Suchergebnisse

BACKGROUND: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no studies from Asia examining the effectiveness of PCVs on hypoxic pneumonia. We describe a novel approach to determine the effectiveness of the 13-valent PCV (PCV13) against hypoxia in children admitted with pneumonia in the Lao People's Democratic Republic. METHODS: A prospective hospital-based, test-negative observational study of children aged up to 59 months admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. Test-negative cases and controls were children with hypoxic and non-hypoxic pneumonia, respectively. PCV13 status was determined by written record. Vaccine effectiveness was calculated using logistic regression. Propensity score and multiple imputation analyses were used to handle confounding and missing data. FINDINGS: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, propensity-score adjusted and multiple-imputation adjusted estimates of vaccine effectiveness against hypoxic pneumonia were 23% (95% confidence interval: -9, 46%; p=0•14); 37% (6, 57%; p=0•02) and 35% (7, 55%; p=0•02) respectively. INTERPRETATION: PCV13 is effective against hypoxic pneumonia in Asia, and should be prioritised for inclusion in national immunisation programs. This single hospital-based, test-negative approach can be used to assess vaccine effectiveness in other similar settings. FUNDING: Funded by the Bill & Melinda Gates Foundation.

Background: Pneumococcal pneumonia is a leading cause of childhood mortality. Pneumococcal conjugate vaccines (PCVs) have been shown to reduce hypoxic pneumonia in children. However, there are no studies from Asia examining the effectiveness of PCVs on hypoxic pneumonia. We describe a novel approach to determine the effectiveness of the 13-valent PCV (PCV13) against hypoxia in children admitted with pneumonia in the Lao People's Democratic Republic. Methods: A prospective hospital-based, test-negative observational study of children aged up to 59 months admitted with pneumonia to a single tertiary hospital in Vientiane was undertaken over 54 months. Pneumonia was defined using the 2013 WHO definition. Hypoxia was defined as oxygen saturation <90% in room air or requiring oxygen supplementation during hospitalisation. Test-negative cases and controls were children with hypoxic and non-hypoxic pneumonia, respectively. PCV13 status was determined by written record. Vaccine effectiveness was calculated using logistic regression. Propensity score and multiple imputation analyses were used to handle confounding and missing data. Findings: There were 826 children admitted with pneumonia, 285 had hypoxic pneumonia and 377 were PCV13-vaccinated. The unadjusted, propensity-score adjusted and multiple-imputation adjusted estimates of vaccine effectiveness against hypoxic pneumonia were 23% (95% confidence interval: -9, 46%; p=0•14); 37% (6, 57%; p=0•02) and 35% (7, 55%; p=0•02) respectively. Interpretation: PCV13 is effective against hypoxic pneumonia in Asia, and should be prioritised for inclusion in national immunisation programs. This single hospital-based, test-negative approach can be used to assess vaccine effectiveness in other similar settings. Funding: Funded by the Bill & Melinda Gates Foundation.

BACKGROUND: In October, 2012, Fiji introduced routine infant immunisation with a ten-valent pneumococcal conjugate vaccine (PCV10) using three primary doses and no booster dose (3 + 0 schedule). Data are scarce for the effect of PCV in the Asia and Pacific region. We aimed to evaluate the effect of PCV10 on pneumonia hospital admissions in children younger than 5 years and adults aged 55 years and older in Fiji, 5 years after vaccine introduction. METHODS: We did a time-series analysis assessing changes in pneumonia hospital admissions at three public tertiary hospitals in Fiji. Four pneumonia outcomes were evaluated: all-cause pneumonia, severe or very severe pneumonia, hypoxic pneumonia, and radiological pneumonia. Participants aged younger than 2 months, 2-23 months, 24-59 months, and 55 years and older were included. Data were extracted from the national hospital admission database according to International Classification of Diseases-tenth revision codes J10·0-18·9, J21, and J22 for all-cause pneumonia. Medical records and chest radiographs were reviewed for the main tertiary hospital to reclassify hospital admissions in children aged younger than 2 years as severe or very severe, hypoxic, or radiological pneumonia as per WHO definitions. Time-series analyses were done using the synthetic control method and multiple imputation to adjust for changes in hospital usage and missing data. FINDINGS: Between Jan 1, 2007, and Dec 31, 2017, the ratio of observed cases to expected cases for all-cause pneumonia was 0·92 (95% CI 0·70-1·36) for children aged younger than 2 months, 0·86 (0·74-1·00) for children aged 2-23 months, 0·74 (0·62-0·87) for children aged 24-59 months, and 1·90 (1·53-2·31) in adults aged 55 years and older, 5 years after PCV10 introduction. These findings indicate a reduction in all-cause pneumonia among children aged 24-59 months and an increase in adults aged 55 years and older, but no change among children aged younger than 2 months. Among children aged 2-23 months, we observed declines of 21% (95% CI 5-35) for severe or very severe pneumonia, 46% (33-56) for hypoxic pneumonia, and 25% (9-38) for radiological pneumonia. Mortality reduced by 39% (95% CI 5-62) for all-cause pneumonia, bronchiolitis, and asthma admissions in children aged 2-23 months. INTERPRETATION: The introduction of PCV10 was associated with a decrease in pneumonia hospital admissions in children aged 2-59 months. This is the first study in a middle-income country in the Asia and Pacific region to show the effect of PCV on pneumonia, filling gaps in the literature on the effects of PCV10 and 3 + 0 schedules. These data support decision making on PCV introduction for other low-income and middle-income countries in the region. FUNDING: Department of Foreign Affairs and Trade of the Australian Government.

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.

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.

Objectives: Pneumococcal conjugate vaccines (PCVs) are effective in reducing pneumococcal disease. We measured 13-valent PCV (PCV13) effect on different pneumococcal outcomes using diverse studies in Lao People's Democratic Republic. Methods: Studies included: pre-PCV13 population-based record review of hospitalized childhood pneumonia cases; acute respiratory infection (ARI) study post-PCV13 to demonstrate effectiveness (VE) against hypoxic pneumonia; invasive pneumococcal disease (IPD) surveillance in all ages (2004–2018); carriage studies in children hospitalized with ARI (2013–2019); community carriage surveys pre- and post-PCV13. Results: Annual pneumonia incidence rate in children pre-PCV13 was 1,530 (95% confidence interval [CI] 1,477–1,584) per 100,000. Adjusted VE against hypoxic pneumonia was 37% (95% CI 6–57%). For IPD, 85% (11/13) of cases were due to vaccine-types pre-PCV13, and 43% (3/7) post-PCV13 in children aged <5 years; for ≥5 years, 61% (27/44) and 42% (17/40), respectively. For ARI cases, adjusted VE for vaccine-type carriage was 39% (95% CI 4–60) in <5 year olds; slightly higher than community surveys (23% [95% CI 4–39%] in 12–23 month olds). Conclusions: Despite limited baseline data, we found evidence of PCV13 impact on disease and carriage. Our approach could be used in similar settings to augment existing WHO PCV evaluation guidelines.

INTRODUCTION: Pneumococcal conjugate vaccines (PCVs) prevent disease through both direct protection of vaccinated individuals and indirect protection of unvaccinated individuals by reducing nasopharyngeal (NP) carriage and transmission of vaccine-type (VT) pneumococci. While the indirect effects of PCV vaccination are well described, the PCV coverage required to achieve the indirect effects is unknown. We will investigate the relationship between PCV coverage and VT carriage among undervaccinated children using hospital-based NP pneumococcal carriage surveillance at three sites in Asia and the Pacific. METHODS AND ANALYSIS: We are recruiting cases, defined as children aged 2-59 months admitted to participating hospitals with acute respiratory infection in Lao People's Democratic Republic, Mongolia and Papua New Guinea. Thirteen-valent PCV status is obtained from written records. NP swabs are collected according to standard methods, screened using lytA qPCR and serotyped by microarray. Village-level vaccination coverage, for the resident communities of the recruited cases, is determined using administrative data or community survey. Our analysis will investigate the relationship between VT carriage among undervaccinated cases (indirect effects) and vaccine coverage using generalised estimating equations. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the relevant ethics committees at participating sites. The results are intended for publication in open-access peer-reviewed journals and will demonstrate methods suitable for low- and middle-income countries to monitor vaccine impact and inform vaccine policy makers about the PCV coverage required to achieve indirect protection.