Newton Sérgio de Carvalho

Universidade Federal do Paraná, Pontal do Paraná, Paraná, Brazil

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Publications (37)153.4 Total impact

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    ABSTRACT: HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15-25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (-128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine.
    Human vaccines & immunotherapeutics. 06/2014; 10(8).
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    ABSTRACT: Background. We examined risk of newly detected HPV infection and cervical abnormalities in relation to HPV-16/18 antibody levels at enrollment in PATRICIA (PApilloma TRIal against Cancer In young Adults; NCT00122681).Methods. Using Poisson regression, we compared risk of newly detected infection and cervical abnormalities associated with HPV-16/18 between seronegative versus seropositive women (15-25 years) in the control arm (DNA-negative at baseline for the corresponding HPV type [HPV-16: n=8193; HPV-18: n=8463]).Results. High titers of naturally-acquired HPV-16 antibodies and/or linear trend for increasing antibody levels were significantly associated with lower risk of incident and persistent infection, atypical squamous cells of undetermined significance or greater (ASC-US+), and cervical intraepithelial neoplasia grade 1, 2 or greater (CIN1+, CIN2+). For HPV-18, while seropositivity was associated with lower risk of ASC-US+ and CIN1+, no association between naturally-acquired antibodies and infection was demonstrated. Naturally-acquired HPV-16 antibody levels of 371 (95% confidence interval: 42-794), 204 (129-480) and 480 (250-5756) EU/mL were associated with 90% reduction of incident infection, 6-month persistent infection, and ASC-US+, respectively.Conclusions. Naturally-acquired antibodies to HPV-16, and to a lesser extent HPV-18, are associated with some reduced risk of subsequent infection and cervical abnormalities associated with the same HPV type.
    The Journal of Infectious Diseases 03/2014; · 5.85 Impact Factor
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    ABSTRACT: Background. Public Health England has reported a decrease of up to 20.8% in new diagnoses of external genital warts (GWs) among women aged <19 years since the national vaccination program with the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was performed to ascertain whether protection against low-risk HPV types was apparent. Methods. Vaccine efficacy (VE) at 48 months was assessed against 6-month persistent infection (6MPI) with low-risk HPV types in the total vaccinated cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. Results. In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5% (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5) for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. Conclusions. The HPV-16/18 AS04-adjuvanted vaccine appears to have moderate efficacy against persistent infections with a number of low-risk HPV types (HPV-6/11/74), which are responsible for the majority of external GWs, and recently, antibody and cell-mediated immune response to HPV-6/11 have been observed. These findings may help to explain the decrease in external GW diagnoses seen in England.
    The Journal of Infectious Diseases 11/2013; 208(9):1391-1396. · 5.85 Impact Factor
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    ABSTRACT: OBJECTIVE: We evaluated baseline data from the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681) on the association between behavioral risk factors and HPV infection and cervical abnormalities. METHODS: Women completed behavioral questionnaires at baseline. Prevalence of HPV infection and cervical abnormalities (detected by cytological or histological procedures) and association with behavioral risk factors were analyzed by univariate and stepwise multivariable logistic regressions. RESULTS: 16782 women completed questionnaires. Among 16748 women with data for HPV infection, 4059 (24.2%) were infected with any HPV type. Among 16757 women with data for cytological abnormalities, 1626 (9.7%) had a cytological abnormality, of whom 1170 (72.0%) were infected with at least one oncogenic HPV type including HPV-16 (22.7%) and HPV-18 (9.3%). Multivariable analysis (adjusted for age and region, N=14404) showed a significant association between infection with any HPV type and not living with a partner, smoking, age <15years at first sexual intercourse, higher number of sexual partners during the past 12months, longer duration of hormonal contraception and history of sexually transmitted infection (STI). For cervical abnormalities, only history of STI (excluding Chlamydia trachomatis) remained significant in the multivariable analysis after adjusting for HPV infection. CONCLUSIONS: Women reporting 3+ sexual partners in the past 12months had the highest risk of HPV infection at baseline. HPV infection was the main risk factor for cervical abnormalities, and history of STIs excluding Chlamydia trachomatis increased risk to a lesser extent. Although behavioral factors can influence risk, all sexually active women are susceptible to HPV infection.
    Gynecologic Oncology 08/2012; · 3.93 Impact Factor
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    ABSTRACT: This study aimed to compare cervical cancer screening by cervicography with screening by Pap test. This was a comparative multicenter study of cervical cytology and cervicography. The cervicography (slides of the cervix) was taken after the Pap test was completed. In total, samples were collected from 1176 patients. Colposcopy with biopsy was considered the gold standard for the final diagnosis of lesions observed by the Pap test and cervicography. Statistical analysis was performed using the binomial test. In cases in which the Pap test was negative for cervical lesions, diagnosis by cervicography was positive in 15 cases of cervical intraepithelial neoplasia 1 (CIN 1) (p = .00052), in 1 case of CIN 2, in 1 case of CIN 3, and in 1 case of cancer. However, cervicography produced 3 false-positive results (p < .0001). Cervicography may be used as a complementary screening method to the Pap test for cervical cancer.
    Journal of Lower Genital Tract Disease 05/2012; 16(4):387-93. · 1.21 Impact Factor
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    ABSTRACT: Prophylactic human papillomavirus (HPV) vaccines are now available and vaccination programs are being widely implemented, targeting adolescent girls prior to sexual debut. Since the risk of HPV exposure persists throughout a woman's sexual life, the duration of protection provided by vaccination is critical to the overall vaccine effectiveness. We report the long-term efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix (®) ) up to 8.4 y after the first vaccine dose. In an initial placebo-controlled study performed in US, Canada and Brazil, women aged 15-25 y with normal cervical cytology, HPV-16/18 seronegative by ELISA, DNA-negative for 14 oncogenic HPV types by PCR, received either the HPV-16/18 vaccine or placebo (n = 1,113). Subjects were followed up to 6.4 y after the first dose (n = 776). We report an additional 2-y follow-up for women enrolled from the Brazilian centers from the initial study (n = 436). During the current follow-up study (HPV-023, NCT00518336), no new infection or lesions associated with HPV-16/18 occurred in the vaccine group. Vaccine efficacy over the entire follow-up (up to 8.4 y) was 95.1% (84.6, 99.0) for incident infection, 100% (79.8, 100) for 6-mo persistent infection, 100% (56.1, 100) for 12-mo persistent infection and 100% (< 0, 100) for CIN2+ associated with HPV-16/18. All women in the vaccine group remained seropositive to both HPV-16/18, with antibody titers for total and neutralizing antibodies remaining several-folds above natural infection levels. The safety profile was clinically acceptable for both vaccine and control groups. This is, to date, the longest follow-up study for a licensed cervical cancer vaccine.
    Human vaccines & immunotherapeutics. 03/2012; 8(3):390-7.
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    ABSTRACT: Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5-100) in the TVC-naive and 45·7% (22·9-62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9-98·7) in the TVC-naive and 45·6% (28·8-58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15-17 year age group and progressively decreased in the 18-20 year and 21-25 year age groups. Vaccine efficacy against all AIS was 100% (31·0-100) and 76·9% (16·0-95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. GlaxoSmithKline Biologicals.
    The Lancet Oncology 11/2011; 13(1):89-99. · 25.12 Impact Factor
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    ABSTRACT: to determine the prevalence of Chlamydia and gonorrhea in a sample of women from Curitiba. this was a cross-sectional study with a sample of sexually active non-pregnant women aged between 16 and 23 years-old, with an intact uterus, with up to four sexual partners, without evidence of fever or purulent cervicitis, submitted to pelvic examination and PCR-based urine- testing for Chlamydia and gonorrhea. Exclusion criteria included: vaccination for HPV, vaccination history for the past 21 days, previous abnormal cytology, history of genital warts, splenectomy, immune disorders, and use of immunosuppressive drugs. An interview regarding sociodemographic and obstetric data and gynecological risk behavior for sexual transmitted diseases was applied. For statistical analysis, we used the χ(2) or Fisher's exact test to assess the association between variables. the prevalence of Chlamydia and gonorrhea infection in the study group was 10.7 and 1.5%, respectively, and the rate of coinfection was 0.9%. No correlation was found between the age range of the volunteers, the onset of sexual activity, the number of sexual partners and of new sexual partners in the last six months, and the presence of Chlamydia or gonorrhea. In women who had vaginal discharge or ectropion, the prevalence of Chlamydia infection was two times higher than in those without such signs. the results of this study were similar to national studies using PCR in urine samples for the detection of Chlamydia and gonorrhea in samples of non-pregnant women of the same age groups and with the same background. Since the volunteers with more than four sexual partners and those who had purulent endocervicitis were excluded, it is believed that the prevalence of Chlamydia and gonorrhea infection could have been greater in this population.
    Revista brasileira de ginecologia e obstetrićia: revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia 11/2011; 33(11):328-33.
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    ABSTRACT: In the last years, the prevalence of HPV infection in the anal region has increased, especially in some groups like homosexual and HIV-positive people. Since this infection can be associated with the development of squamous anal cancer due to its progression from HPV infection to anal intraepithelial neoplasia (AIN) and finally to cancer, the screening and evaluation of these conditions are important. Anal cytology and high resolution anoscopy are good methods that are available and can be used. Although useful, these methods should be performed correctly and not indiscriminately in all patients. Patients for whom anal cytology screening is recommended are: HIV-infected patients, homosexuals, women who present with high-grade vulvar squamous intraepithelial neoplasia, vulvar cancer or cervical cancer. An abnormal anal cytology should be further evaluated with high resolution anoscopy.
    The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 10/2011; 15(5):473-7. · 1.04 Impact Factor
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    ABSTRACT: To determine the prevalence of cervical human papillomavirus (HPV) infection and risk factors in young women from Brazil, Canada, and the USA. Cross-sectional study in 3204 healthy women, aged 15 to 25 years. Cervical samples were collected for cytology and for HPV DNA detection (SPF 10-LiPA 25 system). Serum samples were collected for the measurement of HPV-16 and HPV-18 antibodies by enzyme-linked immunosorbent assay. Risk factors were obtained through a questionnaire. Overall, 26.6% of women had DNA detected for at least 1 HPV type. The prevalence for oncogenic HPV types was 21.7% (25% in Brazil, 16.9% in Canada, and 19.1% in the USA). HPV-16 was the most prevalent oncogenic type (5.2%). The next most common oncogenic HPV types were 51 (3.3%), 52 (3.3%), 31 (2.9%), 66 (2.3%), and 39 (2.0%). Multiple oncogenic types were detected in one-third of the infections. The prevalence of HPV-16 and/or HPV-18 infections detected by DNA and/or enzyme-linked immunosorbent assay was 24.8%. The majority of women (85%) had a normal cervical cytology. Sexual behavior was the main determinant for HPV-16/18 infections and squamous intraepithelial lesions. The prevalence of HPV oncogenic infections was high and linked to sexual behavior. Strategies to reduce the burden of oncogenic HPV infection, such as prophylactic vaccination programs, are likely to impact the burden of disease due to cervical precancer and cancer.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 03/2011; 30(2):173-84. · 2.07 Impact Factor
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    ABSTRACT: Group B streptococcal (GBS) capsular polysaccharide (CPS)-based conjugate vaccine, which includes types Ia, Ib, II, III, and V, could potentially prevent neonatal, pediatric, adult, and pregnancy-associated diseases. However, since GBS CPS types included in that vaccine are prevalent serotypes found in North America and Europe, it may not provide the necessary protection for individuals in countries in which other capsular types have been found.
    Vaccine 03/2011; 29(21):3729-30. · 3.77 Impact Factor
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    ABSTRACT: the purpose of this research was to evaluate the morphological aspects and vasculature of the corpus luteum (CL) based on ultrasound parameters during early pregnancy and to assess their relationship with early pregnancy loss. this was a prospective cohort study of 90 pregnant patients between 6 and 8 weeks plus 6 days weeks of gestation. We included women at low risk, without acute or chronic systemic disease and with spontaneous conception. Exclusion criteria: use of drugs or smoking, drugs inducing ovulation, history of more than one abortion, no heartbeat visible in the embryo and impossibility of visualization of the corpus luteum. The size, volume, morphological aspects, resistive index, and peak systolic velocity of the corpus luteum were measured by transvaginal sonography. ninety patients were included in the study. Maternal age ranged from 15 to 41 years (mean 28.6 ± 5.8 years). The corpus luteum could be visualized in 87 patients (96.7%), 79 patients had normal pregnancies (90.1%), whereas spontaneous losses occurred in 8 cases (9.9%). In a comparison of the survivors and losses, there was no difference in mean CL diameter (21.8 versus 20.0 mm; p=0.108, Mann-Whitney test), mean CL volume (4.2 versus 3.0 cm³; p=0.076, Mann-Whitney test), mean resistive index (0.55 versus 0,58; p=0.220, Mann-Whitney test), peak systolic velocity (15 versus 15 cm/s; p=0.757, Mann-Whitney test). There was a positive relation between maternal age and resistive index. no apparent correlation was found between the morphological and vascular aspects of the corpus luteum in early normal pregnancies and first-trimester pregnancy losses.
    Revista brasileira de ginecologia e obstetrićia: revista da Federação Brasileira das Sociedades de Ginecologia e Obstetrícia 11/2010; 32(11):549-55.
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    ABSTRACT: One-hundred sixty-eight group B streptococcal (GBS) isolates from a Brazilian hospital were phenotypically and genotypically characterized. Isolates were recovered from human sources from April 2006 to May 2008 and classified as either invasive, noninvasive, or colonizing isolates. Classical methods for serotyping and antibiotic resistance profiling were employed. Clonal groups were also defined by pulsed-field gel electrophoresis (PFGE). Results showed that susceptibility to beta-lactam antimicrobials was predominant among the isolates. Only 4.7% were resistant to erythromycin and clindamycin. The erm(B) gene was widely detected in our GBS isolates, according to our phenotypic results (constitutive macrolide-lincosamide-streptogramin B [cMLSB] resistance phenotype), and the erm(A) gene was also detected in some isolates. MLSB resistance was restricted to strains isolated from patients with noninvasive infections and carriers. Serotype Ia was predominant (38.1%), serotype IV isolates were found at a high frequency (13.1%), and few isolates of serotype III were identified (3%). Pulsed-field gel electrophoresis results revealed a variety of types, reflecting the substantial genetic diversity among GBS strains, although a great number of isolates could be clustered into two major groups with a high degree of genetic relatedness. Three main PFGE clonal groups were found, and isolates sharing the same PFGE type were grouped into different serotypes. Furthermore, in a few cases, isolates from the same patients and possessing the same PFGE type were of different serotypes. These findings could be related to the occurrence of capsular switching by horizontal transfer of capsular genes.
    Journal of clinical microbiology 09/2010; 48(12):4397-403. · 4.16 Impact Factor
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    ABSTRACT: We report efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine up to 7.3 years post-vaccination. The study was conducted in a population (N=433) of women enrolled in Brazilian centres from an initial placebo-controlled study. Women were aged 15-25 years at first vaccination. During the most recent year of follow-up, approximately 7 years after initial vaccination, no cases of infection or cytohistological lesions associated with HPV-16/18 were observed in the vaccinees. Vaccine efficacy (95% confidence interval) up to 7.3 years was 94.5% (82.9, 98.9) for incident infection, 100% (55.7, 100) for 12-month persistent infection and 100% (-129.8, 100) for cervical intraepithelial neoplasia grade 2+. Antibody titres for total IgG and neutralising antibodies remained several folds above natural infection levels and >or=96% of women were seropositive. Vaccine safety was similar to placebo. This is the longest follow-up study for a licensed cervical cancer vaccine.
    Vaccine 08/2010; 28(38):6247-55. · 3.77 Impact Factor
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    ABSTRACT: To determine the relationship between human papillomavirus (HPV) and endometrial carcinogenesis by comparing data from women with endometrial carcinoma to those of women with normal endometrial tissue. The survey was conducted for 100 women (50 with endometrial carcinoma and 50 with normal endometrial tissue) through HPV-DNA testing of paraffin-embedded endometrial tissue sections by polymerase chain reaction. Age, cigarette consumption, squamous differentiation and tumor grade, endometrium trophism, and HPV types detected in endometrial tissues were studied. HPV estimated odds ratio was similar in endometrial carcinoma and in normal endometrial tissue. The presence of HPV was not associated with age, tobacco abuse, endometrial histology status, squamous differentiation, or tumoral grade. DNA sequences of HPV types 16 and 18 were the most frequently detected in both groups. An association between HPV and endometrial carcinoma was not observed.
    International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 08/2009; 28(4):322-7. · 2.07 Impact Factor
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    ABSTRACT: The present survey was conducted among medical students and physicians affiliated to the Federal University of Paraná, Curitiba, Brazil, between August 2006 and December 2007. 252 individuals responded to a questionnaire composed of 13 items regarding their individual status and their personal knowledge of the HPV vaccine properties. The data analysis that was carried out using chi-square test showed that 79.7% of the interviewed population would indicate the vaccine, and mostly, to girls aged 10-15 years old. While vaccine effectiveness and prophylaxis appeared to have been adequately understood, some of its properties such as safety and immunity duration still need further elucidation.
    Vaccine 06/2009; 27(20):2637-40. · 3.49 Impact Factor
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    Newton Sergio De Carvalho
    Arquivos de gastroenterologia 01/2009; 46(3):164-6.
  • International Journal of Gynecology & Obstetrics - INT J GYNECOL OBSTET. 01/2009; 107.
  • Newton Sergio De Carvalho
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    ABSTRACT: Prophylactic VLP-based vaccines effectively prevent papillomavirus infections with a high level of antibodies and safety. An 18% increased efficacy against CIN 2+ lesions associated with HPVs 16/18 has been observed with the appliance of the HPV16/18 AS04 adjuvanted recombinant vaccine.
    Vaccine 10/2008; 26(50):6293-4. · 3.49 Impact Factor
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    ABSTRACT: Group B Streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. We followed up 78 pregnant couples for < or =2 months to estimate the risk of GBS transmission. Among couples with discordant GBS status, we observed 1 male-to-female transmission event (1 of 3 couples in which the woman was GBS negative at enrollment), but no female-to-male transmission events (0 of 8 couples in which the man was GBS negative at enrollment).
    The Journal of Infectious Diseases 09/2008; 198(9):1375-8. · 5.85 Impact Factor

Publication Stats

2k Citations
153.40 Total Impact Points

Institutions

  • 2004–2014
    • Universidade Federal do Paraná
      • Hospital de Clínicas
      Pontal do Paraná, Paraná, Brazil
    • Geisel School of Medicine at Dartmouth
      • Department of Obstetrics and Gynecology
      Hanover, New Hampshire, United States
  • 2013
    • Queen Mary, University of London
      • Centre for Cancer Prevention
      London, ENG, United Kingdom
  • 2012
    • GlaxoSmithKline plc.
      Londinium, England, United Kingdom
  • 2011
    • University of Tampere
      • Department of Public Health
      Tampere, Western Finland, Finland
    • Secretariat of Health, Sao Paulo
      San Paulo, São Paulo, Brazil
  • 2010
    • Pontifícia Universidade Católica do Paraná (PUC-PR)
      Curityba, Paraná, Brazil
  • 2009
    • Federal University of Santa Catarina
      Nossa Senhora do Destêrro, Santa Catarina, Brazil
  • 2007
    • Visalia Medical Clinic
      Visalia, California, United States
    • University of Helsinki
      • Department of Obstetrics and Gynaecology
      Helsinki, Province of Southern Finland, Finland