Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
1.
J Infect Dis ; 230(1): e189-e198, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-39052729

ABSTRACT

BACKGROUND: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage. METHODS: The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015-2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children. RESULTS: Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing. CONCLUSIONS: A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.


Subject(s)
Bacterial Capsules , Phylogeny , Pneumococcal Infections , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Humans , Pneumococcal Vaccines/immunology , Pneumococcal Vaccines/administration & dosage , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/immunology , Streptococcus pneumoniae/classification , Pneumococcal Infections/prevention & control , Pneumococcal Infections/microbiology , Pneumococcal Infections/immunology , Bacterial Capsules/immunology , Bacterial Capsules/genetics , Malawi , Adult , Whole Genome Sequencing , Child, Preschool , Child , Vaccines, Conjugate/immunology , Male , Genome, Bacterial , Female , Young Adult , Infant , Genotype , Carrier State/microbiology
2.
J Clin Microbiol ; 61(1): e0080222, 2023 01 26.
Article in English | MEDLINE | ID: mdl-36515506

ABSTRACT

Streptococcus mitis is a common oral commensal and an opportunistic pathogen that causes bacteremia and infective endocarditis; however, the species has received little attention compared to other pathogenic streptococcal species. Effective and easy-to-use molecular typing tools are essential for understanding bacterial population diversity and biology, but schemes specific for S. mitis are not currently available. We therefore developed a multilocus sequence typing (MLST) scheme and defined sequence clusters or lineages of S. mitis using a comprehensive global data set of 322 genomes (148 publicly available and 174 newly sequenced). We used internal 450-bp sequence fragments of seven housekeeping genes (accA, gki, hom, oppC, patB, rlmN, and tsf) to define the MLST scheme and derived the global S. mitis sequence clusters using the PopPUNK clustering algorithm. We identified an initial set of 259 sequence types (STs) and 258 global sequence clusters. The schemes showed high concordance (100%), capturing extensive S. mitis diversity with strains assigned to multiple unique STs and global sequence clusters. The tools also identified extensive within- and between-host S. mitis genetic diversity among isolates sampled from a cohort of healthy individuals, together with potential transmission events, supported by both phylogeny and pairwise single nucleotide polymorphism (SNP) distances. Our novel molecular typing and strain clustering schemes for S. mitis allow for the integration of new strain data, are electronically portable at the PubMLST database (https://pubmlst.org/smitis), and offer a standardized approach to understanding the population structure of S. mitis. These robust tools will enable new insights into the epidemiology of S. mitis colonization, disease and transmission.


Subject(s)
Streptococcus mitis , Streptococcus , Humans , Multilocus Sequence Typing , Streptococcus mitis/genetics , Streptococcus/genetics , Cluster Analysis , Phylogeny
3.
Clin Infect Dis ; 71(9): e478-e486, 2020 12 03.
Article in English | MEDLINE | ID: mdl-32060523

ABSTRACT

BACKGROUND: Third-generation cephalosporins (3GC) remain the first-choice empiric antibiotic for severe infection in many sub-Saharan African hospitals. In Malawi, the limited availability of alternatives means that strategies to prevent the spread of 3GC resistance are imperative; however, suitable approaches to antimicrobial stewardship (AMS) in low-income settings are not well studied. METHODS: We introduced an AMS intervention to Queen Elizabeth Central Hospital in Blantyre. The intervention consisted of a prescribing application for smartphones and regular point-prevalence surveys with prescriber feedback. We evaluate the effects of the intervention on 3GC usage and on the cost of providing antibiotics. Using a thematic analysis of semi-structured interviews and participant observations, we additionally evaluate the acceptability of the stewardship program. RESULTS: The proportion of antibiotic prescriptions for a 3GC reduced from 193/241 (80.1%) to 177/330 (53.6%; percentage decrease, 26.5%; 95% confidence interval, 18.7-34.1) with no change in the case-fatality rate. The cost analysis estimated an annual savings of US$15 000. Qualitative research revealed trust in the guideline and found that its accessibility through smartphones helpful to guide clinical decisions. Operational health-system barriers and hierarchal clinical relationships lead to continued reliance on 3GC. CONCLUSIONS: We report the successful introduction of an antimicrobial stewardship approach in Malawi. By focusing on pragmatic interventions and simple aims, we demonstrate the feasibility, acceptability, and cost savings of a stewardship program where resources are limited. In doing so, we provide a suitable starting point for expansions of AMS interventions in this and other low-income settings.


Subject(s)
Antimicrobial Stewardship , Adult , Anti-Bacterial Agents/therapeutic use , Cephalosporins/therapeutic use , Hospitals, Urban , Humans , Inpatients , Malawi
4.
Microb Genom ; 10(6)2024 Jun.
Article in English | MEDLINE | ID: mdl-38896467

ABSTRACT

Since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Malawi in 2011, there has been persistent carriage of vaccine serotype (VT) Streptococcus pneumoniae, despite high vaccine coverage. To determine if there has been a genetic change within the VT capsule polysaccharide (cps) loci since the vaccine's introduction, we compared 1022 whole-genome-sequenced VT isolates from 1998 to 2019. We identified the clonal expansion of a multidrug-resistant, penicillin non-susceptible serotype 23F GPSC14-ST2059 lineage, a serotype 14 GPSC9-ST782 lineage and a novel serotype 14 sequence type GPSC9-ST18728 lineage. Serotype 23F GPSC14-ST2059 had an I253T mutation within the capsule oligosaccharide repeat unit polymerase Wzy protein, which is predicted in silico to alter the protein pocket cavity. Moreover, serotype 23F GPSC14-ST2059 had SNPs in the DNA binding sites for the cps transcriptional repressors CspR and SpxR. Serotype 14 GPSC9-ST782 harbours a non-truncated version of the large repetitive protein (Lrp), containing a Cna protein B-type domain which is also present in proteins associated with infection and colonisation. These emergent lineages also harboured genes associated with antibiotic resistance, and the promotion of colonisation and infection which were absent in other lineages of the same serotype. Together these data suggest that in addition to serotype replacement, modifications of the capsule locus associated with changes in virulence factor expression and antibiotic resistance may promote vaccine escape. In summary, the study highlights that the persistence of vaccine serotype carriage despite high vaccine coverage in Malawi may be partly caused by expansion of VT lineages post-PCV13 rollout.


Subject(s)
Bacterial Capsules , Pneumococcal Infections , Pneumococcal Vaccines , Serogroup , Streptococcus pneumoniae , Streptococcus pneumoniae/genetics , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/pathogenicity , Pneumococcal Vaccines/immunology , Humans , Malawi , Bacterial Capsules/genetics , Pneumococcal Infections/microbiology , Pneumococcal Infections/prevention & control , Vaccines, Conjugate , Polysaccharides, Bacterial/genetics , Polysaccharides, Bacterial/immunology , Virulence/genetics , Genotype , Whole Genome Sequencing , Bacterial Proteins/genetics , Virulence Factors/genetics , Child, Preschool , Polymorphism, Single Nucleotide , Infant , Male
5.
Nat Commun ; 15(1): 7812, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39242612

ABSTRACT

Streptococcus mitis is a leading cause of infective endocarditis (IE). However, our understanding of the genomic epidemiology and pathogenicity of IE-associated S. mitis is hampered by low IE incidence. Here we use whole genome sequencing of 129 S. mitis bloodstream infection (BSI) isolates collected between 2001-2016 from clinically diagnosed IE cases in the UK to investigate genetic diversity, antimicrobial resistance, and pathogenicity. We show high genetic diversity of IE-associated S. mitis with virtually all isolates belonging to distinct lineages indicating no predominance of specific lineages. Additionally, we find a highly variable distribution of known pneumococcal virulence genes among the isolates, some of which are overrepresented in disease when compared to carriage strains. Our findings suggest that S. mitis in patients with clinically diagnosed IE is not primarily caused by specific hypervirulent or antimicrobial resistant lineages, highlighting the accidental pathogenic nature of S. mitis in patients with clinically diagnosed IE.


Subject(s)
Bacteremia , Streptococcal Infections , Streptococcus mitis , Humans , Streptococcus mitis/genetics , Streptococcus mitis/isolation & purification , United Kingdom/epidemiology , Streptococcal Infections/microbiology , Streptococcal Infections/epidemiology , Ireland/epidemiology , Bacteremia/microbiology , Bacteremia/epidemiology , Endocarditis/microbiology , Endocarditis/epidemiology , Genome, Bacterial/genetics , Whole Genome Sequencing , Male , Female , Genetic Variation , Genomics , Aged , Phylogeny , Middle Aged , Drug Resistance, Bacterial/genetics , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/epidemiology , Adult , Virulence Factors/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Virulence/genetics
6.
Nat Commun ; 15(1): 6291, 2024 Jul 26.
Article in English | MEDLINE | ID: mdl-39060226

ABSTRACT

Malawi experienced its deadliest Vibrio cholerae (Vc) outbreak following devastating cyclones, with >58,000 cases and >1700 deaths reported between March 2022 and May 2023. Here, we use population genomics to investigate the attributes and origin of the Malawi 2022-2023 Vc outbreak isolates. Our results demonstrate the predominance of ST69 clone, also known as the seventh cholera pandemic El Tor (7PET) lineage, expressing O1 Ogawa (~ 80%) serotype followed by Inaba (~ 16%) and sporadic non-O1/non-7PET serogroups (~ 4%). Phylogenetic reconstruction revealed that the Malawi outbreak strains correspond to a recent importation from Asia into Africa (sublineage AFR15). These isolates harboured known antimicrobial resistance and virulence elements, notably the ICEGEN/ICEVchHai1/ICEVchind5 SXT/R391-like integrative conjugative elements and a CTXφ prophage with the ctxB7 genotype compared to historical Malawian Vc isolates. These data suggest that the devastating cyclones coupled with the recent importation of 7PET serogroup O1 strains, may explain the magnitude of the 2022-2023 cholera outbreak in Malawi.


Subject(s)
Cholera , Disease Outbreaks , Phylogeny , Vibrio cholerae , Malawi/epidemiology , Cholera/epidemiology , Cholera/microbiology , Humans , Vibrio cholerae/genetics , Vibrio cholerae/classification , Genomics , Genome, Bacterial/genetics , Prophages/genetics , Genotype , Serogroup
7.
bioRxiv ; 2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37693504

ABSTRACT

Introduction: Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). Aim: To characterise lineages and antimicrobial resistance in 16F isolates obtained from South Africa and placed the local findings in a global context. Methodology: We analysed 10923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and Global Pneumococcal Sequence Clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19,607, collected from 49 countries across five continents, years covered (1995 - 2018), accessed on 17 th March 2022). Results: Nine percent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2% (419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26% (346/1353) and 53% (716/1353), respectively. Serotype 16F isolates were identified globally, however, most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95% CI) 0.24 (0.09 - 0.66); p=0.003], while GPSC46 was associated with disease [OR (95% CI) 19.9 (2.56 - 906.50); p=0.0004]. 10% (37/346) and 15% (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18% (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters which may suggest emerging resistant lineages. Discussion: Serotype 16F lineages are common in Southern Africa. Some of these lineages are associated with disease, and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine long term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. DATA SUMMARY: The sequencing reads for the genomes analysed have been deposited in the European Nucleotide Archive and the accession numbers for each isolate are listed in Supplementary Table1 . Phylogenetic tree of serotype 16F pneumococcal genomes and associated metadata are available for download and visualisation on the Microreact website: Phylogenies of seotype 16F, GPSC33 and GPSC46 are available on the Microreact serotype-16F , GPSC33 and GPSC46 , respectively. IMPACT STATEMENT: This study shows that serotype 16F lineages are predominant in Southern Africa and are associated with disease and antimicrobial resistance. Although serotype 16F has been included in the newer formulation of the upcoming vaccine formulations of PCV21 and IVT-25, continuous surveillance to determine long term impact of serotype 16F lineages on vaccines and antimicrobial therapy remains essential.

8.
Microb Genom ; 9(11)2023 Nov.
Article in English | MEDLINE | ID: mdl-37917136

ABSTRACT

Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). To characterize lineages and antimicrobial resistance in 16F isolates obtained from South Africa and place the local findings in a global context, we analysed 10 923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and global pneumococcal sequence clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19 607, collected from 49 countries across 5 continents, 1995-2018, accessed 17 March 2022). Nine per cent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2 %(419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26 % (346/1353) and 53 % (716/1353), respectively. Serotype 16F isolates were identified globally, but most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95 % CI) 0.24 (0.09-0.66); P=0.003], while GPSC46 was associated with disease [OR (95 % CI) 19.9 (2.56-906.50); P=0.0004]. Ten per cent (37/346) and 15 % (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18 % (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters, which may suggest emerging resistant lineages. Serotype 16F lineages were common in southern Africa. Some of these lineages were associated with disease and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine the long-term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. This paper contains data hosted by Microreact.


Subject(s)
Streptococcus pneumoniae , Trimethoprim, Sulfamethoxazole Drug Combination , Infant , Humans , Streptococcus pneumoniae/genetics , Serogroup , Genomics , Anti-Bacterial Agents/pharmacology , South Africa/epidemiology , Penicillins , Pneumococcal Vaccines
9.
Nat Commun ; 14(1): 7477, 2023 11 17.
Article in English | MEDLINE | ID: mdl-37978177

ABSTRACT

Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into "Metabolic genotypes" (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.


Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Child , Humans , Animals , Mice , Infant , Child, Preschool , Streptococcus pneumoniae/genetics , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Malawi/epidemiology , Virulence/genetics , Drug Resistance, Bacterial/genetics , Pneumococcal Vaccines , Serogroup , Nasopharynx , Carrier State/epidemiology
10.
BMJ Open ; 13(5): e069560, 2023 05 12.
Article in English | MEDLINE | ID: mdl-37173105

ABSTRACT

INTRODUCTION: Vaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study will evaluate the impact of vaccination on reducing carriage prevalence of resistant Streptococcus pneumoniae and extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella species. We will leverage two large ongoing cluster-randomised vaccine evaluations in Malawi assessing; first, adding a booster dose to the 13-valent pneumococcal conjugate vaccine (PCV13) schedule, and second, introduction of the RTS,S/AS01 malaria vaccine. METHODS AND ANALYSIS: Six cross-sectional surveys will be implemented within primary healthcare centres (n=3000 users of outpatient facilities per survey) and their local communities (n=700 healthy children per survey): three surveys in Blantyre district (PCV13 component) and three surveys in Mangochi district (RTS,S/AS01 component). We will evaluate antibiotic prescription practices and AMR carriage in children ≤3 years. For the PCV13 component, surveys will be conducted 9, 18 and 33 months following a 3+0 to 2+1 schedule change. For the RTS,S/AS01 component, surveys will be conducted 32, 44 and 56 months post-RTS,S/AS01 introduction. Six health centres in each study component will be randomly selected for study inclusion. Between intervention arms, the primary outcome will be the difference in penicillin non-susceptibility prevalence among S. pneumoniae nasopharyngeal carriage isolates in healthy children. The study is powered to detect an absolute change of 13 percentage points (ie, 35% vs 22% penicillin non-susceptibility). ETHICS AND DISSEMINATION: This study has been approved by the Kamuzu University of Health Sciences (Ref: P01-21-3249), University College London (Ref: 18331/002) and University of Liverpool (Ref: 9908) Research Ethics Committees. Parental/caregiver verbal or written informed consent will be obtained prior to inclusion or recruitment in the health centre-based and community-based activities, respectively. Results will be disseminated via the Malawi Ministry of Health, WHO, peer-reviewed publications and conference presentations.


Subject(s)
Malaria Vaccines , Malaria , Pneumococcal Infections , Humans , Child , Infant , Child, Preschool , Streptococcus pneumoniae , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross-Sectional Studies , Malawi/epidemiology , Drug Resistance, Bacterial , Pneumococcal Vaccines , Vaccination , Penicillins , Nasopharynx , Malaria/epidemiology , Malaria/prevention & control , Carrier State/epidemiology
11.
Trends Microbiol ; 30(12): 1135-1145, 2022 12.
Article in English | MEDLINE | ID: mdl-35843855

ABSTRACT

Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and septicaemia worldwide. Pneumococcal antimicrobial resistance (AMR) has been highlighted by the WHO as an important public health concern, with emerging serotypes showing resistance to multiple antibiotics. Indeed, although the introduction of pneumococcal conjugate vaccines (PCVs) has been associated with an overall decline in pneumococcal AMR, there have been increases in prevalence of potentially disease-causing AMR serotypes not targeted by vaccination. Here, we discuss a variety of evolutionary mechanisms at the host, pathogen, and environmental levels that may contribute to changes in the prevalence of pneumococcal AMR in the post-vaccination era. The relative importance of these factors may vary by population, pneumococcal lineage, geography, and time, leading to the complex relationship between vaccination, antibiotic use, and AMR.


Subject(s)
Pneumococcal Infections , Streptococcus pneumoniae , Humans , Infant , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial , Pneumococcal Vaccines , Vaccination
12.
Lancet Infect Dis ; 22(12): 1737-1747, 2022 12.
Article in English | MEDLINE | ID: mdl-36029796

ABSTRACT

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi. METHODS: For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age <3 months to 57-59 months). FINDINGS: We evaluated 638 plasma samples: 556 primary samples and 82 unique secondary samples (each linked to one primary sample). Immunogenicity profiles revealed a consistent pattern among vaccine serotypes except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3, we observed no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination nadir (from 11·2 months [19A] to 27·3 months [7F]). The age at peak IgG titre ranged from 2·69 months (5) to 6·64 months (14). Titres dropped below CoPs against IPD among nine vaccine serotypes (1, 3, 4, 5, 6B, 7F, 9V, 18C, and 23F) and below CoPs against carriage for ten vaccine serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F). Increasing antibody concentrations among older children and seroincident events were consistent with ongoing vaccine-serotype exposure. INTERPRETATION: A 3 + 0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several vaccine serotypes, potentially contributing to persistent vaccine-serotype carriage and residual vaccine-serotype IPD in Malawi and other similar settings. Policy decisions should consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody titres, and thus control. FUNDING: Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research.


Subject(s)
Antibodies, Bacterial , Pneumococcal Infections , Child , Humans , Infant , Adolescent , Child, Preschool , Vaccines, Conjugate , Malawi/epidemiology , Prospective Studies , Pneumococcal Vaccines , Pneumococcal Infections/epidemiology , Pneumococcal Infections/prevention & control , Immunoglobulin G
13.
Microb Genom ; 7(9)2021 09.
Article in English | MEDLINE | ID: mdl-34550067

ABSTRACT

Streptococcus pneumoniae is an important global pathogen that causes bacterial pneumonia, sepsis and meningitis. Beta-lactam antibiotics are the first-line treatment for pneumococcal disease, however, their effectiveness is hampered by beta-lactam resistance facilitated by horizontal genetic transfer (HGT) with closely related species. Although interspecies HGT is known to occur among the species of the genus Streptococcus, the rates and effects of HGT between Streptococcus pneumoniae and its close relatives involving the penicillin binding protein (pbp) genes remain poorly understood. Here we applied the fastGEAR tool to investigate interspecies HGT in pbp genes using a global collection of whole-genome sequences of Streptococcus mitis, Streptococcus oralis and S. pneumoniae. With these data, we established that pneumococcal serotypes 6A, 13, 14, 16F, 19A, 19F, 23F and 35B were the highest-ranking serotypes with acquired pbp fragments. S. mitis was a more frequent pneumococcal donor of pbp fragments and a source of higher pbp nucleotide diversity when compared with S. oralis. Pneumococci that acquired pbp fragments were associated with a higher minimum inhibitory concentration (MIC) for penicillin compared with pneumococci without acquired fragments. Together these data indicate that S. mitis contributes to reduced ß-lactam susceptibility among commonly carried pneumococcal serotypes that are associated with long carriage duration and high recombination frequencies. As pneumococcal vaccine programmes mature, placing increasing pressure on the pneumococcal population structure, it will be important to monitor the influence of antimicrobial resistance HGT from commensal streptococci such as S. mitis.


Subject(s)
Drug Resistance, Bacterial/genetics , Nasopharynx/microbiology , Penicillin-Binding Proteins/genetics , Serogroup , Streptococcus mitis/genetics , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/genetics , Bacterial Proteins/genetics , Gene Transfer, Horizontal , Genes, Bacterial , Humans , Microbial Sensitivity Tests , Penicillins , Phylogeny , Pneumococcal Infections/microbiology , Pneumococcal Vaccines , Streptococcus/classification , Streptococcus/genetics , Streptococcus oralis , Whole Genome Sequencing , beta-Lactam Resistance
SELECTION OF CITATIONS
SEARCH DETAIL