ABSTRACT
Background To enhance the production and availability of influenza vaccines in different regions of the world is paramount to mitigate the global burden of this disease. Instituto Butantan developed and manufactured an embryonated egg-based inactivated split-virion trivalent seasonal influenza vaccine as part of a technology transfer partnership with Sanofi Pasteur. Methods This is a phase IV, randomized, double-blind, active-controlled, multicenter clinical trial including adults 18–60 and > 60 years recruited during the 2019 southern hemisphere influenza season. Subjects were randomized 1:1 to receive either the Sanofi Pasteur Trivalent Seasonal Influenza Vaccine (SP-TIV) or Instituto Butantan Trivalent Seasonal Influenza Vaccine (IB-TIV). Hemagglutinin inhibition antibody titers were assessed pre-vaccination and 21 days post-vaccination. Results 624 participants were randomized and vaccinated. In both intention-to-treat and per-protocol analysis, non-inferiority of the SP-TIV versus IB-TIV was demonstrated for the three influenza strains. In the per-protocol analysis, the SP-GMT/IB-GMT ratios for H1N1, H3N2, and B were 0.9 (95%CI, 0.7–1.1), 1.2 (95%CI, 1.0–1.4), and 1.1 (95%CI, 0.9–1.3), respectively. Across vaccination groups, the most common adverse reactions (AR) were limited to the injection-site, including pain and tenderness. The majority of the ARs were graded 1 and/or 2 and lasted less than one day. No serious adverse reaction was observed. Conclusion This study demonstrated the non-inferiority of the immunogenicity of a single-dose of Instituto Butantan versus a single dose of the Sanofi Pasteur Seasonal Trivalent Influenza Vaccine in adults. Both vaccines were well tolerated and presented similar safety profiles.
ABSTRACT
Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.
ABSTRACT
The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15μg H7N9, 1B) IB160 + 7.5μg H7N9, 1C) IB160 + 3.75μg H7N9, 2A) SE + 15μg H7N9, 2B) SE + 7.5μg H7N9, 2C) SE + 3.75μg H7N9, 3) unadjuvanted vaccine 15μg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.
ABSTRACT
INTRODUCTION: Active pharmacovigilance studies are pivotal to better characterize vaccine safety. METHODS: These are multicenter prospective cohort studies to evaluate the safety of the 2017 and 2018 seasonal trivalent influenza vaccines (TIVs) manufactured by Instituto Butantan, by means of active pharmacovigilance practices. Elderly, children, healthcare workers, pregnant women, and women in the puerperium period were invited to participate in the study during the 2017 and 2018 Brazilian national seasonal influenza vaccination campaigns. Following immunization, participants were observed for 30 minutes and they received a participant card to register adverse events information. All safety information registered were checked at a clinical site visit 14 days after immunization and by a telephone contact 42 days after immunization for unsolicited Adverse Events (AE) and Guillain-Barré Syndrome (GBS). RESULTS: A total of 942 volunteers participated in the two studies: 305 elderly, 109 children, 108 pregnant women, 32 women in the postpartum period, and 388 health workers. Overall, the median number of AR per participant ranged from 1 to 4. The lowest median number of AR per participant was observed among healthcare workers (1 AR per participant) and the highest among pregnant women (4 AR per participant). Overall, local pain (46.6%) was the most frequent solicited local AR. The most frequent systemic ARs were: headache (22.5%) followed by fatigue (16.0%), and malaise (11.0%). The majority of solicited ARs (96%) were mild, Grades 1 or 2), only 3% were Grade 3, and 1% was Grade 4. No serious AEs, including Guillain-Barré Syndrome, were reported up to 42 days postvaccination. CONCLUSION: The results from the two studies confirmed that the 2017 and 2018 seasonal trivalent influenza vaccines produced by Instituto Butantan were safe and that active pharmacovigilance studies should be considered, when it is feasible, as an important initiative to monitor vaccine safety in the post-marketing period.
Subject(s)
Influenza Vaccines/adverse effects , Pharmacovigilance , Aged , Brazil , Child , Child, Preschool , Female , Health Personnel/statistics & numerical data , Humans , Infant , Male , Pregnant WomenABSTRACT
Active pharmacovigilance studies are pivotal to better characterize vaccine safety. Methods: These are multicenter prospective cohort studies to evaluate the safety of the 2017 and 2018 seasonal trivalent influenza vaccines (TIVs) manufactured by Instituto Butantan, by means of active pharmacovigilance practices. Elderly, children, healthcare workers, pregnant women, and women in the puerperium period were invited to participate in the study during the 2017 and 2018 Brazilian national seasonal influenza vaccination campaigns. Following immunization, participants were observed for 30 minutes and they received a participant card to register adverse events information. All safety information registered were checked at a clinical site visit 14 days after immunization and by a telephone contact 42 days after immunization for unsolicited Adverse Events (AE) and Guillain-Barré Syndrome (GBS). Results: A total of 942 volunteers participated in the two studies: 305 elderly, 109 children, 108 pregnant women, 32 women in the postpartum period, and 388 health workers. Overall, the median number of AR per participant ranged from 1 to 4. The lowest median number of AR per participant was observed among healthcare workers (1 AR per participant) and the highest among pregnant women (4 AR per participant). Overall, local pain (46.6%) was the most frequent solicited local AR. The most frequent systemic ARs were: headache (22.5%) followed by fatigue (16.0%), and malaise (11.0%). The majority of solicited ARs (96%) were mild, Grades 1 or 2), only 3% were Grade 3, and 1% was Grade 4. No serious AEs, including Guillain-Barré Syndrome, were reported up to 42 days postvaccination. Conclusion: The results from the two studies confirmed that the 2017 and 2018 seasonal trivalent influenza vaccines produced by Instituto Butantan were safe and that active pharmacovigilance studies should be considered, when it is feasible, as an important initiative to monitor vaccine safety in the post-marketing period.
ABSTRACT
This cross-sectional seroepidemiological survey presents the seroprevalence of SARS-CoV-2 in a population living in 15 Long-Term Care Facilities (LTCFs), after two intra-institutional outbreaks of COVID-19 in the city of Botucatu, Sao Paulo State, Brazil. Residents were invited to participate in the serological survey performed in June and July 2020. Sociodemographic and clinical characterization of the participants as well as the LTCF profile were recorded. Blood samples were collected, processed and serum samples were tested using the rapid One Step COVID-19 immunochromatography test to detect IgM and IgG anti-SARS-CoV-2. Among 209 residents, the median of age was 81 years old, 135 (64.6%) were female and 171 (81.8%) self-referred as being white. An overall seroprevalence of 11.5% (95% CI: 7.5% – 16.6%) was found. The highest seroprevalences of 100% and 76.9% were observed in LTCFs that had experienced COVID-19 outbreaks. Most residents with positive immunochromatography tests (70.8%) referred previous contact with a confirmed COVID-19 case. Although there was a relatively low seroprevalence of COVID-19 in the total number of elderly people, this population is highly vulnerable and LTCFs are environments at higher risk for COVID-19 dissemination. A well-established test for COVID-19 policies, the adequate characterization of the level of interaction between residents and the healthcare provider team and the level of complexity of care are crucial to monitor and control the transmission of SARS-CoV-2 in these institutions.
