Subject(s)
Tuberculosis, Pulmonary , Tuberculosis , Humans , Private Sector , Tuberculosis/diagnosis , Tuberculosis/epidemiology , IndiaABSTRACT
This study aimed to evaluate the durability of the immunogenicity of MVA85A beyond infancy. Participants in an immunogenicity study of MVA85A administered at age of 4 months had additional evaluation 14 months after initial vaccination for IFN-γ ELISPOT responses to Ag85A peptide and ESAT6/CFP-10 and tuberculin skin test (TST). 112 children participated in this study. The anthropometry, biochemical and haematological safety profile were similar between the MVA85A recipients and controls. MVA85A recipients still had significantly higher immune responses to Ag85A compared to the controls. The majority of these children had negative responses to the TST as well as the ESAT6/CFP-10 antigens. In summary, MVA85A-vaccinated children had a persistently higher Ag85A immune response 14 months following vaccination than controls. All the children had negligible evidence of latent infection with M. tuberculosis (Mtb), suggesting that deploying a prophylactic vaccine against Mtb infection at this age could still be effective in this setting.
Subject(s)
Tuberculosis Vaccines/administration & dosage , Tuberculosis Vaccines/immunology , Vaccination/methods , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , Acyltransferases/immunology , Africa , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Enzyme-Linked Immunospot Assay , Female , Humans , Immunologic Memory , Infant , Male , Time Factors , Tuberculin Test , Vaccines, DNAABSTRACT
The antihypertensive effect of aqueous extracts of the calyx of Hibiscus sabdariffa (HS) has been investigated in anaesthetized rats. Hibiscus sabdariffa caused a dose-dependent decrease in mean arterial pressure (MAP) of the rats. Sectioning of the right and left vagi nerves did not have a significant effect on the fall in MAP produced by HS. Cholinergic blockade with 0.2 mgkg-1 atropine and histaminergic blockade with 1 mgkg-1 cimetidine and 15 mgkg-1 promethazine significantly attenuated the hypotensive response to HS. Pretreatment of the rats with 20 mgkg-1 HS extract did not have a significant effect on increase in blood pressure induced by bilateral carotid occlusion (48.05 +/- 6.83 mmHg vs 46.53 +/- 7.49 mmHg). The cumulative addition of HS to noradrenaline precontracted aortic rings produced dose-dependent relaxation of the rings. The maximum relaxation response was 86.96 +/- 5.20% and this was observed at the dose of 1.70 mgml-1. These findings suggest that the antihypertensive effect of the extracts of calyx of HS is not mediated through inhibition of the sympathetic nervous system but it could be mediated through acetylcholine-like and histamine-like mechanisms as well as via direct vaso-relaxant effects.
Subject(s)
Blood Pressure/drug effects , Medicine, African Traditional , Plant Extracts/pharmacology , Animals , Atropine/pharmacology , Cimetidine/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Histamine H1 Antagonists/pharmacology , Histamine H2 Antagonists/pharmacology , Muscarinic Antagonists/pharmacology , Nigeria , Promethazine/pharmacology , Rats , Rats, Sprague-DawleyABSTRACT
To help to elucidate the changes induced by Trypanosoma brucei gambiense in the central nervous system (CNS) in advanced sleeping sickness patients, levels of interleukin-1 (IL-1) and prostaglandins D2 (PGD2) and E2 (PGE2) were measured by radioimmunoassay in the cerebrospinal fluid (CSF) from 24 patients diagnosed on the criteria of CSF protein, leucocyte count and parasite presence as having CNS (i.e. late stage) involvement, and from 12 patients without CNS involvement. PGD2 concentrations were selectively and markedly elevated in the late stage patients. The increased PGD2 may in part account for the increased somnolence and the immunosuppression within the CNS. Measurement of PGD2 levels in CSF may be a useful criterion for CNS involvement.
Subject(s)
Immune Tolerance/physiology , Prostaglandin D2/cerebrospinal fluid , Sleep/physiology , Trypanosoma brucei gambiense , Trypanosomiasis, African/cerebrospinal fluid , Adolescent , Adult , Animals , Child , Child, Preschool , Dinoprostone/cerebrospinal fluid , Humans , Interleukin-1/cerebrospinal fluid , Middle Aged , T-Lymphocytes/immunologyABSTRACT
Catecholamines, indolealkylamines and their analogues are oxidized at neutral or alkaline pH, producing hydrogen peroxide, quinones and free radicals. Several of these amines were tested for trypanocidal effects on Trypanosoma brucei, which possess a well-documented vulnerability to such oxidation products. Dopamine, 5-hydroxydopamine (5-OHDA), 6-hydroxydopamine (6-OHDA), 5-hydroxytryptamine (5-HT), 5,6-dihydroxytryptamine (5,6-DHT) and 5,7-dihydroxytryptamine (5,7-DHT) killed the parasites in vitro, using a fibroblast feeder layer cell culture system, in four to 48 hours at concentrations of 10(-5)-10(-7) M. The 5-OHDA, 6-OHDA, 5,6-DHT and 5,7-DHT were also effective in vivo when tested by intraperitoneal injection of infected mice.
Subject(s)
Catecholamines/pharmacology , Dihydroxytryptamines/pharmacology , Serotonin/pharmacology , Trypanosoma brucei brucei/drug effects , Trypanosomiasis, African/drug therapy , Animals , Catecholamines/therapeutic use , Cell Line , Dihydroxytryptamines/therapeutic use , Dopamine/pharmacology , Dopamine/therapeutic use , Hydroxydopamines/pharmacology , Hydroxydopamines/therapeutic use , Mice , Mice, Inbred C3H , Oxidation-Reduction , Serotonin/therapeutic useABSTRACT
Limited studies have been undertaken on the treatment of infections with trypanosomes of the subgenus Herpetosoma, either in comparative studies on the effects of trypanocidal drugs or as potential non-pathogenic models for evaluating trypanocidal activities. The development of an in vitro cell culture system is described which enabled testing of trypanocides against 5 different species of Herpetosoma. The trypanocides used were Samorin, Novidium, Trypacide and Berenil. Variations were observed in the trypanocidal activity of the drugs on the different Herpetosoma parasites, e.g. T. lewisi and Samorin and T. microti and Novidium, compared with other parasites. Minimum effective concentration of Trypacide and Berenil against 5 Herpetosoma trypanosomes were of the order 10 mg ml-1. The results indicate that these parasites are much less sensitive to the drugs used than pathogenic, salivarian trypanosomes.
