RESUMO
Glioblastoma is the most common primary malignant brain tumor. Despite treatments combining excisional surgery, chemotherapy, and radiotherapy, overall survival remains low and the incidence of tumor recurrence remains high. Advances in the understanding of the disease, particularly its molecular biology and the mechanisms of action of systemic and radiotherapeutic treatments, as well as the development of image-guided surgical techniques, offer hope for the control of this hitherto incurable disease.
Le glioblastome est la tumeur cérébrale maligne primitive la plus fréquente. Malgré des traitements combinant la chirurgie d'exérèse, la chimiothérapie et la radiothérapie, la survie globale reste faible avec une incidence élevée de récidive tumorale. Les progrès dans la compréhension de la maladie, et en particulier de la biologie moléculaire et des mécanismes d'action des traitements systémiques et radiothérapeutiques, de même que le développement des techniques chirurgicales guidées par l'image, permettent d'entrevoir un espoir dans le contrôle de cette maladie jusqu'ici incurable.
Assuntos
Neoplasias Encefálicas , Glioblastoma , Biomarcadores Tumorais , Neoplasias Encefálicas/terapia , Metilação de DNA , Glioblastoma/genética , Glioblastoma/terapia , Humanos , Mutação , Recidiva Local de Neoplasia/genética , PrognósticoRESUMO
This study examined the prevalence and factors associated with Mycoplasma genitalium (MG) infection among HIV-positive women and the association between MG and vaginal HIV-1 RNA shedding. HIV-positive women attending an outpatient clinic in New Orleans, Louisiana, USA, from 2002 to 2005 were examined for a battery of sexually transmitted infections (STIs) and underwent a behavioural survey. A selected subset had a measurement of vaginal shedding analysed. Of the 324 HIV-positive women, 32 (9.9%) were infected with MG. HIV-positive women with MG were more likely to be co-infected with Neisseria gonorrhoeae and Chlamydia trachomatis and to have had ≥1 male sexual partners in the last month. In the subset (n = 164), no differences were found in the presence of detectable vaginal HIV-1 RNA between women infected and not infected with MG (30.8% versus 34.8% shedding; P = 0.69). While MG was a common co-STI in this sample of HIV-positive women, it was not associated with vaginal HIV shedding.
Assuntos
Infecções por HIV/microbiologia , Infecções por Mycoplasma/virologia , Mycoplasma genitalium/isolamento & purificação , Vagina/virologia , Adolescente , Adulto , Estudos Transversais , Feminino , HIV/genética , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Modelos Logísticos , Louisiana/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Infecções por Mycoplasma/epidemiologia , Prevalência , RNA Viral/análise , Fatores de Risco , Fatores Socioeconômicos , Eliminação de Partículas ViraisRESUMO
BACKGROUND: Nongonococcal urethritis (NGU) is a common chlamydia-associated syndrome in men; however, Trichomonas vaginalis and Mycoplasma genitalium are associated with its etiology and should be considered in approaches to therapy. We sought to determine whether the addition of tinidazole, an anti-trichomonal agent, to the treatment regimen would result in higher cure rates than those achieved with treatment with doxycycline or azithromycin alone. A secondary aim was to compare the efficacy of doxycycline therapy and with that of azithromycin therapy. METHODS: Randomized, controlled, double-blinded phase IIB trial of men with NGU. Participants were randomized to receive doxycycline plus or minus tinidazole or azithromycin plus or minus tinidazole and were observed for up to 45 days. RESULTS: The prevalences of Chlamydia trachomatis, M. genitalium, and T. vaginalis were 43%, 31%, and 13%, respectively. No pathogens were identified in 29% of participants. Clinical cure rates at the first follow-up visit were 74.5% (111 of 149 patients) for doxycycline-containing regimens and 68.6% (107 of 156 patients) for azithromycin-containing regimens. By the final visit, cure rates were 49% (73 of 149 patients) for doxycycline-containing regimens and 43.6% (68 of 156 patients) for azithromycin-containing regimens. There were no significant differences in clinical response rates among the treatment arms. However, the chlamydia clearance rate was 94.8% (55 of 58 patients) for the doxycycline arm and 77.4% (41 of 53 patients) for the azithromycin arm (P = .011), and the M. genitalium clearance rate was 30.8% (12 of 39 patients) for the doxycycline arm and 66.7% (30 of 45 patients) for the azithromycin arm (P = .002). CONCLUSIONS: Addition of tinidazole to the treatment regimen did not result in higher cure rates but effectively eradicated trichomonas. Clinical cure rates were not significantly different between patients treated with doxycycline and those treated with azithromycin; however, doxycycline had significantly better efficacy against Chlamydia, whereas azithromycin was superior to doxycycline for the treatment of M. genitalium.
Assuntos
Antibacterianos/administração & dosagem , Antiprotozoários/administração & dosagem , Azitromicina/administração & dosagem , Doxiciclina/administração & dosagem , Tinidazol/administração & dosagem , Uretrite/tratamento farmacológico , Adolescente , Adulto , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis/isolamento & purificação , Método Duplo-Cego , Quimioterapia Combinada/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycoplasma/tratamento farmacológico , Mycoplasma genitalium/isolamento & purificação , Resultado do Tratamento , Tricomoníase/tratamento farmacológico , Trichomonas vaginalis/isolamento & purificação , Uretrite/microbiologia , Uretrite/parasitologia , Adulto JovemRESUMO
OBJECTIVE: To determine the prevalence of Neisseria gonorrhoeae in a student population before hurricane Katrina and after their residential neighbourhoods were devastated in the wake of the hurricane. METHODS: Students in a New Orleans public high school were offered urine screening for N gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests before (n = 346) and after (n = 333) hurricane Katrina. Based on studies showing gonorrhea clustering in physically deteriorated neighbourhoods, it was hypothesised that the post-Katrina gonorrhea prevalence would be higher among students whose neighbourhoods still showed signs of deterioration in the aftermath of the hurricane. RESULTS: Before and after hurricane Katrina, the prevalence of gonorrhea increased from 2.3% (8/346, 95% CI 1.3% to 4.6%) to 5.1% (17/333, 95% CI 3.1% to 8.2%), respectively (one-sided p = 0.027). In logistic regression of gonorrhea controlling for gender, age, chlamydia infection and exposure to hurricane-affected residential neighbourhood conditions, gonorrhea was significantly associated with female gender (odds ratio (OR) 2.6, 95% CI 1.0 to 6.3; p = 0.04) and with chlamydia infection (OR 9.2, 95% CI 3.9 to 21.7; p<0.001). Although of weak statistical significance, there was a strong independent positive trend toward testing positive for gonorrhea after the hurricane (OR 2.2, 95% CI 0.9 to 5.4; p = 0.09). CONCLUSIONS: The analysis indicates that the odds of testing positive for gonorrhea more than doubled among students after the hurricane, indicating that surveillance activities should be restored to monitor sexually transmitted infections (STIs) among at-risk populations. Redoubled efforts should be put into STI screening programmes as soon as possible following natural disasters to prevent resurgent STI incidence rates.
Assuntos
Infecções por Chlamydia/epidemiologia , Tempestades Ciclônicas , Desastres , Gonorreia/epidemiologia , Adolescente , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/urina , Chlamydia trachomatis/isolamento & purificação , Feminino , Gonorreia/diagnóstico , Gonorreia/urina , Humanos , Masculino , Programas de Rastreamento , Neisseria gonorrhoeae/isolamento & purificação , Nova Orleans/epidemiologia , Técnicas de Amplificação de Ácido Nucleico , Prevalência , Características de Residência , Serviços de Saúde Escolar , EstudantesRESUMO
OBJECTIVES: As the aetiology of bacterial vaginosis (BV) is not well understood, this study sought to determine the relationships between several fastidious microbes, BV and selected clinical characteristics of BV. METHODS: Endometrial and cervical specimens from 50 women with non-gonococcal, non-chlamydial endometritis were tested for Leptotrichia sanguinegens/amnionii, Atopobium vaginae, bacterial vaginosis-associated bacteria 1 (BVAB1), Ureaplasma urealyticum biovar 2 (UU-2) and Ureaplasma parvum using PCR. BV was categorised using Nugent's and Amsel's criteria. Odds ratios (OR) adjusted for age and race were estimated using multivariable logistic regression. RESULTS: Although elevated pH was a universal feature, other BV characteristics differed by pathogen, suggesting variable clinical presentation. Only UU-2 was strongly associated with vaginal discharge, but a positive whiff test and a 20% or greater classification of epithelial cells as clue cells were more common among women with L sanguinegens/amnionii, A vaginae and BVAB1. For each of these bacteria, there were trends towards associations with BV defined by Amsel's criteria (L sanguinegens/amnionii OR 2.9, 95% CI 0.5 to 15.7; A vaginae OR 2.6, 95% CI 0.6 to 11.4; BVAB1 OR 5.7, 95% CI 1.0 to 31.1) and significant associations with BV defined by Gram stain (L sanguinegens/amnionii OR 17.7, 95% CI 2.8 to 113.0; A vaginae OR 19.2, 95% CI 3.7 to 98.7; BVAB1 OR 21.1, 95% CI 2.2 to 198.5). CONCLUSIONS: L sanguinegens/amnionii, A vaginae and BVAB1 are associated with clinical characteristics consistent with BV and BV defined by Nugent's and Amsel's criteria. These fastidious bacteria may cause unrecognised infection, as none was associated with abnormal vaginal discharge.
Assuntos
Actinobacteria/isolamento & purificação , Leptotrichia/isolamento & purificação , Ureaplasma/isolamento & purificação , Descarga Vaginal/microbiologia , Vaginose Bacteriana/microbiologia , Adolescente , Adulto , Biópsia , Reações Falso-Negativas , Feminino , Humanos , Concentração de Íons de Hidrogênio , Modelos Logísticos , Masculino , Odorantes , Doença Inflamatória Pélvica/microbiologia , Reação em Cadeia da Polimerase/métodos , Distribuição Aleatória , Fatores de Risco , Ureaplasma/classificação , Útero/microbiologia , Útero/patologia , Vaginose Bacteriana/diagnóstico , Adulto JovemRESUMO
BACKGROUND: In dystrophic skeletal muscle, osmotic stimuli somehow relieve inhibitory control of dihydropyridine receptors (DHPR) on spontaneous sarcoplasmic reticulum elementary Ca(2+) release events (ECRE) in high Ca(2+) external environments. Such 'uncontrolled' Ca(2+) sparks were suggested to act as dystrophic signals. They may be related to mechanosensitive pathways but the mechanisms are elusive. Also, it is not known whether truncated dystrophins can correct the dystrophic disinhibition. METHODOLOGY/PRINCIPAL FINDINGS: We recorded ECRE activity in single intact fibers from adult wt, mdx and mini-dystrophin expressing mice (MinD) under resting isotonic conditions and following hyper-/hypo-osmolar external shock using confocal microscopy and imaging techniques. Isotonic ECRE frequencies were small in wt and MinD fibers, but were markedly increased in mdx fibers. Osmotic challenge dramatically increased ECRE activity in mdx fibers. Sustained osmotic challenge induced marked exponential ECRE activity adaptation that was three times faster in mdx compared to wt and MinD fibers. Rising external Ca(2+) concentrations amplified osmotic ECRE responses. The eliminated ECRE suppression in intact osmotically stressed mdx fibers was completely and reversibly resuscitated by streptomycine (200 microM), spider peptide GsMTx-4 (5 microM) and Gd(3+) (20 microM) that block unspecific, specific cationic and Ca(2+) selective mechanosensitive channels (MsC), respectively. ECRE morphology was not substantially altered by membrane stress. During hyperosmotic challenge, membrane potentials were polarised and a putative depolarisation through aberrant MsC negligible excluding direct activation of ECRE through tubular depolarisation. CONCLUSIONS/SIGNIFICANCE: Dystrophin suppresses spontaneous ECRE activity by control of mechanosensitive pathways which are suggested to interact with the inhibitory DHPR loop to the ryanodine receptor. MsC-related disinhibition prevails in dystrophic muscle and can be resuscitated by transgenic mini-dystrophin expression. Our results have important implications for the pathophysiology of DMD where abnormal MsC in dystrophic muscle confer disruption of microdomain Ca(2+) homeostasis. MsC blockers should have considerable therapeutic potential if more muscle specific compounds can be found.
Assuntos
Sinalização do Cálcio/fisiologia , Distrofina/metabolismo , Canais Iônicos/metabolismo , Mecanotransdução Celular/fisiologia , Músculo Esquelético/fisiopatologia , Adulto , Animais , Canais de Cálcio Tipo L/metabolismo , Distrofina/genética , Humanos , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos mdx , Camundongos Transgênicos , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/citologia , Músculo Esquelético/fisiologia , Distrofia Muscular de Duchenne/fisiopatologia , Pressão Osmótica , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismoRESUMO
Thiamine diphosphate-dependent enzymes are involved in a wide variety of metabolic pathways. The molecular mechanism behind active site communication and substrate activation, observed in some of these enzymes, has since long been an area of debate. Here, we report the crystal structures of a phenylpyruvate decarboxylase in complex with its substrates and a covalent reaction intermediate analogue. These structures reveal the regulatory site and unveil the mechanism of allosteric substrate activation. This signal transduction relies on quaternary structure reorganizations, domain rotations, and a pathway of local conformational changes that are relayed from the regulatory site to the active site. The current findings thus uncover the molecular mechanism by which the binding of a substrate in the regulatory site is linked to the mounting of the catalytic machinery in the active site in this thiamine diphosphate-dependent enzyme.
Assuntos
Carboxiliases/metabolismo , Tiamina Pirofosfato/química , Sítio Alostérico , Sítios de Ligação , Carboxiliases/química , Catálise , Cristalografia por Raios X/métodos , Modelos Biológicos , Modelos Moleculares , Conformação Molecular , Raízes de Plantas/metabolismo , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Transdução de Sinais , Especificidade por Substrato , Difração de Raios XAssuntos
Enfisema Mediastínico , Complicações do Trabalho de Parto , Enfisema Subcutâneo , Adulto , Feminino , Humanos , Enfisema Mediastínico/diagnóstico , Enfisema Mediastínico/etiologia , Complicações do Trabalho de Parto/diagnóstico , Gravidez , Enfisema Subcutâneo/diagnóstico , Enfisema Subcutâneo/etiologiaRESUMO
The Centers for Disease Control and Prevention recommended confirming positive screening tests for Chlamydia trachomatis when positive predictive values are <90%. It is accepted that less sensitive tests (i.e., culture and immunoassays) should not be used to confirm the results of more sensitive nucleic acid amplification tests (NAATs). We show that the same principle applies when NAATs are used for confirmation.
Assuntos
Chlamydia trachomatis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Centers for Disease Control and Prevention, U.S. , Chlamydia trachomatis/genética , Feminino , Humanos , Masculino , Sensibilidade e Especificidade , Estados UnidosRESUMO
A clinical evaluation was conducted in six North American centers to determine the ability of APTIMA CT (ACT) and APTIMA GC (AGC) nucleic acid amplification assays to detect Chlamydia trachomatis and Neisseria gonorrhoeae infections in 1,322 men by testing their urethral swabs and first-catch urine (FCU). The results obtained with ACT and AGC assays were compared to an infected patient status determined by testing the specimens with the APTIMA Combo 2 and the BD ProbeTec energy transfer multiplex assays. Symptoms did not influence the values. Positive and negative agreements of the ACT and AGC assays for individual specimens were high, with each comparator assay ranging between 94.3 and 100% for positives and 93.9 and 99.4% for negatives. The ACT and AGC assays performed on noninvasive specimens such as FCU effectively identified C. trachomatis or N. gonorrhoeae infections in symptomatic and asymptomatic men and should be suitable for screening male populations.
Assuntos
Chlamydia trachomatis/isolamento & purificação , Neisseria gonorrhoeae/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Manejo de Espécimes/métodos , Uretra/microbiologia , Urina/microbiologia , Adolescente , Adulto , Idoso , Infecções por Chlamydia/microbiologia , Gonorreia/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
The greater sensitivity of nucleic acid amplification tests (NAATs) for Chlamydia trachomatis and Neisseria gonorrhoeae permits the use of urine and other noninvasive specimens, which can increase the reach and decrease the costs of public health screening programs aimed at controlling these infections. This study evaluated the performance of the APTIMA Combo 2 assay, a multiplex assay based on the transcription-mediated amplification reaction, for the simultaneous detection of both pathogens in endocervical swab and urine specimens from females. Combo 2 assay results were compared with patient infected status, which were available by using other commercial NAATs. Sensitivity and specificity for C. trachomatis were 94.2 and 97.6%, respectively, in swabs and 94.7 and 98.9%, respectively, in first-catch urine (FCU). Sensitivity and specificity for N. gonorrhoeae were 99.2 and 98.7%, respectively, in swabs and 91.3 and 99.3%, respectively, in FCU. The assay reliably detected both infections in coinfected patients. The Combo 2 assay can be recommended for use with endocervical swab and urine specimens from females, especially for screening tests for asymptomatic women in sexually transmitted disease surveillance programs. This Food and Drug Administration-cleared assay can be a useful tool in efforts to reduce the prevalence and incidence of C. trachomatis and N. gonorrhoeae infections in sexually active women and to prevent their costly and serious sequelae.
Assuntos
Colo do Útero/microbiologia , Chlamydia trachomatis/isolamento & purificação , Neisseria gonorrhoeae/isolamento & purificação , Urina/microbiologia , Feminino , Humanos , Kit de Reagentes para DiagnósticoRESUMO
The objectives of the study were to assess the overall prevalence of backache in gynaecologists and determine its impact on work, and to identify possible occupational risk factors. The sample comprised gynaecologists, both active and retired, listed as members of the Ulster Obstetrical and Gynaecological Society, who were asked to complete and return a postal questionnaire. The response rate was 94% (107/114). The prevalence of backache, which included pain arising in the thoracic and lumbosacral regions, was 72%. Fifty-three per cent of those with back pain blamed it on working in obstetrics and gynaecology. Overall, 32% of gynaecologists required a change of their work practice, 20% had taken time off work and 8% had required surgery. We conclude that significant morbidity results from backache in gynaecologists. This has economic implications and requires further assessment to improve prevention, with emphasis on individual training and ergonomic evaluation of work-related postures.
Assuntos
Dor nas Costas/epidemiologia , Ginecologia/estatística & dados numéricos , Doenças Profissionais/epidemiologia , Adulto , Dor nas Costas/etiologia , Dor nas Costas/prevenção & controle , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Irlanda do Norte/epidemiologia , Obstetrícia , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Prevalência , Fatores de Risco , Licença Médica/estatística & dados numéricos , Inquéritos e QuestionáriosRESUMO
The COBAS AMPLICOR CT/NG test for Neisseria gonorrhoeae cross-reacts with certain strains of nonpathogenic Neisseria species. In some strains, the target sequence is identical to that of N. gonorrhoeae, whereas other strains have a small number of mismatches within the regions recognized by the primers or probe used in the COBAS AMPLICOR NG test. These cross-reactive strains are occasionally present in urogenital specimens, causing false-positive results in the COBAS AMPLICOR NG test. Analysis of the data generated in a large multicenter clinical trial showed that 2.9% of the specimens gave signals between A(660)s of 0.2 and 3.5 but that one-half of these equivocal specimens did not contain N. gonorrhoeae. Most of these equivocal specimens were correctly classified as true positive or true negative by retesting in duplicate and defining a PCR-positive result as two of three results with an A(660) of > or =2.0. If specimens had been classified as positive or negative based on a single test result using a cutoff of an A(660) of 0.2, specificity would have ranged from 96.2 to 98.9% depending on specimen type, sex, and presence of symptoms. By employing the equivocal zone-retesting algorithm, specificity increased to 98.6 to 99.9% with little effect (0.1 to 4.9% decrease) on sensitivity in most specimen types, enabling the test to achieve a positive predictive value of at least 90% in populations with a prevalence of 4% or higher. In lower-prevalence populations, the test could be used to screen for presumptive infections that would have to be confirmed by an independent test.
Assuntos
Gonorreia/diagnóstico , Gonorreia/microbiologia , Neisseria gonorrhoeae/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Adulto , Algoritmos , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/genética , Reações Falso-Positivas , Feminino , Humanos , Masculino , Neisseria/genética , Neisseria/isolamento & purificação , Neisseria gonorrhoeae/genética , Reação em Cadeia da Polimerase/normas , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Treatment of gonorrhea is complicated by widespread resistance of Neisseria gonorrhoeae to antimicrobial agents of choice, including decreased susceptibility to ciprofloxacin. GOAL: To demonstrate the efficacy and safety of gatifloxacin, a novel 8-methoxy fluoroquinolone antibiotic, compared with ofloxacin in treating patients with uncomplicated gonococcal infection. STUDY DESIGN: In a double-blind, randomized (2:2:1), controlled trial, 340 men and 388 women with uncomplicated gonorrhea who were 16 years or older received a single oral dose of gatifloxacin (400 mg or 600 mg) or ofloxacin (400 mg). Primary analysis of efficacy was based on bacteriologic eradication from sites of infection. Secondary analyses examined clinical response and adverse event profiles. RESULTS: Bacteriologic eradication rates for gatifloxacin in evaluable men with urethral gonorrhea were 99% (400 mg) and 100% (600 mg) versus 100% for ofloxacin (n = 117, 122, and 55, respectively; P = ns). Eradication rates in evaluable women with endocervical gonorrhea were 99% for both 400 mg and 600 mg gatifloxacin versus 100% for ofloxacin (n = 101, 104, and 55, respectively; P = ns). Eradication rates were 100% for both rectal (n = 43) and pharyngeal (n = 31) infection across all treatment groups. All three drug regimens were well tolerated and exhibited similar clinical response profiles. CONCLUSION: Gatifloxacin is safe and effective as a single 400-mg or 600-mg dose for the treatment of uncomplicated gonorrhea. Similar efficacy rates were observed with the 400-mg and 600-mg doses. A single 400-mg dose can be recommended for treatment of uncomplicated gonorrhea.
Assuntos
Anti-Infecciosos/administração & dosagem , Fluoroquinolonas , Gonorreia/tratamento farmacológico , Ofloxacino/administração & dosagem , Administração Oral , Adolescente , Adulto , Método Duplo-Cego , Esquema de Medicação , Feminino , Gatifloxacina , Humanos , Masculino , Resultado do Tratamento , Estados UnidosRESUMO
Urine ligase chain reaction (LCR) and PCR tests and urethral swab culture were compared for their abilities to detect Chlamydia trachomatis infection in 3,639 asymptomatic men by using one-, two-, and three-test reference standards. Frozen urine at four of five participating centers was also tested by a transcription-mediated amplification assay which was used as a reference test. LCR increased the yield of positive results by 27% and PCR increased the yield of positive results by 26% over the yield of positive results by culture (n = 295). LCR and PCR sensitivities were similar, ranging from 80.4 to 93.5%, depending on the reference standard. Culture sensitivity was substantially less. A multiple-test standard yielded LCR, PCR, and culture specificities of 99.6%, with or without discrepant analysis. Test performance varied among centers partly due to different interpretations of the testing protocols. The study confirms that urine LCR and PCR for the detection of C. trachomatis have substantially improved sensitivities over that of urethral swab culture for testing of asymptomatic men, enabling screening of this important target group. These tests, perhaps in combination, are also candidate reference tests for the conduct of test evaluation studies.
Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Reação em Cadeia da Ligase , Reação em Cadeia da Polimerase , Animais , Infecções por Chlamydia/urina , Masculino , Padrões de Referência , Sensibilidade e Especificidade , Uretra/microbiologiaRESUMO
The intent of this article is to provide an overview of the epidemiology and pharmacotherapy, including cost analyses, of Chlamydia trachomatis infections in pregnant women. Chlamydia is a common sexually transmitted infection. For pregnant women, there are concerns both for the mother (post-partum endometritis, horizontal transmission) and the newborn (conjunctivitis, delayed pneumonia). Therapeutic options are restricted because of the fetus and include multi-day treatment with erythromycin, amoxicillin, clindamycin or single dose azithromycin. Clinical cure rates with these options are 86, 92, 93 and 95%, respectively. Pharmacoeconomic analyses have been conducted to determine if the initial increase in acquisition cost of azithromycin (approximately 3-fold higher than erythromycin or amoxicillin) is offset by improvement in compliance and drug efficacy. Clindamycin has received little attention because of its expense (4-fold more than azithromycin). Analyses have been retrospective. As models incorporate more complications of failure to cure, azithromycin increasingly becomes more cost effective and is our recommended treatment.
Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis , Clindamicina/uso terapêutico , Penicilinas/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto , Amoxicilina/economia , Antibacterianos/economia , Azitromicina/economia , Clindamicina/economia , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Cooperação do Paciente , Penicilinas/economia , Gravidez , Estudos RetrospectivosRESUMO
The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG tests were evaluated in a multicenter trial for their ability to detect Neisseria gonorrhoeae infections. Test performance compared to that of culturing was evaluated for 2,192 matched endocervical swab and urine specimens obtained from women and for 1, 981 matched urethral swab and urine specimens obtained from men. Culture-negative, PCR-positive specimens that tested positive in a confirmatory PCR test for an alternative target sequence within the N. gonorrhoeae 16S rRNA gene were considered to be true positives. The overall prevalences of gonorrhea were 6.6% in women and 20.1% in men. The COBAS AMPLICOR and AMPLICOR formats yielded concordant results for 98.8% of the specimens and exhibited virtually identical sensitivities and specificities. The results that follow are for the COBAS AMPLICOR format. With the infected patient as the reference standard, the resolved sensitivities of PCR were 92.4% for endocervical swab specimens and 64.8% for female urine specimens. There were no significant differences in these rates between women with and without symptoms. Among symptomatic men, COBAS AMPLICOR sensitivities were 94.1% for urine and 98.1% for urethral swabs; for asymptomatic men, the results were 42.3 and 73.1%, respectively. In comparison, the sensitivities of culturing were 84.8% for endocervical specimens, 92.7% for symptomatic male urethral specimens, and only 46.2% for urethral specimens obtained from asymptomatic men. When PCR results were analyzed as if only a single test had been performed on a single specimen type, the resolved sensitivity was always higher. The resolved specificities of PCR were 99.5% for endocervical swab specimens, 99.8% for female urine specimens, 98.9% for male urethral swab specimens, and 99.9% for male urine specimens. The internal control revealed that 2.1% of specimens were inhibitory when initially tested. Nevertheless, valid results were obtained for 99.2% of specimens because 60.0% of the inhibitory specimens were not inhibitory when a second aliquot was tested. The COBAS AMPLICOR CT/NG test for N. gonorrhoeae exhibited high sensitivity and specificity with urethral swab and urine specimens from men and endocervical swab specimens from women and thus is well suited for diagnosing and screening for N. gonorrhoeae infection.
Assuntos
Gonorreia/diagnóstico , Neisseria gonorrhoeae/isolamento & purificação , Animais , Automação/instrumentação , Automação/métodos , Feminino , Gonorreia/epidemiologia , Humanos , Neisseria gonorrhoeae/classificação , Neisseria gonorrhoeae/genética , Reação em Cadeia da Polimerase/métodos , Prevalência , RNA Ribossômico 16S/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores Sexuais , Estados Unidos/epidemiologia , Esfregaço VaginalRESUMO
The fully automated COBAS AMPLICOR CT/NG and semiautomated AMPLICOR CT/NG tests were evaluated in a multicenter trial for the ability to detect Chlamydia trachomatis infections. Test performance compared to that of culture was evaluated for 2,236 matched endocervical swab and urine specimens obtained from women and for 1,940 matched urethral swab and urine specimens obtained from men. Culture-negative, PCR-positive specimens that tested positive in a direct fluorescent-antibody test or in a confirmatory PCR test for an alternative target sequence were resolved as true positives. The overall prevalences of chlamydia were 2.4% in women and 7.2% in men. The COBAS AMPLICOR and AMPLICOR formats yielded concordant results for 98.1% of the specimens. With the infected patient as the reference standard, the resolved sensitivities of COBAS AMPLICOR were 89.7% for endocervical swab specimens, 89.2% for female urine specimens, 88.6% for male urethral swab specimens, and 90.3% for male urine specimens. When results were analyzed as if only a single test had been performed on a single specimen type, the resolved sensitivity was always higher. The resolved specificities of PCR were 99.4% for endocervical swab specimens, 99.0% for female urine specimens, 98.7% for male urethral swab specimens, and 98.4% for male urine specimens. The internal control revealed that 2.4% of the specimens were inhibitory when initially tested. Nevertheless, valid results were obtained for 98.6% of the specimens because 59.1% of the inhibitory specimens were not inhibitory when a second aliquot was tested. The COBAS AMPLICOR and AMPLICOR CT/NG tests for C. trachomatis exhibited equally high sensitivity and specificity with both urogenital swab and urine specimens and thus are well suited for screening for C. trachomatis infection.
Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis , Automação/instrumentação , Automação/métodos , Infecções por Chlamydia/urina , Chlamydia trachomatis/isolamento & purificação , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Uretra/microbiologia , Urina/microbiologia , Esfregaço VaginalRESUMO
OBJECTIVES: To determine whether repeated school-based screening and treatment for chlamydia and gonorrhea will decrease the prevalence of infection among students. DESIGN: At three high schools serving over 2000 students, all 9th through 12th grade students were given the opportunity to be tested during three consecutive school years for chlamydia and gonorrhea, using urine ligase chain reaction tests. Five comparable schools with 5063 students enrolled served as wait-listed controls. SETTING: Eight urban public high schools in Louisiana. PARTICIPANTS: Annually, 52% to 65% of all enrolled students participated; among those enrolled in schools for > or = 2 years, 83.4% of students were tested at least once. INTERVENTION: Education of all students; counseling and treatment of infected students with oral single-dose antibiotic therapy. MAIN OUTCOME MEASURE: Prevalence of Chlamydia trachomatis and gonorrhea infection. RESULTS: At first test, 286 (11.5%) of 2497 girls and 143 (6.2%) of 2308 boys were infected with chlamydia, and 48 (2.5%) of 1883 girls and 19 (1.2%) of 1628 boys had gonorrhea. Over 90% of infections were asymptomatic. With repeated testing, chlamydia prevalence among boys dropped to half the rate of comparison schools (3.2% vs 6.4%). Among girls chlamydia prevalence declined only slightly (10.3% vs 11. 9% in comparison schools). CONCLUSION: There are high rates of asymptomatic sexually transmitted diseases (STDs) in the general urban school population. Repeated screening and treatment are associated with declines in chlamydia prevalence among boys. Expansion of STD screening and treatment programs to school settings is likely to be a critical component of a national strategy to control bacterial STDs.
Assuntos
Programas de Rastreamento/métodos , Serviços de Saúde Escolar , Infecções Sexualmente Transmissíveis/epidemiologia , Adolescente , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/prevenção & controle , Estudos de Viabilidade , Feminino , Gonorreia/epidemiologia , Gonorreia/prevenção & controle , Humanos , Louisiana/epidemiologia , Masculino , Programas de Rastreamento/estatística & dados numéricos , Seleção de Pacientes , Prevalência , Serviços de Saúde Escolar/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/prevenção & controle , População Urbana/estatística & dados numéricosRESUMO
OBJECTIVE: To determine the seroprevalence of and risk factors for human papillomavirus (HPV) type 16 capsid antibodies in a large cohort of pregnant women. METHODS: Antibodies against in vitro produced HPV-16 capsids were measured in stored sera from 2597 pregnant women enrolled from 1984 through 1989 in the Vaginal Infection and Prematurity Study, New Orleans site. RESULTS: Women in this study were primarily black (83.4%) with a mean age of 23.4 years (standard deviation [SD], 5.1), mean number of sexual partners in lifetime was 3.3 (SD, 6.6), and the mean age at sexual debut was 16.7 years (SD, 2.2). Overall, 28.0% (n = 727) of these women were positive for HPV-16 capsid antibodies. In bivariate analysis, the presence of antibodies against HPV-16 was correlated with numerous demographic characteristics as well as history of various sexually transmitted diseases. However, neither current cervical or vaginal infection nor adverse obstetric outcome was associated with increased detection of HPV-16 antibodies. In multivariate logistic regression analysis, factors predictive of HPV-16 seropositivity were: more than five lifetime sexual partners (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.28, 2.52), 6 or more years of sexual activity (OR, 1.84; 95% CI, 1.22, 2.78), level of education (OR, 1.26; 95% CI, 1.03, 1.55), and history of Neisseria gonorrhoeae infection (OR, 1.53; 95% CI, 1.20, 1.96). CONCLUSION: HPV-16 seropositivity correlates with measures of sexual activity, confirming its role as a sexually transmitted disease, and its prevalence is similar to that in nonpregnant populations. HPV-16 seropositivity does not predict an adverse obstetric outcome.