Neil French, United Kingdom

Poster Author Of 1 e-Poster

Online Abstracts Vaccines - Impact of Vaccine programs and Serotype Replacement C2 Impact of Vaccine programs and Serotype Replacement

Author Of 6 Presentations

INCREASE IN FREQUENCY OF PNEUMOCOCCAL METABOLIC GENOTYPES CHARACTERISED BY ANTIMICROBIAL RESISTANCE AND ADAPTATIONS FOR COLONIZATION AFTER PCV13 INTRODUCTION IN BLANTYRE, MALAWI. (ID 416)

Abstract

Background

Streptococcus pneumoniae naturally undergoes fluctuations in genotype. We previously showed a high residual prevalence of vaccine serotype (VT) pneumococci (18% in under 5’s) 7 years after PCV13 introduction in Malawi. In this context, we hypothesised the emergence and fixation of S. pneumoniae lineages with genetic traits conveying a competitive advantage in the nasopharyngeal niche.

Methods

1826 S. pneumoniae genomes were analysed from isolates collected during rolling cross-sectional carriage surveys in Blantyre, 4-7 years after PCV13 introduction. The metabolic core-genome includes 175 discrete metabolic genotypic profiles (metabolic types, MTs). Relative fitness was assessed by in-vitro growth and adhesive potential evaluated using Detroit 562 nasopharyngeal epithelial cells.

Results

High residual pneumococcal carriage is characterised by persistent MTs in VT (e.g. 3 and 23F) and emerging new MTs in non-VT (NVT; 38 and 23B). Increase in AMR MTs among 38 and 23B was observed. Emerging MTs show characteristic sequences of virulence genes and are characterised phenotypically by higher growth potential and propensity for better adherence to NP cell. We identified convergent evolution between MTs isolated in different countries, result of genetic bottlenecks.

Conclusions

This shift in metabolic genotypes, antimicrobial resistance and colonization adaptations may facilitate vaccine escape.

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ASSOCIATION BETWEEN PNEUMOCOCCAL CARRIAGE AND ANTIMICROBIAL ACTIVITY IN URINE OF MALAWIAN CHILDREN HOSPITALIZED WITH ACUTE RESPIRATORY INFECTION (ID 445)

Session Name
Clinical Sciences - Treatment of Pneumococcal Disease in Infants, Children/Youth, and Adults

Abstract

Background

Following the 2011 introduction of PCV13 in Malawi, 77% of healthy children carry pneumococci in the nasopharynx, while 41% of children hospitalized for acute respiratory infection (ARI) are colonized. We assessed if there is an association between pneumococcal carriage and pre-hospital antibiotic exposure.

Methods

Participants included 69 children aged 1-4 years admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi 2016-2019 due to ARI. Information on pre-hospital antibiotics was collected from parents and/or the child´s health passport. Antimicrobial activity was detected by a urine bioassay. Pneumococci were isolated from a nasopharyngeal sample and tested for antibiotic susceptibility.

Results

Among the 40/69 (58%) samples showing antibiotic activity, 6 (8.7%) were from children with no report of pre-hospital antibiotics. Pneumococci was isolated from 55% of children with urine antimicrobial activity, while carriage was 74% in children with no activity. No difference in pneumococcal penicillin susceptibility was found between children with or without urine antimicrobial activity.

Conclusions

The urine bioassay is a useful tool for assessment of antibiotic exposure in resource limited settings, since patient´s reported history may not be reliable. Pre-hospital antibiotics may explain lower pneumococcal carriage prevalence among those hospitalized compared to healthy. However, pre-hospital antibiotics have not selected for penicillin resistance.

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THE EMERGENCE OF A STREPTOCOCCUS PNEUMONIAE SEROTYPE 3 VARIANT CARRIAGE IN THE 8 YEARS FOLLOWING POST-PCV13 INTRODUCTION IN BLANTYRE, MALAWI. (ID 606)

Abstract

Background

Several studies have demonstrated limited PCV13 efficacy against carriage of serotype 3 Streptococcus pneumoniae. In Blantyre, no direct vaccine effect was identified on serotype 3 carriage 8 years after PCV13 introduction, and population-based serology showed limited induction of serotype 3-specific antibodies by vaccine or natural exposure. We hypothesised that sequence variability of the CPS locus could at least partly explain these observations.

Methods

CPS loci of 540 serotype 3 isolates (from Africa, Asia, Europe and America) were analysed. ML-phylogeny, antimicrobial resistance (tetM, mefA, ermB, cat gene presence and pbpX allelic profiles) and MLST were calculated. Colony morphology was assessed in microaerophilic and anaerobic conditions.

Results

We identified a serotype 3 CPS locus variant in 82% of Blantyre isolates (2015-2019), characterized by an 8-gene cluster deletion but unchanged colony morphology. This variant appeared independently in at least 3 distinct phylogenetic clusters, including ST700 and ST3214. These strains are characterised by the presence of AMR genes and higher MIC to penicillin. The missing CPS genes have hypothetical protein annotation.

Conclusions

This CPS variant segregated with an AMR genotype, which may have contributed to its emergence. Whether this CPS variation will influence immunogenicity remains to be determined.

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RAPID WANING OF VACCINE-INDUCED IMMUNITY AMONG PCV13-VACCINATED CHILDREN UNDER 5 YEARS OLD IN MALAWI WITH SUBSEQUENT ACQUISITION OF NATURAL ANTIBODY THROUGH NATURAL EXPOSURE (ID 267)

PNEUMOCOCCAL SEROTYPES IN INFANTS LESS THAN 90 DAYS OLD BEFORE AND AFTER INTRODUCTION OF PNEUMOCOCCAL CONJUGATE VACCINE (PCV) IN BLANTYRE, MALAWI (ID 1071)

Abstract

Background

Malawi introduced PCV13 into its Expanded Program on Immunization in November 2011. Our aim was to describe the change in serotype distribution causing invasive pneumococcal disease (IPD) in neonates and young infants in Blantyre, Malawi.

Methods

We conducted a retrospective study of IPD in infants aged <90 days admitted to Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi between 2005 and 2018. IPD was defined as culture-confirmed Streptococcus pneumoniae from blood or cerebrospinal fluid, collected when clinically indicated. Serotype was determined by Latex agglutination.

Results

We identified and serotyped samples of 130 cases of IPD. Results show that overall, serotypes 5 (19%), 1 (11%), 7F (5%), 6A/B (3%), and 23F (3%) were most common in this population over the time period studied. Non-vaccine serotype (NVT) accounted for 19% of cases and 40 samples were not typeable. Serotypes 5 and 1 were the predominant cause of IPD before as well as after PCV13 introduction.

Conclusions

Overall IPD cases have been on the decline in this population. Vaccine-type serotypes were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. Vaccine strategies should be considered to optimise the potential for reducing VT-IPD in this setting among this vulnerable population.

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