Dynamics of Salmonella enterica and antimicrobial resistance in the Brazilian poultry industry and global impacts on public health.

Non-typhoidal Salmonella enterica is a common cause of diarrhoeal disease; in humans, consumption of contaminated poultry meat is believed to be a major source. Brazil is the world's largest exporter of chicken meat globally, and previous studies have indicated the introduction of Salmonella serovars through imported food products from Brazil. Here we provide an in-depth genomic characterisation and evolutionary analysis to investigate the most prevalent serovars and antimicrobial resistance (AMR) in Brazilian chickens and assess the impact to public health of products contaminated with S. enterica imported into the United Kingdom from Brazil. To do so, we examine 183 Salmonella genomes from chickens in Brazil and 357 genomes from humans, domestic poultry and imported Brazilian poultry products isolated in the United Kingdom. S. enterica serovars Heidelberg and Minnesota were the most prevalent serovars in Brazil and in meat products imported from Brazil into the UK. We extended our analysis to include 1,259 publicly available Salmonella Heidelberg and Salmonella Minnesota genomes for context. The Brazil genomes form clades distinct from global isolates, with temporal analysis suggesting emergence of these Salmonella Heidelberg and Salmonella Minnesota clades in the early 2000s, around the time of the 2003 introduction of the Enteritidis vaccine in Brazilian poultry. Analysis showed genomes within the Salmonella Heidelberg and Salmonella Minnesota clades shared resistance to sulphonamides, tetracyclines and beta-lactams conferred by sul2, tetA and blaCMY-2 genes, not widely observed in other co-circulating serovars despite similar selection pressures. The sul2 and tetA genes were concomitantly carried on IncC plasmids, whereas blaCMY-2 was either co-located with the sul2 and tetA genes on IncC plasmids or independently on IncI1 plasmids. Long-term surveillance data collected in the UK showed no increase in the incidence of Salmonella Heidelberg or Salmonella Minnesota in human cases of clinical disease in the UK following the increase of these two serovars in Brazilian poultry. In addition, almost all of the small number of UK-derived genomes which cluster with the Brazilian poultry-derived sequences could either be attributed to human cases with a recent history of foreign travel or were from imported Brazilian food products. These findings indicate that even should Salmonella from imported Brazilian poultry products reach UK consumers, they are very unlikely to be causing disease. No evidence of the Brazilian strains of Salmonella Heidelberg or Salmonella Minnesota were observed in UK domestic chickens. These findings suggest that introduction of the Salmonella Enteritidis vaccine, in addition to increasing antimicrobial use, could have resulted in replacement of salmonellae in Brazilian poultry flocks with serovars that are more drug resistant, but less associated with disease in humans in the UK. The plasmids conferring resistance to beta-lactams, sulphonamides and tetracyclines likely conferred a competitive advantage to the Salmonella Minnesota and Salmonella Heidelberg serovars in this setting of high antimicrobial use, but the apparent lack of transfer to other serovars present in the same setting suggests barriers to horizontal gene transfer that could be exploited in intervention strategies to reduce AMR. The insights obtained reinforce the importance of One Health genomic surveillance.

Prevalence and antimicrobial resistance of Escherichia coli and Salmonella spp. in animal feed in Colombia.

Objective: To determine the prevalence and antimicrobial resistance of Escherichia coli and Salmonella spp. in animal feed samples collected between 2018 and 2021 in Colombia. Methods: This was a laboratory-based cross-sectional study using routine data from the program for inspection, surveillance, and control of animal feed at the Colombian Agriculture Institute. Samples of animal feed for swine, poultry, canine, feline, leporine, piscine, and equine species were processed for detection of E. coli and Salmonella spp. using enrichment and selective culture methods. Isolates were tested for antimicrobial susceptibility using an automated microdilution method. Results: Of 1 748 animal feed samples analyzed, 83 (4.7%) were positive for E. coli and 66 (3.8%) for Salmonella spp. The presence of E. coli and Salmonella spp. was highest in feed for poultry (6.4% and 5.5%) and swine (6.1% and 4.3%). Antimicrobial resistance testing was performed in 27 (33%) E. coli isolates and 26 (39%) Salmonella isolates. Among E. coli, resistance was most frequently observed to ampicillin (44.5%) followed by cefazolin (33.3%), ciprofloxacin (29.6%), ampicillin/sulbactam (26%), and ceftriaxone (11.1%). The highest resistance levels in Salmonella spp. isolates were against cefazolin (7.7%) and piperacillin/tazobactam (7.7%). Conclusions: This is the first study from Colombia reporting on the prevalence and antimicrobial resistance of E. coli and Salmonella spp. in animal feed samples. Its results establish a baseline over a wide geographical distribution in Colombia. It highlights the need to integrate antimicrobial resistance surveillance in animal feed due to the emergence of resistant bacteria in this important stage of the supply chain.

Multidrug-resistant Salmonella spp. in fecal samples of pigs with suspected salmonellosis in Antioquia, Colombia, 2019-2021.

Objectives: To determine the proportion of Salmonella enterica in fecal samples of live pigs with suspected salmonellosis analyzed at the diagnostic unit of the University of Antioquia, Colombia between 2019 and 2021, and examine the serotypes and antimicrobial resistance patterns. Methods: This was a laboratory-based cross-sectional study of routine data on fecal samples received from pig farms in all nine subregions of Antioquia state, Colombia. Salmonella spp. detection at the university is done using enrichment, selective culture, and polymerase chain reaction. Serotypes were identified using the Kauffmann-White scheme and isolates were tested for antimicrobial susceptibility using broth microdilution. Results: Of 653 samples tested, 149 (23%) were positive for S. enterica. Nine serotypes were identified. The most common were Salmonella Typhimurium (56%) and its monophasic variant (35%). Resistance to ampicillin (70%) was most frequently observed, followed by ciprofloxacin (55%), and sulfamethoxazole-trimethoprim (52%). No isolates were resistant to amikacin and gentamicin. Multidrug resistance (resistance to ≥ 3 classes of antibiotics) was observed in 61 (44%) isolates. Multidrug resistance was highest in S. Typhimurium (57%) compared with the other serotypes. Serotype was associated with multidrug resistance (p = 0.01), but age of the pig and sub-region were not. Conclusions: The proportion of Salmonella spp. and the associated high levels of multidrug resistance are of concern and may indicate irrational use of antimicrobials and poor management practices in pig production systems in the region. Strengthened surveillance is needed to monitor and improve farm management practices and the use of antimicrobials in farms in Colombia.

Lessons learned from the implementation of integrated serosurveillance of communicable diseases in the Americas.

Objective: Systematize the experience and identify challenges and lessons learned in the implementation of an initiative for integrated serosurveillance of communicable diseases using a multiplex bead assay in countries of the Americas. Methods: Documents produced in the initiative were compiled and reviewed. These included concept notes, internal working papers, regional meetings reports, and survey protocols from the three participating countries (Mexico, Paraguay, and Brazil) and two additional countries (Guyana and Guatemala) where serology for several communicable diseases was included in neglected tropical diseases surveys. Information was extracted and summarized to describe the experience and the most relevant challenges and lessons learned. Results: Implementing integrated serosurveys requires interprogrammatic and interdisciplinary work teams for the design of survey protocols to respond to key programmatic questions aligned to the needs of the countries. Valid laboratory results are critical and rely on the standardized installment and roll-out of laboratory techniques. Field teams require adequate training and supervision to properly implement survey procedures. The analysis and interpretation of serosurveys results should be antigen-specific, contextualizing the responses for each disease, and triangulated with programmatic and epidemiological data for making decisions tailored to specific population socioeconomic and ecologic contexts. Conclusions: Integrated serosurveillance as a complementary tool for functional epidemiological surveillance systems is feasible to use and key components should be considered: political engagement, technical engagement, and integrated planning. Aspects such as designing the protocol, selecting target populations and diseases, laboratory capacities, anticipating the capacities to analyze and interpret complex data, and how to use it are key.

Current status of the knowledge on the epidemiology of tungiasis in the Americas.

Objectives: To present the state-of-the-knowledge on the epidemiology of tungiasis in the Region of the Americas. Methods: A search of publications on the epidemiology of tungiasis in the Americas was performed in PubMed and LILACS databases from January 2007 to June 2021. In addition, a manual literature search on articles on the epidemiology of tungiasis was performed. Results: A total of 83 articles were analyzed which contained relevant information on tungiasis cases and their geographical distribution, prevalence and risk factors, life cycle, sites where transmission takes place, and zoonotic aspects. The on-host and off-host life cycles have been researched in detail. In certain contexts, the whole life cycle is completed indoors enabling transmission around the whole year. Cases were reported from 10 countries; 71% of them were from Brazil. In the general population, the prevalence varied between 1.0% and 82.6% according to the settings. Age-specific prevalence indicated that children and the elderly bear the highest disease burden. Risk factor studies indicate that tungiasis is associated with severe poverty. Conclusions: In the Americas, there are important gaps in information and knowledge of tungiasis. Understanding the burden, epidemiology, distribution, magnitude, related risk factors, and reservoirs, among others, is needed to develop and implement integrated control measures tailored to the context and patterns of transmission in the affected communities.

Neurological outcomes of transcatheter aortic valve implantation with or without cerebral embolic protection devices: A meta-analysis.

INTRODUCTION: Cerebral embolic protection devices (CEPDs) are designed to prevent embolization of debris during transcatheter aortic valve implantation (TAVI). Current evidence from randomized clinical trials (RCTs) and observational studies is controversial. AIMS: The purpose of this meta-analysis was to study the influence of CEPDs on stroke, silent ischemic lesions and neurocognitive function. METHODS: A systematic search was conducted including RCTs or adjusted observational studies comparing TAVI with or without CEPDs. Pooled odds ratios, risk ratios or standardized mean differences with 95% confidence intervals were calculated using the inverse of variance method. Risk of bias sensitivity analyses and meta regression for CEPD type were also conducted. RESULTS: Five RCTs and five adjusted observational studies were included (n= 159,865). Mean age of the patients was 81.1 (SD 1.04) years in CEPDs and 81 (SD 1.86) in non-CEPD. The overall quality of evidence using the GRADE system for each endpoint was low to very low, mainly due to serious risk of bias, inconsistency and imprecision. Random effects meta-analysis detected no significant differences between CEPD and non-CEPD (OR= 0.74; 95% CI 0.51-1.07; P= 0.105; I2= 82.1%) for 30-day stroke. This finding was consistent in meta regression for CEPD type and subgroup analyses by study type and CEPD type. No significant differences between groups were observed in cerebral DW-MRI assessment and neurocognitive function evaluation. CONCLUSION: In the present meta- analysis of five RCTs and five adjusted observational studies, the use of a CEPD during TAVI was not associated with a significant benefit on 30- day stroke, total lesion volume per patient, number of ischemic lesions per patient and neurocognitive function assessments.

COVID-19 and inequities in the Americas: lessons learned and implications for essential health services.

The COVID-19 pandemic has exacerbated social, economic, and health-related disparities, which disproportionately affect persons living in conditions of vulnerability. Such populations include ethnic groups who face discrimination and experience barriers to accessing comprehensive health care. The COVID-19 pandemic has exposed these health disparities, and disruptions of essential health services have further widened the gaps in access to health care. Noncommunicable diseases are more prevalent among groups most impacted by poor social determinants of health and have been associated with an increased likelihood of severe COVID-19 disease and higher mortality. Disruptions in the provision of essential health services for noncommunicable diseases, mental health, communicable diseases such as HIV, tuberculosis, and malaria, and maternal and child health services (including sexual and reproductive health), are projected to also increase poor health outcomes. Other challenges have been an increased frequency of interpersonal violence and food insecurity. Countries in the Americas have responded to the disruptions caused by the pandemic by means of health service delivery through telemedicine and other digital solutions and stepping up social service support interventions. As vaccinations for COVID-19 create the opportunity to overcome the pandemic, countries must strengthen primary health care and essential health services with a view to ensuring equity, if the region is to achieve universal health coverage in fulfillment of the Sustainable Development Goals.

La pandemia de COVID-19 ha acentuado las desigualdades sociales, económicas y relacionadas con la salud, que afectan desproporcionadamente a las personas en situación de vulnerabilidad. Esta población incluye grupos étnicos que se enfrentan a la discriminación y obstáculos para el acceso a la atención integral de salud. La pandemia de COVID-19 ha expuesto estas desigualdades de salud, y las interrupciones de los servicios esenciales de salud han ampliado aún más las brechas en el acceso a la atención de salud. Las enfermedades no transmisibles son más prevalentes en los grupos que han sufrido un mayor impacto de los determinantes sociales de la salud deficientes y se han asociado con una mayor probabilidad de presentar un cuadro grave de COVID-19 y una mayor mortalidad. Asimismo, se proyecta que las interrupciones en la prestación de servicios esenciales de salud para las enfermedades no transmisibles, la salud mental, las enfermedades transmisibles como la infección por el VIH, la tuberculosis y la malaria, y los servicios de salud maternoinfantil (como la salud sexual y reproductiva) incrementen los resultados deficientes en materia de salud. Otros retos son una mayor frecuencia de la violencia interpersonal y la inseguridad alimentaria. Los países de la Región de las Américas han respondido a las interrupciones causadas por la pandemia con la prestación de servicios de salud mediante la telemedicina y otras soluciones digitales, y la aceleración de las intervenciones de apoyo de los servicios sociales. A medida que la vacunación contra la COVID-19 crea la oportunidad de superar la pandemia, los países deben fortalecer su atención primaria de salud y sus servicios de salud esenciales a fin de garantizar la equidad, para que la Región logre la cobertura universal de salud en cumplimiento de los Objetivos de Desarrollo Sostenible.

A pandemia de COVID-19 exacerbou as disparidades sociais, econômicas e as relacionadas à saúde, que afetam de maneira desproporcional as pessoas que vivem em situação de vulnerabilidade. Essas populações incluem grupos étnicos que enfrentam discriminação e barreiras para o acesso à atenção integral à saúde. A pandemia de COVID-19 expôs essas disparidades, e as interrupções nos serviços essenciais de saúde ampliaram ainda mais as lacunas no acesso aos cuidados de saúde. As doenças não transmissíveis são mais prevalentes entre os grupos mais afetados por determinantes sociais da saúde deficientes e estão associadas a um aumento na probabilidade de doença grave pela COVID-19 e mortalidade mais elevada. Prevê-se que as interrupções na prestação de serviços essenciais de saúde para doenças não transmissíveis, saúde mental, doenças transmissíveis como HIV, tuberculose e malária, bem como dos serviços de saúde materno-infantil (incluindo saúde sexual e reprodutiva) também aumentem os desfechos adversos de saúde. Outros desafios são o aumento da frequência da violência interpessoal e insegurança alimentar. Os países das Américas responderam às interrupções causadas pela pandemia com a prestação de serviços de saúde por meio da telemedicina e outras soluções digitais, e a aceleração de intervenções de apoio dos serviços sociais. À medida em que a vacinação contra a COVID-19 oferece a oportunidade de superar a pandemia, os países devem fortalecer a atenção primária à saúde e os serviços essenciais de saúde com o objetivo de garantir a equidade, para que a região atinja a cobertura universal de saúde em cumprimento aos Objetivos de Desenvolvimento Sustentável.

Phylogenomic Investigation of IncI1-Iγ Plasmids Harboring blaCMY-2 and blaSHV-12 in Salmonella enterica and Escherichia coli in Multiple Countries.

The objective of this study was to elucidate the genetic and evolutionary relatedness of blaCMY-2- and blaSHV-12-carrying IncI1-Iγ plasmids. Phylogenomic analysis based on core genome alignments and gene presence/absence was performed for different IncI1-Iγ sequence types (STs). Most IncI1-Iγ/ST12 and IncI1-Iγ/ST231 plasmids had near-identical core genomes. The data suggest that widely occurring blaCMY-2-carrying IncI1-Iγ/ST12 plasmids originate from a common ancestor. In contrast, blaSHV-12 was inserted independently into different IncI1-Iγ/ST231-related plasmids.

The decline of dengue in the Americas in 2017: discussion of multiple hypotheses.

OBJECTIVE: Since the 1980s, dengue incidence has increased 30-fold. However, in 2017, there was a noticeable reduction in reported dengue incidence cases within the Americas, including severe and fatal cases. Understanding the mechanism underlying dengue's incidence and decline in the Americas is vital for public health planning. We aimed to provide plausible explanations for the decline in 2017. METHODS: An expert panel of representatives from scientific and academic institutions, Ministry of Health officials from Latin America and PAHO/WHO staff met in October 2017 to propose hypotheses. The meeting employed six moderated plenary discussions in which participants reviewed epidemiological evidence, suggested explanatory hypotheses, offered their expert opinions on each and developed a consensus. RESULTS: The expert group established that in 2017, there was a generalised decreased incidence, severity and number of deaths due to dengue in the Americas, accompanied by a reduction in reported cases of both Zika and chikungunya virus infections, with no change in distribution among age groups affected. This decline was determined to be unlikely due to changes in epidemiological surveillance systems, as similar designs of surveillance systems exist across the region. Although sudden surveillance disruption is possible at a country or regional level, it is unlikely to occur in all countries simultaneously. Retrospective modelling with epidemiological, immunological and entomological information is needed. Host or immunological factors may have influenced the decline in dengue cases at the population level through immunity; however, herd protection requires additional evidence. Uncertainty remains regarding the effect on the outcome of sequential infections of different dengue virus (DENV) types and Zika virus (ZIKV), and vice versa. Future studies were recommended that examine the epidemiological effect of prior DENV infection on Zika incidence and severity, the epidemiological effect of prior Zika virus infection on dengue incidence and severity, immune correlates based on new-generation ELISA assays, and impact of prior DENV/other arbovirus infection on ZIKV immune response in relation to number of infections and the duration of antibodies in relation to interval of protection. Follow-up studies should also investigate whether increased vector control intensification activities contributed to the decline in transmission of one or more of these arboviruses. Additionally, proposed studies should focus on the potential role of vector competence when simultaneously exposed to various arboviruses, and on entomological surveillance and its impact on circulating vector species, with a goal of applying specific measures that mitigate seasonal occurrence or outbreaks. CONCLUSIONS: Multifactorial events may have accounted for the decline in dengue seen in 2017. Differing elements might explain the reduction in dengue including elements of immunity, increased vector control, and even vector and\or viruses changes or adaptations. Most of the results of this expert consensus group meeting are hypothetical and based on limited evidence. Further studies are needed.

OBJECTIF: Depuis les années 1980, l'incidence de la dengue a été multipliée par 30. Cependant, en 2017, il y a eu une réduction notable du nombre de cas d'incidence de dengue rapportés dans les Amériques. Nous voulions fournir des explications plausibles à la baisse en 2017. MÉTHODES: Un groupe d'experts constitué de représentants d'institutions scientifiques et académiques, d'officiels des Ministères de la Santé d'Amérique Latine et de membres du personnel de l'OPS/OMS s'est réuni en octobre 2017 pour proposer et évaluer des hypothèses. RÉSULTATS: En 2017, il y a eu une baisse généralisée de l'incidence, de la sévérité et du nombre de décès dus à la dengue dans les Amériques, accompagnée d'une réduction des cas rapportés d'infections par le virus Zika et par le virus du chikungunya, sans modification dans la répartition entre les groupes d'âge affectés. Il a été déterminé que ce déclin était peu probablement dû aux changements dans les systèmes de surveillance épidémiologique, étant donné que des systèmes de surveillance similaires existaient dans toute la région. Bien que des perturbations soudaines dans la surveillance soient possibles au niveau national ou régional, il est peu probable que cela se produise simultanément dans tous les pays. Une modélisation rétrospective avec des informations épidémiologiques, immunologiques et entomologiques est nécessaire. Des facteurs liés à l'hôte ou immunologiques peuvent avoir influencé le déclin des cas de dengue au niveau de la population par le biais de l'immunité; cependant, l'évidence d'une protection conférée par l'effet du troupeau nécessite des données supplémentaires. Une incertitude subsiste quant à l'effet sur le résultat des infections séquentielles de différents types du virus de la dengue (DENV) et du virus Zika (ZIKV), et vice-versa. Les études à venir devraient examiner (1) l'effet épidémiologique d'une infection antérieure par le DENV sur l'incidence et la sévérité du virus Zika, (2) l'effet épidémiologique d'une infection antérieure par le virus Zika sur l'incidence et la sévérité de la dengue, (3) les corrélats immunitaires basés sur des tests ELISA de nouvelle génération, (4) l' impact d'une infection antérieure à DENV/autres arbovirus sur la réponse immunitaire au ZIKV en fonction du nombre d'infections et de la durée des anticorps en fonction de l'intervalle de protection, (5) si des activités d'intensification de la lutte antivectorielle ont contribué à la diminution de la transmission d'un ou plusieurs de ces arbovirus, (6) le rôle potentiel de la compétence vectorielle lorsqu'ils sont exposés simultanément à différents arbovirus, (7) la surveillance entomologique et son impact sur la circulation d'espèces de vecteurs, dans le but d'appliquer des mesures spécifiques qui réduisent l'occurrence saisonnière d'épidémies. CONCLUSIONS: Des événements multifactoriels pourraient expliquer le déclin observé de la dengue en 2017. La plupart des résultats de cette réunion du groupe de consensus d'experts sont hypothétiques, reposent sur des données limitées et requièrent des investigations supplémentaires.

Trachoma elimination in Latin America: prioritization of municipalities for surveillance activities.

OBJECTIVE: To identify and prioritize municipalities in 22 countries of Latin America for trachoma surveillance activities, to measure the absence or prevalence of trachoma, and to support validation and trachoma elimination efforts in the Region of the Americas. METHODS: A prioritization scale was developed in 2017 to rank each municipality by considering a combination of three characteristics: (a) its trachoma vulnerability index, derived from three socioeconomic factors known to be risks for trachoma-lack of access to improved sanitation, to clean drinking water, and to adequate education, according to housing census data from early 2017; (b) its history of trachoma in countries where the disease was not a known public health problem in 2016; and (c) whether or not it shares a border with a municipality where trachoma was a known public health problem in 2016. Municipalities in 22 countries were classified as either very high, high, medium, or low priority for trachoma surveillance. From the Caribbean, only Trinidad and Tobago met inclusion criteria. RESULTS: The prioritization scale identified 1 053 municipalities in Brazil, Colombia, and Guatemala as very high priority for trachoma surveillance. In Ecuador, El Salvador, Guyana, Paraguay, Peru, Suriname, and Venezuela, 183 municipalities were ranked as high priority, and in Argentina, Belize, Bolivia, Chile, Dominican Republic, Honduras, Nicaragua, Panama, and Uruguay, 677 municipalities were designated a medium priority for trachoma surveillance. CONCLUSIONS: This prioritization scale will be useful to countries in Latin America that still need to ascertain their current trachoma situation. The absence or prevalence of trachoma in countries designated as very high and high priority for trachoma surveillance activities must be studied to determine the extent of the disease in Latin America.

Thoracic Stent Grafting through Transapical Approach for Type III Endoleak due to Prosthetic Disconnection.

Thoracic endovascular aortic repair is a well-established treatment of descending thoracic aneurysms, and increasingly complex endovascular procedures including aortic arch and ascending aorta are being performed. However, follow-up complications may be expected, which will enhance the need for alternative approaches such as transapical, in case of complex anatomies and reinterventions. We report the case of a man with prior history of ischemic cardiopathy and multiple endovascular aortic interventions with proximal landing in zone 1 and distal landing proximal to celiac trunk. During the follow-up, the patient developed a 9-cm proximal thoracic aneurysm due to type III endoleak secondary to proximal prosthetic disconnection. Because of severe aortic elongation, inadequate usual vessel accesses (transfemoral/subclavian), and proximity to aortic arch, transapical approach was thought to be the best option in this case. The stent graft was correctly deployed without complications, and the postoperative imaging revealed an excellent result.

[Experience with development of tools to monitor vaccination coverage and preventive chemotherapy coverageExperiência do desenvolvimento de ferramentas para o monitoramento da cobertura vacinal e quimioprofilaxia]. / Experiencia del desarrollo de herramientas para el monitoreo de coberturas de vacunación y quimioterapia preventiva.

OBJETIVO: Describir la experiencia y las lecciones aprendidas en el desarrollo de herramientas para el monitoreo de las coberturas de vacunación y de quimioterapia preventiva en las Américas. MÉTODOS: Se compiló y revisó la documentación disponible en los programas regionales de inmunización integral de la familia y de las enfermedades infecciosas desatendidas de la Organización Panamericana de la Salud/Organización Mundial de la Salud producida durante el proceso de desarrollo de las herramientas entre 2012 y 2017 incluidos: búsqueda sistemática de literatura, reportes técnicos, informes de reuniones internas, reporte de la prueba piloto e informes y resultados de las evaluaciones de los talleres de entrenamiento en doce países de las Américas. La documentación se organizó, se extrajo la información más relevante sobre el desarrollo de las herramientas y se consensuaron las principales lecciones aprendidas en el proceso. RESULTADOS: El proceso facilitó la organización y sistematización de las herramientas aplicadas durante las últimas dos décadas en los programas de vacunación en las Américas para el análisis y monitoreo de las coberturas y su rápida adaptación para el monitoreo de las coberturas de la quimioterapia preventiva. Se integró un conjunto de herramientas cuya aplicación se define con un algoritmo de decisiones y pueden ser utilizadas por los países. CONCLUSIONES: Las lecciones aprendidas pueden aplicarse para desarrollos similares y para promover el trabajo interprogramático en salud pública. El trabajo integrado aceleró el desarrollo de herramientas útiles para los países.

OBJETIVO: Descrever a experiência e as lições aprendidas no desenvolvimento de ferramentas para o monitoramento da cobertura vacinal e quimioprofilaxia nas Américas. MÉTODOS: Foi coletada e revisada a documentação disponível nos programas regionais de imunização integral da família e doenças infecciosas negligenciadas da Organização Pan-Americana da Saúde/Organização Mundial da Saúde, produzida no processo de desenvolvimento de ferramentas entre 2012 e 2017. Os arquivos englobavam resultados de busca sistemática da literatura, relatórios técnicos, atas de reuniões internas, informe de teste-piloto e relatórios e resultados das avaliações dos seminários de capacitação em 12 países das Américas. A documentação foi organizada e foram extraídos os dados mais relevantes sobre o desenvolvimento das ferramentas. As principais lições aprendidas no processo foram decididas por consenso. RESULTADOS: O processo facilitou a organização e a sistematização das ferramentas empregadas nas últimas duas décadas nos programas de vacinação nas Américas para avaliação e monitoramento da cobertura vacinal e sua rápida adaptação para o monitoramento da cobertura da quimioprofilaxia. Foi integrado um conjunto de ferramentas cuja aplicação é definida com um algoritmo de decisões e que pode ser utilizado pelos países. CONCLUSÕES: As lições aprendidas podem ser aplicadas em processos semelhantes de desenvolvimento e para promover o trabalho interprogramático em saúde pública. O trabalho integrado acelerou o desenvolvimento de ferramentas úteis para os países.

Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat.

In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound 1) was evaluated. Compound 1 showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in duodenum or jejunum. Also, Compound 1 possess two ionic species, first above of pH 4.43 and, the second one is present over pH 6.08. The apparent permeability in everted sac rat intestine model was 8.73 × 10-6 cm/s in duodenum and 1.62 × 10-5 cm/s in jejunum, suggesting that Compound 1 has low permeability. Elimination constant after an oral administration of 50 µg/kg in Wistar rat was 1.81 h-1, absorption constant was 3.05 h-1, Cmax was 3.57 µg/mL at 0.33 h, AUC0-α was 956.54 µ/mL·h and distribution volume was 419.4 mL. To IV administration at the same dose, ke was 1.21 h-1, Vd was 399.6 mL and AUC0-α was 747.81 µ/mL·h. No significant differences were observed between pharmacokinetic parameters at every administration route. Bioavailability evaluated was 10.4%. Compound 1 is metabolized to Compound 2 probably by enzymatic hydrolysis, and it showed a half-life of 9.24 h. With these properties, Compound 1 would be considered as a prodrug of Compound 2 with potential as an antidiabetic and anti dyslipidemic agent.

Determinants of tuberculosis in countries of Latin America and the Caribbean.

Objectives To explore the relationships among social, economic, environmental, and health services determinants of tuberculosis (TB) morbidity and mortality, and to identify the mechanisms that mediate such associations in countries of Latin America and the Caribbean (LAC). Methods This was an ecological study of 26 LAC countries that had accurate data available on 38 selected variables for the year 2010. The countries represented 99% of the TB burden in LAC. Multivariate linear regression was used to identify associations among determinants of health and TB morbidity and mortality. Results TB-HIV coinfection and multidrug resistant TB (MDR-TB) in previously treated cases were found to be positively associated to TB morbidity and negatively associated to improved basic sanitation and water coverage-pointing to an increase of TB morbidity in the first two variables and a decrease of TB morbidity in the last two. Regarding TB mortality, indigenous people and MDR-TB in previously treated cases were positively associated. In contrast, literacy among women, basic sanitation, water coverage, and nutritional status were negatively associated to mortality, denoting that improvements in these areas could reduce TB mortality. Conclusions The study findings support intersectoral actions that address social, economic, environmental, and health services determinants within the Stop TB strategy. The mechanisms by which social determinants of health affect current trend outcomes extend beyond medical interventions to control TB, but more research is needed to understand how and to develop actionable recommendations.

Antinociceptive Activity of an Ethanol Extract of Justicia spicigera.

Preclinical Research The aim of the present study was to evaluate the antinociceptive and sedative activity of an ethanol extract of Justicia spicigera an evergreen used in Mexican traditional medicine for the relief of pain, wounds, fever and inflammation. At 200 mg/kg po, the maximum dose examined, the ethanol extract of J. spicigera (JSE) had analgesic activity in mice in the acetic acid writhing test, the second phase of the formalin test and the tail flick test that was similar in efficacy to the NSAID, naproxen (150 mg/kg po). JSE was inactive in the hot plate test and and the ketamine-induced sleeping time test; it had no sedative effects. These results show that the ethanol extract from the leaves of J. spicigera has antinociceptive effects in mice without inducing sedation. Drug Dev Res 77 : 180-186, 2016. © 2016 Wiley Periodicals, Inc.

Off-Pump to On-Pump Emergency Conversion: Incidence, Risk Factors, and Impact on Short- and Long-Term Results.

BACKGROUND AND AIM OF THE STUDY: Emergency conversion to on-pump during off-pump coronary artery bypass surgery (CABG) increases morbidity and mortality. We analyze its risk factors and impact on short- and long-term outcomes. METHODS: All patients undergoing isolated CABG between 2006 and 2012 were included. Postoperative and midterm mortality and the combined event (death, myocardial infarction, cerebrovascular accident, and repeat revascularization) were compared between patients with and without conversion. Multivariate analysis and propensity score matching were performed. RESULTS: A total of 1268 patients were operated off pump and 37 patients required an emergency conversion. Postoperative death and combined event were more frequent among patients who were converted (31.6% vs. 3.31%, p < 0.001 and 43.2% vs. 11.5%, p < 0.001, respectively). Conversion was an independent predictor of both events (OR = 6.22, 95%CI: 2.01 to 19.3 and OR = 5.06, 95%CI: 2.41 to 10.61, respectively). Mean follow-up was 32.5 months. At four years, survival and freedom from the combined event was poorer for conversion (75% vs. 88%, p < 0.001 and 50% vs. 79%, p < 0.001, respectively). Conversion was an independent predictor for late mortality (HR = 2.4, 95%CI: 1.1 to 5.22) and the risk of combined event (HR = 2.97, 95%CI: 1.79 to 4.91). A 3:1 propensity score matching analysis was performed: conversion increased both perioperative and four-year mortality (12.6% vs. 4.5%, p < 0.001 and 25% vs. 12%, p = 0.007); and early and late incidence of the combined event (43.2% vs. 11.7%, p < 0.001 and 53% vs. 24%, p = 0.001). Preoperative atrial fibrillation and previous percutaneous coronary intervention were independent predictors of conversion. CONCLUSIONS: Emergency conversion from off- to on-pump CABG dramatically worsens early and late outcomes. Previous percutaneous coronary intervention and atrial fibrillation increase the risk of conversion.

Interruption of vector transmission by native vectors and "the art of the possible".

In a recent article in the Reader's Opinion, advantages and disadvantages of the certification processes of interrupted Chagas disease transmission (American trypanosomiasis) by native vector were discussed. Such concept, accepted by those authors for the case of endemic situations with introduced vectors, has been built on a long and laborious process by endemic countries and Subregional Initiatives for Prevention, Control and Treatment of Chagas, with Technical Secretariat of the Pan American Health Organization/World Health Organization, to create a horizon target and goal to concentrate priorities and resource allocation and actions. With varying degrees of sucess, which are not replaceable for a certificate of good practice, has allowed during 23 years to safeguard the effective control of transmission of Trypanosoma cruzi not to hundreds of thousands, but millions of people at risk conditions, truly "the art of the possible."

Advanced considerations in survival analysis.

Investigation of survival during the follow-up period is common in cardiovascular research and has intrinsic issues that require precise knowledge, such as survival or censoring. Besides, as the follow-up period lengthens and events other than mortality are studied, the analysis becomes more complex, so Kaplan-Meier analyses or Cox models are not always sufficient. In this primer, we provide the reader with detailed information on the interpretation of the most common survival analyses and delve into methods to analyse competing risks or alternatives to the conventional methods when the proportional hazards assumption is not met.

Prognostic impact of shock in patients with type A acute aortic syndrome. Results of a nationwide multicenter study.

OBJECTIVE: To evaluate the clinical characteristics, imaging findings, treatment, and prognosis of patients with type A acute aortic syndrome (AAS-A) presenting with shock. To assess the impact of surgery on this patient population. METHODS: The study included 521 patients with A-AAS enrolled in the Spanish Registry of Acute Aortic Syndrome (RESA-III) from January 2018 to December 2019. The RESA-III is a prospective, multicenter registry that contains AAS data from 30 tertiary-care hospitals. Patients were classified into two groups according to their clinical presentation, with or without shock. Shock was defined as persistent systolic blood pressure <80 mmHg despite adequate volume resuscitation. RESULTS: 97 (18.6%) patients with A-AAS presented with shock. Clinical presentation with syncope was much more common in the Shock group (45.4% vs 10.1%, p = 0.001). Patients in the Shock group had more complications at diagnosis and before surgery: cardiac tamponade (36.2% vs 9%, p < 0.001), acute renal failure (28.9% vs 18.2%, p = 0.018), and need for orotracheal intubation (40% vs 9.1%, p < 0.001). There were no significant differences in aortic regurgitation (51.6% vs 46.7%, p = 0.396) between groups. In-hospital mortality was higher among patients with shock (48.5% vs 27.4%, p < 0.001). Surgery was associated with a significant mortality reduction both in patients with and without shock. Surgery had an independent protective effect on mortality (OR 0.03, 95% CI (0.00-0.32)). CONCLUSION: Patients with AAS-A admitted with shock have a heavily increased risk of mortality. Syncope and pericardial effusion at diagnosis are strongly associated with shock. Surgery was independently associated with a mortality reduction in patients with AAS-A and shock.