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1.
BJOG ; 128(1): 97-100, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33021026

RESUMO

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the vaginal secretions of both reproductive-aged and postmenopausal women during acute SARS-CoV-2 infection. DESIGN: Prospective study. SETTING: A single tertiary, university-affiliated medical centre in Israel. Time period, 1 June 2020 through to 31 July 2020. POPULATION: Women who were hospitalised in a single tertiary medical centre, who were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. METHODS: Women were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. Vaginal RT-PCR swabs were obtained from all study participants after a proper cleansing of the perineum. MAIN OUTCOME MEASURES: Detection of SARS-CoV-2 in vaginal RT-PCR swabs. RESULTS: Vaginal and nasopharyngeal swabs were obtained from 35 women, aged 21-93 years. Twenty-one women (60%) were in their reproductive years, of whom, five were in their third trimester of pregnancy. Most of the participants (57%) were healthy without any underlying medical conditions. Of the 35 patients sampled, 2 (5.7%) had a positive vaginal RT-PCR for SARS-CoV-2, one was premenopausal and the other was a postmenopausal woman. Both women had mild disease. CONCLUSION: Our findings contradict most previous reports, which did not detect the presence of viral colonisation in the vagina. Although passage through the birth canal exposes neonates to the vaginal polymicrobial flora, an acquisition of pathogens does not necessarily mandate neonatal infection or clinical disease. Nevertheless, when delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation, even if it is uncommon. TWEETABLE ABSTRACT: When delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation.


Assuntos
Complicações Infecciosas na Gravidez , Vagina/virologia , Adulto , Idoso , /epidemiologia , /métodos , Feminino , Humanos , Recém-Nascido , Israel/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Prospectivos , Esfregaço Vaginal/métodos , Esfregaço Vaginal/estatística & dados numéricos
2.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(12): 2135-2140, 2020 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-33378829

RESUMO

Objective: To study the relations of human papillomavirus (HPV) infection, vaginal micro-environmental disorder with cervical lesion. Methods: A total of 1 019 women including 623 with normal cervical (NC), 303 with low-grade cervical lesion (CIN Ⅰ) and 93 with high-grade cervical lesion (CIN Ⅱ/Ⅲ) were enrolled in this study from the communities in Shanxi province, China. Case-control method was adopted, with NC as the control group and CIN as the case group. Related information was collected including demographic characteristics and relevant factors related to cervical lesions. HPV genotypes were detected by flow-through hybridization technology. Vaginal pH was detected by the pH test paper. Vaginal H(2)O(2) was detected by the combined detection kit of aerobic vaginitis and bacterial vaginosis. Vaginal cleanliness was detected by smear method. Results: Data from the unconditional logistic regression analysis showed that HPV infection (CINⅠ: aOR=1.39, 95%CI: 1.01-1.90; CINⅡ/Ⅲ: aOR=11.74, 95%CI: 6.96-19.80), H(2)O(2) (CINⅠ: aOR=2.09, 95%CI: 1.47-2.98; CINⅡ/Ⅲ: aOR=4.12, 95%CI: 2.01-8.43), cleanliness (CIN Ⅱ/Ⅲ: aOR=2.62, 95%CI: 1.65-4.14), and composite indicators (CINⅠ: aOR=1.67, 95%CI: 1.24-2.25; CINⅡ/Ⅲ: aOR=4.24, 95%CI: 2.30-7.81) all had increased the risk of cervical lesion and the trend on the severity (P<0.001) of cervical lesions. Additionally, we observed a synergic effect between HPV infection and vaginal micro-environmental composite indicator in CINⅡ/Ⅲ. With or without HPV infection, the ORs value of CINⅠ caused by vaginal micro-environment disorder remained close. Conclusions: Results from our study revealed that vaginal micro-environmental composite indicator could increase the risk for cervical lesion, in particular with the high-grade ones which all posed stronger risks when combined with HPV infection. However, the role of vaginal micro-environment disorder in the occurrence of CIN Ⅰ should not be ignored.


Assuntos
Neoplasia Intraepitelial Cervical , Infecções por Papillomavirus , Microambiente Tumoral , Vagina , Neoplasia Intraepitelial Cervical/epidemiologia , China/epidemiologia , Feminino , Humanos , Infecções por Papillomavirus/epidemiologia , Vagina/microbiologia , Vagina/virologia , Esfregaço Vaginal
3.
J Virol ; 94(18)2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32611749

RESUMO

Us3 proteins of herpes simplex virus 1 (HSV-1) and HSV-2 are multifunctional serine-threonine protein kinases. Here, we identified an HSV-2 tegument protein, UL7, as a novel physiological substrate of HSV-2 Us3. Mutations in HSV-2 UL7, which precluded Us3 phosphorylation of the viral protein, significantly reduced mortality, viral replication in the vagina, and development of vaginal disease in mice following vaginal infection. These results indicated that Us3 phosphorylation of UL7 in HSV-2 was required for efficient viral replication and pathogenicity in vivo Of note, this phosphorylation was conserved in UL7 of chimpanzee herpesvirus (ChHV), which phylogenetically forms a monophyletic group with HSV-2 and the resurrected last common ancestral UL7 for HSV-2 and ChHV. In contrast, the phosphorylation was not conserved in UL7s of HSV-1, which belongs to a sister clade of the monophyletic group, the resurrected last common ancestor for HSV-1, HSV-2, and ChHV, and other members of the genus Simplexvirus that are phylogenetically close to these viruses. Thus, evolution of Us3 phosphorylation of UL7 coincided with the phylogeny of simplex viruses. Furthermore, artificially induced Us3 phosphorylation of UL7 in HSV-1, in contrast to phosphorylation in HSV-2, had no effect on viral replication and pathogenicity in mice. Our results suggest that HSV-2 and ChHV have acquired and maintained Us3 phosphoregulation of UL7 during their evolution because the phosphoregulation had an impact on viral fitness in vivo, whereas most other simplex viruses have not because the phosphorylation was not necessary for efficient fitness of the viruses in vivo IMPORTANCE It has been hypothesized that the evolution of protein phosphoregulation drives phenotypic diversity across species of organisms, which impacts fitness during their evolution. However, there is a lack of information regarding linkage between the evolution of viral phosphoregulation and the phylogeny of virus species. In this study, we clarified the novel HSV-2 Us3 phosphoregulation of UL7 in infected cells, which is important for viral replication and pathogenicity in vivo We also showed that the evolution of Us3 phosphoregulation of UL7 was linked to the phylogeny of viruses that are phylogenetically close to HSV-2 and to the phosphorylation requirements for the efficient in vivo viral fitness of HSV-2 and HSV-1, which are representative of viruses that have and have not evolved phosphoregulation, respectively. This study reports the first evidence showing that evolution of viral phosphoregulation coincides with phylogeny of virus species and supports the hypothesis regarding the evolution of viral phosphoregulation during viral evolution.


Assuntos
Regulação Viral da Expressão Gênica , Herpes Genital/virologia , Herpesvirus Humano 2/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas da Matriz Viral/genética , Proteínas Virais/genética , Proteínas Estruturais Virais/genética , Sequência de Aminoácidos , Animais , Chlorocebus aethiops , Modelos Animais de Doenças , Evolução Molecular , Feminino , Aptidão Genética , Células HEK293 , Herpes Genital/mortalidade , Herpesvirus Humano 1/classificação , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/classificação , Herpesvirus Humano 2/metabolismo , Herpesvirus Humano 2/patogenicidade , Humanos , Camundongos , Fosforilação , Filogenia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Vagina/virologia , Células Vero , Proteínas da Matriz Viral/metabolismo , Proteínas Virais/metabolismo , Proteínas Estruturais Virais/metabolismo , Virulência , Replicação Viral
5.
Nat Commun ; 11(1): 3195, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581216

RESUMO

Penile acquisition of HIV accounts for most infections among men globally. Nevertheless, candidate HIV interventions for men advance to clinical trials without preclinical efficacy data, due primarily to a paucity of relevant animal models of penile HIV infection. Using our recently developed macaque model, we show that a single subcutaneous administration of broadly neutralizing antibody (bNAb) 10-1074 conferred durable protection against repeated penile exposures to simian-human immunodeficiency virus (SHIVSF162P3). Macaques co-administered bNAbs 10-1074 and 3BNC117, or 3BNC117 alone, also exhibited significant protection against repeated vaginal SHIVAD8-EO exposures. Regression modeling estimated that individual plasma bNAb concentrations of 5 µg ml-1 correlated with ≥99.9% relative reduction in SHIV infection probability via penile (10-1074) or vaginal (10-1074 or 3BNC117) challenge routes. These results demonstrate that comparably large reductions in penile and vaginal SHIV infection risk among macaques were achieved at clinically relevant plasma bNAb concentrations and inform dose selection for the development of bNAbs as long-acting pre-exposure prophylaxis candidates for use by men and women.


Assuntos
Vacinas contra a AIDS/administração & dosagem , Anticorpos Amplamente Neutralizantes/administração & dosagem , Anticorpos Anti-HIV/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Vírus da Imunodeficiência Símia/imunologia , Vacinas contra a AIDS/sangue , Animais , Anticorpos Amplamente Neutralizantes/sangue , Modelos Animais de Doenças , Feminino , Anticorpos Anti-HIV/sangue , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Meia-Vida , Imunização Passiva , Macaca mulatta , Masculino , Pênis/imunologia , Pênis/virologia , Profilaxia Pré-Exposição , Vagina/imunologia , Vagina/virologia
6.
Int J Gynaecol Obstet ; 150(1): 53-57, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32350871

RESUMO

OBJECTIVE: To study vaginal delivery outcomes and neonatal prognosis and summarize the management of vaginal delivery during the COVID-19 pandemic. METHODS: A retrospective analysis of medical records and comparison of vaginal delivery outcomes between 10 pregnant women with clinical diagnosis of COVID-19 and 53 pregnant women without COVID-19 admitted to Zhongnan Hospital of Wuhan University between January 20 and March 2, 2020. Results of laboratory tests, imaging tests, and SARS-CoV-2 nucleic acid tests were also analyzed in neonates delivered by pregnant women with clinical diagnosis of COVID-19. RESULTS: There were no significant differences in gestational age, postpartum hemorrhage, and perineal resection rates between the two groups. There were no significant differences in birth weight of neonates and neonatal asphyxia rates between the two groups. Neonates delivered by pregnant women with clinical diagnosis of COVID-19 tested negative for SARS-CoV-2 infection. CONCLUSIONS: Under the premise of full evaluation of vaginal delivery conditions and strict protection measures, pregnant women with ordinary type COVID-19 can try vaginal delivery without exacerbation of COVID-19 and without increasing the risk of SARS-CoV-2 infection in neonates.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Parto Obstétrico/métodos , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez/epidemiologia , Adulto , Peso ao Nascer , China/epidemiologia , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Hemorragia Pós-Parto/epidemiologia , Hemorragia Pós-Parto/virologia , Gravidez , Estudos Retrospectivos , Vagina/virologia
7.
BMC Infect Dis ; 20(1): 375, 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460721

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) cause a major public health problem that affect both men and women in developing and developed countries. The aim of the study was to estimate the prevalence of 11 STIs among women who voluntarily participated in the study, while seeking gynecological checkup. The existence of an association between the presence of pathogens and symptoms and various sociodemographic risk factors was assessed. METHODS: A total of 505 vaginal and cervical specimens were collected from women above 18 years of age, with or without symptoms related to gynecological infections. Nucleic acid was extracted and samples were tested by real-time PCR for the following pathogens: Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Ureaplasma urealyticum, Urealplasma parvum, Trichomonas vaginalis, Mycoplasma hominis, Mycoplasma girerdii, Gardnerella vaginalis, Candida albicans and Human Papillomavirus (HPV). Positive HPV samples underwent genotyping using a microarray system. RESULTS: Of the 505 samples, 312 (62%) were screened positive for at least one pathogen. Of these, 36% were positive for Gardnerella vaginalis, 35% for Ureaplasma parvum, 8% for Candida albicans, 6.7% for HPV, 4.6% for Ureaplasma urealyticum, 3.6% for Mycoplasma hominis, 2% for Trichomonas vaginalis, 0.8% for Chlamydia trachomatis, 0.4% for Mycoplasma girerdii, 0.2% for Mycoplasma genitalium and 0.2% for Neisseria gonorrhoeae. Lack of symptoms was reported in 187 women (37%), among whom 61% were infected. Thirty-four samples were HPV positive, with 17 high risk HPV genotypes (HR-HPV); the highest rates being recorded for types 16 (38%), 18 (21%) and 51 (18%). Out of the 34 HPV positives, 29 participants had HR-HPV. Association with various risk factors were reported. CONCLUSIONS: This is the first study that presents data about the presence of STIs among women in Lebanon and the MENA region by simultaneous detection of 11 pathogens. In the absence of systematic STI surveillance in Lebanon, concurrent screening for HPV and PAP smear is warranted.


Assuntos
Doenças Sexualmente Transmissíveis/epidemiologia , Adulto , Colo do Útero/microbiologia , Colo do Útero/parasitologia , Colo do Útero/virologia , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Estudos Transversais , Feminino , Gardnerella vaginalis/genética , Gardnerella vaginalis/isolamento & purificação , Humanos , Líbano/epidemiologia , Masculino , Epidemiologia Molecular , Infecções por Mycoplasma/epidemiologia , Mycoplasma genitalium/genética , Mycoplasma genitalium/isolamento & purificação , Mycoplasma hominis/genética , Mycoplasma hominis/isolamento & purificação , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/isolamento & purificação , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Fatores de Risco , Doenças Sexualmente Transmissíveis/microbiologia , Doenças Sexualmente Transmissíveis/parasitologia , Doenças Sexualmente Transmissíveis/virologia , Trichomonas vaginalis/genética , Trichomonas vaginalis/isolamento & purificação , Ureaplasma/genética , Ureaplasma/isolamento & purificação , Vagina/microbiologia , Vagina/parasitologia , Vagina/virologia , Esfregaço Vaginal , Adulto Jovem
8.
Sci Rep ; 10(1): 8514, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444843

RESUMO

The immunology and microbiota of the female genital tract (FGT) are key determinants of HIV susceptibility. Cervical cytobrush sampling is a relatively non-invasive method permitting the longitudinal assessment of endocervical immune cells, but effects on FGT immunology are unknown. Blood, cervico-vaginal secretions and cervical cytobrushes were collected from sexually transmitted infection (STI)-free women at baseline and after either 6 hours or 48 hours. Endocervical immune cell subsets were assessed by flow cytometry, and pro-inflammatory cytokines by multiplex ELISA. The density of Lactobacillus species and key bacterial vaginosis-associated bacterial taxa were determined by qPCR. Paired changes were assessed before and after cytobrush sampling. After 6 hours there were significant increases in CD4 + T cell, antigen presenting cell (APC) and neutrophil numbers; APC elevations persisted at 48 hours, while neutrophil and CD4 + T cell numbers returned to baseline. In addition, pro-inflammatory cytokine levels were increased at 6 hours and returned to baseline by 48 hours. No significant changes were observed in the absolute abundance of Lactobacillus species or BV-associated bacteria at either time point. Overall, cytobrush sampling altered genital immune parameters at 6 hours, but only APC number increases persisted at 48 hours. This should be considered in longitudinal analyses of FGT immunology.


Assuntos
Colo do Útero/imunologia , Infecções por HIV/epidemiologia , HIV/isolamento & purificação , Microbiota/imunologia , Manejo de Espécimes/métodos , Vagina/imunologia , Vaginose Bacteriana/imunologia , Adolescente , Adulto , Canadá/epidemiologia , Colo do Útero/microbiologia , Colo do Útero/virologia , Citocinas/análise , Citocinas/imunologia , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/etiologia , Humanos , Estudos Prospectivos , Vagina/microbiologia , Vagina/virologia , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/virologia , Carga Viral , Adulto Jovem
10.
Eur J Obstet Gynecol Reprod Biol ; 250: 246-249, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32418711

RESUMO

The risk of vertical transmission during vaginal delivery in COVID-19 pregnant patients is currently a topic of debate. Obstetric norms on vaginal birth assistance to reduce the potential risk of perinatal infection should be promoted by ensuring that the risk of contamination from maternal anus and faecal material is reduced during vaginal delivery.


Assuntos
Betacoronavirus , Infecções por Coronavirus/transmissão , Parto Obstétrico/métodos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez/virologia , Infecções por Coronavirus/virologia , Feminino , Humanos , Pandemias , Pneumonia Viral/virologia , Gravidez , Vagina/virologia
12.
BJOG ; 127(9): 1109-1115, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32369656

RESUMO

OBJECTIVE: To assess whether vaginal secretions and breast milk of women with coronavirus disease 2019 (COVID-19) contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN: Single centre cohort study. SETTING: Renmin Hospital of Wuhan University, Wuhan, Hubei province, China. POPULATION: We studied 13 SARS-CoV-2-infected pregnant women diagnosed between 31 January and 9 March 2020. METHODS: We collected clinical data, vaginal secretions, stool specimens and breast milk from SARS-CoV-2-infected women during different stages of pregnancy and collected neonatal throat and anal swabs. MAIN OUTCOMES AND MEASURES: We assessed viral presence in different biosamples. RESULTS: Of the 13 women with COVID-19, five were in their first trimester, three in their second trimester and five in their third trimester. Of the five women in their third trimester who gave birth, all delivered live newborns. Among these five deliveries, the primary adverse perinatal outcomes included premature delivery (n = 2) and neonatal pneumonia (n = 2). One of nine stool samples was positive; all 13 vaginal secretion samples, and five throat swabs and four anal swabs collected from neonates, were negative for the novel coronavirus. However, one of three samples of breast milk was positive by viral nucleic acid testing. CONCLUSIONS: In this case series of 13 pregnant women with COVID-19, we observed negative viral test results in vaginal secretion specimens, suggesting that a vaginal delivery may be a safe delivery option. However, additional research is urgently needed to examine breast milk and the potential risk for viral contamination. TWEETABLE ABSTRACT: New evidence for the safety of vaginal delivery and breastfeeding in pregnant women infected with SARS-CoV-2, positive viral result in a breast-milk sample.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Leite Humano/virologia , Pneumonia Viral/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Vagina/virologia , Adulto , Canal Anal/virologia , Aleitamento Materno , China , Estudos de Coortes , Infecções por Coronavirus/transmissão , Parto Obstétrico , Fezes/virologia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doença Infecciosa , Pandemias , Faringe/virologia , Pneumonia Viral/transmissão , Gravidez , Complicações Infecciosas na Gravidez/virologia
13.
PLoS One ; 15(4): e0232105, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32320451

RESUMO

Cervical cancer is a significant public health problem, especially in low- and middle-income countries, where women have little access to cervical cancer screening; consequently 80% of cervical cancer related mortality occurs in these regions. The development of screening methods that need less infrastructure thus represents an urgent medical need. The study aims to compare the detection rates of high-risk human papillomavirus 16 and 18 E6 oncoprotein in urine, vaginal self-collected, and cervical scrapes of women using the OncoE6™ Cervical Test and compare the HPV16 and/or HPV18 E6 detection rates with the HPV DNA testing. Paired urine, vaginal self-collected and cervical specimens were collected from 124 women who participated in cervical cancer screening or treatment in this proof-of-concept study and underwent to HPV16/18-E6 testing and high-risk HPV DNA testing prior to treatment of cervical neoplasia or cancer. Concordance between urinary, vaginal and cervical HPV16/18-E6 and HPV-DNA testing was evaluated for patients classified as negative group (

Assuntos
Proteínas de Ligação a DNA/urina , Imunoensaio/métodos , Proteínas Oncogênicas Virais/urina , Proteínas Repressoras/urina , Adulto , Proteínas de Ligação a DNA/genética , Feminino , Testes de DNA para Papilomavírus Humano , Papillomavirus Humano 16/genética , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/virologia , Proteínas Repressoras/genética , Neoplasias do Colo do Útero/virologia , Vagina/virologia
14.
BJOG ; 127(9): 1116-1121, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32339382

RESUMO

OBJECTIVE: To report mode of delivery and immediate neonatal outcome in women infected with COVID-19. DESIGN: Retrospective study. SETTING: Twelve hospitals in northern Italy. PARTICIPANTS: Pregnant women with COVID-19-confirmed infection who delivered. EXPOSURE: COVID 19 infection in pregnancy. METHODS: SARS-CoV-2-infected women who were admitted and delivered from 1 to 20 March 2020 were eligible. Data were collected from the clinical records using a standardised questionnaire on maternal general characteristics, any medical or obstetric co-morbidity, course of pregnancy, clinical signs and symptoms, treatment of COVID 19 infection, mode of delivery, neonatal data and breastfeeding. MAIN OUTCOME AND MEASURES: Data on mode of delivery and neonatal outcome. RESULTS: In all, 42 women with COVID-19 delivered at the participating centres; 24 (57.1%, 95% CI 41.0-72.3) delivered vaginally. An elective caesarean section was performed in 18/42 (42.9%, 95% CI 27.7-59.0) cases: in eight cases the indication was unrelated to COVID-19 infection. Pneumonia was diagnosed in 19/42 (45.2%, 95% CI 29.8-61.3) cases: of these, 7/19 (36.8%, 95% CI 16.3-61.6) required oxygen support and 4/19 (21.1%, 95% CI 6.1-45.6) were admitted to a critical care unit. Two women with COVID-19 breastfed without a mask because infection was diagnosed in the postpartum period: their newborns tested positive for SARS-Cov-2 infection. In one case, a newborn had a positive test after a vaginal operative delivery. CONCLUSIONS: Although postpartum infection cannot be excluded with 100% certainty, these findings suggest that vaginal delivery is associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn. TWEETABLE ABSTRACT: This study suggests that vaginal delivery may be associated with a low risk of intrapartum SARS-Cov-2 transmission to the newborn.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Parto Obstétrico/efeitos adversos , Transmissão Vertical de Doença Infecciosa , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , Feminino , Humanos , Recém-Nascido , Itália , Masculino , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Retrospectivos , Vagina/virologia
15.
J Virol ; 94(12)2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32295905

RESUMO

We demonstrate that female C57BL/6J mice are susceptible to a transient lower genital tract infection with MmuPV1 mouse papillomavirus and display focal histopathological abnormalities resembling those of human papillomavirus (HPV) infection. We took advantage of strains of genetically deficient mice to study in vivo the role of innate immune signaling in the control of papillomavirus. At 4 months, we sacrificed MmuPV1-infected mice and measured viral 757/3139 spliced transcripts by TaqMan reverse transcription-PCR (RT-PCR), localization of infection by RNAscope in situ hybridization, and histopathological abnormities by hematoxylin and eosin (H&E) staining. Among mice deficient in receptors for pathogen-associated molecular patterns, MyD88-/- and STING-/- mice had 1,350 and 80 copies of spliced transcripts/µg RNA, respectively, while no viral expression was detected in MAVS-/- and Ripk2-/- mice. Mice deficient in an adaptor molecule, STAT1-/-, for interferon signaling had 46,000 copies/µg RNA. Among mice with targeted deficiencies in the inflammatory response, interleukin-1 receptor knockout (IL-1R-/-) and caspase-1-/- mice had 350 and 30 copies/µg RNA, respectively. Among mice deficient in chemokine receptors, CCR6-/- mice had 120 copies/µg RNA, while CXCR2-/- and CXCR3-/- mice were negative. RNAscope confirmed focal infection in MyD88-/-, STAT1-/-, and CCR6-/- mice but was negative for other gene-deficient mice. Histological abnormalities were seen only in the latter mice. Our findings and the literature support a working model of innate immunity to papillomaviruses involving the activation of a MyD88-dependent pathway and IL-1 receptor signaling, control of viral replication by interferon-stimulated genes, and clearance of virus-transformed dysplastic cells by the action of the CCR6/CCL20 axis.IMPORTANCE Papillomaviruses infect stratified squamous epithelia, and the viral life cycle is linked to epithelial differentiation. Additionally, changes occur in viral and host gene expression, and immune cells are activated to modulate the infectious process. In vitro studies with keratinocytes cannot fully model the complex viral and host responses and do not reflect the contribution of local and migrating immune cells. We show that female C57BL/6J mice are susceptible to a transient papillomavirus cervicovaginal infection, and mice deficient in select genes involved in innate immune responses are susceptible to persistent infection with variable manifestations of histopathological abnormalities. The results of our studies support a working model of innate immunity to papillomaviruses, and the model provides a framework for more in-depth studies. A better understanding of mechanisms of early viral clearance and the development of approaches to induce clearance will be important for cancer prevention and the treatment of HPV-related diseases.


Assuntos
Interações Hospedeiro-Patógeno/imunologia , Fator 88 de Diferenciação Mieloide/imunologia , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , RNA Mensageiro/imunologia , RNA Viral/imunologia , Receptores Tipo I de Interleucina-1/imunologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Processamento Alternativo , Animais , Caspase 1/deficiência , Caspase 1/genética , Caspase 1/imunologia , Colo do Útero/imunologia , Colo do Útero/virologia , Feminino , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/deficiência , Fator 88 de Diferenciação Mieloide/genética , Papillomaviridae/crescimento & desenvolvimento , Papillomaviridae/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , RNA Mensageiro/genética , RNA Viral/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/deficiência , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/imunologia , Receptores CCR6/deficiência , Receptores CCR6/genética , Receptores CCR6/imunologia , Receptores CXCR3/deficiência , Receptores CXCR3/genética , Receptores CXCR3/imunologia , Receptores Tipo I de Interleucina-1/deficiência , Receptores Tipo I de Interleucina-1/genética , Receptores de Interleucina-8B/deficiência , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/imunologia , Fator de Transcrição STAT1/deficiência , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/imunologia , Transdução de Sinais , Vagina/imunologia , Vagina/virologia
16.
Clin Infect Dis ; 71(15): 813-817, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32241022

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spread mainly through respiratory droplets or direct contact. However, the infection condition of the genital system is unknown. Our aim in this study was to determine if SARS-CoV-2 is present in the vaginal fluid of women with coronavirus disease 2019 (COVID-19). METHODS: Ten women with confirmed severe COVID-19 pneumonia admitted to the Tongji Zhongfa Hospital intensive care unit from 4 February 2020 through 24 February 2020 were included. Clinical records, laboratory results, and computed tomography examinations were retrospectively reviewed. The potential for genital infection was accessed by testing for the presence of SARS-CoV-2 in vaginal fluids obtained from vaginal swab samples. Reverse transcriptase polymerase chain reaction was used to confirm the SARS-CoV-2 infection in vaginal fluids. RESULTS: The clinical characteristics of the 10 women were similar to those reported in other severe COVID-19 patients. All 10 patients were tested for SARS-CoV-2 in vaginal fluid, and all samples tested negative for the virus. CONCLUSIONS: Findings from this small group of cases suggest that SARS-CoV-2 virus does not exist in the vaginal fluids of severe COVID-19 patients.


Assuntos
Secreções Corporais/virologia , Líquidos Corporais/virologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Vagina/virologia , Betacoronavirus/genética , Feminino , Humanos , Pandemias , Estudos Retrospectivos , Síndrome Respiratória Aguda Grave/virologia
17.
J Virol ; 94(11)2020 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188737

RESUMO

Zika virus (ZIKV) infection is now firmly linked to congenital Zika syndrome (CZS), including fetal microcephaly. While Aedes species of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse, and nonhuman primate (NHP) semen. It is critical to establish NHP models of the vertical transfer of ZIKV that recapitulate human pathogenesis. We hypothesized that vaginal deposition of ZIKV-infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Epidemiological studies suggest an increased rate of CZS in the Americas compared to the original link to CZS in French Polynesia; therefore, we also compared the French Polynesian (FP) ZIKV isolate to the Puerto Rican (PR) isolate. Timed-pregnant baboons (n = 6) were inoculated via vaginal deposition of baboon semen containing 106 focus-forming units (FFU) of ZIKV (n = 3 for FP isolate H/PF/2013; n = 3 for PR isolate PRVABC59) at midgestation (86 to 95 days of gestation [dG]; term, 183 dG) on day 0 (all dams) and then at 7-day intervals through 3 weeks. Maternal blood, saliva, and cervicovaginal wash (CVW) samples were obtained. Animals were euthanized at 28 days (n = 5) or 39 days (n = 1) after the initial inoculation, and maternal/fetal tissues were collected. Viremia was achieved in 3/3 FP ZIKV-infected dams and 2/3 PR ZIKV-infected dams. ZIKV RNA was detected in CVW samples of 5/6 dams. ZIKV RNA was detected in lymph nodes but not the ovaries, uterus, cervix, or vagina in FP isolate-infected dams. ZIKV RNA was detected in lymph nodes (3/3), uterus (2/3), and vagina (2/3) in PR isolate-infected dams. Placenta, amniotic fluid, and fetal tissues were ZIKV RNA negative in the FP isolate-infected dams, whereas 2/3 PR isolate-infected dam placentas were ZIKV RNA positive. We conclude that ZIKV-infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of widespread dissemination to tissues, including reproductive tissues and placenta, than the FP isolate.IMPORTANCE Zika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the first study in nonhuman primates to demonstrate infection via vaginal deposition of Zika virus-infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika virus infection of reproductive tissues. We also found that compared to the French Polynesian isolate, the Puerto Rican Zika virus isolate led to greater spread throughout the body, particularly in reproductive tissues. The American isolates of Zika virus appear to have acquired mutations that increase their efficacy.


Assuntos
Doenças dos Macacos , Complicações Infecciosas na Gravidez , Sêmen/virologia , Vagina/virologia , Infecção por Zika virus , Zika virus/metabolismo , Animais , Feminino , Masculino , Doenças dos Macacos/metabolismo , Doenças dos Macacos/patologia , Doenças dos Macacos/transmissão , Doenças dos Macacos/virologia , Papio anubis , Gravidez , Complicações Infecciosas na Gravidez/metabolismo , Complicações Infecciosas na Gravidez/patologia , Complicações Infecciosas na Gravidez/veterinária , RNA Viral/metabolismo , Vagina/patologia , Infecção por Zika virus/metabolismo , Infecção por Zika virus/patologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/veterinária
18.
Anticancer Res ; 40(3): 1513-1517, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132051

RESUMO

BACKGROUND/AIM: Cervical cancer is the most common cancer among women in Ethiopia. The objective was to evaluate the participation rate of a free of charge vaginal self-sample (Aptima multitest swab, Hologic) for the detection of human papillomavirus (HPV) in an Ethiopian cohort. PATIENTS AND METHODS: Specimens were collected from women employed by Ethiopian Airlines in Addis Abeba (N=5950). Samples were analysed for the presence of high-risk (HR) HPV mRNA by the Aptima HPV assay (Hologic) and HPV positive women were referred for cytology. Identification of HPV types among HPV positive samples was performed by Modified general primer-PCR and Luminex assay. RESULTS: Participation rate was 3.1% and the prevalence of HPV mRNA was 20.6% (37/180). CONCLUSION: Primary HPV mRNA screening with vaginal self-sampling may be an acceptable approach in Ethiopia. One out of five women harbor HPV in their vaginal self-sample in agreement with other similar studies from the region.


Assuntos
Papillomaviridae/genética , RNA Mensageiro/análise , RNA Viral/análise , Vagina/virologia , Adolescente , Adulto , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/estatística & dados numéricos , Etiópia/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prevalência , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vagina/patologia , Esfregaço Vaginal , Adulto Jovem
19.
J Immunol ; 204(7): 1703-1707, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32122994

RESUMO

The presence of tissue-resident memory T cells at barrier tissues is critical for long-lasting protective immune responses. Previous work has shown that tissue-resident memory T cells can be established by "pulling" virus-specific effector T cells from circulation to the genital mucosa via topical vaginal application of chemokines in mice. Once established, these cells protect hosts against genital herpes infection. We recently showed that vaginal application of aminoglycoside antibiotics induces robust activation of the IFN signaling pathway, including upregulation of chemokine expression within the tissue in mice. In this study, we show that a single topical application of neomycin, an inexpensive and vaginally nontoxic antibiotic, is sufficient to pull CD8 T cells to the vaginal mucosa and provide protection against genital herpes infection in mice.


Assuntos
Aminoglicosídeos/imunologia , Vacinas Virais/imunologia , Administração Tópica , Animais , Antibacterianos/imunologia , Linfócitos T CD8-Positivos/imunologia , Quimiocinas/imunologia , Feminino , Herpes Genital/imunologia , Herpes Genital/virologia , Memória Imunológica/imunologia , Interferons/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Membrana Mucosa/imunologia , Membrana Mucosa/virologia , Neomicina/imunologia , Transdução de Sinais/imunologia , Regulação para Cima/imunologia , Vagina/imunologia , Vagina/virologia
20.
Proc Natl Acad Sci U S A ; 117(11): 6121-6128, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32123072

RESUMO

Virus replication requires critical interactions between viral proteins and cellular proteins that mediate many aspects of infection, including the transport of viral genomes to the site of replication. In human papillomavirus (HPV) infection, the cellular protein complex known as retromer binds to the L2 capsid protein and sorts incoming virions into the retrograde transport pathway for trafficking to the nucleus. Here, we show that short synthetic peptides containing the HPV16 L2 retromer-binding site and a cell-penetrating sequence enter cells, sequester retromer from the incoming HPV pseudovirus, and inhibit HPV exit from the endosome, resulting in loss of viral components from cells and in a profound, dose-dependent block to infection. The peptide also inhibits cervicovaginal HPV16 pseudovirus infection in a mouse model. These results confirm the retromer-mediated model of retrograde HPV entry and validate intracellular virus trafficking as an antiviral target. More generally, inhibiting virus replication with agents that can enter cells and disrupt essential protein-protein interactions may be applicable in broad outline to many viruses.


Assuntos
Proteínas do Capsídeo/metabolismo , Peptídeos Penetradores de Células/farmacologia , Papillomavirus Humano 16/efeitos dos fármacos , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/tratamento farmacológico , Internalização do Vírus/efeitos dos fármacos , Animais , Peptídeos Penetradores de Células/uso terapêutico , Colo do Útero/virologia , Modelos Animais de Doenças , Feminino , Células HEK293 , Células HeLa , Papillomavirus Humano 16/fisiologia , Humanos , Camundongos , Infecções por Papillomavirus/virologia , Ligação Proteica/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacos , Vagina/virologia
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