Paediatrics (RCH) - Research Publications
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ItemChildren and Adults in a Household Cohort Study Have Robust Longitudinal Immune Responses Following SARS-CoV-2 Infection or Exposure(FRONTIERS MEDIA SA, 2021-10-13)Children have reduced severity of COVID-19 compared to adults and typically have mild or asymptomatic disease. The immunological mechanisms underlying these age-related differences in clinical outcomes remain unexplained. Here, we quantify 23 immune cell populations in 141 samples from children and adults with mild COVID-19 and their PCR-negative close household contacts at acute and convalescent time points. Children with COVID-19 displayed marked reductions in myeloid cells during infection, most prominent in children under the age of five. Recovery from infection in both children and adults was characterised by the generation of CD8 TCM and CD4 TCM up to 9 weeks post infection. SARS-CoV-2-exposed close contacts also had immunological changes over time despite no evidence of confirmed SARS-CoV-2 infection on PCR testing. This included an increase in low-density neutrophils during convalescence in both exposed children and adults, as well as increases in CD8 TCM and CD4 TCM in exposed adults. In comparison to children with other common respiratory viral infections, those with COVID-19 had a greater change in innate and T cell-mediated immune responses over time. These findings provide new mechanistic insights into the immune response during and after recovery from COVID-19 in both children and adults.
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ItemPersistence of SARS-CoV-2-Specific IgG in Children 6 Months After Infection, Australia(CENTERS DISEASE CONTROL & PREVENTION, 2021-08)The duration of the humoral immune response in children infected with severe acute respiratory syndrome coronavirus 2 is unknown. We detected specific IgG 6 months after infection in children who were asymptomatic or had mild symptoms of coronavirus disease. These findings will inform vaccination strategies and other prevention measures.
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ItemInnate cell profiles during the acute and convalescent phase of SARS-CoV-2 infection in children(NATURE PORTFOLIO, 2021-02-17)Children have mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) confirmed disease (COVID-19) compared to adults and the immunological mechanisms underlying this difference remain unclear. Here, we report acute and convalescent innate immune responses in 48 children and 70 adults infected with, or exposed to, SARS-CoV-2. We find clinically mild SARS-CoV-2 infection in children is characterised by reduced circulating subsets of monocytes (classical, intermediate, non-classical), dendritic cells and natural killer cells during the acute phase. In contrast, SARS-CoV-2-infected adults show reduced proportions of non-classical monocytes only. We also observe increased proportions of CD63+ activated neutrophils during the acute phase to SARS-CoV-2 in infected children. Children and adults exposed to SARS-CoV-2 but negative on PCR testing display increased proportions of low-density neutrophils that we observe up to 7 weeks post exposure. This study characterises the innate immune response during SARS-CoV-2 infection and household exposure in children.
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ItemProspective Surveillance of Invasive Group A Streptococcal Disease, Fiji, 2005-2007(CENTERS DISEASE CONTROL & PREVENTION, 2009-02)We undertook a prospective active surveillance study of invasive group A streptococcal (GAS) disease in Fiji over a 23-month period, 2005-2007. We identified 64 cases of invasive GAS disease, which represents an average annualized all-ages incidence of 9.9 cases/100,000 population per year (95% confidence interval [CI] 7.6-12.6). Rates were highest in those >65 years of age and in those <5 years, particularly in infants, for whom the incidence was 44.9/100,000 (95% CI 18.1-92.5). The case-fatality rate was 32% and was associated with increasing age and underlying coexisting disease, including diabetes and renal disease. Fifty-five of the GAS isolates underwent emm sequence typing; the types were highly diverse, with 38 different emm subtypes and no particular dominant type. Our data support the view that invasive GAS disease is common in developing countries and deserves increased public health attention.
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ItemHigh Burden of Impetigo and Scabies in a Tropical Country(PUBLIC LIBRARY SCIENCE, 2009-06)BACKGROUND: Impetigo and scabies are endemic diseases in many tropical countries; however the epidemiology of these diseases is poorly understood in many areas, particularly in the Pacific. METHODOLOGY/PRINCIPAL FINDINGS: We conducted three epidemiological studies in 2006 and 2007 to determine the burden of disease due to impetigo and scabies in children in Fiji using simple and easily reproducible methodology. Two studies were performed in primary school children (one study was a cross-sectional study and the other a prospective cohort study over ten months) and one study was performed in infants (cross-sectional). The prevalence of active impetigo was 25.6% (95% CI 24.1-27.1) in primary school children and 12.2% (95% CI 9.3-15.6) in infants. The prevalence of scabies was 18.5% (95% CI 17.2-19.8) in primary school children and 14.0% (95% CI 10.8-17.2) in infants. The incidence density of active impetigo, group A streptococcal (GAS) impetigo, Staphylococcus aureus impetigo and scabies was 122, 80, 64 and 51 cases per 100 child-years respectively. Impetigo was strongly associated with scabies infestation (odds ratio, OR, 2.4, 95% CI 1.6-3.7) and was more common in Indigenous Fijian children when compared with children of other ethnicities (OR 3.6, 95% CI 2.7-4.7). The majority of cases of active impetigo in the children in our study were caused by GAS. S. aureus was also a common cause (57.4% in school aged children and 69% in infants). CONCLUSIONS/SIGNIFICANCE: These data suggest that the impetigo and scabies disease burden in children in Fiji has been underestimated, and possibly other tropical developing countries in the Pacific. These diseases are more than benign nuisance diseases and consideration needs to be given to expanded public health initiatives to improve their control.
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ItemImmune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19(NATURE PORTFOLIO, 2020-11-11)Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.