Subject(s)
Typhoid-Paratyphoid Vaccines , Polysaccharides, Bacterial , Typhoid Fever , Placebos , Clinical Trial, Phase II , ChinaABSTRACT
OBJECTIVE: To test the efficacy of locally produced Vi vaccine over a time period of longer than one year. METHODS: A double-blinded, randomized field trial was performed in Guangxi Zhuang Autonomous Region in south-western China, using 30 micrograms doses of locally produced Vi. Enrolled subjects were 3-50 years of age, although the majority (92%) were school-aged children, who have the highest rate of typhoid fever in this setting. A total of 131,271 people were systematically allocated a single dose of 30 micrograms of Vi polysaccharide or saline placebo. The study population was followed for 19 months, with passive surveillance conducted in the Ministry of Health and the Regional Health and Anti-epidemic Centre (HAEC). Clinically suspected cases of typhoid fever were confirmed by blood culture, or by serological reaction with O-antigen (Widal tests). FINDINGS: After 19 months, there were 23 culture-confirmed cases of typhoid fever in the placebo group versus 7 cases in the Vi group (Protective efficacy (PE) = 69%; 95% CI = 28%, 87%). Most of the isolates were from school-aged children: 22 cases in the placebo group versus 6 in the Vi group (PE = 72%; 95% CI = 32%, 82%). No serious post-injection reactions were observed. The locally produced Vi polysaccharide vaccine showed levels of protective efficacy similar to those for Vi vaccine produced in industrial countries. CONCLUSION: The slightly higher dose of vaccine did not seem to alter efficacy significantly in China.
Subject(s)
Antigens, Bacterial/administration & dosage , Polysaccharides, Bacterial/administration & dosage , Typhoid Fever/prevention & control , Typhoid-Paratyphoid Vaccines/administration & dosage , Adolescent , Adult , Antibodies, Bacterial/blood , Child , Child, Preschool , China , Double-Blind Method , Female , Humans , Male , Middle Aged , Placebos , Salmonella paratyphi A/isolation & purification , Salmonella typhi/isolation & purification , Treatment Outcome , Typhoid Fever/immunology , Typhoid Fever/microbiology , Typhoid-Paratyphoid Vaccines/immunologyABSTRACT
Experiments were performed on anaesthetized Wistar or Sprague-Dawley rats of both sexes. Microinjection of an acetylcholinesterase inhibitor physostigmine (0.4 microgram/0.1 microliter/site) or acetylcholine (ACh, 25 ng/0.1 microliter/site) into the rostral ventrolateral medulla (rVLM) caused an increase in blood pressure (BP), heart rate (HR) and the pressor response produced by stimulation of the dorsal periaqueductal grey (dPAG) in the midbrain. Prior microinjection of the calcium channel blocker verapamil (0.25 microgram/0.1 microliter/site) into the same sites blocked the cardiovascular effect in response to the respective microinjection of the drugs mentioned above. Moreover, verapamil pretreatment blocked the pressor and tachycardiac effect induced by respective microinjection of corticosterone (40 ng/0.1 microliter/site) or aldosterone (40 ng/0.1 microliter/site) into the rVLM, as well as the enhancement of the pressor response to stimulation of the dPAG induced by microinjection of corticoids into the rVLM. These results suggest that the enhancement of cardiovascular activities mediated by cholinergic mechanisms may be due to the activation of postsynaptic calcium channels of neurons in the rVLM. The corticosteroid effect seems to be mediated by similar mechanisms.
