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SummaryWe describe a case of culture-negative infective endocarditis due to Neisseria gonorrhoeae, where the application of metagenomics shotgun sequencing in blood played a pivotal role in elucidating the underlying aetiology, guiding targeted therapy and ultimately resulting in the patient's complete recovery. Beyond its immediate clinical impact, prompt treatment bears significant implications for public health. The utilisation of molecular testing emerges as a valuable strategy to enhance diagnostic accuracy, particularly in cases involving fastidious organisms that are infrequently associated with infective endocarditis.
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Antibacterianos , Endocardite Bacteriana , Gonorreia , Neisseria gonorrhoeae , Valva Tricúspide , Humanos , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Gonorreia/complicações , Neisseria gonorrhoeae/isolamento & purificação , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/tratamento farmacológico , Masculino , Valva Tricúspide/microbiologia , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Adulto , EcocardiografiaRESUMO
Neisseria gonorrhoeae (Ng) is a major cause of morbidity among sexually active individuals, occasionally leading to serious complications if left untreated. We describe a case of gonococcal peritonitis as a rare complication of Ng infection in a woman presenting with acute abdomen and intestinal subacute occlusion. Due to the rarity of this clinical presentation, we review the scientific literature to identify best practices and inform guidelines.
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Antibacterianos , Gonorreia , Neisseria gonorrhoeae , Peritonite , Humanos , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Gonorreia/complicações , Gonorreia/microbiologia , Peritonite/microbiologia , Peritonite/tratamento farmacológico , Peritonite/diagnóstico , Feminino , Neisseria gonorrhoeae/isolamento & purificação , Antibacterianos/uso terapêutico , Adulto , Resultado do Tratamento , Ceftriaxona/uso terapêuticoRESUMO
ABSTRACT: Disseminated gonococcal infection is the causative agent of approximately 0.6%-1.2% of septic arthritis cases in North America and Europe. Typical presentations of this disorder include tenosynovitis, dermatitis, polyarthralgia, or oligoarticular purulent arthritis affecting the distal joints. Diagnosis is contingent on clinical presentation, with urine nucleic acid amplification testing as the preferred diagnostic modality. Synovial fluid cultures, along with imaging, can confirm diagnosis. The recommended treatment is a third-generation cephalosporin, such as intravenous ceftriaxone for 7-14 days and a dose of oral azithromycin.
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Artrite Infecciosa , Gonorreia , Humanos , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/tratamento farmacológico , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Gonorreia/complicações , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Azitromicina/uso terapêutico , Masculino , Feminino , AdultoRESUMO
Introduction: We aimed to investigate the overlapping epidemiologies of human immunodeficiency virus (HIV), herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhea, and syphilis in sexual networks of men who have sex with men (MSM), and to explore to what extent the epidemiology of one sexually transmitted infection (STI) relates to or differs from that of another STI. Methods: An individual-based Monte Carlo simulation model was employed to simulate the concurrent transmission of STIs within diverse sexual networks of MSM. The model simulated sexual partnering, birth, death, and STI transmission within each specific sexual network. The model parameters were chosen based on the current knowledge and understanding of the natural history, transmission, and epidemiology of each considered STI. Associations were measured using the Spearman's rank correlation coefficient (SRCC) and maximal information coefficient (MIC). Results: A total of 500 sexual networks were simulated by varying the mean and variance of the number of partners for both short-term and all partnerships, degree correlation, and clustering coefficient. HSV-2 had the highest current infection prevalence across the simulations, followed by HIV, chlamydia, syphilis, and gonorrhea. Threshold and saturation effects emerged in the relationship between STIs across the simulated networks, and all STIs demonstrated moderate to strong associations. The strongest current infection prevalence association was between HIV and gonorrhea, with an SRCC of 0.84 (95% CI: 0.80-0.87) and an MIC of 0.81 (95% CI: 0.74-0.88). The weakest association was between HSV-2 and syphilis, with an SRCC of 0.54 (95% CI: 0.48-0.59) and an MIC of 0.57 (95% CI, 0.49-0.65). Gonorrhea exhibited the strongest associations with the other STIs while syphilis had the weakest associations. Across the simulated networks, proportions of the population with zero, one, two, three, four, and five concurrent STI infections were 48.6, 37.7, 11.1, 2.4, 0.3, and < 0.1%, respectively. For lifetime exposure to these infections, these proportions were 13.6, 21.0, 22.9, 24.3, 13.4, and 4.8%, respectively. Conclusion: STI epidemiologies demonstrate substantial overlap and associations, alongside nuanced differences that shape a unique pattern for each STI. Gonorrhea exhibits an "intermediate STI epidemiology," reflected by the highest average correlation coefficient with other STIs.
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Chlamydia , Gonorreia , Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Masculino , Humanos , Gonorreia/epidemiologia , Gonorreia/complicações , Sífilis/epidemiologia , Herpesvirus Humano 2 , Homossexualidade Masculina , HIV , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Infecções Sexualmente Transmissíveis/epidemiologiaRESUMO
The incidence of gonorrhea has increased significantly in recent years in the United States, especially among sexually active twenty-year-olds. Although the incidence of gonorrhea has decreased in Korea since the early 2000s, it is still common among people in their twenties. Nucleic acid amplification test (NAAT) is the most sensitive diagnostic test for detecting gonococcal infection. Gram-staining is a simple and useful laboratory test for diagnosing symptomatic male gonococcal urethritis. Although bacterial culture can be used to detect antimicrobial susceptibility, its sensitivity is lower than that of NAAT. Treatment for uncomplicated gonorrhea infection is a single intramuscular injection of ceftriaxone 500 mg. Doxycycline (100 mg twice daily for 7 days) is added if there is a possibility of co-infection with chlamydia. If ceftriaxone is difficult to use, spectinomycin 2 g can be injected intramuscularly in Korea. Patients with gonorrhea should have repeated examinations within three months at the exposure site because of a high risk of re-infection. A person diagnosed with gonorrhea should discuss the nature of the infection, the importance of informing partners, when sexual activity can resume, and how to reduce the risk of sexually transmitted infections.
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Gonorreia , Infecções Urinárias , Humanos , Masculino , Gonorreia/complicações , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Ceftriaxona/uso terapêutico , Inflamação , República da Coreia/epidemiologiaRESUMO
ABSTRACT: Neisseria gonorrhoeae is a human obligate pathogen whose clinical expression of disease ranges from localized genital infection to involvement of extragenital sites such as the conjunctiva and throat. We describe the second case of a thyroglossal duct abscess due to N. gonorrhoeae, an uncommon complication of pharyngeal gonococcal infection. The fortuitous occurrence in the same individual of these 2 conditions that both exhibit an occult clinical presentation likely accounts for rarity of this infection. We discuss the pertinent gonococcal and host factors that underlie the clinical manifestations of this infection. A particular focus is the fundamental role that the binding of the gonococcal opacity-associated protein to the ubiquitous human carcinoembryonic cell adhesion molecule plays in the pathogenesis of pharyngeal gonorrhea.
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Gonorreia , Cisto Tireoglosso , Humanos , Genitália , Gonorreia/complicações , Gonorreia/diagnóstico , Neisseria gonorrhoeae , Faringe , Cisto Tireoglosso/cirurgiaRESUMO
BACKGROUND: Disseminated gonococcal infection (DGI), a complication of untreated gonorrhea, is rarely reported through routine surveillance. We sought to improve local surveillance system capacity to estimate and monitor the incidence of DGI in Virginia. METHODS: We modified surveillance protocols to identify possible DGI cases using information extracted from gonorrhea case reports and performed provider follow-up using standardized case report forms to confirm DGI diagnosis and collect clinical information. Suspect cases included those with a laboratory report indicating sterile site of specimen collection (e.g., blood, synovial fluid) and/or intravenous (IV) treatment. We performed descriptive analyses to summarize the characteristics of suspect and confirmed DGIs and estimated incidence. RESULTS: After piloting protocols in 2018 to 2019, we identified 405 suspect DGI cases from 29,294 gonorrhea cases reported in 2020 to 2021 (1.4%). We initiated investigations for 298 (73.6%) of the suspect cases, received provider responses for 105 (25.9%), and confirmed 19 DGI cases (4.7%). Positive laboratory reports from nonmucosal sites were the most reliable predictor of confirmed DGI status, but most were not confirmed as DGI even when provider follow-up was successful. The confirmed and estimated incidence of DGI were 0.06% and 0.22%, respectively. Sixteen (84%) of the confirmed cases were older than 25 years, 3 (16%) were HIV positive, and approximately half were male and non-Hispanic Black. Most (15 [74%]) were hospitalized, and common manifestations included septic arthritis and bacteremia. CONCLUSIONS: We improved surveillance for DGI in Virginia while incurring minor programmatic costs. Additional efforts to improve the completeness and quality of surveillance data for DGI are needed.
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Artrite Infecciosa , Gonorreia , Humanos , Masculino , Feminino , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Gonorreia/complicações , Neisseria gonorrhoeae , Virginia/epidemiologia , Artrite Infecciosa/diagnósticoRESUMO
Hematogenous spread of Neisseria gonorrhoeae, a sexually transmitted pathogen, results in disseminated gonococcal disease (DGD), also known as arthritis-dermatitis syndrome, due to the development of skin lesions, tenosynovitis, and arthritis. The most frequently affected population is young adults. We describe the case of an adolescent female who acutely developed skin lesions, arthritis, tenosynovitis, and constitutional symptoms. The causal agent was identified by a culture of vaginal secretion and treated with ceftriaxone for 7 days with complete recovery. It is important to differentiate this clinical picture from other types of arthritis developed in adolescence.
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Artrite Infecciosa , Gonorreia , Tenossinovite , Adolescente , Adulto Jovem , Humanos , Feminino , Criança , Tenossinovite/complicações , Antibacterianos/uso terapêutico , Gonorreia/complicações , Gonorreia/diagnóstico , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae , Artrite Infecciosa/diagnósticoRESUMO
A gay man with well-controlled HIV and vaccinated against mpox presented with severe proctitis. Testing revealed anorectal mpox, herpes simplex virus, lymphogranuloma venereum, Neisseria gonorrhoeae and Mycoplasma genitalium Serology was indicative of infectious syphilis. This case highlights the need to consider a wide range of concurrent sexually transmitted infections in patients with proctitis, including those vaccinated against mpox.
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Gonorreia , Infecções por HIV , Linfogranuloma Venéreo , Mpox , Mycoplasma genitalium , Proctite , Sífilis , Masculino , Humanos , Linfogranuloma Venéreo/complicações , Linfogranuloma Venéreo/diagnóstico , Linfogranuloma Venéreo/tratamento farmacológico , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/tratamento farmacológico , Gonorreia/complicações , Gonorreia/diagnóstico , Proctite/etiologia , Simplexvirus , Infecções por HIV/complicações , Homossexualidade MasculinaRESUMO
OBJECTIVES.: Monkeypox (Mpox) is a zoonotic disease, endemic in some areas of Africa. But since May 2022, multiple cases of Mpox have been reported in non-endemic countries. We present the case of a patient with a history of HIV, as well as rash in several areas of the body, mostly in the gluteal region, associated with cervical lymphadenopathy and infectious proctitis. Diagnosis was confirmed by real-time polymerase chain reaction (RT-PCR) of skin lesion samples. Treponema pallidum and Neisseria gonorrhoeae infection was confirmed by serology and rectal discharge culture, respectively. The patient received antibiotics specific for gonorrhea and syphilis and his condition improved due to symptomatic and immunomodulatory therapy.
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Gonorreia , Infecções por HIV , Mpox , Sífilis , Humanos , Animais , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/epidemiologia , Gonorreia/complicações , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Zoonoses , Infecções por HIV/epidemiologiaRESUMO
Disseminated gonococcal infection (DGI) is a rare and emerging disease that should be considered in individuals who present with acute polyarthralgias, skin lesions and/or tenosynovitis, even in the absence of genitourinary symptoms.We describe a 29 years old man presenting with fever, arthralgias, skin lesions and signs of tenosynovitis. The diagnostic approach identified a disseminated gonococcal infection and an unrecognized and latent autoimmune diabetes.We emphasize not only the particularities of diagnostic and treatment approach currently required by this emergent infection, but also the importance of investigation of rare risk factors associated with an underlying immunosuppression. In latent autoimmune diabetes of adults a timely recognition and individualized treatment are fundamental for prognostic
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Humanos , Masculino , Adulto , Gonorreia/diagnóstico , Diabetes Autoimune Latente em Adultos/complicações , Diabetes Autoimune Latente em Adultos/diagnóstico , Autoanticorpos/análise , Neisseria gonorrhoeae/isolamento & purificação , Gonorreia/complicações , Autoimunidade , Diabetes Autoimune Latente em Adultos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos/análise , Ribonucleoproteínas/análise , Diabetes Autoimune Latente em Adultos/patologiaRESUMO
La enfermedad gonocócica diseminada es una manifestación infrecuente de la afectación por Neisseria gonorrhoeae, que presenta una clínica variada y no bien definida, siendo la afectación articular un hallazgo característico. Presentamos el caso de una mujer de 64 años con enfermedad gonocócica diseminada de inicio agudo, que comenzó con deterioro generalizado y oligoartritis. Se realizó artrocentesis de carpo, obteniéndose un líquido sinovial de aspecto purulento, cuyo estudio microbiológico identificó Neisseira gonorrhoeae. En el estudio se objetivó un complemento hemolítico total (CH50) de cero, no detectándose la fracción C2 del complemento. Son muy pocos los casos descritos en la literatura de enfermedad gonocócica diseminada asociada a déficit de C2. Presentamos un nuevo caso y revisamos los previamente publicados
Disseminated gonococcal infection is a rare presentation of the sexually transmitted pathogen, Neisseria gonorrhoeae. Here, we report the case of a 64-year-old woman with disseminated gonococcal infection, which started with symptoms of oligoarthritis and malaise. Neisseria gonorrhoeae was identified in the carpal synovial fluid. The follow-up study revealed an absence of total hemolytic complement and complement C2 was not detected. Being relatively common, C2 deficiency has been associated with disseminated gonococcal infection in a few cases. We present a new case and discuss those previously published
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Humanos , Feminino , Pessoa de Meia-Idade , Artrite Infecciosa/microbiologia , Complemento C2/deficiência , Gonorreia/complicaçõesRESUMO
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Humanos , Uretrite/classificação , Gonorreia/complicações , Uretrite/etiologia , Uretra/microbiologia , Neisseria gonorrhoeaeRESUMO
Abstract: Background: Urethral discharge syndrome (UDS) is characterized by the presence of purulent or mucopurulent urethral discharge.The main etiological agents of this syndrome are Neisseria gonorrhoeae and Chlamydia trachomatis. Objectives: To evaluate the effectiveness of the syndromic management to resolve symptoms in male urethral discharge syndrome cases in Manaus, Amazonas, Brazil. Methods: Retrospective cohort of male cases of urethral discharge syndrome observed at a clinic for sexually transmitted disease (STD) in 2013. Epidemiological and clinical data, as well as the results of urethral swabs, bacterioscopy, hybrid capture for C.trachomatis, wet-mount examination, and culture for N.gonorrhoeae, were obtained through medical chart reviews. Results: Of the 800 urethral discharge syndrome cases observed at the STD clinic, 785 (98.1%) presented only urethral discharge syndrome, 633 (79.1%) returned for follow-up, 579 (91.5%) were considered clinically cured on the first visit, 41(6.5 %) were considered cured on the second visit, and 13(2.0%) did not reach clinical cure after two appointments. Regarding the etiological diagnosis, 42.7% of the patients presented a microbiological diagnosis of N.gonorrhoeae, 39.3% of non-gonococcal and non-chlamydia urethritis, 10.7% of C.trachomatis and 7.3% of co-infection with chlamydia and gonococcus. The odds of being considered cured in the first visit were greater in those who were unmarried, with greater schooling, and with an etiological diagnosis of gonorrhea. The diagnosis of non-gonococcal urethritis reduced the chance of cure in the first visit. Study limitation: A study conducted at a single center of STD treatment. Conclusion: Syndromic management of male urethral discharge syndrome performed in accordance with the Brazilian Ministry of Health STD guidelines was effective in resolving symptoms in the studied population. More studies with microbiological outcomes are needed to ensure the maintenance of the syndromic management.
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Humanos , Masculino , Adulto Jovem , Doenças Uretrais/microbiologia , Doenças Uretrais/tratamento farmacológico , Infecções por Chlamydia/complicações , Gonorreia/complicações , Gerenciamento Clínico , Fatores Socioeconômicos , Supuração , Síndrome , Brasil , Infecções por Chlamydia/tratamento farmacológico , Gonorreia/tratamento farmacológico , Chlamydia trachomatis/isolamento & purificação , Análise Multivariada , Estudos Retrospectivos , Resultado do Tratamento , Neisseria gonorrhoeae/isolamento & purificaçãoRESUMO
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Humanos , Feminino , Gravidez , Adolescente , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Proctite/complicações , Proctite/prevenção & controle , Doenças dos Genitais Femininos/complicações , Doenças dos Genitais Femininos/prevenção & controle , Zidovudina/uso terapêutico , Lamivudina/uso terapêutico , Infecções Sexualmente Transmissíveis/fisiopatologia , Infecções Sexualmente Transmissíveis/psicologia , Gonorreia/complicações , Gonorreia/prevenção & controle , Sífilis/fisiopatologia , Ritonavir/uso terapêuticoRESUMO
OBJETIVO: Avaliar a prevalência de infecção por Chlamydia trachomatis e Neisseria gonorrhoeae em mulheres submetidas à reprodução assistida em um serviço público de referência da região Centro-Oeste do Brasil. MÉTODOS: Estudo transversal com 340 mulheres com idade entre 20 e 47 anos, histórico de infertilidade, submetidas às técnicas de reprodução assistida. Foram analisadas as infecções por Chlamydia trachomatis e Neisseria gonorrhoeae detectadas em amostras de urina pela técnica de PCR e o perfil da infertilidade. Utilizou-se o teste do χ2 ou o teste exato de Fisher para avaliar a associação entre a infecção e as variáveis. RESULTADOS: Observou-se prevalência de 10,9% das mulheres com infecção por Chlamydia trachomatis, sendo que houve coinfecção por Neisseria gonorrhoeae em 2 casos. Mulheres infectadas por Chlamydia trachomatis apresentaram mais de 10 anos de infertilidade (54,1%; p<0,0001). O fator tubário foi a principal causa nos casos com infecção (56,8%; p=0,047). A obstrução tubária foi encontrada em 67,6% dos casos com infecção positiva (p=0,004). CONCLUSÃO: Houve associação da obstrução tubária com a infecção por Chlamydia trachomatis e Neisseria gonorrhoeae, reforçando a necessidade de estratégias efetivas para detecção precoce das doenças sexualmente transmissíveis, principalmente em mulheres assintomáticas em idade fértil. .
PURPOSE: To evaluate the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in women undergoing assisted reproduction in a public reference service in the midwestern region of Brazil. METHODS: A cross-sectional study was conducted on 340 women aged from 20 to 47 years with a history of infertility, undergoing assisted reproduction techniques. Infections with Chlamydia trachomatis and Neisseria gonorrhoeae identified in urine specimens by PCR, and the profile of infertility were analyzed. We used the χ2 test or Fisher's exact test to evaluate the association between infection and variables. RESULTS: The prevalence of Chlamydia trachomatis infection was 10.9%, and Neisseria gonorrhoeae co-infection was observed in 2 cases. Women infected with Chlamydia trachomatis had more than 10 years of infertility (54.1%; p<0.0001). The tubal factor was the main cause in infected cases (56.8%; p=0.047). Tubal occlusion was found in 67.6% of cases with positive infection (p=0.004). CONCLUSION: There was an association of tubal obstruction with infection by Chlamydia trachomatis and Neisseria gonorrhoeae, reinforcing the need for effective strategies for an early detection of sexually transmitted diseases, especially in asymptomatic women of childbearing age. .
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Adulto , Feminino , Humanos , Chlamydia trachomatis , Infecções por Chlamydia/complicações , Infecções por Chlamydia/epidemiologia , Gonorreia/complicações , Gonorreia/epidemiologia , Infertilidade Feminina/microbiologia , Estudos Transversais , Hospitais Públicos , Prevalência , Técnicas de Reprodução Assistida , Estudos RetrospectivosRESUMO
OBJETIVO: Avaliar a prevalência de infecção por Chlamydia trachomatis (CT) e Neisseria gonorrhoeae (NG) em mulheres candidatas ao tratamento tópico e de fertilização in vitro (FIV) em serviço público de referência da Região Sudeste do Brasil. MÉTODOS: Mulheres que tiveram indicação de FIV, no período de 1º de abril de 2008 a 31 de outubro de 2009, foram admitidas sequencialmente no estudo. Foi aplicado um questionário sobre antecedentes ginecológicos e obstétricos e coletada amostra de swab endocervical para pesquisa de CT e NG através de captura híbrida e PCR. As variáveis estudadas foram: faixa etária, cor, escolaridade, tempo de infertilidade, número de gestações e filhos vivos, antecedentes de aborto, gestação ectópica, número de parceiros, Doença Inflamatória Pélvica (DIP), cirurgia pélvica, manipulação de cavidade uterina, tabagismo e uso de drogas ilícitas. As mulheres foram distribuídas segundo presença ou não de infecção por clamídia e a análise foi descritiva. RESULTADOS: Entre as 176 mulheres estudadas a prevalência de infecção por CT foi de 1,1%, não houve infecção por NG. Dois terços das mulheres tinham idade >30 anos, escolaridade >8 anos, <5 anos de infertilidade e 56,2% não tinham filhos. Os principais antecedentes foram cirurgia pélvica (77,8%), manipulação de cavidade uterina (62,5%) e DIP (27,8%). O fator tubário foi o mais prevalente, em 129 mulheres (73,3%), 37,5% com e 35,8% sem laqueadura, os demais fatores tiveram prevalência <30%. CONCLUSÕES: As infecções por CT e NG tiveram baixa prevalência na amostra estudada e são necessários estudos em outros centros do país para confirmar a prevalência de infecções nesse grupo particular de mulheres inférteis.
PURPOSE: To evaluate the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among women candidates to in vitro fertilization (IVF) in a reference public service in southeastern Brazil. METHODS: Women who were referred for IVF from April 1st, 2008 to December 31st, 2009 were enrolled sequentially in the study. A ginecological-obstetrical background questionnaire was applied and endocervical swab samples were obtained to search for CT and NG using hybrid capture and PCR. The variables studied were: age, color, education, duration of infertility, number of pregnancies and living children, history of miscarriage, ectopic pregnancy, number of sex partners, pelvic inflammatory disease (PID), pelvic surgery, manipulation of the uterine cavity, smoking, and illicit drug use. The women were distributed according to the presence/absence of confirmed chlamydia infection and descriptive analysis was employed. RESULTS: Among 176 women tested the prevalence of CT infection was 1.1% and there was no NG infection. Two thirds of the women were >30 years old, with schooling >8 years and <5 years of infertility, and 56.2% had no children. The main background data were pelvic surgery (77.8%), manipulation of the uterine cavity (62.5%) and PID (27.8%). The tubal factor was the most prevalent, 73.3% of women (from 129), 37.5% had been sterilized, 35.8% had not been sterilized, and other factors had a prevalence <30%. CONCLUSIONS: CT and NG infections had a low prevalence in this sample. Studies at other centers in the country are needed to confirm the prevalence of infection in this particular group of infertile women.