Paediatrics (RCH) - Research Publications
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ItemA case report describing the immune response of an infant with congenital heart disease and severe COVID-19(SPRINGERNATURE, 2021-11-15)BACKGROUND: Children with SARS-CoV-2 infection generally present with milder symptoms or are asymptomatic in comparison with adults, however severe disease occurs in a subset of children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterised. METHODS: We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19 using high-dimensional flow cytometry and multiplex cytokine analysis. RESULTS: Systemic cellular and cytokine profiling show an initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8 + T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4 + T (but not CD8 + T) cells occurred over time, with a predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Substantial in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory. CONCLUSIONS: These findings provide important insights into the immune response of a young infant with severe COVID-19 and will help to inform future research into therapeutic targets for high-risk groups.
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ItemImmune Responses in an Infant with Congenital Heart Disease and Severe COVID-19( 2021)Children have lower hospitalisation and mortality rates for coronavirus disease-2019 (COVID-19) than adults; however, younger children (<4 years of age) 1 may develop more severe disease than older children. To date, the immune correlates of severe COVID-19 in young children have been poorly characterized. We report the kinetics of immune responses in relation to clinical and virological features in an infant with acute severe COVID-19. Systemic cellular and cytokine profiling showed initial increase in neutrophils and monocytes with depletion of lymphoid cell populations (particularly CD8+ T and NK cells) and elevated inflammatory cytokines. Expansion of memory CD4+T (but not CD8+T) cells occurred over time, with predominant Th2 bias. Marked activation of T cell populations observed during the acute infection gradually resolved as the child recovered. Significant in vitro activation of T-cell populations and robust cytokine production, in response to inactivated SARS-CoV-2 stimulation, was observed 3 months after infection indicating durable, long-lived cellular immune memory.
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ItemNon-antibiotic medication use in an Indonesian community cohort 0-18 months of age(PUBLIC LIBRARY SCIENCE, 2020-11-18)BACKGROUND: Rational medication use for treatment is mandatory, particularly in children as they are vulnerable to possible hazards of drugs. Understanding the medication use pattern is of importance to identify the problems of drug therapy and to improve the appropriate use of medication among this population. METHODS: A post-hoc study of the RV3-BB Phase IIb trial to children aged 0-18 months which was conducted in Indonesia during January 2013 to July 2016. Any concomitant medication use and health events among 1621 trial participants during the 18 months of follow-up were documented. Information on medication use included the frequency, formulation, indication, duration of usage, number of regimens, medication types, and therapeutic classes. RESULTS: The majority of participants (N = 1333/1621; 82.2%) used at least one non-antibiotic medication for treatment during the 18-month observation period. A total of 7586 medication uses were recorded, mostly in oral formulation (90.5%). Of all illnesses recorded, 24.7% were treated with a single drug regimen of non-antibiotic medication. The most common therapeutic classes used were analgesics/antipyretics (30.1%), antihistamines for systemic use (17.4%), cough and cold preparations (13.5%), vitamins (8.6%), and antidiarrheals (6.6%). The main medication types used were paracetamol (29.9%), chlorpheniramine (16.8%), guaifenesin (8.9%), zinc (4.6%), and ambroxol (4.1%). Respiratory system disorder was the most common reason for medication use (51.9%), followed by gastrointestinal disorders (19.2%), pyrexia (16.9%), and skin disorders (7.0%). CONCLUSION: A large number of children were exposed to at least one medication during their early life, including those where evidence of efficacy and safety in a pediatric population is lacking. This supports the need for further research on pediatric drug therapy to improve the appropriate use of medication in this population.
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ItemAntimicrobial use in an Indonesian community cohort 0-18 months of age(PUBLIC LIBRARY SCIENCE, 2019-08-05)BACKGROUND: Antimicrobial resistance has become a global health emergency and is contributed to by inappropriate antibiotic use in community clinical settings. The aim of this study was to evaluate the antimicrobial use pattern in infants from birth until 18 months of age in Indonesia. METHODS: A post-hoc analysis was conducted in 1621 participants from the RV3BB Phase IIb trial conducted in Indonesia from January 2013 through July 2016. Any health events were documented in the trial as adverse events. Concomitant medication surveillance recorded all medications, including antibiotics during the 18 months of follow-up. Information included the frequency, duration of usage, formulation, classes, and their indications, including prophylactic antibiotic and perinatal use. RESULTS: Of 1621 participants, 551 (33.99%) received at least one antibiotic for treatment of infections during the 18 months observation period. Additionally, during the perinatal period, prophylactic antibiotics were used in 1244 (76.74%) participants and antibiotics consumed in 235 mothers of participants (14.50%). A total of 956 antibiotic consumptions were recorded for 18 months follow up, 67 (7.01%) as part of antimicrobial combinations. The average duration of antibiotic course was 4.92 days. Penicillin and sulfonamides were the most common antibiotic classes consumed (38.81% and 24.48%, respectively). CONCLUSIONS: Despite the low community consumption rate, the overuse of antibiotic in URTIs and non-bloody diarrhea in our setting represents a major opportunity for antimicrobial stewardship, particularly in early life.
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ItemMolecular epidemiology of adenovirus isolates from patients diagnosed with intussusception in Melbourne, Australia(AMER SOC MICROBIOLOGY, 2006-09)Twenty-one intussusception (IS)-associated and 59 temporally linked adenoviral isolates from clinical infections were compared. Species C (15/21 IS- and 32/59 non-IS-associated isolates) dominated. Of these, serotype 2 (AdV-2) (7/15 IS-associated isolates) and serotype 1 (AdV-1) (16/32 non-IS-associated isolates) were the most commonly identified serotypes. DNA restriction analysis of AdV-2 isolates identified six genomic types; of these, type D2 (3/7 IS- and 8/11 non-IS-associated isolates) was the dominant type after BamHI and SmaI digestion. IS-associated isolates are similar to circulating non-IS-associated strains.