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1.
Transpl Infect Dis ; : e13209, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31698532

RESUMO

BACKGROUND: Reactivation of Chagas disease after heart transplantation is characterized by proliferation and dissemination of Trypanosoma cruzi parasites to several organs. Reactivation affecting the allograft can simulate acute cellular rejection, from which it should be distinguished through the analysis of endomyocardial biopsies (EMB). METHODS: We evaluated retrospectively 100 EMB collected in the first year of follow-up from 13 heart-transplanted, chagasic patients who presented reactivation and were successfully treated. Additionally, 37 EMB from 8 patients who did not present reactivation constituted the control group. We reviewed histopathology and performed a real-time PCR-based assay in order to evaluate the T cruzi parasitic load of each EMB. RESULTS: The parasitic load of the EMB at the time of reactivation ranged from 22.80 to 190 000/106 cells (median: 1555). In 6 patients, none of the EMB obtained prior to reactivation amplified T cruzi DNA. On the other hand, 10 EMB from 7 patients, obtained 9-105 days before reactivation (median: 26 days), showed parasitic load ranging from 8.25 to 625/106 cells (median: 167.55). In all patients, the parasitic load increased at the time of reactivation, usually sharply. After initiation of treatment, all patients showed negative PCR or a dramatic reduction of the parasitic load in the following EMB. None of the EMB from the control group amplified T cruzi DNA. CONCLUSIONS: Sequential measurement of T cruzi parasitic load in EMB is useful for monitoring Chagas disease reactivation after heart transplantation. Its increase suggests imminent reactivation and its decrease after treatment indicates favorable evolution for cure of the episode of reactivation.

4.
PLoS One ; 14(8): e0215708, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374094

RESUMO

The accurate diagnosis and seroprevalence investigations of Zika virus (ZKV) infections remain complex due to cross reactivity with other flaviviruses. Two assay formats, both using labelled Zika virus NS1 antigen as a revealing agent (a double antigen binding assay, DABA, and an immunoglobulin Ig capture assay, G capture) were initially developed and compared with the indirect EuroimmunZ assay for the detection of anti-Zika antibody. Of 147 pre-Zika period serum samples, 39 (27%) were reactive in the EuroimmunZ or the DABA assays, 28 sera concordantly so. Such false reactivity was influenced by the serotype of Dengue virus (DV) to which individuals had been exposed to. Thus, of sera from patients undergoing secondary Dengue virus infection of known serotype, 91%, 45% and 28% of Dengue virus serotype 2, 3 and 4 respectively were reactive in one or more of the three assays. A novel method of quenching false sero-reactivity was therefore developed for the DABA and G capture assays. Initial addition of a single homologous Dengue virus serotype 3 NS1Ag quench significantly ablated false reactivities in the pre-Zika period sera. An equipotent quadrivalent quench comprising homologous Dengue virus serotypes 1 to 4 NS1Ag was shown to be optimum yet retained sensitivity for the detection of specific anti-Zika antibody. Comparing DABA and G capture assays using quenched and unquenched conjugates in comparison with EuroimmunZ early in the course of PCR-confirmed infection indicated that a significant component of the apparent early anti-ZIKA antibody response is likely to be due to a Zika virus-driven anamnestic anti-Dengue virus response. The increased specificity provided by homologous antigen quenching is likely to provide a significant improvement in sero-diagnostics and to be of clinical value.

5.
Lancet infect. dis ; 19(7): 750-758, July 2019. ilus, tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IIERPROD, Sec. Est. Saúde SP | ID: biblio-1016885

RESUMO

BACKGROUND: Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of São Paulo city, Brazil. METHODS: In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in São Paolo­the Hospital das Clínicas, University of São Paulo and the Infectious Diseases Institute "Emilio Ribas". Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death). FINDINGS: Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clínicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute "Emilio Ribas". 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5·1 log10 copies/mL or greater died (95% CI 72­100), compared with only three (11%) of 27 (95% CI 2­29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5·1 log10 copies/mL. INTERPRETATION: We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever


Assuntos
Humanos , Febre Amarela/mortalidade , Brasil/epidemiologia
6.
Cancer Prev Res (Phila) ; 12(8): 539-546, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31189569

RESUMO

Every year there are approximately 16,000 new cases of cervical cancer in Brazil. Novel screening technologies may reduce this number by expanding the population coverage but also by improving the detection rate of precursor lesions. We aimed to evaluate human papillomaviruses (HPV)-DNA testing in the context of routine cervical cancer screening in the public health system of the city of São Paulo, Brazil. Women participating in the primary screening program were invited to enroll. Liquid-based cytology samples were collected and cytology and Hr-HPV DNA testing were performed in parallel. Cytologists were blind to HPV results. Women older than 24 years with a positive high-risk HPV test and/or cytology class ≥ ASC-US were referred to colposcopy. From December 2014 to December 2016, 16,102 women joined the study. High-risk human papillomavirus (HR HPV) DNA prevalence was 14.9%, whereas cytologic abnormalities were found in 7.2% of the women. Per protocol, 1,592 Hr-HPV+ women, in addition to 72 patients with cytologic classification > low-grade squamous intraepithelial lesion (LSIL) were referred. A total of 80 cervical intraepithelial neoplasia (CIN2+) cases were diagnosed, 79 were Hr-HPV DNA+ and 18 had normal cytology. Hr-HPV DNA detected a significant number of patients with premalignant lesions missed by cytology and all 16 CIN3+ cases were Hr-HPV DNA+ HPV genotyping may be useful in the management of Hr-HPV+ women, reducing the burden of colposcopic referral for those harboring genotypes with a weaker association to CIN3+ Use of HPV-DNA testing was shown to be feasible and advantageous over current cytologic screening in the public health system.

7.
Lancet Infect Dis ; 19(7): 750-758, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104909

RESUMO

BACKGROUND: Yellow fever virus infection results in death in around 30% of symptomatic individuals. The aim of this study was to identify predictors of death measured at hospital admission in a cohort of patients admitted to hospital during the 2018 outbreak of yellow fever in the outskirts of São Paulo city, Brazil. METHODS: In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in São Paolo-the Hospital das Clínicas, University of São Paulo and the Infectious Diseases Institute "Emilio Ribas". Patients older than 18 years admitted to hospital with fever or myalgia, headache, arthralgia, oedema, rash, or conjunctivitis were consecutively screened for inclusion in the present study. Consenting patients were included if they had travelled to geographical areas in which yellow fever virus cases had been previously confirmed. Yellow fever infection was confirmed by real-time PCR in blood collected at admission or tissues at autopsy. We sequenced the complete genomes of yellow fever virus from infected individuals and evaluated demographic, clinical, and laboratory findings at admission and investigated whether any of these measurements correlated with patient outcome (death). FINDINGS: Between Jan 11, 2018, and May 10, 2018, 118 patients with suspected yellow fever were admitted to Hospital das Clínicas, and 113 patients with suspected yellow fever were admitted to Infectious Diseases Institute "Emilio Ribas". 95 patients with suspected yellow fever were included in the study, and 136 patients were excluded. Three (3%) of 95 patients with suspected yellow fever who were included in the study were excluded because they received a different diagnosis, and 16 patients with undetectable yellow fever virus RNA were excluded. Therefore, 76 patients with confirmed yellow fever virus infection, based on detectable yellow fever virus RNA in blood (74 patients) or yellow fever virus confirmed only at the autopsy report (two patients), were included in our analysis. 27 (36%) of 76 patients died during the 60 day period after hospital admission. We generated 14 complete yellow fever virus genomes from the first 15 viral load-detectable samples. The genomes belonged to a single monophyletic clade of the South America I genotype, sub-genotype E. Older age, male sex, higher leukocyte and neutrophil counts, higher alanine aminotransferase, aspartate transaminase (AST), bilirubin, and creatinine, prolonged prothrombin time, and higher yellow fever virus RNA plasma viral load were associated with higher mortality. In a multivariate regression model, older age, elevated neutrophil count, increased AST, and higher viral load remained independently associated with death. All 11 (100%) patients with neutrophil counts of 4000 cells per mL or greater and viral loads of 5·1 log10 copies/mL or greater died (95% CI 72-100), compared with only three (11%) of 27 (95% CI 2-29) among patients with neutrophil counts of less than 4000 cells per mL and viral loads of less than 5·1 log10 copies/mL. INTERPRETATION: We identified clinical and laboratory predictors of mortality at hospital admission that could aid in the care of patients with yellow fever virus. Identification of these prognostic markers in patients could help clinicians prioritise admission to the intensive care unit, as patients often deteriorate rapidly. Moreover, resource allocation could be improved to prioritise key laboratory examinations that might be more useful in determining whether a patient could have a better outcome. Our findings support the important role of the virus in disease pathogenesis, suggesting that an effective antiviral could alter the clinical course for patients with the most severe forms of yellow fever. FUNDING: São Paulo Research Foundation (FAPESP).

8.
Blood Cells Mol Dis ; 77: 23-28, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30939337

RESUMO

BACKGROUND: There is a significant inter-individual heterogeneity of Vel antigen expression which can lead to inaccuracies on Vel phenotyping of blood donors and, potentially, to hemolytic post-transfusion reactions. Our aim was to evaluate the impact of genetic variants in the SMIM1 intron 2 on the expression of Vel antigen among Brazilian blood donors harboring the c.64_80del17 deletion in heterozygosity. METHODS: Donors presenting the SMIM1 c.64_80del17 in heterozygosity were included in the study and subjected to SMIM1 intron 2 direct sequencing aiming to genotype the following polymorphisms: rs143702418, rs1181893, rs191041962, rs6673829, rs1175550 and rs9424296. RESULTS: SMIM1 intron 2 sequencing was performed on two hundred donors presenting one c.64_80del17 allele. The rs1175550 polymorphism significantly impacted on Vel antigen expression. Variations in the strength of agglutination on Vel phenotyping were also observed according to the rs6673829 genotype, but this difference did not persist with statistical relevance after multivariate analysis. CONCLUSION: The presence of the rs1175550A allele of SMIM1 is significantly and independently associated with a decrease in Vel antigen expression. Even though the population in Brazil is intensely mixed, the allele frequencies obtained in the current study were very similar to that reported for Europeans.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30970110

RESUMO

Zika virus (ZIKV) clinical presentation and frequency/duration of shedding need further clarification. Symptomatic ZIKV-infected individuals identified in two hospitals in Sao Paulo State, Brazil, were investigated regarding clinical characteristics, shedding in body fluids, and serodynamics. Ninety-four of 235 symptomatic patients (Site A: 58%; Site B: 16%) had Real-Time PCR-confirmed ZIKV infection; fever, headache and gastrointestinal symptoms were less frequent, and rash was more frequent compared to ZIKV-negative patients. Real-Time PCR in serum had worse performance compared to plasma, while urine had the highest sensitivity. Shedding in genital fluids and saliva was rare. IgM positivity was the highest <14 days after the symptoms onset (86%), decreasing >28 days (24%); IgG positivity increased >14 days (96%) remaining positive in 94% of patients >28 days. ZIKV prevalence varied importantly in two neighboring cities during the same transmission season. Urine Real-Time PCR can improve diagnostic sensitivity; serum testing is less useful. Accurate serological tests are needed to improve diagnosis and surveillance.


Assuntos
Secreções Corporais/virologia , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Brasil/epidemiologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Sensibilidade e Especificidade , Carga Viral , Infecção por Zika virus/epidemiologia
10.
Int J Infect Dis ; 81: 4-5, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30660799

RESUMO

OBJECTIVES: This study was performed to determine whether neutralizing antibodies against yellow fever virus (YFV) generated by YFV vaccine could interfere in the specificity of dengue virus (DENV) and Zika virus (ZIKV) IgG ELISA tests. METHODS: Seventy-nine pairs of serum samples (pre- and post-vaccination), collected during the years 1997-1998 from children with no history of yellow fever disease who had been vaccinated against YFV, were tested. The seroconversion post-vaccination was evaluated through plaque reduction neutralization test (PRNT), and four different commercial ELISA kits were used for the detection of DENV and ZIKV IgG antibodies. RESULTS: A cross-reactivity rate of 3.9% with DENV IgG antibodies was found only with the Dengue Virus IgG Dx Select kit (Focus Diagnostics). CONCLUSIONS: As several countries have local transmission of multiple arboviruses, the absence of cross-reactivity or minimum cross-reactivity of YFV neutralizing antibodies with DENV and ZIKV antigens is a relevant finding, since the interpretation of sero-epidemiological investigations would be seriously impacted in many regions where YFV vaccination is mandatory.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Vírus da Dengue/imunologia , Vacina contra Febre Amarela/imunologia , Zika virus/imunologia , Antígenos Virais , Criança , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G/sangue , Testes de Neutralização , Vírus da Febre Amarela/imunologia
11.
PLoS One ; 13(7): e0201262, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30036381

RESUMO

OBJECTIVE: To evaluate both the performance and acceptability of a method coupling self-sampling with detection of cervical malignancy via elevated HPV 16 and 18 E6 oncoproteins (OncoE6™ Cervical Test) in remote areas in Brazil. METHODS: Women living in rural villages in proximity to Coari city, Amazonas, Brazil were invited to participate in a cervical cancer screening study. 412 subjects were enrolled; there were no refusals. In addition to E6 protein detection, DNA was extracted from the brushes and evaluated for HPV genotypes by PCR (PGMY09/11), followed by typing by the Papillocheck™ if positive. Subjects who were found to be positive for OncoE6 or HPV-DNA were referred for colposcopy. RESULTS: For 110 subjects (27%) this was the first cervical cancer exam. Overall the HPV-DNA prevalence was 19.1% (n = 79); 1.4% (n = 6) were positive by the OncoE6 Test. Fifty-six women attended the invitation for colposcopy where nine had an abnormal cervix and were subsequently biopsied. Histopathological analysis revealed 2 CIN3, 2 carcinomas and 5 CIN1. OncoE6 called two out of the three HPV 16 or 18 associated CIN3+ lesions. CONCLUSIONS: The findings suggest that self-administered sample collection in combination with OncoE6 Test is feasible in this population. This could enable expanded screening coverage while ensuring a high specificity which is imperative given the remote geographic location, since women bearing abnormal test results would necessitate travel and logistical burden to access colposcopy and treatment.


Assuntos
Proteínas de Ligação a DNA/análise , Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Proteínas Oncogênicas Virais/análise , Infecções por Papillomavirus/virologia , Proteínas Repressoras/análise , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Brasil/epidemiologia , Colposcopia , DNA Viral/análise , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , População Rural , Manejo de Espécimes , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal/métodos , Adulto Jovem
12.
Oncol Lett ; 16(2): 1785-1790, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30008866

RESUMO

There has been an increase in the incidence of anal cancer in the past two decades, with squamous cell carcinoma (SCC) being the most frequent histological type identified. Among the risk factors, high-risk human papillomavirus (HPV) infection is the most pervasive. Raf kinase inhibitor protein (RKIP) is expressed in a number of normal human tissues and previous studies have demonstrated the prognostic value of the loss of RKIP expression in several gastrointestinal tumors. Therefore, the present study aimed to evaluate the clinical implications of RKIP expression in a series of neoplastic lesions of the anal canal. The resected tumors of 48 patients [8 high-grade intraepithelial lesions (HSILs), 14 adenocarcinomas and 26 squamous cell carcinomas (SCCs)] were immunohistochemically evaluated for RKIP expression, and the results were correlated with clinicopathological data. The results identified a decreased 5-year overall survival rate in patients with adenocarcinoma (40.8%) compared with patients with SCC (76.7%), and a decreased 5-year disease-free survival rate in patients at clinical stages III/IV (37.3 vs. 62.5 and 82.6% for clinical stages 0 and I/II, respectively). Low RKIP expression was revealed in 62.5% of HSILs, 88.5% of SCCs and 100.0% of the adenocarcinomas. High RKIP expression was associated with patient ethnicity (37.5% in non-Caucasians vs. 7.5% in Caucasians) and patient age (33.3% in younger patients vs. 0.0% in older patients). Finally, high RKIP expression was correlated with HPV16 infection status (40% in HPV- vs. 5.3% in HPV+ patients). A correlation was identified between high RKIP expression and lesions with a generally improved prognosis, such as those diagnosed in younger patients, in situ lesions and lesions of lower clinical grades; there was also a negative correlation between high RKIP expression and HPV16 positivity in patients.

13.
Lancet Infect Dis ; 18(11): e355-e361, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29934112

RESUMO

Pandemic arboviruses have emerged as a major global health problem in the past four decades. Predicting where and when the next arbovirus epidemic will occur is a challenge, but history suggests that arboviral black swan events (epidemics that are difficult to predict and that have an extreme effect) will continue to occur as urban growth and globalisation expand. We briefly review unexpected arbovirus epidemics that have occurred in the past 50 years, with emphasis on the American and Pacific regions, to illustrate their unpredictability, and to highlight the need for improved global preparedness, including laboratory-based surveillance, prevention, and control programmes.


Assuntos
Infecções por Arbovirus/epidemiologia , Infecções por Arbovirus/veterinária , Arbovirus/isolamento & purificação , Surtos de Doenças , Animais , Aves , Saúde Global , Humanos , Clima Tropical
14.
Front Med (Lausanne) ; 5: 71, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29594126

RESUMO

Historically, emerging infectious agents have been an important driving force toward the enhancement of blood safety, illustrated by the sharp reduction in the transmission of infectious agents by blood transfusion after human immunodeficiency virus (HIV) epidemics. In general, Latin American (LATAM) countries have introduced screening for microorganisms with proven blood transmission with some delay in comparison to developed countries, but, nowadays, all LATAM countries comply with a minimum standard of screening which includes Hepatitis B, C, HIV, Treponema pallidum, and Trypanosoma cruzi. Noticeably, all those agents, in addition to HTLV, cause chronic infections. By contrast, in the last decade, the region has witnessed explosive outbreaks of arboviral diseases, representing a new challenge to the blood system, threatening not only blood safety but also availability. So far, the clinical impact of transfusion-transmitted Dengue, Chikungunya, or Zika has not been evident, precluding immediate reaction from the authorities. A number of other arboviruses are endemic in the region and may, unpredictably, originate new epidemics. Several measures must be taken in preparedness for the potential emergence of another arbodisease.

15.
Am J Clin Pathol ; 149(4): 316-323, 2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29471316

RESUMO

Objectives: This study aimed to evaluate the influence of prior knowledge of human papillomavirus (HPV) status in cervical cytopathology readings. Methods: Participants comprised 2,376 women who underwent parallel cytology and HPV-DNA testing. Smears were read twice by the same team, first with previous knowledge of HPV-DNA status. Results: Overall, 239 (10.2%) smears had their cytology classification altered by the HPV-informed review. Cytology readings with prior knowledge of the HPV status revealed 10.5% of abnormal smears (atypical squamous cells of undetermined significance or higher), while without prior knowledge, this rate dropped to 7.6%. When HPV status was informed, a significant increase in all categories of altered smears was observed. Cytology with prior knowledge of HPV status detected more cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) compared with blinded: 86.7% vs 60.0%. Conclusions: Our data indicate that cytology interpreted with prior knowledge of the HPV status provides higher sensitivity for CIN 2+ lesions while marginally reducing the overall specificity compared with HPV status blinded cytology.


Assuntos
Neoplasia Intraepitelial Cervical/patologia , Competência Clínica , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/virologia , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/diagnóstico , Sensibilidade e Especificidade , Método Simples-Cego , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Adulto Jovem
17.
PLoS One ; 13(1): e0191701, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29377909

RESUMO

We investigated how somatic changes in HNSCC interact with environmental and host risk factors and whether they influence the risk of HNSCC occurrence and outcome. 180-paired samples diagnosed as HNSCC in two high incidence regions of Europe and South America underwent targeted sequencing (14 genes) and evaluation of copy number alterations (SCNAs). TP53, PIK3CA, NOTCH1, TP63 and CDKN2A were the most frequently mutated genes. Cases were characterized by a low copy number burden with recurrent focal amplification in 11q13.3 and deletion in 15q22. Cases with low SCNAs showed an improved overall survival. We found significant correlations with decreased overall survival between focal amplified regions 4p16, 10q22 and 22q11, and losses in 12p12, 15q14 and 15q22. The mutational landscape in our cases showed an association to both environmental exposures and clinical characteristics. We confirmed that somatic copy number alterations are an important predictor of HNSCC overall survival.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Adolescente , Adulto , Idoso , Cromossomos Humanos , Variações do Número de Cópias de DNA , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Adulto Jovem
18.
PLoS Negl Trop Dis ; 12(1): e0006154, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29357366

RESUMO

Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are predominantly transmitted via mosquito bites. Both viruses are responsible for a growing number of infections in tropical and subtropical regions. DENV infection can cause lethargy with severe morbidity and dengue shock syndrome leading to death in some cases. ZIKV is now linked with Guillain-Barré syndrome and fetal malformations including microcephaly and developmental disorders (congenital Zika syndrome). The protective and pathogenic roles played by the immune response in these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells with potent anti-bacterial activity. MAIT cells have also been postulated to play a role in the immune response to viral infections. In this study, we evaluated MAIT cell frequency, phenotype, and function in samples from subjects with acute and convalescent DENV infection. We found that in acute DENV infection, MAIT cells had elevated co-expression of the activation markers CD38 and HLA-DR and had a poor IFNγ response following bacterial stimulation. Furthermore, we found that MAIT cells can produce IFNγ in response to in vitro infection with ZIKV. This MAIT cell response was independent of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may play an important role in the immune response to Flavivirus infections.


Assuntos
Vírus da Dengue/imunologia , Dengue/patologia , Células T Invariáveis Associadas à Mucosa/imunologia , Infecção por Zika virus/patologia , Zika virus/imunologia , ADP-Ribosil Ciclase 1/análise , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Antígenos HLA-DR/análise , Humanos , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-18/metabolismo , Masculino , Glicoproteínas de Membrana/análise , Pessoa de Meia-Idade , Células T Invariáveis Associadas à Mucosa/química , Adulto Jovem
19.
Braz. j. infect. dis ; 22(1): 16-23, Jan.-feb. 2018. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-951626

RESUMO

ABSTRACT Introduction: Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women. Methods: 723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models. Results: Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8-11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9-1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3-2.2) and 3.2-fold (95% CI 1.5-7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7-94.6] for 12 months and 80.9% [95% CI 77.2-84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9-100.0] for 12 months and 99.0 [95% CI 97.6-99.7] for 36 months). Conclusions: Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology.

20.
Braz J Infect Dis ; 22(1): 16-23, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29207280

RESUMO

INTRODUCTION: Cervical cancer remains an important burden for HIV-infected women in the era of combination antiretroviral therapy. Recommendations for cervical screening in these women diverge and may include high-risk HPV (HRHPV) testing. We aimed to evaluate the clinical usefulness of a single HRHPV testing for cervical screening of HIV-infected women. METHODS: 723 HIV-infected women from a Brazilian prospective cohort were included between 1996 and 2012. Inclusion criteria were: normal cervical cytology at baseline and having a HRHPV-test at baseline. We calculated incidence rates of any squamous intraepithelial lesion (SIL) and high grade SIL+ (HSIL+) and negative predictive values (NPV) within 12 and 36 months. Hazard Ratios were obtained using Cox proportional hazards regression models. RESULTS: Incidence rate for both outcomes was low (9.9 cases per 100 PY [95% CI 8.8-11.0] for any SIL and 1.3 cases per 100 PY [95% IC 0.9-1.8] for HSIL+). Women with a HRHPV positive status at baseline had 1.7-fold (95% CI 1.3-2.2) and 3.2-fold (95% CI 1.5-7.1) increased risk of presenting any SIL and HSIL+, respectively, during follow-up. Negative-HRHPV test presented high NPV for both periods and outcomes (any SIL: 92.4% [95% CI 89.7-94.6] for 12 months and 80.9% [95% CI 77.2-84.3] for 36 months; and HSIL+: 99.8% [95% CI 98.9-100.0] for 12 months and 99.0 [95% CI 97.6-99.7] for 36 months). CONCLUSIONS: Incidence of any and high grade cytological abnormality was significantly higher among HIV-infected women with positive-HRHPV test. A single negative-HRHPV test helped reassure follow-up free of cytological abnormalities through three years of follow-up in HIV-infected women with negative cytology.


Assuntos
Infecções por HIV/complicações , Programas de Rastreamento/métodos , Infecções por Papillomavirus/complicações , Medição de Risco/métodos , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/virologia , Adulto , Brasil , Contagem de Linfócito CD4 , Diagnóstico Precoce , Feminino , Humanos , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Risco , Lesões Intraepiteliais Escamosas Cervicais/patologia , Fatores de Tempo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Carga Viral
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