Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults.

BACKGROUND: Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. METHODS: In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. RESULTS: Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). CONCLUSIONS: A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).

Characteristics of patients diagnosed with cervical cancer in Brazil: preliminary results of the prospective cohort EVITA study (EVA001/LACOG 0215).

OBJECTIVES: Cervical cancer is the fourth most common cancer in women worldwide. Epidemiological and quality of life (QoL) data in patients with cervical cancer from low- and middle-income countries are scarce. We aimed to describe sociodemographic and clinicopathological characteristics and quality of life of patients with cervical cancer at diagnosis in Brazil. METHODS: EVITA is a prospective cohort study of newly diagnosed patients with cervical cancer from May 2016 to December 2017, stages I-IVB, from 16 Brazilian sites representing the five Brazilian regions. At baseline, medical evaluation was performed and European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24/C30 questionnaires were administered. RESULTS: A total of 631 patients were included. Mean±SD age was 49.3±13.9 years; skin color was non-white in 65.3%, and 68.0% had ≤8 years of formal education. In total, 85.1% of patients had a Pap smear. The main reasons reported by patients for not having a Pap smear were: lack of interest (46.9%), shame or embarrassment (19.7%), lack of knowledge (19.7%), and difficulty with access (9.1%). Most patients were diagnosed with locally advanced or metastatic disease (FIGO clinical stage II-IV in 81.8%- stage II in 35.2%, stage III in 36.1%, and stage IV in 10.5%). Patients with clinical stage III-IV had worse physical functioning and role functioning. CONCLUSIONS: Cervical cancer in Brazil is usually diagnosed at an advanced stage. Most patients have low formal education and are unemployed. Lack of interest was identified as a main reason for not having a screening test, and limited access was reported as a reason by <10% of the patients. Awareness campaigns must be a governmental priority, specially focused on the needy population, along with wide access to treatment.

Phase 2 randomized study on chloroquine, hydroxychloroquine or ivermectin in hospitalized patients with severe manifestations of SARS-CoV-2 infection.

Objective: Given the urgent need for strategies to minimize the damage caused by this pandemic, this study performed a randomized, double-blind phase 2 study to assess the safety of the effectiveness of chloroquine (CQ), hydroxychloroquine (HCQ) or ivermectin in severe forms of COVID-19, in addition to identifying predictors of mortality in this group of patients.Methods: Phase 2, double-blind, randomized study to assess the safety and efficacy of enteral CQ, HCQ or ivermectin in patients hospitalized for SARS-CoV-2 infection, admitted to a Reference Hospital in Roraima (Brazil) in may 2020. Patients were randomized in a 1:1:1 ratio. The endpoints were need of supplemental O2, invasive ventilation, admission in ICU and death. The study was approved by an independent IRB.Results: 168 patients were randomized. The mean age was 53.4 years (±15.6), most participants were male (n = 95; 58.2%). Therapy with corticosteroid, anticoagulant or antibiotics was a decision of the attending physicians, and there was no difference between the groups. The mortality was similar in three groups (22.2%; 21.3% and 23.0%) suggesting ineffectiveness of the drugs. No difference in the incidence of serious adverse events were observed. To be older than 60 years of age, obesity, diabetes, extensive pulmonary involvement and low SaO2 at hospital admission due to independent risk factors for mortality.Conclusion: Although CQ, HCQ or ivermectin revealed a favorable safety profile, the tested drugs do not reduce the need for supplemental oxygen, ICU admission, invasive ventilation or death, in patients hospitalized with a severe form of COVID-19.

Comparison of three human papillomavirus DNA detection methods: Next generation sequencing, multiplex-PCR and nested-PCR followed by Sanger based sequencing.

To compare the diagnostic performance for HPV infection using three laboratorial techniques. Ninty-five cervicovaginal samples were randomly selected; each was tested for HPV DNA and genotypes using 3 methods in parallel: Multiplex-PCR, the Nested PCR followed by Sanger sequencing, and the Next_Gen Sequencing (NGS) with two assays (NGS-A1, NGS-A2). The study was approved by the Brazilian National IRB (CONEP protocol 16,800). The prevalence of HPV by the NGS assays was higher than that using the Multiplex-PCR (64.2% vs. 45.2%, respectively; P = 0.001) and the Nested-PCR (64.2% vs. 49.5%, respectively; P = 0.003). NGS also showed better performance in detecting high-risk HPV (HR-HPV) and HPV16. There was a weak interobservers agreement between the results of Multiplex-PCR and Nested-PCR in relation to NGS for the diagnosis of HPV infection, and a moderate correlation for HR-HPV detection. Both NGS assays showed a strong correlation for detection of HPVs (k = 0.86), HR-HPVs (k = 0.91), HPV16 (k = 0.92) and HPV18 (k = 0.91). NGS is more sensitive than the traditional Sanger sequencing and the Multiplex PCR to genotype HPVs, with promising ability to detect multiple infections, and may have the potential to establish an alternative method for the diagnosis and genotyping of HPV.

[Validity of cervicovaginal cytology in a Brazilian State with high incidence rate of cervical cancer]. / Acurácia dos exames citológicos cervicovaginais em Estado de elevada incidência de câncer de colo de útero.

PURPOSE: To evaluate the validity of cervicovaginal cytology performed at LAPER, the main Laboratory of Pathology of the State of Roraima, Brazil, by interrater agreement (external monitoring) and agreement with histopathologic results. METHODS: One hundred women were included, a population-based convenience sample. Their cervical cytological exams were evaluated by the laboratory staff and reviewed by expert medical pathologists, external to the laboratory. Cohen's Kappa index, sensitivity and specificity were evaluated. The study was approved by LAPER coordination and Federal University of Roraima Research Ethics Commitee. RESULTS: Regarding the prevalence of human papillomavirus-related atypical, there was no concordance between the results issued by LAPER and by the external pathologists (k=0.21). A low sensitivity (28.5%) and specificity (89,2%) was detected for the diagnostic performance of LAPER, with a high proportion of false positive and false negative results. The cytological reports of the external pathologists showed higher sensitivity and specificity (71.4 and 98.9%, respectively), ruling out the possibility that errors related to collection methods and staining would explain the low performance of the laboratory. CONCLUSION: A low diagnostic accuracy of cervicovaginal cytology can be a barrier against the control of cervical cancer in Roraima. We emphasize the need for professional training and internal and external monitoring in Brazilian states with a high incidence of cervical cancer.

[Neoadjuvant chemotherapy followed by radical surgery in pregnant patient with invasive cervical cancer: case report and literature review]. / Quimioterapia neoadjuvante seguida de cirurgia radical em paciente grávida com câncer de colo de útero: relato de caso e revisão de literatura.

The treatment options for pregnant patients with invasive cervical cancer (ICC) depend on gestational age, clinical stage and the patient's wishes. Some authors have reported cases of neoadjuvant chemotherapy followed by radical surgery in these patients. The aim of this paper was to revisit this subject and to add a new case and review the literature. We report the case of a 30 year-old woman in the 24th week of gestation. She was diagnosed with ICC (squamous cell carcinoma grade 2), stage IIB (International Federation of Gynecology and Obstetrics - FIGO). Nulliparous, the patient refused to interrupt the pregnancy. After meticulous counseling, the patient accepted treatment with neoadjuvant chemotherapy (cisplatin 75 mg/m² and vincristine 1 mg/m²) and subsequent evaluation of radical surgery concomitant to a cesarean section. Four complete cycles of chemotherapy were administered without delays or significant adverse effects. A few days before the date scheduled for surgery, the patient was admitted in advanced labor (37th week of gestation). Due to tumor clinical response, the obstetric team decided to monitor the labor, and the patient gave birth to a male newborn (2,450 g) uneventfully. Radical surgery was performed three days after birth, and histopathology analysis revealed carcinoma confined to the cervix without lymphatic involvement. Mother and son are in good general condition 12 months after delivery. Cisplatin-based chemotherapy during the second or third trimester of pregnancy appears to be a safe option for patients who do not wish to interrupt a pregnancy while awaiting fetal maturity. However, additional studies are needed to confirm the prognosis and assure the safety of newborns and patients.

[Epidemiology and economic impact of cervical cancer in Roraima, a Northern state of Brazil: the public health system perspective]. / Epidemiologia e impacto econômico do câncer de colo de útero no Estado de Roraima: a perspectiva do SUS.

PURPOSE: to evaluate the incidence and direct economic impact of cervical cancer (CC) in Roraima, in 2009, and to analyze the epidemiological profile of patients with this disease. METHODS: the histopathologic reports issued in Roraima in 2009 were reviewed, as were hospital records of female patients under treatment for cancer. Clinical data and medical procedures related to CC were recorded. CC carriers were treated under expenses of the public Brazilian health system (SUS) in Roraima underwent an interview dealing with socio-economic topics. RESULTS: we registered 90 cases of CC and high grade pre-invasive lesions. Roraima has the highest incidence of CC of Brazil (46.21 cases/100,000 women), which is 3 times higher than that of breast cancer, comparable to low-income developing countries. The epidemiological profile shows patients with economic deprivation, social disadvantage, low education, early first intercourse (mean age is 13.8 years), and high parity (medium of 5.5 gestations). Among the patients included in this report, 71.7% had never been submited to a Pap smear, and ignorance about it was the main reported reason (47.4%). As a public health problem, the management of CC generates direct annual expenditures of more than R$ 600,000, with an average cost per patient of R$ 8,711. CONCLUSIONS: CC is the most common cancer among women from Roraima, and represents a serious public health problem in Roraima. Its high economic impact favors the implementation of preventive strategies from the standpoint of cost-effectiveness. The profile of patients reveals the ineffectiveness of preventive services in reaching patients with a socio-economic exclusion profile at high risk for cervical cancer.