Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Population-based repeat cross-sectional seroprevalence survey of SARS-CoV-2 IgG antibodies in Pimpri Chinchwad Municipal Corporation Area, Maharashtra, India

Context: Population-based seroepidemiological studies are recommended to measure the extent of spread of coronavirus disease of 2019 (COVID-19) infection in an area. The present seroprevalence survey was planned with the aim to estimate the cumulative burden of the COVID-19 disease in the Pimpri Chinchwad corporation area. Aims: To estimate the cumulative burden of the COVID-19 disease in the Pimpri Chinchwad corporation area. Settings and Design: The study was carried out in Pimpri Chinchwad Municipal Corporation (PCMC) city area. It was a descriptive cross-sectional survey. Materials and Methods: A population-based seroprevalence study for immunoglobulin G (IgG) antibodies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was carried out among 10082 residents in the age group of 6 years and above selected by cluster random sampling. Thirty-five clusters were in slums, 45 clusters in tenements and 120 clusters from housing societies. The fieldwork for the collection of samples was carried out from 16 June to 17 June 2021. For antibody testing, a kit from Abbott (SARS-CoV-2 IgG) was used which employs chemiluminescent microparticle immunoassay (CMIA) technology. Statistical Analysis Used: Frequency analysis was done for sociodemographic variables, the cumulative incidence of COVID-19, age-stratified infection rate, risk factors and COVID symptomatic versus asymptomatic cases. Chi-square test of association was applied to test the association between seropositivity and sociodemographic and clinical profile of participants. Results: The overall seropositivity for IgG antibodies was 81.34%. Those living in the Gaothan area (tenements) had a positivity rate of 84.5%. The age group between 45 and 60 years had a seropositivity of 91%. Conclusions: The study indicates that a considerable proportion of the population had encountered the novel coronavirus approaching herd immunity