In 2010, a ten-valent pneumococcal conjugate vaccine (PCV10) was introduced in the routine infant national immunization program in Brazil. Invasive pneumococcal disease (IPD) caused by serotype 19A ...(Spn19A) increased after the introduction of PCVs in several countries. We compared the frequency, antimicrobial resistance and molecular patterns of invasive Spn19A strains before and after PCV10 introduction in Brazil using data from the national laboratory-based surveillance.
We analyzed invasive Spn19A strains isolated from 2005-2009 (pre-PCV10 period), 2011-2015 and 2016-2017 (post-PCV10 periods). Antimicrobial susceptibility was performed for all Spn19A strains, and multilocus sequence typing (MLST) was performed for strains isolated in the age groups <5 years and ≥50 years.
Among the study period, a total of 9,852 invasive Spn strains were analyzed, and 673 (6.8%) belonged to serotype 19A. Overall, the proportion of Spn19A among the total number of IPD strains increased from 2.8% in 2005-2009 to 7.0% and 16.4% in 2011-2015 and 2016-2017, respectively. The relative increase in Spn19A was observed especially in children <5 years old (2005-2009: 3.2%; 2011-2015: 15.5%; 2016-2017: 31.2%). The percentage of penicillin resistance (MIC 2.0-4.0 μg/mL), erythromycin resistance and multidrug resistance (MDR) increased after PCV10 introduction due to the expansion of the MDR clonal complex CC320 (2005-2009: 8.6%; 2011-2015: 56.1%; 2016-2017: 66.5%).
We observed an expansion of MDR-CC320 among invasive Spn19A strains after PCV10 introduction in Brazil, probably related to a combination of factors, such as vaccination and antimicrobial pressure. Continued surveillance of Spn19A strains is necessary to monitor the sustainability of this clonal complex in the Brazilian population.
A difteria é doença infecciosa causada pelo bacilo Gram positivo Corynebacterium diphtheriae. Em geral, a infecção se expressa clinicamente pelo acometimento de trato respiratório ou cutâneo, sendo ...rara a infecção de corrente sanguínea. Infecções assintomáticas podem ocorrer e são mais frequentes quando associadas a cepas não toxigênicas. Epidemiologicamente a difteria está controlada em diversas regiões do mundo, incluindo-se o Brasil, como resultado da vacinação de rotina. Ainda que a doença e respectivas manifestações graves tenham apresentado importante redução em incidência com a vacina, a real prevalência de portadores assintomáticos da C. diphtheriae e frequência de infecções atípicas não são bem estabelecidas. P.C.M, feminina, 24 anos, previamente hígida, procurou a emergência em 14/08/21 com adinamia por quatro semanas, em piora progressiva, associada à febre noturna não aferida e calafrios. Relatou também episódio de síncope, após palpitação e vertigem, no dia anterior. Apresentava febre, palidez mucocutânea, anemia normocítica e normocrômica (4,8g/dL/15,7%), neutropenia (11.080 leucócitos/440 neutrófilos) e plaquetopenia (10.000). Internada para investigação diagnóstica pela Hematologia. Após coleta de 4 amostras de hemocultura, iniciado tratamento antimicrobiano para neutropenia febril com cefepima + vancomicina. Hemocultura de 20/08/21 com C. diphtheriae, em uma amostra, identificado pelo Maldi Tof, resultado posteriormente confirmado C. diphtheriae não toxigênica, por PCR, pelo laboratório de referência (Instituto Adolfo Lutz). Não apresentava clínica ou antecedentes epidemiológicos compatíveis com difteria, e possuía histórico vacinal completo. Como complementação diagnóstica, ecocardiograma transtorácico sem evidências de miocardite ou endocardite. Paciente evoluiu afebril e sem complicações, recebendo alta com diagnóstico final de Leucemia linfoide aguda após dez dias de antibioticoterapia e sem ter recebido soro antidiftérico. O presente caso revela que, apesar do controle da difteria com vacinação de rotina, é possível a ocorrência de portadores assintomáticos de C. diphtheriae, bem como possíveis casos de infecção de corrente sanguínea. Nesse contexto, a utilização de métodos mais sensíveis para diagnóstico microbiológico pode vir a contribuir para detecção de casos e melhor compreensão da frequência da infecção invasiva pelo C. diphtheriae.
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.
We aimed to investigate the nasopharyngeal colonization (NPC) by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in the elderly population and to assess the demographic ...factors associated with NPC. This was an observational cohort study in which outpatients aged ≥60 years were enrolled from April to August 2017, with a follow-up visit from September through December 2017. Nasopharyngeal (NP) swabs were collected, bacteria were detected and isolated, and isolates were subjected to phenotypic and molecular characterization using standard microbiological techniques. At enrolment, the rates of S. aureus, methicillin-resistant S. aureus (MRSA), H. influenzae, and S. pneumoniae among 776 elderly outpatients were 15.9%, 2.3%, 2.5%, and 2.2%, respectively. Toxin production was detected in 21.1% of methicillin-susceptible S. aureus, and three SCCmec types were identified: II/IIb, IVa, and VI. At the follow-up visit, all carriage rates were similar (p > 0.05) to the rates at enrolment. Most of S. pneumoniae serotypes were not included in pneumococcal conjugate vaccines (PCVs), except for 7F, 3, and 19A. All strains of H. influenzae were non-typeable. Previous use of antibiotics and 23-valent pneumococcal polysaccharide vaccination (p < 0.05) were risk factors for S. aureus and MRSA carriage; S. aureus colonization was also associated with chronic kidney disease (p = 0.021). S. pneumoniae carriage was associated with male gender (p = 0.032) and an absence of diabetes (p = 0.034), while not receiving an influenza vaccine (p = 0.049) and chronic obstructive pulmonary disease (p = 0.031) were risk factors for H. influenzae colonization. The frailty of study participants was not associated with colonization status. We found a higher S. aureus carriage rate compared with the S. pneumoniae- and H. influenzae-carriage rates in a well-attended population in a geriatric outpatient clinic. This is one of the few studies conducted in Brazil that can support future colonization studies among elderly individuals.
Regarding the use of different sources of data, Andrade and colleagues did a record linkage of Brazil's Information System for Notifiable Diseases (SINAN) and SIREVA to enhance case ascertainment of ...invasive pneumococcal disease in children younger than 5 years.2 Although 4314 cases from SINAN had not been notified to SIREVA, 3308 cases from SIREVA (isolates from cerebrospinal fluid, 671 20·3%; isolates from blood, 2190 66·2%; isolates from other sterile fluids, 447 13·5%) were not found in SINAN. ...use of SINAN data as a proxy for invasive pneumococcal disease might be limited by underestimations of cases. SINAN was upgraded on its operational system in 2007, which could have interfered with the surveillance practice.3 Azevedo and colleagues used SINAN to evaluate trends in bacterial meningitis during 2000–11, and observed a significant decrease in pneumococcal meningitis cases in children aged 0–23 months in 2009–10, although with substantial data missing on aetiological information.3 Thus, in accordance with Camargo and colleagues, factors other than PCV10 can lead to a potential bias when evaluating the effect of PCV10. The trend analysis based on population rates presented by Camargos and colleagues was considered in our Article (appendix of our Article, pp 50–55).1 We also did a joinpoint regression, estimated as annual reported rates per 100 000 children younger than 5 years, with the caveat that laboratory-surveillance data are not incidence data.
In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the ...seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children.
Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype).
In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules.
In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes.
Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.
Highlights • Four years of MCC vaccination in infants reduced significantly MenC in children <5 y. • Children <12 m presented highest MenC rates; no second peak observed for adolescents. • An ...indirect protection was observed where mass vaccination targeted individuals ≤24 y. • Almost 1000 MenC cases were averted in Brazil in individuals aged <40 y after 4 years.
Invasive pneumococcal disease (IPD) risk increases with age for older adults whereas the population size benefiting from pneumococcal vaccines and robustness of immunogenic response to vaccination ...decline. We estimate how demographics, vaccine efficacy/effectiveness (VE), and waning VE impact on optimal age for a single-dose pneumococcal vaccination. Age- and vaccine-serotype-specific IPD cases from routine surveillance of adults ≥ 55 years old (y), ≥ 4-years after infant-pneumococcal vaccine introduction and before 2020, and VE data from prior studies were used to estimate IPD incidence and waning VE which were then combined in a cohort model of vaccine impact. In Brazil, Malawi, South Africa and England 51, 51, 54 and 39% of adults older than 55 y were younger than 65 years old, with a smaller share of annual IPD cases reported among < 65 years old in England (4,657; 20%) than Brazil (186; 45%), Malawi (4; 63%), or South Africa (134, 48%). Vaccination at 55 years in Brazil, Malawi, and South Africa, and at 70 years in England had the greatest potential for IPD prevention. Here, we show that in low/middle-income countries, pneumococcal vaccines may prevent a substantial proportion of residual IPD burden if administered earlier in adulthood than is typical in high-income countries.
Multidrug-resistant
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
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
-type and Tn
-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
-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.
OBJETIVOS: Analizar las características fenotípicas y la susceptibilidad a antibióticos de las cepas circulantes de Streptococcus pneumoniae, Haemophilus influenzae y Neisseria meningitidis en ...América Latina y el Caribe entre 2000 y 2005. Se evaluó la cobertura potencial de las vacunas conjugadas. MÉTODOS: Se estudió por métodos convencionales la distribución de los serotipos o serogrupos de 17 303 cepas de S. pneumoniae, 2 782 cepas de H. influenzae y 6 955 cepas de N. meningitidis aisladas de casos de neumonía, meningitis, sepsis, bacteriemias y otros procesos invasivos. Se evaluó la susceptibilidad a los antibióticos de las cepas estudiadas. Los aislamientos procedían de 453 centros centinelas de 19 países de América Latina y 4 del Caribe, como parte del proyecto SIREVA II. RESULTADOS: El serotipo 14 de S. pneumoniae fue el más frecuentemente aislado (21,1%), especialmente en niños menores de 6 años (29,1%). Las coberturas potenciales de las vacunas conjugadas antineumocócicas hepta, nona, deca y tridecavalentes fueron de 59,0%, 73,4%, 76,5% y 85,9%, respectivamente. De los aislamientos, 63,3% eran sensibles a la penicilina. El serotipo b de H. influenzae estuvo presente en 72,2% de los aislamientos en niños menores de 2 años, mientras 8,6% correspondieron a los serotipos a, c, d, e y f; 19,2% resultaron no serotipables. La proporción de cepas de H. influenzae productoras de betalactamasa en aislamientos en niños menores de 2 años fue de 16,3%. Los serogrupos de N. meningitidis más frecuentes fueron el B (69,0%) y el C (25,7%); 65,8% y 99,2% de las cepas fueron sensibles a la penicilina y a la rifampicina, respectivamente. CONCLUSIONES: Estos resultados resaltan la importancia de la vigilancia epidemiológica integral de S. pneumoniae, H. influenzae y N. meningitidis en América Latina y el Caribe. La gran heterogeneidad en la distribución de los serotipos de S. pneumoniae en los países estudiados podría reducir la cobertura de las vacunas aplicadas. Se recomienda realizar un análisis específico por país para ajustar la introducción de nuevas vacunas conjugadas y decidir el esquema de vacunación más adecuado.
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