NATHALIA CAROLINE SANTIAGO E SOUZA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
LIM/52 - Laboratório de Virologia, Hospital das Clínicas, Faculdade de Medicina
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- Predictors of mortality in patients with yellow fever: an observational cohort study(2019) KALLAS, Esper G.; ZANELLA, Luiz Gonzaga F. A. B. D'Elia; V, Carlos Henrique Moreira; BUCCHERI, Renata; DINIZ, Gabriela B. F.; CASTINEIRAS, Anna Carla P.; COSTA, Priscilla R.; DIAS, Juliana Z. C.; MARMORATO, Mariana P.; SONG, Alice T. W.; MAESTRI, Alvino; BORGES, Igor C.; JOELSONS, Daniel; CERQUEIRA, Natalia B.; SOUZA, Nathalia C. Santiago e; CLARO, Ingra Morales; SABINO, Ester C.; LEVI, Jose Eduardo; I, Vivian Avelino-Silva; HO, Yeh-LiBackground 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 Sao Paulo city, Brazil. Methods In this observational cohort study, we enrolled patients with yellow fever virus from two hospitals in Sao Paolo-the Hospital das Clinicas, University of Sao 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 Clinicas, 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 log(10) 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 log(10) 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.
- Evaluation of serological cross-reactivity between yellow fever and other flaviviruses(2019) SOUZA, Nathalia Caroline Santiago e; FELIX, Alvina Clara; PAULA, Anderson Vicente de; LEVI, Jose Eduardo; PANNUTI, Claudio Sergio; ROMANO, Camila MaltaObjectives: 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. (C) 2019 The Authors.
conferenceObject RE-EMERGENCE OF DENV-2 IN THE STATE OF SAO PAULO, BRAZIL(2019) LUNA, Expedito J.; FIGUEIREDO, Gerusa M.; CAMPOS, Sergio R.; LEVI, Jose E.; FIGUEIREDO, Walter M.; COSTA, Angela A.; FELIX, Alvina C.; SOUZA, Nathalia S.; PANNUTI, Claudio S.- Modulated Zika virus NS1 conjugate offers advantages for accurate detection of Zika virus specific antibody in double antigen binding and Ig capture enzyme immunoassays(2019) TEDDER, Richard S.; DICKS, Steve; IJAZ, Samreen; SOUZA, Nathalia Caroline Santiago de; PAULA, Anderson Vincente de; LEVY, Flavia; MEDIALDEA-CARRERA, Raquel; LEVI, Jose Eduardo; PANNUTI, Claudio S.; SEQUEIRA, Patricia Carvalho de; BROWN, David W. G.; LUMB, Ines UshiroThe 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.
- Zika virus infection among symptomatic patients from two healthcare centers in Sao Paulo State, Brazil: prevalence, clinical characteristics, viral detection in body fluids and serodynamics(2019) TOZETTO-MENDOZA, Tania Regina; AVELINO-SILVA, Vivian Iida; FONSECA, Silvia; CLARO, Ingra Morales; PAULA, Anderson Vicente de; LEVIN, Anna Sara; SABINO, Ester Cerdeira; MENDES-CORREA, Maria Cassia; FIGUEIREDO, Walter Manso; FELIX, Alvina Clara; SOUZA, Nathalia C. Santiago; COSTA, Angela Aparecida; INENAMI, Maria; SILVA, Rosangela M. Gasparetto da; LEVI, Jose Eduardo; ROMANO, Camila Malta; PARANHOS-BACCALA, Glaucia; SEGURADO, Aluisio Cotrim; MAYAUD, PhilippeZika 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.