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To measure changes in muscle thickness and echogenicity, reflecting muscle bulk and quality, respectively, of quadriceps femoris (QF), in critically ill children.This study was done on 58 children aged 1-18 y requiring mechanical ventilation, admitted in a pediatric intensive care unit (PICU) of a tertiary care hospital from January 2018 to June 2019. QF thickness was measured twice in longitudinal plane and twice in transverse plane, and an average of these four measurements was used. Muscle quality was assessed using ImageJ software to determine the mean echogenicity, and was calculated separately for vastus intermedius and rectus femoris. These observations were repeated on day 3 and day 7 of the ICU stay.The median muscle thickness of QF was 1.58 cm, and vastus intermedius and rectus femoris echogenicity was 35.5 and 25.88 units, respectively in the present cohort, with median age of 6 y. Only 36 of the 58 patients underwent day 7 ultrasonography, as the remainder were either extubated or died. There was no significant change in the muscle thickness over 7 d. Rectus femoris echogenicity increased significantly over 7 d by 16.1% (p = 0.03). Baseline vastus intermedius echogenicity was significantly higher in patients who subsequently died during the course of their illness (p = 0.026).There was a significant change in rectus femoris echogenicity, but not in QF thickness. Echogenicity rather than muscle thickness may be a more sensitive marker for changes in muscle properties.

To evaluate if the use of a quality improvement (QI) initiative improves initiation and acceptability of noninvasive ventilation (NIV) in critically ill children with respiratory distress.The study was carried out in 3 phases over a period of 6 mo in the pediatric intensive care unit of a tertiary care hospital in children aged 2 mo to 14 y of age. In phase 1, data were collected for 1 mo and reasons for NIV failure were identified. In phase 2, process changes like adherence to checklist, monitoring, and one-day orientation program were instituted. The plan-do-study-act (PDSA) cycle was carried out in each phase. In phase 3, which was for 2 mo, the acceptance of NIV was measured and results were compared with phase 1.A total of 37 patients were included, 12 in phase 1 and 25 in phase 3. NIV failure was recorded in 5 (42%) and 2 (8%) patients in phase 1 and phase 3 (p = 0.025), respectively. The cause of NIV failure was intolerance to the interface in both phases. Sedation was used in 18 (72%) patients in phase 3, as compared to 2 patients in phase 1.The use of a quality improvement initiative in the form of a protocol, checklist, and training of the treating team resulted in improved tolerance to NIV, and thereby, its success. Use of sedation may help improve tolerance to the interface and contribute to its success.

Rapid, cost-effective, and sensitive diagnostic assays are essential for global tuberculosis (TB) control, especially in high TB burden, resource-limited settings. The current study was designed to evaluate diagnostic accuracy of Truenat MTB-Rif Dx (MolBio) in children less than 18 years of age, with symptoms suggestive of TB. Gastric aspirate, induced sputum, and broncho-alveolar lavage samples were subjected simultaneously to AFB-smear, GeneXpert MTB/RIF, liquid culture (MGIT-960) and Truenat MTB-Rif Dx. The index-test results were evaluated against microbiological reference standards (MRS). Truenat MTB-Rif Dx had a sensitivity of 57.1%, specificity of 92% against MRS. The sensitivity and specificity of the Truenat MTB-RIF Dx compared with liquid culture was 58.7% and 87.5% while GeneXpert MTB/RIF was 56% and 91.4%. The performance of both GeneXpert MTB/RIF and Truenat MTB-Rif Dx are comparable. Result of our study demonstrates that Truenat MTB-Rif can aid in early and efficient diagnosis of TB in children.

ObjectiveThe objective of this subanalysis of data from centres across urban areas in India of the Global Asthma Network (GAN) was to study 1) the prevalence of symptoms of asthma in children and adults, 2) the change in prevalence of asthma and its trigger factors since the International Study of Asthma and Allergies in Childhood (ISAAC), and 3) current asthma treatment practice.MethodsIn this cross-sectional, multicentre, school-based and self-administered questionnaire, responses from children aged 6–7 years and 13–14 years, and their respective parents, were analysed.ResultsThe GAN Phase I study included 20 084 children in the 6–7-year age group, 25 887 children in the 13–14-year age group and 81 296 parents. The prevalence of wheeze in the previous 12 months was 3.16%, 3.63% and 3.30% in the three groups, respectively. In comparison to the ISAAC studies, there was a significant reduction in the prevalence of current wheeze (pConclusionThe prevalence of current wheeze and its causal factors showed a significant reduction compared to previous ISAAC studies. Among subjects with current wheeze and symptoms of severe asthma, the problem of under-diagnosis and under-treatment was widespread.

BackgroundSuboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level.MethodsWe systematically searched MEDLINE, Embase and Web of Science (1990–2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration–time curve from 0 to 24 h post-dose (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0–24andCmaxwere assessed with linear mixed-effects models.ResultsOf 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0–24were summarised for isoniazid (18.7 (95% CI 15.5–22.6) h·mg·L−1), rifampicin (34.4 (95% CI 29.4–40.3) h·mg·L−1), pyrazinamide (375.0 (95% CI 339.9–413.7) h·mg·L−1) and ethambutol (8.0 (95% CI 6.4–10.0) h·mg·L−1). Our multivariate models indicated that younger age (especially 0–24for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0–24for isoniazid and pyrazinamide.N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0–24and slow acetylators had higher isoniazid AUC0–24than intermediate acetylators. Determinants ofCmaxwere generally similar to those for AUC0–24.ConclusionsThis study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.

Asthma is a chronic airway inflammatory disease that results from a complex interplay of genetic, environmental, and lifestyle factors. There is no cure for asthma, and the management is usually as per published guidelines. As in many chronic diseases conditions, various alternative or complimentary therapies have been tried. Of these, yoga and pranayama have gained wider attention in recent years. While the term yoga is a complex term encompassing eight limbs as per Patamjai in the yoga sutras, in simple terms, yoga is described as a combination of ‘asana’ (physical exercises) and ‘pranayama’ (breathing exercise). The term “asthma” has been derived from the Greek word “panting,”, which indicates a rapid and shallow breathing. The main aim of yoga and pranayama in asthma is to synchronize and control breathing, thus decreasing hyperventilation. Besides this, they also decrease the stress/strain/anxiety, change in behavior, boost immunity, and improve strength/endurance of respiratory muscles that are helpful in any subject with asthma. There have been a good number of studies including clinical trials in children with asthma that have found some beneficial effects. In the present review, the physiology of yoga and pranayama, rationale for their use in children with asthma along with a summary of various studies conducted till date, have been discussed. These are followed by recommendations regarding their incorporation in the standard of care of children with asthma.

Asthma is common in children and exacerbations are usually triggered by respiratory viruses. There was considerable concern about the impact of COVID-19 on children with asthma. It was expected that children with asthma would fare poorly during the pandemic. However, the reported effect of the COVID-19 pandemic on pediatric asthma including acute asthma admissions, does not appear to be significant, but this needs careful follow-up. The socioeconomic effects of the pandemic and reduced healthcare access could potentially impact on ongoing delivery of health care in chronic respiratory conditions including asthma, especially in resource-poor settings. Children with chronic asthma need to be treated as per internationally published guidelines with innovative models of disease monitoring and ongoing care during the pandemic. During the pandemic, children with acute asthma need to be managed carefully based on local guidelines and using strict infection control policies. The use of technology such as telehealth and various tools of asthma management including questionnaires and digital monitoring will play an important role in asthma management during the pandemic. Medical professionals, healthcare administrators, and governments should be sensitive to the evolving needs of the community and work closely to continue to provide services in a challenging yet unresolved pandemic.

To describe prevalence of various imaging findings in chronic granulomatous disease (CGD) patients; and find imaging biomarkers for differentiating chest infections caused by different micro-organisms.A retrospective study was conducted on 15 patients (49 scans) with proven CGD. Scans which had a correlative microbiological diagnosis for organisms were included in the analysis. The scans were reviewed by 3 radiologists on a predefined proforma, under the lung parenchymal, airway, pleural, mediastinal, and extrathoracic abnormalities. Analysis of various imaging parameters on a semiquantitative scale was performed, followed by a correlation of each imaging findings with causative organisms.The mean age of presentation was nearly 7 y, with a male preponderance. Definitive proof of causative organisms was obtained in 22 scans. Bacterial infection was found in 7, fungal in 12, tubercular in 2, and viral in 1 scan. Most prevalent thoracic imaging manifestations included lymphadenopathy (commonest), consolidation, nodules, air trapping, and bronchiectasis. Fungal infections showed necrotic conglomerate lymphadenopathy, cavitating nodules, and multilobar consolidation more frequently than bacterial infections (though not statistically significant). Abscesses and lymphadenopathy were the most common extrathoracic manifestations.In patients with CGD, multifocal or multilobar consolidation, mass-like consolidation, cavitating nodules, and conglomerate necrotic lymphadenopathy should alert the radiologist to a possible fungal cause.

To study the clinical, laboratory characteristics and outcomes of multisystem inflammatory syndrome in children (MIS-C) temporally related to coronavirus disease 2019 (COVID-19) in a resource-limited setting. All children meeting the World Health Organization case definition of MIS-C were prospectively enrolled. Baseline clinical and laboratory parameters were compared between survivors and non-survivors. Enrolled subjects were followed up for 4–6 weeks for evaluation of cardiac outcomes using echocardiography. The statistical data were analyzed using the stata-12 software. Thirty-one children with MIS-C were enrolled in an 11-month period. Twelve children had preexisting chronic systemic comorbidity. Fever was a universal finding; gastrointestinal and respiratory manifestations were noted in 70.9% and 64.3%, respectively, while 57.1% had a skin rash. Fifty-eight percent of children presented with shock, and 22.5% required mechanical ventilation. HSP like rash, gangrene and arthritis were uncommon clinical observations.The median duration of hospital stay was 9 (6.5–18.5) days: four children with preexisting comorbidities succumbed to the illness. The serum ferritin levels (ng/ml) [median (IQR)] were significantly higher in non-survivors as compared to survivors [1061 (581, 2750) vs 309.5 (140, 720.08), p value = 0.045]. Six patients had coronary artery involvement; five recovered during follow-up, while one was still admitted. Twenty-six children received immunomodulatory drugs, and five improved without immunomodulation. The choice of immunomodulation (steroids or intravenous immunoglobulin) did not affect the outcome. Most children with MIS-C present with acute hemodynamic and respiratory symptoms.The outcome is favorable in children without preexisting comorbidities.Raised ferritin level may be a poor prognostic marker. The coronary outcomes at follow-up were reassuring. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-05030-y.

Childhood asthma poses significant health and psychological burden on children and parents alike. Care of children with asthma requires a firm partnership and understanding between parents and physicians with regular medications and outpatient visits. Though asthma is less common in the developing world, it is more commonly associated here with severe symptoms. Environmental and economic factors, and lack of education adversely affect efficient care of children with asthma. Poor education and understanding of disease, inadequate trained pediatricians, and lack of resources for pulmonary function testing in children hamper early diagnosis of asthma in children. Hence, children frequently receive symptomatic management for acute episodes instead of long-term preventive therapy. Misconceptions regarding side effects and possible dependence on inhaled medications are frequently seen in the caretakers. This leads to abundant use of alternative medicines. Increasing ambient air pollution due to rapid urbanization and industrial growth in developing countries also adversely affects the pulmonary health of children with asthma. Community-wide campaigns are needed to improve the awareness of parents about childhood asthma and safety of inhaled medications. States should make efforts to improve infrastructure needs of children with asthma.

To develop a diagnostic algorithm for cystic fibrosis (CF) in the setting of unavailability of sweat chloride, based on clinical features and basic laboratory investigations.In a prospective observational study, we enrolled children with recurrent/persistent pneumonia with either malabsorption or poor growth, undergoing a sweat chloride test, between January 2019 and December 2020. They were simultaneously evaluated for aquagenic wrinkling of hands, stool fat globules, sputum for bacterial culture, blood gas, and serum electrolytes. Sensitivity and specificity were calculated for parameters having a significant difference between CF and non-CF groups. Scoring systems and algorithms for the diagnosis of CF were developed.Of 134 children enrolled, 46 (34%) had CF. The sensitivity and specificity of various parameters to diagnose CF was: sibling death due to respiratory illness (30.43%, 96.59%), aquagenic wrinkling (76.74%, 47.67%), metabolic alkalosis (17.78%, 94.12%), hyponatremia (28.89%, 89.41%), stool fat globules (38.46%, 81.18%), and presence of Pseudomonas in sputum culture (23.68%, 98.80%). Using coefficients of significant parameters on stepwise logistic regression, the composite score for diagnosis of CF was calculated as: 3X sibling death due to respiratory illness + 1.5X hyponatremia + 1.5X metabolic alkalosis + 1.5X aquagenic wrinkling + 1X stool fat globules + 2.5X presence of Pseudomonas in sputum culture (each of the variables scores 0 or 1 for absence and presence, respectively). The cut-off of ≥2.5 had sensitivity and specificity of 81.82% and 76.83%, respectively.In resource-limited settings, the proposed diagnostic algorithm can be used for the diagnosis of presumptive CF with fair sensitivity and specificity.

Children with cystic fibrosis (CF) constitute a high-risk group for COVID-19 with underlying chronic lung disease. COVID-19 severity varying from mild infection to need of intensive care has been described in children with CF. Two children with significant underlying pulmonary morbidity are described here, who developed severe disease following SARS-CoV-2 infection. Case 1 (a 9-y-old boy) had pneumonia with respiratory failure requiring noninvasive ventilation support. He had delayed clearance of SARS-CoV-2, with recurrence of symptomatic disease with short asymptomatic period in between. He was also diagnosed with CF-related diabetes and allergic bronchopulmonary aspergillosis during the second episode. Case 2 (an 18-mo-old boy) had two episodes of SARS-CoV-2–related severe lower respiratory infection within a period of 2 mo, requiring high-flow nasal oxygen support. Both children had 3rd pulmonary exacerbation but SARS-CoV-2 was not detected in respiratory secretions. To conclude, children with CF with underlying pulmonary morbidity, can develop severe COVID-19 and prolonged SARS-CoV-2 shedding. Supplementary Information The online version contains supplementary material available at 10.1007/s12098-021-04057-0.

Allergic bronchopulmonary aspergillosis (ABPA) is an IgE-mediated hypersensitivity reaction predominantly occurring in patients of asthma and cystic fibrosis. The typical radiological findings in ABPA include central bronchiectasis and fleeting opacities. In this retrospective study, the aim was to describe cases of ABPA in children who had a mass-like lesion in the lung. There were 5 cases of ABPA in children, who presented as mass-like lesions that responded very well to treatment for ABPA. All cases, except 1, had asthma as the underlying disease. There was a delay in the diagnosis of ABPA in all 5 cases. There had been unnecessary invasive investigations in some of these cases before the diagnosis of ABPA was made. To conclude, children with ABPA may present with a mass-like lesion in the lung and high index of suspicion is required to diagnose ABPA timely to prevent its consequences.

Chikungunya virus (CHIKV) infection is endemic in many different countries. CHIKV outbreaks are emerging in new areas and re-emerging in previously exposed geographical regions, thus making it a significant public health concern. CHIKV infections are often clinically inapparent, especially in children, which poses a challenge to testing and evaluating any vaccine. During CHIKV infection, CHIKV-specific antibodies are produced, and some of these antibodies can neutralize viruses released from infected cells before they can enter uninfected cells. In this study, we evaluated IgG binding and neutralizing antibody responses in paired serum samples from CHIKV-infected children and those with other febrile illness, using a recombinant truncated E2 protein and whole CHIKV particles as test antigens. Antibody detection using the truncated E2 protein showed a significant overlap between CHIKV-infected subjects and those with other febrile illnesses. This overlap was greater when binding antibody titers were determined using fixed CHIKV particles as the test antigen. Acute- and convalescent-phase sera collected from children after CHIKV infection showed significant differences in their neutralizing capacity. The neutralizing and binding antibody response showed a significant positive correlation. We detected IgG antibodies in most cases during the acute phase of infection. This was observed at two different geographical locations, one of which is not considered highly endemic. Conventional wisdom would suggest this to be a marker of re-infection (secondary infection). However, dissenting opinions have been voiced in other viral diseases (such as Ebola) where studies have detected IgG in acute illness. In the absence of any significant body of work documenting secondary CHIKV infections, we believe further work is needed to understand the early IgG response that we observed.

The present study explored the association between daily ambient air pollution and daily emergency room (ER) visits due to acute respiratory symptoms in children of Delhi. The daily counts of ER visits (ERV) of children (≤15 years) having acute respiratory symptoms were obtained from two hospitals of Delhi for 21 months. Simultaneously, data on daily concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3) and weather variables were provided by the Delhi Pollution Control Committee. K-means clustering with time-series approach and multi-pollutant generalized additive models with Poisson link function was used to estimate the 0-6-day lagged change in daily ER visits with the change in multiple pollutants levels. Out of 1,32,029 children screened, 19,120 eligible children having acute respiratory symptoms for ≤2 weeks and residing in Delhi for the past 4 weeks were enrolled. There was a 29% and 21% increase in ERVs among children on high and moderate level pollution cluster days, respectively, compared to low pollution cluster days on the same day and previous 1-6 days of exposure to air pollutants. There was percentage increase (95% CI) 1.50% (0.76, 2.25) in ERVs for acute respiratory symptoms for 10 μg/m3 increase of NO2 on previous day 1, 46.78% (21.01, 78.05) for 10 μg/m3 of CO on previous day 3, and 13.15% (9.95, 16.45) for 10 μg/m3 of SO2 on same day of exposure. An increase in the daily ER visits of children for acute respiratory symptoms was observed after increase in daily ambient air pollution levels in Delhi.

Background Cyclic neutropenia is a rare genetic disorder causing the arrest of neutrophil function and is characterized by periodic neutropenia and recurrent infections. Patients with cyclic neutropenia with autosomal dominant, sporadic, and X-linked may have mutations in the ELANE gene, and autosomal recessive cases have homozygous/compound heterozygous variants in the HAX1 gene primarily. Observation The authors describe a novel variant in the HAX1 gene, which was detected by next-generation sequencing in an 8-year-old male child who presented with recurrent infections and neutropenia. Conclusion The patient extends the clinical variability associated with HAX1 variants and highlights the importance of genetic investigations in patients with suspected cyclic neutropenia.

There is a paucity of data on use of dexmedetomidine as a sedative agent in mechanically ventilated children. To compare the efficacy of dexmedetomidine and midazolam for sedation in mechanically ventilated children aged 1 month — 15 years. Secondary objectives were to compare the need for top-up doses of fentanyl and paralytic agents, duration of mechanical ventilation, ICU stay and hospital stay, and adverse events. Open label, non-inferiority, randomized controlled trial. PICU of a tertiary care teaching hospital in India. Consecutive children aged 1 month to 15 years who were mechanically ventilated. Children were randomized to either dexmedetomidine or midazolam and the doses were titrated to maintain target sedation score of 4 or 5 as measured by Penn State Children Hospital Sedation algorithm. The percentage of time spent in level 4 or 5 of Penn State Children Hospital sedation algorithm for ventilated children. 49 children were randomized (24 to ‘midazolam group’ and 25 to ‘dexmedetomidine group’). There was no difference in the percentage of time spent in the targeted sedation between the groups [midazolam 67.3% (18.8) vs. dexmedetomidine 56.3 %. (28.6); P=0.12]. The absolute difference in the percentage of time spent was −10.9% [SE (95% CI) 7.05: (−25.15 to 3.25)]. The lower end of 95% CI for the difference breached the non-inferiority limit of −20%. Number of fentanyl boluses, duration of mechanical ventilation, ICU stay, and hospital stay were similar. Four (17.4%) children in dexmedetomidine group developed persistent bradycardia. Non-inferiority of dexmedetomidine compared to midazolam for sedation in children on mechanical ventilation could not be established.

Objectives To examine if the use of honey (medicated) for dressing is superior to standard care in terms of time to complete wound healing in stages 1-3 of pressure injuries in children admitted to the PICU. Design Multicenter, open-label, parallel-group, randomized trial. Setting Tertiary-care PICU from August 2017 to January 2019. Patients Critically ill children, 2 months to 17 years old, who developed pressure injury (stages 1-3) were included; those on more than two inotropes or with signs of acute wound infection or wounds with greater than 5 cm diameter or known allergy to honey were excluded. Interventions Children were randomized to receive either medicated honey dressing or standard (routine) wound care for the management of their pressure injury. Measurements and main results The primary outcome was the time to complete wound healing. Manuka or active Leptospermum honey dressing/gel was used in the intervention group. Enrolled children were followed up until death or discharge from the hospital. A total of 99 children were enrolled: 51 in the intervention group and 48 in the standard care group. Baseline characteristics, including the nutritional status, were comparable between the groups. The most common sites of injury were bony prominences at face mask contact points. The median time to complete healing was 7 days (95% CI, 6-7 d) versus 9 days (7-10 d) in the intervention and standard care groups, respectively (p = 0.002; log-rank test). At any random time, children in the intervention group were about 1.9-fold more likely to have their pressure injury completely healed than those in the standard care group (hazard ratio 1.86; 95% CI, 1.21-2.87). There were no allergic reactions or secondary wound infections in the intervention group. Conclusions The use of medicated honey dressings decreased the time to wound healing in critically ill children with pressure injuries. There were no allergic reactions or secondary bacterial infections in any of these children.

BACKGROUND Bronchoalveolar lavage (BAL) via flexible bronchoscopy is a valuable diagnostic technique in children. The quality of BAL is directly related to the volume of the fluid recovered. Continuous wall suctioning and handheld syringe suctioning are the 2 commonly used methods, but they are rarely compared in children. We aimed to compare the above 2 suctioning techniques for BAL in the pediatric age group. METHODS This randomized controlled study enrolled children from 1 month to 18 years of age undergoing flexible bronchoscopy and BAL. We compared continuous wall suctioning and the handheld syringe suctioning technique. The primary outcome was the percentage of BAL fluid recovery in 2 different suctioning techniques. Secondary outcomes included technical acceptable BAL and yield of various diagnostic tests in BAL. RESULTS The study included 73 children (48 boys) with a median (interquartile range) age of 30 (8, 108) months. There were 37 children in the wall mount group and 36 children in the syringe suction group. Baseline characteristics of the groups were similar. The wall mount suction had more recovery of BAL fluid compared with the syringe method (43.6±8.4% vs. 37.8±8.5%, P=0.004). The proportion of BAL having a fluid recovery of ≥40% was also high in the wall mount suction [31 (83.8%) vs. 17 (47.2%); P=0.001]. There was no difference in diagnostic yield between the groups. CONCLUSION Wall mount suction had better BAL fluid recovery compared with handheld syringe suction in children undergoing flexible bronchoscopy. The diagnostic yield was similar in both groups.

BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and transesophageal bronchoscopic ultrasound-guided fine-needle aspiration (EUS-B-FNA) are established modalities for evaluation of mediastinal/hilar lymphadenopathy in adults. Limited literature is available on the utility of these modalities in the pediatric population. Herein, we perform a systematic review and meta-analysis on the yield and safety of EBUS-TBNA and EUS-B-FNA in children. METHODS We performed a systematic search of the PubMed and EMBASE databases to extract the studies reporting the utilization of EBUS-TBNA/EUS-B-FNA in children (

RATIONALE The extent of diaphragmatic atrophy and dysfunction in critically ill children from developing countries is not established. OBJECTIVES To estimate changes in ultrasound measurements of diaphragmatic thickness over the first week of mechanical ventilation. To assess magnitude and risk factors of diaphragmatic atrophy. METHODS In an observational cohort study, children aged 1-18 years, requiring mechanical ventilation were included. Ultrasound measurements of diaphragmatic thickness at end-expiration (DTe) and end-inspiration (DTi), and diaphragmatic thickening fraction (DTF) were performed daily during the first week of admission, and pre- and post-extubation. Diaphragmatic atrophy (%) and atrophy rate (rate of decline in DTe, % per day) were calculated. MEASUREMENTS AND MAIN RESULTS Of 55 children (74.6% boys) enrolled, 20 (36.4%) died. Of 35 children with planned extubation, 5 (14.3%) required reintubation. Baseline median (interquartile range [IQR]) DTe, DTi, and DTF were 1.27 mm (1, 1.6), 1.76 mm (1.35, 2.10), and 33.75% (26.90, 44.60), respectively. There was a significant reduction in DTe over the first week of mechanical ventilation (p

Broadly neutralizing antibodies (bnAbs) develop in a subset of HIV-1 infected individuals over 2–3 years of infection. Infected infants develop plasma bnAbs frequently and as early as 1-year post-infection suggesting factors governing bnAb induction in infants are distinct from adults. Understanding viral characteristics in infected infants with early bnAb responses will provide key information about antigenic triggers driving B cell maturation pathways towards induction of bnAbs. Herein, we evaluate the presence of plasma bnAbs in a cohort of 51 HIV-1 clade-C infected infants and identify viral factors associated with early bnAb responses. Plasma bnAbs targeting V2-apex on the env are predominant in infant elite and broad neutralizers. Circulating viral variants in infant elite neutralizers are susceptible to V2-apex bnAbs. In infant elite neutralizers, multivariant infection is associated with plasma bnAbs targeting diverse autologous viruses. Our data provides information supportive of polyvalent vaccination approaches capable of inducing V2-apex bnAbs against HIV-1., Some infants develop broadly neutralizing antibodies (bnAbs) to HIV in a shorter time frame than adults, but the reasons aren’t well understood. Here, the authors study a cohort of 51 HIV-1 clade C perinatally infected infants of Indian origin and find that multivariant infection is associated with bnAbs in elite neutralizers.

Leukocyte adhesion deficiencies (LADs) are a type of primary immunodeficiencies characterized by delayed detachment of the umbilical cord, impaired wound healing, leukocytosis, and recurrent infections. The disease is caused by genetic defects affecting different steps in the process of leukocyte adhesion cascade such as rolling, integrin activation, and adhesion of leukocytes, resulting in the impairment of leukocyte trafficking. Till date, three types of LAD have been documented: type I, II and III. Type I LAD is caused by congenital defect in the β2 integrin receptor complex CD11/CD18 on the cell surface of leukocytes, which results in impaired leukocytes connection to endothelial cells and migration. Type II LAD is caused by defect in the fucose metabolism resulting in the absence of fucosylated selectin ligands on neutrophils and impaired rolling phase of the leukocyte adhesion cascade. Type III LAD is caused by mutations in the kindlin-3 gene resulting in defective integrin activation. In this article, we present a review of literature for type I LAD, and successful treatment of patient using umbilical cord blood stem cell transplantation.

To evaluate association between total IgE levels and wheezing in preschool children from India. Data were collected in a prospective birth cohort study related to wheezing till three years of age. Total IgE was measured at enrolment, at one year and two years of age and correlated with wheezing episodes. A total of 310 (167 boys) children were enrolled. Total IgE levels increased with age (P

Background & objectives: Pulmonary disease is the main cause of morbidity and mortality in cystic fibrosis (CF). The infection occurs with a unique spectrum of bacterial pathogens that are usually acquired in an age-dependent fashion. The objective of this study was to find out the aetiological agents in respiratory specimens from children with CF during pulmonary exacerbation and relate with demographic variables. Methods: In this observational study, airway secretions from children (n=104) with CF presenting with pulmonary exacerbations were collected and tested for bacteria, fungi, mycobacteria and viral pathogens using appropriate laboratory techniques. The frequencies of isolation of various organisms were calculated and associated with various demographic profiles. Results: Bacteria were isolated in 37 (35.5%) and viral RNA in 27 (29.3%) children. Pseudomonas was the most common bacteria grown in 31 (29.8%) followed by Burkholderia cepacia complex (Bcc) in three (2.8%) patients. Among viruses, Rhinovirus was the most common, identified in 16 (17.4%) samples followed by coronavirus in four (4.3%). Fungi and mycobacteria were isolated from 23 (22.1%) and four (3.8%) children, respectively. Aspergillus flavus was the most common fungus isolated in 13 (12.5%) children. Interpretation & conclusions: Pseudomonas was the most common organism isolated during exacerbation. Non-tuberculous mycobacteria were not isolated, whereas infection with Bcc and Mycobacterium tuberculosis was observed, which could probably have a role in CF morbidity. Polymicrobial infections were associated with severe exacerbations.

Purpose: The purpose of this study is to determine the antimicrobial susceptibility pattern, serotype distribution and sequence type (ST) of Streptococcus pneumoniae isolates from invasive and non-invasive infection and correlate it with isolates from commensal nasopharyngeal flora to ascertain their role in infection. Materials and Methods: S. pneumoniae isolates from blood, cerebrospinal fluid, pleural fluid and respiratory secretions (sputum, bronchoalveolar lavage and nasopharyngeal swab/throat swab) were analysed to determine ST, serotype and antimicrobial susceptibility pattern. Serotyping was performed by multiplex polymerase chain reactions as well as by quellung reaction. Antimicrobial susceptibility testing was determined using Kirby Bauer's disc diffusion method as per the Clinical Laboratory Standards Institute guidelines. Minimum inhibitory concentration was determined using E-test for penicillin. Multilocus sequence typing (MLST) was done to understand genetic relatedness and evolutionary relationship among strains. Results: A total of 125 S. pneumoniae isolates were collected, including 25 from invasive pneumococcal disease, 25 from non-invasive and 75 from nasopharyngeal swab of healthy children (Commensal). Resistance to penicillin, erythromycin, and co-trimoxazole was observed in 14.4%, 12% and 81.6% of the isolates, respectively, by KirbyBauer's disc diffusion method. Serotype 14 was found to be the most prevalent in invasive and non-invasive isolates, while serotype 6 was the most common in commensal isolates. New STs were found among invasive (ST13826, ST13827), non-invasive (ST13823, ST13824, and ST13961) and commensal (ST13825) isolates. Conclusion: MLST sequence analysis shows that invasive isolates were found to be clustered with non-invasive and commensal isolates. Analysis of MLST suggests the possibility of genetic relatedness and exchange of genetic material between invasive, non-invasive and commensal isolates.

To develop a normal reference range of Infant pulmonary function test (IPFT) indices for Indian children. Prospective birth cohort study. Division of Pediatric Pulmonology of a tertiary-care institute in India from August 2012 to March 2017. All neonates born at the institute during the study period were screened for eligibility. IPFT at baseline and every 6-month until 36-months of age. Tidal breathing flow-volume loop (TBFVL), Rapid thoracoabdominal compression (RTC), and Raised volume RTC (RVRTC) indices at baseline and follow-up. 310 newborns were enrolled in the cohort; 281 of them (169 male) had completed 36-months of follow-up at the end of the study period. There was no influence of gender on the baseline IPFT indices. Tidal volume per unit body weight (VT/kg) significantly increased from baseline to 36 months of age (P

Background:arious complementary or alternative medicines (including breathing exercises and yoga/pranayama) have been tried as an attractive option to pharmacotherapy in childhood asthma.Objective:To evaluate the role of breathing exercise and yoga/pranayama as add on therapy to the “pharmacologically recommended treatment” of childhood asthma.Methods:We searched the published literature in the major databases: Medline via Ovid, PubMed, CENTRAL, Embase, and Google Scholar till June 2018. Randomized trials comparing breathing exercises and yoga/ pranayama versus control or as part of a composite intervention versus control were included. The primary outcome measures were quality of life and change in asthma symptoms. Secondary outcomes were: decrease in medication use, number of exacerbations, change in lung function and immunological parameters, school absenteeism and adverse events.Results:A total of 10 trials (466 children, 6-14 years age) were included. The severity of asthma varied among the trials. The data for primary outcome measures could not be pooled, there were mixed results for both primary and secondary outcomes. No significant benefit was obtained in acute asthma and the lung function tests [except PEFR % at 4-6 weeks, PEF absolute at 3 months, and FVC absolute at 3 months] in chronic asthma. One trial compared breathing exercise versus yoga and found no difference. Adverse events were not significant.Conclusion:Breathing exercise and yoga/ pranayama may have some additive role in the treatment of childhood asthma. However, at present, it cannot be recommended as a standard of care due to insufficient data.

Background Scrub typhus was once thought to be a disease of rural origin and was confined to specific pockets in South Asia. Early diagnosis and treatment is extremely important as it is associated with high mortality if left untreated. Aim To delineate the clinical and molecular epidemiology of scrub typhus in patients presenting with acute febrile illness from various parts of India. Methods During the study period of 5 years (October 2013 to October 2018), a total of 1742 patients with acute febrile illness Results A total of 210 (12.1%) patients were diagnosed with scrub typhus. Of these, nested PCR was positive in only 85 patients. Sequencing and phylogenetic analysis showed that the predominant circulating genotypes were Gilliam and Karp. On multivariate analysis, acute respiratory distress syndrome, myocarditis, encephalitis/encephalopathy, jaundice and splenomegaly were significantly more common in those patients who were diagnosed with scrub typhus. A total of 14 patients diagnosed with scrub typhus succumbed to the illness. Conclusion Patients with fever, headache, pulmonary manifestations, CNS manifestations, myocarditis, transaminitis or thrombocytopenia presenting in the monsoon and post-monsoon season should be evaluated for scrub typhus irrespective of the geographical location in India.

Over the past 15 years, and despite many difficulties, significant progress has been made to advance child and adolescent tuberculosis (TB) care. Despite increasing availability of safe and effective treatment and prevention options, TB remains a global health priority as a major cause of child and adolescent morbidity and mortality—over one and a half million children and adolescents develop TB each year. A history of the global public health perspective on child and adolescent TB is followed by 12 narratives detailing challenges and progress in 19 TB endemic low and middle-income countries. Overarching challenges include: under-detection and under-reporting of child and adolescent TB; poor implementation and reporting of contact investigation and TB preventive treatment services; the need for health systems strengthening to deliver effective, decentralized services; and lack of integration between TB programs and child health services. The COVID-19 pandemic has had a significant negative impact on case detection and treatment outcomes. Child and adolescent TB working groups can address country-specific challenges to close the policy–practice gaps by developing and supporting decentral ized models of care, strengthening clinical and laboratory diagnosis, including of multidrug-resistant TB, providing recommended options for treatment of disease and infection, and forging strong collaborations across relevant health sectors.