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Background. We investigated the impact of infant pneumococcal conjugate vaccine (PCV) immunization on pneumococcal colonization among human immunodeficiency virus (HIV)-infected and HIV-uninfected motherchild pairs. Methods. Pneumococcal colonization was assessed in May 2010-February 2011 (period 1; 7-valent PCV era) and May 2012-April 2013 (period 2; 13-valent PCV era). Standard microbiological methods were used for pneumococcus isolation and serotyping. Results. In children 0-12 years, PCV13-serotype colonization decreased from period 1 to period 2 among HIVuninfected (adjusted odds ratio [OR], 0.32; 95% confidence interval [CI], .25-.40) and HIV-infected children (adjusted OR, 0.37; 95% CI, .28-.49), while there was an increase in nonvaccine serotype colonization. Decreases in PCV13-serotype colonization were observed in HIV-uninfected women (adjusted OR, 0.44; 95% CI, .23-.81), with a similar trend in HIV-infected women. HIV-infected compared to -uninfected women had higher prevalence of overall (20.5% vs 9.7% in period 1; 13.8% vs 9.7% in period 2) and PCV 13-serotype colonization (8.7% vs 5.4% in period 1; 4.8% vs 2.0% in period 2), P<.04 for all observations. Conclusions. Targeted PCV vaccination of African infants in a setting with high HIV prevalence was associated with PCV 13-serotype colonization reduction, including among unvaccinated HIV-infected women.

To assess the impact of immunization with pneumococcal conjugate vaccines on all-cause pneumonia hospitalizations among children in Soweto, South Africa. We used data collected at the Chris Hani Baragwanath Hospital in Soweto between 2006 and 2014 - i.e. before and after April 2009, when a pneumococcal conjugate vaccine was first included in South Africa's routine immunization programme. Using a Bayesian generalized seasonal autoregressive moving-average model and the data collected in 2006-2008, we estimated the numbers of children that would have been hospitalized for pneumonia between 2010 and 2014 if no pneumococcal conjugate vaccines had been used. These estimates were then compared with the corresponding numbers of hospitalizations observed. Between 2006 and 2014, 26 778 children younger than five years - including 3388 known to be infected with human immunodeficiency virus (HIV) - were admitted to the study hospital for pneumonia. We estimated that, for the children known to be infected with HIV and for the other children, pneumococcal conjugate vaccines reduced the numbers of hospitalizations for pneumonia in 2014 by 33% (50% credible interval, CrI: 6 to 52) and 39% (50% CrI: 24 to 50), respectively. In the study hospital in 2012-2014, as a result of immunizations with these vaccines, there were an estimated 3100 fewer pneumonia hospitalizations of children younger than five years. In our study hospital, following the introduction of pneumococcal conjugate vaccines into the national immunization programme, there were significant reductions in pneumonia hospitalizations among children.

Objective To assess the impact of immunization with pneumococcal conjugate vaccines on all-cause pneumonia hospitalizations among children in Soweto, South Africa. Methods We used data collected at the Chris Hani Baragwanath Hospital in Soweto between 2006 and 2014-i.e. before and after April 2009, when a pneumococcal conjugate vaccine was first included in South Africa's routine immunization programme. Using a Bayesian generalized seasonal autoregressive moving-average model and the data collected in 2006-2008, we estimated the numbers of children that would have been hospitalized for pneumonia between 2010 and 2014 if no pneumococcal conjugate vaccines had been used. These estimates were then compared with the corresponding numbers of hospitalizations observed. Findings Between 2006 and 2014, 26778 children younger than five years--including 3388 known to be infected with human immunodeficiency virus (HIV)--were admitted to the study hospital for pneumonia. We estimated that, for the children known to be infected with HIV and for the other children, pneumococcal conjugate vaccines reduced the numbers of hospitalizations for pneumonia in 2014 by 33% (50% credible interval, Crl: 6 to 52) and 39% (50% Crl: 24 to 50), respectively. In the study hospital in 2012-2014, as a result of immunizations with these vaccines, there were an estimated 3100 fewer pneumonia hospitalizations of children younger than five years. Conclusion In our study hospital, following the introduction of pneumococcal conjugate vaccines into the national immunization programme, there were significant reductions in pneumonia hospitalizations among children. Objectif Evaluer l'impact de ('immunisation a l'aide de vaccins antipneumococciques conjugues sur les hospitalisationsd'enfants atteints de pneumonie, toutes causes confondues, a Soweto, en Afrique du Sud. Methodes Nous avons utilise des donnees recueillies aupres de i'hopital Chris Hani Baragwanath a Soweto entre 2006 et 2014, c'est-a-dire avant et apres avril 2009, date a laquelle un vaccin antipneumococcique conjugue a ete inclus pour Ia premiere fois dans le programme de vaccination systematique en l'Afrique du Sud. A l'aide d'un modele bayesien generalise salsonnier a moyenne mobile autoregressive et des donnees recueillies entre 2006 et 2008, nous avons estime le nombre d'enfants qui auraient ete hospitalises pour une pneumonie entre 2010 et 2014 si aucun vaccin antipneumococcique conjugue n'avait ete utilise. Ces estimations ont ensuite ete comparees au nombre d'hospitalisations observees correspondant. Resultats Entre 2006 et 2014, 26 778 enfants ages de moins de cinq ans--parmi lesquels 3388 dont la seropositivite au virus de Hmmunodeficience humaine (VIH) etait connue--ont ete admis au sein de l'hopital d'etude pour une pneumonie. Nous avons estime qu'en 2014, les vaccins antipneumococciques conjugues avaient permis de reduire le nombre d'hospitalisations pour une pneumonie de 33% (intervalle de credibilite, ICr, a 50%: 6-52) dans le cas des enfants dont la seropositivite au VIH etait connue, et de 39% (ICr a 50%: 24-50) dans le cas des autres enfants. D'apres nos estimations, le nombre d'hospitalisations pour une pneumonie d'enfants ages de moins de cinq ans a diminue de 3100 dans l'hopital detude entre 2012 et 2014 grace a ees vaccins. Conclusion Suite a l'indusion des vaccins antipneumococciques conjugues dans le programme de vaccination national, nous avons constate une forte diminution du nombre denfants hospitalises pour une pneumonie dans l'hopital d'etude. Objetivo Evaluar el impacto de la inmunizacion con vacunas antineumococicas conjugadas en todos los casos de hospitalizacion por neumonia entre ninos en Soweto, Sudafrica. Metodos Se utilizaron datos recopilados en el Chris Hani Baragwanath Hospital en Soweto entre 2006 y 2014, es decir, antes y despues de abril de 2009, cuando la vacuna antineumococica conjugada se incluyo por primera vez en el programa de inmunizacion rutinaria de Sudafrica. A traves de un modelo bayesiano de promedio movil, generalizado, temporal y autoagreslvo y los datos recopilados entre 2006 y 2008, se estimo el numero de ninos que habrian sido hospitalizados por neumonia entre 2010 y 2014 si no se hubiera utilizado la vacuna antineumococica conjugada. Estas estimaciones se compararon con los numeros correspondientes a las hospitalizaciones observadas. Resultados Entre 2006 y 2014, 26 778 ninos menores de 5 anos ingresaron por neumonia en el hospital del estudio, incluyendo 3 388 infectados por el virus de la inmunodeficiencia humana (VIH). Se estimo que, tanto para los ninos infectados por el VIH como para el resto, las vacunas antineumococias conjugadas redujeron el numero de hospitalizaciones por neumonia en 2014 en un 33% (intervalo creible, ICr, del 50%: de 6 a 52) y en un 39% (ICr del 50%: de 24 a 50), respectivamente. En el hospital del estudio entre 2012 y 2014, como resultado de las inmunizaciones con estas vacunas, hubo una reduccion de cerca de 3 100 hospitalizaciones por neumonia de ninos menores de 5 anos. Conclusion En nuestro hospital del estudio, despues de la introduccion de las vacunas antineumococicas conjugadas en el programa nacional de inmunizacion, hubo reducciones significativas en las hospitalizaciones por neumonia entre los ninos.

Invasive pneumococcal disease remains an important health priority owing to increasing disease incidence caused by pneumococci expressing non-vaccine serotypes. We previously defined 621 Global Pneumococcal Sequence Clusters (GPSCs) by analysing 20 027 pneumococcal isolates collected worldwide and from previously published genomic data. In this study, we aimed to investigate the pneumococcal lineages behind the predominant serotypes, the mechanism of serotype replacement in disease, as well as the major pneumococcal lineages contributing to invasive pneumococcal disease in the post-vaccine era and their antibiotic resistant traits. We whole-genome sequenced 3233 invasive pneumococcal disease isolates from laboratory-based surveillance programmes in Hong Kong (n=78), Israel (n=701), Malawi (n=226), South Africa (n=1351), The Gambia (n=203), and the USA (n=674). The genomes represented pneumococci from before and after pneumococcal conjugate vaccine (PCV) introductions and were from children younger than 3 years. We identified predominant serotypes by prevalence and their major contributing lineages in each country, and assessed any serotype replacement by comparing the incidence rate between the pre-PCV and PCV periods for Israel, South Africa, and the USA. We defined the status of a lineage as vaccine-type GPSC (≥50% 13-valent PCV [PCV13] serotypes) or non-vaccine-type GPSC (>50% non-PCV13 serotypes) on the basis of its initial serotype composition detected in the earliest vaccine period to measure their individual contribution toward serotype replacement in each country. Major pneumococcal lineages in the PCV period were identified by pooled incidence rate using a random effects model. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. The five most prevalent serotypes in the PCV13 period varied between countries, with only serotypes 5, 12F, 15B/C, 19A, 33F, and 35B/D common to two or more countries. These serotypes were associated with more than one lineage, except for serotype 5 (GPSC8). Serotype replacement was mainly mediated by expansion of non-vaccine serotypes within vaccine-type GPSCs and, to a lesser extent, by increases in non-vaccine-type GPSCs. A globally spreading lineage, GPSC3, expressing invasive serotypes 8 in South Africa and 33F in the USA and Israel, was the most common lineage causing non-vaccine serotype invasive pneumococcal disease in the PCV13 period. We observed that same prevalent non-vaccine serotypes could be associated with distinctive lineages in different countries, which exhibited dissimilar antibiotic resistance profiles. In non-vaccine serotype isolates, we detected significant increases in the prevalence of resistance to penicillin (52 [21%] of 249 vs 169 [29%] of 575, p=0·0016) and erythromycin (three [1%] of 249 vs 65 [11%] of 575, p=0·0031) in the PCV13 period compared with the pre-PCV period. Globally spreading lineages expressing invasive serotypes have an important role in serotype replacement, and emerging non-vaccine serotypes associated with different pneumococcal lineages in different countries might be explained by local antibiotic-selective pressures. Continued genomic surveillance of the dynamics of the pneumococcal population with increased geographical representation in the post-vaccine period will generate further knowledge for optimising future vaccine design. Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control.

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn 916 -type and Tn 1207.1 -type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly sampled Tn 1207.1 -type insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence, selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.

Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0–2 SNPs) with the common ancestor dated around 2017. The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination.

is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location. The extent and mechanisms of spread, and vaccine-driven changes in fitness and antimicrobial resistance (AMR), remain largely unquantified. Using geolocated genome sequences from South Africa (N=6910, 2000-2014) we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately we estimated the population level changes in fitness of strains that are (vaccine type, VT) and are not (non-vaccine type, NVT) included in the vaccine, first implemented in 2009, as well as differences in strain fitness between those that are and are not resistant to penicillin. We estimated that pneumococci only become homogenously mixed across South Africa after about 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Further, in the years following vaccine implementation the relative fitness of NVT compared to VT strains increased (RR: 1.29 [95% CI 1.20-1.37]) - with an increasing proportion of these NVT strains becoming penicillin resistant. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in AMR may be transient.

We reported a novel tetracycline-resistant gene in Streptococcus pneumoniae and investigated its temporal spread in relation to nationwide clinical interventions. We whole genome sequenced 12,254 pneumococcal isolates from twenty-nine countries on an Illumina HiSeq Sequencer. Serotypes, sequence types and antibiotic resistance were inferred from genomes. Phylogeny was built based on single-nucleotide variants. Temporal changes of spread were reconstructed using a birth-death model. We identified tet(S/M) in 131 pneumococcal isolates, 97 (74%) caused invasive pneumococcal diseases among young children (59% HIV-positive, where HIV status was available) in South Africa. A majority of tet(S/M)-positive isolates (129/131) belong to clonal complex (CC)230. A global phylogeny of CC230 (n=389) revealed that tet(S/M)-positive isolates formed a sub-lineage that exhibited multidrug-resistance. Using the genomic data and a birth-death model, we detected an unrecognised outbreak of this sub-lineage in South Africa between 2000 and 2004 with an expected secondary infections (R) of ~2.5. R declined to ~1.0 in 2005 and <1.0 in 2012. The declining epidemic coincided and could be related to the nationwide implementation of anti-retroviral treatment (ART) for HIV-infected individuals in 2004 and PCVs in late 2000s. Capsular switching from vaccine serotype 14 to non-vaccine serotype 23A was observed within the sub-lineage. The prevalence of tet(S/M) in pneumococci was low and its dissemination was due to an unrecognised outbreak of CC230 in South Africa prior to ART and PCVs. However, capsular switching in this multidrug-resistant sub-lineage highlighted its potential to continue to cause disease in the post-PCV13 era.

We reviewed Corynebacterium spp. infection cases reported in South Africa during 2015-2023. We analyzed 84 isolates from 83 patients with C. diphtheriae, as well as 1 C. belfantii and 3 C. ulcerans isolates. Among C. diphtheriae cases, we observed respiratory diphtheria (26/83 patients [31%]), endocarditis (14/83 [17%]), cutaneous diphtheria (22/83 [27%]), nonspecific respiratory illnesses (5/83 [6%]), and asymptomatic carriage (16/83 [19%]). The median patient age was 19 (range 0-88) years. Diphtheria-tetanus-pertussis vaccination was incomplete for 26% (5/19) or unknown for 68% (13/19) of children 0-9 years of age. C. diphtheriae was intermediately resistant to penicillin (82/84 [98%] isolates; MIC 0.5 μg/mL) but susceptible to erythromycin (83/84 [99%] isolates; MIC 0.25 μg/mL). Eighteen unique sequence types were identified, corroborating C. diphtheriae heterogeneity. Toxin-producing strains were detected among cutaneous and respiratory diphtheria cases, indicating all forms of disease require monitoring and prompt public health action to curb transmission.

Background. The public health impact of rotavirus vaccination in African settings with a high human immunodeficiency virus (HIV) infection prevalence is yet to be established. We evaluated trends in all-cause diarrheal hospitalizations in Soweto, Johannesburg, before and after the introduction of rotavirus vaccine into South Africa's national immunization program in August 2009. Methods. Hospitalizations in children <5 years of age with a diagnosis of diarrhea, defined by International Classification of Diseases, Tenth Revision codes A00–A05, A06.0–A06.3, A06.9, A07.0–A07.2, A07.9, and A08–A09, were identified at the Chris Hani Baragwanath Academic Hospital from 1 January 2006 to 31 December 2014. The median annual prevaccine (2006–2008) hospitalization incidence was compared to that of the vaccine era (2010–2014), and stratified by age group and HIV infection status. Results. Incidence reductions (per 1000 population) were greatest in children aged <12 months: 54.4 in the prevaccine era vs 30.0, 23.6, 20.0, 18.8, and 18.9 in the postvaccine years 2010–2014, respectively (a 44.9%–65.4% reduction). Lower incidence reductions (39.8%–49.4%) were observed among children aged 12–24 months from the second year post–vaccine introduction onward. Reductions were observed in both HIV-infected and HIV-uninfected children. There was a change in the seasonal pattern of diarrheal hospitalizations post–vaccine introduction, with flattening of the autumn–winter peaks seen in the prevaccine years. Conclusions. An accelerated and sustained decline in all-cause diarrheal hospitalizations, temporally associated with rotavirus vaccine introduction, was observed in children <2 years of age. However, the impact of other interventions such as improved sanitation and changes in HIV management cannot be discounted.