Effect of heatwaves on daily hospital admissions in Portugal, 2000-18: an observational study.

BACKGROUND: Climate change has increased the frequency, intensity, and duration of heatwaves, posing a serious threat to public health. Although the link between high temperatures and premature mortality has been extensively studied, the comprehensive quantification of heatwave effects on morbidity remains underexplored. METHODS: In this observational study, we assessed the relationship between heatwaves and daily hospital admissions at a county level in Portugal. We considered all major diagnostic categories and age groups (<18 years, 18-64 years, and ≥65 years), over a 19-year period from 2000 to 2018, during the extended summer season, defined as May 1, to Sept 30. We did a comprehensive geospatial analysis, integrating over 12 million hospital admission records with heatwave events indexed by the Excess Heat Factor (EHF), covering all 278 mainland counties. We obtained data from the Hospital Morbidity Database and E-OBS daily gridded meteorological data for Europe from 1950 to present derived from in-situ observations. To estimate the effect of heatwaves on hospital admissions, we applied negative binomial regression models at both national and county levels. FINDINGS: We found a statistically significant overall increase in daily hospital admissions during heatwave days (incidence rate ratio 1·189 [95% CI 1·179-1·198]; p<0·0001). All age groups were affected, with children younger than 18 years being the most affected (21·7% [20·6-22·7] increase in admissions; p<0·0001), followed by the working-age (19·7% [18·7-20·7]; p<0·0001) and elderly individuals (17·2% [16·2-18·2]; p<0·0001). All 25 major disease diagnostic categories showed significant increases in hospital admissions, particularly burns (34·3% [28·7-40·1]; p<0·0001), multiple significant trauma (26·8% [22·2-31·6]; p<0·0001), and infectious and parasitic diseases (25·4% [23·5-27·3]; p<0·0001). We also found notable increases in endocrine, nutritional, and metabolic diseases (25·1% [23·4-26·8]; p<0·0001), mental diseases and disorders (23·0% [21·1-24·8]; p<0·0001), respiratory diseases (22·4% [21·2-23·6]; p<0·0001), and circulatory system disorders (15·8% [14·7-16·9]; p<0·0001). INTERPRETATION: Our results provide statistically significant evidence of the association between heatwaves and increased hospitalisations across all age groups and for all major causes of disease. To our knowledge, this is the first study to estimate the full extent of heatwaves' impact on hospitalisations using the EHF index over a 19-year period, encompassing an entire country, and spanning 25 disease categories during multiple heatwave events. Our data offer crucial information to guide policy makers in effectively and efficiently allocating resources to address the profound health-care consequences resulting from climate change. FUNDING: None.

Prioritization criteria in policies and management of human resources for health: a proposal for a validated methodology.

Objective: To create and validate criteria for prioritizing problems related to policies and management of the health workforce. Methods: This methodological study was divided into three stages. First, the criteria were elaborated by means of a systematized literature review. Second, the criteria were evaluated online by a committee of judges comprised of eight specialists. In the third stage, an evaluation was carried out by the target audience in a hybrid workshop. The participants evaluated the material using the Suitability Assessment of Materials instrument, adapted for the research. Results: Three prioritization criteria (relevance, window of opportunity and acceptability) and a scoring scale were developed based on the literature review. In the evaluation by the committee of judges, the approval percentage of the criteria and prioritization method was 84%. Modifications were made based on suggestions in relation to the material presented to the specialists. In the pre-test stage, the approval percentage varied by item, with six of them reaching a maximum approval of 100% (corresponding to approximately 46% of the items), four reaching 92% and three achieving 83% each, indicating positive results. Conclusions: The developed criteria were considered valid for use in the context of policies and management in the area of human resources for health.

A recombinant chimeric antigen constructed with B-cell epitopes from Mycobacterium leprae hypothetical proteins is effective for the diagnosis of leprosy.

The diagnosis if leprosy is difficult, as it requires clinical expertise and sensitive laboratory tests. In this study, we develop a serological test for leprosy by using bioinformatics tools to identify specific B-cell epitopes from Mycobacterium leprae hypothetical proteins, which were used to construct a recombinant chimeric protein, M1. The synthetic peptides were obtained and showed good reactivity to detect leprosy patients, although the M1 chimera have showed sensitivity (Se) and specificity (Sp) values higher than 90.0% to diagnose both paucibacillary (PB) and multibacillary (MB) leprosy patients, but not those developing tegumentary or visceral leishmaniasis, tuberculosis, Chagas disease, malaria, histoplasmosis and aspergillosis, in ELISA experiments. Using sera from household contacts, values for Se and Sp were 100% and 65.3%, respectively. In conclusion, our proof-of-concept study has generated data that suggest that a new recombinant protein could be developed into a diagnostic antigen for leprosy.

Polycyclic aromatic hydrocarbons in seawater after the mysterious oil spill of 2019 on the Pernambuco coast, northeast Brazil.

In 2019, one of Brazil's most significant environmental disasters occurred, involving an oil spill that directly affected Pernambuco state. Contamination along the coast was evaluated by the quantification of polycyclic aromatic hydrocarbons (PAHs) in fifty seawater samples collected in the summer and winter of 2021. Analysis using fluorescence spectroscopy revealed that for all the samples, levels of dissolved/dispersed petroleum hydrocarbons (DDPHs) were higher than the regional baseline for tropical western shores of the Atlantic Ocean. GC-MS analyses quantified 17 PAHs in the samples, with highest total PAHs concentrations of 234 ng L-1 in summer and 33.3 ng L-1 in winter, which were consistent with the highest risks observed in ecotoxicity assays. The use of diagnostic ratios showed that the coast was impacted by a mixture of PAHs from petrogenic and pyrolytic sources. The results indicated the need for continuous monitoring of the regions affected by the 2019 spill.

Delayed recovery from ataxic dementia following liposuction.

A 19-year-old student developed hypoventilation and cyanosis at the end of a cosmetic liposuction procedure. She was awake, but severely abulic, disoriented, and unable to stand and walk due to severe locomotor ataxia. Neuropsychological evaluation showed psychomotor slowness, and deficits in memory encoding and retrieval, and on executive, and visuospatial and visuoperceptual tests; oral comprehension and constructional praxis were spared. ¹H-MRS showed a reduction of NAA. A year later, her cognitive and neurological exam, and NAA returned to normal, and she resumed her normal life. The severity of the acute manifestations of hypoxic encephalopathy not always entail a poor prognosis.

Guillain-Barré Syndrome After a SARS-CoV-2 Vaccine.

The worldwide mass vaccination campaign against COVID-19 has been the largest one ever undertaken. Although the short-term safety profile of the different vaccines has been well established, neuroinflammatory complications have been described, including rare cases of acute demyelinating inflammatory polyneuropathy. We report a 63-year-old man who presented to the emergency department with proximal muscle weakness and paresthesia. He had received the first dose of the AZD1222 SARS-CoV-2 vaccine (Oxford, AstraZeneca) two weeks before presentation. The diagnosis of Guillain-Barré syndrome (GBS) was confirmed by clinical features, cerebrospinal fluid analysis, and electromyography. On the second hospital day, progression to flaccid tetraplegia, cranial nerve involvement, and respiratory failure, requiring invasive mechanical ventilation, were noted, and he was admitted to the intensive care unit. Despite the prompt diagnosis and immunosuppressive treatment initiation, the patient was left with severe disability. Although the COVID-19 vaccination was generally safe and socially beneficial, individual adverse reactions, including neuroinflammatory severe complications, may occur.

IgG4-related disease: Case report and 6-year follow-up of an elusive diagnosis mimicking malignancy.

Key Clinical Message: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

DArTseq-based SNP markers reveal high genetic diversity among early generation fall armyworm tolerant maize inbred lines.

Diversity analysis using molecular markers serves as a powerful tool in unravelling the intricacies of inclusivity within various populations and is an initial step in the assessment of populations and the development of inbred lines for host plant resistance in maize. This study was conducted to assess the genetic diversity and population structure of 242 newly developed S3 inbred lines using 3,305 single nucleotide polymorphism (SNP) markers and to also assess the level of homozygosity achieved in each of the inbred lines. A total of 1,184 SNP markers were found highly informative, with a mean polymorphic information content (PIC) of 0.23. Gene diversity was high among the inbred lines, ranging from 0.04 to 0.50, with an average of 0.27. The residual heterozygosity of the 242 S3 inbred lines averaged 8.8%, indicating moderately low heterozygosity levels among the inbred lines. Eighty-four percent of the 58,322 pairwise kinship coefficients among the inbred lines were near zero (0.00-0.05), with only 0.3% of them above 0.50. These results revealed that many of the inbred lines were distantly related, but none were redundant, suggesting each inbred line had a unique genetic makeup with great potential to provide novel alleles for maize improvement. The admixture-based structure analysis, principal coordinate analysis, and neighbour-joining clustering were concordant in dividing the 242 inbred lines into three subgroups based on the pedigree and selection history of the inbred lines. These findings could guide the effective use of the newly developed inbred lines and their evaluation in quantitative genetics and molecular studies to identify candidate lines for breeding locally adapted fall armyworm tolerant varieties in Ghana and other countries in West and Central Africa.

Assessment of the Risk Impact of SARS-CoV-2 Infection Prevalence between Cats and Dogs in America and Europe: A Systematic Review and Meta-Analysis.

The COVID-19 pandemic represented a huge obstacle for public health and demonstrated weaknesses in surveillance and health promotion systems around the world. Its etiological agent, SARS-CoV-2, of zoonotic origin, has been the target of several studies related to the control and prevention of outbreaks and epidemics of COVID-19 not only for humans but also for animals. Domestic animals, such as dogs and cats, have extensive contact with humans and can acquire the infection both naturally and directly from humans. The objective of this article was to summarize the seroprevalence findings of SARS-CoV-2 in dogs and cats and correlate them with the strength of infection risk between each of them. This is a systematic review and meta-analysis following the recommendations of PRISMA 2020. The search and selection of papers was carried out using in vivo experimental works with animals using the descriptors (MeSH/DeCS) "Animal", "Public Health", "SARS-CoV-2" and "Pandemic" (together with AND) in English, Portuguese or Spanish for Science Direct, PUBMED, LILACS and SciELO databases. The ARRIVE checklist was used for methodological evaluation and the Comprehensive Meta-Analysis v2.2 software with the Difference Risk (RD) test to evaluate statistical inferences (with subgroups by continent). Cats showed greater susceptibility to SARS-CoV-2 compared to dogs both in a joint analysis of studies (RD = 0.017; 95% CI = 0.008-0.025; p < 0.0001) and in the American subgroup (RD = 0.053; 95% CI = 0.032-0.073; p < 0.0001), unlike the lack of significant difference on the European continent (RD = 0.009; 95% CI = -0.001-0.018; p = 0.066). Therefore, it was observed that cats have a greater interest in health surveillance due to the set of biological and ecological aspects of these animals, but also that there are a set of factors that can influence the spread and possible spillover events of the virus thanks to the anthropozoonotic context.

Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity.

Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6',2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA-[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA-[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA-[RuII(bd)(NO2)(tpy)]+ and fs-DNA-[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.

CD20+ T cells in monoclonal B cell lymphocytosis and chronic lymphocytic leukemia: frequency, phenotype and association with disease progression.

Introduction: In monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), the expansion of malignant B cells disrupts the normal homeostasis and interactions between B cells and T cells, leading to immune dysregulation. CD20+ T cells are a subpopulation of T cells that appear to be involved in autoimmune diseases and cancer. Methods: Here, we quantified and phenotypically characterized CD20+ T cells from MBL subjects and CLL patients using flow cytometry and correlated our findings with the B-cell receptor mutational status and other features of the disease. Results and discussion: CD20+ T cells were more represented within the CD8+ T cell compartment and they showed a predominant memory Tc1 phenotype. CD20+ T cells were less represented in MBL and CLL patients vs healthy controls, particularly among those with unmutated IGVH gene. The expansion of malignant B cells was accompanied by phenotypic and functional changes in CD20+ T cells, including an increase in follicular helper CD4+ CD20+ T cells and CD20+ Tc1 cells, in addition to the expansion of the TCR Vß 5.1 in CD4+ CD20+ T cells in CLL.

Effects of cancer-induced cachexia and administration of L-glutathione on the intestinal mucosa in rat.

Walker-256 tumor is an experimental model known to promote cachexia syndrome, oxidative stress, and systemic inflammation. This study evaluated the duodenal mucosa of rats with Walker-256 tumor administered with 1% L-glutathione, intending to evaluate the damage caused by cancer-associated cachexia in the gastrointestinal tract and the effects of antioxidant administration on mucosal protection. Twenty-four 55-day-old male Wistar rats were distributed into four groups: control (C); control administered with 1% L-glutathione (C-GSH); Walker-256 tumor (W) and Walker-256 tumor administered with 1% L-glutathione (W-GSH). After 14 days of treatment, the duodenum was harvested for morphometric analysis of the mucosa, proliferation, apoptosis, immunostaining of varicosities immunoreactive (IR) to vasoactive intestinal peptide (VIP) and 5-HT-IR cells, and quantification of mast cells and goblet cells. Walker-256 tumor-bearing rats showed cachexia syndrome, mucosal atrophy, reduced cell proliferation, reduced 5-HT-IR cells, and increased goblet cells and VIPergic varicosities, which were not reversed by L-glutathione. On the other hand, L-glutathione caused a reduction of cells in apoptosis and mast cell recruitment, demonstrating a partial recovery of the damage detected in the intestinal mucosa.

Periparturient blood T-lymphocyte PD-1 and CTLA-4 expression as potential predictors of new intramammary infections in dairy cows during early lactation (short communication).

BACKGROUND: The periparturient period in dairy cows is marked by immunosuppression which increases the likelihood of infectious disorders, particularly also mastitis. An in-depth understanding of peripartum leukocyte biology is vital for the implementation of highly successful post-partum disease prevention measures. Immune checkpoint molecules, such as programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are critical inhibitory receptors expressed on immune cells, particularly T cells, that drive immunosuppressive signaling pathways. However, the potential role of immune checkpoint molecules expression in T-cells on udder health has never been explored. Thus, the association between the occurrence of new postpartum intramammary infections (IMIs) and the expression of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on blood T-cells during the peripartum period was investigated. RESULTS: In this study, the incidence of IMIs by any pathogen in early lactation was not associated with a higher expression of PD-1 and CTLA-4 in the periparturient period. However, the incidence of IMIs by major pathogens throughout the first month of lactation was significantly associated with higher expression of PD-1 at 14 days before calving (P = 0.03) and CTLA-4 at parturition (P = 0.03) by blood T-cells. Also, the expression of CTLA-4 at D0 (P = 0.012) by T-cells was associated with the occurrence of persistent IMIs during the first month of lactation. CONCLUSIONS: To our knowledge, this is the first report to investigate the expression of PD-1 and CTLA-4 by blood T-lymphocytes during the periparturient period in dairy cows and to explore their relationship with the incidence of new IMIs in the postpartum period. Thus, a comprehensive understanding of leukocyte biology during peripartum would appear to be a prerequisite for the identification of resilient dairy cows or targets innovative (immunological) non-antibiotic approaches in the transition period.

Vertical Migration of Second-stage Juveniles of Meloidogyne enterolobii as Influenced by Temperature and Host.

Infective second-stage juveniles (J2) of Meloidogyne spp. migrate towards host roots, which depends on several factors, including root exudates and soil temperature. Although Meloidogyne enterolobii is a highly virulent nematode that affects major agricultural crops worldwide, there is limited ecological data about it. The objective of this study was to determine the J2 migration pattern vertically in 14-cm long segmented soil columns towards tomato (Solanum lycopersicum) and marigold (Tagetes patula) roots, each grown at two soil temperatures (20 or 26ºC). Bottomless cups with tomatoes or marigolds were attached to the top of each column; cups with no plants were used as untreated controls. Juveniles (1,000/column) were injected into a hole located 1 cm from the bottom of each column. The apparatuses were placed in growth chambers at 20 or 26ºC, and J2 were allowed to migrate for 3, 6, 9, or 12 days after injection (DAI). At each harvest, J2 were extracted from each ring of the columns and counted to compare their distribution, and root systems were stained to observe root penetration. M. enterolobii migrated over 13 cm vertically 3 DAI regardless of temperature, even without plant stimuli. The vertical migration was greater at 26ºC, where 60% of active J2 were found at distances >13 cm at 12 DAI. Temperature did not affect root penetration. Overall, a greater number of J2 was observed in tomato roots, and root penetration increased over time.

Salicylic Acid and Water Stress: Effects on Morphophysiology and Essential Oil Profile of Eryngium foetidum.

The exogenous application of bioregulators, such as salicylic acid (SA), has exhibited promising outcomes in alleviating drought stress. Nevertheless, its impact on culantro (Eryngium foetidum L.) remains unexplored. Thus, the aim of this study was to assess how SA impacts the growth, morphophysiology, and essential oil composition of culantro when subjected to drought. To achieve this, culantro plants were grown under three different watering regimes: well-watered, drought-stressed, and re-watered. Additionally, they were either treated with SA (100 µM) or left untreated, with water serving as the control. SA application did not mitigate the effects of drought in biomass production but increased biomass, leaf number, leaf area, and photosynthetic pigments under well-irrigated and re-watered conditions. After a drought period followed by re-watering, plants recovered membrane integrity independently of SA application. Water stress and the exogenous application of SA also modulated the profile of essential oils. This is the first report about SA and drought affecting growth and essential oil composition in culantro.

Biomedical and Biotechnological Potential of Animal Venoms: Bothrops Snake Venoms and their Antimicrobial Applications.

The pursuit of novel treatment alternatives to address the accumulated resistance to antimicrobials over the years has prompted the scientific community to explore biodiversity, particularly animal venom, as a potential source of new antimicrobial drugs. Snake venoms, with their complex mixtures of components, are particularly promising targets for investigation in this regard. The search for novel molecules exhibiting antimicrobial activity against multidrug-resistant strains is of paramount importance for public health and numerous research groups worldwide. High expectations within the healthcare field are supported by the scientific literature, which highlights the potential development of innovative drugs through in vivo and in vitro application, depending on dose titration. Snake venoms and their molecules and peptides offer exponential possibilities for biotechnological applications as antimicrobial agents. However, many uncertainties and unexplored avenues remain, presenting opportunities for discoveries and research.

Adhesive restorations in primary dentition: A retrospective analysis of survival rate and associated factors.

BACKGROUND: Several clinical and individual factors may play a role in the survival rate of dental restorations, such as characteristics related to the child's age and oral hygiene, and factors associated with the tooth, such as the type of material and number of surfaces to be restored. AIM: To analyse the survival rate of adhesive restorations on primary teeth and factors associated with restoration survival. DESIGN: The study included dental records of children aged 3-12 years having received adhesive restorations on primary teeth at a Brazilian dental school between 2009 and 2019. A Kaplan-Meier survival curve was used to plot survival rates using the log-rank test. A multivariate Cox regression model was run to identify individual and dental factors associated with restoration failure. RESULTS: The sample comprised 269 restored teeth in 111 children. Survival curves were similar for all materials (p = .20) and types of isolation (p = .05). The annual failure rate was 3.60% for glass ionomer cement, 1.23% for resin-modified glass ionomer cement and 0.40% for composite resin. The following variables were associated with more failures: Class II restoration compared with Class I (HR = 1.96; 95%CI: 1.28-2.99, p < .001), proportion of decayed teeth (HR = 11.89; 95%CI: 2.80-50.57, p < .001) and child's age (HR = 1.17; 95%CI: 1.06-1.29, p < .001). CONCLUSION: The different materials and types of isolation had similar survival rates. Children with more decayed teeth have an increased risk of restoration failure.

Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination.

BACKGROUND: We explored the impact of prior Yellow fever (YF) or Japanese encephalitis (JE) vaccination on the efficacy of Takeda's dengue vaccine candidate, TAK-003 (NCT02747927). METHODS: Children 4-16 years of age were randomized 2:1 to receive TAK-003 or placebo and were under active febrile surveillance. Symptomatic dengue was confirmed by serotype-specific RT-PCR. YF and JE vaccination history was recorded. RESULTS: Of the 20,071 children who received TAK-003 or placebo, 21.1% had a YF and 23.9% had a JE vaccination history at randomization. Fifty-seven months after vaccination, vaccine efficacy was 55.7% (95% CI, 39.7%-67.5%) in those with YF vaccination, 77.8% (70.8%-83.1%) for JE vaccination, and 53.5% (45.4%-60.4%) for no prior YF/JE vaccination. Regional differences in serotype distribution confound these results. The apparent higher vaccine efficacy in the JE vaccination subgroup could be largely explained by serotype-specific efficacy of TAK-003. Within 28 days of any vaccination, the proportions of participants with serious adverse events in the YF/JE prior vaccination population were comparable between the TAK-003 and placebo groups. CONCLUSIONS: The available data do not suggest a clinically relevant impact of prior JE or YF vaccination on TAK-003 performance. Overall, TAK-003 was well-tolerated and efficacious in different epidemiological settings.