Jason Hinds, United Kingdom

St George's, University of London Institute for Infection and Immunity

Author Of 10 Presentations

THE IMPACT OF PNEUMOCOCCAL CONJUGATE VACCINE INTRODUCTION IN NEPAL: A SIX-YEAR PAEDIATRIC SURVEILLANCE STUDY (ID 516)

Abstract

Background

S. pneumoniae is a major cause of bacterial pneumonia and an important cause of invasive bacterial disease (IBD) in children under-five years of age in Nepal. Pneumococcal conjugate vaccine, PCV10, was introduced in 2015 with a 2+1 schedule.

Methods

We assessed the programmatic impact of PCV10 introduction using surveillance for nasopharyngeal (NP) colonisation, pneumonia and IBD. NP swabs from pneumonia inpatients and from healthy children, blood cultures from inpatients with suspected IBD, and chest x-rays from inpatient pneumonia cases were obtained over a 6-year period (2014-2019).

Results

The proportion of pneumonia cases with radiographic endpoint-consolidation (likely bacterial) was 34% lower (95%CI 19-46%) in 2018 compared with the pre-vaccine period (2014-2015). Vaccine serotype (VT) carriage in children under 2-years of age with pneumonia in 2019 was 78% lower (95%CI 30-93%) than in the pre-vaccine period.

Among healthy 6-23 month old children (urban and rural cohorts), VT-carriage declined 74% (95%CI 43-82%) by 2019. An increase in PCV13-additional-serotype carriage was seen in 2018 among rural-children (prevalence-ratio 1.65, 95%CI 1.17-2.32), but not urban-children.

Serotype 1 remains the dominant serotype detected in cases of invasive pneumococcal disease.

Conclusions

A decrease in prevalence of endpoint-consolidation-pneumonia and a decrease in vaccine-serotype circulation have been observed post PCV introduction in Nepal.

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MONITORING VACCINE IMPACT ON COMMUNITY CARRIAGE IN NEPAL REVEALS CHANGES IN THE CIRCULATING POPULATION OF PNEUMOCOCCAL SEROTYPES AND ANTIMICROBIAL RESISTANCE GENES (ID 977)

Abstract

Background

Community carriage of pneumococcal serotypes in children was assessed pre- and post-PCV10 introduction in Nepal to monitor pneumococcal vaccine impact. Molecular serotyping by microarray enabled detection of multiple-serotype carriage plus non-encapsulated pneumococcal lineages, related Streptococcus species and selected antimicrobial resistance genes.

Methods

Nasopharyngeal swabs were collected from healthy Nepalese children in 2014-15 (pre-PCV10) and 2017-18 (post-PCV10). DNA was extracted from plate sweeps of 1,241 and 1,445 swab cultures for pre- and post-vaccine periods respectively and analysed by Senti-SP molecular serotyping microarray.

Results

Comparing carriage among children pre- and post-PCV10, there was a decrease in PCV10 serotype carriage (37% vs 17%) and an increase in non-vaccine serotype carriage (67% vs 73%). There was no change for non-encapsulated pneumococcal lineages (16% vs 16%), an increase in related Streptococcal species (22% vs 25%) and an increase in detection of antimicrobial resistance genes (65% vs 74%). Multiple pneumococcal serotype carriage decreased (24% vs 16%) and multiple carriage including non-encapsulated pneumococci and related Streptococcal species also decreased (45% vs 41%).

Conclusions

Introduction of PCV10 in Nepal has resulted in a decrease in vaccine type carriage within two years. However, increases in carriage of non-vaccine types as well as antimicrobial resistance genes and related Streptococcal species were observed.

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MICROARRAY RESULTS FROM NASOPHARYNGEAL LYTA-POSITIVE CHILDREN AND ADULTS: OBSERVATIONAL DATA FROM THE TRANSMISSION OF PNEUMOCOCCUS STUDY (ID 728)

Abstract

Background

Quantification of Streptococcus pneumoniae (Sp) carriage density and identification of serotypes in contacts contribute to understanding Sp transmission and thus evaluating pneumococcal conjugate vaccine impact.

Methods

266 lytA-positive nasopharyngeal samples (NPS) taken during season 1 (of 2, October-December 2017) of the Transmission of Pneumococcus (TOP) study (see abstract 715) were analysed by microarray. NPS were collected from 120 families, 2-weekly over 2 months.

Results

83/120 index children (2-year-olds) were lytA positive at baseline (visit 1): the three most common serotypes were 11A, 15B and 35F (n=83) (Graph 1).

In 17/28 families (28 index children, 45 contacts: 26 <16-year-olds and 19), index children shared ≥1 strain/serotype with ≥1 household contact.

40% (107/266) of lytA-positive NPS analysed had multiple serotypes/strains.

Sp was not detected in some lytA-positive samples but rather related streptococcal species, particularly from participants aged ≥5 years (Table 1).

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Conclusions

NP carriage of the same Sp serotypes by multiple household members suggests that household Sp transmission occurs.

Multiple serotype carriage was observed in a significant proportion of participants.

Among young children, the age group most likely to transmit Sp, lytA was more predictive of true Sp infection than it was among older persons.

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SEROTYPE-SPECIFIC PNEUMOCOCCAL CARRIAGE DENSITY AMONG HEALTHY NEPALESE CHILDREN POST-PCV10 INTRODUCTION (ID 1047)

Abstract

Background

The density of pneumococcal carriage provides an insight into the dynamics of transmission, colonisation and vaccine effect. We aimed to measure serotype-specific carriage density 2-3 years after 10-valent pneumococcal conjugate vaccine (PCV10) introduction, using qPCR and bacterial DNA microarray.

Methods

Nasopharyngeal swabs were collected from healthy Nepalese children from the Kathmandu Valley between April 2017 and August 2018. DNA was extracted from the swab media and qPCR performed for pneumococcal autolysin (lytA). Swab media were also plated on blood agar, incubated overnight, and plate sweeps collected. DNA was extracted from plate sweeps and molecular serotyped using the Senti-SPv1.5 microarray (BUGS Bioscience, UK).

Results

1264 swabs were collected and analysed by both microarray and qPCR. The mean density of PCV10 serotypes was significantly higher than non-PCV10 serotypes (10^3.9 vs 10^3.4 copies/ml, p=0.004). Serotypes 1 (10^4.6 copies/ml, 95% CI 10^3.4-5.9) and 6B (10^4.6 copies/ml, 95% CI 10^3.9-5.3) had the highest mean density. Serotypes 4 (10^2.8 copies/ml, 95% CI 10^1.1-4.5) and 9N (10^2.9copies/ml, 95% CI 10^2.1-3.7) had the lowest mean carriage density.

Conclusions

Serotype 1, which causes the greatest proportion of invasive pneumococcal disease in this setting, was found to have the highest carriage density. Further evaluation of the PCV10 impact on carriage density is needed.

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HIGH RATES OF MULTIPLE NASOPHARYNGEAL PNEUMOCOCCAL CARRIAGE IN CHILDREN WITH PNEUMONIA IN PAPUA NEW GUINEA FOLLOWING PNEUMOCOCCAL CONJUGATE VACCINE INTRODUCTION (ID 731)

Abstract

Background

Pneumococcal carriage rates in Papua New Guinean (PNG) children are among the highest globally. One aim of the multi-site PneuCAPTIVE study is to determine the impact of PCV13 (introduced in 2014) on nasopharyngeal carriage in PNG.

Methods

Nasopharyngeal (NP) swabs and blood were collected from children aged <5 years with moderate or severe pneumonia, and/or suspected meningitis at Eastern Highlands Provincial Hospital or outpatient clinics in Goroka (2016-2018). Pneumococci were identified and quantified by lytA qPCR, and serotyped by microarray. IPD was identified by standard blood culture.

Results

PCV13 coverage was 62%. 1043 were enrolled: 90% had pneumococcal carriage, with median density of 6.59 log10 genome equivalents (GE)/ml (IQR 6.00-7.11). Serotype data were available on 914 cases: 37% were PCV13-types; and 55% had multiple pneumococcal-type carriage. 74 different serotypes and genetic lineages of acapsular pneumococci were identified, the most common being acapsular lineage NT2>19A>15B/C>16F>14. PCV13-type carriage was 28% in vaccinated children vs 46% in unvaccinated children. IPD was confirmed in 7 cases (vaccinated – serotype 1; unvaccinated – serotypes 2, 6B, 15F, 19A, 23A, 29): 4/7 carried the homologous serotype.

Conclusions

There is some evidence of PCV13 being effective against PCV13-types but the high diversity of serotypes in PNG warrants extended valency vaccines.

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