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1.
Front Immunol ; 13: 830497, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173740

RESUMO

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 is rising, making TB prevention and control more challenging. Vaccination has been considered the best approach to reduce the TB burden. Unfortunately, BCG, the only TB vaccine currently approved for use, offers some protection against childhood TB but is less effective in adults. Therefore, it is urgent to develop new TB vaccines that are more effective than BCG. Accumulating data indicated that peptides or epitopes play essential roles in bridging innate and adaptive immunity and triggering adaptive immunity. Furthermore, innovations in bioinformatics, immunoinformatics, synthetic technologies, new materials, and transgenic animal models have put wings on the research of peptide-based vaccines for TB. Hence, this review seeks to give an overview of current tools that can be used to design a peptide-based vaccine, the research status of peptide-based vaccines for TB, protein-based bacterial vaccine delivery systems, and animal models for the peptide-based vaccines. These explorations will provide approaches and strategies for developing safer and more effective peptide-based vaccines and contribute to achieving the WHO's End TB Strategy.


Assuntos
Vacina BCG/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/prevenção & controle , Vacinas de Subunidades/imunologia , Animais , Proteínas de Bactérias/imunologia , Modelos Animais de Doenças , Humanos , Camundongos , Peptídeos/imunologia , Tuberculose/imunologia , Tuberculose/mortalidade , Vacinação
2.
PLoS One ; 17(1): e0247894, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35077447

RESUMO

INTRODUCTION: Tuberculosis is one of the ten leading causes of death and the leading infectious cause worldwide. The disease represents a challenge to health systems around the world. In 2018, it is estimated that 10 million people were affected by tuberculosis, and approximately 1.5 million people died due to the disease worldwide, including 251,000 patients coinfected with HIV. In Brazil, the disease caused 4,490 deaths, with rate of 2.2 deaths per 100,000 inhabitants. The objective of this study was to analyze the time behavior, spatial, spatial-temporal distribution, and the effects of social vulnerability on the incidence of TB in Brazil during the period from 2001 to 2017. MATERIALS AND METHODS: A spatial-temporal ecological study was conducted, including all new cases of tuberculosis registered in Brazil during the period from 2001 to 2017. The following variables were analyzed: incidence rate of tuberculosis, the Social Vulnerability Index, its subindices, its 16 indicators, and an additional 14 variables available on the Atlas of Social Vulnerability. The statistical treatment of the data consisted of the following three stages: a) time trend analysis with a joinpoint regression model; b) spatial analysis and identification of risk areas based on smoothing of the incidence rate by local empirical Bayesian model, application of global and local Moran statistics, and, finally, spatial-temporal scan statistics; and c) analysis of association between the incidence rate and the indicators of social vulnerability. RESULTS: Brazil reduced the incidence of tuberculosis from 42.8 per 100,000 to 35.2 per 100,000 between 2001 and 2017. Only the state of Minas Gerais showed an increasing trend, whereas nine other states showed a stationary trend. A total of 326 Brazilian municipalities were classified as high priority, and 22 high-risk spatial-temporal clusters were identified. The overall Social Vulnerability Index and the subindices of Human Capital and Income and Work were associated with the incidence of tuberculosis. It was also observed that the incidence rates were greater in municipalities with greater social vulnerability. CONCLUSIONS: This study identified clusters with high risk of TB in Brazil. A significant association was observed between the incidence rate of TB and the indices of social vulnerability.


Assuntos
Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Teorema de Bayes , Brasil/epidemiologia , Comorbidade , Infecções por HIV/mortalidade , Humanos , Incidência , Mortalidade , Análise de Regressão , Vulnerabilidade Social , Análise Espaço-Temporal , Tuberculose/mortalidade
4.
Lancet Glob Health ; 10(2): e207-e215, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34895517

RESUMO

BACKGROUND: Many children who develop tuberculosis are thought to be missed by diagnostic and reporting systems. We aimed to estimate paediatric tuberculosis incidence and underreporting between 2013 and 2019 in countries representing more than 99% of the global tuberculosis burden. METHODS: We developed a mathematical model of paediatric tuberculosis natural history, accounting for key mechanisms and risk factors for infectious exposure (HIV, malnutrition, and BCG non-vaccination), the probability of infection given exposure, and progression to disease among infected individuals. We extracted paediatric population estimates from UN Population Division data, and we used WHO estimates for adult tuberculosis incidence rates. We parameterised this model for 185 countries and calibrated it using data from countries with stronger case detection and reporting systems. Using this model, we estimated trends in paediatric incidence, and the proportion of these cases that are diagnosed and reported (case detection ratio [CDR]) for each country, age group, and year. FINDINGS: For 2019, we estimated 997 500 (95% credible interval [CrI] 868 700-1 163 100) incident tuberculosis cases among children, with 481 000 cases (398 400-587 400) among those aged 0-4 years and 516 500 cases (442 900-608 000) among those aged 5-14 years. The paediatric CDR was estimated to be lower in children aged 0-4 years (41%, 95% CrI 34-50) than in those aged 5-14 years (63%, 53-75) and varied widely between countries. Estimated CDRs increased substantially over the study period, from 18% (15-20) in 2013 to 53% (45-60) in 2019, with improvements concentrated in the Eastern Mediterranean, South-East Asia, and Western Pacific regions. Over the study period, global incidence was estimated to have declined slowly at an average annual rate of 1·52% (1·42-1·66). INTERPRETATION: Paediatric tuberculosis causes substantial morbidity and mortality, and these data indicate that cases (and, thus, probably associated mortality) are currently substantially underreported. These findings reinforce the need to ensure prompt diagnosis and care for children developing tuberculosis, strengthen reporting systems, and invest in research to develop more accurate and easy-to-use diagnostics for paediatric tuberculosis in high-burden settings. FUNDING: National Institutes of Health.


Assuntos
Saúde Global , Modelos Teóricos , Tuberculose/epidemiologia , Adolescente , Fatores Etários , Teorema de Bayes , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Fatores de Risco , Tuberculose/mortalidade , Organização Mundial da Saúde
5.
JAMA Netw Open ; 4(12): e2136853, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34860244

RESUMO

Importance: Tuberculosis (TB) and COVID-19 are respiratory diseases that disproportionately occur among medically underserved populations; little is known about their epidemiologic intersection. Objective: To characterize persons diagnosed with TB and COVID-19 in California. Design, Setting, and Participants: This cross-sectional analysis of population-based public health surveillance data assessed the sociodemographic, clinical, and epidemiologic characteristics of California residents who were diagnosed with TB (including cases diagnosed and reported between September 3, 2019, and December 31, 2020) and COVID-19 (including confirmed cases based on positive results on polymerase chain reaction tests and probable cases based on positive results on antigen assays reported through February 2, 2021) in close succession compared with those who were diagnosed with TB before the COVID-19 pandemic (between January 1, 2017, and December 31, 2019) or diagnosed with COVID-19 alone (through February 2, 2021). This analysis included 3 402 713 California residents with COVID-19 alone, 6280 with TB before the pandemic, and 91 with confirmed or probable COVID-19 diagnosed within 120 days of a TB diagnosis (ie, TB/COVID-19). Exposures: Sociodemographic characteristics, medical risk factors, factors associated with TB severity, and health equity index. Main Outcomes and Measures: Frequency of reported successive TB and COVID-19 (TB/COVID-19) diagnoses within 120 days, frequency of deaths, and age-adjusted mortality rates. Results: Among the 91 persons with TB/COVID-19, the median age was 58.0 years (range, 3.0-95.0 years; IQR, 41.0-73.0 years); 52 persons (57.1%) were male; 81 (89.0%) were born outside the US; and 28 (30.8%) were Asian or Pacific Islander, 4 (4.4%) were Black, 55 (60.4%) were Hispanic or Latino, 4 (4.4%) were White. The frequency of reported COVID-19 among those who received a TB diagnosis between September 3, 2019, and December 31, 2020, was 225 of 2210 persons (10.2%), which was similar to that of the general population (3 402 804 of 39 538 223 persons [8.6%]). Compared with persons with TB before the pandemic, those with TB/COVID-19 were more likely to be Hispanic or Latino (2285 of 6279 persons [36.4%; 95% CI, 35.2%-37.6%] vs 55 of 91 persons [60.4%; 95% CI, 49.6%-70.5%], respectively; P < .001), reside in low health equity census tracts (1984 of 6027 persons [32.9%; 95% CI, 31.7%-34.1%] vs 40 of 89 persons [44.9%; 95% CI, 34.4%-55.9%]; P = .003), live in the US longer before receiving a TB diagnosis (median, 19.7 years [IQR, 7.2-32.3 years] vs 23.1 years [IQR, 15.2-31.5 years]; P = .03), and have diabetes (1734 of 6280 persons [27.6%; 95% CI, 26.5%-28.7%] vs 42 of 91 persons [46.2%; 95% CI, 35.6%-56.9%]; P < .001). The frequency of deaths among those with TB/COVID-19 successively diagnosed within 30 days (8 of 34 persons [23.5%; 95% CI, 10.8%-41.2%]) was more than twice that of persons with TB before the pandemic (631 of 5545 persons [11.4%; 95% CI, 10.6%-12.2%]; P = .05) and 20 times that of persons with COVID-19 alone (42 171 of 3 402 713 persons [1.2%; 95% CI, 1.2%-1.3%]; P < .001). Persons with TB/COVID-19 who died were older (median, 81.0 years; IQR, 75.0-85.0 years) than those who survived (median, 54.0 years; IQR, 37.5-68.5 years; P < .001). The age-adjusted mortality rate remained higher among persons with TB/COVID-19 (74.2 deaths per 1000 persons; 95% CI, 26.2-122.1 deaths per 1000 persons) compared with either disease alone (TB before the pandemic: 56.3 deaths per 1000 persons [95% CI, 51.2-61.4 deaths per 1000 persons]; COVID-19 only: 17.1 deaths per 1000 persons [95% CI, 16.9-17.2 deaths per 1000 persons]). Conclusions and Relevance: In this cross-sectional analysis, TB/COVID-19 was disproportionately diagnosed among California residents who were Hispanic or Latino, had diabetes, or were living in low health equity census tracts. These results suggest that tuberculosis and COVID-19 occurring together may be associated with increases in mortality compared with either disease alone, especially among older adults. Addressing health inequities and integrating prevention efforts could avert the occurrence of concurrent COVID-19 and TB and potentially reduce deaths.


Assuntos
COVID-19/diagnóstico , Comorbidade , Mortalidade/tendências , Fatores de Tempo , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/mortalidade , California/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Humanos , Pessoa de Meia-Idade , Tuberculose/epidemiologia , Tuberculose/mortalidade
6.
PLoS One ; 16(12): e0261149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34890421

RESUMO

BACKGROUND: Drug resistance remains from among the most feared public health threats that commonly challenges tuberculosis treatment success. Since 2010, there have been rapid evolution and advances to second-line anti-tuberculosis treatments (SLD). However, evidence on impacts of these advances on incidence of mortality are scarce and conflicting. Estimating the number of people died from any cause during the follow-up period of SLD as the incidence proportion of all-cause mortality is the most informative way of appraising the drug-resistant tuberculosis treatment outcome. We thus aimed to estimate the pooled incidence of mortality and its predictors among persons receiving the SLD in sub-Saharan Africa. METHODS: We systematically identified relevant studies published between January, 2010 and March, 2020, by searching PubMed/MEDLINE, EMBASE, SCOPUS, Cochrane library, Google scholar, and Health Technology Assessment. Eligible English-language publications reported on death and/or its predictors among persons receiving SLD, but those publications that reported death among persons treated for extensively drug-resistant tuberculosis were excluded. Study features, patients' clinical characteristics, and incidence and/or predictors of mortality were extracted and pooled for effect sizes employing a random-effects model. The pooled incidence of mortality was estimated as percentage rate while risks of the individual predictors were appraised based on their independent associations with the mortality outcome. RESULTS: A total of 43 studies were reviewed that revealed 31,525 patients and 4,976 deaths. The pooled incidence of mortality was 17% (95% CI: 15%-18%; I2 = 91.40; P = 0.00). The studies used varied models in identifying predictors of mortality. They found diagnoses of clinical conditions (RR: 2.36; 95% CI: 1.82-3.05); excessive substance use (RR: 2.56; 95% CI: 1.78-3.67); HIV and other comorbidities (RR: 1.96; 95% CI: 1.65-2.32); resistance to SLD (RR: 1.75; 95% CI: 1.37-2.23); and male sex (RR: 1.82; 95% CI: 1.35-2.44) as consistent predictors of the mortality. Few individual studies also reported an increased incidence of mortality among persons initiated with the SLD after a month delay (RR: 1.59; 95% CI: 0.98-2.60) and those persons with history of tuberculosis (RR: 1.21; 95% CI: 1.12-1.32). CONCLUSIONS: We found about one in six persons who received SLD in sub-Saharan Africa had died in the last decade. This incidence of mortality among the drug-resistant tuberculosis patients in the sub-Saharan Africa mirrors the global average. Nevertheless, it was considerably high among the patients who had comorbidities; who were diagnosed with other clinical conditions; who had resistance to SLD; who were males and substance users. Therefore, modified measures involving shorter SLD regimens fortified with newer or repurposed drugs, differentiated care approaches, and support of substance use rehabilitation programs can help improve the treatment outcome of persons with the drug-resistant tuberculosis. TRIAL REGISTRATION NUMBER: CRD42020160473; PROSPERO.


Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/mortalidade , África ao Sul do Saara/epidemiologia , Estudos de Coortes , Humanos , Incidência , Valor Preditivo dos Testes , Taxa de Sobrevida , Resultado do Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia
7.
PLoS One ; 16(12): e0258964, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34932563

RESUMO

INTRODUCTION: In resource-limited settings, the mortality rate among tuberculosis and human Immunodeficiency virus co-infected children is higher. However, there is no adequate evidence in Ethiopia in general and in the study area in particular. Hence, this study aims to estimate lifetime survival and predictors of mortality among TB with HIV co-infected children after test and treat strategies launched in Northwest Ethiopia Hospitals, 2021. METHODS: Institution-based historical follow-up study was conducted in Northwest Ethiopia Hospitals among 227 Tuberculosis and Human Immunodeficiency Virus co-infected children from March 1, 2014, to January 12, 2021. The data were entered into Epi info-7 and then exported to STATA version 14 for analysis. The log-rank test was used to estimate the curve difference of the predictor variables. Bivariable cox-proportional hazard models were employed for each predictor variable. Additionally, those variables having a p-value < 0.25 in bivariate analysis were fitted into a multivariable cox-proportional hazards model. P-value < 0.05 was used to declare significance associated with the dependent variable. RESULTS: From a total of 227 TB and HIV co-infected children, 39 died during the follow-up period. The overall mortality rate was 3.7 (95% CI (confidence interval): 2.9-4.7) per 100 person-years with a total of 1063.2-year observations. Cotrimoxazole preventive therapy (CPT) non-users [Adjusted Hazarded Ratio (AHR) = 3.8 (95% CI: 1.64-8.86)], presence of treatment failure [AHR = 3.0 (95% CI: 1.14-78.17)], and Cluster of differentiation 4(CD4) count below threshold [AHR = 2.7 (95% CI: 1.21-6.45)] were significant predictors of mortality. CONCLUSION: In this study, the mortality rate among TB and HIV co-infected children was found to be very high. The risk of mortality among TB and HIV co-infected children was associated with treatment failure, CD4 count below the threshold, and cotrimoxazole preventive therapy non-users. Further research should conduct to assess and improve the quality of ART service in Northwest Ethiopia Hospitals.


Assuntos
Coinfecção , Infecções por HIV , HIV-1 , Mycobacterium tuberculosis , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Tuberculose , Contagem de Linfócito CD4 , Criança , Pré-Escolar , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Coinfecção/mortalidade , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Lactente , Masculino , Tuberculose/sangue , Tuberculose/diagnóstico , Tuberculose/mortalidade , Tuberculose/prevenção & controle
8.
Recurso na Internet em Português | LIS - Localizador de Informação em Saúde | ID: lis-48470

RESUMO

A pandemia de COVID-19 reverteu anos de progresso global no combate à tuberculose e, pela primeira vez em mais de uma década, as mortes pela doença aumentaram, de acordo com o relatório global da Organização Mundial da Saúde (OMS) de 2021.


Assuntos
Tuberculose/mortalidade , COVID-19
10.
Sci Rep ; 11(1): 19346, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588552

RESUMO

The study aim was to determine the association of a one United States dollar (USD) dollar incentive and tuberculosis (TB) treatment outcomes among people with TB receiving treatment at a rural hospital in Uganda under programmatic settings. We conducted a quasi-experiment in which people with TB were randomised (1:1 ratio) to receive either a one USD incentive at months 0, 2, 5 and 6 (Dollar arm) or routine care (Routine arm). A second control group (Retrospective controls) consisted of participants who had a treatment outcome in the preceding 6 months. Treatment outcomes were compared between the intervention and control groups using Pearson's chi-square and Fisher's exact tests. The association between the incentive and treatment outcomes was determined using Poisson regression analysis with robust variances. Between November 2018 and October 2019, we enrolled 180 participants (60 in the Dollar arm and 120 in the Control group). TB cure (33.3% vs. 20.8%, p = 0.068) and treatment success (70.0% vs. 59.2% p = 0.156) were higher in the Dollar arm than the Control group, while loss-to-follow-up was lower in the Dollar arm (10.0% vs. 20.8% p = 0.070). Participants in the Dollar arm were more likely to be cured (adjusted incidence rate ratio (aIRR): 1.59, 95% CI 1.04-2.44, p = 0.032) and less likely to be lost to follow-up (aIRR: 0.44, 95% CI 0.20-0.96, p = 0.040). A one-dollar incentive was associated with higher TB cure and lower loss-to-follow-up among people with TB in rural Uganda.


Assuntos
Motivação , Cooperação do Paciente/estatística & dados numéricos , População Rural/estatística & dados numéricos , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Perda de Seguimento , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose/mortalidade , Uganda/epidemiologia , Adulto Jovem
11.
Bull Exp Biol Med ; 171(4): 445-448, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34542757

RESUMO

We studied the effectiveness of anti-tuberculosis vaccination with BCG in mice of inbred strains and F1 hybrids (highly resistant to tuberculosis infection) that represent a wide range of genetically determined differences in susceptibility to infection with virulent Mycobacterium tuberculosis. The greatest relative effect was found in susceptible mice, with the exception of highly susceptible I/St mice that were practically not protected by vaccination. Despite significant effect of vaccination in inbred mice, their resistance to M. tuberculosis infection did not exceed that of non-vaccinated highly resistant F1 hybrids.


Assuntos
Vacina BCG/uso terapêutico , Patrimônio Genético , Tuberculose/prevenção & controle , Animais , Feminino , Interações Hospedeiro-Patógeno/genética , Camundongos , Camundongos Endogâmicos AKR , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/patogenicidade , Tuberculose/genética , Tuberculose/mortalidade , Vacinação
12.
Lancet Glob Health ; 9(10): e1372-e1379, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34487685

RESUMO

BACKGROUND: The tuberculosis targets for the UN Sustainable Development Goals (SDGs) call for a 90% reduction in tuberculosis deaths by 2030, compared with 2015, but meeting this target now seems highly improbable. To assess the economic impact of not meeting the target until 2045, we estimated full-income losses in 120 countries, including those due to excess deaths resulting from COVID-19-related disruptions to tuberculosis services, for the period 2020-50. METHODS: Annual mortality risk changes at each age in each year from 2020 to 2050 were estimated for 120 countries. This risk change was then converted to full-income risk by calculating a population-level mortality risk change and multiplying it by the value of a statistical life-year in each country and year. As a comparator, we assumed that current rates of tuberculosis continue to decline through the period of analysis. We calculated the full-income losses, and mean life expectancy losses per person, at birth and at age 35 years, under scenarios in which the SDG targets are met in 2030 and in 2045. We defined the cost of inaction as the difference in full-income losses and tuberculosis mortality between these two scenarios. FINDINGS: From 2020 to 2050, based on the current annual decrease in tuberculosis deaths of 2%, 31·8 million tuberculosis deaths (95% uncertainty interval 25·2 million-39·5 million) are estimated to occur, corresponding to an economic loss of US$17·5 trillion (14·9 trillion-20·4 trillion). If the SDG tuberculosis mortality target is met in 2030, 23·8 million tuberculosis deaths (18·9 million-29·5 million) and $13·1 trillion (11·2 trillion-15·3 trillion) in economic losses can be avoided. If the target is met in 2045, 18·1 million tuberculosis deaths (14·3 million-22·4 million) and $10·2 trillion (8·7 trillion-11·8 trillion) can be avoided. The cost of inaction of not meeting the SDG tuberculosis mortality target until 2045 (vs 2030) is, therefore, 5·7 million tuberculosis deaths (5·1 million-8·1 million) and $3·0 trillion (2·5 trillion-3·5 trillion) in economic losses. COVID-19-related disruptions add $290·3 billion (260·2 billion-570·1 billion) to this cost. INTERPRETATION: Failure to achieve the SDG tuberculosis mortality target by 2030 will lead to profound economic and health losses. The effects of delay will be greatest in sub-Saharan Africa. Affected countries, donor nations, and the private sector should redouble efforts to finance tuberculosis programmes and research because the economic dividend of such strategies is likely to be substantial. FUNDING: None.


Assuntos
Expectativa de Vida , Tuberculose/economia , Tuberculose/mortalidade , COVID-19 , Carga Global da Doença/economia , Infecções por HIV/complicações , Humanos , Desenvolvimento Sustentável , Tuberculose/prevenção & controle
13.
Sci Rep ; 11(1): 18008, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504192

RESUMO

The programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of the PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the effect of blocking this pathway in pulmonary Mycobacterium avium-intracellulare complex (MAC) infection is not fully understood. Wild-type, PD-1-deficient mice, and PD-L1-deficient mice were intranasally infected with Mycobacterium avium bacteria. Depletion of PD-1 or PD-L1 did not affect mortality and bacterial burden in MAC-infected mice. However, marked infiltration of CD8-positive T lymphocytes was observed in the lungs of PD-1 and PD-L1-deficient mice compared to wild-type mice. Comprehensive transcriptome analysis showed that levels of gene expressions related to Th1 immunity did not differ according to the genotypes. However, genes related to the activity of CD8-positive T cells and related chemokine activity were upregulated in the infected lungs of PD-1 and PD-L1-deficient mice. Thus, the lack of change in susceptibility to MAC infection in PD-1 and PD-L1-deficient mice might be explained by the absence of obvious changes in the Th1 immune response. Furthermore, activated CD8-positive cells in response to MAC infection in these mice seemed to not be relevant in the control of MAC infection.


Assuntos
Antígeno B7-H1/genética , Linfócitos T CD8-Positivos/imunologia , Mycobacterium avium/imunologia , Receptor de Morte Celular Programada 1/genética , Células Th1/imunologia , Tuberculose/genética , Animais , Antígeno B7-H1/deficiência , Antígeno B7-H1/imunologia , Linfócitos T CD8-Positivos/microbiologia , Movimento Celular , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genótipo , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Ativação Linfocitária , Camundongos , Camundongos Knockout , Mycobacterium avium/patogenicidade , Receptor de Morte Celular Programada 1/deficiência , Receptor de Morte Celular Programada 1/imunologia , Análise de Sobrevida , Células Th1/microbiologia , Transcriptoma , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/mortalidade
14.
Am J Trop Med Hyg ; 105(5): 1326-1334, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491226

RESUMO

Our aim was to identify the risk factors associated with unsuccessful outcomes of tuberculosis (TB) treatment in patients diagnosed between 2014 and 2016 in the 125 municipalities of Antioquia, Colombia. We studied a retrospective cohort of patients with TB diagnosed between 2014 and 2016, from national routine surveillance systems, in 125 municipalities of Antioquia. Factors associated with unsuccessful tuberculosis treatment outcomes (treatment failed, lost to follow up, or death) were identified utilizing a Poisson regression with robust variance. Over 3 years, of the 6,739 drug-susceptible tuberculosis patients, 73.4% had successful treatment and 26.6% unsuccessful outcomes (17% lost to follow up, 8.9% deaths, and 0.7% treatment failures). Patients with subsidized health insurance (Relative risk [RR]: 2.4; 95% CI: 2.1-2.8) and without health insurance (RR: 2.5; 95% CI: 2.1-3.0) had a higher risk for unsuccessful tuberculosis treatment compared to those with contributive health insurance. Other risk factors included age over 15 years, male sex, homelessness, people living with HIV, previous treatment, and primary diagnosis during hospitalization. Protective factors were living in a rural area and extrapulmonary disease. It is important to generate strategies that improves tuberculosis diagnosis in primary healthcare institutions. In addition, it is imperative to initiate new research about the barriers and obstacles related to patients, healthcare workers and services, and the health system, including the analysis of urban violence, to understand why the goal of TB treatment success has not been reached.


Assuntos
Antituberculosos/uso terapêutico , Falha de Tratamento , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose/mortalidade , População Urbana/estatística & dados numéricos , População Urbana/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Cidades/estatística & dados numéricos , Estudos de Coortes , Colômbia/epidemiologia , Estudos Epidemiológicos , Feminino , Previsões , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vigilância da População , Estudos Retrospectivos , Adulto Jovem
15.
PLoS One ; 16(9): e0256515, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34496000

RESUMO

BACKGROUND: The epidemiological transition, touted as occurring in Ghana, requires research that tracks the changing patterns of diseases in order to capture the trend and improve healthcare delivery. This study examines national trends in mortality rate and cause of death at health facilities in Ghana between 2014 and 2018. METHODS: Institutional mortality data and cause of death from 2014-2018 were sourced from the Ghana Health Service's District Health Information Management System. The latter collates healthcare service data routinely from government and non-governmental health institutions in Ghana yearly. The institutional mortality rate was estimated using guidelines from the Ghana Health Service. Percent change in mortality was examined for 2014 and 2018. In addition, cause of death data were available for 2017 and 2018. The World Health Organisation's 11th International Classification for Diseases (ICD-11) was used to group the cause of death. RESULTS: Institutional mortality decreased by 7% nationally over the study period. However, four out of ten regions (Greater Accra, Volta, Upper East, and Upper West) recorded increases in institutional mortality. The Upper East (17%) and Volta regions (13%) recorded the highest increase. Chronic non-communicable diseases (NCDs) were the leading cause of death in 2017 (25%) and 2018 (20%). This was followed by certain infectious and parasitic diseases (15% for both years) and respiratory infections (10% in 2017 and 13% in 2018). Among the NCDs, hypertension was the leading cause of death with 2,243 and 2,472 cases in 2017 and 2018. Other (non-ischemic) heart diseases and diabetes were the second and third leading NCDs. Septicaemia, tuberculosis and pneumonia were the predominant infectious diseases. Regional variations existed in the cause of death. NCDs showed more urban-region bias while infectious diseases presented more rural-region bias. CONCLUSIONS: This study examined national trends in mortality rate and cause of death at health facilities in Ghana. Ghana recorded a decrease in institutional mortality throughout the study. NCDs and infections were the leading causes of death, giving a double-burden of diseases. There is a need to enhance efforts towards healthcare and health promotion programmes for NCDs and infectious diseases at facility and community levels as outlined in the 2020 National Health Policy of Ghana.


Assuntos
Diabetes Mellitus/mortalidade , Instalações de Saúde , Cardiopatias/mortalidade , Hipertensão/mortalidade , Doenças não Transmissíveis/mortalidade , Pneumonia/mortalidade , Sepse/mortalidade , Tuberculose/mortalidade , Causas de Morte/tendências , Doença Crônica/epidemiologia , Doença Crônica/mortalidade , Atenção à Saúde , Diabetes Mellitus/epidemiologia , Feminino , Gana/epidemiologia , Carga Global da Doença , Cardiopatias/epidemiologia , Humanos , Hipertensão/epidemiologia , Masculino , Doenças não Transmissíveis/epidemiologia , Pneumonia/epidemiologia , População Rural , Sepse/epidemiologia , Tuberculose/epidemiologia , População Urbana
16.
Cell Rep ; 36(11): 109696, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34525366

RESUMO

CD4 T cells are essential for immunity to tuberculosis because they produce cytokines, including interferon-γ. Whether CD4 T cells act as "helper" cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Tuberculose/imunologia , Animais , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/metabolismo , Modelos Animais de Doenças , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Interferon gama/metabolismo , Interleucina-2/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis/patogenicidade , Mycobacterium tuberculosis/fisiologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Família de Moléculas de Sinalização da Ativação Linfocitária/genética , Família de Moléculas de Sinalização da Ativação Linfocitária/metabolismo , Taxa de Sobrevida , Linfócitos T Auxiliares-Indutores/citologia , Linfócitos T Auxiliares-Indutores/metabolismo , Transcriptoma , Tuberculose/mortalidade , Tuberculose/patologia
17.
Asian Pac J Cancer Prev ; 22(8): 2701-2708, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34452577

RESUMO

BACKGROUND AND OBJECTIVE: We aimed to investigate the survival time and its related factors among cancer patients with co-morbid tuberculosis (TB) in Thailand. METHODS: We conducted this retro-prospective cohort study on cancer patients without co-morbid TB using the data from population-based cancer registry of Khon Kaen, TB databases from the Khon Kaen Central Hospital, and the Region 7 Office of Disease Prevention and Control from 2001 to 2015 to determine the onset of TB after cancer. The cancer patients were then followed up until 2017 to assess their survival status. The Kaplan-Meier method, log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves, compare various survival distributions, and adjusted hazard ratios. RESULTS: Lung, head and neck, and liver cancers led to a  significantly different survival time between patients with and without co-morbid TB. After adjustment, it was found that patients suffering from lung, head and neck, or liver cancer and co-morbid TB had significantly lower risk of death than those without co-morbid TB. Based on the stratified analysis, lung cancer patients with distant metastasis and co-morbid TB had 3.01-fold and 2.99-fold significantly increased risk of death compared to those without co-morbid TB. CONCLUSION: We found that cancer patients with co-morbid TB were at lower risk of death compared with those without co-morbid TB. In addition to cancer stage, it seems that cancer comorbidity with TB could modify the risk of death for lung cancer patients.There is a need for further studies to support our findings including other related risk factors. 
.


Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Neoplasias Pulmonares/mortalidade , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose/mortalidade , Idoso , Comorbidade , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Tailândia/epidemiologia , Tuberculose/complicações , Tuberculose/epidemiologia , Tuberculose/patologia
18.
Sci Rep ; 11(1): 16624, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404835

RESUMO

Tuberculosis (TB) incidence and mortality rates are still high in Sub-Saharan Africa, and the knowledge about the current patterns is valuable for policymaking to decrease the TB burden. Based on the Global Burden of Disease (GBD) study 2019, we used a Joinpoint regression analysis to examine the variations in the trends of TB incidence and mortality, and the age-period-cohort statistical model to evaluate their risks associated with age, period, and cohort in males and females from Cameroon (CAM), Central African Republic (CAR), Chad, and the Democratic Republic of the Congo (DRC). In the four countries, TB incidence and mortality rates displayed decreasing trends in men and women; except for the males from DRC that recorded an almost steady pattern in the trend of TB incidence between 1990 and 2019. TB incidence and mortality rates decreased according to the overall annual percentage changes over the adjusted age category in men and women of the four countries, and CAM registered the highest decrease. Although TB incidence and mortality rates increased with age between 1990 and 2019, the male gender was mainly associated with the upward behaviors of TB incidence rates, and the female gender association was with the upward behaviors of TB mortality rates. Males and females aged between 15-54 and 15-49 years old were evaluated as the population at high risks of TB incidence and mortality respectively in CAM, CAR, Chad, and DRC. The period and cohort relative risks (RRs) both declined in men and women of the four countries although there were some upward behaviors in their trends. Relatively to the period and cohort RRs, females and males from CAM recorded the most significant decrease compared to the rest of the countries. New public health approaches and policies towards young adults and adults, and a particular focus on elderlies' health and life conditions should be adopted in CAM, CAR, DRC, and Chad to rapidly decrease TB incidence and mortality in both genders of the four countries.


Assuntos
Tuberculose/epidemiologia , Adulto , África Central/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tuberculose/mortalidade , Adulto Jovem
19.
Sci Rep ; 11(1): 15894, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354135

RESUMO

In 2011, the South African HIV treatment eligibility criteria were expanded to allow all tuberculosis (TB) patients lifelong ART. The impact of this change on TB mortality in South Africa is not known. We evaluated mortality in all adults (≥ 15 years old) treated for drug-susceptible TB in South Africa between 2009 and 2016. Using a Cox regression model, we quantified risk factors for mortality during TB treatment and present standardised mortality ratios (SMR) stratified by year, age, sex, and HIV status. During the study period, 8.6% (219,618/2,551,058) of adults on TB treatment died. Older age, male sex, previous TB treatment and HIV infection (with or without the use of ART) were associated with increased hazard of mortality. There was a 19% reduction in hazard of mortality amongst all TB patients between 2009 and 2016 (adjusted hazard ratio: 0.81 95%CI 0.80-0.83). The highest SMR was in 15-24-year-old women, more than double that of men (42.3 in 2016). Between 2009 and 2016, the SMR for HIV-positive TB patients increased, from 9.0 to 19.6 in women, and 7.0 to 10.6 in men. In South Africa, case fatality during TB treatment is decreasing and further interventions to address specific risk factors for TB mortality are required. Young women (15-24-year-olds) with TB experience a disproportionate burden of mortality and interventions targeting this age-group are needed.


Assuntos
Coinfecção/mortalidade , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Coinfecção/complicações , Coinfecção/microbiologia , Feminino , Infecções por HIV/complicações , HIV-1/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Estudos Retrospectivos , Fatores de Risco , África do Sul/epidemiologia , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade
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