Limited data from Asia are available on long-term effects of pneumococcal conjugate vaccine introduction on pneumococcal carriage. Here we assess the impact of 13-valent pneumococcal conjugate ...vaccine (PCV13) introduction on nasopharyngeal pneumococcal carriage prevalence, density and antimicrobial resistance. Cross-sectional carriage surveys were conducted pre-PCV13 (2015) and post-PCV13 introduction (2017 and 2022). Pneumococci were detected and quantified by real-time PCR from nasopharyngeal swabs. DNA microarray was used for molecular serotyping and to infer genetic lineage (Global Pneumococcal Sequence Cluster). The study included 1461 infants (5–8 weeks old) and 1489 toddlers (12–23 months old) enrolled from family health clinics. We show a reduction in PCV13 serotype carriage (with non-PCV13 serotype replacement) and a reduction in the proportion of samples containing resistance genes in toddlers six years post-PCV13 introduction. We observed an increase in pneumococcal nasopharyngeal density. Serotype 15 A, the most prevalent non-vaccine-serotype in 2022, was comprised predominantly of GPSC904;9. Reductions in PCV13 serotype carriage will likely result in pneumococcal disease reduction. It is important for ongoing surveillance to monitor serotype changes to potentially inform new vaccine development.Pneumococcal carriage is a useful outcome to evaluate pneumococcal conjugate vaccine (PCV) introduction. Here the authors conducted cross-sectional carriage surveys before (2015) and after 13-valent PCV introduction (2017 and 2022) in Mongolia to determine vaccine impact.
Abstract
Background
Data on influenza vaccine effectiveness (IVE) against mortality are limited, with no Australian data to guide vaccine uptake. We aimed to assess IVE against influenza-related ...mortality in Australian hospitalized patients, assess residual confounding in the association between influenza vaccination and mortality, and assess whether influenza vaccination reduces the severity of influenza illness.
Methods
Data were collected between 2010 and 2017 from a national Australian hospital-based sentinel surveillance system using a case-control design. Adults and children admitted to the 17 study hospitals with acute respiratory symptoms were tested for influenza using nucleic acid testing; all eligible test-positive cases, and a subset of test-negative controls, were included. Propensity score analysis and multivariable logistic regression were used to determine the adjusted odds ratio (aOR) of vaccination, with IVE = 1 – aOR × 100%. Residual confounding was assessed by examining mortality in controls.
Results
Over 8 seasons, 14038 patients were admitted with laboratory-confirmed influenza. The primary analysis included 9298 cases and 6451 controls, with 194 cases and 136 controls dying during hospitalization. Vaccination was associated with a 31% (95% confidence interval CI, 3%–51%; P = .033) reduction in influenza-related mortality, with similar estimates in the National Immunisation Program target group. Residual confounding was identified in patients ≥65 years old (aOR, 1.92 95% CI, 1.06–3.46; P = .031). There was no evidence that vaccination reduced the severity of influenza illness (aOR, 1.07 95% CI, .76–1.50; P = .713).
Conclusions
Influenza vaccination is associated with a moderate reduction in influenza-related mortality. This finding reinforces the utility of the Australian vaccination program in protecting those most at risk of influenza-related deaths.
Using data collected over 8 Australian influenza seasons, we observed a moderate reduction in influenza-related mortality in vaccinated hospitalized patients. There was no evidence that vaccination attenuated influenza illness.
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.
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.
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).
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.
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.
Nasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines ...(PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia.
We conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5–8 weeks old) and 989 children eligible for vaccination (12–23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray.
One year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12–23 month olds (adjusted prevalence ratio aPR 0.48 95% confidence interval CI 0.39–0.59), with evidence of non-PCV13 serotype replacement (aPR 1.55 95% CI 1.30–1.85), compared with the pre-PCV period. In 5–8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 95% CI 0.33–0.73) with no significant change in non-PCV13 serotype carriage (aPR 1.10 95% CI 0.83–1.46). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed.
This study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring.
Infant colic is a distressing condition of unknown etiology. An aberrant gastrointestinal microbiota has been associated, and Lactobacillus reuteri supplementation has been shown to reduce crying ...and/or fussing time ('crying time') in some infants with colic. The relationship between L. reuteri gut colonization and crying time has not been examined. We investigated the relationship between L. reuteri colonization and fecal microbiota (microbial diversity and Escherichia coli), intestinal inflammation, and crying time in infants with colic, using a subset of 65 infants from the Baby Biotics trial, which randomized healthy term infants aged <13 weeks with infant colic to receive probiotic L. reuteri DSM 17938 (1 × 10
colony forming units) or placebo daily for 28 days. We observed an overall reduction in median crying time, regardless of L. reuteri colonization status (n = 14 colonized). There were no differences in E. coli colonization rates or densities, microbial diversity or intestinal inflammation by L. reuteri colonization status. We found that L. reuteri density positively correlated with crying time, and E. coli density negatively correlated with microbial diversity. As density of L. reuteri was associated with increased crying time, L. reuteri supplementation may not be an appropriate treatment for all infants with colic.
Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income ...settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3 + 0 schedule (doses at 6, 10 and 14 weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5–8 week old infants (n = 1000) and 12–23 month old children (n = 1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12–23 months (adjusted prevalence ratio aPR 0.77 0.61–0.96), and no significant change in non-PCV13 serotype carriage (aPR 1.11 0.89–1.38). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 0.43–1.27) or non-PCV13 serotypes (aPR 1.29 0.85–1.96), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p < 0.001). In 12–23 month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p = 0.004 and p < 0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.
Conjunctival pneumococcal serotypes among members of a community have not been investigated well. We determined the prevalence and association of Streptococcus pneumoniae in the nasopharynx and ...conjunctiva among children in a community before pneumococcal conjugate vaccine introduction. In October 2016, conjunctival and nasopharyngeal swabs were collected from children (< 24 months old) and nasopharyngeal swabs from mothers in Nha Trang, Vietnam. Quantitative lytA PCR and DNA microarray were performed to detect and serotype S. pneumoniae. The association between S. pneumoniae in the nasopharynx and conjunctiva was evaluated using multivariable logistic regression model. Among 698 children, 62 (8.9%, 95% CI 6.9-11.2%) were positive for S. pneumoniae in the conjunctiva. Non-encapsulated S. pneumoniae were most commonly identified, followed by serotypes 6A, 6B, and 14. Nasopharyngeal and conjunctival detection were positively associated (aOR 47.30, 95% CI 24.07-92.97). Low birth-weight, day-care attendance, and recent eye symptoms were independently associated with S. pneumoniae detection in the conjunctiva (aOR 11.14, 95% CI 3.76-32.98, aOR 2.19, 95% CI 1.45-3.31, and aOR 3.59, 95% CI 2.21-5.84, respectively). Serotypes and genotypes in the conjunctiva and nasopharynx matched in 87% of the children. Three mothers' nasopharyngeal pneumococcal samples had matched serotype and genotype with their child's in the conjunctiva and nasopharynx. S. pneumoniae presence in nasopharynx and conjunctiva were strongly associated. The high concordance of serotypes suggests nasopharyngeal carriage may be a source of transmission to the conjunctiva.
Objective To determine whether the probiotic Lactobacillus reuteri DSM 17938 reduces crying or fussing in a broad community based sample of breastfed infants and formula fed infants with colic aged ...less than 3 months. Design Double blind, placebo controlled randomised trial. Setting Community based sample (primary and secondary level care centres) in Melbourne, Australia. Participants 167 breastfed infants or formula fed infants aged less than 3 months meeting Wessel’s criteria for crying or fussing: 85 were randomised to receive probiotic and 82 to receive placebo. Interventions Oral daily L reuteri (1×108 colony forming units) versus placebo for one month. Main outcomes measures The primary outcome was daily duration of cry or fuss at 1 month. Secondary outcomes were duration of cry or fuss; number of cry or fuss episodes; sleep duration of infant at 7, 14, and 21 days, and 1 and 6 months; maternal mental health (Edinburgh postnatal depression subscale); family functioning (paediatric quality of life inventory), parent quality adjusted life years (assessment of quality of life) at 1 and 6 months; infant functioning (paediatric quality of life inventory) at 6 months; infant faecal microbiota (microbial diversity, colonisation with Escherichia coli), and calprotectin levels at 1 month. In intention to treat analyses the two groups were compared using regression models adjusted for potential confounders. Results Of 167 infants randomised from August 2011 to August 2012, 127 (76%) were retained to primary outcome; of these, a subset was analysed for faecal microbial diversity, E coli colonisation, and calprotectin levels. Adherence was high. Mean daily cry or fuss time fell steadily in both groups. At 1 month, the probiotic group cried or fussed 49 minutes more than the placebo group (95% confidence interval 8 to 90 minutes, P=0.02); this mainly reflected more fussing, especially for formula fed infants. The groups were similar on all secondary outcomes. No study related adverse events occurred. ConclusionsL reuteri DSM 17938 did not benefit a community sample of breastfed infants and formula fed infants with colic. These findings differ from previous smaller trials of selected populations and do not support a general recommendation for the use of probiotics to treat colic in infants. Trial registration Current Controlled Trials ISRCTN95287767.
Infant colic is a condition of unknown cause which can result in carer distress and attachment difficulties. Recent studies have implicated the gut microbiota in infant colic, and certain probiotics ...have demonstrated possible efficacy. We aim to investigate whether the intestinal microbiota composition in infants with colic is associated with cry/fuss time at baseline, persistence of cry/fuss at 4-week follow-up, or child behavior at 2 years of age. Fecal samples from infants with colic (n = 118, 53% male) were analyzed using 16S rRNA sequencing. After examining the alpha and beta diversity of the clinical samples, we performed a differential abundance analysis of the 16S data to look for taxa that associate with baseline and future behavior, while adjusting for potential confounding variables. In addition, we used random forest classifiers to evaluate how well baseline gut microbiota can predict future crying time. Alpha diversity of the fecal microbiota was strongly influenced by birth mode, feed type, and child gender, but did not significantly associate with crying or behavioral outcomes. Several taxa within the microbiota (including Bifidobacterium, Clostridium, Lactobacillus, and Klebsiella) associate with colic severity, and the baseline microbiota composition can predict further crying at 4 weeks with up to 65% accuracy. The combination of machine learning findings with associative relationships demonstrates the potential prognostic utility of the infant fecal microbiota in predicting subsequent infant crying problems.
PDF
