Management of Children Admitted to Hospitals across Bangladesh with Suspected or Confirmed COVID-19 and the Implications for the Future: A Nationwide Cross-Sectional Study.

There is an increasing focus on researching children admitted to hospital with new variants of COVID-19, combined with concerns with hyperinflammatory syndromes and the overuse of antimicrobials. Paediatric guidelines have been produced in Bangladesh to improve their care. Consequently, the objective is to document the management of children with COVID-19 among 24 hospitals in Bangladesh. Key outcome measures included the percentage prescribed different antimicrobials, adherence to paediatric guidelines and mortality rates using purposely developed report forms. The majority of 146 admitted children were aged 5 years or under (62.3%) and were boys (58.9%). Reasons for admission included fever, respiratory distress and coughing; 86.3% were prescribed antibiotics, typically parenterally, on the WHO 'Watch' list, and empirically (98.4%). There were no differences in antibiotic use whether hospitals followed paediatric guidance or not. There was no prescribing of antimalarials and limited prescribing of antivirals (5.5% of children) and antiparasitic medicines (0.7%). The majority of children (92.5%) made a full recovery. It was encouraging to see the low hospitalisation rates and limited use of antimalarials, antivirals and antiparasitic medicines. However, the high empiric use of antibiotics, alongside limited switching to oral formulations, is a concern that can be addressed by instigating the appropriate programmes.

Validation of rapid neurodevelopmental assessment for 2- to 5-year-old children in Bangladesh.

OBJECTIVE: Validate a tool to determine neurodevelopmental impairments (NDIs) in >2- to 5-year-old children in a country with limited child development expertise. METHODS: Rapid Neurodevelopmental Assessment (RNDA) is a tool designed to detect functional status and NDIs across multiple neurodevelopmental domains. Validity was determined in 77 children enrolled by door-to-door sampling in Dhaka and who were administered the RNDA by 1 of 6 testers (4 developmental therapists, 2 special education teachers) and simultaneously administered a test of adaptive behavior (AB; Independent Behavior Assessment Scale) and intelligence quotient (IQ) tests (Bayley Scales of Infant Development II, Stanford Binet Intelligence Scale, Wechsler Preschool and Primary Scales of Intelligence) by psychologists. RESULTS: Interrater reliability ranged from good to excellent. There were significant differences in AB in mean percentile scores on the Independent Behavior Assessment Scale for motor (P = .0001), socialization (P = .001), communication (P = .001), and full-scale (P = .001) scores in children with ≥1 NDI ("any NDI") versus no NDI. Significant differences in those with versus those without "any NDI" were found on IQ scores. Sensitivity and specificity for "significant difficulties" (defined as AB z-scores < -2 SDs and/or IQ <70) and "mild difficulties included" (AB z-scores < -1SD and/or IQ <85) were 90% and 60% and 80% and 76%, respectively. CONCLUSIONS: The RNDA validity results are promising for use by child care professionals in field and clinical settings, but the tool needs further replication and refinement for assessment of specific impairments of vision, hearing, and seizures.

Validation of rapid neurodevelopmental assessment instrument for under-two-year-old children in Bangladesh.

OBJECTIVE: The objective of this study was to determine the reliability and validity of a comprehensive assessment procedure for ascertaining neurodevelopmental status of children aged 0 to 24 months for use by multidisciplinary professionals in a developing country. METHODS: We developed the Rapid Neurodevelopmental Assessment (RNDA) to determine functional status in the following domains: primitive reflexes, gross motor, fine motor, vision, hearing, speech, cognition, behavior, and seizures. Reliability was determined for 50 children who were aged <3 months and 30 children who were aged > or =3 to 24 months and were administered the RNDA by 8 different professionals (3 physicians, 4 therapists, and 1 special teacher). Validity was determined on 34 children aged <3 months in hospital and 81 children aged > or =3 to 24 months in urban (n = 47) and rural (n = 34) community-based populations by any 1 of the 8 professionals, with simultaneous administration of the adapted Bayley Scales of Infant Development II by a psychologist as the gold standard. RESULTS: Mean kappa coefficients of agreement among professionals in overall and individual domains in the 2 age groups ranged from good to excellent. For both younger and older children, there was good concurrent validity (ie, significantly lower mean Mental Development Index and Psychomotor Development Index scores) for children with > or =1 neurodevelopmental impairment and for children with impairments in most functional domains, compared with children with no impairments. Significantly more impairments were found in children from disadvantaged compared with socioeconomically more advantaged communities, indicating good discriminant validity. CONCLUSIONS: The RNDA can be used by professionals from a range of backgrounds with high reliability and validity for determining functional status of children who are younger than 2 years. The study findings have important practical implications for early identification and intervention to mitigate neurodevelopmental impairments in large populations that live in developing countries where professional expertise is sparse.

Accelerated induction of mycobacterial antigen-specific CD8+ T cells in the Mycobacterium tuberculosis-infected lung by subcutaneous vaccination with Mycobacterium bovis bacille Calmette-Guérin.

Both CD4(+) and CD8(+) T cells are important in protection against Mycobacterium tuberculosis infection. To evaluate the effect of vaccination with Mycobacterium bovis bacille Calmette-Guérin (BCG) on the CD8(+) T-cell response to pulmonary M. tuberculosis infection, we analyzed the kinetics of CD8(+) T cells specific to the mycobacterial Mtb32a(309-318) epitope, which is shared by M. tuberculosis and M. bovis BCG, in the lung of mice infected with M. tuberculosis. The CD8(+) T cells were detected by staining lymphocytes with pentameric major histocompatibility complex (MHC) class I H-2D(b-)Mtb32a(209-318) peptide complex and were analysed by flow cytometry. Mtb32a-specific CD8(+) T cells became detectable on day 14, and reached a plateau on day 21, in the lung of M. tuberculosis-infected unvaccinated mice. Subcutaneous vaccination with M. bovis BCG in the footpads induced Mtb32a-specific CD8(+) T cells in the draining lymph nodes (LNs) on day 7 and their numbers further increased on day 14. When M. bovis BCG-vaccinated mice were exposed to pulmonaryinfection with M. tuberculosis 4 weeks after vaccination, the Mtb32a-specific CD8(+) T cells in the infected lung became detectable on day 7 and reached a plateau on day 14, which was 1 week earlier than in the unvaccinated mice. The pulmonary CD8(+) T cells from the BCG-vaccinated M. tuberculosis-infected mice produced interferon-gamma in response to Mtb32a(209-318) peptide on day 7 of the infection, whereas those of unvaccinated mice did not. The results demonstrate that induction of mycobacterial antigen-specific protective CD8(+) T cells in the M. tuberculosis-infected lung is accelerated by subcutaneous vaccination with M. bovis BCG.

Diploid/polyploid syntenic shuttle mapping and haplotype-specific chromosome walking toward a rust resistance gene (Bru1) in highly polyploid sugarcane (2n approximately 12x approximately 115).

The genome of modern sugarcane cultivars is highly polyploid (approximately 12x), aneuploid, of interspecific origin, and contains 10 Gb of DNA. Its size and complexity represent a major challenge for the isolation of agronomically important genes. Here we report on the first attempt to isolate a gene from sugarcane by map-based cloning, targeting a durable major rust resistance gene (Bru1). We describe the genomic strategies that we have developed to overcome constraints associated with high polyploidy in the successive steps of map-based cloning approaches, including diploid/polyploid syntenic shuttle mapping with two model diploid species (sorghum and rice) and haplotype-specific chromosome walking. Their applications allowed us (i) to develop a high-resolution map including markers at 0.28 and 0.14 cM on both sides and 13 markers cosegregating with Bru1 and (ii) to develop a physical map of the target haplotype that still includes two gaps at this stage due to the discovery of an insertion specific to this haplotype. These approaches will pave the way for the development of future map-based cloning approaches for sugarcane and other complex polyploid species.