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1.
Sci Rep ; 9(1): 19749, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874964

RESUMO

Women-who-have-sex-with-women (WSW) are at increased risk of bacterial vaginosis (BV). We investigated the impact of practices and past BV on the vaginal microbiota within a two-year longitudinal cohort of Australian WSW. Self-collected vaginal swabs were used to characterise the vaginal microbiota using 16S-rRNA gene sequencing. Hierarchical clustering defined community state types (CSTs). Bacterial diversity was calculated using the Shannon diversity index and instability of the vaginal microbiota was assessed by change of CST and Bray-Curtis dissimilarity. Sex with a new partner increased the bacterial diversity (adjusted-coefficient = 0.41, 95%CI: 0.21,0.60, p < 0.001) and instability of the vaginal microbiota, in terms of both change of CST (adjusted-odds-ratio = 2.65, 95%CI: 1.34,5.22, p = 0.005) and increased Bray-Curtis dissimilarity (adjusted-coefficient = 0.21, 95%CI: 0.11,0.31, p < 0.001). Women reporting sex with a new partner were more likely than women reporting no new partner to have a vaginal microbiota characterised by Gardnerella vaginalis (adjusted-relative-risk-ratio[aRRR] = 3.45, 95%CI: 1.42,8.41, p = 0.006) or anaerobic BV-associated bacteria (aRRR = 3.62, 95%CI: 1.43,9.14, p = 0.007) relative to a Lactobacillus crispatus dominated microbiota. Sex with a new partner altered the vaginal microbiota of WSW by increasing the diversity and abundance of BV-associated bacteria. These findings highlight the influence of practices on the development of a non-optimal vaginal microbiota and provide microbiological support for the sexual exchange of bacteria between women.

2.
Vaccine ; 37(46): 6907-6914, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31562001

RESUMO

BACKGROUND: Australia introduced a school-based human papillomavirus (HPV) vaccination program for females aged 12-13 years in 2007, with a three-year catch-up to age 26; and for boys aged 12-13 from 2013, with a two-year catch-up to age 15. This study aimed to compare the prevalence of penile HPV between teenage heterosexual males in cohorts eligible or non-eligible for the school-based male vaccination program. METHODS: Between 2014 and 2017, sexually active heterosexual males aged 17-19 were recruited from sexual health centres and community sources across Australia. Males provided a self-collected penile swab for 37 HPV genotypes using Roche Linear Array and completed a questionnaire. We calculated adjusted prevalence ratios (aPR) of HPV between males in two periods: 2014-2015 (preceding implementation of school-based male vaccination) and 2016-2017 (eligible for school-based male vaccination). Self-reported vaccine doses were confirmed with doses reported to the National HPV Vaccination Program Register. RESULTS: Overall, 152 males were recruited in 2014-2015 and 146 in 2016-2017. Numbers of female sex partners and condom use did not differ between the two periods. The prevalence of quadrivalent vaccine-preventable [4vHPV] genotypes (6/11/16/18) was low in both periods (2.6% [2014-15] versus 0.7% [2016-17]; p = 0.371; aPR 0.28 [95% CI: 0.03-2.62]). Compared with men in 2014-2015, men in 2016-2017 had a lower prevalence of any of the 37 HPV genotypes tested (21.7% versus 11.6%; aPR 0.62 [95% CI: 0.36-1.07]) and any of the 13 high-risk genotypes tested (15.8% versus 7.5%; aPR 0.59 [95% CI: 0.30-1.19]). Prevalence of low-risk HPV genotypes did not differ between the two periods. Of the males recruited in 2016-2017, 55% had received ≥1 vaccine dose. CONCLUSION: The prevalence of 4vHPV genotypes among teenage heterosexual males in both cohorts was low, presumably due to herd protection from the female-only vaccination program. Further studies are required to determine the impact of universal HPV vaccination on HPV prevalence in males.

3.
Lancet Infect Dis ; 19(8): 833-842, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31196813

RESUMO

BACKGROUND: Antibiotic-resistant gonorrhoea represents a global public health threat, and new therapies are needed. We aimed to compare the efficacy and safety of solithromycin, a fourth generation macrolide, with ceftriaxone plus azithromycin for the treatment of gonorrhoea. METHODS: We did an open-label, multicentre, non-inferiority trial of patients aged 15 years or older with uncomplicated untreated genital gonorrhoea at two sites in Australia and one site in the USA. Patients were randomly assigned (1:1) to receive single dose oral solithromycin 1000 mg or intramuscular ceftriaxone 500 mg plus oral azithromycin 1000 mg. Neisseria gonorrhoeae cultures were obtained at baseline and test of cure (day 7 ±â€ˆ2). The primary outcome was the proportion of patients with eradication of genital N gonorrhoeae based on culture at test of cure, assessed in the microbiological intention-to-treat (mITT) population, which included all randomly assigned patients who received any dose of study drug and had a positive genital culture for N gonorrhoeae at baseline. Non-inferiority of solithromycin was to be concluded if the lower limit of the 95% CI for the between-group differences was greater than -10%. Safety was analysed in all patients who received any dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02210325. FINDINGS: Between Sept 3, 2014, and Aug 27, 2015, 262 patients were randomly assigned and 261 received treatment (130 in the solithromycin group and 131 in the ceftriaxone plus azithromycin group). In the mITT population, 99 (80%) of 123 patients in the solithromycin group and 109 (84%) of 129 patients in the ceftriaxone plus azithromycin group had N gonorrhoeae eradication at test of cure (difference -4·0%, 95% CI -13·6 to 5·5), thus solithromycin did not meet the criterion for non-inferiority at the prespecified -10% margin. The frequency of adverse events was higher in the solithromycin group than the ceftriaxone plus azithromycin group (69 [53%] of 130 patients vs 45 [34%] of 131 patients), the most common of which were diarrhoea (31 [24%] of 130 patients vs 20 [15%] of 131 patients), and nausea (27 [21%] of 130 patients vs 15 [11%] of 131 patients). INTERPRETATION: Solithromycin as a single 1000 mg dose is not a suitable alternative to ceftriaxone plus azithromycin as first-line treatment for gonorrhoea. If insufficient duration of solithromycin exposure at the infection site in a subset of individuals was the reason for treatment failures, this might be adequately addressed with dose adjustment. However, any further trials with longer dosing need to consider the potential risk of gastrointestinal effects and liver enzyme elevations. FUNDING: Cempra Pharmaceuticals.

4.
BMC Microbiol ; 18(1): 184, 2018 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424728

RESUMO

BACKGROUND: The ProPrems trial, a multi-center, double-blind, placebo-controlled randomized trial, previously reported a 54% reduction in necrotizing enterocolitis (NEC) of Bell stage 2 or more from 4.4 to 2.0% in 1099 infants born before 32 completed weeks' gestation and weighing < 1500 g, receiving probiotic supplementation (with Bifidobacterium longum subsp. infantis BB-02, Streptococcus thermophilus TH-4 and Bifidobacterium animalis subsp. lactis BB-12). This sub-study investigated the effect of probiotic supplementation on the gut microbiota in a cohort of very preterm infants in ProPrems. RESULTS: Bifidobacterium was found in higher abundance in infants who received the probiotics (AOR 17.22; 95% CI, 3.49-84.99, p < 0.001) as compared to the placebo group, and Enterococcus was reduced in infants receiving the probiotic during the supplementation period (AOR 0.27; 95% CI, 0.09-0.82, p = 0.02). CONCLUSION: Probiotic supplementation with BB-02, TH-4 and BB-12 from soon after birth increased the abundance of Bifidobacterium in the gut microbiota of very preterm infants. Increased abundance of Bifidobacterium soon after birth may be associated with reducing the risk of NEC in very preterm infants.


Assuntos
Suplementos Nutricionais/análise , Enterocolite Necrosante/prevenção & controle , Microbioma Gastrointestinal , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Probióticos/administração & dosagem , Bifidobacterium/genética , Bifidobacterium/isolamento & purificação , Bifidobacterium/efeitos da radiação , Estudos de Coortes , Método Duplo-Cego , Enterocolite Necrosante/microbiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Streptococcus thermophilus/genética , Streptococcus thermophilus/isolamento & purificação , Streptococcus thermophilus/fisiologia
5.
Papillomavirus Res ; 6: 70-76, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30391365

RESUMO

The performance of different clinical screening algorithms comprising point-of-care HPV-DNA testing using self-collected vaginal ('V') specimens, and visual inspection of the cervix with acetic acid (VIA) was evaluated in Papua New Guinea. Women aged 30-59 years provided V specimens that were tested at point-of-care using the Xpert HPV Test (Cepheid, Sunnyvale, CA). A clinician-collected cervical ('C') specimen was then collected for point-of-care Xpert testing, and liquid-based cytology (LBC). Following this, VIA examination was conducted, blind to HPV test results, and ablative cervical cryotherapy provided if indicated. Detection of high-grade squamous intraepithelial lesion (HSIL) by LBC was the reference standard used to evaluate clinical screening algorithms. Of 1005 women, 36 had HSIL+. Xpert HPV Test performance using V specimens (sensitivity 91.7%, specificity 87.0%, PPV 34.0%, NPV 99.3%) was superior to VIA examination alone (51.5%, 81.4%, 17.5%, 95.6% respectively) in predicting underlying HSIL+. A screening algorithm comprising V specimen HPV testing followed by VIA examination had low sensitivity (45.5%) but comparable specificity, PPV and NPV to HPV testing alone (96.3%, 45.5%, 96.3% respectively). A 'test-and-treat' screening algorithm based on point-of-care HPV testing of V specimens had superior performance compared with either VIA examination alone, or a combined screening algorithm comprising HPV testing plus VIA.


Assuntos
Técnicas Citológicas/métodos , DNA Viral/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , Manejo de Espécimes/métodos , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Vagina/virologia , Ácido Acético/administração & dosagem , Adulto , Algoritmos , Colo do Útero/patologia , DNA Viral/genética , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Indicadores e Reagentes , Pessoa de Meia-Idade , Papua Nova Guiné , Autoexame/métodos , Sensibilidade e Especificidade
6.
Lancet Infect Dis ; 18(10): 1117-1126, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30303108

RESUMO

BACKGROUND: Timely diagnosis and treatment of sexually transmissible infections will prevent morbidity and onward transmission. We aimed to assess the efficacy of a point-of-care molecular test for Chlamydia trachomatis and Neisseria gonorrhoeae infections at the cluster level to improve infection management among Indigenous Australian communities with high prevalence of sexually transmissible infections. METHODS: In this cluster-randomised crossover study, we recruited primary health services in Western Australia, Far North Queensland, and South Australia that provide care to Indigenous people in regional or remote locations. The services were eligible if they did 150 or more tests for C trachomatis or N gonorrhoeae infection per year among individuals aged 16-29 years, and if C trachomatis or N gonorrhoeae positivity was 10% or higher. Services were randomly assigned (1:1) by use of a random-number generator, stratified by geographical region, to either standard care conditions with routine laboratory-based sexually transmissible infection testing for 12 months followed by 12 months of intervention with molecular point-of-care testing, or the reverse sequence. The primary outcome was the proportion of people (aged 16-29 years) found to have C trachomatis or N gonorrhoeae who had a positive result at retesting 3 weeks to 3 months after treatment, and a secondary outcome was treatment within 7 days, both in those aged 16-29 years and at the cluster level. We did these analyses using data from all participants who had a positive result at testing, by point-of-care of laboratory testing (ie, the intention-to-treat population). The trial is registered with Australian and New Zealand Clinical Trials Registry (ACTRN12613000808741). FINDINGS: Between June 1, 2013, and Feb 29, 2016, 12 health services were enrolled and randomly assigned to standard care followed by intervention (six) and the reverse sequence (six). After randomisation, one health service that was initially assigned to standard care was excluded because it no longer met the inclusion criteria. 455 individuals tested positive for C trachomatis or N gonorrhoeae infection in the intervention group, and 405 tested positive in the standard care group. In the intervention group, 12 (19%) of 63 individuals retested had a positive test result, compared with nine (13%) of 67 with positive retests in the standard care group (relative ratio [RR] 1·42, 95% CI 0·64-3·13; p=0·405), and 347 (76%) were treated within 7 days in the intervention group, compared with 191 (47%) in the standard care group (RR 1·66, 1·41-1·93; p<0·0001). INTERPRETATION: Retesting rates were too low to draw conclusions on the effect of the intervention on repeat infections. Further research will be needed to determine whether point-of-care tests have an effect on reinfection rates, and the sustainability of using this technology. However, our findings show that time to treatment of C trachomatis or N gonorrhoeae infections in primary care clinics in remote areas in Australia with a high prevalence of sexually transmissible infections could be substantially reduced by the use of molecular point-of-care tests. FUNDING: The National Health and Medical Research Council, Australia.


Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis , Gonorreia/diagnóstico , Testes Imediatos , Atenção Primária à Saúde , Adolescente , Adulto , Austrália , Infecções por Chlamydia/prevenção & controle , Estudos Cross-Over , Feminino , Gonorreia/prevenção & controle , Humanos , Masculino , Adulto Jovem
7.
J Med Microbiol ; 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30303481

RESUMO

PURPOSE: Chlamydia trachomatis is responsible for trachoma-associated blindness as well as the most common sexually transmitted bacterial infection worldwide, although the genovars for the former are typically A-C, whilst for the latter they are D-K and for the uncommon infection lymphogranuloma venereum they are L1-3. Nucleotide variations within the ompA gene facilitate the identification of C. trachomatis genovars. This study describes a colorimetric multiplex PCR/RLB typing assay (mPCR-RLB) directed to the VD2 region of the ompA gene for general C. trachomatis positivity and the identification of 14 individual C. trachomatis genovars. METHODOLOGY: The assay was validated by analysing 40 blinded samples that included reference strains of C. trachomatis genovars and other non-chlamydial micro-organisms that had been analysed previously using quantitative PCR (qPCR). Ninety clinical samples that had previously been found to be C. trachomatis-positive by qPCR were also evaluated using the mPCR-RLB assay. RESULTS: The mPCR-RLB assay showed 100 % agreement with the qPCR in the detection of C. trachomatis reference strains and no cross-reaction of non-chlamydial micro-organisms was observed. In the analysis of the chlamydial clinical samples, 97.8 % were C. trachomatis-positive by mPCR/RLB assay and there was a 96.6 % concordance with the qPCR at the group identification level and a 92.2 % concordance at the genovar level. CONCLUSION: The mPCR-RLB assay is a rapid and sensitive methodology for the identification of C. trachomatis genovars associated with urogenital infections, trachoma or lymphogranuloma venereum diseases that can be implemented in clinical settings, helping to identify reinfections and treatment failures and establish the appropriate treatment course.

8.
Eur J Clin Microbiol Infect Dis ; 37(11): 2117-2122, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30109584

RESUMO

Spontaneous resolution of urogenital Chlamydia trachomatis (CT) without treatment has previously been described, but a limitation of these reports is that DNA or RNA-based amplification tests used do not differentiate between viable infection and non-viable DNA. We modified a previously published CT mRNA detection (omp2) method to differentiate between viable infection and non-viable DNA in a sample of CT DNA PCR positive women. We modified a CT mRNA detection (omp2) method from reverse transcriptase qPCR (RTqPCR) to digital PCR (dPCR) and evaluated it in samples from CT DNA positive women. Firstly, CT infected McCoy B cells treated with azithromycin in vitro identified detectable mRNA levels disappeared <2 days, while DNA persisted up to 6 days. We used 55 self-collected vaginal swabs from a cohort of women diagnosed as DNA positive for chlamydia obtained pre- and 7 days of post-azithromycin treatment. Concordance with DNA results was higher for dPCR than RTqPCR (74.5% versus 65.5%). At visit 1, there was a strong linear relationship between DNA and mRNA (r = 0.9, p < 0.000); 24 samples had both mRNA and DNA detected (82.8%) and 5 had only DNA detected with a potential false positive proportion of 17.2% (95%CI: 5.8, 35.8). At visit 2, there was poor correlation between DNA and mRNA (r = 0.14, p = 0.55); eight specimens had only DNA detected (42.1%; 95%CI: 20.25, 66.50) and one had mRNA detected. DNA detection methods alone may detect non-viable DNA. Consideration should be given to further develop mRNA assays as ancillary tests to improve detection of viable chlamydia.


Assuntos
Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/genética , RNA Bacteriano , RNA Mensageiro , Reação em Cadeia da Polimerase em Tempo Real , Carga Bacteriana , Biomarcadores , Feminino , Humanos , Viabilidade Microbiana
9.
J Infect Dis ; 218(12): 2006-2015, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-30099516

RESUMO

Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods: Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent. Results: The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.


Assuntos
Predisposição Genética para Doença , Antígenos HLA-C/genética , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Receptores KIR/genética , Neoplasias do Colo do Útero/virologia , Estudos de Casos e Controles , Feminino , Dosagem de Genes , Genótipo , Antígenos HLA-C/imunologia , Papillomavirus Humano 16 , Humanos , Polimorfismo de Nucleotídeo Único , Receptores KIR/imunologia
10.
Pathology ; 50(6): 659-664, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30139535

RESUMO

Human papillomavirus (HPV) DNA testing has become routine in many diagnostic laboratories, particularly with changes from cervical cytology to HPV DNA as primary screening as of 1 December 2017 in Australia. External quality assurance (EQA) is essential for assessment of laboratory performance once HPV testing is implemented. The aim of this study was to develop a pilot program to evaluate and determine stability of material that could be utilised in an ongoing external quality assurance program (EQAP). Two sample types were evaluated: cells in PreservCyt solution (ThinPrep) from stored clinical specimens and HPV-seeded swabs. Two panels sent 5 months apart were distributed to 18 Australian and two New Zealand laboratories (participants) for testing by Hybrid Capture 2 (HC2) or alternative molecular methods. Participants were given 1 month to test specimens. Eight ThinPrep specimens in Panel 1 were reported correctly by 73% (11/15) of HC2 participants and 40% (2/5) of participants performing alternative methods. Of eight dry swab specimens, 58% (23/40) and 78% (25/32) were correctly identified by HC2 and alternative methods, respectively. Panel 2 included four ThinPrep and two swab specimens. ThinPrep specimens were reported correctly by 100% (60/60) of participants utilising HC2 and 95% (19/20) utilising alternative methods. Dry swab specimens were reported correctly by 89% (25/28) of participants utilising HC2 and 100% (10/10) of participants utilising alternative methods. These results indicate that both specimen types are suitable for utilisation in an EQAP and outline some issues of EQAP for ongoing assessment of HPV molecular methods in diagnostic molecular laboratories.


Assuntos
DNA Viral/isolamento & purificação , Programas de Rastreamento/normas , Técnicas de Diagnóstico Molecular/normas , Infecções por Papillomavirus/diagnóstico , Garantia da Qualidade dos Cuidados de Saúde , Adulto , Idoso , Austrália , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/métodos , Nova Zelândia , Infecções por Papillomavirus/complicações , Projetos Piloto , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia
11.
Oncol Lett ; 16(2): 2511-2516, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30013645

RESUMO

Certain variants of human papillomavirus (HPV)type 58 are associated with an increased risk of high grade squamous intraepithelial lesions and cervical cancer. However, little is known about the persistence of HPV58 E6/E7 variants in women with incident HPV58 infections. The aim of the present study was to evaluate the presence and persistence of HPV58 E6/E7 variants in 71 women with incident HPV58 infection throughout their follow-up. These women belonged to a cohort examined in a longitudinal study of 1,610 Colombian women, who were HPV-negative and had normal baseline cytology. E6/E7 DNA regions of HPV58-positive samples were amplified and sequenced using automated direct sequencing. A total of 639 samples were analyzed from the 71 women, and 117 samples (18.3%) were HPV58-positive. HPV58 E6/E7 variants were detected in 85.5% of the samples. The T307/A694/G744/A761 variant was identified in 88% of the samples, the T307/G744 variant was identified in 9% of samples and the T187/T307/A367/G744/G793/T798/A801/T840/C852 was identified in 3% of the samples. Overall, 50% of the HPV58 infections were present after 1 year of follow-up and all infections were cleared after 7 years. Women who had first sexual intercourse at >15 years of age had a lower clearance rate than those who had sexual intercourse for the first time at ≤15 years of age [hazard ratio (HR)=0.29; 95% confidence interval (CI)=0.09-0.92]. Likewise, parous women had a higher clearance rate than nulliparous women (HR=3.43, 95% CI=1.23-9.60). There was no difference in clearance rates between HPV58 E6/E7 variants. In conclusion, HPV58 variants were not associated with persistence of the infection in this group of women.

12.
Open Forum Infect Dis ; 5(7): ofy147, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30019002

RESUMO

Background: This study examined the cellular immunity of 0, 1, 2, and 3 doses of Gardasil vaccine (4vHPV) in girls after 6 years and their responses to a subsequent dose of Cervarix vaccine (2vHPV). Methods: A subset of girls (n = 59) who previously received 0, 1, 2, or 3 doses of 4vHPV 6 years earlier were randomly selected from a cohort study of Fijian girls (age 15-19 years). Blood was collected before and 28 days after a dose of 2vHPV. The HPV16- and HPV18-specific cellular immune response was determined by IFNγ-ELISPOT and by measurement of cytokines in peripheral blood mononuclear cell supernatants. Results: Six years after 4vHPV vaccination, HPV18-specific responses were significantly lower in the 1- (1D) or 2-dose (2D) recipients compared with 3-dose recipients (2D: IFNγ-ELISPOT: P = .008; cytokines, IFNγ: P = .002; IL-2: P = .022; TNFα: P = .016; IL-10: P = .018; 1D: IL-2: P = .031; IL-10: P = .014). These differences were no longer significant post-2vHPV. No significant differences in HPV16 responses (except IL-2, P < .05) were observed between the 2- or 1-dose recipients and 3-dose recipients. Conclusions: These data suggest that cellular immunity following reduced-dose schedules was detectable after 6 years, although the responses were variable between HPV types and dosage groups. The clinical significance of this is unknown. Further studies on the impact of reduced dose schedules are needed, particularly in high-disease burden settings.

13.
Vaccine ; 36(29): 4311-4316, 2018 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-29880245

RESUMO

BACKGROUND: Cervical cancer occurrence and mortality are strongly correlated with socioeconomic disadvantage, largely due to unequal access to screening and treatment. Universal human papillomavirus (HPV) vaccination provides the opportunity to greatly reduce this global health disparity. Australian Indigenous women have substantially higher rates of cervical cancer than non-Indigenous women, primarily due to under-screening. We investigated HPV infection rates in Indigenous women 7 years after implementation of the national HPV vaccination program. METHODS: We used a repeat cross-sectional design, with the baseline being provided by an HPV prevalence survey among Indigenous women attending clinics for cervical cytology screening, prior to the start of the vaccination program in 2007. We returned to clinics in four locations during 2014-15, and invited women aged 18-26 years attending for screening to provide a cervical specimen for HPV testing, as well as to complete a short questionnaire and consent to allow access of their records in the National HPV Vaccination Program Register. We used well-established laboratory methods to test specimens for specific HPV genotypes. RESULTS: A total of 142 women were recruited at participating sites and compared to 155 who had been recruited at the same locations in the 2007 pre-vaccine survey. The two groups were identical in regard to age, with the more recent group having a higher proportion of hormonal contraception users, and a lower proportion of smokers. The proportion found to have any HPV type fell from 58 to 36% with the decline being entirely due to reductions in vaccine types, which fell by 94% from 24 to 1.4%. CONCLUSION: Australia's national HPV vaccination program appears to be successfully protecting a very high proportion of Indigenous women against vaccine targeted HPV types, who have in the past been at elevated risk of cervical cancer.


Assuntos
Colo do Útero/virologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Adolescente , Adulto , Austrália/epidemiologia , Estudos Transversais , Feminino , Genótipo , Humanos , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Grupos Populacionais , Prevalência , Adulto Jovem
14.
Sex Transm Infect ; 94(5): 340-345, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29748180

RESUMO

OBJECTIVES: A new molecular test for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) (GeneXpert CT/NG) has been demonstrated to be as accurate as conventional nucleic acid amplification tests (NAAT), but performance has not been evaluated in routine primary care, performed at the point of care by clinicians. We aimed to examine its diagnostic performance when used by clinicians in remote community health services in Australia with high prevalences of CT and NG infection. The trial was registered with the Australian and New Zealand Clinical Trials Registry (#12613000808741) METHODS: At 12 health services, training was provided to 99 clinicians in the use of the GeneXpert CT/NG assay who tested specimens from all patients undergoing STI screening. Specimens were also sent in parallel for conventional laboratory-based NAATs and the concordance of results was evaluated. RESULTS: Clinicians conducted 2486 tests: CT concordance was 99.4% (95% CI 99.1 to 99.7) with a positive concordance of 98.6% (95% CI 95.9 to 99.7) and negative concordance of 99.5% (95% CI 99.1 to 99.8); NG concordance was 99.9% (95% CI 99.7 to 100.0) with a positive concordance of 100.0% (95% CI 97.5 to 100.0) and negative concordance of 99.9% (95% CI 99.7 to 100.0). CONCLUSIONS: In this first study reporting routine point-of-care use of GeneXpert CT/NG by primary care clinicians, we found excellent concordance with conventional NAATs. The use of the GeneXpert CT/NG at the point of care could potentially transform management and control of these infections in many endemic settings, including low/middle-income countries.


Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/genética , Gonorreia/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Neisseria gonorrhoeae/genética , Testes Imediatos , Austrália/epidemiologia , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Centros Comunitários de Saúde , Estudos Cross-Over , Feminino , Gonorreia/epidemiologia , Humanos , Masculino , Técnicas de Diagnóstico Molecular/instrumentação , Neisseria gonorrhoeae/isolamento & purificação , Nova Zelândia/epidemiologia , Técnicas de Amplificação de Ácido Nucleico , Grupo com Ancestrais Oceânicos , Médicos de Atenção Primária , Atenção Primária à Saúde/estatística & dados numéricos , Manejo de Espécimes/métodos
15.
Vaccine ; 36(23): 3221-3230, 2018 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-29724506

RESUMO

OBJECTIVES: The VACCINE [Vaccine Against Cervical Cancer Impact and Effectiveness] study evaluated the prevalence of quadrivalent vaccine-targeted human papillomavirus (HPV) genotypes (HPV 6, 11, 16, 18) amongst young women of vaccine-eligible age. METHODS: Between October 2011 - June 2015, women aged 18-25 years from Victoria, Australia, were recruited through targeted advertising on the social networking website Facebook. Participants completed an online questionnaire and provided a self-collected vaginal swab for HPV DNA detection and genotyping (Linear Array HPV genotyping assay). Self-reported HPV vaccination details were verified with the National HPV Vaccination Program Register (NHVPR). RESULTS: Of 1223 who agreed to participate, 916 (74.9%) completed the survey and, for 1007 (82.3%) sexually-active participants, 744 (73.9%) returned the self-collected swab, of which 737 contained detectable DNA. 184/737 (25.0%) were positive for HPV. Vaccine-targeted HPV genotypes were detected in only 13 (1.7%) women: 11 HPV 16 (six vaccinated after sexual debut, five unvaccinated) and two HPV 6. Prevalence of any of HPV 31/33/45 collectively was 2.9%, varying significantly by vaccination status (fully 2.0%, unvaccinated 6.8%; p = 0.01). Vaccination rates among the sexually-active cohort were high, with 65.6%, 71.6% and 74.2% of participants having received three, at least two or at least one dose of vaccine, respectively. Of women self-reporting HPV vaccination, the NHVPR confirmed one or more doses were received in 90%. Strong associations were observed between vaccination status, age, language spoken at home and country of birth, as well as between HPV detection and the number of male sexual partners. CONCLUSION: Surveillance five to eight years' post-initiation of a national HPV vaccination program demonstrated a consistent and very low prevalence of vaccine-related HPV genotypes and some evidence of cross protection against related types amongst vaccine-eligible women from Victoria, Australia.


Assuntos
Alphapapillomavirus/genética , Programas de Imunização/estatística & dados numéricos , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/uso terapêutico , Adolescente , Adulto , Alphapapillomavirus/imunologia , Alphapapillomavirus/patogenicidade , Colo do Útero/virologia , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/imunologia , Humanos , Masculino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Prevalência , Comportamento Sexual , Fatores Socioeconômicos , Vitória/epidemiologia
17.
J Infect Dis ; 217(10): 1590-1600, 2018 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-29425358

RESUMO

Introduction: A quadrivalent human papillomavirus vaccination program targeting females aged 12-13 years commenced in Australia in 2007, with catch-up vaccination of 14-26 year olds through 2009. We evaluated the program's impact on HPV prevalence among women aged 18-35 in 2015. Methods: HPV prevalence among women aged 18-24 and 25-35 was compared with prevalence in these age groups in 2005-2007. For women aged 18-24, we also compared prevalence with that in a postvaccine study conducted in 2010-2012. Results: For the 2015 sample, Vaccination Register-confirmed 3-dose coverage was 53.3% (65.0% and 40.3% aged 18-24 and 25-35, respectively). Prevalence of vaccine HPV types decreased from 22.7% (2005-2007) and 7.3% (2010-2012), to 1.5% (2015) (P trend < .001) among women aged 18-24, and from 11.8% (2005-2007) to 1.1% (2015) (P = .001) among those aged 25-35. Conclusions: This study, reporting the longest surveillance follow-up to date, shows prevalence of vaccine-targeted HPV types has continued to decline among young women. A substantial fall also occurred in women aged 25-35, despite lower coverage. Strong herd protection and effectiveness of less than 3 vaccine doses likely contributed to these reductions.


Assuntos
Papillomaviridae/imunologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/imunologia , Vacinas contra Papillomavirus/imunologia , Adolescente , Adulto , Austrália/epidemiologia , Feminino , Humanos , Programas de Imunização/métodos , Prevalência , Vacinação/métodos , Adulto Jovem
18.
PLoS One ; 13(1): e0190199, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29293559

RESUMO

OBJECTIVES: Recurrence following recommended treatment for bacterial vaginosis is unacceptably high. While the pathogenesis of recurrence is not well understood, recent evidence indicates re-infection from sexual partners is likely to play a role. The aim of this study was to assess the acceptability and tolerability of topical and oral antimicrobial therapy in male partners of women with bacterial vaginosis (BV), and to investigate the impact of dual-partner treatment on the vaginal and penile microbiota. METHODS: Women with symptomatic BV (Nugent Score of 4-10 and ≥3 Amsel criteria) and their regular male sexual partner were recruited from Melbourne Sexual Health Centre, Melbourne, Australia. Women received oral metronidazole 400mg twice daily (or intra-vaginal 2% clindamycin cream, if contraindicated) for 7-days. Male partners received oral metronidazole 400mg twice daily and 2% clindamycin cream topically to the penile skin twice daily for 7-days. Couples provided self-collected genital specimens and completed questionnaires at enrolment and then weekly for 4-weeks. Genital microbiota composition was determined by 16S rRNA gene sequencing. Changes in genital microbiota composition were assessed by Bray-Curtis index. Bacterial diversity was measured by the Shannon Diversity Index. RESULTS: Twenty-two couples were recruited. Sixteen couples (76%) completed all study procedures. Adherence was high; most participants took >90% of prescribed medication. Medication, and particularly topical clindamycin in males, was well tolerated. Dual-partner treatment had an immediate and sustained effect on the composition of vaginal microbiota (median Bray-Curtis score day 0 versus day 8 = 0.03 [IQR 0-0.15], day 0 vs day 28 = 0.03 [0.02-0.11]). We observed a reduction in bacterial diversity of the vaginal microbiota and a decrease in the prevalence and abundance of BV-associated bacteria following treatment. Treatment had an immediate effect on the composition of the cutaneous penile microbiota (median Bray-Curtis score day 0 vs day 8 = 0.09 [0.04-0.17]), however this was not as pronounced at day 28 (median Bray-Curtis score day 0 vs day 28 = 0.38 [0.11-0.59]). A decrease in the prevalence and abundance of BV-associated bacteria in the cutaneous penile microbiota was observed immediately following treatment at day 8. CONCLUSION: Combined oral and topical treatment of male partners of women with BV is acceptable and well tolerated. The combined acceptability and microbiological data presented in this paper supports the need for larger studies with longer follow up to characterize the sustained effect of dual partner treatment on the genital microbiota of couples and assess the impact on BV recurrence.


Assuntos
Antibacterianos/uso terapêutico , Pênis/microbiologia , Parceiros Sexuais , Vagina/microbiologia , Vaginose Bacteriana/tratamento farmacológico , Administração Oral , Administração Tópica , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Feminino , Humanos , Masculino , Microbiota , Projetos Piloto , Pele/microbiologia
19.
Emerg Infect Dis ; 24(2): 328-335, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29350154

RESUMO

High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10 increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.


Assuntos
Antibacterianos/farmacologia , Macrolídeos/farmacologia , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/efeitos dos fármacos , Pristinamicina/uso terapêutico , Adulto , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Infecções por Mycoplasma/microbiologia , Mycoplasma genitalium/genética
20.
Aust N Z J Obstet Gynaecol ; 58(5): 576-581, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29380356

RESUMO

BACKGROUND: Papua New Guinea (PNG) has among the highest estimated burdens of cervical cancer globally but currently has no national cervical screening program. Visual inspection of the cervix with acetic acid (VIA) is a low-cost screening strategy endorsed by the World Health Organization that has been adopted in many low-resource settings but not previously evaluated in PNG. AIM: To evaluate the association between VIA examination findings and high-risk HPV (hrHPV) infection; and the impact of concomitant genital Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis on the interpretation of VIA findings. METHODS: A prospective clinical cohort study among women aged 30-59 years attending Well Woman Clinics in PNG. Main outcome measures were VIA examination findings and laboratory-confirmed hrHPV, C. trachomatis, N. gonorrhoeae and T. vaginalis. RESULTS: A total of 614 women were enrolled, of whom 87.5% (537/614) underwent VIA, and 12.5% (77/614) did not due to pre-existing cervicitis or inability to visualise the transformation zone. Among the 537 women who underwent VIA, 21.6% were VIA positive, 63.7% VIA negative, and 14.7% had indeterminate findings. The prevalence of hrHPV infection (n = 614) was 14.7%; C. trachomatis, 7.5%; N. gonorrhoeae, 8.0%; and T. vaginalis, 15.0%. VIA positive women were more likely to have HPV16 (odds ratio: 5.0; 95%CI: 1.6-15.6; P = 0.006) but there was no association between HPV18/45, all hrHPV types (combined), C. trachomatis, N. gonorrhoeae or T. vaginalis. CONCLUSIONS: VIA positivity was associated with HPV16, but not with other hrHPV infections, nor with genital C. trachomatis, N. gonorrhoeae or T. vaginalis in this setting.


Assuntos
Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Infecções por Chlamydia/epidemiologia , Gonorreia/epidemiologia , Infecções por Papillomavirus/epidemiologia , Vaginite por Trichomonas/epidemiologia , Ácido Acético , Adolescente , Adulto , Fatores Etários , Chlamydia trachomatis , Coito , Comorbidade , Feminino , Papillomavirus Humano 16 , Humanos , Neisseria gonorrhoeae , Infecções por Papillomavirus/virologia , Papua Nova Guiné/epidemiologia , Prevalência , Estudos Prospectivos , Trichomonas vaginalis
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