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BACKGROUND: A single-dose dengue vaccine that protects individuals across a wide age range and regardless of dengue serostatus is an unmet need. We assessed the safety and efficacy of the live, attenuated, tetravalent Butantan-dengue vaccine (Butantan-DV) in adults, adolescents, and children. We previously reported the primary and secondary efficacy and safety endpoints in the initial 2 years of follow-up. Here we report the results through an extended follow-up period, with an average of 3·7 years of follow-up. METHODS: In this double-blind, randomised, placebo-controlled, phase 3, multicentre trial in Brazil, healthy participants (aged 2-59 years) who had not previously received a dengue vaccine were enrolled and randomly assigned 2:1 (stratified by age 18-59 years, 7-17 years, and 2-6 years) using a central electronic randomisation system to receive 0·5 mL of Butantan-DV (containing approximately 103 plaque-forming units of each of the four vaccine virus strains) or placebo, administered subcutaneously. Syringes containing vaccine or placebo were prepared by an unmasked trial pharmacist who was not involved in any subsequent participant assessments; other site staff and the participants remained unaware of the group allocations. Vaccine efficacy was calculated with the accrual of virologically confirmed dengue (VCD) cases (by RT-PCR) at least 28 days after vaccination up until the cutoff (at least 2 years of follow-up from the last participant enrolled). The primary endpoint was vaccine efficacy against VCD after day 28 by any dengue virus (DENV) serotype regardless of dengue serostatus at baseline in the per-protocol population. The primary and secondary safety endpoints up until day 21 were previously reported; secondary safety endpoints include the frequency of unsolicited vaccine-related adverse events after day 22. Safety analyses were done on all participants as treated. This trial is registered with ClinicalTrials.gov (NCT02406729) and is ongoing. FINDINGS: Of 16 363 participants assessed for eligibility, 16 235 were randomly assigned between Feb 22, 2016, and July 5, 2019, and received single-dose Butantan-DV (10 259 participants) or placebo (5976 participants). 16 162 participants (Butantan-DV n=10 215; placebo n=5947) were included in the per-protocol population and 16 235 (Butantan-DV n=10 259; placebo n=5976) in the safety population. At the data cutoff (July 13, 2021), participants had 2-5 years of follow-up (mean 3·7 years [SD 1·0], median 4·0 years [IQR 3·2-4·5]). 356 VCD cases were captured through the follow-up (128 in the vaccine group and 228 in the placebo group). Vaccine efficacy against VCD caused by any DENV serotype was 67·3% (95% CI 59·4-73·9); cases caused by DENV-3 or DENV-4 were not observed. The proportions of participants who had serious adverse events were similar between treatment groups (637 [6·2%] in the vaccine group and 395 [6·6%] in the placebo group) up until the cutoff. INTERPRETATION: A single dose of Butantan-DV was generally well tolerated and efficacious against symptomatic VCD (caused by DENV-1 and DENV-2) for a mean of 3·7 years. These findings support the continued development of Butantan-DV to prevent dengue disease in children, adolescents, and adults regardless of dengue serostatus. FUNDING: Instituto Butantan and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

RESUMO

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.).

Assuntos

Vacinas contra Dengue , Vírus da Dengue , Dengue , Vacinas Atenuadas , Adulto , Criança , Pré-Escolar , Humanos , Anticorpos Antivirais , Dengue/prevenção & controle , Vacinas contra Dengue/efeitos adversos , Vacinas contra Dengue/uso terapêutico , Vírus da Dengue/imunologia , Método Duplo-Cego , Vacinação , Vacinas , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/uso terapêutico , Brasil , Eficácia de Vacinas , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Seguimentos

RESUMO

Introduction: Brazil has one of the largest prison populations globally, with over 682,000 imprisoned people. Prison health is a public health emergency as it presents increasingly aggravating disease rates, mainly sexually transmitted infections (STI). And this problem already affects both developed and developing nations. Therefore, when thinking about intervention strategies to improve this scenario in Brazil, the course "Health Care for People Deprived of Freedom" (ASPPL), aimed at prison health, was developed. This course was implemented in the Virtual Learning Environment of the Brazilian Health System (AVASUS). Given this context, this study analyzed the aspects associated with massive training through technological mediation and its impacts on prison health. Methods: This cross-sectional study analyzed data from 8,118 ASPPL course participants. The data analyzed were collected from six sources, namely: (i) AVASUS, (ii) National Registry of Health Care Facilities (CNES), (iii) Brazilian Occupational Classification (CBO), (iv) National Prison Department (DEPEN); (v) Brazilian Institute of Geography and Statistics (IBGE); and the (iv) Brazilian Ministry of Health (MoH), through the Outpatient Information System of the Brazilian National Health System (SIA/SUS). A data processing pipeline was conducted using Python 3.8.9. Results: The ASPPL course had 8,118 participants distributed across the five Brazilian regions. The analysis of course evaluation by participants who completed it shows that 5,190 (63.93%) reported a significant level of satisfaction (arithmetic mean = 4.9, median = 5, and standard deviation = 0.35). The analysis revealed that 3,272 participants (40.31%) are health workers operating in distinct levels of care. The prison system epidemiological data shows an increase in syphilis diagnosis in correctional facilities. Conclusions: The course enabled the development of a massive training model for various health professionals at all care levels and regions of Brazil. This is particularly important in a country with a continental size and a large health workforce like Brazil. As a result, social and prison health impacts were observed.

Assuntos

Atenção à Saúde , Prisões , Brasil , Estudos Transversais , Liberdade , Educação em Saúde , Humanos

RESUMO

Sporotrichosis is a fungal infection of man and animals caused by Sporothrix complex. It usually presents as a lymphocutaneous form, but disseminated disease may occur. Given the paucity of data about HIV/AIDS and sporotrichosis co-infection, a systematic review of reported cases of HIV-associated sporotrichosis found via Pubmed (1984-2013) was done. A total of 39 papers were included, and 58 patients' data analyzed. Thirty-three (56.9 %) cases were from Brazil and 18 (31 %) from the USA. Patients' mean age was 37.8 ± 10.4 years; males predominated (84.5 %). The median CD4(+) cell count was 97 cells/mm(3). The most common clinical forms were disseminated and disseminated cutaneous with 33 (56.9 %) and 10 (17.5 %) patients, respectively. There was a correlation between CD4(+) count and clinical categories (p = 0.002). Mortality was 30 % and there was a correlation between central nervous system involvement and death (p < 0.001).

Assuntos

Infecções por HIV/complicações , Sporothrix/isolamento & purificação , Esporotricose/epidemiologia , Distribuição por Idade , Animais , Brasil/epidemiologia , Contagem de Linfócito CD4 , Infecções por HIV/imunologia , Humanos , Distribuição por Sexo , Estados Unidos/epidemiologia

RESUMO

Objective. Evaluate the effect of increasing P intake on nutrient digestibility, and compare the true and apparent absorption coefficients of P and Ca in lambs. Materials and methods. Twenty-four Santa Ines sheep, with an average weight of 33.6 ± 1.6 kg, were distributed into four treatments (0, 2, 4 and 6 g/day of supplementary P) with forage: concentrate ratio of 70:30. The study of apparent nutrient digestibility was conducted during the first week, using the total feces collection method. During the second week, after injection of 7.4 MBq of 32P and 7.7 MBq of 45Ca, apparent (AAC) and true (TAC) absorption coefficients of P and Ca were determined. The lambs were kept in metabolic cages. Results. The increase in P intake did not affect (p>0.05) dry matter, crude protein, NDF or ADF digestibility, but the TAC of P and Ca and mineral matter digestibility decreased. The AAC was not affected (p=0.10). A cubic relationship was observed between P intake and TAC (TAC=2.16–1.95X+0.55X2-0.04X3; R2=0.38) and linear relationship with the TAC of Ca (TAC=0.559–0.03X; R2=0.26). TAC and AAC values were different (p<0.001). Conclusions. The increase in P intake doesn’t impact organic matter digestibility, but does affect P and Ca absorption. Apparent digestibility is not a reliable parameter to determine the efficiency of P and Ca absorption.

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Objetivo. Evaluar el efecto del incremento en la ingestión de P sobre la digestibilidad de los nutrientes, y comparar los coeficientes de digestibilidad real y aparente de Ca y P en ovinos. Materiales y métodos. Veinticuatro ovinos de la raza Santa Inés, con 33.6±1.6 kg de peso, fueron asignados a cuatro tratamientos (0, 2, 4 y 6 g/día de P suplementario) con relación forraje:concentrado de 70:30. El estudio de digestibilidad aparente de los nutrientes se realizó la primera semana usando el método de colecta total de heces. La segunda semana, luego de inyectar 7.4 MBq de 32P y 7.7 MBq de 45Ca, se realizó el estudio de absorción real (CAV) y aparente (AAC), en jaulas de estudio de metabolismo. Resultados. El incremento en la ingestión de P no afectó (p>0.05) la digestibilidad aparente de la materia seca, proteína bruta, FDN o FDA. El CAV de Ca y de P y la digestibilidad de la materia mineral presentaron una reducción. EL AAC no fue afectado (p=0.10). La ecuación CAV=2.16–1.95X+0.55X2-0.04X3 (R2 = 0.38) explicó la relación entre el CAV de P y el incremento en su ingestión, y la ecuación TAC=0.559 – 0.03X (R2=0.26), la relación entre el CAV de Ca y la ingestión de P. Los valores de AAC y CAV difirieron entre sí (p<0.001). Conclusiones. La ingestión de P no afectó la digestibilidad de la fracción orgánica del alimento, pero sí la absorción de P y Ca. El coeficiente de absorción aparente no fue un parámetro confiable para determinar la eficiencia de absorción de P y Ca.

Assuntos

Animais , Absorção , Radioisótopos de Cálcio , Fósforo , Ruminantes