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BackgroundAntimicrobial resistance (AMR) of Mycoplasma genitalium (MG) is a growing concern worldwide and surveillance is needed. In Belgium, samples are sent to the National Reference Centre of Sexually Transmitted Infections (NRC-STI) on a voluntary basis and representative or robust national AMR data are lacking.AimWe aimed to estimate the occurrence of resistant MG in Belgium.MethodsBetween July and November 2022, frozen remnants of MG-positive samples from 21 Belgian laboratories were analysed at the NRC-STI. Macrolide and fluoroquinolone resistance-associated mutations (RAMs) were assessed using Sanger sequencing of the 23SrRNA and parC gene. Differences in resistance patterns were correlated with surveillance methodology, socio-demographic and behavioural variables via Fisher's exact test and logistic regression analysis.ResultsOf the 244 MG-positive samples received, 232 could be sequenced for macrolide and fluoroquinolone RAMs. Over half of the sequenced samples (55.2%) were resistant to macrolides. All sequenced samples from men who have sex with men (MSM) (24/24) were macrolide-resistant. Fluoroquinolone RAMs were found in 25.9% of the samples and occurrence did not differ between socio-demographic and sexual behaviour characteristics.ConclusionAlthough limited in sample size, our data suggest no additional benefit of testing MG retrieved from MSM for macrolide resistance in Belgium, when making treatment decisions. The lower occurrence of macrolide resistance in other population groups, combined with emergence of fluoroquinolone RAMs support macrolide-resistance testing in these groups. Continued surveillance of resistance in MG in different population groups will be crucial to confirm our findings and to guide national testing and treatment strategies.
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Infecções por Mycoplasma , Mycoplasma genitalium , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Masculino , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Homossexualidade Masculina , Mycoplasma genitalium/genética , Bélgica/epidemiologia , Macrolídeos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/epidemiologia , Mutação , RNA Ribossômico 23S/genética , Fluoroquinolonas/farmacologiaRESUMO
Background: Antimicrobial resistance to macrolides and fluoroquinolones in Mycoplasma genitalium (MG) among men who have sex with men (MSM) is worryingly high in high-resource countries. Data in Africa are lacking. We aimed to assess the burden of MG including the presence of resistance-associated mutations (RAMs) in MG among MSM using human immunodeficiency virus preexposure prophylaxis in Burkina Faso, Côte d'Ivoire, Mali, and Togo. Methods: MSM were included in a prospective cohort study (2017-2021). Molecular detection of MG in urine, anorectal, and pharyngeal samples was performed at baseline and after 6 and 12 months. Detection of RAMs to macrolides and fluoroquinolones was performed by sequencing the 23S ribosomal RNA, parC, and gyrA genes. A sample was found to be possibly resistant to fluoroquinolones if alterations were found in ParC position 83/87. Results: Of 598 participants, 173 (28.9%) were positive at least once for MG and global point-prevalence was 19.4%. Interestingly, 238 of 250 (95.2%) infections were asymptomatic and 72 of 138â MG infections with follow-up data (52.2%) cleared during the study. Only 1 macrolide RAM was found (0.6%). Prevalence of fluoroquinolones RAMs was 11.3% overall, ranging from 2.4% in Burkina Faso to 17.5% in Mali. Conclusions: Although MG was highly prevalent in these MSM, macrolide resistance was almost nonexistent. Nevertheless, >10% of the samples were possibly resistant to fluoroquinolones. Heterogeneity in the prevalence of fluoroquinolone RAMs between countries may be explained by different antimicrobial consumption in humans and animals.
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The magnitude of the 2022 multi-country monkeypox virus (MPXV) outbreak has surpassed any preceding outbreak. It is unclear whether asymptomatic or otherwise undiagnosed infections are fuelling this epidemic. In this study, we aimed to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. We retrospectively screened 224 samples collected for gonorrhea and chlamydia testing using an MPXV PCR assay and identified MPXV-DNA-positive samples from four men. At the time of sampling, one man had a painful rash, and three men had reported no symptoms. Upon clinical examination 21-37 days later, these three men were free of clinical signs, and they reported not having experienced any symptoms. Serology confirmed MPXV exposure in all three men, and MPXV was cultured from two cases. These findings show that certain cases of monkeypox remain undiagnosed and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak.
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Mpox , Saúde Sexual , Masculino , Humanos , Monkeypox virus , Mpox/diagnóstico , Mpox/epidemiologia , Estudos Retrospectivos , Bélgica/epidemiologiaRESUMO
BACKGROUND: Men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP) recurrently infected with STIs are playing a pivotal role in contemporary Sexually transmitted infections (STI) epidemics. Our aim was to assess whether these individuals had more Mycoplasma genitalium (M. genitalium) infections and more resistance to macrolides and fluoroquinolones of M. genitalium compared to those who were not recurrently infected with STIs. METHODS: The study was performed on 179 Belgian MSM PrEP users that were followed up for 18 months. STIs including M. genitalium were detected quarterly. Detection of resistance-associated mutations (RAMs) to macrolides and fluoroquinolones was performed via Sanger sequencing of the 23S rRNA gene and parC gene (conferring mutations at position 83/87 in ParC). Differences in M. genitalium positivity rate and presence of RAMs between both groups were assessed using mixed-effects logistic regression. RESULTS: A total of 91 new M. genitalium infections were detected among 70 participants. MSM experiencing recurrent STIs have significantly more M. genitalium infections compared to those without (11.7% vs. 4.7% OR: 2.69). Importantly, the prevalence of RAMs to macrolides (95.2% vs. 77.4%) and fluoroquinolones (35.7% vs. 12.9%) was much higher among individuals with recurrent STIs. The difference was only statistically significant for macrolides (OR 5.83, p = .036). CONCLUSIONS: MSM recurrently infected with STIs play a central role in the emergence of antimicrobial resistance in M. genitalium. The use of macrolides and fluoroquinolones should preferably be minimized in this population in order to avoid further emergence of multi-resistant M. genitalium.
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Infecções por Mycoplasma , Mycoplasma genitalium , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Homossexualidade Masculina , Humanos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Masculino , Mutação , Infecções por Mycoplasma/tratamento farmacológico , Infecções por Mycoplasma/epidemiologia , Mycoplasma genitalium/genética , Prevalência , Infecções Sexualmente Transmissíveis/tratamento farmacológicoRESUMO
OBJECTIVES: The number of reported cases of multiresistant Mycoplasma genitalium (MG) is increasing globally. The aim of this study was to estimate the prevalence of macrolide and possible fluoroquinolone resistance-associated mutations (RAMs) of MG in Belgium. METHODS: The study was performed retrospectively on two sets of MG-positive samples collected in Belgium between 2015 and 2018. The first set of samples originated from routine surveillance activities and the second set came from a cohort of men who have sex with men (MSM) using pre-exposure prophylaxis to prevent HIV transmission. Detection of RAMs to macrolides and fluoroquinolones was performed on all samples using DNA sequencing of the 23S ribosomal RNA gene, the gyrA gene and the parC gene. RESULTS: Seventy-one per cent of the MG samples contained a mutation conferring resistance to macrolides or fluoroquinolones (ParC position 83/87). RAMs were more frequently found among men compared with women for fluoroquinolones (23.9% vs 9.1%) and macrolides (78.4% vs 27.3%). Almost 90% of the MG infections among MSM possessed a RAM to macrolides (88.4%). In addition, 18.0% of the samples harboured both macrolides and fluoroquinolone RAMs; 3.0% in women and 24.2% in MSM. Being MSM was associated with macrolide RAMs (OR 15.3), fluoroquinolone RAMs (OR 3.8) and having a possible multiresistant MG infection (OR 7.2). CONCLUSION: The study shows an alarmingly high prevalence of MG with RAMs to macrolides and fluoroquinolones in Belgium. These results highlight the need to improve antimicrobial stewardship in Belgium in order to avoid the emergence of untreatable MG.
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Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/farmacologia , Macrolídeos/farmacologia , Mutação , Infecções por Mycoplasma/genética , Mycoplasma genitalium/genética , Adulto , Bélgica/epidemiologia , DNA Girase/análise , DNA Topoisomerase IV/análise , DNA Bacteriano/química , Feminino , Humanos , Masculino , Prevalência , RNA Ribossômico 23S/análise , Estudos Retrospectivos , Análise de Sequência de DNARESUMO
OBJECTIVES: The diagnosis of repeat syphilis and its follow-up remains challenging. We aimed to investigate if IgM testing may assist in the diagnosis of syphilis reinfection/relapse and its treatment follow-up. METHODS: This substudy was conducted in the context of a syphilis biomarker discovery study (ClinicalTrials.gov Nr: NCT02059525). Sera were collected from 120 individuals with a new diagnosis of syphilis (72 with repeat infections) and 30 syphilis negative controls during a cohort study investigating syphilis biomarkers conducted at a sexually transmitted infection/HIV clinic in Antwerp, Belgium. Syphilis was diagnosed based on a simultaneous positive treponemal and non-treponemal assay result and/or positive serum PCR targeting polA. Specimens collected at visit of diagnosis, and 3 and 6 months post-treatment were tested by two enzyme immunoassays (EIAs), recomWell (Mikrogen; MI) and Euroimmun (EU), to detect anti-treponemal IgM. Baseline specimens were also tested for anti-treponemal IgM using a line immunoassay (LIA) recomLine (MI). Quantitative kinetic decay curves were constructed from the longitudinal quantitative EIA results. RESULTS: An overall sensitivity for the diagnosis of syphilis of 59.8% (95% CI: 50.3%-68.7%), 75.0% (95% CI: 66.1%-82.3%) and 63.3% (95% CI: 54.8%-72.6%) was obtained for the EU, MI EIAs and MI LIA, respectively. When only considering repeat syphilis, the diagnostic sensitivity decreased to 45.7% (95% CI: 33.9%-58.0%), 63.9% (95% CI: 51.7%-74.6%) and 47.2% (95% CI: 35.5%-59.3%), respectively. IgM seroreverted in most cases 6 months after treatment. Post-treatment IgM concentrations decreased almost 30% faster for initial syphilis compared with repeat infection. The IgM EIAs and IgM LIA agreed from fairly to moderately (Cohen's kappa (κ): 0.36 (EU EIA); κ: 0.53 (MI EIA); κ: 0.40 (MI LIA)) with the diagnosis of syphilis. CONCLUSIONS: IgM detection was not a sensitive method to diagnose syphilis and was even poorer in the diagnosis of syphilis repeat infections.
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Sífilis , Anticorpos Antibacterianos , Bélgica , Estudos de Coortes , Seguimentos , Humanos , Imunoglobulina M , Estudos Prospectivos , Sensibilidade e Especificidade , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Sorodiagnóstico da Sífilis , Treponema pallidumRESUMO
Objectives: To investigate the efficacy of performing a pooling strategy of triple-anatomical site samples (pharyngeal, anorectal and urine samples) for simultaneous Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) nucleic acid amplification detection.Methods: A total of 117 specimen sets (pharyngeal, anorectal and urine) were collected from 98 men between 2014 and 2016. Double sampling of pharyngeal, anorectal and urine samples allowed for pooled and unpooled analyses using a multiplex Abbott Real Time CT/NG assay, together with confirmatory PCR testing in case of CT/NG positivity. Clinical and demographic data were analyzed.Results: The positivity rate for the triple-site pooled testing for CT and NG was 8.5% (10/117) and 6.8%, (8/117), respectively, compared to the single-site testing total positivity rate, which was 9.4% (11/117) and 4.3% (5/117) for CT and NG, respectively. Pooled analysis missed one CT-positive urine sample and one CT-positive anorectal sample could not be confirmed. In addition, less PCR inhibition was reported for the pooled sample (PS) testing and ERV-3 qPCR testing revealed ineffective sampling of self-collected anorectal swabs in two cases. No pharyngeal samples were positive for CT, nor were any urine samples positive for NG.Conclusion: This small study showed that PS testing is a possible testing strategy for screening high-risk men who have sex with men attending pre-exposure prophylaxis (PrEP) clinics. However, due to the low positivity rate of CT/NG in this study, larger evaluations are needed to confirm the effectiveness of CT/NG screening with multiple-site PS nucleic acid amplification test (NAAT) screening practices.
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Infecções por Chlamydia , Chlamydia trachomatis/genética , Gonorreia , Tipagem Molecular/métodos , Neisseria gonorrhoeae/genética , Adulto , Canal Anal/microbiologia , Bélgica , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Estudos Transversais , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Faringe/microbiologia , Manejo de EspécimesRESUMO
BACKGROUND: The Presto combined qualitative real-time assay for Chlamydia trachomatis and Neisseria gonorrhoeae (Presto CT/NG PCR assay) is appealing for developing countries, because it can be used with multiple DNA extraction methods and polymerase chain reaction (PCR) platforms. OBJECTIVES: The objective of the study was to implement and evaluate the Presto CT/NG PCR assay at the National Reference Laboratory (NRL) in Kigali, Rwanda, where no real-time PCR assays for the detection of C. trachomatis or N. gonorrhoeae were available. METHODS: The Presto CT/NG PCR assay was first evaluated at the Institute of Tropical Medicine (ITM) in Antwerp, Belgium. Next, NRL laboratory technicians were trained to use the assay on their ABI PRISM 7500 real-time PCR instrument and their competencies were assessed prior to trial initiation. During the trial, endocervical swabs were tested at the NRL, with bi-monthly external quality control testing monitored by the ITM. The final NRL results were evaluated against extended gold standard testing at the ITM, consisting of the Abbott m2000 RealTime System with confirmation of positive results by an in-house real-time PCR assay for C. trachomatis or N. gonorrhoeae. RESULTS: Of the 192 samples analysed using the Presto assay at the NRL, 16 samples tested positive for C. trachomatis and 17 tested positive for N. gonorrhoeae; four of these were infected with both. The sensitivity and specificity of the Presto assay were 93.3% (95% confidence interval [CI]: 68.1% - 99.8%) and 99.4% (95% CI: 96.8% - 100%) for C. trachomatis and 100% (95% CI: 76.8% - 100%) and 98.8% (95% CI: 95.8% - 99.9%) for N. gonorrhoeae. CONCLUSION: C. trachomatis and N. gonorrhoeae testing with the Presto assay was feasible in Kigali, Rwanda, and good performance was achieved. KEYWORDS: qPCR; Chlamydia trachomatis; Neisseria gonorrhoeae.
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OBJECTIVES: Pre-exposure prophylaxis (PrEP) users are screened bi-annual for sexually transmitted infections (STIs). A novel device, called the Colli-Pee, collects first-void urine in a standardised way and the collector tube can be easily delivered by regular post to a certified laboratory. The aim of the study was a one-to-one comparison between the STI test results obtained with the urine collected in the clinic, versus urine collected at home in a real-life setting by Men who have Sex with Men (MSM) in Belgium. The user-friendliness and acceptability of the Colli-Pee device by the users was also evaluated. DESIGN: A single-site nested substudy in a prospective PrEP demonstration project (Be-PrEP-ared) among MSM in Belgium. PARTICIPANTS: A total of 473 home-based samples from 213 MSM were received with a mean age of 38.5 years. INTERVENTIONS: Participants were requested to collect a urine sample at home using the Colli-Pee device and to send it to the laboratory via regular mail. PRIMARY AND SECONDARY OUTCOME MEASURES: The presence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) was determined using molecular amplification assays. Agreement between test results of samples collected at the clinic and collected at home were evaluated using Cohen's kappa statistic. RESULTS: TV was not detected. A very good to almost perfect agreement was found for CT, NG and MG of κ=0.75, 0.87 and 0.85, respectively. Using the Colli-Pee device only one low positive CT and two MG infections were missed, however, three additional CT, two NG and six MG infections were detected. CONCLUSIONS: The Colli-Pee device is a feasible and convenient way to collect urine at home for STI testing. This may be particularly relevant for populations that need frequent STI testing, such as PrEP users and patients who prefer home-sampling. TRIAL REGISTRATION NUMBER: NCT02552914; Pre-results.
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Infecções Sexualmente Transmissíveis/urina , Manejo de Espécimes/métodos , Coleta de Urina/métodos , Adulto , Bélgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Autocuidado/métodos , Adulto JovemRESUMO
BACKGROUND: Sexually transmitted infections, such as HIV and syphilis, are one of the major health care problems worldwide, especially in low- and middle income countries. HIV screening programmes have been widely used for many years. The introduction of rapid point-of-care tests (RDTs) that can detect both HIV and syphilis, using one single blood specimen, would be a promising tool to integrate the detection of syphilis into HIV programmes and so improve the accessibility of syphilis testing and treatment. METHODS: As part of the World Health Organization pre-qualification of in vitro diagnostics assessment, the laboratory performance of four dual HIV-Syphilis rapid diagnostic tests (SD Bioline HIV/Syphilis Duo, DPP HIV-Syphilis Assay, Multiplo Rapid TP/HIV Antibody Test and Insti Multiplex HIV-1/HIV-2/Syphilis Antibody Test) was assessed using a well characterized multiregional panel of stored sera specimens. RESULTS: In total 400 specimens were tested with each assay, resulting in excellent sensitivities and specificities for HIV, ranging from 99.5 to 100% and from 93.5 to 99.5%, respectively. Results obtained for the Treponema pallidum antibodies were lower, with the lowest sensitivity of 73.5% for Multiplo and the highest of 87% for SD Bioline. Specificities ranged from 99.0 to 100%. CONCLUSION: Although these results suggest that the tests could further improve in accuracy in detection of treponemal antibodies, their introduction into screening programmes to increase the accessibility of HIV/Syphilis diagnosis and treatment for difficult to reach populations in the world is promising.
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Testes Diagnósticos de Rotina , Infecções por HIV/diagnóstico , Sífilis/diagnóstico , Anticorpos Antibacterianos/sangue , Anticorpos Anti-HIV/sangue , HIV-1/imunologia , HIV-2/imunologia , Humanos , Imunoensaio , Laboratórios , Programas de Rastreamento/métodos , Testes Imediatos , Sensibilidade e Especificidade , Testes Sorológicos , Sorodiagnóstico da Sífilis/métodos , Treponema pallidum/imunologiaRESUMO
BACKGROUND: The number of cases of Lymphogranuloma venereum (LGV) is increasing in Europe. The described epidemic is mostly confined to HIV positive men who have sex with men (MSM). However, dissemination of LGV from HIV positive to HIV negative MSM could take place due to the implementation of pre-exposure prophylaxis (PrEP) and subsequent possible decrease in condom use. We describe here the LGV epidemiology in Belgium before the PrEP-era, starting from 2011 up to the end of the first half of 2017. METHODS: A descriptive analysis of the socio-demographic and clinical characteristics of all LGV cases was performed. Fisher's exact test was used to compare symptomatic to asymptomatic patients. Logistic regression models were used to check for trends over time for: number of LGV cases, HIV status and symptoms. RESULTS: The number of LGV cases rose by a factor four, from 21 in 2011 to 88 in 2016, and regression models showed a positive trend estimate of 14% increase per half year (p < 0.001). LGV decreased among HIV positive cases (odds ratio (OR): 0.79, p < 0.001) and increased among HIV negative cases (OR: 1.27, p < 0.001). In addition, a rise in the number of asymptomatic LGV cases (6.7%) was observed (OR:1.39, p = 0.047). Asymptomatic cases were also less likely to be HIV (p = 0.046) or Hepatitis C positive (p = 0.027). CONCLUSIONS: The rise of LGV in HIV negative MSM has now been documented. If we aim to halt the epidemic in HIV negative MSM, future public health strategies should include LGV testing of all Chlamydia trachomatis positive samples from MSM.
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Homossexualidade Masculina/estatística & dados numéricos , Linfogranuloma Venéreo/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bélgica/epidemiologia , Chlamydia trachomatis/isolamento & purificação , HIV , Soronegatividade para HIV , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Minorias Sexuais e de Gênero/estatística & dados numéricos , Adulto JovemRESUMO
We report on the performance of the APTIMA Combo 2 assay for the detection of chlamydial infection and gonorrhea using self-administered vaginal specimens in specimen transport medium and specimen kept dry. The results are compared with the results using the Amplicor assay and the BD ProbeTec assay™.
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Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/genética , Gonorreia/diagnóstico , Neisseria gonorrhoeae/genética , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Estudos Transversais , Feminino , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Técnicas de Diagnóstico Molecular , Prevalência , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Profissionais do Sexo , Manejo de Espécimes , Vagina/microbiologiaRESUMO
BACKGROUND: The vaginal microbiome plays an important role in urogenital health. Quantitative real time Polymerase Chain Reaction (qPCR) assays for the most prevalent vaginal Lactobacillus species and bacterial vaginosis species G. vaginalis and A. vaginae exist, but qPCR information regarding variation over time is still very limited. We set up qPCR assays for a selection of seven species and defined the temporal variation over three menstrual cycles in a healthy Caucasian population with a normal Nugent score. We also explored differences in qPCR data between these healthy women and an 'at risk' clinic population of Caucasian, African and Asian women with and without bacterial vaginosis (BV), as defined by the Nugent score. RESULTS: Temporal stability of the Lactobacillus species counts was high with L. crispatus counts of 108 copies/mL and L. vaginalis counts of 106 copies/mL. We identified 2 types of 'normal flora' and one 'BV type flora' with latent class analysis on the combined data of all women. The first group was particularly common in women with a normal Nugent score and was characterized by a high frequency of L. crispatus, L. iners, L. jensenii, and L. vaginalis and a correspondingly low frequency of L. gasseri and A. vaginae. The second group was characterized by the predominance of L. gasseri and L. vaginalis and was found most commonly in healthy Caucasian women. The third group was commonest in women with a high Nugent score but was also seen in a subset of African and Asian women with a low Nugent score and was characterized by the absence of Lactobacillus species (except for L. iners) but the presence of G. vaginalis and A. vaginae. CONCLUSIONS: We have shown that the quantification of specific bacteria by qPCR contributes to a better description of the non-BV vaginal microbiome, but we also demonstrated that differences in populations such as risk and ethnicity also have to be taken into account. We believe that our selection of indicator organisms represents a feasible strategy for the assessment of the vaginal microbiome and could be useful for monitoring the microbiome in safety trials of vaginal products.
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Bactérias/classificação , Bactérias/genética , Biodiversidade , Metagenoma , Técnicas de Amplificação de Ácido Nucleico/métodos , Vagina/microbiologia , Adolescente , Adulto , Carga Bacteriana/métodos , Etnicidade , Feminino , Humanos , Adulto JovemRESUMO
Bronchopulmonary dysplasia and retinopathy of prematurity affect premature infants exposed to supplemental oxygen. Susceptibility to oxygen-induced retinopathy in the rat is heritable, with inbred Dark Agouti (DA) rats being more susceptible than Fischer 344 (F344) rats. To establish if hyperoxic exposure sufficient to induce florid retinopathy would induce strain-specific lung changes, newborn DA and F344 rats were exposed to cyclic hyperoxia or room air for up to 18 days. Lung function was assessed at 18 days, and standardized morphometry and immunohistochemistry were performed at intervals. No differences in arterial blood gases or protein concentration of bronchoalveolar lavage fluid were observed amongst groups at 18 days, although lung wet-to-dry weights were significantly lower for F344 than for DA rats. Pulmonary vascularity increased in all oxygen-exposed animals compared with room air-exposed controls, but there was no significant difference between strains. The lung surface area of oxygen-exposed F344 rats was significantly increased at day 10 compared with F344 controls and oxygen-treated DA rats, but at 14 and 17 days the oxygen-exposed DA rats showed increased lung surface area compared with oxygen-exposed F344 rats. The minor morphological differences found in the lung did not affect pulmonary function, suggesting that mechanisms inducing oxygen-induced retinopathy and bronchopulmonary dysplasia are fundamentally different, and that susceptibility to bronchopulmonary dysplasia is not heritable in the rat.
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Displasia Broncopulmonar/etiologia , Hiperóxia/complicações , Pulmão/fisiopatologia , Neovascularização Patológica/etiologia , Retinopatia da Prematuridade/etiologia , Células Epiteliais Alveolares/patologia , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/patologia , Displasia Broncopulmonar/fisiopatologia , Modelos Animais de Doenças , Humanos , Hiperóxia/patologia , Hiperóxia/fisiopatologia , Imuno-Histoquímica , Recém-Nascido , Pulmão/irrigação sanguínea , Pulmão/patologia , Neovascularização Patológica/patologia , Neovascularização Patológica/fisiopatologia , Ratos , Ratos Endogâmicos F344 , Testes de Função Respiratória , Retinopatia da Prematuridade/patologia , Retinopatia da Prematuridade/fisiopatologia , Especificidade da Espécie , Fatores de TempoRESUMO
Endotoxin stimulus plays a significant role in various forms of acute lung injury (ALI) which may be exacerbated by mechanical ventilation. Here, we identify the temporal pathophysiologic sequence following inhaled lipopolysaccharide (LPS) and subsequently examine both LPS dose and V(T) relationships. Rats received intratracheal LPS (3, 9 or 15 mg/kg) prior to mechanical ventilation (V(T)=6, 9 or 12 ml/kg) and measurement of forced impedance mechanics for up to 4h. LPS-induced lung injury was achieved within the 15 min of LPS instillation with a 78% decrease in PaO(2) promptly followed by approximately 30% deterioration in tissue elastance. Despite a 41% increase in total surfactant, the active disaturated phospholipid fraction decreased 3-7% with decreasing PaO(2) and tissue mechanics and with increases in total lung lavage protein (150%) and wet-to-dry lung weight ratio (10%). V(T)=12 ml/kg resulted in an additional deterioration in tissue resistance (130%) and elastance (63%). These results suggest that LPS-induced lung injury is both LPS dose and V(T) sensitive, supporting a 'two hit' model of ALI.
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Lipopolissacarídeos/toxicidade , Pneumopatias/induzido quimicamente , Pneumopatias/fisiopatologia , Pulmão/fisiopatologia , Mecânica Respiratória/fisiologia , Volume de Ventilação Pulmonar/fisiologia , Animais , Líquido da Lavagem Broncoalveolar/química , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Masculino , Fosfolipídeos/metabolismo , Ratos , Ratos Sprague-Dawley , Tensoativos/farmacologiaRESUMO
RATIONALE: Chronic elevation of pulmonary microvascular pressure in chronic heart failure results in compensatory changes in the lung that reduce alveolar fluid filtration and protect against pulmonary microvascular rupture. OBJECTIVES: To determine whether these compensatory responses may have maladaptive effects on lung function. METHODS: Six weeks after myocardial infarction (chronic heart failure model) rat lung composition, both gross and histologic; air and saline mechanics; surfactant production; and immunological mediators were examined. MEASUREMENTS AND MAIN RESULTS: An increase in dry lung weight, due to increased insoluble protein, lipid and cellular infiltrate, without pulmonary edema was found. Despite this, both forced impedance and air pressure-volume mechanics were normal. However, there was increased tissue stiffness in the absence of surface tension (saline pressure-volume curve) with a concurrent increase in both surfactant content and alveolar type II cell numbers, suggesting a novel homeostatic phenomenon. CONCLUSIONS: These studies suggest a compensatory reduction in pulmonary surface tension that attenuates the effect of lung parenchymal remodeling on lung mechanics, hence work of breathing.
Assuntos
Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Pulmão/patologia , Pulmão/fisiopatologia , Mecânica Respiratória/fisiologia , Resistência Vascular/fisiologia , Resistência das Vias Respiratórias/fisiologia , Animais , Doença Crônica , Modelos Animais de Doenças , Insuficiência Cardíaca/complicações , Masculino , Microcirculação/fisiologia , Tamanho do Órgão , Circulação Pulmonar/fisiologia , Proteínas Associadas a Surfactantes Pulmonares/fisiologia , Ratos , Ratos Sprague-Dawley , Tensão SuperficialRESUMO
OBJECTIVE: Low tidal volume (V(T)) ventilation strategies may be associated with permissive hypercapnia, which has been shown by ex vivo and in vivo studies to have protective effects. We hypothesized that hypercapnic acidosis may be synergistic with low V(T) ventilation; therefore, we studied the effects of hypercapnia and V(T) on unstimulated and lipopolysaccharide-stimulated isolated perfused lungs. MATERIALS AND METHODS: Isolated perfused rat lungs were ventilated for 2 hours with low (7 mL/kg) or moderately high (20 mL/kg) V(T) and 5% or 20% CO(2), with lipopolysaccharide or saline added to the perfusate. RESULTS: Hypercapnia resulted in reduced pulmonary edema, lung stiffness, tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the lavage and perfusate. The moderately high V(T) did not cause lung injury but increased lavage IL-6 and perfusate IL-6 as well as TNF-alpha. Pulmonary edema and respiratory mechanics improved, possibly as a result of a stretch-induced increase in surfactant turnover. Lipopolysaccharide did not induce significant lung injury. CONCLUSIONS: We conclude that hypercapnia exerts a protective effect by modulating inflammation, lung mechanics, and edema. The moderately high V(T) used in this study stimulated inflammation but paradoxically improved edema and lung mechanics with an associated increase in surfactant release.