MARIA CASSIA JACINTHO MENDES CORREA
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina - Líder
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- Resistance mutations are rare among protease inhibitor treatment-naive hepatitis C genotype-1 patients with or without HIV coinfection(2015) LISBOA-NETO, Gaspar; NOBLE, Caroline F.; PINHO, Joao R. Rebello; MALTA, Fernanda M.; GOMES-GOUVEA, Michele S.; ALVARADO-MORA, Monica V.; SILVA, Mariliza H. da; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; RODRIGUES, Flaviane K.; CARRILHO, Flair J.; MENDES-CORREA, Maria C.Background: HCV has a high replication rate and a lack of proofreading activity, leading to a greatly diverse viral population. This diversity may lead to emergence of resistant strains in direct-acting antiviral therapy. The frequency of naturally occurring HCV protease inhibitor (PI) mutations has been addressed in many countries, but there are few data on the prevalence of these mutations in Brazilian patients. Methods: We evaluated the sequence of HCV NS3 protease gene in 247 patients (135 HCV-monoinfected and 112 HIV-HCV-coinfected patients). HCV RNA was extracted from plasma and a fragment of 765 base pairs from the NS3 region was amplified and sequenced with Sanger-based technology. Results: HIV-HCV-coinfected patients were more likely to be older than 40 years and have an HCV subtype-1a infection. Overall, 21.9% of patients had at least one amino acid substitution in the NS3 region; 14 patients (5.7%) harboured at least one resistance mutation (T54S, V55A, Q80R) and the Q80K mutation was not found in our case series. There was no difference between monoinfected and coinfected patients regarding the frequency of natural polymorphisms and resistance mutations. Conclusions: Baseline HCV NS3 amino acid substitutions identified herein are considered mostly natural polymorphisms with no clinical impact on PI-based therapy. The identified resistance mutations may be associated with low-level resistance to PIs in vitro. Q80K substitution seems to be a rare event in Brazil. HIV coinfection was not associated with a greater frequency of such substitutions in the studied sample.
- How are HCV-infected patients being identified in Brazil: a multicenter study(2019) PORTARI-FILHO, Luiz H.; ALVARES-DA-SILVA, Mario R.; GONZALEZ, Aline; FERREIRA, Adalgisa P.; VILLELA-NOGUEIRA, Cristiane A.; MENDES-CORREA, Maria C.; LIMA, Jose M.; LOPES, Edmundo P.; BRANDAO, Carlos E.; IVANTES, Claudia; LYRA, Andre; LINDENBERG, Andreia; FERRAZ, Maria L.Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. Results: Two thousand patients were included; 55.1% were male, mean age 58 +/- 11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients. (C) 2019 Sociedade Brasileira de Infectologia.
- Viral hepatitis and HIV: update and management(2013) NUNEZ, Marina; MENDES-CORREA, Maria C.HCV-related liver disease is an important contributor to morbidity and mortality in the HIV-infected population. Successful treatment of HIV-HCV-coinfected patients is followed by favourable clinical outcomes. While the combination of pegylated interferon and ribavirin remains the mainstay in the treatment of non-1 HCV genotypes, the first generation of HCV protease inhibitors are being incorporated into existing HCV genotype-1 (HCV-1) treatment protocols. Although data are limited, the triple combination does improve the sustained virological response in HIV-HCV-1-coinfected subjects. However, with still very limited data in this setting, clinical decisions for triple therapy have to be individualized and made based on multiple considerations. Chronic HBV infection increases mortality in HIV-infected subjects. In the treatment of HIV-HBV coinfection, it is very important to coordinate HBV and HIV therapies. HBV-active HAART improves the outcome of patients with HIV-HBV coinfection and tenofovir has become a key component of the treatment for these patients, although a number of clinical situations require a case-by-case approach.
- Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir +/- Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis(2018) PESSOA, Mario G.; V, Jose Ramalho-Madruga; ALVES, Katia; NUNES, Estevao P.; CHEINQUER, Hugo; BRANDAO-MELLO, Carlos E.; MENDES-CORREA, Maria C.; FERRAZ, Maria L.; FERREIRA, Paulo R. A.; ALVARES-DA-SILVA, Mario R.; COELHO, Henrique S.; AFFONSO-DE-ARAUJO, Evaldo S.; FURTADO, Juvencio; PARANA, Raymundo; SILVA, Giovanni; LARI, Sara A.; LIU, Li; TRIPATHI, Rakesh; PILOT-MATIAS, Tami; COHEN, Daniel E.; SHULMAN, Nancy S.; MARTINELLI, AnaIntroduction and aim. Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. Material and methods. All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12). Results. The study enrolled 222 patients, 214 achieved an SVR 12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR 12 was achieved in 111/112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event. Discussion. The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).
- Detailed characterization of Redondovirus in saliva of SARS-CoV-2-infected individuals in Sao Paulo, Brazil(2023) COSTA, Antonio Charlys da; MENDES-CORREA, Maria C.; TOZETTO-MENDOZA, Tania Regina; VILLAS-BOAS, Lucy S.; PAULA, Anderson Vicente de; PAIAO, Heuder Gustavo Oliveira; LEAL, Fabio E.; FERREIRA, Noely E.; HONORATO, Layla; LEAL, Elcio; GRANDI, Giuliano; MORAIS, Vanessa dos Santos; MANULI, Erika R.; SABINO, Ester C.; WITKIN, Steven S.BackgroundRedondovirus (ReDoV) is a DNA virus present in the respiratory tract of many healthy individuals. Since SARS-CoV-2, the virus responsible for COVID-19, also primarily infects the same site, we evaluated whether ReDoV was present at increased frequency in patients with COVID-19 and influenced infection parameters.MethodsSaliva samples were collected weekly from 59 individuals with COVID-19 and from 132 controls. ReDoV was detected by polymerase chain reaction and the genotypes were identified by metagenomics. Torque Teno Virus (TTV) in these samples were previously reported.ResultsReDoV was detected in saliva more frequently from COVID-19 patients (72.9%) than from controls (50.0%) (p = 0.0015). There were no associations between ReDoV detection and either continuous or intermittent SARS-CoV-2 shedding, the duration of SARS-CoV-2 detection in saliva, patients' sex or if infection was by the B1 or Gamma strain. The two ReDoV strains, Brisavirus and Vientovirus, were present in equivalent frequencies in ReDoV-positive COVID-19 patients and controls. Phylogenetic analysis suggested that the two ReDoV strains in Brazil were similar to strains previously detected on other continents.ConclusionReDoV expression in saliva is increased in males and females in Brazil with mild COVID-19 but its presence does not appear to influence properties of the SARS-CoV-2 infection.
- Torquetenovirus in saliva: A potential biomarker for SARS-CoV-2 infection?(2021) MENDES-CORREA, Maria C.; TOZETTO-MENDOZA, Tania Regina; FREIRE, Wilton S.; PAIAO, Heuder G. O.; FERRAZ, Andrea B. C.; MAMANA, Ana C.; FERREIRA, Noely E.; V, Anderson de Paula; FELIX, Alvina C.; ROMANO, Camila M.; BRAZ-SILVA, Paulo H.; LEAL, Fabio E.; GRESPAN, Regina M. Z.; SABINO, Ester C.; COSTA, Silvia F.; WITKIN, Steven S.Torquetenovirus (TTV) is present in biological fluids from healthy individuals and measurement of its titer is used to assess immune status in individuals with chronic infections and after transplants. We assessed if the titer of TTV in saliva varied with the presence of SARS-CoV-2 in the nasopharynx and could be a marker of COVID-19 status. Saliva from 91 individuals positive for SARS-CoV-2 in nasal-oropharyngeal samples, and from 126 individuals who were SARS-CoV-2-negative, all with mild respiratory symptoms, were analyzed. Both groups were similar in age, gender, symptom duration and time after symptom initiation when saliva was collected. Titers of TTV and SARS-CoV-2 were assessed by gene amplification. Loss of smell (p = 0.0001) and fever (p = 0.0186) were more prevalent in SARS-CoV-2-positive individuals, while sore throat (p = 0.0001), fatigue (p = 0.0037) and diarrhea (p = 0.0475) were more frequent in the SARS-CoV-2 negative group. The saliva TTV and nasal-oropharyngeal SARS-CoV-2 titers were correlated (p = 0.0085). The TTV level decreased as symptoms resolved in the SARS-CoV-2 infected group (p = 0.0285) but remained unchanged in the SARS-CoV-2 negative controls. In SARS-CoV-2 positive subjects who provided 2-4 saliva samples and in which TTV was initially present, the TTV titer always decreased over time as symptoms resolved. We propose that sequential TTV measurement in saliva is potentially useful to assess the likelihood of symptom resolution in SARS-CoV-2-positive individuals and to predict prognosis.
- Performance of at-home self-collected saliva and nasal-oropharyngeal swabs in the surveillance of COVID-19(2021) BRAZ-SILVA, Paulo H.; MAMANA, Ana C.; ROMANO, Camila M.; FELIX, Alvina C.; V, Anderson de Paula; FEREIRA, Noeli E.; BUSS, Lewis F.; TOZETTO-MENDOZA, Tania R.; V, Rafael A. Caixeta; LEAL, Fabio E.; GRESPAN, Regina M. Z.; BIZARIO, Joao C. S.; FERRAZ, Andrea B. C.; SAPKOTA, Dipak; GIANNECCHINI, Simone; TO, Kelvin K.; DOGLIO, Alain; MENDES-CORREA, Maria C.Background: SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of transmission. Aim: To compare the performance of at-home self-collected samples - saliva and combined nasal-oropharyngeal swabs (NOP) - for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance. Material and methods: We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar (R) SARS-CoV-2 RT-PCR Kit 1.0. Results: There was an overall significant agreement (kappa coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva. Conclusion: Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.
- Characterization of clinical predictors of naturally occurring NS3/NS4A protease polymorphism in genotype 1 hepatitis C virus mono and HIV co-infected patients(2017) NETO, Gaspar Lisboa; MALTA, Fernanda M.; GOMES-GOUVEA, Michele S.; NOBLE, Caroline F.; ROMANO, Camila M.; PINHO, Joao R. Rebello; SILVA, Mariliza H.; LEITE, Andrea G. B.; PICCOLI, Leonora Z.; CARRILHO, Flair J.; MENDES-CORREA, Maria C.Spontaneously occurring resistance may impair the success of protease inhibitors based regimens in HCV treatment. This study aimed to evaluate associations between amino acid substitutions in NS3/NS4A domain and clinical features of 247 HCV mono or HCV/HIV co-infected patients. Fourteen samples (5.7%) harbored at least one resistance-associated substitution (RAS). The following RASs were detected in NS3 region: T54S (6-2.4%), V55A (7-2.8%), and Q80R (2-0.8%). S122G occurred in 86.9% of HCV genotype 1b samples with either natural polymorphisms or RASs. Advanced liver fibrosis and HIV co-infection were not related to NS3/NS4A amino acid substitutions.
- The vaginal Torquetenovirus titer varies with vaginal microbiota composition in pregnant women(2022) TOZETTO-MENDOZA, Tania Regina; MENDES-CORREA, Maria C.; MORON, Antonio F.; FORNEY, Larry J.; LINHARES, Iara M.; SILVA JR., Almir Ribeiro da; HONORATO, Layla; WITKIN, Steven S.Torquetenovirus (TTV) is a nonpathogenic endogenous virus whose abundance varies with the extent of immune system activation. We determined if the TTV titer in the vagina of pregnant women was associated with vaginal microbiota composition and levels of compounds in vaginal secretions. Vaginal TTV and microbiota composition in 494 second trimester pregnant women were identified by gene amplification and analysis. Vaginal matrix metalloproteinases (MMPs), tissue inhibitors of MMP (TIMP) and lactic acid isomers were measured by ELISA. Dominance was defined as the relative abundance of a specific bacterium or species at >50% of the total number of bacteria identified. Clinical data were obtained by chart review. The median log(10) TTV titer was lowest when Lactobacillus species other than L. iners were dominant (<1.0) as compared to when L. iners (4.1, p = 0.0001), bacteria other than lactobacilli (4.5, p = 0.0016) or no bacterium (4.7, p = 0.0009) dominated. The TTV titer was inversely proportional to L. crispatus abundance (p<0.0001) and directly proportional to levels of G. vaginalis (p = 0.0008) and L. iners (p = 0.0010). The TTV titer was proportional to TIMP-1, TIMP-2, MMP-8 and MMP-9 abundance (p <= 0.0002) and inversely proportional to the level of D-lactic acid (p = 0.0024). We conclude that the association between variations in the TTV titer and the relative abundance of specific bacterial species and vaginal compounds indicates that local changes in immune status likely influence vaginal fluid composition.
- Torquetenovirus Titer in Vaginal Secretions from Pregnant and Postpartum Women: Association with Absence ofLactobacillus crispatusand Levels of Lactic Acid and Matrix Metalloproteinase-8(2020) TOZETTO-MENDOZA, Tania R.; BONGIOVANNI, Ann Marie; MINIS, Evelyn; LINHARES, Iara M.; BOESTER, Allison; FREIRE, Wilton S.; LIMA, Silvia H.; OLIVEIRA, Natan P. G. de; MENDES-CORREA, Maria C.; FORNEY, Larry J.; WITKIN, Steven S.Vaginal samples from women with term deliveries were tested for torquetenovirus (TTV) by gene amplification, matrix metalloproteinase (MMP)-8 and D- and L-lactic acid by ELISA, and microbiome composition by analysis of the bacterial 16S ribosomal RNA gene. TTV was detected in 43.2%, 31.5%, and 41.4% of first trimester, third trimester, and postpartum samples, respectively. The viral titer was higher in postpartum than in the first (p = 0.0018) or third (p = 0.0013) trimester. The mean gestational age at delivery was lower in women positive for TTV in their first trimester (p = 0.0358). In the first and third trimester, the MMP-8 level was higher if TTV was also present (p < 0.0091). The D-lactic acid level was lower in first trimester samples if TTV was present (p = 0.0334).Lactobacillus crispatusdominance in first and third trimester samples was higher when TTV was absent (p < 0.0033). We conclude that TTV is present in the vagina in many women with normal pregnancy outcomes and that its occurrence is associated with a lack ofL. crispatusdominance, an increase in vaginal MMP-8 and a decrease in D-lactic acid.