Outcome of COVID-19 in Children With Tuberculosis: Single-Center Experience.

OBJECTIVE: To evaluate the outcome of Coronavirus disease 2019 (COVID-19) infection in children and adolescents with tuberculosis. METHODS: We analyzed hospital records for the period May, 2020 to September, 2021 for children who were severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase-polymerase chain reaction (RT-PCR) positive or SARS-CoV-2 antibody positive. They were divided into two groups viz., those with tuberculosis (tuberculosis group) and those without tuberculosis (non-TB group). Demographic information, symptoms, and outcomes of COVID-19 were compared between the two groups. RESULTS: Median (IQR) age of participants was 11 (8,14) and 4.5 (2,9) year for the tuberculosis and non-TB groups, respectively. 93.5% and 36.1% of children were asymptomatic in the tuberculosis and non-TB group, respectively. No variable in the study was significantly associated with COVID-19 positivity in children with tuberculosis. No difference was found in the outcomes of COVID-19 infection in children having tuberculosis. CONCLUSIONS: No differences were noted in the outcomes of COVID-19 infection in children having tuberculosis.

Patterns and distribution of de novo mutations in multiplex Middle Eastern families.

While de novo mutations (DNMs) are key to genetic diversity, they are also responsible for a high number of rare disorders. To date, no study has systematically examined the rate and distribution of DNMs in multiplex families in highly consanguineous populations. Leveraging WGS profiles of 645 individuals in 146 families, we implemented a combinatorial approach using 3 complementary tools for DNM discovery in 353 unique trio combinations. We found a total of 27,168 DNMs (median: 70 single-nucleotide and 6 insertion-deletions per individual). Phasing revealed around 80% of DNMs were paternal in origin. Notably, using whole-genome methylation data of spermatogonial stem cells, these DNMs were significantly more likely to occur at highly methylated CpGs (OR: 2.03; p value = 6.62 × 10-11). We then examined the effects of consanguinity and ethnicity on DNMs, and found that consanguinity does not seem to correlate with DNM rate, and special attention has to be considered while measuring such a correlation. Additionally, we found that Middle-Eastern families with Arab ancestry had fewer DNMs than African families, although not significant (p value = 0.16). Finally, for families with diseased probands, we examined the difference in DNM counts and putative impact across affected and unaffected siblings, but did not find significant differences between disease groups, likely owing to the enrichment for recessive disorders in this part of the world, or the small sample size per clinical condition. This study serves as a reference for DNM discovery in multiplex families from the globally under-represented populations of the Middle-East.

Predictors of outcomes in children with Central Nervous System tuberculosis.

BACKGROUND: Central Nervous system tuberculosis (CNS-Tb) is the most lethal form of extra-pulmonary tuberculosis in children. The lack of markers of outcome provides little information on the efficacy of the current treatment protocols for CNS-Tb and thus results in a higher mortality rate than other extrapulmonary manifestations of tuberculosis. This study aims to identify significant factors that will reliably predict the outcomes at discharge in children admitted with CNS-Tb. METHODS AND MATERIAL: This is a prospective observational study in children with neurotuberculosis admitted at a tertiary care hospital. Clinical presentations at the time of admission were studied. Outcomes at the end of in-patient care (completely cured, survival with some/severe disability or death) were correlated with clinical, laboratory, microbiological, and radiological parameters. Univariate and multivariate analyses were applied to study the parameters and a p-value ≤ 0.05 with a confidence interval (CI) of 95% was considered as statistically significant. FINDINGS: The study included 100 children between 4 months and 12 years of age with a mean of 5.84 (±3.5) years. At discharge, 55% of children recovered completely, 20% had some or severe disability and 25% died. On multivariate analysis, high CSF protein (p = 0.050) and drug resistance (p = 0.034) were highly associated with fatality. Meningeal enhancements with basal exudates (p = 0.021) and CSF lymphocyte count >90% were highly associated with survival with disability. Stage I disease at presentation (p < 0.0001) was the only variable associated with complete recovery. INTERPRETATION: Reliable prognostic markers for CNS-Tb can aid in predicting the efficacy of the current treatment and the anticipated outcome in the children with this disease. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Drug Resistance in Children with Central Nervous System Tuberculosis from a Tertiary Care Center in Mumbai.

INTRODUCTION: Central Nervous System tuberculosis (CNS-TB) is the most lethal form of extra-pulmonary TB, especially in children. In this study, we have discussed patterns of drug resistance in pediatric CNS-TB. MATERIALS AND METHODS: Prospective observational study conducted on 100 children at a tertiary care center. Diagnosed cases of CNS-TB were enrolled. GeneXpert MTB/RIF was used upfront for diagnosis, and in cases where TB MGIT culture was positive, a phenotypic Drug Susceptibility Test (DST) was done. Patients were divided into resistant to at least one drug (DR) and drug-susceptible (DS). Various parameters were compared between these groups. RESULTS: Mean age of participants was 5.84 ± 3.5 years, with a male-to-female ratio of 1.08 : 1; 14% of children had drug-resistant CNS TB (DR-CNS-TB). A higher proportion of children previously treated for TB were associated with drug resistance (p = 0.009), and those with disseminated TB also had a higher drug resistance (p = 0.002). Apart from this, the DR and DS groups had no statistically significant differences in demographic, clinical or epidemiological parameters. CONCLUSIONS: Previous history of being treated for TB and disseminated TB was an independent risk factor for DR-CNS-TB. Ensuring proper adherence and compliance to anti-tubercular treatment could help in preventing the emergence of DR TB.