Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-26 (of 26 Records) |
Query Trace: Pimenta FC[original query] |
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Nasopharyngeal carriage of Streptococcus pneumoniae among children and their household members in southern Mozambique five years after PCV10 introduction
Kahn R , Moiane B , Lessa FC , Massora S , Mabombo V , Chauque A , Tembe N , Mucavele H , Whitney CG , Sacoor C , Matsinhe G , Pimenta FC , da Gloria Carvalho M , Sigauque B , Verani J . Vaccine 2025 47 126691 BACKGROUND: Streptococcus pneumoniae is an important cause of pneumonia, sepsis, and meningitis, which are leading causes of child mortality. Pneumococcal conjugate vaccines (PCVs) protect against disease and nasopharyngeal colonization with vaccine serotypes, reducing transmission to and among unvaccinated individuals. Mozambique introduced 10-valent PCV (PCV10) in 2013. In 2017-2019, 13-valent PCV (PCV13) replaced PCV10, and in September 2019 the schedule changed from three primary doses to two primary doses and a booster; the booster-containing schedule may increase indirect effects. We examined pneumococcal carriage in Mozambique to establish a baseline for estimating the impact of policy changes and to estimate the long-term impact of PCV10 in children aged <5 years. METHODS: We calculated prevalence of carriage of PCV10 serotypes and the 3 additional PCV13 serotypes ('PCV13-unique') among children aged <5 years and their household members in southern Mozambique, between October 2018 and July 2019. Nasopharyngeal swabs were cultured, and isolates underwent Quellung serotyping. For children, we compared these "long-term post-PCV10" data with prior surveys ("pre-PCV" (2012-2013) and "post-PCV10" (2015-2016)) that used the same methods. RESULTS: In 2018-2019, among 1319 children aged under five years, 1064 (80.7 %) were colonized with pneumococcus, among 614 children aged 5- < 18 years, 355 (57.8 %) were colonized, and among 804 adults (aged ≥18 years), 285 (35.4 %) were colonized. The most frequently observed serotypes were 19 A (n = 154, 8.5 % of isolates) and 6 A (n = 107, 5.9 %), both PCV13-unique serotypes. Overall carriage prevalence among children under five years remained stable at approximately 80 % across the carriage studies conducted between 2012 and 2019; between 2015 and 2016 and 2018-2019, the prevalence of PCV10-type carriage declined from 17.7 % to 10.1 %. CONCLUSIONS: Despite substantial declines in PCV10-type carriage initially following vaccine introduction, the continued circulation of PCV10 serotypes and relative high prevalence of PCV13-unique serotypes underscore the need to understand the impact of policy changes on pneumococcus transmission. |
Long-term impact of 10-valent pneumococcal conjugate vaccine in Kenya: Nasopharyngeal carriage among children in a rural and an urban site six years after introduction
Verani JR , Omondi D , Odoyo A , Odiembo H , Ouma A , Ngambi J , Aol G , Audi A , Kiplangat S , Agumba N , Munywoki PK , Onyango C , Hunsperger E , Farrar JL , Kim L , Kobayashi M , Breiman RF , Pimenta FC , da Gloria Carvalho M , Lessa FC , Whitney CG , Bigogo G . Vaccine 2024 BACKGROUND: Kenya introduced Synflorix™ (GlaxoSmithKline, PCV10-GSK), a 10-valent pneumococcal conjugate vaccine, in 2011, using three primary doses and, in select areas, catch-up campaigns. Surveys conducted 1-2 years post-introduction showed a stable prevalence of pneumococcal colonization, with declines in vaccine-type carriage. However, little is known about the long-term impact of PCV10-GSK in Kenya. METHODS: We conducted a cross-sectional survey of pneumococcal carriage among children aged <5 years in November-December 2017 in Kibera (Nairobi informal settlement, no catch-up) and Asembo (rural western Kenya, 2-dose catch-up for children 1-4 years), using the same methods and settings as prior annual surveys from 2009 to 2013. Participants were randomly selected from an ongoing population-based surveillance platform. Nasopharyngeal swabs were frozen in skim milk-tryptone-glucose-glycerin media within 4 h and underwent culture with broth enrichment for pneumococcus. Isolates were serotyped by polymerase chain reaction and Quellung. RESULTS: We enrolled 504 children, including 252 from each site; >90 % of participants had received 3 doses of PCV10-GSK. Pneumococcal colonization was detected in 210 (83.3 %) participants in Kibera and 149 (59.1 %) in Asembo, which was significantly lower than the prevalence observed in 2013 (92.9 % and 85.7 %, respectively). PCV10-GSK serotypes were detected in 35/252 (13.9 %) participants in Kibera and 23/252 (9.1 %) in Asembo, respectively; these prevalences were lower, but not statistically different, from vaccine-type carriage prevalences in 2013 (17.3 % and 13.3 %, respectively). In 2017 in both sites, serotypes 3, 6A, 19A, 19F, and 35B were among the most common serotypes. CONCLUSION: Six years post-PCV10-GSK introduction, the prevalence of pneumococcal carriage among children has decreased, and the impact of PCV10-GSK on vaccine-type carriage has plateaued. Kenya recently changed from PCV10-GSK to Pneumosil™ (Serum Institute of India), a 10-valent PCV that includes serotypes 6A and 19A; these data provide historical context for interpreting changes in vaccine-type carriage following the PCV formulation switch. |
Nasopharyngeal carriage of Streptococcus pneumoniae among children <5 years of age in Indonesia prior to pneumococcal conjugate vaccine introduction
Safari D , Daningrat WOD , Milucky JL , Khoeri MM , Paramaiswari WT , Tafroji W , Salsabila K , Winarti Y , Soebandrio A , Hadinegoro SR , Prayitno A , Childs L , Pimenta FC , Carvalho MDG , Pilishvili T . PLoS One 2024 19 (1) e0297041 Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged <5 years before 13-valent PCV (PCV13) introduction. Nasopharyngeal swabs were collected during visits to community integrated health service posts at one peri-urban and one rural study site. Specimens were analyzed by culture, and isolates were serotyped using sequential multiplex polymerase chain and Quellung reaction. Antibiotic susceptibility was performed by broth microdilution method. We enrolled 1,007 children in Gunungkidul District, Yogyakarta (peri-urban) and 815 in Southwest Sumba, East Nusa Tenggara (rural). Pneumococcal carriage prevalence was 30.9% in Gunungkidul and 87.6% in Southwest Sumba (combined: 56.3%). PCV13 serotypes (VT) carriage was 15.0% in Gunungkidul and 52.6% in Southwest Sumba (combined: 31.8%). Among pneumococcal isolates identified, the most common VT were 6B (16.4%), 19F (15.8%), and 3 (4.6%) in Gunungkidul (N = 323) and 6B (17.6%), 19F (11.0%), and 23F (9.3%) in Southwest Sumba (N = 784). Factors associated with pneumococcal carriage were age (1-2 years adjusted odds ratio (aOR) 1.9, 95% CI 1.4-2.5; 3-4 years aOR 1.5, 95% CI 1.1-2.1; reference <1 year), other children <5 years old in the household (aOR 1.5, 95% CI 1.1-2.0), and presence of ≥1 respiratory illness symptom (aOR 1.8, 95% CI 1.4-2.2). Overall, 61.5% of the pneumococcal isolates were non-susceptible to ≥1 antibiotic class and 13.2% were multi-drug non-susceptible (MDNS) (non-susceptible to ≥3 classes of antibiotics). Among 602 VT isolates, 73.9% were non-susceptible and 19.9% were MDNS. These findings are critical to establish a pre-PCV13 carriage prevalence and demonstrate the complexity in evaluating the impact of PCV13 introduction in Indonesia given the wide variability in the carriage prevalence as shown by the two study sites. |
Nasopharyngeal colonization by Streptococcus pneumoniae in children and adults before the introduction of the 10-valent conjugate vaccine, Paraguay
Chamorro G , Kawabata A , Carvalho MDG , Pimenta FC , Lessa FC , Torres C , Lerea MJ , León ME . PLoS One 2023 18 (2) e0280722 Streptococcus pneumoniae is a cause of invasive diseases such as pneumonia, meningitis, and other serious infections among children and adults in Paraguay. This study was conducted to establish S. pneumoniae baseline prevalence, serotype distribution, and antibiotic resistance patterns in healthy children aged 2 to 59 months and adults ≥60 years of age prior to the introduction of PCV10 in the national childhood immunization program in Paraguay. Between April and July 2012, a total of 1444 nasopharyngeal swabs were collected, 718 from children aged 2 to 59 months and 726 from adults ≥60 years of age. The pneumococcal isolation, serotyping, and antibiotic susceptibility testing were performed using standard tests. Pneumococcal colonization prevalence was 34.1% (245/718) in children and 3.3% (24/726) in adults. The most frequent pneumococcal vaccine-types (VT) detected in the children were 6B (42/245), 19F (32/245), 14 (17/245), and 23F (20/245). Carriage prevalence with PCV10 serotypes was 50.6% (124/245) and PCV13 was 59.5% (146/245). Among colonized adults, prevalence of PCV10 and PCV13 serotypes were 29.1% (7/24) and 41.6% (10/24), respectively. Colonized children were more likely to share a bedroom, have a history of respiratory infection or pneumococcal infection compared to non-colonized children. no associations were found in adults. However, no significant associations were found in children and neither in adults. Vaccine-type pneumococcal colonization was highly prevalent in children and rare in adults in Paraguay prior to vaccine introduction, supporting the introduction of PCV10 in the country in 2012. These data will be useful to evaluate the impact of PCV introduction in the country. |
Histopathology Is Key to Interpreting Multiplex Molecular Test Results From Postmortem Minimally Invasive Tissue Samples
Ritter JM , Seixas JN , Walong E , Dawa J , Onyango C , Pimenta FC , da Gloria Carvalho M , Silva-Flannery L , Jenkinson T , Howard K , Bhatnagar J , Diaz M , Winchell JM , Zaki SR , Chaves SS , Martines RB . Clin Infect Dis 2021 73 S351-s359 BACKGROUND: Minimally invasive tissue sampling (MITS) is an alternative to complete autopsy for determining causes of death. Multiplex molecular testing performed on MITS specimens poses challenges of interpretation, due to high sensitivity and indiscriminate detection of pathogenic, commensal, or contaminating microorganisms. METHODS: MITS was performed on 20 deceased children with respiratory illness, at 10 timepoints up to 88 hours postmortem. Samples were evaluated by multiplex molecular testing on fresh tissues by TaqMan® Array Card (TAC) and by histopathology, special stains, immunohistochemistry (IHC), and molecular testing (PCR) on formalin-fixed, paraffin-embedded (FFPE) tissues. Results were correlated to determine overall pathologic and etiologic diagnoses and to guide interpretation of TAC results. RESULTS: MITS specimens collected up to 3 days postmortem were adequate for histopathologic evaluation and testing. Seven different etiologic agents were detected by TAC in 10 cases. Three cases had etiologic agents detected by FFPE or other methods and not TAC; 2 were agents not present on TAC, and 2 were streptococci that may have been species other than those present on TAC. Result agreement was 43% for TAC and IHC or PCR, and 69% for IHC and PCR. Extraneous TAC results were common, especially when aspiration was present. CONCLUSIONS: TAC can be performed on MITS up to 3 days after death with refrigeration and provides a sensitive method for detection of pathogens but requires careful interpretation in the context of clinicoepidemiologic and histopathologic findings. Interpretation of all diagnostic tests in aggregate to establish overall case diagnoses maximizes the utility of TAC in MITS. |
Nonpneumococcal Strains Recently Recovered from Carriage Specimens and Expressing Capsular Serotypes Highly Related or Identical to Pneumococcal Serotypes 2, 4, 9A, 13, and 23A
Gertz RE Jr , Pimenta FC , Chochua S , Larson S , Venero AK , Bigogo G , Milucky J , Carvalho MDG , Beall B . mBio 2021 12 (3) The polysaccharide capsule is a key virulence factor of Streptococcus pneumoniae There are numerous epidemiologically important pneumococcal capsular serotypes, and recent findings have demonstrated that several of them are commonly found among nonpathogenic commensal species. Here, we describe 9 nonpneumococcal strains carrying close homologs of pneumococcal capsular biosynthetic (cps) loci that were discovered during recent pneumococcal carriage studies of adults in the United States and Kenya. Two distinct Streptococcus infantis strains cross-reactive with pneumococcal serotype 4 and carrying cps4-like capsular biosynthetic (cps) loci were recovered. Opsonophagocytic killing assays employing rabbit antisera raised against S. infantis US67cps4 revealed serotype 4-specific killing of both pneumococcal and nonpneumococcal strains. An S. infantis strain and two Streptococcus oralis strains, all carrying cps9A-like loci, were cross-reactive with pneumococcal serogroup 9 strains in immunodiffusion assays. Antiserum raised against S. infantis US64cps9A specifically promoted killing of serotype 9A and 9V pneumococcal strains as well as S. oralis serotype 9A strains. Serotype-specific PCR of oropharyngeal specimens from a recent adult carriage study in the United States indicated that such nonpneumococcal strains were much more common in this population than serotype 4 and serogroup 9 pneumococci. We also describe S. oralis and S. infantis strains expressing serotypes identical or highly related to serotypes 2, 13, and 23A. This study has expanded the known overlap of pneumococcal capsular serotypes with related commensal species. The frequent occurrence of nonpneumococcal strains in the upper respiratory tract that share vaccine and nonvaccine capsular serotypes with pneumococci could affect population immunity to circulating pneumococcal strains.IMPORTANCE The distributions and frequencies of individual pneumococcal capsular serotypes among nonpneumococcal strains in the upper respiratory tract are unknown and potentially affect pneumococcal serotype distributions among the population and immunity to circulating pneumococcal strains. Repeated demonstration that these nonpneumococcal strains expressing so-called pneumococcal serotypes are readily recovered from current carriage specimens is likely to be relevant to pneumococcal epidemiology, niche biology, and even to potential strategies of employing commensal live vaccines. Here, we describe multiple distinct nonpneumococcal counterparts for each of the pneumococcal conjugate vaccine (PCV) serotypes 4 and 9V. Additional data from contemporary commensal isolates expressing serotypes 2, 13, and 23A further demonstrate the ubiquity of such strains. Increased focus upon this serological overlap between S. pneumoniae and its close relatives may eventually prove that most, or possibly all, pneumococcal serotypes have counterparts expressed by the common upper respiratory tract commensal species Streptococcus mitis, Streptococcus oralis, and Streptococcus infantis. |
Prevalence, serotype and antibiotic susceptibility of Group B Streptococcus isolated from pregnant women in Jakarta, Indonesia
Safari D , Gultom SM , Tafroji W , Azzahidah A , Soesanti F , Khoeri MM , Prayitno A , Pimenta FC , da Gloria Carvalho M , Uiterwaal Cspm , Putri ND . PLoS One 2021 16 (5) e0252328 Group B Streptococcus (GBS) is a bacterial pathogen which is a leading cause of neonatal infection. Currently, there are limited GBS data available from the Indonesian population. In this study, GBS colonization, serotype distribution and antimicrobial susceptibility profile of isolates were investigated among pregnant women in Jakarta, Indonesia. Demographics data, clinical characteristics and vaginal swabs were collected from 177 pregnant women (mean aged: 28.7 years old) at 29-40 weeks of gestation. Bacterial culture identification tests and latex agglutination were performed for GBS. Serotyping was done by conventional multiplex PCR and antibiotic susceptibility testing by broth microdilution. GBS colonization was found in 53 (30%) pregnant women. Serotype II was the most common serotype (30%) followed by serotype III (23%), Ia and IV (13% each), VI (8%), Ib and V (6% each), and one non-typeable strain. All isolates were susceptible to vancomycin, penicillin, ampicillin, cefotaxime, daptomycin and linezolid. The majority of GBS were resistant to tetracycline (89%) followed by clindamycin (21%), erythromycin (19%), and levofloxacin (6%). The serotype III was more resistant to erythromycin, clindamycin, and levofloxacin and these isolates were more likely to be multidrug resistant (6 out of 10) compared to other serotypes. This report provides demographics of GBS colonization and isolate characterization in pregnant women in Indonesia. The results may facilitate preventive strategies to reduce neonatal GBS infection and improve its treatment. |
Effect of 10-valent pneumococcal conjugate vaccine on Streptococcus pneumoniae nasopharyngeal carriage among children less than 5 years old: 3 years post-10-valent pneumococcal conjugate vaccine introduction in Mozambique
Valenciano SJ , Moiane B , Lessa FC , Chaúque A , Massora S , Pimenta FC , Mucavele H , Verani JR , da Gloria Carvalho M , Whitney CG , Tembe N , Sigaúque B . J Pediatric Infect Dis Soc 2020 10 (4) 448-456 BACKGROUND: Mozambique introduced 10-valent pneumococcal conjugate vaccine (PCV10) in 2013 with doses at ages 2, 3, and 4 months and no catch-up or booster dose. We evaluated PCV10 impact on the carriage of vaccine-type (VT), non-VT, and antimicrobial non-susceptible pneumococci 3 years after introduction. METHODS: We conducted cross-sectional carriage surveys among HIV-infected and HIV-uninfected children aged 6 weeks to 59 months: 1 pre-PCV10 (2012-2013 [Baseline]) and 2 post-PCV10 introductions (2014-2015 [Post1] and 2015-2016 [Post2]). Pneumococci isolated from nasopharyngeal swabs underwent Quellung serotyping and antimicrobial susceptibility testing. Non-susceptible isolates (intermediate or resistant) were defined using Clinical and Laboratory Standards Institute 2018 breakpoints. We used log-binomial regression to estimate changes in the pneumococcal carriage between survey periods. We compared proportions of non-susceptible pneumococci between Baseline and Post2. RESULTS: We enrolled 720 children at Baseline, 911 at Post1, and 1208 at Post2. Baseline VT carriage was similar for HIV-uninfected (36.0%, 110/306) and HIV-infected children (34.8%, 144/414). VT carriage was 36% (95% confidence interval [CI]: 19%-49%) and 27% (95% CI: 11%-41%) lower in Post1 vs baseline among HIV-uninfected and HIV-infected children, respectively. VT carriage prevalence declined in Post2 vs Post1 for HIV-uninfected but remained stable for HIV-infected children. VT carriage prevalence 3 years after PCV10 introduction was 14.5% in HIV-uninfected and 21.0% in HIV-infected children. Pneumococcal isolates non-susceptible to penicillin declined from 66.0% to 56.2% (P= .0281) among HIV-infected children. CONCLUSIONS: VT and antimicrobial non-susceptible pneumococci carriage dropped after PCV10 introduction, especially in HIV-uninfected children. However, VT carriage remained common, indicating ongoing VT pneumococci transmission. |
Limited added value of oropharyngeal swabs for detecting pneumococcal carriage in adults
Farrar JL , Odiembo H , Odoyo A , Bigogo G , Kim L , Lessa FC , Feikin DR , Breiman RF , Whitney CG , Carvalho MG , Pimenta FC . Open Forum Infect Dis 2020 7 (9) ofaa368 We compared pneumococcal isolation rates and evaluated the benefit of using oropharyngeal (OP) specimens in addition to nasopharyngeal (NP) specimens collected from adults in rural Kenya. Of 846 adults, 52.1% were colonized; pneumococci were detected from both NP and OP specimens in 23.5%, NP only in 22.9%, and OP only in 5.7%. Ten-valent pneumococcal conjugate vaccine strains were detected from both NP and OP in 3.4%, NP only in 4.1%, and OP only in 0.7%. Inclusion of OP swabs increased carriage detection by 5.7%; however, the added cost of collecting and processing OP specimens may justify exclusion from future carriage studies among adults. |
Dried blood spots for Streptococcus pneumoniae and Haemophilus influenzae detection and serotyping among children < 5 years old in rural Mozambique.
Pimenta FC , Moiane B , Lessa FC , Venero AL , Moura I , Larson S , Massora S , Chauque A , Tembe N , Mucavele H , Verani JR , Whitney CG , Sigauque B , Carvalho MGS . BMC Pediatr 2020 20 (1) 326 ![]() BACKGROUND: Dried blood spots (DBS) have been proposed as potentially tool for detecting invasive bacterial diseases. METHODS: We evaluated the use of DBS for S. pneumoniae and H. influenzae detection among children in Mozambique. Blood for DBS and nasopharyngeal (NP) swabs were collected from children with pneumonia and healthy aged < 5 years. Bacterial detection and serotyping were performed by quantitative PCR (qPCR) (NP and DBS; lytA gene for pneumococcus and hpd for H. influenzae) and culture (NP). Combined detection rates were compared between children with pneumonia and healthy. RESULTS: Of 325 children enrolled, 205 had pneumonia and 120 were healthy. Pneumococci were detected in DBS from 20.5 and 64.2% of children with pneumonia and healthy, respectively; NP specimens were positive for pneumococcus in 80.0 and 80.8%, respectively. H. influenzae was detected in DBS from 22.9% of children with pneumonia and 59.2% of healthy; 81.4 and 81.5% of NP specimens were positive for H. influenzae, respectively. CONCLUSION: DBS detected pneumococcal and H. influenzae DNA in children with pneumonia and healthy. Healthy children were often DBS positive for both bacteria, suggesting that qPCR of DBS specimens does not differentiate disease from colonization and is therefore not a useful diagnostic tool for children. |
Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area, southern Mozambique
Massora S , Lessa FC , Moiane B , Pimenta FC , Mucavele H , Chauque A , Cossa A , Verani JR , Tembe N , da Gloria Carvalho M , Munoz-Almagro C , Sigauque B . Vaccine 2019 37 (51) 7470-7477 ![]() BACKGROUND: Invasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction. METHODS: We used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged<5years in Manhia, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI>1 indicated high invasive disease potential and OR and 95% CI<1 indicated low invasive disease potential. RESULTS: In the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5]). CONCLUSION: The number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period. |
PCR-based national bacterial meningitis surveillance in Turkey years 2006 to 2009
Toprak D , Soysal A , Torunoglu MA , Turgut M , Turkoglu S , Pimenta FC , Carvalho MG , Wang X , Mayer L , Altnkanat G , Söyletir G , Mete B , Bakr M . Pediatr Infect Dis J 2014 33 (10) 1087-1089 Polymerase chain reaction-based surveillance for bacterial meningitis including 841 children revealed 246 with bacterial DNA in cerebrospinal fluid samples of which 53% were Streptococcus pneumoniae, 19% Neisseria meningitidis, and 16% Haemophilus influenzae type b. The most common S. pneumoniae serotypes/serogroups were 1, 19F, 6A/6B, 23F, 5, 14, 18 and 19A. Among 47 meningococci, 86% were serogroup B, 6% serogroup C, 3% serogroup A, 3% serogroup X and 3% serogroup W. |
Direct effect of 10-valent conjugate pneumococcal vaccination on pneumococcal carriage in children Brazil
Andrade AL , Ternes YM , Vieira MA , Moreira WG , Lamaro-Cardoso J , Kipnis A , Cardoso MR , Brandileone MC , Moura I , Pimenta FC , da Gloria Carvalho M , Saraiva FO , Toscano CM , Minamisava R . PLoS One 2014 9 (6) e98128 BACKGROUND: 10-valent conjugate pneumococcal vaccine/PCV10 was introduced in the Brazilian National Immunization Program along the year of 2010. We assessed the direct effectiveness of PCV10 vaccination in preventing nasopharyngeal/NP pneumococcal carriage in infants. METHODS: A cross-sectional population-based household survey was conducted in Goiania Brazil, from December/2010-February/2011 targeting children aged 7-11 m and 15-18 m. Participants were selected using a systematic sampling. NP swabs, demographic data, and vaccination status were collected from 1,287 children during home visits. Main outcome and exposure of interest were PCV10 vaccine-type carriage and dosing schedules (3p+0, 2p+0, and one catch-up dose), respectively. Pneumococcal carriage was defined by a positive culture and serotyping was performed by Quellung reaction. Rate ratio/RR was calculated as the ratio between the prevalence of vaccine-types carriage in children exposed to different schedules and unvaccinated for PCV10. Adjusted RR was estimated using Poisson regression. PCV10 effectiveness/VE on vaccine-type carriage was calculated as 1-RR*100. RESULTS: The prevalence of pneumococcal carriage was 41.0% (95%CI: 38.4-43.7). Serotypes covered by PCV10 and PCV13 were 35.2% and 53.0%, respectively. Vaccine serotypes 6B (11.6%), 23F (7.8%), 14 (6.8%), and 19F (6.6%) were the most frequently observed. After adjusted for confounders, children who had received 2p+0 or 3p+0 dosing schedule presented a significant reduction in pneumococcal vaccine-type carriage, with PCV10 VE equal to 35.9% (95%CI: 4.2-57.1; p = 0.030) and 44.0% (95%CI: 14.-63.5; p = 0.008), respectively, when compared with unvaccinated children. For children who received one catch-up dose, no significant VE was detected (p = 0.905). CONCLUSION: PCV10 was associated with high protection against vaccine-type carriage with 2p+0 and 3p+0 doses for children vaccinated before the second semester of life. The continuous evaluation of carriage serotypes distribution is likely to be useful for evaluating the long-term effectiveness and impact of pneumococcal vaccination on serotypes reduction. |
Non-pneumococcal mitis-group streptococci confound detection of pneumococcal capsular serotype-specific loci in upper respiratory tract
Carvalho Mda G , Pimenta FC , Moura I , Roundtree A , Gertz RE Jr , Li Z , Jagero G , Bigogo G , Junghae M , Conklin L , Feikin DR , Breiman RF , Whitney CG , Beall BW . PeerJ 2013 1 e97 We performed culture-based and PCR-based tests for pneumococcal identification and serotyping from carriage specimens collected in rural and urban Kenya. Nasopharyngeal specimens from 237 healthy children <5 years old (C-NPs) and combined nasopharyngeal/oropharyngeal specimens from 158 adults (A-NP/OPs, 118 HIV-positive) were assessed using pneumococcal isolation (following broth culture enrichment) with Quellung-based serotyping, real-time lytA-PCR, and conventional multiplexed PCR-serotyping (cmPCR). Culture-based testing from C-NPs, HIV-positive A-NP/OPs, and HIV-negative A-NP/OPs revealed 85.2%, 40.7%, and 12.5% pneumococcal carriage, respectively. In contrast, cmPCR serotypes were found in 93.2%, 98.3%, and 95.0% of these sets, respectively. Two of 16 lytA-negative C-NPs and 26 of 28 lytA-negative A-NP/OPs were cmPCR-positive for 1-10 serotypes (sts) or serogroups (sgs). A-NP/OPs averaged 5.5 cmPCR serotypes/serogroups (5.2 in HIV-positive, 7.1 in HIV-negative) and C-NPs averaged 1.5 cmPCR serotypes/serogroups. cmPCR serotypes/serogroups from lytA-negative A-NP/OPs included st2, st4, sg7F/7A, sg9N/9L, st10A, sg10F/10C/33C, st13, st17F, sg18C/18A/18B/18F, sg22F/22A, and st39. Nine strains of three non-pneumococcal species (S. oralis, S. mitis, and S. parasanguinis) (7 from A-OP, 1 from both A-NP and A-OP, and 1 from C-NP) were each cmPCR-positive for one of 7 serotypes/serogroups (st5, st13, sg15A/15F, sg10F/10C/33C, sg33F/33A/37, sg18C/18A/18B/18F, sg12F/12A/12B/ 44/46) with amplicons revealing 83.6-99.7% sequence identity to pneumococcal references. In total, 150 cmPCR amplicons from carriage specimens were sequenced, including 25 from lytA-negative specimens. Amplicon sequences derived from specimens yielding a pneumococcal isolate with the corresponding serotype were identical or highly conserved (>98.7%) with the reference cmPCR amplicon for the st, while cmPCR amplicons from lytA-negative specimens were generally more divergent. Separate testing of 56 A-OPs and 56 A-NPs revealed that approximately 94% of the positive cmPCR results from A-NP/OPs were from OP microbiota. In contrast, A-NPs yielded >2-fold more pneumococcal isolates than A-OPs. Verified and suspected non-pneumococcal cmPCR serotypes/serogroups appeared to be relatively rare in C-NPs and A-NPs compared to A-OPs. Our findings indicate that non-pneumococcal species can confound serotype-specific PCR and other sequence-based assays due to evolutionarily conserved genes most likely involved in biosynthesis of surface polysaccharide structures. |
Sequential triplex real-time PCR assay for detecting 21 pneumococcal capsular serotypes that account for a high global disease burden.
Pimenta FC , Roundtree A , Soysal A , Bakir M , du Plessis M , Wolter N , von Gottberg A , McGee L , Carvalho MG , Beall B . J Clin Microbiol 2012 51 (2) 647-52 ![]() We developed and validated a real-time PCR assay consisting of 7 triplexed reactions to identify 11 individual serotypes plus 10 small serogroups representing the majority of disease-causing isolates of Streptococcus pneumoniae. This assay targets the 13 serotypes included within the 13-valent conjugate vaccine and 8 additional key serotypes or serogroups. Advantages over other serotyping assays are described. The assay will be expanded to 40 serotypes/serogroups. We will provide periodic updates at our protocol web site. |
Potential non-pneumococcal confounding of PCR-based determination of serotype in carriage
Carvalho MD , Jagero G , Bigogo GM , Junghae M , Pimenta FC , Moura I , Roundtree A , Li Z , Conklin L , Feikin DR , Breiman RF , Whitney CG , Beall B . J Clin Microbiol 2012 50 (9) 3146-7 ![]() Monitoring pneumococcal carriage serotype distributions is increasingly used to study pneumococcal biology, disease epidemiology, and vaccine impact.... |
Molecular epidemiological investigation to determine the source of a fatal case of serotype 22F pneumococcal meningitis.
Lamaro-Cardoso J , de Lemos AP , Carvalho Mda G , Pimenta FC , Roundtree A , Motta L , Vieira MA , Sgambatti S , Thorn LK , Pessoa-Junior V , Minamisava R , Harrison LH , Beall BW , Brandileone MC , Andrade AL . J Med Microbiol 2012 61 686-92 ![]() A child's death due to pneumococcal meningitis after contracting the disease in an after-school programme prompted an investigation to assess nasopharyngeal (NP) carriage among her contacts. The serotype of the meningitis case isolate was determined, together with the serotypes of the NP specimens of contacts, comprising the case patient's brother, the case patient's after-school programme contacts and the brother's day-care centre (DCC) contacts. NP swabs from 155 children and 69 adults were obtained. Real-time PCR and conventional multiplex PCR (CM-PCR) assays were used to detect pneumococcal carriage and determine serotypes. Broth-enriched culture of NP specimens followed by pneumococcal isolation and Quellung-based serotyping were also performed. DNA extracts prepared from cerebrospinal fluid of the index case and from the NP strain isolated from the brother and from one attendee of the brother's DCC were subjected to genotyping. Pneumococcal carriage assessed by real-time PCR and culture was 49.6 and 36.6 %, respectively (P<0.05). Twenty-three serotypes were detected using CM-PCR, with serotypes 6A/6B, 14, 19F, 6C/6D, 22F/22A, 23F and 11A/11D being the most frequent. All eight serotype 22F/22A NP specimens recovered were from children attending the brother's DCC. The meningitis case isolate and the NP carriage isolate from the patient's brother were both serotype 22F and shared the same new multilocus sequence type (ST6403) with the attendee of the brother's DCC. CM-PCR proved to be useful for assessing carriage serotype distribution in a setting of high-risk pneumococcal transmission. The causal serotype appeared to be linked to the brother of the case patient and attendees of his DCC. |
Serotype and genotype distributions of pneumococcal carriage isolates recovered from Brazilian children attending day-care centres.
Pimenta FC , Carvalho MG , Gertz RE Jr , Bastos-Rocha CG , Oliveira LS , Lacerda Pigosso L , Lima JA , Marquez Franco C , Andrade AL , Beall BW . J Med Microbiol 2011 60 1455-9 ![]() Pneumococcal nasopharyngeal carriage isolates recovered from Brazilian children attending day-care centres in 2005 were assessed for serotype, genotype and penicillin susceptibility phenotype. As 124 of the 253 isolates (49 %) were characterized previously with respect to serotype and penicillin susceptibility, the primary objectives were to examine clonal associations and penicillin susceptibility within major serotypes and to assess the suitability of conventional multiplex PCR for deducing carriage serotypes within this population. Using a combination of PCR-based serotyping and the Quellung reaction, serotypes were identified for 81 % (205/253) of the isolates, with serogroups or types 14, 6, 23F, 19F and 18 being predominant. Included within the 205 isolates successfully serotyped by PCR were 28 isolates that had become non-viable. Forty-eight isolates were non-typable using both the PCR method and the Quellung reaction. Penicillin non-susceptibility was observed within 16 of the 18 multilocus sequence types detected. Thus, this study provides further evidence from a diverse collection of pneumococcal clones that PCR-based serotype deduction is useful for providing supportive evidence for pneumococcal conjugate vaccine implementation. |
Pre- and post-conjugate vaccine epidemiology of pneumococcal serotype 6C invasive disease and carriage within Navajo and White Mountain Apache communities
Millar EV , Pimenta FC , Roundtree A , Jackson D , Carvalho MD , Perilla MJ , Reid R , Santosham M , Whitney CG , Beall BW , O'Brien KL . Clin Infect Dis 2010 51 (11) 1258-65 BACKGROUND: A second-generation 13-valent pneumococcal conjugate vaccine, PCV13, was recently licensed. Although PCV13 includes serotype 6A, the usefulness of that antigen may be limited by the emergence of a new serotype, 6C, which was identified among isolates initially characterized (Quellung reaction) as serotype 6A. The epidemiology of serotype 6C prior to and after 7-valent PCV (PCV7) introduction is incompletely understood. METHODS: We analyzed conventionally serotyped 6A (CS6A) pneumococci from invasive disease case patients of all ages and carriage isolates from children and adults obtained in population-based studies among Navajo and White Mountain Apache communities during 1994-2009. Samples were tested by triplex polymerase chain reaction to resolve serotypes 6C and 6A. RESULTS: A total of 74 invasive CS6A episodes occurred. All were retyped by polymerase chain reaction; 40 (54.1%) were serotype 6C. The mean annual incidence of serotype 6C invasive disease was 0.3 (95% confidence interval, 0.03-0.9), 0.7 (95% confidence interval, 0.2-1.3), and 1.5 (95% confidence interval, 1.0-2.1) cases per 100,000 population in the years prior to the PCV7 efficacy trial, during the time the PCV7 trial was conducted, and following PCV7 introduction and routine use, respectively ([Formula: see text]). In the routine vaccination era, 76% of invasive CS6As were serotype 6C; nearly all cases occurred in adults. The proportion of serotype 6C among CS6A carriage isolates increased from 42% to 61% to 94% in the prevaccine, early vaccine, and routine vaccination eras, respectively. CONCLUSION: In the PCV7 routine use era, virtually all serogroup 6 invasive pneumococcal disease and carriage strains among Navajo and White Mountain Apache communities are 6C. Monitoring and evaluation of this and other emerging serotypes among invasive disease and carriage isolates is warranted. |
Association of 2009 pandemic influenza A (H1N1) infection and increased hospitalization with parapneumonic empyema in children in Utah
Ampofo K , Herbener A , Blaschke AJ , Heyrend C , Poritz M , Korgenski K , Rolfs R , Jain S , Carvalho MD , Pimenta FC , Daly J , Mason EO , Byington CL , Pavia AT . Pediatr Infect Dis J 2010 29 (10) 905-9 BACKGROUND: During previous influenza pandemics, many deaths were associated with secondary bacterial infection. In April 2009, a previously unknown 2009 influenza A virus (2009 H1N1) emerged, causing a global influenza pandemic. We examined the relationship between circulating 2009 H1N1 and the occurrence of secondary bacterial parapneumonic empyema in children. METHODS: Children hospitalized with parapneumonic empyema from August 2004 to July 2009, including a period when the 2009 H1N1 circulated in Utah, were identified using International Classification of Diseases, Ninth Revision codes. We compared the average number of children diagnosed with influenza A and the number of admissions for empyema per month for the previous 4 seasons to rates of empyema during the 2009 H1N1 outbreak. We identified causative bacteria using culture and polymerase chain reaction (PCR). RESULTS: We observed an increase in hospitalization of children with pneumonia complicated by empyema during a severe outbreak of 2009 H1N1 during the spring and summer of 2009, compared with historical data for the previous 4 seasons. Streptococcus pneumoniae and Streptococcus pyogenes were the predominant bacteria identified. CONCLUSIONS: Similar to previous pandemics, secondary bacterial infection with S. pneumoniae and S. pyogenes were associated with the 2009 H1N1 outbreak. There is an urgent need to better understand bacterial complications of pandemic influenza. In the interim, influenza vaccines, antiviral agents, and pneumococcal vaccines should be used to prevent cases of secondary bacterial pneumonia whenever possible. |
Revisiting pneumococcal carriage using broth-enrichment and PCR techniques for enhanced detection of carriage and serotypes
Carvalho MD , Pimenta FC , Jackson D , Roundtree A , Ahmad Y , Millar EV , O'Brien KL , Whitney CG , Cohen AL , Beall BW . J Clin Microbiol 2010 48 (5) 1611-8 ![]() The measurement of pneumococcal carriage in the nasopharyngeal reservoir is subject to potential confounders that include low-density and multiple-strain colonization. To compare different methodologies, we picked a random sampling of 100 nasopharyngeal (NP) specimens recovered from infants less than 2 years of age that were previously assessed for pneumococcal carriage and serotypes using a conventional method employing direct plating from the transport/storage medium (50 pneumococcal culture-negative and 50 pneumococcal culture-positive). We used a broth enrichment approach and a conventional PCR approach (with and without broth-enrichment) for determining pneumococcal carriage and serotypes to compare to initial conventional culture-based results. Additionally we used lytA-targeted real time PCR for pneumococcal detection. Broth enrichment for both culture-based and PCR based methods enhanced the isolation of pneumococci and detection of serotype diversity, with the most effective serotype-deduction method employing broth enrichment prior to sequential multiplex PCR. Similarly, we also found that broth enrichment followed by lytA-specific real time PCR was most sensitive for detecting apparent pneumococcal carriage. The broth enrichment, conventional multiplex PCR, and real time PCR approaches used in this study were effective in detecting pneumococcal carriage within the 50 specimens that were negative using conventional direct plating from transport medium (ranging from 8/50 - 22/50 (16-44%) positives), and the 3 different serotyping approaches employing broth-enrichment increased the number of serotype identifications from the 100 specimens (12 - 29 additional identifications). A PCR-based approach that employed a broth enrichment step appeared to best enhance the detection of mixed serotypes and low density pneumococcal carriage. |
Increased penicillin nonsusceptibility of nonvaccine-serotype invasive pneumococci other than serotypes 19A and 6A in post-7-valent conjugate vaccine era
Gertz RE Jr , Li Z , Pimenta FC , Jackson D , Juni BA , Lynfield R , Jorgensen JH , Carvalho MG , Beall BW . J Infect Dis 2010 201 (5) 770-5 According to population-based invasive pneumococcal surveillance in the United States during 2007, 898 (26%) of 3,511 isolates were penicillin nonsusceptible. Non-7-valent pneumococcal conjugate vaccine (PCV7) serotypes other than 19A accounted for 40% of these penicillin-nonsusceptible isolates; of these, serotypes 15A (11%), 23A (8%), 35B (8%), and 6C (5%) were most common (cumulatively 32% of penicillin-nonsusceptible isolates). Each except 6C represented a single serotype and clonal complex combination that predated the introduction of PCV7. We evaluated the genetic characteristics and nonsusceptibility to penicillin of non- PCV7 serotypes, and we found increased proportions of specific penicillin-nonsusceptible clones in serotypes 15A, 23A, 35B, and 6C, which potentially indicates a basic change of population structure within these individual serotypes. |
Survey of nonsusceptible nasopharyngeal streptococcus pneumoniae isolates in children attending day-care centers in Brazil
Franco CM , Andrade AL , Andrade JG , Silva SA , Oliveira CR , Pimenta FC , Lamaro-Cardoso J , Brandao AP , Almeida SC , Calix JJ , Nahm MH , de Cunto Brandileone MC . Pediatr Infect Dis J 2009 29 (1) 77-9 A survey of nasopharyngeal carriage of penicillin nonsusceptible pneumococcal (PNSp) isolates was conducted among 1192 children attending 62 day care centers in Brazil, where pneumococcal vaccination has not been routinely introduced. Nasopharyngeal pneumococcal carriage was detected in 686 (57.6%) infants, and 178 (25.9%) of them carried PNSp isolates. Being less than 24 months of age, hospitalization in the previous 3 months, and recurrent acute otitis media were independently associated with PNSp. Serotypes 14, 23F, 19A, 6A, 6B and 19F were the most common serotype isolated accounting for 80% of the PNSp. A high proportion (35/332) of non-(sero)typeable isolates was detected, 62.9% of them PNSp. Serotypes coverage projected for the pneumococcal conjugate vaccine (PCV) 13-valent vaccine (72%) was significantly higher compared with PCV7 (58.4%) and PCV 10-valent vaccine (59.3%). |
Molecular epidemiology and risk factors for nasal carriage of Staphylococcus aureus and methicillin-resistant S. aureus in infants attending day-care centers in Brazil
Lamaro-Cardoso J , de Lencastre H , Kipnis A , Pimenta FC , Oliveira LS , Oliveira RM , Nouer S , Aires-de-Sousa M , Milheirico C , Andrade AL . J Clin Microbiol 2009 47 (12) 3991-7 ![]() Investigations regarding Staphylococcus aureus carriage among Brazilian children are scarce. We evaluated the determinants of S. aureus and methicillin-resistant S. aureus (MRSA) nasal carriage in infants attending day-care centers (DCCs) and the molecular features of the MRSA strains. A total of 1,192 children aged 2 months to 5 years attending 62 DCCs were screened for S. aureus and MRSA nasal carriage. MRSA isolates were characterized by pulsed-field gel electrophoresis, multilocus sequence typing, spa typing, staphylococcal cassette chromosome (SCC) mec typing and the presence of the Panton-Valentine leukocidin gene. Logistic regression was performed to determine risk factors associated with S. aureus and MRSA colonization. S. aureus and MRSA carriage were detected in 371 (31.1%) and 14 (1.2%) children, respectively. Variables found to be independently associated with an increased risk for S. aureus carriage included being older than 24 months (OR=1.8; 95%CI 1.3-2.6) and previous DCC attendance (OR=1.5; 95%CI 1.0-2.2). Having a mother with a high degree of education was a protective factor for nasal colonization (OR=0.4; 95%CI 0.2-0.8). Moreover, we observed that more children carrying MRSA had younger siblings compared to children not colonized by MRSA. Among the 14 MRSA strains, three SCCmec types (IIIA, IV and V) were detected, together with a multidrug resistant dominant MRSA lineage sharing 82.7% genetic similarity with the Brazilian clone (ST239-MRSA-IIIA). Although SCCmec type V was recovered from one healthy child who had been exposed to known risk factors for hospital associated MRSA, its genetic background was compatible with community-related MRSA. Our data suggest that DCC attendees could be contributing to MRSA cross-transmission between healthcare and community settings. |
[Detection of mecA gene in oxacillin-resistant coagulase-negative staphylococci isolated from the saliva of nursing professionals]
Rosa Jde O , de Moura JP , Palos MA , Gir E , Reis C , Kipnis A , Canini SR , Belissimo-Rodrigues F , Pimenta FC . Rev Soc Bras Med Trop 2009 42 (4) 398-403 ![]() Coagulase-negative staphylococci are frequently associated with nosocomial infections, and healthcare professionals can be reservoirs and spread them in hospitals and in the community. The aim of this study was to identify species of coagulase-negative staphylococci isolated from the saliva of nursing professionals, determine the resistance profile and detect the mecA gene. One hundred coagulase-negative staphylococci were selected: 41 were identified as Staphylococcus epidermidis, 25 as Staphylococcus saprophyticus, 18 as Staphylococcus haemolyticus, eight as Staphylococcus cohnii, four as Staphylococcus lugdunenses, three as Staphylococcus capitis and one as Staphylococcus simulans. Of these, 32% presented oxacillin resistance, 84.4% mupirocin resistance and 32% cefoxitin resistance, and all were vancomycin sensitive. Among the oxacillin-resistant coagulase-negative staphylococci, 93.7% developed in oxacillin agar (6microg/ml) and the mecA gene was detected in 75%. The results indicate that higher investments should be directed towards identifying coagulase-negative staphylococcus species in healthcare institutions and in the community. |
Rarely occurring 19A-like cps locus from a serotype 19F pneumococcal isolate indicates continued need of serology-based quality control for PCR-based serotype determinations
Pimenta FC , Gertz RE Jr , Roundtree A , Yu J , Nahm MH , McDonald RR , Carvalho Mda G , Beall BW . J Clin Microbiol 2009 47 (7) 2353-4 ![]() Determination of the DNA sequences corresponding to all 91 pneumococcal capsular biosynthetic (cps) loci (1, 3, 6, 9) has allowed serotype determinations from pneumococcal isolates and clinical specimens using conventional PCR assays (2, 4, 7, 8, 10). We developed sequential, multiplexed PCR schemes that resolve 33 serologic specificities, including 20 serotypes and 13 serotype subsets (4, 7, 8). We recently expanded the scheme to 40 specificities (www.cdc.gov/ncidod/biotech/strep/pcr.htm). | PCR primers targeted serotype-specific open reading frames within central portions of known cps loci (4, 7, 8). Subsequent information (1, 3, 6) revealed that we primarily targeted serotype-specific oligosaccharide repeat unit polymerases (wzy encoded), glycosyl transferases, and flippases (wzx encoded). Our serotype 19A primers, however, targeted the mnaA gene that encodes UDP-N-acetylglucosamine-2-epimerase (8). Although the mnaA sequence differs markedly among the 15 cps loci that harbor it (serotypes 19A, -B, -C, -F; 12A, -B, -F; 9A, -N, -L, -V; 4; 36; 44; 46), due to potential exchanges of heterologous mnaA genes, we recently changed the 19A PCR assay to target wzy (our unpublished data). The wzy19A and wzy19F genes putatively provide the basis of the structural difference between the related 19A and 19F capsules (1). |
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