Paediatrics (RCH) - Research Publications
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ItemDirect and indirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with pneumonia from formal and informal settlements in Mongolia: an observational study(ELSEVIER, 2021-10)BACKGROUND: Within Ulaanbaatar, Mongolia, risk factors for pneumonia are concentrated among children living in informal settlements comprised of temporary shelters (gers). We used pneumococcal carriage surveillance among children from formal and informal settlements hospitalised with pneumonia to evaluate the direct and indirect effects of 13-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) pneumococcal carriage following a phased introduction of PCV13. METHODS: We enrolled and collected nasopharyngeal swabs from children 2-59 months of age presenting to hospital. Pneumococci were detected using lytA qPCR and serotyped using microarray on a random monthly selection of swabs between November 2015 and March 2019 from two districts in Ulaanbaatar. PCV13 status was determined using written records. We quantified the associations between individual PCV13 status (direct effects) and district-level PCV13 coverage (indirect effects) and VT carriage using generalised estimating equations and explored interactions by settlement type. FINDINGS: A total of 1 292 swabs from 6 046 participants were tested for pneumococci. Receipt of PCV13 and increasing PCV13 coverage independently reduced the risk of VT carriage. For each percent increase in PCV13 coverage, the adjusted odds of VT carriage decreased by 1•0% (OR 95% CI 0•983-0•996; p=0•001), with a predicted decrease in VT carriage rate from 29•1% to 13•1% as coverage reached 100%. There was a trend towards a slower decline within informal settlements (p=0•100). Adjusted PCV13 vaccine effectiveness against VT carriage was 39•1% (95% CI 11•4-58•1%, p=0•009). INTERPRETATION: Substantial indirect effects were observed following PCV13 introduction, including among children living within informal settlements. FUNDING: Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance.
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ItemIndirect effects of 13-valent pneumococcal conjugate vaccine on pneumococcal carriage in children hospitalised with acute respiratory infection despite heterogeneous vaccine coverage: an observational study in Lao People's Democratic Republic(BMJ PUBLISHING GROUP, 2021-06)INTRODUCTION: Empiric data on indirect (herd) effects of pneumococcal conjugate vaccines (PCVs) in settings with low or heterogeneous PCV coverage are limited. The indirect effects of PCV, which benefits both vaccinated and non-vaccinated individuals, are mediated by reductions in vaccine-type (VT) carriage (a prerequisite for disease). The aim of this study among hospitalised children in Lao People's Democratic Republic (Lao PDR) is to determine the effectiveness of a 13-valent PCV (PCV13) against VT pneumococcal nasopharyngeal carriage (direct effects) and the association between village-level PCV13 coverage and VT carriage (indirect effects). METHODS: Pneumococcal nasopharyngeal carriage surveillance commenced in December 2013, shortly after PCV13 introduction (October 2013). We recruited and swabbed children aged 2-59 months admitted to hospital with acute respiratory infection. Pneumococci were detected using lytA quantitative real-time PCR and serotyped using microarray. PCV13 status and village-level PCV13 coverage were determined using written immunisation records. Associations between both PCV13 status and village-level PCV13 coverage and VT carriage were calculated using generalised estimating equations, controlling for potential confounders. RESULTS: We enrolled 1423 participants and determined PCV13 coverage for 368 villages (269 863 children aged under 5 years). By 2017, median village-level vaccine coverage reached 37.5%, however, the IQR indicated wide variation among villages (24.1-56.4). Both receipt of PCV13 and the level of PCV13 coverage were independently associated with a reduced odds of VT carriage: adjusted PCV13 effectiveness was 38.1% (95% CI 4.1% to 60.0%; p=0.032); and for each per cent increase in PCV13 coverage, the estimated odds of VT carriage decreased by 1.1% (95% CI 0.0% to 2.2%; p=0.056). After adjustment, VT carriage decreased from 20.0% to 12.8% as PCV13 coverage increased from zero to 60% among under 5. CONCLUSIONS: Despite marked heterogeneity in PCV13 coverage, we found evidence of indirect effects in Lao PDR. Individual vaccination with PCV13 was effective against VT carriage.
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ItemNasopharyngeal Pneumococcal Colonization Density Is Associated With Severe Pneumonia in Young Children in the Lao People's Democratic Republic(OXFORD UNIV PRESS INC, 2022-04-01)BACKGROUND: No studies have explored the association between pneumococcal nasopharyngeal density and severe pneumonia using the World Health Organization (WHO) 2013 definition. In Lao People's Democratic Republic (Lao PDR), we determine the association between nasopharyngeal pneumococcal density and severe pneumonia in children. METHODS: A prospective observational study was undertaken at Mahosot Hospital, Vientiane, from 2014 to mid-2018. Children <5 years admitted with acute respiratory infections (ARIs) were included. Clinical and demographic data were collected alongside nasopharyngeal swabs for pneumococcal quantification by lytA real-time quantitative polymerase chain reaction. Severe pneumonia was defined using the 2013 WHO definition. For pneumococcal carriers, a logistic regression model examined the association between pneumococcal density and severe pneumonia, after adjusting for potential confounders including demographic and household factors, 13-valent pneumococcal conjugate vaccine status, respiratory syncytial virus co-detection, and preadmission antibiotics. RESULTS: Of 1268 participants with ARI, 32.3% (n = 410) had severe pneumonia and 36.9% (n = 468) had pneumococcal carriage. For pneumococcal carriers, pneumococcal density was positively associated with severe pneumonia (adjusted odds ratio, 1.4 [95% confidence interval, 1.1-1.8]; P = .020). CONCLUSIONS: Among children with ARIs and pneumococcal carriage, pneumococcal carriage density was positively associated with severe pneumonia in Lao PDR. Further studies may determine if pneumococcal density is a useful marker for pneumococcal conjugate vaccine impact on childhood pneumonia.
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ItemEffect of ten-valent pneumococcal conjugate vaccine introduction on pneumococcal carriage in Fiji: results from four annual cross-sectional carriage surveys(ELSEVIER SCI LTD, 2018-12)BACKGROUND: The indirect effects of pneumococcal conjugate vaccines (PCVs) are mediated through reductions in carriage of vaccine serotypes. Data on PCVs in Asia and the Pacific are scarce. Fiji introduced the ten-valent PCV (PCV10) in 2012, with a schedule consisting of three priming doses at 6, 10, and 14 weeks of age and no booster dose (3 + 0 schedule) without catch-up. We investigated the effects of PCV10 introduction using cross-sectional nasopharyngeal carriage surveys. METHODS: We did four annual carriage surveys (one pre-PCV10 and three post-PCV10) in the greater Suva area in Fiji, during 2012-15, of 5-8-week-old infants, 12-23-month-old children, 2-6-year-old children, and their caregivers (total of 8109 participants). Eligible participants were of appropriate age, had axillary temperature lower than 37°C, and had lived in the community for at least 3 consecutive months. We used purposive quota sampling to ensure a proper representation of the Fiji population. Pneumococci were detected by real-time quantitative PCR, and molecular serotyping was done with microarray. FINDINGS: 3 years after PCV10 introduction, vaccine-serotype carriage prevalence declined, with adjusted prevalences (2015 vs 2012) of 0·56 (95% CI 0·34-0·93) in 5-8-week-old infants, 0·34 (0·23-0·49) in 12-23-month-olds, 0·47 (0·34-0·66) in 2-6-year-olds, and 0·43 (0·13-1·42) in caregivers. Reductions in PCV10 serotype carriage were evident in both main ethnic groups in Fiji; however, carriage of non-PCV10 serotypes increased in Indigenous Fijian infants and children. Density of PCV10 serotypes and non-PCV10 serotypes was lower in PCV10-vaccinated children aged 12-23 months than in PCV10-unvaccinated children of the same age group (PCV10 serotypes -0·56 [95% CI -0·98 to -0·15], p=0·0077; non-PCV10 serotypes -0·29 [-0·57 to -0·02], p=0·0334). INTERPRETATION: Direct and indirect effects on pneumococcal carriage post-PCV10 are likely to result in reductions in pneumococcal disease, including in infants too young to be vaccinated. Serotype replacement in carriage in Fijian children, particularly Indigenous children, warrants further monitoring. Observed changes in pneumococcal density might be temporal rather than vaccine related. FUNDING: Department of Foreign Affairs and Trade of the Australian Government through the Fiji Health Sector Support Program; Victorian Government's Operational Infrastructure Support Program; Bill & Melinda Gates Foundation.
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ItemThe association between pneumococcal vaccination, ethnicity, and the nasopharyngeal microbiota of children in Fiji(BMC, 2019-07-16)BACKGROUND: Streptococcus pneumoniae is a significant global pathogen that colonises the nasopharynx of healthy children. Pneumococcal conjugate vaccines, which reduce nasopharyngeal colonisation of vaccine-type S. pneumoniae, may have broader effects on the nasopharyngeal microbiota; however, data are limited. In Fiji, nasopharyngeal carriage prevalence of S. pneumoniae and other colonising species differ between the two main ethnic groups. Here, we examined the association between the 7-valent pneumococcal conjugate vaccine (PCV7) and the nasopharyngeal microbiota of children in Fiji, including for each of the two main ethnic groups-indigenous Fijians (iTaukei) and Fijians of Indian descent (FID). METHOD: The nasopharyngeal microbiota of 132 Fijian children was examined using nasopharyngeal swabs collected from 12-month-old iTaukei and FID children who were vaccinated (3 doses PCV7) or unvaccinated in infancy as part of a phase II randomised controlled trial. Microbiota composition was determined by sequencing the V4 region of the 16S rRNA gene. Species-specific carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus was determined using real-time quantitative PCR. Associations between microbiota composition and other host and environmental factors were considered in the analysis. RESULTS: PCV7 had no overall impact on microbial diversity or composition. However, ethnic differences were observed in both diversity and composition with iTaukei children having higher relative abundance of Moraxella (p = 0.004) and Haemophilus (p = 0.004) and lower relative abundance of Staphylococcus (p = 0.026), Dolosigranulum (p = 0.004) and Corynebacterium (p = 0.003) compared with FID children. Further, when we stratified by ethnicity, associations with PCV7 could be detected: vaccinated iTaukei children had a lower relative abundance of Streptococcus and Haemophilus compared with unvaccinated iTaukei children (p = 0.022 and p = 0.043, respectively); and vaccinated FID children had a higher relative abundance of Dolosigranulum compared with unvaccinated FID children (p = 0.037). Children with symptoms of an upper respiratory tract infection (URTI) had a significantly different microbiota composition to children without symptoms. The microbiota composition of iTaukei children without URTI symptoms was most similar to the microbiota composition of FID children with URTI symptoms. CONCLUSIONS: Associations between PCV7 and nasopharyngeal microbiota differed within each ethnic group. This study highlights the influence that ethnicity and URTIs have on nasopharyngeal microbiota.
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ItemFactors associated with pneumococcal carriage and density in children and adults in Fiji, using four cross-sectional surveys(PUBLIC LIBRARY SCIENCE, 2020-04-01)This study describes predictors of pneumococcal nasopharyngeal carriage and density in Fiji. We used data from four annual (2012-2015) cross-sectional surveys, pre- and post-introduction of ten-valent pneumococcal conjugate vaccine (PCV10) in October 2012. Infants (5-8 weeks), toddlers (12-23 months), children (2-6 years), and their caregivers participated. Pneumococci were detected and quantified using lytA qPCR, with molecular serotyping by microarray. Logistic and quantile regression were used to determine predictors of pneumococcal carriage and density, respectively. There were 8,109 participants. Pneumococcal carriage was negatively associated with years post-PCV10 introduction (global P<0.001), and positively associated with indigenous iTaukei ethnicity (aOR 2.74 [95% CI 2.17-3.45] P<0.001); young age (infant, toddler, and child compared with caregiver participant groups) (global P<0.001); urban residence (aOR 1.45 [95% CI 1.30-2.57] P<0.001); living with ≥2 children <5 years of age (aOR 1.42 [95% CI 1.27-1.59] P<0.001); low family income (aOR 1.44 [95% CI 1.28-1.62] P<0.001); and upper respiratory tract infection (URTI) symptoms (aOR 1.77 [95% CI 1.57-2.01] P<0.001). Predictors were similar for PCV10 and non-PCV10 carriage, except PCV10 carriage was negatively associated with PCV10 vaccination (0.58 [95% CI 0.41-0.82] P = 0.002) and positively associated with exposure to household cigarette smoke (aOR 1.21 [95% CI 1.02-1.43] P = 0.031), while there was no association between years post-PCV10 introduction and non-PCV10 carriage. Pneumococcal density was positively associated with URTI symptoms (adjusted median difference 0.28 [95% CI 0.16, 0.40] P<0.001) and toddler and child, compared with caregiver, participant groups (global P = 0.008). Predictors were similar for PCV10 and non-PCV10 density, except infant, toddler, and child participant groups were not associated with PCV10 density. PCV10 introduction was associated with reduced the odds of overall and PCV10 pneumococcal carriage in Fiji. However, after adjustment iTaukei ethnicity was positively associated with pneumococcal carriage compared with Fijians of Indian Descent, despite similar PCV10 coverage rates.