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Background A major goal of tuberculosis (TB) epidemiological studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on the determinants of TB treatment outcomes is also important. Methods We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for the study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts. Findings A total of 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection, and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, the presence of diabetes, and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts. Conclusions There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases.

BackgroundTuberculosis (TB) is a worldwide public health problem, especially in countries that also report high numbers of people living with HIV (PLWH) and/or diabetes mellitus (DM). However, the unique features of persons with TB-HIV-DM are incompletely understood. This study compared anti-TB treatment (ATT) outcomes of diabetic and non-diabetic TB/HIV co-infected patients.MethodsA nationwide retrospective observational investigation was performed with data from the Brazilian Tuberculosis Database System among patients reported to have TB-HIV co-infection between 2014 and 2019. This database includes all reported TB cases in Brazil. Exploratory and association analyses compared TB treatment outcomes in DM and non-DM patients. Unfavorable outcomes were defined as death, treatment failure, loss to follow-up or recurrence. Multivariable stepwise logistic regressions were used to identify the variables associated with unfavorable ATT outcomes in the TB-HIV population.ResultsOf the 31,070 TB-HIV patients analyzed, 999 (3.2%) reported having DM. However, in these TB-HIV patients, DM was not associated with any unfavorable treatment outcome [adjusted Odds Ratio (aOR): 0.97, 95% CI: 0.83–1.12, p = 0.781]. Furthermore, DM was also not associated with any specific type of unfavorable outcome in this study. In both the TB-HIV group and the TB-HIV-DM subpopulation, use of alcohol, illicit drugs and tobacco, as well as non-white ethnicity and prior TB were all characteristics more frequently observed in persons who experienced an unfavorable ATT outcome.ConclusionDM is not associated with unfavorable TB treatment outcomes in persons with TB-HIV, including death, treatment failure, recurrence and loss to follow up. However, consumption habits, non-white ethnicity and prior TB are all more frequently detected in those with unfavorable outcomes in both TB-HIV and TB-HIV-DM patients.

BackgroundThere are scarce data on the prevalence and disease presentation of HIV in patients with tuberculosis (TB) and dysglycemia (diabetes [DM] and prediabetes [PDM]), especially in TB-endemic countries.MethodsWe assessed the baseline epidemiological and clinical characteristics of patients with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort in Brazil (RePORT-Brazil) during 2015-2019. Dysglycemia was defined by elevated glycated hemoglobin and stratified as PDM or DM. Additionally, we used data from TB cases obtained through the Brazilian National Notifiable Diseases Information System (SINAN), during 2015-2019. In SINAN, diagnosis of diabetes was based on self-report. Logistic regression models were performed to test independent associations between HIV, dysglycemia status, and other baseline characteristics in both cohorts.ResultsIn the RePORT-Brazil cohort, the prevalence of DM and of PDM was 23.7% and 37.8%, respectively. Furthermore, the prevalence of HIV was 21.4% in the group of persons with TB-dysglycemia and 20.5% in that of patients with TBDM. In the SINAN cohort, the prevalence of DM was 9.2%, and among the TBDM group the prevalence of HIV was 4.1%. Logistic regressions demonstrated that aging was independently associated with PDM or DM in both the RePORT-Brazil and SINAN cohorts. In RePORT-Brazil, illicit drug use was associated with PDM, whereas a higher body mass index (BMI) was associated with DM occurrence. Of note, HIV was not associated with an increased risk of PDM or DM in patients with pulmonary TB in both cohorts. Moreover, in both cohorts, the TBDM-HIV group presented with a lower proportion of positive sputum smear and a higher frequency of tobacco and alcohol users.ConclusionThere is a high prevalence of dysglycemia in patients with pulmonary TB in Brazil, regardless of the HIV status. This reinforces the idea that DM should be systematically screened in persons with TB. Presence of HIV does not substantially impact clinical presentation in persons with TBDM, although it is associated with more frequent use of recreational drugs and smear negative sputum samples during TB screening.

Background It is unclear whether diabetes or prediabetes affects unfavorable treatment outcomes and death in people with tuberculosis (PWTB). Methods Culture-confirmed, drug-susceptible PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)–Brazil cohort between 2015 and 2019 (N = 643) were stratified based on glycemic status according to baseline glycated hemoglobin. Unfavorable tuberculosis (TB) outcome was defined as treatment failure or modification, recurrence, or death; favorable outcome was cure or treatment completion. We corroborated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015–2019 (N = 20 989). Logistic regression models evaluated associations between glycemic status and outcomes. Results In both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with smoking, illicit drug use, and human immunodeficiency virus infection. Diabetes, but not prediabetes, was associated with unfavorable outcomes in the RePORT-Brazil (adjusted relative risk [aRR], 2.45; P < .001) and SINAN (aRR, 1.76; P < .001) cohorts. Furthermore, diabetes was associated with high risk of death (during TB treatment) in both RePORT-Brazil (aRR, 2.16; P = .040) and SINAN (aRR, 1.93; P = .001). Conclusions Diabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve TB treatment outcomes in persons with diabetes are needed.

Due to ethical issues associated with the use of blood for mosquito laboratory experiments, an artificial diet that supports the production of eggs and larvae is highly desirable. We report the development of an artificial diet using direct feeding on protein-rich sugar solution (PRSS) as an alternative to whole blood and evaluated its effects on several biologic parameters of Anopheles darlingi (Root). Field-collected females were fed with different PRSSs containing bovine serum albumin (BSA) at 200 and 400 mg/ml with or without supplemental salts. Engorged mosquitoes were monitored for survival to oviposition, before being forced to oviposit. The proportion ovipositing, number of eggs, and number of larvae were recorded for each treatment. Mosquitoes promptly engorged on PRSSs. The mean proportion of mosquitoes fed with PRSS that survived to oviposition did not differ statistically from that of blood-fed ones. The oviposition proportion of females fed with PRSS at 200 mg/ml was similar to that of blood-fed mosquitoes, whereas mean egg production was lower for most PRSS-fed females, except for those fed with BSA at 400 mg/ml. However, the mean larval production of PRSS-fed mosquitoes was significantly lower than that of blood-fed females. Although feeding An. darlingi on simple PRSS triggered oogenesis and embryogenesis, our results highlight the need for additional nutrients to increase the number of larvae to improve overall reproduction potential.

Anopheles darlingi (Diptera: Culicidae) is the most important vector of malaria in South America and has already been found in peri-urban areas that commonly contain toxic nitrogenous compounds, such as ammonia. The adaptation of mosquitoes to polluted breeding sites can increase their distribution and affect the dynamics of vector-borne diseases such as malaria. Therefore, the present study investigated the tolerance of larval instars of An. darlingi to ammonia under acute and chronic exposure conditions. Anopheles darlingi larval mortality, development time, and pupal and adult production using larvae of the 1st (L1) and 3rd (L3) instar were assessed as both acute and chronic effects of exposure to different concentrations of ammonia. Lethal concentrations (LCs) for L1 larvae were lower than LCs for L3 larvae. In general, higher ammonia concentrations caused an increase in larval mortality, especially in chronically exposed L1 larvae. The larval development time in L1 and L3 was longer with chronic treatment and decreased with increasing concentrations of ammonia. The number of pupae was very low for acutely exposed L1 and L3 larvae. Likewise, the probability of adult production decreased with increasing ammonia concentrations. This is the first report on the tolerance of An. darlingi to pollutants.

BjcuL is a C-type lectin isolated from Bothrops jararacussu snake venom with specificity for binding β-d-galactose units. BjcuL is not toxic to human peripheral blood mononuclear cells (PBMCs), but it inhibits PBMC proliferation and stimulates these cells to produce superoxide anions and hydrogen peroxide primarily via lymphocyte stimulation; it does not stimulate the production of nitric oxide and PGE2. The purpose of this study was to investigate the effect of BjcuL on PBMC activation with a focus on cytokine release modulating PBMC proliferation. The results showed for the first time that BjcuL coupled to FITC interacted with monocytes, B cells, natural killer (NK) cells, and with subpopulations of T cells. These cell-cell interactions can lead to cell activation and inflammatory cytokines release, such as IL-6 and TNF-α, as well as the anti-inflammatory cytokine IL-10. In addition, TNF-α release was attributed to NK cells and monocytes, whereas IL-10 was attributed to TCD4+ and Treg cells when stimulated by BjcuL. The temporal cytokines profile produced by cells when stimulated with this lectin allows us to assert that BjcuL has immunomodulatory activity in this context.

BackgroundIt is unclear whether diabetes or prediabetes drives adverse treatment outcomes and death in people with tuberculosis (PWTB).MethodsCulture-confirmed PWTB, enrolled in the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between 2015 and 2019 (n=756) were stratified based on glycemic status by baseline glycated hemoglobin levels. Unfavorable TB outcome was defined as treatment failure or modification, recurrence or death, whereas favorable outcome was cure or treatment completion. We validated the findings using data from PWTB reported to the Brazilian National System of Diseases Notification (SINAN) during 2015-2019 (n=20,989). Stepwise binary multivariable regression analysis models evaluated associations between glycemic status and unfavorable outcomes.ResultsIn both cohorts, in univariate analysis, unfavorable outcomes were more frequently associated with drug resistance and HIV infection. Diabetes was associated with unfavorable outcomes in the RePORT (aOR: 2.85, p=0.001) and in SINAN (aOR: 1.56, p=0.040) cohorts. Furthermore, diabetes was associated with higher risk of death in both, RePORT-Brazil (aOR:3.23, p=0.006) and in the SINAN (aOR:2.75, p= 0.047) cohorts.ConclusionDiabetes was associated with an increased risk of unfavorable outcomes and mortality in Brazilian PWTB. Interventions to improve tuberculosis treatment outcomes in persons with diabetes are needed.40-word summary of the article’s main pointIn a multicenter prospective cohort study from Brazil, diabetes was associated with an increased risk of unfavorable treatment outcomes, including mortality, in pulmonary tuberculosis patients. These observations were validated in the Brazilian National Disease Notification System during the same period.

Background: Approximately 1·4 million people die annually worldwide from tuberculosis. Large epidemiologic studies can identify determinants of unfavorable clinical outcomes according to age, which can guide implementation of public health policies and clinical management to improve outcomes. Methods: We obtained data from the national tuberculosis case registry: cases reported to the Brazilian National Program (SINAN) between 2010-2019. Clinical and epidemiologic variables were compared between age groups (child

Background: A major goal of tuberculosis (TB) epidemiologic studies is to obtain results that can be generalized to the larger population with TB. The ability to extrapolate findings on determinants of TB treatment outcomes is also important. Methods: We compared baseline clinical and demographic characteristics and determinants of anti-TB treatment outcomes between persons enrolled into the Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil cohort between June 2015 and June 2019, and the registry of TB cases reported to the Brazilian National TB Program (Information System for Notifiable Diseases [SINAN]) during the same time period. Multivariable regression models adjusted for study site were performed using second-generation p-values, a novel statistical approach. Associations with unfavorable treatment outcomes were tested for both RePORT-Brazil and SINAN cohorts. Findings: 1,060 culture-confirmed TB patients were enrolled in RePORT-Brazil and 455,873 TB cases were reported to SINAN. Second-generation p-value analyses revealed that the cohorts were strikingly similar with regard to sex, age, use of antiretroviral therapy and positive initial smear sputum microscopy. However, diabetes, HIV infection and smoking were more frequently documented in RePORT-Brazil. Illicit drug use, presence of diabetes and history of prior TB were associated with unfavorable TB treatment outcomes; illicit drug use was associated with such outcomes in both cohorts. Interpretations: There were important similarities in demographic characteristics and determinants of clinical outcomes between the RePORT-Brazil cohort and the Brazilian National registry of TB cases. Funding Statement: Fundacao Jose Silveira and Ministerio da Saude, Brazil and the National Institutes of Allergy and Infectious Diseases. Declaration of Interests: All authors: none reported. Ethics Approval Statement: All clinical investigations were conducted according to the principles of the Declaration of Helsinki. The RePORT-Brazil protocol, informed consent, and study documents were approved by the institutional review boards at each study site and at Vanderbilt University Medical Center. Participation in RePORT Brazil was voluntary, and written informed consent was obtained from all such participants. For the data extracted from SINAN, the anonymity of study subjects was preserved, and all data were de-identified.