Publications by authors named "Sushil Kumar Kabra"

90 Publications

Role of Breathing Exercises in Asthma-Yoga and Pranayama.

Indian J Pediatr 2021 Nov 23. Epub 2021 Nov 23.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

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.
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http://dx.doi.org/10.1007/s12098-021-03998-wDOI Listing
November 2021

Outcomes of multisystem inflammatory syndrome in children temporally related to COVID-19: a longitudinal study.

Rheumatol Int 2021 Oct 19. Epub 2021 Oct 19.

All India Institute of Medical Sciences, New Delhi, India.

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.
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http://dx.doi.org/10.1007/s00296-021-05030-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8524205PMC
October 2021

Immunophenotyping and Transcriptional Profiling of Human Plasmablasts in Dengue.

J Virol 2021 Nov 15;95(23):e0061021. Epub 2021 Sep 15.

ICGEB-Emory Vaccine Center, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

Plasmablasts represent a specialized class of antibody-secreting effector B cells that transiently appear in blood circulation following infection or vaccination. The expansion of these cells generally tends to be massive in patients with systemic infections such as dengue or Ebola that cause hemorrhagic fever. To gain a detailed understanding of human plasmablast responses beyond antibody expression, here, we performed immunophenotyping and RNA sequencing (RNA-seq) analysis of the plasmablasts from dengue febrile children in India. We found that plasmablasts expressed several adhesion molecules and chemokines or chemokine receptors that are involved in endothelial interactions or homing to inflamed tissues, including skin, mucosa, and intestine, and upregulated the expression of several cytokine genes that are involved in leukocyte extravasation and angiogenesis. These plasmablasts also upregulated the expression of receptors for several B-cell prosurvival cytokines that are known to be induced robustly in systemic viral infections such as dengue, some of which generally tend to be relatively higher in patients manifesting hemorrhage and/or shock than in patients with mild febrile infection. These findings improve our understanding of human plasmablast responses during the acute febrile phase of systemic dengue infection. Dengue is globally spreading, with over 100 million clinical cases annually, with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody-dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the early cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the transcriptional profiles of human plasmablasts from dengue patients.
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http://dx.doi.org/10.1128/JVI.00610-21DOI Listing
November 2021

The Childhood and Adolescent Sleep Evaluation Questionnaire (CASEQ): Development and validation of an ICSD-3-based screening instrument, a community and hospital-based study.

J Sleep Res 2021 Sep 8:e13479. Epub 2021 Sep 8.

Child Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Sleep disorders are common in children and adolescents. Polysomnography is the gold-standard diagnostic method; however, it is a tedious procedure. The objective of the study was to develop a screening questionnaire for sleep problems based on International Classification of Sleep Disorders-3 in children and adolescents, and validate it with clinical evaluation and polysomnography. A questionnaire was developed in English and Hindi with content validation by eight multidisciplinary experts. Respondents were parents of children and adolescents, aged 2-18 years, recruited from a public school and a tertiary care teaching hospital in north India. A subset of these children and adolescents underwent overnight polysomnography and detailed clinical evaluation within 4 weeks of applying the questionnaire. The questionnaire, named Childhood and Adolescent Sleep Evaluation Questionnaire, contains primary questions covering all subgroups of disorders under International Classification of Sleep Disorders-3, and secondary questions on sleep hygiene and comorbidities. The questionnaire was filled by 750 respondents, out of which 100 cases underwent polysomnography and clinical evaluation. The internal consistency in the form of Cronbach's α was 0.8 for the questionnaire. The sensitivity, specificity, positive and negative predictive values for the questionnaire in identifying those with sleep problems compared with detailed clinical and polysomnographic evaluations were 85%, 100%, 100% and 62.5%, respectively. For individual subgroups of disorders, the sensitivity, specificity, positive and negative predictive values varied between 72.7% and 100%, 88.9% and 100%, 62.5% and 100% and 81.6% and 100%, respectively. The Childhood and Adolescent Sleep Evaluation Questionnaire has good psychometric properties, moreover, its simplicity and translatability make it ideal for use at the community and hospital settings.
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http://dx.doi.org/10.1111/jsr.13479DOI Listing
September 2021

Primary Esophageal Tuberculosis.

Indian J Pediatr 2021 09 12;88(9):947. Epub 2021 Jul 12.

Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, 110029, India.

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http://dx.doi.org/10.1007/s12098-021-03876-5DOI Listing
September 2021

Feasibility of Pediatric Non-Invasive Respiratory Support in Low and Middle-Income Countries.

Indian Pediatr 2021 May 3. Epub 2021 May 3.

Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Correspondence to: Dr Rakesh Lodha, Professor, Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, Ansari Nagar, New Delhi,110 029, India.

Non-Invasive respiratory support can be viewed as mechanical respiratory support without endotracheal intubation and it includes Continuous Positive Airway Pressure, Bi-Level Positive Airway Pressure, High Flow Nasal Cannula, and Non-invasive Positive Pressure Ventilation. Over past few years, non-invasive respiratory support is getting more popular across pediatric intensive care units for acute respiratory failure as well as for long-term ventilation support at home. It reduces the need for invasive mechanical ventilation, decreases the risk of nosocomial pneumonia as well as mortality in selected pediatric and adult population. Unfortunately, majority of available studies on non-invasive respiratory support have been conducted in high-income countries, which are different from low- and middle-income countries (LMICs) in terms of resources, man-power, and the disease profile. Hence, we need to consider disease profile, severity on admission to ICU or ward, availability of age-appropriate equipment, ability of health care professionals to manage patients on non-invasive respiratory support, and cost-benefit ratio. In view of the relatively high cost of equipment, there is a need to innovate to develop indigenous kits/ devices with available resources in LMICs to reduce the cost and potentially benefit health system. In this review, we highlight the role of non-invasive respiratory support in different clinical conditions, practical problems encountered in LMICs setting, and few indigenous techniques to provide non-invasive respiratory support.
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May 2021

Chikungunya-specific IgG and neutralizing antibody responses in natural infection of Chikungunya virus in children from India.

Arch Virol 2021 Jul 27;166(7):1913-1920. Epub 2021 Apr 27.

Department of Pediatrics, All India Institute of Medical sciences, New Delhi, 110029, India.

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.
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http://dx.doi.org/10.1007/s00705-021-05049-3DOI Listing
July 2021

Effects of ambient air pollution on emergency room visits of children for acute respiratory symptoms in Delhi, India.

Environ Sci Pollut Res Int 2021 Sep 21;28(33):45853-45866. Epub 2021 Apr 21.

Indian Council of Medical Research, New Delhi, 110029, India.

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 (PM and PM), nitrogen dioxide (NO), sulfur dioxide (SO), carbon monoxide (CO), and ozone (O) 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/m increase of NO on previous day 1, 46.78% (21.01, 78.05) for 10 μg/m of CO on previous day 3, and 13.15% (9.95, 16.45) for 10 μg/m of SO 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.
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http://dx.doi.org/10.1007/s11356-021-13600-7DOI Listing
September 2021

Dexmedetomidine vs Midazolam for Sedation in Mechanically Ventilated Children: A Randomized Controlled Trial.

Indian Pediatr 2021 02;58(2):117-122

Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Correspondence to: Dr Rakesh Lodha, Professor, Division of Pediatric Pulmonology and Intensive Care, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India.

Background: There is a paucity of data on use of dexmedetomidine as a sedative agent in mechanically ventilated children.

Objectives: 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.

Design: Open label, non-inferiority, randomized controlled trial.

Setting: PICU of a tertiary care teaching hospital in India.

Patients: Consecutive children aged 1 month to 15 years who were mechanically ventilated.

Intervention: Children were randomized to either dexmedeto-midine 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.

Outcome: The percentage of time spent in level 4 or 5 of Penn State Children Hospital sedation algorithm for ventilated children.

Results: 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.

Conclusion: Non-inferiority of dexmedetomidine compared to midazolam for sedation in children on mechanical ventilation could not be established.
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February 2021

Psychiatric Morbidity and Behavioral Problems in Children and Adolescents with Bronchial Asthma.

Indian J Pediatr 2021 Oct 24;88(10):968-973. Epub 2021 Feb 24.

Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.

Objectives: Psychiatric morbidity and behavioral problems are quite common in children and adolescents with bronchial asthma, yet they remain underexplored and often ignored in clinical settings. This can impact the child's overall quality of life. There seems to be a dearth of Indian literature and so the current study was planned to assess psychological impact of asthma on the pediatric population.

Methods: Thirty children and adolescents, attending the Pediatric Chest Clinic at a tertiary care hospital in North India in the age group of 8-15 y having moderate to severe asthma formed the study group and matched healthy controls formed the other group. Sociodemographic and clinical details were obtained. Mini International Neuropsychiatric Interview (M.I.N.I. KID) and Child Behavior Checklist (CBCL) were applied.

Results: Irregular attendance at school was reported by 23.33% of the participants with asthma. About 17% of the thirty study-participants were diagnosed with specific phobia, 10% with conduct disorder, and 7% with attention deficit hyperactivity disorder (ADHD). Participants in the study group had significantly more behavioral problems in the syndrome domain anxious/depressed and attention problems. Total CBCL scores were significantly higher in the study group as compared to the control group (t = 3.816, p = 0.0003), indicating the presence of more behavioral problems in pediatric population with bronchial asthma.

Conclusion: Children and adolescents with bronchial asthma have co-morbid psychiatric morbidities and behavioral problems.
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http://dx.doi.org/10.1007/s12098-021-03661-4DOI Listing
October 2021

Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children.

J Gen Virol 2020 12 11;101(12):1289-1299. Epub 2020 Sep 11.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

Protective antibody responses to human immunodeficiency virus (HIV)-1 infection evolve only in a fraction of infected individuals by developing broadly neutralizing antibodies (bnAbs) and/or effector functions such as antibody-dependent cellular cytotoxicity (ADCC). HIV-1 chronically infected adults and children on combination antiretroviral therapy (cART) showed a reduction in ADCC activity and improvement in HIV-1 specific neutralizing antibody (nAb) responses. Early initiation of cART in infected adults is found to be beneficial in reducing the viral load and delaying disease progression. Herein, we longitudinally evaluated the effect of cART on HIV-1 specific plasma ADCC and nAb responses in a cohort of 20 perinatally HIV-1 subtype-C infected infants and children ≤2 years of age, pre-cART and up to 1 year post-cART initiation. Significant reductions in HIV-1 specific plasma ADCC responses to subtype-C and subtype-B viruses and improvement in HIV-1 neutralization were observed in HIV-1 infected children 1 year post-cART initiation. A positive correlation between reduction in viral load and the loss of ADCC response was observed. This study provides information aiding the understanding of the effects of early initiation of cART on antibody effector functions and viral neutralization in HIV-1 infected children, which needs to be further evaluated in large cohorts of HIV-1 infected children on cART to plan future intervention strategies.
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http://dx.doi.org/10.1099/jgv.0.001480DOI Listing
December 2020

Broadly neutralizing plasma antibodies effective against autologous circulating viruses in infants with multivariant HIV-1 infection.

Nat Commun 2020 09 2;11(1):4409. Epub 2020 Sep 2.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029, India.

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.
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http://dx.doi.org/10.1038/s41467-020-18225-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468291PMC
September 2020

Molecular capsular typing and multi locus sequence typing of invasive, non-invasive and commensal isolates from North India.

Indian J Med Microbiol 2020 Jan-Mar;38(1):78-86

Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India.

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.
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http://dx.doi.org/10.4103/ijmm.IJMM_20_111DOI Listing
January 2021

A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex.

J Virol 2020 09 15;94(19). Epub 2020 Sep 15.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

The envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is the sole target of broadly neutralizing antibodies (bnAbs). Several mechanisms, such as the acquisition of mutations, variability of the loop length, and alterations in the glycan pattern, are employed by the virus to shield neutralizing epitopes on Env to sustain survival and infectivity within the host. The identification of mutations that lead to viral evasion of the host immune response is essential for the optimization and engineering of Env-based trimeric immunogens. Here, we report a rare leucine-to-phenylalanine escape mutation (L184F) at the base of hypervariable loop 2 (population frequency of 0.0045%) in a 9-month-old perinatally HIV-1-infected infant broad neutralizer. The L184F mutation altered the trimer conformation by modulating intramolecular interactions stabilizing the trimer apex and led to viral escape from autologous plasma bnAbs and known N160 glycan-targeted bnAbs. The L184F amino acid change led to the acquisition of a relatively open trimeric conformation, often associated with tier 1 HIV-1 isolates and increased susceptibility to neutralization by polyclonal plasma antibodies of weak neutralizers. While there was no impact of the L184F mutation on free virus transmission, a reduction in cell-to-cell transmission was observed. In conclusion, we report a naturally selected viral mutation, L184F, that influenced a change in the conformation of the Env trimer apex as a mechanism of escape from contemporaneous plasma V2 apex-targeted nAbs. Further studies should be undertaken to define viral mutations acquired during natural infection, to escape selection pressure exerted by bnAbs, to inform vaccine design and bnAb-based therapeutic strategies. The design of HIV-1 envelope-based immunogens capable of eliciting broadly neutralizing antibodies (bnAbs) is currently under active research. Some of the most potent bnAbs target the quaternary epitope at the V2 apex of the HIV-1 Env trimer. By studying naturally circulating viruses from a perinatally HIV-1-infected infant with plasma neutralizing antibodies targeted to the V2 apex, we identified a rare leucine-to-phenylalanine substitution, in two out of six functional viral clones, that destabilized the trimer apex. This single-amino-acid alteration impaired the interprotomeric interactions that stabilize the trimer apex, resulting in an open trimer conformation and escape from broadly neutralizing autologous plasma antibodies and known V2 apex-directed bnAbs, thereby favoring viral evasion of the early bnAb response of the infected host. Defining the mechanisms by which naturally occurring viral mutations influence the sensitivity of HIV-1 to bnAbs will provide information for the development of vaccines and bnAbs as anti-HIV-1 reagents.
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http://dx.doi.org/10.1128/JVI.00814-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495384PMC
September 2020

Successful reconstitution of leukocyte adhesion defect after umbilical cord blood stem cell transplant.

Cent Eur J Immunol 2020 ;45(1):117-121

Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.

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.
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http://dx.doi.org/10.5114/ceji.2020.94713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226562PMC
January 2020

Aetiological agents for pulmonary exacerbations in children with cystic fibrosis: An observational study from a tertiary care centre in northern India.

Indian J Med Res 2020 01;151(1):65-70

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

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.
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http://dx.doi.org/10.4103/ijmr.IJMR_1275_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055172PMC
January 2020

Effect of acute respiratory infections in infancy on pulmonary function test at 3 years of age: a prospective birth cohort study.

BMJ Open Respir Res 2020 02;7(1)

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, Delhi, India

Introduction: Acute respiratory infections (ARIs) in infancy may have a long-term impact on the developing respiratory system. We planned a prospective cohort study to determine the impact of ARI during infancy on the pulmonary function test indices at 3 years of age.

Methods: A cohort of normal, full-term newborns were followed up 6 monthly and during ARI episodes. Infant pulmonary function tests (IPFTs) were performed at baseline and each follow-up visit using tidal breathing flow-volume loop, rapid thoracoabdominal compression (RTC) and raised volume RTC manoeuvres. During each ARI episode, nasopharyngeal aspirates were tested for respiratory pathogens by real-time PCR.

Results: We screened 3421 neonates; 310 were enrolled; IPFT was performed in 225 (boys: 125 (55.6%)) at 3 years. During infancy, 470 ARI episodes were documented in 173 infants. At 3 years, children with history of any ARI episode during infancy had lower forced expiratory volume in 1 s (FEV), forced expiratory volume in 0.75 s (FEV), forced expiratory volume in 0.5 s (FEV), forced expiratory flow between 25% and 75% of FVC (FEF), and maximal expiratory flow at 25% of FVC (MEF) as compared with those without any ARI episode during infancy. The ratio of tidal expiratory flow (TEF) at 25% or 50% of tidal expiratory volume to peak TEF (TEF or TEF/peak TEF) at 3 years was significantly increased in children who had ARI in infancy.

Conclusions: ARI during infancy is associated with impaired pulmonary function indices such as increased resistance and decreased forced expiratory flow and volume at 3 years of age.
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http://dx.doi.org/10.1136/bmjresp-2019-000436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047475PMC
February 2020

Novel mutation in the CD27 gene in a patient presenting with hypogammaglobulinemia, bronchiectasis and EBV-driven lymphoproliferative disease.

BMJ Case Rep 2020 Feb 9;13(2). Epub 2020 Feb 9.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

CD27 deficiency is a rare primary immune deficiency which affects T cells, B cells and NK cells and is associated with hypogammaglobulinemia. Clinical presentation varies from asymptomatic disease to life-threatening Epstein Barr Virus (EBV)-driven complications including malignancy. Delay in diagnosis and late presentation adversely affects the clinical outcome and survival. We report a 10-year-old girl who had been symptomatic since 3 years of age with recurrent infections, developed bronchiectasis and was found to have hypogammaglobulinemia. Initially diagnosed as common variable immune deficiency, she had persistent lymphadenopathy, hepatosplenomegaly and pancytopenia, raising a clinical suspicion of a lymphoproliferative condition. On investigation, she was found to have a novel mutation involving the CD27 gene with very high EBV load. She was given rituximab injections to which she showed partial response and later developed non-Hodgkin's lymphoma .
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http://dx.doi.org/10.1136/bcr-2019-233482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035825PMC
February 2020

'Intermittent' versus 'continuous' ScvO monitoring in children with septic shock: a randomised, non-inferiority trial.

Intensive Care Med 2020 01 28;46(1):82-92. Epub 2019 Nov 28.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Purpose: To compare the effect of 'intermittent' central venous oxygen saturation (ScvO) monitoring with 'continuous' ScvO monitoring on shock resolution and mortality in children with septic shock.

Methods: Primary outcome was the achievement of therapeutic goals or shock resolution in the first 6 h. We randomly assigned children < 17 years' age with septic shock to 'intermittent ScvO' or 'continuous ScvO' groups. All children were subjected to subclavian/internal jugular line insertion and managed as per Surviving Sepsis Campaign Guidelines. To guide resuscitation, we used ScvO estimated at other clinical and laboratory parameters were monitored similarly in both groups.

Results: We enrolled 75 and 77 children [median (IQR) age: 6 (1.5-10) years] in the 'intermittent' and 'continuous' groups, respectively. Baseline characteristics were comparable between the groups. When compared to the 'continuous' group, fewer children in the 'intermittent' group achieved shock resolution within first 6 h [19% vs. 36%; relative risk (RR) 0.51; 95% CI 0.29-0.89; risk difference - 18.0%; 95% CI - 32.0 to - 4.0]. The lower bound of confidence interval, however, crossed the pre-specified non-inferiority margin. There was no difference in the proportion of children attaining shock resolution within 24 h (63% vs. 69%; RR 0.86; 95% CI 0.68-1.08) or risk of mortality between the groups (47% vs. 43%; RR 1.06; 95% CI 0.74-1.51).

Conclusions: Given that a greater proportion of children attained therapeutic end points in the first 6 h, continuous monitoring of ScvO should preferably be used to titrate therapy in the first few hours in children with septic shock. In the absence of such facility, intermittent monitoring of ScvO can be used to titrate therapy in these children, given the lack of difference in the proportion of patients achieving shock resolution at 24 h or in risk of mortality between the intermittent and continuous groups.
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http://dx.doi.org/10.1007/s00134-019-05858-wDOI Listing
January 2020

Effects of Exercise Intervention Program on Bone Mineral Accretion in Children and Adolescents with Cystic Fibrosis: A Randomized Controlled Trial.

Indian J Pediatr 2019 11 8;86(11):987-994. Epub 2019 Jul 8.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029, India.

Objective: To evaluate effect of one year exercise intervention program on bone mineral accrual in children and adolescent with cystic fibrosis (CF).

Methods: Fifty-two CF children (mean age 149.79 mo) were randomized into experimental (15 boys and 10 girls) and control groups (15 boys and 12 girls). Experimental group performed prescribed exercises three times/week, while control group continued with routine physical activities for one year. Following were assessed at baseline and at one year: Bone mineral density (BMD) of whole body and lumbar spine, pulmonary function, exercise capacity, quality of life and habitual activity.

Results: Change in whole body and lumbar spine BMD over 12 mo in experimental group was lower by 0.006 g/cm (95% CI -0.02 to 0.02) and higher by 0.001 g/cm (95% CI -0.04 to 0.03) than controls, respectively. However, difference between groups was non-significant for both parameters. Experimental group had a significant improvement in their exercise capacity (p = 0.006), quality of life, and serum vitamin D (p = 0.007) levels. Differences between groups for changes in pulmonary function and habitual activity were non-significant.

Conclusions: Exercise regime was not associated with significant improvement in BMD of CF patients, but it had a positive impact on both physical and psychological health of these patients.
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http://dx.doi.org/10.1007/s12098-019-03019-xDOI Listing
November 2019

Current antibiotic use in the treatment of enteric fever in children.

Indian J Med Res 2019 02;149(2):263-269

Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India.

Background & Objectives: Antimicrobial resistance is a major challenge in the treatment of typhoid fever with limited choices left to empirically treat these patients. The present study was undertaken to determine the current practices of antibiotic use in children attending a tertiary care hospital in north India.

Methods: This was a descriptive observational study in children suffering from enteric fever as per the case definition including clinical and laboratory parameters. The antibiotic audit in hospitalized children was measured as days of therapy per 1000 patient days and in outpatient department (OPD) as antibiotic prescription on the treatment card.

Results: A total of 128 children with enteric fever were included in the study, of whom, 30 were hospitalized and 98 were treated from OPD. The mean duration of fever was 9.5 days at the time of presentation. Of these, 45 per cent were culture positive with Salmonella Typhi being aetiological agent in 68 per cent followed by S. Paratyphi A in 32 per cent. During hospitalization, the average length of stay was 10 days with mean duration of defervescence 6.4 days. Based on antimicrobial susceptibility ceftriaxone was given to 28 patients with mean duration of treatment being six days. An additional antibiotic was needed in six patients due to clinical non-response. In OPD, 79 patients were prescribed cefixime and additional antibiotic was needed in five during follow up visit.

Interpretation & Conclusions: Based on our findings, ceftriaxone and cefixime seemed to be the first line of antibiotic treatment for typhoid fever. Despite susceptibility, clinical non-response was seen in around 10 per cent of the patients who needed combinations of antibiotics.
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http://dx.doi.org/10.4103/ijmr.IJMR_199_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563751PMC
February 2019

Late dumping syndrome in an infant on feeding jejunostomy.

BMJ Case Rep 2019 May 21;12(5). Epub 2019 May 21.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

This article presents the case of a 3-month-old male child, who while on bolus jejunostomy tube feeds, developed recurrent episodes of hypoglycaemia. This infant had presented with failure to thrive with moderate gastroesophageal reflux necessitating a feeding jejunostomy. The infant was started on bolus feeds through the jejunostomy tube but developed recurrent episodes of hypoglycaemia. On evaluation, these episodes were hyperinsulinaemic and the baby was subsequently diagnosed with a late dumping syndrome. On changing the feeds to a continuous infusion and by eliminating added sugar from the feeds, the glucose fluctuations resolved. Dumping syndrome is a well-known complication in adults undergoing gastric surgeries. In the paediatric age group, dumping syndrome has been reported rarely, most commonly as a complication of Nissen fundoplication.
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http://dx.doi.org/10.1136/bcr-2018-228471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559811PMC
May 2019

Hematopoietic stem cell transplantation in children with Griscelli Syndrome type 2: Experience and outcomes.

Indian J Pathol Microbiol 2019 Apr-Jun;62(2):279-282

Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.

Griscelli syndrome is a rare autosomal recessive inherited disorder characterized by hypopigmentation, silver colored hair, and associated immunological deficiency, which proves fatal in the absence of timely intervention. Our patients diagnosed with Griscelli syndrome-2 presented with fever, hepatosplenomegaly, and deranged hematological and biochemical parameters. Both cases underwent detailed investigations comprising of hair mount microscopic examination, degranulation assay, and mutational studies. Our cases showed defective degranulation activity by NK cells and gene mutation analysis revealed RAB27A mutation that causes defect of cytotoxic granule exocytosis from natural killer (NK) and T-cells, manifesting clinically as hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplantation in one of the patients resulted in stable chimerism; however, the second case relapsed within a month after SCT. Stem cell transplantation is the only curative therapeutic option for GS2; thus, improvement in posttransplantation management may reduce mortality and posttransplant complications. Hence, any child who presents with partial albinism and clinical features suggestive of HLH, a peripheral blood, hair shaft mount examination along with basic immunological NK and T-cell cytotoxicity assay by flow cytometry will help clinch the diagnosis early. It can subsequently be confirmed by molecular study. Timely therapeutic intervention can prevent relapses and severe infection and improve outcome in these cases.
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http://dx.doi.org/10.4103/IJPM.IJPM_645_18DOI Listing
August 2019

Virus load and clinical features during the acute phase of Chikungunya infection in children.

PLoS One 2019 1;14(2):e0211036. Epub 2019 Feb 1.

Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi, India.

Background: Chikungunya virus (CHIKV) infection is a long known mosquito-borne disease that is associated with severe morbidity, characterized by fever, headache, rashes, joint pain, and myalgia. It is believed that virus load has relation with severity of clinical features.

Objectives: We performed this study to assess the relationship between virus load and clinical features in children during the acute phase of CHIKV infection, in order to draw insights for better-informed treatment.

Study Design: Between June 1, 2009, and May 31, 2010, 338 patients with fever and susceptive to CHIKV during first 4 days of illness were prospectively enrolled from Karnataka Institute of Medical Sciences, Hubli in our hospital based cross sectional observational study. Sybr green quantitative reverse transcription polymerase chain reaction was performed to estimate the virus load.

Results: Quantitative RT-PCR was positive for CHIKV in 54 patients. The median copy number of CHIKV was 1.3x 108 copies/ml (1.7x105-9.9x109 copies/ml). Among the observed clinical features, a statistically significant difference in log mean virus load was found between patients with and without myalgia (log mean 7.50 vs 8.34, P = 0.01).

Conclusion: Patients with myalgia had lower virus load and those without myalgia had a higher virus load.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0211036PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358158PMC
October 2019

Role of Breathing Exercises and Yoga/Pranayama in Childhood Asthma: A Systematic Review.

Curr Pediatr Rev 2019 ;15(3):175-183

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Background: Various 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.

Conclusions: 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.
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http://dx.doi.org/10.2174/1573396315666190121122452DOI Listing
April 2020

Analysis of dengue specific memory B cells, neutralizing antibodies and binding antibodies in healthy adults from India.

Int J Infect Dis 2019 Jul 15;84S:S57-S63. Epub 2019 Jan 15.

ICGEB-Emory Vaccine Center, International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, 110067, India. Electronic address:

Background: The Indian population is facing highest dengue burden worldwide supporting an urgent need for vaccines. For vaccine introduction, evaluation and interpretation it is important to gain a critical understanding of immune memory induced by natural exposure. However, immune memory to dengue remains poorly characterized in this region.

Methods: We enumerated levels of dengue specific memory B cells (MBC), neutralizing (NT) and binding antibodies in healthy adults (n=70) from New Delhi.

Results: NT-antibodies, binding antibodies and MBC were detectable in 86%, 86.56% and 81.63% of the subjects respectively. Among the neutralizing positive subjects, 58%, 27%, 5% and 10% neutralized all four, any three, any two and any one dengue serotypes respectively. The presence of the neutralizing antibodies was associated with the presence of the MBC and binding antibodies. However, a massive interindividual variation was observed in the levels of the neutralizing antibodies (range, <1:50-1:30,264), binding antibodies (range, 1:3,000-1:134,000,) as well as the MBC (range=0.006%-5.05%).

Conclusion: These results indicate that a vast majority of the adults are immune to multiple dengue serotypes and show massive interindividual variation in neutralizing/binding antibodies and MBCs - emphasizing the importance of monitoring multiple parameters of immune memory in order to properly plan, evaluate and interpret dengue vaccines.
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http://dx.doi.org/10.1016/j.ijid.2019.01.018DOI Listing
July 2019

Association of Fluid Overload with Mortality in Critically-ill Mechanically Ventilated Children.

Indian Pediatr 2018 Nov;55(11):957-961

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India. Correspondence to: Dr Rakesh Lodha, Professor, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Objective: To study the association of fluid overload with mortality and morbidity in critically-ill mechanically ventilated children.

Design: Prospective observational study.

Setting: Pediatric Intensive Care Unit (PICU) of a tertiary care hospital, New Delhi, India.

Participants: 118 children (age 1 mo - 15 y) requiring mechanical ventilation.

Outcome Measures: Primary: Association of fluid overload with mortality. Secondary: Association of fluid overload with oxygenation, organ dysfunction, duration of mechanical ventilation and PICU stay.

Results: Cumulative fluid overload of ≥15% was observed in 74 (62.7%) children. About 50% of these children reached cumulative fluid overload of ≥15% within the first 5 days of PICU stay. The mortality was 40.5% in those with ≥15% cumulative fluid compared to 34% in the rest [OR (95% CI): 1.02 (0.97, 1.07)]. On multivariate analysis, after adjusting for confounders, cumulative fluid overload ≥15% was associated with higher maximum PELOD (pediatric logistic organ dysfunction) score (Median: 21 vs. 12; P = 0.03), longer median duration of mechanical ventilation (10 vs. 4 d; P <0.0001) and PICU stay (13.5 vs. 6 d; P <0.0001). There was no significant association of fluid overload with oxygenation index (P=0.32).

Conclusions: There is no association of fluid overload with mortality. However, it is associated with poor organ function, longer duration of mechanical ventilation and PICU stay in critically-ill, mechanically ventilated children.
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November 2018

An HIV-1 Broadly Neutralizing Antibody from a Clade C-Infected Pediatric Elite Neutralizer Potently Neutralizes the Contemporaneous and Autologous Evolving Viruses.

J Virol 2019 02 5;93(4). Epub 2019 Feb 5.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

Broadly neutralizing antibodies (bNAbs) have demonstrated protective effects against HIV-1 in primate studies and recent human clinical trials. Elite neutralizers are potential candidates for isolation of HIV-1 bNAbs. The coexistence of bNAbs such as BG18 with neutralization-susceptible autologous viruses in an HIV-1-infected adult elite controller has been suggested to control viremia. Disease progression is faster in HIV-1-infected children than in adults. Plasma bNAbs with multiple epitope specificities are developed in HIV-1 chronically infected children with more potency and breadth than in adults. Therefore, we evaluated the specificity of plasma neutralizing antibodies of an antiretroviral-naive HIV-1 clade C chronically infected pediatric elite neutralizer, AIIMS_330. The plasma antibodies showed broad and potent HIV-1 neutralizing activity with >87% (29/33) breadth, a median inhibitory dilution (ID) value of 1,246, and presence of N160 and N332 supersite-dependent HIV-1 bNAbs. The sorting of BG505.SOSIP.664.C2 T332N gp140 HIV-1 antigen-specific single B cells of AIIMS_330 resulted in the isolation of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01. The AIIMS-P01 neutralized 67% of HIV-1 cross-clade viruses, exhibited substantial indels despite limited somatic hypermutations, interacted with native-like HIV-1 trimer as observed in negative stain electron microscopy, and demonstrated high binding affinity. In addition, AIIMS-P01 neutralized the coexisting and evolving autologous viruses, suggesting the coexistence of vulnerable autologous viruses and HIV-1 bNAbs in the AIIMS_330 pediatric elite neutralizer. Such pediatric elite neutralizers can serve as potential candidates for isolation of novel HIV-1 pediatric bNAbs and for understanding the coevolution of virus and host immune response. More than 50% of the HIV-1 infections globally are caused by clade C viruses. To date, there is no effective vaccine to prevent HIV-1 infection. Based on the structural information of the currently available HIV-1 bNAbs, attempts are under way to design immunogens that can elicit correlates of protection upon vaccination. Here, we report the isolation and characterization of an HIV-1 N332 supersite-dependent bNAb, AIIMS-P01, from a clade C chronically infected pediatric elite neutralizer. The N332 supersite is an important epitope and is one of the current HIV-1 vaccine targets. AIIMS-P01 potently neutralized the contemporaneous and autologous evolving viruses and exhibited substantial indels despite low somatic hypermutations. Taken together with the information on infant bNAbs, further isolation and characterization of bNAbs contributing to the plasma breadth in HIV-1 chronically infected children may help provide a better understanding of their role in controlling HIV-1 infection.
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http://dx.doi.org/10.1128/JVI.01495-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364018PMC
February 2019

Lymphangioleiomyomatosis (LAM) presenting as recurrent pneumothorax in an infant with tuberous sclerosis: treated successfully with sirolimus.

BMJ Case Rep 2018 Nov 8;2018. Epub 2018 Nov 8.

Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Lymphangioleiomyomatosis (LAM) either sporadic or a part of tuberous sclerosis complex is rare in paediatric age group. Here, we report a case of LAM with tuberous sclerosis in an infant. She was referred to our institute at the age of 4 months as a case of recurrent bilateral pneumothorax requiring intercostal tube drainage. Detailed history revealed that patient was symptomatic since 1 month of age in the form of seizures. She had respiratory symptoms for last 15 days. General physical examination revealed whitish macular patches. Brain imaging was suggestive of cortical tubers and subependymal nodules. The echocardiography showed right atrial rhabdomyoma. Chest CT revealed multiple cysts suggesting LAM. On the basis of above findings, a diagnosis of tuberous sclerosis complex with LAM was made. The infant was started on sirolimus and there was significant clinical and radiological improvement over a period of 2 and half years without any side effects.
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http://dx.doi.org/10.1136/bcr-2018-226244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6229132PMC
November 2018

Decreasing the Time to Administration of First Dose of Antibiotics in Children With Severe Sepsis.

J Healthc Qual 2019 Jan/Feb;41(1):32-38

Objectives: To measure difference in median time to antibiotic administration in severe sepsis before and after making process changes and clinical outcomes such as duration of hospitalization and mortality.

Methods: The study was carried out in the emergency department in children <17 years of age with severe sepsis/septic shock. In phase 1, data were collected and reasons for delayed antibiotic administration were identified. Following this, process changes like creating a triage tool, re-enforcing the severe sepsis protocol and increasing the number of nurses were made to correct the delay. In phase 2, we measured outcomes to compare the effect of the process changes.

Results: A total of 28 and 13 children each were included during phase 1 and phase 2 of the study respectively. The median interquartile range time to administration of antibiotics from the time of admission decreased significantly from 50 minutes (18, 65) to 20 minutes (15, 20) (p = .02). Duration of hospital stay was longer in phase 1 as compared to phase 2 (12 days vs. 6 days). However, the difference was not statistically significant (p = .1).

Conclusions: Use of a triage tool, severe sepsis protocol, and increasing the number of nurses resulted in earlier recognition and administration of first dose of antibiotics in children with severe sepsis.
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http://dx.doi.org/10.1097/JHQ.0000000000000141DOI Listing
February 2020
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