Paediatrics (RCH) - Research Publications

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    The impact of 10-valent pneumococcal vaccine introduction on invasive disease in Fiji
    Reyburn, R ; Tuivaga, EJ ; Ratu, FT ; Dunne, EM ; Nand, D ; Kado, J ; Jenkins, K ; Tikoduadua, L ; Jenney, A ; Howden, BP ; Ballard, SA ; Fox, K ; Devi, R ; Satzke, C ; Rafai, E ; Kama, M ; Flasche, S ; Mulholland, EK ; Russell, FM (ELSEVIER, 2022-03)
    BACKGROUND: In 2012, Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10). We assessed the impact of PCV10 on invasive pneumococcal disease (IPD), probable bacterial or pneumococcal meningitis (PBPM), meningitis and sepsis 3-5 years post-introduction. METHODS: Laboratory-confirmed IPD and PBPM cases were extracted from national laboratory records. ICD-10-AM coded all-cause meningitis and sepsis cases were extracted from national hospitalisation records. Incidence rate ratios were used to compare outcomes pre/post-PCV10, stratified by age groups: 1-23m, 2-4y, 5-9y, 10-19y, 20-54y, ≥55y. To account for different detection and serotyping methods in the pre-and post-PCV10 period, a Bayesian inference model estimated serotype-specific changes in IPD, using pneumococcal carriage and surveillance data. FINDINGS: There were 423 IPD, 1,029 PBPM, 1,391 all-cause meningitis and 7,611 all-cause sepsis cases. Five years post-PCV10 introduction, IPD declined by 60% (95%CI: 37%, 76%) in children 1-23m months old, and in age groups 2-4y, 5-9y, 10-19y although confidence intervals spanned zero. PBPM declined by 36% (95%CI: 21%, 48%) among children 1-23 months old, and in all other age groups, although some confidence intervals spanned zero. Among children <5y of age, PCV10-type IPD declined by 83% (95%CI; 70%, 90%) and with no evidence of change in non-PCV10-type IPD (9%, 95%CI; -69, 43%). There was no change in all-cause meningitis or sepsis. Post-PCV10, the most common serotypes in vaccine age-eligible and non-age eligible people were serotypes 8 and 23B, and 3 and 7F, respectively. INTERPRETATIONS: Our study demonstrates the effectiveness of PCV10 against IPD in a country in the Asia-Pacific of which there is a paucity of data. FUNDING: This study was support by the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.
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    Prevention of bacterial complications of scabies using mass drug administration: A population-based, before-after trial in Fiji, 2018-2020
    Thean, LJ ; Romani, L ; Engelman, D ; Wand, H ; Jenney, A ; Mani, J ; Paka, J ; Cua, T ; Taole, S ; Silai, M ; Ashwini, K ; Sahukhan, A ; Kama, M ; Tuicakau, M ; Kado, J ; Parnaby, M ; Carvalho, N ; Whitfeld, M ; Kaldor, J ; Steer, AC (ELSEVIER, 2022-05)
    BACKGROUND: Scabies is an important predisposing factor of impetigo which can lead to serious bacterial complications. Ivermectin-based mass drug administration can substantially reduce scabies and impetigo prevalence in endemic settings, but the impact on serious bacterial complications is not known. METHODS: We conducted a before-after trial in the Northern Division of Fiji (population: 131,914) of mass drug administration for scabies control. Prospective surveillance was conducted from 2018 to 2020. Mass drug administration took place in 2019, involving two doses of oral ivermectin or topical permethrin, delivered alongside diethylcarbamazine and albendazole for lymphatic filariasis. The primary outcomes were incidence of hospitalisations with skin and soft tissue infections, and childhood invasive infections and post-streptococcal sequelae. Secondary outcomes included presentations to primary healthcare with skin infections and community prevalence of scabies and impetigo. FINDINGS: The incidence of hospitalisations with skin and soft tissue infections was 17% lower after the intervention compared to baseline (388 vs 467 per 100,000 person-years; incidence rate ratio 0.83, 95% CI, 0.74 to 0.94; P = 0.002). There was no difference in incidence of childhood invasive infections and post-streptococcal sequelae. Incidence of primary healthcare presentations with scabies and skin infections was 21% lower (89.2 vs 108 per 1000 person-years, incidence rate ratio, IRR 0.79, 95% CI, 0.78 to 0.82). Crude community prevalence of scabies declined from 14.2% to 7.7% (cluster-adjusted prevalence 12.5% to 8.9%; prevalence ratio 0.71, 95% CI, 0.28 to 1.17). Cluster-adjusted prevalence of impetigo declined from 15.3% to 6.1% (prevalence ratio 0.4, 95% CI, 0.18 to 0.86). INTERPRETATION: Mass drug administration for scabies control was associated with a substantial reduction in hospitalisations for skin and soft tissue infections. FUNDING: National Health and Medical Research Council of Australia and Scobie and Claire Mackinnon Trust.
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    Prospective surveillance for invasive Staphylococcus aureus and group A Streptococcus infections in a setting with high community burden of scabies and impetigo
    Thean, LJ ; Jenney, A ; Engelman, D ; Romani, L ; Wand, H ; Mani, J ; Paka, J ; Cua, T ; Taole, S ; Soqo, V ; Sahukhan, A ; Kama, M ; Tuicakau, M ; Kado, J ; Carvalho, N ; Whitfeld, M ; Kaldor, J ; Steer, AC (ELSEVIER SCI LTD, 2021-07)
    BACKGROUND: Invasive Staphylococcus aureus (iSA) and group A Streptococcus (iGAS) impose significant health burdens globally. Both bacteria commonly cause skin and soft tissue infections (SSTIs), which can result in invasive disease. Understanding of the incidence of iSA and iGAS remains limited in settings with a high SSTI burden. METHODS: Prospective surveillance for admissions with iSA or iGAS was conducted at the referral hospital in Fiji's Northern Division over 48 weeks between July 2018 and June 2019. RESULTS: There were 55 admissions for iSA and 15 admissions for iGAS (incidence 45.2 and 12.3 per 100,000 person-years, respectively). The highest incidence was found in patients aged ≥65 years (59.6 per 100,000 person-years for iSA and iGAS). The incidence of iSA was higher in indigenous Fijians (iTaukei) (71.1 per 100,000 person-years) compared with other ethnicities (incidence rate ratio 9.7, 95% confidence interval 3.5-36.9). SSTIs were found in the majority of cases of iSA (75%) and iGAS (53.3%). Thirteen of the 14 iGAS strains isolated belonged to emm cluster D (n = 5) or E (n = 8). The case fatality rate was high for both iSA (10.9%) and iGAS (33.3%). CONCLUSIONS: The incidence of iSA and iGAS in Fiji is very high. SSTIs are common clinical foci for both iSA and iGAS. Both iSA and iGAS carry a substantial risk of death. Improved control strategies are needed to reduce the burden of iSA and iGAS in Fiji.
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    Genotype Diversity before and after the Introduction of a Rotavirus Vaccine into the National Immunisation Program in Fiji
    Thomas, S ; Donato, CM ; Covea, S ; Ratu, FT ; Jenney, AWJ ; Reyburn, R ; Khan, AS ; Rafai, E ; Grabovac, V ; Serhan, F ; Bines, JE ; Russell, FM (MDPI, 2021-03)
    The introduction of the rotavirus vaccine, Rotarix, into the Fiji National Immunisation Program in 2012 has reduced the burden of rotavirus disease and hospitalisations in children less than 5 years of age. The aim of this study was to describe the pattern of rotavirus genotype diversity from 2005 to 2018; to investigate changes following the introduction of the rotavirus vaccine in Fiji. Faecal samples from children less than 5 years with acute diarrhoea between 2005 to 2018 were analysed at the WHO Rotavirus Regional Reference Laboratory at the Murdoch Children's Research Institute, Melbourne, Australia, and positive samples were serotyped by EIA (2005-2006) or genotyped by heminested RT-PCR (2007 onwards). We observed a transient increase in the zoonotic strain equine-like G3P[8] in the initial period following vaccine introduction. G1P[8] and G2P[4], dominant genotypes prior to vaccine introduction, have not been detected since 2015 and 2014, respectively. A decrease in rotavirus genotypes G2P[8], G3P[6], G8P[8] and G9P[8] was also observed following vaccine introduction. Monitoring the rotavirus genotypes that cause diarrhoeal disease in children in Fiji is important to ensure that the rotavirus vaccine will continue to be protective and to enable early detection of new vaccine escape strains if this occurs.
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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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    Hospital admissions for skin and soft tissue infections in a population with endemic scabies: A prospective study in Fiji, 2018-2019
    Thean, LJ ; Jenney, A ; Engelman, D ; Romani, L ; Wand, H ; Mudaliar, J ; Paka, J ; Cua, T ; Taole, S ; Sahukhan, A ; Kama, M ; Tuicakau, M ; Kado, J ; Carvalho, N ; Whitfeld, M ; Kaldor, J ; Steer, AC ; Ramos, AN (PUBLIC LIBRARY SCIENCE, 2020-12)
    Scabies is an important predisposing factor for impetigo but its role in more serious skin and soft tissue infections (SSTIs) is not well understood. Information is limited on incidence of SSTIs in the presence of endemic scabies. We conducted a prospective study of hospital admissions for SSTIs in the Northern Division of Fiji (population: 131,914). Prospective surveillance for admissions with impetigo, abscess, cellulitis, wound infection, pyomyositis, necrotizing fasciitis, infected scabies, and crusted scabies was conducted at the Division's referral hospital between 2018 to 2019. Information was collected on demographic characteristics, clinical features, microbiology, treatment and outcomes. Over the study period, 788 SSTI admissions were recorded corresponding to a population incidence 647 per 100,000 person-years (95%CI 571-660). Incidence was highest at the extremes of age with peak incidence in children aged <5 years (908 per 100,000) and those aged ≥65 years (1127 per 100,000). Incidence was 1.7 times higher among the Indigenous Fijian population (753 per 100,000) compared to other ethnicities (442 per 100,000). Overall case fatality rate was 3.3%, and 10.8% for those aged ≥65 years. Scabies was diagnosed concurrently in 7.6% of all patients and in 24.6% of admitted children <5 years. There is a very high burden of hospital admissions for SSTIs in Fiji compared to high-income settings especially among the youngest, oldest and indigenous population which is concordant with scabies and impetigo distribution in this population. Our findings highlight the need for strategies to reduce the burden of SSTIs in Fiji and similar settings.
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    Prospective Surveillance of Invasive Group A Streptococcal Disease, Fiji, 2005-2007
    Steer, AC ; Jenney, A ; Kado, J ; Good, MF ; Batzloff, M ; Waqatakirewa, L ; Mullholland, EK ; Carapetis, JR (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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    High Burden of Impetigo and Scabies in a Tropical Country
    Steer, AC ; Jenney, AWJ ; Kado, J ; Batzloff, MR ; La Vincente, S ; Waqatakirewa, L ; Mulholland, EK ; Carapetis, JR ; Franco-Paredes, C (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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    The clinical and molecular epidemiology of Staphylococcus aureus infections in Fiji
    Jenney, A ; Holt, D ; Ritika, R ; Southwell, P ; Pravin, S ; Buadromo, E ; Carapetis, J ; Tong, S ; Steer, A (BMC, 2014-03-24)
    BACKGROUND: There are few data describing the microbiology and genetic typing of Staphylococcus aureus that cause infections in developing countries. METHODS: In this study we observed S. aureus infections in Pacific Island nation of Fiji in both the community and hospital setting with an emphasis on clonal complex (CC) genotyping and antimicrobial susceptibility. RESULTS: S. aureus was commonly found in impetigo lesions of school children and was recovered from 57% of impetigo lesions frequently in conjunction with group A streptococcal infection. Methicillin-resistant S. aureus (MRSA) comprised 7% (20/299) of isolates and were all non-multi-resistant and all genotyped as CC1. In contrast, there was a diverse selection of 17 CCs among the 105 genotyped methicillin-susceptible S.aureus (MSSA) strains. Isolates of the rare, phylogenetically divergent and non-pigmented CC75 lineage (also called S. argenteus) were found in Fiji.From hospitalized patients the available 36 MRSA isolates from a 9-month period were represented by five CCs. The most common CCs were CC1 and CC239. CC1 is likely to be a community-acquired strain, reflecting what was found in the school children, whereas the CC239 is the very successful multi-drug resistant MRSA nosocomial lineage. Of 17 MSSA isolates, 59% carried genes for Panton-Valentine leukocidin. The S. aureus bacteraemia incidence rate of 50 per 100,000 population is among the highest reported in the literature and likely reflects the high overall burden of staphylococcal infections in this population. CONCLUSIONS: S. aureus is an important cause of disease in Fiji and there is considerable genotypic diversity in community skin infections in Fijian schoolchildren. Community acquired- (CA)- MRSA is present at a relatively low prevalence (6.7%) and was solely to CC1 (CA-MRSA). The globally successful CC239 is also a significant pathogen in Fiji.
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    Real-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji
    Dunne, EM ; Mantanitobua, S ; Singh, SP ; Reyburn, R ; Tuivaga, E ; Rafai, E ; Tikoduadua, L ; Porter, B ; Satzke, C ; Strachan, JE ; Fox, KK ; Jenkins, KM ; Jenney, A ; Baro, S ; Mulholland, EK ; Kama, M ; Russell, FM (NATURE PORTFOLIO, 2016-12-23)
    As part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Of 266 samples tested, pathogens were identified in 47 (17.7%). S. pneumoniae was the most common pathogen detected (n = 17) followed by N. meningitidis (n = 13). The use of qPCR significantly increased detection of IB-VPD pathogens (P = 0.0001): of 35 samples that were qPCR positive for S. pneumoniae, N. meningitidis, and H. influenzae, only 10 were culture positive. This was particularly relevant for N. meningitidis, as only 1/13 cases was culture positive. Molecular serotyping by microarray was used to determine pneumococcal serotypes from 9 of 16 (56%) of samples using DNA directly extracted from CSF specimens. Results indicate that qPCR significantly increases detection of S. pneumoniae, N. meningitidis, and H. influenzae in CSF, and that application of molecular diagnostics is a feasible way to enhance local and global surveillance for IB-VPD.