Paediatrics (RCH) - Research Publications

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    Children and Adults in a Household Cohort Study Have Robust Longitudinal Immune Responses Following SARS-CoV-2 Infection or Exposure
    Neeland, MR ; Bannister, S ; Clifford, V ; Nguyen, J ; Dohle, K ; Overmars, I ; Toh, ZQ ; Anderson, J ; Donato, CM ; Sarkar, S ; Do, LAH ; McCafferty, C ; Licciardi, PV ; Ignjatovic, V ; Monagle, P ; Bines, JE ; Mulholland, K ; Curtis, N ; McNab, S ; Steer, AC ; Burgner, DP ; Saffery, R ; Tosif, S ; Crawford, NW (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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    The impact of the rotavirus vaccine on diarrhoea, five years following national introduction in Fiji
    Jenney, AWJ ; Reyburn, R ; Ratu, FT ; Tuivaga, E ; Nguyen, C ; Covea, S ; Thomas, S ; Rafai, E ; Devi, R ; Bright, K ; Jenkins, K ; Temple, B ; Tikoduadua, L ; Kado, J ; Mulholland, EK ; Kirkwood, CD ; Fox, KK ; Bines, JE ; Grabovac, V ; Khan, AS ; Kama, M ; Russell, FM (ELSEVIER, 2021-01)
    BACKGROUND: In 2012, Fiji became the first independent Pacific island country to introduce rotavirus vaccine. We describe the impact of rotavirus vaccine on all-cause diarrhoea admissions in all ages, and rotavirus diarrhoea in children <5 years of age. METHODS: An observational study was conducted retrospectively on all admissions to the public tertiary hospitals in Fiji (2007-2018) and prospectively on all rotavirus-positive diarrhoea admissions in children <5 years at two hospital sites (2006-2018, and 2010-2015), along with rotavirus diarrhoea outpatient presentations at one secondary public hospital (2010-2015). The impact of rotavirus vaccine was determined using incidence rate ratios (IRR) of all-cause diarrhoea admissions and rotavirus diarrhoea, comparing the pre-vaccine and post-vaccine periods. All-cause admissions were used as a control. Multiple imputation was used to impute missing stool samples. FINDINGS: All-cause diarrhoea admissions declined among all age groups except among infants ≤2 months old and adults ≥55 years. For children <5 years, all-cause diarrhoea admissions declined by 39% (IRR)=0•61, 95%CI; 0•57-0•65, p-value<0•001). There was an 81% (95%CI; 51-94%) reduction in mortality among all-cause diarrhoea admissions in children under <5 years. Rotavirus diarrhoea admissions at the largest hospital among children <5 years declined by 87% (IRR=0•13, 95%CI; 0•10-0•17, p-value<0•001). Among rotavirus diarrhoea outpatient presentations, the IRR was 0•39 (95%CI; 0•11, 1.21, p-value=0.077). INTERPRETATIONS: Morbidity and mortality due to rotavirus and all-cause diarrhoea in Fiji has declined in people aged 2 months to 54 years after the introduction of the RV vaccine. FUNDING: Supported by WHO and the Australian Government.
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    Immune responses to SARS-CoV-2 in three children of parents with symptomatic COVID-19
    Tosif, S ; Neeland, MR ; Sutton, P ; Licciardi, PV ; Sarkar, S ; Selva, KJ ; Lien, AHD ; Donato, C ; Toh, ZQ ; Higgins, R ; Van de Sandt, C ; Lemke, MM ; Lee, CY ; Shoffner, SK ; Flanagan, KL ; Arnold, KB ; Mordant, FL ; Mulholland, K ; Bines, J ; Dohle, K ; Pellicci, DG ; Curtis, N ; McNab, S ; Steer, A ; Saffery, R ; Subbarao, K ; Chung, AW ; Kedzierska, K ; Burgner, DP ; Crawford, NW (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.
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    The burden of hospitalised rotavirus infections in Fiji
    Jenney, A ; Tikoduadua, L ; Buadromo, E ; Barnes, G ; Kirkwood, CD ; Boniface, K ; Bines, J ; Mulholland, K ; Russell, F (ELSEVIER SCI LTD, 2009-11-20)
    Rotavirus is the most common cause of acute severe dehydrating diarrhoea in young children worldwide. We describe the burden of rotavirus disease and the rotavirus types causing it in the largest city in Fiji. During 2006 and 2007, 592 children under 5 years of age were admitted to hospital in Suva, Fiji with acute diarrhoea. Of the 454 children for whom a stool specimen was tested, 39% were positive for rotavirus and the predominant strain found was the serotype G3[P8]. There is a significant burden of disease due to rotavirus in Fiji and the introduction of rotavirus vaccines into the national immunization schedule may drastically reduce inpatient diarrhoeal disease.