Tuberculous meningitis (TBM) results from the haematogenous dissemination of Mycobacterium tuberculosis from the lung to the brain. Dissemination is believed to occur early during infection, before the development of adaptive immunity. Toll-like receptor 2 (TLR2) mediates recognition of M. tuberculosis and initiates the innate immune response to infection. We hypothesized that polymorphisms in the TLR2 gene influence bacterial dissemination and the development of TBM. A casecontrol study was designed to test the hypothesis. Cases of bacteriologically confirmed pulmonary tuberculosis (TB) (n ¼ 183) and TBM (n ¼ 175), and cord blood controls (n ¼ 389) were enrolled in Vietnam. TLR2 genotype 597CC was associated with susceptibility to TB (odds ratio (OR) ¼ 2.22, 95% confidence interval (CI): 1.23À3.99). The association was found with meningeal rather than pulmonary TB (TBM vs control, OR ¼ 3.26, 95% CI: 1.72À6.18), and was strongest when miliary TB was found on chest radiography (controls vs TBM with miliary TB, OR ¼ 5.28, 95% CI: 2.20À12.65). Furthermore, the association increased with the severity of neurologic symptoms (grade I TBM, OR ¼ 1.93, 95% CI: 0.54À6.92; grade II, OR ¼ 3.32, 95% CI: 0.84À13.2; and grade III, OR ¼ 5.70, 95% CI: 1.81À18.0). These results demonstrate a strong association of TLR2 SNP T597C with the development of TBM and miliary TB and indicate that TLR2 influences the dissemination of M. tuberculosis.
CM appears to involve only subtle functional changes in BBB integrity with minimal intraparenchymal inflammatory responses compared with other neurologic infections. This focuses attention on local events within and around the cerebral microvasculature in CM, rather than indicating widespread parenchymal disease.
Abstract. The qinghaosu (artemisinin) group of drugs is the most important new class of antimalarials developed in the last fifty years. Although there has been no clinical evidence of neurotoxicity, an unusual pattern of damage to specific brain-stem nuclei has been reported in experimental animals receiving high doses of arteether or artemether. Detailed clinical examinations, audiometry, and brain stem auditory evoked potentials (BSAEPs) were assessed in 242 Vietnamese subjects who had previously received up to 21 antimalarial treatment courses of artemisinin or artesunate alone and 108 controls from the same location who had not received these drugs. There was no evidence of a drug effect on the clinical or neurophysiological parameters assessed. In this population there was no clinical or neurophysiological evidence of brain-stem toxicity that could be attributed to exposure to artemisinin or artesunate.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.