Adjunctive Dexamethasone for Tuberculous Meningitis in HIV-Positive Adults.

BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).

Distinct Forms of Spinal Cysticercosis: A Vietnamese Case Series.

INTRODUCTION: Neurocysticercosis (NCC), a major contributor to the burden of seizure disorders and epilepsy in the world, is one of the most common parasitic infections of the central nervous system, which is usually located in the brain. Medical therapy for NCC should initially cover appropriate symptom control and then the use of antiparasitic agents should be considered. Antiparasitic treatment is of benefit in most cases of viable and degenerating NCC. Nevertheless, cysticercosis of the spinal cord is very uncommon. CASE SERIES: In this article, we recorded 5 cases of extramedullary-intradural lumbar spinal cysticercosis, in which one case displayed cystic lesions in both brain and spine, one case showed an independent cystic lesion in the spine, and three remaining cases showed diffuse lesions in the spinal canal. CONCLUSION: Thus, in any case of single or numerous cystic lesions or dispersed lesions entering the spinal canal, spinal cysticercosis should be considered.

The tetravalent formulation of domain III-capsid proteins recalls memory B- and T-cell responses induced in monkeys by an experimental dengue virus infection.

Tetra DIIIC is a vaccine candidate against dengue virus (DENV) composed by four chimeric proteins that fuse the domain III of the envelope protein of each virus to the corresponding capsid protein. Containing B- and T-cell epitopes, these proteins form aggregates after the incubation with an immunostimulatory oligodeoxynucleotide, and their tetravalent formulation induces neutralizing antibodies and cellular immune response in mice and monkeys. Also, Tetra DIIIC protects mice after challenge with each DENV, and the monovalent formulation obtained from DENV-2 protects monkeys upon homologous viral challenge. However, in the last years, new evidences have arisen regarding domain III of DENV envelope protein as irrelevant target for neutralizing antibodies in humans. Nevertheless, vaccination with domain III induces a neutralizing antibody response that confers protection against re-infection. In addition, it has been demonstrated that the induction of a cellular immune response is essential to protect during the infection. This response can also avoid severe manifestations of dengue disease, associated to the antibody-dependent enhancement of the infection. In this study, we observed that Tetra DIIIC was able to boost the antiviral and neutralizing antibody responses previously generated in monkeys during an experimental DENV infection, demonstrating that domain III is targeted by B cells during the viral infection. Additionally, Tetra DIIIC successfully boosted the cellular immune response generated by the viruses, probably against T-cells epitopes in the capsid proteins. These results highlight the functionality of Tetra DIIIC as a vaccine candidate against DENV.