Impact of quadrivalent influenza vaccines in Brazil: a cost-effectiveness analysis using an influenza transmission model.

BACKGROUND: Influenza epidemics significantly weight on the Brazilian healthcare system and its society. Public health authorities have progressively expanded recommendations for vaccination against influenza, particularly to the pediatric population. However, the potential mismatch between the trivalent influenza vaccine (TIV) strains and those circulating during the season remains an issue. Quadrivalent vaccines improves vaccines effectiveness by preventing any potential mismatch on influenza B lineages. METHODS: We evaluate the public health and economic benefits of the switch from TIV to QIV for the pediatric influenza recommendation (6mo-5yo) by using a dynamic epidemiological model able to consider the indirect impact of vaccination. Results of the epidemiological model are then imputed in a health-economic model adapted to the Brazilian context. We perform deterministic and probabilistic sensitivity analysis to account for both epidemiological and economical sources of uncertainty. RESULTS: Our results show that switching from TIV to QIV in the Brazilian pediatric population would prevent 406,600 symptomatic cases, 11,300 hospitalizations and almost 400 deaths by influenza season. This strategy would save 3400 life-years yearly for an incremental direct cost of R$169 million per year, down to R$86 million from a societal perspective. Incremental cost-effectiveness ratios for the switch would be R$49,700 per life-year saved and R$26,800 per quality-adjusted life-year gained from a public payer perspective, and even more cost-effective from a societal perspective. Our results are qualitatively similar in our sensitivity analysis. CONCLUSIONS: Our analysis shows that switching from TIV to QIV to protect children aged 6mo to 5yo in the Brazilian influenza epidemiological context could have a strong public health impact and represent a cost-effective strategy from a public payer perspective, and a highly cost-effective one from a societal perspective.

Diversity and distribution of avian malaria and related haemosporidian parasites in captive birds from a Brazilian megalopolis.

BACKGROUND: The role of zoos in conservation programmes has increased significantly in last decades, and the health of captive animals is essential to guarantee success of such programmes. However, zoo birds suffer from parasitic infections, which often are caused by malaria parasites and related haemosporidians. Studies determining the occurrence and diversity of these parasites, aiming better understanding infection influence on fitness of captive birds, are limited. METHODS: In 2011-2015, the prevalence and diversity of Plasmodium spp. and Haemoproteus spp. was examined in blood samples of 677 captive birds from the São Paulo Zoo, the largest zoo in Latin America. Molecular and microscopic diagnostic methods were used in parallel to detect and identify these infections. RESULTS: The overall prevalence of haemosporidians was 12.6%. Parasites were mostly detected by the molecular diagnosis, indicating that many birds harbour subclinical or abortive infections. In this project, birds of 17 orders (almost half of all the orders currently accepted in taxonomy of birds), 29 families, and 122 species, were tested, detecting positive individuals in 27% of bird species. Birds from the Anatidae were the most prevalently infected (64.7% of all infected animals). In all, infections with parasites of the genus Plasmodium (overall prevalence 97.6%) predominated when compared to those of the genus Haemoproteus (2.4%). In total, 14 cytochrome b (cytb) lineages of Plasmodium spp. and 2 cytb lineages of Haemoproteus spp. were recorded. Eight lineages were new. One of the reported lineages was broad generalist while others were reported in single or a few species of birds. Molecular characterization of Haemoproteus ortalidum was developed. CONCLUSION: This study shows that many species of birds are at risk in captivity. It is difficult to stop haemosporidian parasite transmission in zoos, but is possible to reduce the infection rate by treating the infected animals or/and while keeping them in facilities free from mosquitoes. Protocols of quarantine should be implemented whenever an animal is transferred between bird maintaining institutions. This is the first survey of haemosporidians in captive birds from different orders maintained in zoos. It is worth emphasizing the necessity of applying practices to control these parasites in management and husbandry of animals in captivity.

Low vaccine coverage and varicella outbreaks in Brazil - 2019-2022.

The persistence of varicella outbreaks in Brazil has underscored the high concern with the low vaccine coverage in the last 4 years. Using publicly available data from the Brazilian Health System (SUS), this study analyzed varicella vaccine coverage and incidence trends from 2019 to 2022 in Brazilian States. Vaccine coverage decreased nationally in 2020, possibly influenced by the COVID-19 pandemic's initial phase. In Bahia State, we have the persistence of varicella with an incidence rate of 3.0 cases per 100,000 inhabitants (higher incidence compared to other States) in 2023. Under 15 months children and young children (4-6 Years old) faced the highest risk, urging the importance of vaccination. Despite a monovalent varicella vaccine being available through Brazil's National Immunization Program (NIP), Bahia fell short of achieving the ≥95 % disease control target for coverage. The study highlight the importance of vaccines to prevent some infectious diseases, as varicella, in poor tropical regions. Addressing vaccine hesitancy and misinformation, and augmenting awareness campaigns, are important to achieve and sustain high vaccine coverage over 80% as WHO guidelines to obtain a safe rate of protection for Brazilian population (Brazil's national immunization program has a target of 95% coverage).

Phylogenetics, Epidemiology and Temporal Patterns of Dengue Virus in Araraquara, São Paulo State.

Dengue virus (DENV) is a prominent arbovirus with global spread, causing approximately 390 million infections each year. In Brazil, yearly epidemics follow a well-documented pattern of serotype replacement every three to four years on average. Araraquara, located in the state of São Paulo, has faced significant impacts from DENV epidemics since the emergence of DENV-1 in 2010. The municipality then transitioned from low to moderate endemicity in less than 10 years. Yet, there remains an insufficient understanding of virus circulation dynamics, particularly concerning DENV-1, in the region, as well as the genetic characteristics of the virus. To address this, we sequenced 37 complete or partial DENV-1 genomes sampled from 2015 to 2022 in Araraquara. Then, using also Brazilian and worldwide DENV-1 sequences we reconstructed the evolutionary history of DENV-1 in Araraquara and estimated the time to the most recent common ancestor (tMRCA) for serotype 1, for genotype V and its main lineages. Within the last ten years, there have been at least three introductions of genotype V in Araraquara, distributed in two main lineages (L Ia and L Ib, and L II). The tMRCA for the first sampled lineage (2015/2016 epidemics) was approximately 15 years ago (in 2008). Crucially, our analysis challenges existing assumptions regarding the emergence time of the DENV-1 genotypes, suggesting that genotype V might have diverged more recently than previously described. The presence of the two lineages of genotype V in the municipality might have contributed to the extended persistence of DENV-1 in the region.

Clinical-epidemiological and laboratory profiles of severe Schistosomiasis mansoni infections at a university hospital.

OBJECTIVE: Schistosomiasis remains a public health problem. This was a descriptive and retrospective study of 42 patients with a severe form of schistosomiasis who were admitted to the outpatient clinic of the Faculdade de Medicina da Universidade de São Paulo, São Paulo, in São Paulo, Brazil. METHODS: A data collection questionnaire was designed from the patient charts, and the following variables were evaluated: age, sex, place of birth, occupation, signs and symptoms of schistosomiasis, data from laboratory and imaging examinations, data regarding treatment outcomes, and the existence of comorbidities. Statistical analysis was carried out using Statistical Package for the Social Sciences 15.0 and Microsoft Excel 2003 software. The significance levels of the tests were fixed, accepting 5% type 1 error (α=0.05). Since this was a retrospective observational study, not all data were available for analysis. RESULTS: The mean age of the patients was 48.24 years; 57.1% were male. Statistically significant associations were observed between splenomegaly and thrombocytopenia (p=0.004) and between splenomegaly and leukopenia (p=0.046); however, only 4.5% of the patients had esophageal hemorrhage. Some patients received a specific treatment; of those, 42% took praziquantel, and 35.4% took oxamniquine. Nonspecific drug therapy was given as follows: 65% received propranolol, 90% omeprazole, and 43.6% aluminum hydroxide. The other treatments were as follows: 92.9% of patients underwent endoscopic treatment, 85% received sclerotherapy, and 62.5% used elastic bandages. CONCLUSION: This preliminary study presents a multidisciplinary outpatient follow-up associated with endoscopic and drug treatments that may be effective at preventing bleeding.

Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance systems accordingly. Targeted studies are needed, especially to better understand the effects of vaccinating seronegative individuals.

Detection of Schistosoma mansoni antibodies in a low-endemicity area using indirect immunofluorescence and circumoval precipitin test.

Parasitological diagnostic methods for schistosomiasis lack sensitivity, especially in regions of low endemicity. The objective of this study was to determine the prevalence of Schistosoma mansoni infections by antibody detection using the indirect immunofluorescence assay (IFA-IgM) and circumoval precipitin test (COPT). Serum samples of 572 individuals were randomly selected. The IFA-IgM and COPT were used to detect anti-S. mansoni antibodies. Of the patients studied, 15.9% (N = 91) were IFA-IgM positive and 5.1% (N = 29) had COPT reactions (P < 0.001 by McNemar's test). Immunodiagnostic techniques showed higher infection prevalence than had been previously estimated. This study suggests that combined use of these diagnostic tools could be useful for the diagnosis of schistosomiasis in epidemiological studies in areas of low endemicity.

Clinical-epidemiological and laboratory profiles of severe Schistosomiasis mansoni infections at a university hospital

OBJECTIVE: Schistosomiasis remains a public health problem. This was a descriptive and retrospective study of 42 patients with a severe form of schistosomiasis who were admitted to the outpatient clinic of the Faculdade de Medicina da Universidade de São Paulo, São Paulo, in São Paulo, Brazil. METHODS: A data collection questionnaire was designed from the patient charts, and the following variables were evaluated: age, sex, place of birth, occupation, signs and symptoms of schistosomiasis, data from laboratory and imaging examinations, data regarding treatment outcomes, and the existence of comorbidities. Statistical analysis was carried out using Statistical Package for the Social Sciences 15.0 and Microsoft Excel 2003 software. The significance levels of the tests were fixed, accepting 5% type 1 error (α=0.05). Since this was a retrospective observational study, not all data were available for analysis. RESULTS: The mean age of the patients was 48.24 years; 57.1% were male. Statistically significant associations were observed between splenomegaly and thrombocytopenia (p=0.004) and between splenomegaly and leukopenia (p=0.046); however, only 4.5% of the patients had esophageal hemorrhage. Some patients received a specific treatment; of those, 42% took praziquantel, and 35.4% took oxamniquine. Nonspecific drug therapy was given as follows: 65% received propranolol, 90% omeprazole, and 43.6% aluminum hydroxide. The other treatments were as follows: 92.9% of patients underwent endoscopic treatment, 85% received sclerotherapy, and 62.5% used elastic bandages. CONCLUSION: This preliminary study presents a multidisciplinary outpatient follow-up associated with endoscopic and drug treatments that may be effective at preventing bleeding.

Molecular characterization of human polyomavirus JC in Brazilian AIDS patients with and without progressive multifocal leukoencephalopathy.

BACKGROUND: JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), is classified in 8 different genotypes. Previous reports have suggested a positive association between specific genotypes and PML. OBJECTIVE: To compare genotypes and adaptive mutations of JCV strains from Brazilian AIDS patients with and without PML. STUDY DESIGN: The VP1 region of JCV was amplified by polymerase chain reaction from cerebrospinal fluid samples from 51 patients with PML and from urine samples of 47 patients with AIDS without central nervous system disease. Genotyping was done by phylogenetic analysis. Amino acid replacement and selection pressures were also investigated. RESULTS: JCV genotype frequency distributions showed that genotypes 2 (32.7%), 1 (26.5%) and 3 (23.5%) were the most prevalent. Genotype 1 had a positive association (p<0.0001) and genotype 3 showed an inverse association (p<0.001) with PML. A previously undescribed point mutation at residue 91 (L/I or L/V) and (L/P), non-genotype-associated, was found in 5/49 (10.2%) and 2/47 (4.3%) JCV sequences from PML and non-PML patients, respectively. This mutation was under positive selection only in PML patients. A previously described substitution of T-A in position 128 showed a significant difference between PML and non-PML cases (70% versus 16%, respectively, p<0.0005). CONCLUSION: In Brazilian patients with AIDS, JCV genotype 1 showed a strong association with PML (p<0.0001) and JCV genotype 3 showed an inverse association with PML. The possible association of aminoacids substitution in residues 91 and 128 with PML in patients with AIDS must be further investigated.