Single nucleotide polymorphism (SNP) rs4291 of the angiotensin-converting enzyme (ACE) gene is associated with the response to losartan treatment in hypertensive patients.

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.

G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. / Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão.

BACKGROUND: Central Illustration : G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. BACKGROUND: Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. OBJECTIVE: To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. METHOD: The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. RESULTS: The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). CONCLUSION: These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Variante da Subunidade Beta 3 da Proteína G ( GNB3 ) Está Associada a Alterações Bioquímicas em Pacientes Brasileiros com Hipertensão / G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.

Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

Angiotensin-converting enzyme gene (ACE) polymorphisms are associated with dysregulation of biochemical parameters in hypertensive patients.

INTRODUCTION: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention. OBJECTIVE: To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH. METHOD: The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn's post-test for multiple comparisons. RESULTS: The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA. CONCLUSION: AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients.

Logistics Workers Are a Key Factor for SARS-CoV-2 Spread in Brazilian Small Towns: Case-Control Study.

BACKGROUND: Data on how SARS-CoV-2 enters and spreads in a population are essential for guiding public policies. OBJECTIVE: This study seeks to understand the transmission dynamics of SARS-CoV-2 in small Brazilian towns during the early phase of the epidemic and to identify core groups that can serve as the initial source of infection as well as factors associated with a higher risk of COVID-19. METHODS: Two population-based seroprevalence studies, one household survey, and a case-control study were conducted in two small towns in southeastern Brazil between May and June 2020. In the population-based studies, 400 people were evaluated in each town; there were 40 homes in the household survey, and 95 cases and 393 controls in the case-control study. SARS-CoV-2 serology testing was performed on participants, and a questionnaire was applied. Prevalence, household secondary infection rate, and factors associated with infection were assessed. Odds ratios (ORs) were calculated by logistic regression. Logistics worker was defined as an individual with an occupation focused on the transportation of people or goods and whose job involves traveling outside the town of residence at least once a week. RESULTS: Higher seroprevalence of SARS-CoV-2 was observed in the town with a greater proportion of logistics workers. The secondary household infection rate was 49.1% (55/112), and it was observed that in most households (28/40, 70%) the index case was a logistics worker. The case-control study revealed that being a logistics worker (OR 18.0, 95% CI 8.4-38.7) or living with one (OR 6.9, 95% CI 3.3-14.5) increases the risk of infection. In addition, having close contact with a confirmed case (OR 13.4, 95% CI 6.6-27.3) and living with more than four people (OR 2.7, 95% CI 1.1-7.1) were also risk factors. CONCLUSIONS: Our study shows a strong association between logistics workers and the risk of SARS-CoV-2 infection and highlights the key role of these workers in the viral spread in small towns. These findings indicate the need to focus on this population to determine COVID-19 prevention and control strategies, including vaccination and sentinel genomic surveillance.

A new Brazilian regional scenario of Type 2 diabetes risk in the next ten years.

AIMS: According to a recent national diabetes screening performed by our group in 2018, 18.4% of the Brazilians were found to have high blood glucose. The objective of the present study was to estimate the risk of developing type 2 DM (T2DM) in the next ten years in Brazilian population. METHODS: A cross-sectional study was carried out in community pharmacies across Brazil, in 2018, where pharmacists applied the FINDRISC questionnaire to estimate the population's risk of developing T2DM within a ten-year period. RESULTS: The study included 977 pharmacists from 345 municipalities distributed across the five geographical regions of Brazil. Of the 17,580 people evaluated, the South region was found to have the highest frequency (59.6%) among people at very low and/or low risk of developing T2DM, while the North region, the most underserved, presented the highest and/or very highest T2DM risk (24.1%). The factors that mostly and importantly impacted these regional differences were body mass index; the highest daily consumption of vegetables and fruits; history of high blood glucose and family history of T1DM/T2DM. CONCLUSION: These results showed an impressive change of direction concerning diabetes numbers between the most underserved region in public health care and one of the most developed and best organized regions concerning health assistance, the North and the South, respectively.

From Spanish Flu to Syndemic COVID-19: long-standing sanitarian vulnerability of Manaus, warnings from the Brazilian rainforest gateway.

A second deadlier wave of COVID-19 and the causes of the recent public health collapse of Manaus are compared with the Spanish flu events in that city, and Brazil. Historic sanitarian problems, and its hub position in the Brazilian airway network are combined drivers of deadly events related to COVID-19. These drivers were amplified by misleading governance, highly transmissible variants, and relaxation of social distancing. Several of these same factors may also have contributed to the dramatically severe outbreak of H1N1 in 1918, which caused the death of 10% of the population in seven months. We modelled Manaus parameters for the present pandemic and confirmed that lack of a proper social distancing might select the most transmissible variants. We succeeded to reproduce a first severe wave followed by a second stronger wave. The model also predicted that outbreaks may last for up to five and half years, slowing down gradually before the disease disappear. We validated the model by adjusting it to the Spanish Flu data for the city, and confirmed the pattern experienced by that time, of a first stronger wave in October-November 1918, followed by a second less intense wave in February-March 1919.

Association between ocular toxoplasmosis and APEX1 and MYD88 polymorphism.

Ocular toxoplasmosis (OT) is the most common form of posterior uveitis, and in some countries, it is the most frequent cause of visual impairment. Studies demonstrate that the polymorphism in genes involved with the immune response can be related both to the occurrence and to the recurrence of OT. Thus, the present study aimed to analyze the association between OT and the polymorphism of the APEX1 (rs1130409) and MyD88 (rs7744) genes. The studied sample consisted of 48 volunteers with OT and 96 asymptomatic volunteers, but positive for anti - T. gondii IgG (control group). Blood collection was performed for serological analysis (ELISA) and DNA extraction. Genotyping of the polymorphism was performed using real-time PCR. To analyze the association between gene polymorphism and OT, logistic regression was performed. The results showed no association between the MYD88 gene polymorphism and the development of OT. However, a significant association was found between OT and APEX1 gene polymorphism, indicating that individuals expressing polymorphic (GG) or heterozygous (GT) alleles are more likely to develop the disease (P-value = 0.02 and 0.03 respectively). These results suggest that APEX1 (rs1130409) polymorphism is a risk factor for the occurrence of ocular toxoplasmosis in the studied population.

Prevalence and factors associated with anxiety among university students of health sciences in Brazil: findings and implications / Prevalência e fatores associados à ansiedade entre universitários de ciências da saúde no Brasil: achados e implicações

OBJECTIVE: The aim was to evaluate the prevalence and factors associated with anxiety disorders among university students of health sciences at Federal University of Ouro Preto, Brazil. METHODS: A cross-sectional study between March to June 2019. Data were collected through a self-administered questionnaire including sociodemographic, academic, family and behavioral issues. The Beck Anxiety Inventory was used to assess anxiety. Estimates were obtained through the prevalence ratio and Poisson multivariate analysis. RESULTS: Four hundred and ninety-three students participated with a mean age of 23.1 and predominantly women (79.9%). All students had some degree of anxiety, with the frequency of the severe, moderate and mild forms being 28.0%, 29.8% and 27.0%, respectively. The factors associated with anxiety included having suffered psychological and/or physical violence in childhood, having suicidal thoughts, having a deceased parent, living with parents, being dissatisfied with the course and being in the exam period. CONCLUSIONS: The prevalence of anxiety was high in our study and family problems prior to entering university seem to significantly influence the degree of anxiety, which may compromise the student's academic and social performance.

OBJETIVO: O objetivo foi avaliar a prevalência e os fatores associados aos transtornos de ansiedade em estudantes universitários de ciências da saúde da Universidade Federal de Ouro Preto, Brasil. MÉTODOS: Estudo transversal, entre março e junho de 2019. Os dados foram coletados por meio de questionário autoaplicável, incluindo questões sociodemográficas, acadêmicas, familiares e comportamentais. O Inventário de Ansiedade de Beck foi usado para avaliar a ansiedade. As estimativas foram obtidas por meio da razão de prevalência e análise multivariada de Poisson. RESULTADOS: Participaram 493 alunos com idade média de 23,1 anos e predominância do sexo feminino (79,9%). Todos os alunos apresentaram algum grau de ansiedade, sendo a frequência da forma grave, moderada e leve de 28,0%, 29,8% e 27,0%, respectivamente. Os fatores associados à ansiedade foram: ter sofrido violência psicológica e/ou física na infância, ter pensamentos suicidas, ter pai falecido, morar com os pais, ter insatisfação com o curso e estar em período de provas. CONCLUSÕES: A prevalência de ansiedade foi elevada em nosso estudo e os problemas familiares anteriores ao ingresso na universidade parecem influenciar significativamente no grau de ansiedade, podendo comprometer o desempenho acadêmico e social do discente.

Spatiotemporal dynamics and risk estimates of COVID-19 epidemic in Minas Gerais State: analysis of an expanding process.

COVID-19 is an infectious disease caused by the recently discovered coronavirus SARS-Cov-2. The disease became pandemic affecting many countries globally, including Brazil. Considering the expansion process and particularities during the initial stages of the epidemic, we aimed to analyze the spatial and spatiotemporal patterns of COVID-19 occurrence and to identify priority risk areas in Minas Gerais State, Southeast Brazil. An ecological study was performed considering all data from human cases of COVID-19 confirmed from the epidemiological week (EW) 11 (March 08, 2020) to EW 26 (June 27, 2020). Crude and smoothed incidence rates were used to analyze the distribution of disease patterns based on global and local indicators of spatial association and space-time risk assessment. Positive spatial autocorrelation and spatial dependence were found. Our results suggest that the metropolitan region of the State capital Belo Horizonte (MRBH) and Vale do Rio Doce mesoregions, as major epidemic foci in the beginning of the expansion process, have had important influence on the dispersion of SARS-CoV-2 in Minas Gerais State. Triangulo Mineiro/Alto Paranaiba region presented the highest risk of infection. In addition, six statistically significant spatiotemporal clusters were identified in the State, three at high risk and three at low risk. Our findings contribute to a greater understanding of the space-time disease dynamic and discuss strategies for identification of priority areas for COVID-19 surveillance and control.

Prevalence of people at risk of developing type 2 diabetes mellitus and the involvement of community pharmacies in a national screening campaign: a pioneer action in Brazil.

BACKGROUND: Brazil is one of top 10 countries with the highest number of people with diabetes mellitus (DM), affecting 16.8 million peoples. It is estimated that 7.7 million people (20-79 years) in the country have not yet been diagnosed, representing an under-diagnosis rate of 46.0%. Herein we aimed to screen people for high blood glucose or risk for developing type 2 DM (T2DM) through community pharmacies in Brazil. METHODS: A cross-sectional study was carried out in November 2018, involving 977 pharmacists from 345 municipalities in Brazil. The study evaluated people between 20 and 79 years old without a previous diagnosis of DM. Glycemia was considered high when its value was ≥ 100 mg/dL fasting and ≥ 140 mg/dL in a casual feeding state. The FINDRISC (Finnish Diabetes Risk Score) was used to estimate the risk for developing T2DM. The prevalence of high blood glucose was estimated and the associated factors were obtained using Poisson's multivariate analysis with robust variance. RESULTS: During the national screening campaign, 17,580 people were tested with the majority of the consultations (78.2%) being carried out in private pharmacies. The population was composed mainly of women (59.5%) and people aged between 20 and 45 years (47.9%). The frequency of participants with high blood glucose was 18.4% (95% CI 17.9-19.0). Considering the FINDRISC, 22.7% of people had a high or very high risk for T2DM. The risk factors associated with high blood glucose were: Body Mass Index > 25 kg/m2, abdominal circumference > 94 cm for men and > 80 cm for women; education level below 15 years of study, no daily intake of vegetables and fruits; previous diagnosis of arterial hypertension; history of high blood glucose and family history of DM. CONCLUSIONS: This is the largest screening study that evaluated the frequency of high blood glucose and its associated factors in a population without a previous diagnosis ever performed in community pharmacies in Brazil. These results may help to improve public health policies and reinforce the role of pharmacists in screening and education actions aimed at this undiagnosed population in a continent-size country such as Brazil.

Worldwide COVID-19 spreading explained: traveling numbers as a primary driver for the pandemic.

The spread of SARS-CoV-2 and the distribution of cases worldwide followed no clear biogeographic, climatic, or cultural trend. Conversely, the internationally busiest cities in all countries tended to be the hardest hit, suggesting a basic, mathematically neutral pattern of the new coronavirus early dissemination. We tested whether the number of flight passengers per time and the number of international frontiers could explain the number of cases of COVID-19 worldwide by a stepwise regression. Analysis were taken by 22 May 2020, a period when one would claim that early patterns of the pandemic establishment were still detectable, despite of community transmission in various places. The number of passengers arriving in a country and the number of international borders explained significantly 49% of the variance in the distribution of the number of cases of COVID-19, and number of passengers explained significantly 14.2% of data variance for cases per million inhabitants. Ecological neutral theory may explain a considerable part of the early distribution of SARS-CoV-2 and should be taken into consideration to define preventive international actions before a next pandemic.

In vitro Infectivity of Strains Isolated From Dogs Naturally Infected With Leishmania infantum Present a Distinct Pathogenic Profile in Hamsters.

Visceral leishmaniasis (VL) is a severe disease caused by Leishmania infantum. Dogs are the parasite's main reservoir, favoring its transmission in the urban environment. The analysis of L. infantum from infected dogs contributes to the identification of more virulent parasites, thereby supporting basic and applied studies such as vaccinal and therapeutic strategies. We proposed the in vitro and in vivo characterization of L. infantum strains from naturally infected dogs from a VL endemic area based on an infectivity and pathogenicity analysis. DH82 canine macrophages were infected in vitro with different strains for infectivity analysis, showing distinct infectivity profiles. The strains that showed greater and lesser infectivity using in vitro analyses (616 and 614, respectively) were used to infect hamsters for pathogenicity analysis. The group infected with strain 616 showed 100% survival while the group infected with strain 614 showed 50% after seven months of follow up. Furthermore, the 614 strain induced more noticeable clinicopathological changes and biochemical abnormalities in liver function, along with high inflammation and parasite load in the liver and spleen. We confirmed high variability of infectivity and pathogenicity in L. infantum strains from infected dogs. The results support the belief that screening for L. infantum infectivity using in vitro experiments is inadequate when it comes to selecting the most pathogenic strain.

Recent advances and new strategies on leishmaniasis treatment.

Leishmaniasis is one of the most important tropical neglected diseases according to the World Health Organization. Even after more than a century, we still have few drugs for the disease therapy and their great toxicity and side effects put in check the treatment control program around the world. Moreover, the emergence of strains resistant to conventional drugs, co-infections such as HIV/Leishmania spp., the small therapeutic arsenal (pentavalent antimonials, amphotericin B and formulations, and miltefosine), and the low investment for the discovery/development of new drugs force researchers and world health agencies to seek new strategies to combat and control this important neglected disease. In this context, the aim of this review is to summarize new advances and new strategies used on leishmaniasis therapy addressing alternative and innovative treatment paths such as physical and local/topical therapies, combination or multi-drug uses, immunomodulation, drug repurposing, and the nanotechnology-based drug delivery systems.Key points• The treatment of leishmaniasis is a challenge for global health agencies.• Toxicity, side effects, reduced therapeutic arsenal, and drug resistance are the main problems.• New strategies and recent advances on leishmaniasis treatment are urgent.• Immunomodulators, nanotechnology, and drug repurposing are the future of leishmaniasis treatment.

Recent advances and new strategies in Leishmaniasis diagnosis.

Leishmaniasis is a set of complex and multifaceted syndromes, with different clinical manifestations, caused by different species of the genus Leishmania spp. that can be characterized by at least four syndromes: visceral leishmaniasis (VL, also known as kala-azar), post-kala-azar dermal leishmaniasis (PKDL), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL). Among the most serious clinical forms, VL stands out, which causes the death of around 59,000 people annually. Fast and accurate diagnosis in VL is essential to reduce the disease's morbidity and mortality. There are a large number of diagnostic tests for leishmaniasis, however they do cross-react with other protozoa and their sensitivity changes according to the clinical form of the disease. Thus, it is essential and necessary to provide a diagnosis that is sufficiently sensitive to detect asymptomatic infected individuals and specific to discriminate individuals with other infectious and parasitic diseases, thus enabling more accurate diagnostic tools than those currently used. In this context, the aim of this review is to summarize the conventional diagnostic tools and point out the new advances and strategies on visceral and cutaneous leishmaniasis diagnosis.

Severe airport sanitarian control could slow down the spreading of COVID-19 pandemics in Brazil.

BACKGROUND: We investigated a likely scenario of COVID-19 spreading in Brazil through the complex airport network of the country, for the 90 days after the first national occurrence of the disease. After the confirmation of the first imported cases, the lack of a proper airport entrance control resulted in the infection spreading in a manner directly proportional to the amount of flights reaching each city, following the first occurrence of the virus coming from abroad. METHODOLOGY: We developed a Susceptible-Infected-Recovered model divided in a metapopulation structure, where cities with airports were demes connected by the number of flights. Subsequently, we further explored the role of the Manaus airport for a rapid entrance of the pandemic into indigenous territories situated in remote places of the Amazon region. RESULTS: The expansion of the SARS-CoV-2 virus between cities was fast, directly proportional to the city closeness centrality within the Brazilian air transportation network. There was a clear pattern in the expansion of the pandemic, with a stiff exponential expansion of cases for all the cities. The more a city showed closeness centrality, the greater was its vulnerability to SARS-CoV-2. CONCLUSIONS: We discussed the weak pandemic control performance of Brazil in comparison with other tropical, developing countries, namely India and Nigeria. Finally, we proposed measures for containing virus spreading taking into consideration the scenario of high poverty.

Knowledge about cervical cancer and HPV immunization dropout rate among Brazilian adolescent girls and their guardians.

BACKGROUND: Infections with Human Papillomavirus (HPV) are the main cause of cervical cancer. Since 2014, the HPV vaccine was introduced in the Brazilian National Vaccination Calendar. The purpose of this study was to assess the knowledge of adolescent girls and their mothers/guardians about HPV and HPV vaccine, identify the factors associated with this knowledge, and evaluate immunization dropout rate. METHODS: This was a cross-sectional study involving adolescent girls and their mothers/guardians. Participants underwent an interview that addressed sociodemographic data, sexual and gynecological history, and knowledge about HPV, HPV vaccine and cervical cancer. The third quartile of the total score was established as a cutoff for assessing knowledge. Adolescents who correctly answered more than four questions and mothers/guardians who obtained more than five correct responses were categorized into high knowledge. Poisson regression analysis was performed to identify variables associated with low knowledge. Vaccination records were used to assess immunization dropout rates. Any adolescent who did not complete the two-dose vaccination schedule was considered dropout. RESULTS: A total of 666 adolescent girls and 623 mothers/guardians were interviewed. Low knowledge was observed in 76.7% of adolescents and 79.8% of mothers/guardians. Most were unaware of the causal relationship between HPV and cervical cancer, signs and symptoms of HPV infection, and had limited knowledge about the HPV vaccine. Factors associated with low knowledge of adolescents were aged 12 years [IRR 1.2 (95% CI 1. 1-1.3)] or less [IRR 1.3 (95% CI (1. 2-1.4)]; household income lower than US$750 [IRR 1.7 (95% CI 1. 1-2.6)] and household income between US$751 and US$1500 [IRR 1.6 (95% CI 1.0-2.6)]. Among mothers/guardians, low knowledge was related to having completed elementary school or less [IRR 1.5 (95% CI 1. 2-2.0)]; and household income lower than US$750 [IRR 1.2 (95% CI 1.0-1.4)]. Knowledge of adolescents and mothers/guardians was not associated with vaccine uptake. HPV immunization dropout rate was considered high (32.3%). CONCLUSION: Knowledge about HPV and cervical cancer as well as vaccine uptake was low. Results highlight the need for educational interventions about HPV and cervical cancer. These actions may contribute to improve adherence to HPV vaccination.

Multiplex flow cytometry serology to diagnosis of canine visceral leishmaniasis.

An accurate diagnosis of visceral leishmaniasis is an essential tool for control of the disease. While serologic methods are very useful, these conventional methodologies still present limitations in terms of sensitivity and specificity. The use of flow cytometry is a worldwide trend in the development of high-performance diagnostic methods. Herein, we describe a new flow cytometry serology test, characterized by the employment of the Cytometric Bead Array microspheres A4 and E4 coated with the recombinant antigens rLci1A and rLci2B respectively, to improve the serodiagnosis of canine visceral leishmaniasis. The tests were conducted in a wide variety of sera groups (n = 140), where the diagnostics development would be optimized accounting not just the ability to identify infected dogs with different clinical status, but also to exclude cross-reaction and differentiate vaccinated dogs from dogs infected. Serological testing of the antigenic system A4-rLci1A showed a sensitivity of 90.0% and specificity of 75%, while the E4-rLci2B testing demonstrated a sensitivity of 95.0% and specificity of 82.5%. The use of a multiplex assay of A4-rLci1A and E4-rLci2B, resulted in a diagnostic improvement, with a sensitivity of 95.0% and specificity of 91.2%. Our results show that this novel flow cytometry serology test is a viable tool for sensitive and specific serodiagnosis. Notably, the combination of distinct antigenic systems allows us to test for antibodies to multiple recombinant antigens from a single serum sample. This benefit emphasizes the importance of this methodology as an alternative in the serological diagnosis.

Canine visceral leishmaniasis biomarkers and their employment in vaccines.

The natural history of canine visceral leishmaniasis (CVL) has been well described, particularly with respect to the parasite load in different tissues and immunopathological changes according to the progression of clinical forms. The biomarkers evaluated in these studies provide support for the improvement of the tools used in developing vaccines against CVL. Thus, we describe the major studies using the dog model that supplies the rationale for including different biomarkers (tissue parasitism, histopathology, hematological changes, leucocytes immunophenotyping, cytokines patterns, and in vitroco-culture systems using purified T-cells subsets and macrophages infected with L. infantum) for immunogenicity and protection evaluations in phases I and II applied to pre-clinical and clinical vaccine trials against CVL. The search for biomarkers related to resistance or susceptibility has revealed a mixed cytokine profile with a prominent proinflammatory immune response as relevant for Leishmania replication at low levels as observed in asymptomatic dogs (highlighted by high levels of IFN-γ and TNF-α and decreased levels in IL-4, TGF-ß and IL-10). Furthermore, increased levels in CD4+ and CD8+ T-cell subsets, presenting intracytoplasmic proinflammatory cytokine balance, have been associated with a resistance profile against CVL. In contrast, a polyclonal B-cell expansion towards plasma cell differentiation contributes to high antibody production, which is the hallmark of symptomatic dogs associated with high susceptibility in CVL. Finally, the different studies used to analyze biomarkers have been incorporated into vaccine immunogenicity and protection evaluations. Those biomarkers identified as resistance or susceptibility markers in CVL have been used to evaluate the vaccine performance against L. infantum in a kennel trial conducted before the field trial in an area known to be endemic for visceral leishmaniasis. This rationale has been a guiding force in the testing and selection of the best vaccine candidates against CVL and provides a way for the veterinary industry to register commercial immunobiological products.