Associations between COVID-19 and Glucose-6-Phosphate Dehydrogenase Activity in Brazil.

Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor for severe disease in patients with COVID-19. We evaluated clinical outcomes and glucose-6 phosphate dehydrogenase (G6PD) activity during and after illness in patients with COVID-19. This prospective cohort study included adult participants (≥ 18 years old) who had clinical and/or radiological COVID-19 findings or positive reverse transcription-polymerase chain reaction results. Epidemiological and clinical data were extracted from electronic medical records. Glucose-6 phosphate dehydrogenase activity was measured using SD Biosensor STANDARD G6PD® equipment on admission and 1 year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms for G6PDd in the Brazilian Amazon. Seven hundred fifty-three patients were included, of whom 123 (16.3%) were G6PD deficient. There was no difference between groups regarding the risks of hospitalization (P = 0.740) or invasive mechanical ventilation (P = 0.31), but the risk of death was greater in patients with normal G6PD levels (P = 0.022). Only 29 of 116 participants (25%) carried the African G6PDd genotype. Of 30 participants tested as G6PD deficient during disease, only 11 (36.7%) results agreed 1 year after discharge. In conclusion, this study does not demonstrate an association of G6PDd with severity of COVID-19. Limitations of the test for detecting enzyme levels during COVID-19 illness were demonstrated by genotyping and retesting after the disease period. Care must be taken when screening for G6PDd in patients with acute COVID-19.

A Brazilian classified data set for prognosis of tuberculosis, between January 2001 and April 2020.

After COVID-19, tuberculosis (TB) is the leading cause of death by an infectious disease in the world. This work presents a data set based on data collected from the Brazilian Information System for Notifiable Diseases (SINAN) for the period from January 2001 to April 2020 relating to patients diagnosed with tuberculosis in Brazil. The data from SINAN was pre-processed to generate a new data set with two distinct treatment outcome classes: CURED and DIED. The data set comprises 37 categorical attributes (including socio-demographic, clinical, and laboratory data) as well as the target class. There are 927,909 records of patients classified as CURED and 36,190 classified as DIED, totaling 964,099 records.

Teachers as multipliers of knowledge about schistosomiasis: a possible approach for health education programmes.

BACKGROUND: In the past decade, Brazil has significantly reduced the prevalence of schistosomiasis through a combined effort of early treatment of infected people, expansion of basic sanitation infrastructure and educational measures. Despite these efforts, in some areas, prevalence of schistosomiasis exceeds 20% of the school population, who lack knowledge of the risks of the disease. Action can be taken in schools to empower this population about their health condition. This paper describes the role of the teacher as a multiplier of knowledge about schistosomiasis and proposes two different approaches to training these teachers. METHODS: This study used mixed methods to evaluate training of teachers and educational intervention with those teachers' pupils. Two training courses, each with 40 h of face-to-face activity, were offered to 19 teachers, using two different but complementary approaches, based on theoretical references and specific educational strategies: Critical Pedagogical Approach (Training Course I, held in 2013) and Creative Play Approach (Training Course II, held in 2014).The courses included classroom activities, laboratory and field work. After the training, the teachers conducted activities on schistosomiasis with their pupils. These activities involved constructing educational materials and cultural productions. The pupils' knowledge about the disease was evaluated before the activities and 12 months later. The teachers' acceptance and perceptions were assessed through structured interviews and subsequent thematic analysis. The Shistosoma mansoni infection status of teachers and their students was also assessed using the Kato Katz stool test. RESULTS: The parasitological study showed 31.6% of the teachers and 21.4% of the pupils to be positive for S. mansoni. The teachers' knowledge of important aspects of schistosomiasis transmission and prevention was fragmented and incorrect prior to the training. The teachers' knowledge changed significantly after the training and they were strongly accepting of the pedagogical methods used during the training. The level of their pupils' knowledge about the disease had increased significantly (p < 0.05). However, pupils responded that, even after the educational activities, they still had contact with the city's contaminated waters (p > 0.05). CONCLUSIONS: The results of this study underline the importance of schools and teachers as partners in controlling and eliminating schistosomiasis. Teacher training on the disease significantly increases their pupils' knowledge, reflecting empowerment with regard to local health conditions.

Global genomic methylation related to the degree of parasitism in cattle.

The objective of the present study was to characterize a herd of 72 ½ Angus × ½ Nellore heifers, identify the resistant, resilient and susceptible animals to parasites, relate the overall DNA methylation of these animals with the degree of parasitism, evaluated by the egg count per gram of feces (EPG), Haematobia irritans count (horn fly) and Rhipicephalus microplus count (bovine tick). The experiment was carried out in a completely randomized design, containing 72 treatments, with each animal considered a treatment, and 11 repetitions, with each collection within a year considered a repetition. The data obtained from the counts of the evaluated parasites were subjected to statistical analysis using the SISVAR program, to classify heifers according to the degree of parasitism in low (resistant), intermediary (resilient) and high (susceptible) parasite load for infection by nematodes, infestation by ticks and flies. Addition the animals in these three groups, by hierarchical grouping using the GENES program, heifers were classified as to the degree of parasitism by the three parasites along with the DNA methylation content of the animals in each group. A negative relationship was observed between resistance and methylated DNA content in both classifications, with the resistant, resilient, and susceptible animals showing the highest, intermediate, and lowest methylated DNA quantifications, respectively. Thus, the methodologies used herein enabled the classification of 72 heifers according to the degree of collective infection by gastrointestinal nematodes and infestation by ticks and horn flies, thereby establishing a link between the degree of parasitic resistance in cattle and the global methylated DNA quantification.

Short-Course of Methylprednisolone Improves Respiratory Functional Parameters After 120 Days in Hospitalized COVID-19 Patients (Metcovid Trial): A Randomized Clinical Trial.

Background: The use of corticosteroids may help control the cytokine storm occurring in acute respiratory failure due to the severe form of COVID-19. We evaluated the postacute effect of corticosteroids used during the acute phase, such as impairment in pulmonary function parameters, on day 120 (D120)-follow-up, in participants who survived over 28 days. Methods: This is a parallel, double-blind, randomized, placebo-controlled phase IIb clinical trial carried out between April 18 and October 9, 2020, conducted in hospitalized patients with clinical-radiological suspicion of COVID-19, aged 18 years or older, with SpO2 ≤ 94% on room air or requiring supplementary oxygen, or under invasive mechanical ventilation (IMV) in a referral center in Manaus, Western Brazilian Amazon. Intravenous methylprednisolone (MP) (0.5 mg/kg) was given two times daily for 5 days to these patients. The primary outcome used for this study was pulmonary function testing at day 120 follow-up visit. Results: Out of the total of surviving patients at day 28 (n = 246) from the Metcovid study, a total of 118 underwent satisfactory pulmonary function testing (62 in the placebo arm and 56 in the MP arm). The supportive treatment was similar between the placebo and MP groups (seven [11%] vs. four [7%]; P = 0.45). At hospital admission, IL-6 levels were higher in the MP group (P < 0.01). Also, the need for ICU (P = 0.06), need for IMV (P = 0.07), and creatine kinase (P = 0.05) on admission also tended to be higher in this group. In the univariate analysis, forced expiratory volume on 1st second of exhalation (FEV1) and forced vital capacity (FVC) at D120 follow-up were significantly higher in patients in the MP arm, being this last parameter also significantly higher in the multivariate analysis independently of IMV and IL-6 levels on admission. Conclusion: The use of steroids for at least 5 days in severe COVID-19 was associated with a higher FVC, which suggests that hospitalized COVID-19 patients might benefit from the use of MP in its use in the long-term, with less pulmonary restrictive functions, attributed to fibrosis. Trial Registration: ClinicalTrials.gov, Identifier: NCT04343729.

Methylprednisolone as Adjunctive Therapy for Patients Hospitalized With Coronavirus Disease 2019 (COVID-19; Metcovid): A Randomized, Double-blind, Phase IIb, Placebo-controlled Trial.

BACKGROUND: Steroid use for coronavirus disease 2019 (COVID-19) is based on the possible role of these drugs in mitigating the inflammatory response, mainly in the lungs, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to evaluate the efficacy of methylprednisolone (MP) among hospitalized patients with suspected COVID-19. METHODS: A parallel, double-blind, placebo-controlled, randomized, Phase IIb clinical trial was performed with hospitalized patients aged ≥18 years with clinical, epidemiological, and/or radiological suspected COVID-19 at a tertiary care facility in Manaus, Brazil. Patients were randomly allocated (1:1 ratio) to receive either intravenous MP (0.5 mg/kg) or placebo (saline solution) twice daily for 5 days. A modified intention-to-treat (mITT) analysis was conducted. The primary outcome was 28-day mortality. RESULTS: From 18 April to 16 June 2020, 647 patients were screened, 416 were randomized, and 393 were analyzed as mITT, with 194 individuals assigned to MP and 199 to placebo. SARS-CoV-2 infection was confirmed by reverse transcriptase polymerase chain reaction in 81.3%. The mortality rates at Day 28 were not different between groups. A subgroup analysis showed that patients over 60 years old in the MP group had a lower mortality rate at Day 28. Patients in the MP arm tended to need more insulin therapy, and no difference was seen in virus clearance in respiratory secretion until Day 7. CONCLUSIONS: The findings of this study suggest that a short course of MP in hospitalized patients with COVID-19 did not reduce mortality in the overall population. CLINICAL TRIALS REGISTRATION: NCT04343729.

Feasibility of GeneXpert® Edge for Tuberculosis Diagnosis in Difficult-to-Reach Populations: Preliminary Results of a Proof-of-Concept Study.

GeneXpert® Edge (GX-Edge) is a new point-of-care platform not yet tested in the field. In this proof-of-concept study conducted for the diagnosis of tuberculosis in communities living alongside two large rivers of the Brazilian Amazon, we demonstrate that GX-Edge implemented in boats to offer onsite testing is a feasible strategy to investigate potentially devastating diseases such as tuberculosis in difficult-to-reach populations, such as riverside communities.

Correction: Social, demographic, health care and co-morbidity predictors of tuberculosis mortality in Amazonas, Brazil: a multiple cause of death approach.

[This corrects the article DOI: 10.1371/journal.pone.0218359.].

Social, demographic, health care and co-morbidity predictors of tuberculosis mortality in Amazonas, Brazil: a multiple cause of death approach.

OBJECTIVES: Estimate TB mortality rates, catalogue multiple causes on death certificates in which TB was reported and identify predictors of TB from reporting on death certificates in the State of Amazonas, Brazil, based on a multiple cause of death approach. METHODS: The death records of residents in the Amazonas state between 2006-2014 were analyzed and separated into three categories: TB not reported on the death certificate (TBNoR), TB reported as the underlying cause of death (TBUC) and TB reported as an associated cause of death (TBAC). Age standardized annual mortality rates for TBUC, TBAC and with TB reported (TBUC plus TBAC) were estimated for the State of Amazonas using the direct standardization method and World Health Organization 2000-2025 standard population. Mortality odds ratios (OR) for reporting of TBUC and TBAC were estimated using multinomial logistic regression. RESULTS: Age standardized annual TBUC and TBAC mortality rates ranged between 5.9-7.8/105 and 2.7-4.0/105, respectively. TBUC was associated with being a resident in the State capital (OR = 0.66), of female gender (OR = 0.87), having an education level of 8 to 11, or 12 or more school years (OR = 0.67 and 0.50 respectively), non-white race/skin color (OR = 1.38) and place of death reported as in the State capital (OR = 1.69). TBAC was related to the triennium in which death occurred (OR = 1.21 and 1.22 for the years 2009-2011 and 2012-2014 respectively), age (OR = 36.1 and 16.5 for ages 15-39 and 40-64 years respectively) and when death occurred in the State capital (OR = 5.8). CONCLUSIONS: TBUC was predominantly associated with predictors of unfavorable socioeconomic conditions and health care access constraints, whereas TBAC was mainly related to ages which were typical of high HIV disease incidence.

Acute lymphoid and myeloid leukemia in a Brazilian Amazon population: Epidemiology and predictors of comorbidity and deaths.

INTRODUCTION: Leukemia is the most common cancer in children and has the highest rates of incidence in industrialized countries, followed by developing countries. This epidemiologic profile can mainly be attributed to the availability of diagnostic resources. In Brazil, leukemia diagnosis is a challenge due to financial viability, lack of hemovigilance services in isolated regions and the vast size of the territory. Its incidence in the state of Amazonas has been increasing since 2010. Therefore, this study aims to describe the epidemiological pattern and spatial distribution of patients with acute lymphoid leukemia and acute myeloid leukemia in Amazonas and identify the predictors of comorbidity and death. MATERIALS AND METHODS: A retrospective cross-sectional study was carried out based on patients' data which was obtained from the database of a referral center for the period of 2005 to 2015. Variables included age, gender, ethnicity, civil status, schooling, income, location of residence, subtype of leukemia, comorbidities, and date of death. The spatial distribution was performed using QGIS v.2.18. Stata software was used for univariable and multivariable logistic regression to evaluate the association between both comorbidities and death for all characteristic groups of ALL and AML. RESULTS: The group that was studied was composed of 577 ALL and 266 AML patients. For both, most patients were male, with a schooling period of 1-4 years, received<1 minimum wage, and lived mostly in Manaus, followed by the municipality of Tefé. There was no association between the development of comorbidities and analyzed variables in patients with ALL. AML patients that were >60 years old and with family history of the disease had the highest risk of developing comorbidities (OR = 5.06, p = 0.038; OR = 2.44, p = 0.041, respectively). Furthermore, patients with ALL and in the 41-50-year age group had a higher risk of death (OR = 31.12; p = 0.001). No association between death and explanatory variables were found in patients with AML. In addition, significant difference was observed in time to death (chi2 = 4,098.32, p = 0.000), with 50% of patients with AML dying within two years after diagnosis, whereas in ALL, this percentual of death only is reached in approximately 5 years. CONCLUSION: Our study describes the data of patients with acute leukemia in Amazonas, a remote region in the north of Brazil. In addition, it highlights the importance of hemovigilance in an Amazon region state, while focusing on peripheral areas which don't have prevention, diagnosis and treatment tools for this disease.

Tuberculosis and malaria walk side by side in the Brazilian Amazon: an ecological approach.

OBJECTIVE: To assess the spatial distribution of TB and malaria incidence, as well as their spatial association with each other, regardless of environmental and socio-economic factors commonly reported as determinants of both disease rates among the municipalities of Amazonas State, Brazil between 2012 and 2015. METHODS: Through an ecological approach considering municipalities of Amazonas, Brazil, as unit of analysis, a negative binomial regression model was used to assess association between malaria and TB rates, in which the dependent variable was the average municipal tuberculosis incidence rate. RESULTS: Positive associations of overall malaria (ß = 0.100 [CI = 0.032, 0.168], P = 0.004), P. vivax malaria (ß = 0.115 [CI = 0.036, 0.195], P = 0.005), and P. falciparum malaria (ß = 0.389 [CI = -0.0124, 0.791], P = 0.057) with TB rates were found, regardless of the sociodemographic factors included in the study. CONCLUSION: In the Brazilian Amazon, TB and malaria are spatially associated. Therefore, it is very likely that co-infections also occur in this region, regardless of the HIV status.

OBJECTIF: Evaluer la distribution spatiale de l'incidence de la tuberculose (TB) et du paludisme, ainsi que leur association spatiale, indépendamment des facteurs environnementaux et socioéconomiques communément rapportés comme déterminants des taux des deux maladie dans les municipalités de l'Etat d'Amazonas, au Brésil, entre 2012 et 2015. MÉTHODES: Dans le cadre d'une approche écologique prenant en considération les municipalités d'Amazonas, au Brésil, comme unité d'analyse, un modèle de régression binomiale négatif a été utilisé pour évaluer l'association entre les taux de paludisme et de TB, dans laquelle la variable dépendante était le taux moyen d'incidence municipale de la TB. RÉSULTATS: Des associations positives entre le paludisme en général (ß = 0,100 [IC= 0,032 à 0,168], p = 0,004), le paludisme à P. vivax (ß = 0,115 [IC: 0,036 à 0,195], p = 0,005) et le paludisme à P. falciparum (ß = 0,389 [IC: - 0,0124 à 0,791], p = 0,057) avec des taux de TB ont été retrouvées quels que soient les facteurs sociodémographiques inclus dans l'étude. CONCLUSION: En Amazonie brésilienne, la TB et le paludisme sont associés spatialement. Par conséquent, il est très probable que des coinfections se produisent également dans cette région, quel que soit le statut VIH.

The role of deforestation on American cutaneous leishmaniasis incidence: spatial-temporal distribution, environmental and socioeconomic factors associated in the Brazilian Amazon.

OBJECTIVE: To analyse the temporal and spatial distribution as well as the environmental and socioeconomic factors associated with cutaneous leishmaniasis incidence in the state of Amazonas, Brazil from 2007 to 2015. METHODS: Spatial and temporal distribution was evaluated from sequential thematic maps of the mean incidence rates of the disease. A negative binomial regression analysis was performed to evaluate the association of the factors studied with the mean incidence rate of ACL. RESULTS: The average proportion of deforestation was negatively associated with the average incidence rate of cutaneous leishmaniasis in municipalities (ß = -2.178; P = 0.019; 95%CI -3.996, -0.361), and the health system performance index (effectiveness) (ß = -0.852; P = 0.008; 95%CI -1.481, -0.225). Conversely, the municipal human development index (MHDI) was a factor positively related to the average incidence among the municipalities (ß = 7.728; P = 0.003; 95%CI 2.716, 12.738). CONCLUSION: Our study shows the important impact of socioeconomic and environmental factors on ACL incidence in the Amazonas State.

OBJECTIF: Analyser la distribution temporelle et spatiale ainsi que les facteurs environnementaux et socioéconomiques associés à l'incidence de la leishmaniose cutanée dans l'Etat de l'Amazonas, au Brésil, de 2007 à 2015. MÉTHODES: La distribution spatiale et temporelle a été évaluée à partir de cartes thématiques séquentielles des taux d'incidence moyens de la maladie. Une analyse de régression binomiale négative a été réalisée pour évaluer l'association des facteurs étudiés avec le taux d'incidence moyen de la LCA. RÉSULTATS: La proportion moyenne de déforestation était négativement associée au taux d'incidence moyen de la leishmaniose cutanée dans les municipalités (ß = -2,178; p = 0,019; IC95%: -3,996 à -0,361) et à l'indice de performance du système de santé (efficacité) (ß = -0,852; p = 0,008; IC95%: -1,481 à -0,225). Par contre, l'indice de développement humain municipal (IDHM) était un facteur positivement lié à l'incidence moyenne dans les municipalités (ß = 7,728; p = 0,003; IC95%: 2,716 à 12,738). CONCLUSION: Notre étude montre l'impact important des facteurs socioéconomiques et environnementaux sur l'incidence de la LCA dans l'Etat d'Amazonas.