 (p < 0.001) and GL5 (p < 0.05) attained this effect as early as the 2nd h. In OGTT, TW80 (p < 0.01) and CA100 (p < 0.01) brought down BGL significantly at 120 min, while CA200 (p < 0.001) and GL5 (p < 0.001) achieved this effect at 60 min indicating the oral glucose load improving activity of the extract. By contrast, CA300 was observed to have no effect on OGTT. Acute toxicity study revealed the safety of the extract even at a dose of 2000 mg/kg. Preliminary phytochemical study demonstrated the presence of various secondary metabolites, including, among others, saponins, flavonoids and alkaloids. CONCLUSION: The results indicate that C. abyssinica is endowed with antidiabetic and oral glucose tolerance improving actions, particularly at the dose of 200 mg/kg in experimental animals. These activities of the plant extract may be related to the presence of secondary metabolites implicated in antidiabetic activities of plant extracts via different hepatic and extra-hepatic mechanisms. These results thus support the traditional use of the leaf extract for the management of diabetes mellitus.     

Rate and Predictors of Ineffective HIV Protection in African Men Who Have Sex with Men Taking Pre-Exposure Prophylaxis

AIDS and Behavior - We investigated the rate and predictors of ineffective HIV protection in men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP) in a prospective cohort study...     

Intravenous immunoglobulin and dendritic cells

Intravenous immunoglobulin (IVIg) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases, and in supportive therapy of immunodeficient patients. Available clinical and experimental evidence suggests, however, that a wide spectrum of immune-mediated conditions could benefit from IVIg, including acute and chronic/relapsing diseases and autoimmune diseases mediated by pathogenic autoantibodies or by autoaggressive T-cells. Dendritic cells (DCs) are professional antigen-presenting cells and because of their capacity to stimulate nave T-cells, they play a central role in the initiation of primary immune responses. Several immunomodulatory agents have been shown to inhibit DC activation. Recently, we examined the effects of IVIg on differentiation, maturation, and functions of DCs. We demonstrate that DCs are one of the targets for the immunomodulatory effects of IVIg.