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•The rBCG expressing rCP40 and rCP09720 proteins protect against C. pseudotuberculosis.•Mycobacterium bovis BCG/cp40 boosted with rCP40 (G5) showed 90% protection after challenge.•Besides eliciting an expected cross-immune response, rBCG induced specific humoral and cellular responses. In this study, we assessed the survival and immune response of mice vaccinated with recombinant Mycobacterium bovis BCG Pasteur that expressed the CP40 or CP09720 proteins after the mice were challenged with a C. pseudotuberculosis MIC-6 virulent strain. Six groups of mice (n = 10 mice per group) were immunised with a sterile 0.9% saline solution (G1), 106 CFU of M. bovis BCG Pasteur (G2), 106 CFU of M. bovis BCG/cp40 (G3), 106 CFU of M. bovis BCG/cp09720 (G4), M. bovis BCG/cp40 boosted with rCP40 (G5), and M. bovis BCG/cp09720 boosted with rCP09720 (G6). The highest survival rate of 90% was observed in the G5 group, followed by 80% in the G6 group and 70% in the G3 and G4 groups. Moreover, a significantly greater induction of IFN-γ and IL-10 was found in the G3 group and higher IL-17 levels were recorded in the G5 group compared to their levels in the control group (G1) (p < 0.05). A specific humoral immune response (total IgG) was found in the G5 and G6 groups on day 42 compared to the level of response in the G1 group. These results indicated that the vector vaccine elicited significantly greater survival of mice in all experimental groups after a strong virulent challenge and induced a strong immune response.

•Mice immunized with rNanH+saponin (G2) exhibited a survival rate of 60%.•Mice immunized with rPknG+saponin (G3) exhibited a survival rate of 20%.•G2 showed the best protection against Corynebacterium pseudotuberculosis challenge.•rNanH induced significant production of IgG2a antibodies.•rNanH induced significant production of cytokines related to a Th1 immune response. Despite the economic and zoonotic relevance of caseous lymphadenitis, a competent immunoprophylaxis tool is still necessary. Here, we evaluated two putative virulence factors of Corynebacterium pseudotuberculosis, rNanH, and rPknG, as recombinant subunit vaccines in a murine model against the infection by C. pseudotuberculosis. Three groups of ten Balb/c mice each were inoculated with a sterile 0.9% saline solution (G1), rNanH (G2), or rPknG (G3) in formulations containing saponin as an adjuvant. The mice received two vaccine doses intercalated by a 21-day interval and were challenged with 2 × 104 CFU/mL of the C. pseudotuberculosis MIC–6 strain 21 days after the last immunization. The total IgG, IgG1, and IgG2a production levels increased significantly in the experimental groups (G2 and G3) on day 42. The highest levels of IgG2a antibodies in G2 and G3 were observed compared to IgG1 levels. G3 showed a significant (p < 0.05) humoral response through higher production of total IgG at day 42 when compared to G2. A significant increase of mRNA expression levels of interleukin (IL)-17, tumor necrosis factor, and interferon-γ was observed only in G2, while IL-4 was significantly produced only by G3. The levels of IL-10 and IL-12 obtained were not significant in any group. The survival rates after the challenge were 20% for G3 and 60% for G2 (p < 0.05). Our findings suggest that the formulation containing rNanH and saponin (G2) resulted in the best protection against the challenge and was able to elicit a Th1 immune response in mice, and can be considered as a promising antigen in the development of an effective vaccine against caseous lymphadenitis.

To analyze the spatiotemporal distribution of hospital admission rates for primary care-sensitive conditions (PCSC) in women and children in the first 1000 days of life in Brazil. Ecological study, with spatiotemporal analyses, using secondary data from Brazilian municipalities. PCSC in women, related to prenatal care and childbirth, and in children under two years old, from 2008 to 2019 were used to characterize trends and formations of spatiotemporal clusters/outliers. Crude PCSC rates were calculated and adjusted by the local empirical Bayesian method, presented in choropleth maps. We also used Anselin Local Moran I type analyses to identify spatial clusters, and space-time cube with clustering by emerging hotspot, followed by time series clustering, for analysis of spatiotemporal trends (alpha = 5%). A total of 1,850,776 PCSC were registered in pregnant women, puerperae, and children under two years of age in Brazil, representing 1.7% of the total number of hospital admissions in the period. PCSC rates showed different behaviors when the groups of women and children were evaluated, with a predominant growing trend of 109% in admissions in the first group and a reduction of 34.4% in the second. The North, Northeast, and Midwest regions had larger high-risk clusters and more significant increasing trends in PCSC in the two subpopulations studied. Health actions and services in primary care may be reducing hospital admissions for children, but they are not being effective in reducing hospital admissions for women for causes related to prenatal care and childbirth, especially in the North, Northeast, and Midwest of Brazil. Investments in the qualification of care over the thousand days are urgent in the country.

Background Oral cancer is a potentially fatal disease, especially when diagnosed in advanced stages. In Brazil, the primary health care (PHC) system is responsible for promoting oral health in order to prevent oral diseases. However, there is insufficient evidence to assess whether actions of the PHC system have some effect on the morbidity and mortality from oral cancer. The purpose of this study was to analyze the effect of PHC structure and work processes on the incidence and mortality rates of oral cancer after adjusting for contextual variables. Methods An ecological, longitudinal and analytical study was carried out. Data were obtained from different secondary data sources, including three surveys that were nationally representative of Brazilian PHC and carried out over the course of 10 years (2002–2012). Data were aggregated at the state level at different times. Oral cancer incidence and mortality rates, standardized by age and gender, served as the dependent variables. Covariables (sociodemographic, structure of basic health units, and work process in oral health) were entered in the regression models using a hierarchical approach based on a theoretical model. Analysis of mixed effects with random intercept model was also conducted (alpha = 5%). Results The oral cancer incidence rate was positively association with the proportion of of adults over 60 years (β = 0.59; p  = 0.010) and adult smokers (β = 0.29; p = 0.010). The oral cancer related mortality rate was positively associated with the proportion of of adults over 60 years (β = 0.24; p  < 0.001) and the performance of preventative and diagnostic actions for oral cancer (β = 0.02; p  = 0.002). Mortality was inversely associated with the coverage of primary care teams (β = −0.01; p  < 0.006) and PHC financing (β = −0.52 −9 ; p  = 0.014). Conclusions In Brazil, the PHC structure and work processes have been shown to help reduce the mortality rate of oral cancer, but not the incidence rate of the disease. We recommend expanding investments in PHC in order to prevent oral cancer related deaths.

•The observed prevalence of malnutrition in the study was 26.1%, according to the subjective global assessment, whereas considering the various Global Leadership Initiative on Malnutrition combinations, the prevalence of malnutrition ranged from 3.9% to 30.0%. None of the Global Leadership Initiative on Malnutrition combinations reached adequate concurrent validity, with the subjective global assessment as the gold standard.•Combinations that included C-reactive protein indicated a higher prevalence of malnutrition and higher sensitivity values compared with combinations with serum albumin as an etiologic criterion.•The presence of malnutrition, according to the Global Leadership Initiative on Malnutrition criteria, was an independent predictor of complications in surgical patients. The Global Leadership Initiative on Malnutrition (GLIM) criteria establish a diagnosis of malnutrition based on the presence of at least one phenotypic and one etiologic criterion. This study aimed to assess the concurrent and predictive validity of the GLIM criteria in hospitalized cancer patients. This is an observational retrospective study, including 885 cancer patients, ages >18 y, admitted to a medical oncology inpatient unit between 2019 and 2020. All patients at risk for malnutrition according to the Nutritional Risk Screening 2002 score were assessed by the subjective global assessment (SGA) and 14 different combinations of the GLIM criteria. The SGA was considered the gold standard for assessing the concurrent validity of the GLIM combinations. For a subsample of patients with data available on inflammatory markers (n = 198), the serum albumin and C-reactive protein were included in the combinations as etiologic criteria. The predictive validity of the different combinations was tested using the occurrence of surgical complications as the clinical outcome. The sensitivity and specificity values were calculated to assess the concurrent validity, univariate and multivariate logistic regression models were used to test predictive validity. Adequate concurrent and predictive validity were determined as sensitivity and specificity values >80% and odds ratio values ≥2.0, respectively. The median age of the patients was 61.0 y (interquartile range = 51.0–70.0). Head and neck cancer was the prevailing diagnosis and 375 patients were at nutritional risk. According to the SGA, 173 (26.1%) patients were malnourished (SGA categories B or C) and the prevalence of malnutrition ranged from 3.9% to 30.0%, according to the GLIM combinations. None of the tested combinations reached adequate concurrent validity; however, the presence of malnutrition according to four combinations independently predicted surgical complications. The predictive validity of the GLIM was satisfactory in surgical cancer patients.

Compared indicators of potential access to oral health services sought in two cycles of the Program for Improvement of Access and Quality of Primary Care (PMAQ-AB), verifying whether the program generated changes in access to oral health services. Transitional analysis of latent classes was used to analyze two cross-sections of the external evaluation of the PMAQ-AB (Cycle I: 2011-2012 and Cycle II: 2013-2014), identifying completeness classes for a structure and work process related to oral health. Consider three indicators of structure (presence of a dental surgeon, existence of a dental office and operating at minimum hours) and five of the work process (scheduling every day of the week, home visits, basic dental procedures, scheduling for spontaneous demand and continuation of treatment). Choropleth maps and hotspots were made. The proportion of elements that had one or more dentist (CD), dental office and operated at minimum hours varied from 65.56% to 67.13 between the two cycles of the PMAQ-AB. The number of teams that made appointments every day of the week increased 8.7% and those that made home visits varied from 44.51% to 52.88%. The reduction in the number of teams that reported guaranteeing the agenda for accommodating spontaneous demand, varying from 62.41% to 60.11% and in the continuity of treatment, varying from 63.41% to 61.11%. For the structure of health requirements, the predominant completeness profile was \"Best completeness\" in both cycles, comprising 71.0% of the sets at time 1 and 67.0% at time 2. The proportion of teams with \"Best completeness\" increased by 89.1%, the one with \"Worst completeness\" increased by 20%, while those with \"Average completeness\" decreased by 66.3%. We identified positive changes in the indicators of potential access to oral health services, expanding the users' ability to use them. However, some access attributes remain unsatisfactory, with organizational barriers persisting.

The objective of this study was to better understand how the lack of emergency child and obstetric care can be related to maternal and neonatal mortality levels. We performed spatiotemporal geospatial analyses using data from Brazilian municipalities. An emergency service accessibility index was derived using the two-step floating catchment area (2SFCA) for 951 hospitals. Mortality data from 2000 to 2015 was used to characterize space-time trends. The data was overlapped using a spatial clusters analysis to identify regions with lack of emergency access and high mortality trends. From 2000 to 2015 Brazil the overall neonatal mortality rate varied from 11,42 to 11,71 by 1000 live births. The maternal mortality presented a slightly decrease from 2,98 to 2,88 by 100 thousand inhabitants. For neonatal mortality the Northeast and North regions presented the highest percentage of up trending. For maternal mortality the North region exhibited the higher volume of up trending. The accessibility index obtained highlighted large portions of the rural areas of the country without any coverage of obstetric or neonatal beds. The analyses highlighted regions with problems of mortality and access to maternal and newborn emergency services. This sequence of steps can be applied to other low and medium income countries as health situation analysis tool. Low and middle income countries have greater disparities in access to emergency child and obstetric care. There is a lack of approaches capable to support analysis considering a spatiotemporal perspective for emergency care. Studies using Geographic Information System analysis for maternal and child care, are increasing in frequency. This approach can identify emergency child and obstetric care saturated or deprived regions. The sequence of steps designed here can help researchers, and policy makers to better design strategies aiming to improve emergency child and obstetric care.

Existing campaign-based healthcare delivery programs used for immunization often fall short of established health coverage targets due to a lack of accurate estimates for population size and location. A microplan, an integrated set of detailed planning components, can be used to identify this information to support programs such as equitable vaccination efforts. Here, we presents a series of steps necessary to create an artificial intelligence-based framework for automated microplanning, and our pilot implementation of this analysis tool across 29 countries of the Americas. Further, we describe our processes for generating a conceptual framework, creating customized catchment areas, and estimating up-to-date populations to support microplanning for health campaigns. Through our application of the present framework, we found that 68 million individuals across the 29 countries are within 5 km of a health facility. The number of health facilities analyzed ranged from 2 in Peru to 789 in Argentina, while the total population within 5 km ranged from 1,233 in Peru to 15,304,439 in Mexico. Our results demonstrate the feasibility of using this methodological framework to support the development of customized microplans for health campaigns using open-source data in multiple countries. The pandemic is demanding an improved capacity to generate successful, efficient immunization campaigns; we believe that the steps described here can increase the automation of microplans in low resource settings.

Background More than 15 million children are born preterm annually. While preterm survival rates have increased in high-income countries. Low- and middle-income countries, like Brazil, continue to battle high neonatal mortality rates due to a lack of adequate postnatal care. Globally, neonatal mortality is higher for preterm infants compared to those born at term. Our study aims to map and analyze the spatial, socioeconomic, and health coverage determinants related to preterm birth in Brazil in order to understand how spatial variations in demographics and access to primary care may affect preterm birth occurrences.  Methods Using publicly available national-level data from the Brazilian health system for 2008–2017, we conducted an ecological study to visualize the spatial distributions of preterm birth along with socioeconomic status, the structure of health services, and primary care work process, each consisting of multiple variables reduced via principal component analysis. Regression models were created to determine predictive effects of numeric and spatial variation of these scores on preterm birth rates. Results In Brazil, preterm birth rates increased from 2008–2017, with small and rural municipalities frequently exhibiting higher rates than urban areas. Scores in socioeconomic status and work process were significant predictors of preterm birth rates, without taking into account spatial adjustment, with more positive scores in socioeconomic status predicting higher preterm birth rates (coefficient 0.001145) and higher scores in work process predicting lower preterm birth rates (coefficient -0.002416). Geographically weighted regression showed socioeconomic status to be a more significant predictor in the North, with the work process indicators being most significant in the Northeast. Conclusions Results support that primary care work process indicators are more significant in estimating preterm birth rates than physical structures available for care. These results emphasize the importance of ensuring the presence of the minimum human resources needed, especially in the most deprived areas of Brazil. The association between social determinants of health and preterm birth rates raises questions regarding the importance of policies dedicated to foster equity in the accessibility of healthcare services, and improve income as protective proxies for preterm birth.

Although the Zika virus (ZIKV) epidemic ceased to be a public health emergency by the end of 2016, studies to improve knowledge about this emerging disease are still needed, especially those investigating a causal relationship between ZIKV in pregnant women and microcephaly in neonates. However, there are still many challenges in describing the relationship between ZIKV and microcephaly. The few studies focusing on the epidemiological profile of ZIKV and its changes over time are largely limited to systematic reviews of case reports and dispersal mapping of ZIKV spread over time without quantitative methods to analyze patterns and their covariates. Since Brazil has been at the epicenter of the ZIKV epidemic, this study examines the geospatial association between ZIKV and microcephaly in Brazil. Our study is categorized as a retrospective, ecological study based on secondary databases. Data were obtained from January to December 2016, from the following data sources: Brazilian System for Epidemiological Surveillance, Disease Notification System, System for Specialized Management Support, and Brazilian Institute of Geography and Statistics. Data were aggregated by municipality. Incidence rates were estimated per 100,000 inhabitants. Analyses consisted of mapping the aggregated incidence rates of ZIKV and microcephaly, followed by a Getis-Ord-Gi spatial cluster analysis and a Bivariate Local Moran's I analysis. The incidence of ZIKV cases is changing the virus's spatial pattern, shifting from Brazil's Northeast region to the Midwest and North regions. The number of municipalities in clusters of microcephaly incidence is also shifting from the Northeast region to the Midwest and North, after a time lag is considered. Our findings suggest an increase in microcephaly incidence in the Midwest and North regions, associated with high levels of ZIKV infection months before. The greatest burden of microcephaly shifted from the Northeast to other Brazilian regions at the beginning of 2016. Brazil's Midwest region experienced an increase in microcephaly incidence associated with ZIKV incidence. This finding highlights an association between an increase in ZIKV infection with a rise in microcephaly cases after approximately three months.