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1.
Cad Saude Publica ; 37(3): e00112020, 2021.
Artículo en Portugués | MEDLINE | ID: mdl-33852663

RESUMEN

The World Health Organization highlights the importance of health services organization and performance in tuberculosis (TB) control activities. This study aimed to assess the performance of primary healthcare services in Belo Horizonte, Minas Gerais State, Brazil, in TB control activities in the dimensions Structure and Process, before and after the use of a validated instrument called Stratification by Degree of Clinical Risk and Tuberculosis Treatment Dropout (ERTB). This was a descriptive and prospective study with two interviews (455 professionals), the second of which after the ERTB. Performance classification was: ≤ 49.9%, critical; 50-79.9%, unsatisfactory, and ≥ 80%, satisfactory. The comparative assessment used the McNemar statistical test with p < 0.05. After risk stratification, most of the variables in each dimension improved significantly. The authors conclude that it was possible to identify satisfactory performance in most of the variables assessed in the Structure and Process dimensions in primary healthcare services in Belo Horizonte in relation to TB control activities, using a standardized questionnaire.


Asunto(s)
Servicios de Salud , Tuberculosis , Brasil , Humanos , Atención Primaria de Salud , Estudios Prospectivos , Tuberculosis/prevención & control
2.
Eur Rev Med Pharmacol Sci ; 25(7): 3132-3135, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33877682

RESUMEN

OBJECTIVE: Vulnerable populations are being more severely impacted by the ongoing pandemic, and the recent release of vaccines for Coronavirus Disease 19 (COVID-19) may offer them protection. The aim of this study was to investigate the willingness of homeless persons to be vaccinated against COVID-19; secondary aims were to analyze the immunization coverage for other conditions. PATIENTS AND METHODS: The acceptance of COVID-19 vaccine and immunization coverage for other conditions were investigated through a form in 112 persons experiencing homelessness referring to the primary care medical services of the Eleemosynaria Apostolica, Holy See. RESULTS: Most subjects, with a male preponderance, were willing to be vaccinated against COVID-19 (64.3%), 3.6% were unsure and 32.1% preferred not to be vaccinated. When answering questions on the immunization coverage for tuberculosis and hepatitis A and B, most subjects reported not to be vaccinated (48.2%, 56.2% and 55.3%, respectively) or did not know (33%, 28.6% and 27.7%). CONCLUSIONS: A significant portion of our sample declared to be willing to be vaccinated against COVID-19. It would be auspicious that the recent statements from several countries on the importance to extend COVID-19 vaccination to fragile populations be followed by the distribution of the vaccine to these populations.


Asunto(s)
Actitud Frente a la Salud , /prevención & control , Personas sin Hogar , Cobertura de Vacunación/estadística & datos numéricos , Adulto , Anciano , Femenino , Hepatitis A/prevención & control , Vacunas contra la Hepatitis A/uso terapéutico , Hepatitis B/prevención & control , Vacunas contra Hepatitis B/uso terapéutico , Humanos , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/prevención & control , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Roma , Tuberculosis/prevención & control , Vacunas contra la Tuberculosis/uso terapéutico , Adulto Joven
4.
Recurso de Internet en Portugués | LIS - Localizador de Información en Salud | ID: lis-48093

RESUMEN

No marco do Dia Mundial da Tuberculose, nesta quarta-feira (24), a Organização Pan-Americana da Saúde (OPAS) alertou que o diagnóstico de novos casos da doença nas Américas caiu entre 15% e 20% durante 2020 em comparação com o ano anterior devido à pandemia COVID-19, uma situação que põe em risco o progresso em direção ao fim da TB.


Asunto(s)
Tuberculosis/diagnóstico , Américas , Pandemias , Tuberculosis/prevención & control
5.
MMWR Morb Mortal Wkly Rep ; 70(12): 427-430, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33764960

RESUMEN

Although tuberculosis (TB) is curable and preventable, in 2019, TB remained the leading cause of death from a single infectious agent worldwide and the leading cause of death among persons living with HIV infection (1). The World Health Organization's (WHO's) End TB Strategy set ambitious targets for 2020, including a 20% reduction in TB incidence and a 35% reduction in the number of TB deaths compared with 2015, as well as zero TB-affected households facing catastrophic costs (defined as costs exceeding 20% of annual household income) (2). In addition, during the 2018 United Nations High-Level Meeting on TB (UNHLM-TB), all member states committed to setting 2018-2022 targets that included provision of TB treatment to 40 million persons and TB preventive treatment (TPT) to 30 million persons, including 6 million persons living with HIV infection and 24 million household contacts of patients with confirmed TB (4 million aged <5 years and 20 million aged ≥5 years) (3,4). Annual data reported to WHO by 215 countries and territories, supplemented by surveys assessing TB prevalence and patient costs in some countries, were used to estimate TB incidence, the number of persons accessing TB curative and preventive treatment, and the percentage of TB-affected households facing catastrophic costs (1). Globally, TB illness developed in an estimated 10 million persons in 2019, representing a decline in incidence of 2.3% from 2018 and 9% since 2015. An estimated 1.4 million TB-related deaths occurred, a decline of 7% from 2018 and 14% since 2015. Although progress has been made, the world is not on track to achieve the 2020 End TB Strategy incidence and mortality targets (1). Efforts to expand access to TB curative and preventive treatment need to be substantially amplified for UNHLM-TB 2022 targets to be met.


Asunto(s)
Erradicación de la Enfermedad , Salud Global/estadística & datos numéricos , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Objetivos , Humanos , Incidencia , Tuberculosis/mortalidad , Naciones Unidas , Organización Mundial de la Salud
7.
Bull World Health Organ ; 99(1): 34-40, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33716332

RESUMEN

Objective: To describe an intervention to scale up tuberculosis preventive treatment for people living with human immunodeficiency virus (HIV) in South Sudan, 2017-2020. Methods: Staff of the health ministry and United States President's Emergency Plan for AIDS Relief designed an intervention targeting the estimated 30 400 people living with HIV on antiretroviral therapy across South Sudan. The intervention comprised: (i) developing sensitization and operational guidance for clinicians to put tuberculosis preventive treatment delivery into clinical practice; (ii) disseminating monitoring and evaluation tools to document scale-up; (iii) implementing a programmatic pilot of tuberculosis preventive treatment; and (iv) identifying a mechanism for procurement and delivery of isoniazid to facilities dispensing tuberculosis preventive treatment. Staff aggregated routine programme data from facility registers on the numbers of people living with HIV who started on tuberculosis preventive treatment across all clinical sites providing this treatment during July 2019-March 2020. Findings: Tuberculosis preventive treatment was implemented in 13 HIV treatment sites during July-October 2019, then in 26 sites during November 2019-March 2020. During July 2019-March 2020, 6503 people living with HIV started tuberculosis preventive treatment. Conclusion: Lessons for other low-resource settings may include supplementing national guidelines with health ministry directives, clinician guidance and training, and an implementation pilot. A cadre of field supervisors can rapidly disseminate a standardized approach to implementation and monitoring of tuberculosis preventive treatment, and this approach can be used to strengthen other tuberculosis-HIV services. Procuring a reliable and steady supply of tuberculosis preventive treatment medication is crucial.


Asunto(s)
Infecciones por VIH/epidemiología , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Antirretrovirales/administración & dosificación , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Incidencia , Masculino , Proyectos Piloto , Prevalencia , Sudán del Sur/epidemiología
8.
Cell Host Microbe ; 29(2): 158-159, 2021 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-33571443

RESUMEN

A limiting factor in identifying effective tuberculosis (TB) vaccines is our incomplete understanding of correlates of protection. In this issue of Cell Host & Microbe, Esaulova et al. reveal cell types associated with TB containment and disease progression in non-human primates, which may provide immunologic goalposts for vaccine design.


Asunto(s)
Mycobacterium tuberculosis , Vacunas contra la Tuberculosis , Tuberculosis , Animales , Mycobacterium tuberculosis/inmunología , Tuberculosis/prevención & control
9.
BMC Infect Dis ; 21(1): 178, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33588804

RESUMEN

BACKGROUND: Tuberculosis (TB) control relies on early diagnosis and treatment. International guidelines recommend systematic TB screening at health facilities, but implementation is challenging. We investigated completion of recommended TB screening steps in Blantyre, Malawi. METHODS: A prospective cohort recruited adult outpatients attending Bangwe primary clinic. Entry interviews were linked to exit interviews. The proportion of participants progressing through each step of the diagnostic pathway were estimated. Factors associated with request for sputum were investigated using multivariable logistic regression. RESULTS: Of 5442 clinic attendances 2397 (44%) had exit interviews. In clinically indicated participants (n = 445) 256 (57.5%) were asked about cough, 36 (8.1%) were asked for sputum, 21 (4.7%) gave sputum and 1 (0.2%) received same-day results. Significant associations with request for sputum were: any TB symptom (aOR:3.20, 95%CI:2.02-5.06), increasing age (aOR:1.02, 95%CI:1.01-1.04 per year) and for HIV-negative participants only, a history of previous TB (aOR:3.37, 95%CI:1.45-7.81). Numbers requiring sputum tests (26/day) outnumbered diagnostic capacity (8-12/day). CONCLUSIONS: Patients were lost at every stage of the TB care cascade, with same day sputum submission following all steps of the diagnosis cascade achieved in only 4.7% if clinically indicated. Infection control strategies should be implemented, with reporting on early steps of the TB care cascade formalised. High-throughput screening interventions, such as digital CXR, that can achieve same-day TB diagnosis are urgently needed to meet WHO End TB goals.


Asunto(s)
Tamizaje Masivo/estadística & datos numéricos , Tuberculosis/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Femenino , Humanos , Entrevistas como Asunto/estadística & datos numéricos , Modelos Logísticos , Malaui/epidemiología , Masculino , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Estudios Prospectivos , Esputo/microbiología , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Adulto Joven
10.
J Infect Dis ; 223(2): 189-191, 2021 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-33535239

RESUMEN

Developers of severe acute respiratory syndrome coronavirus 2 vaccines should consider some of the lessons from a "new" vaccine introduced in 1921, namely bacille Calmette-Guérin.


Asunto(s)
Vacuna BCG/inmunología , /prevención & control , /inmunología , Animales , Vacuna BCG/administración & dosificación , /virología , Humanos , Pandemias/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Tuberculosis/inmunología , Tuberculosis/prevención & control
11.
Artículo en Inglés | MEDLINE | ID: mdl-33540763

RESUMEN

Tuberculosis (TB) is an infectious communicable disease, which despite global efforts, still needs special attention in regions with difficult access. This study aims to describe the spatial and epidemiological trends of TB incidences from 2013 to 2018 in Marajó Island, the Amazonian region, Pará, Brazil. We have obtained secondary data from the Brazilian TB databases and performed geospatial and statistical analyses on the data for new TB cases, relapses, and re-admissions. From 2013 to 2018, 749 new cases were reported, in which the diagnostics (culture) was not performed for 652 (87.2%) patient samples, the drug resistance test (DST) was performed for nine (1.2%) samples, and one (0.13%) was multidrug-resistant TB (MDR-TB). The rapid molecular testing (RMT) was performed on 40 (5.3%) patient samples, with results indicating that eight (20%) were susceptible to rifampicin and two (5%) were rifampicin resistant. Overall, the cure rate was 449 (66.7%), while relapses and re-admissions were 41 and 44, respectively. On the geospatial distribution, the municipality of Soure stands out with a high number of incidences, relapses, and re-admissions. Spatially, the eight MDR cases were randomly distributed. Our data highlight the urgent need for TB control measures in this region, by introducing the Xpert-Ultra® MTB/RIF (Cepheid, Sunnyvale, CA, USA) and Ogawa-Kudoh.


Asunto(s)
Antibióticos Antituberculosos , Mycobacterium tuberculosis , Tuberculosis , Antibióticos Antituberculosos/uso terapéutico , Brasil/epidemiología , Humanos , Recurrencia Local de Neoplasia , Sensibilidad y Especificidad , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis/prevención & control
12.
ABCS health sci ; 46: e021204, 09 fev. 2021. tab
Artículo en Inglés | LILACS | ID: biblio-1147174

RESUMEN

INTRODUCTION: The Brazilian National Tuberculosis Control Program was created to recommend and direct clinical actions, organizational setting, information systems and surveillance of tuberculosis. The process of implementation of control actions in Primary Care took place in several formats and with different outcomes, due to the influences of local organizational configuration. OBJECTIVE: To identify the facilities and difficulties reported by nurses in the implementation of the Tuberculosis Control Program in Primary Health Care. METHODS: A descriptive cross-sectional study with a quantitative approach, conducted in the city of Natal, Brazil. Data collected from November from 2017 to February 2018, with 80 nurses from Primary Health Care, through a structured questionnaire. Data were categorized according to similarity criteria and analyzed using descriptive statistics. RESULTS: The availability of nurses to work in the program (47.5%) and the presence of materials (31.2%) were the most frequently mentioned facilities. The most frequently mentioned difficulties were: adherence to treatment (21.2%) and the performance of complementary tests (15.0%). CONCLUSION: The findings of the study may contribute to reflection and planning of actions by health teams, as well as a tool for local managers to organize their services, in order to ensure the person with tuberculosis comprehensive care.


INTRODUÇÃO: O Programa Nacional de Controle da Tuberculose Brasileiro foi criado no intuito de preconizar e direcionar ações clínicas, das configurações organizacionais, de sistemas de informações e vigilância da tuberculose. O processo de implantação das ações de controle na Atenção Primária ocorreu em diversos formatos e com resultados diferenciados, devido às influências da configuração organizacionais locais. OBJETIVO: Identificar as facilidades e dificuldades referidas por enfermeiros na implantação do Programa de Controle da Tuberculose na Atenção Primária à Saúde. MÉTODOS: Estudo descritivo, realizado de forma transversal, com abordagem quantitativa, conduzido no município de Natal, a partir de dados coletados entre novembro de 2017 a fevereiro de 2018, com 80 enfermeiros da Atenção Primária à Saúde, mediante questionário estruturado. Os dados foram categorizados de acordo com critérios de semelhança e analisados por meio da estatística descritiva. RESULTADOS: Verificou-se que a disponibilidade do enfermeiro para atuação no programa (47,5%) e a presença de materiais (31,2%) foram as facilidades mais frequentemente referidas. As dificuldades mais referidas foram: adesão ao tratamento (21,2%) e a realização de exames complementares (15,0%). CONCLUSÃO: Os achados do estudo podem contribuir para reflexão e planejamento das ações pelas equipes de saúde, bem como ferramenta para os gestores locais organizarem seus serviços, no intuito de garantir à pessoa com tuberculose um cuidado integral.


Asunto(s)
Humanos , Atención Primaria de Salud , Tuberculosis/prevención & control , Planes y Programas de Salud , Enfermeras y Enfermeros , Evaluación en Salud
14.
Lancet HIV ; 8(1): e8-e15, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33387480

RESUMEN

BACKGROUND: Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups. METHODS: We searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400. FINDINGS: Of 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49-0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43-1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per µL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR. INTERPRETATION: Isoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV. FUNDING: National Institutes of Health and National Institute of Allergy and Infectious Diseases.


Asunto(s)
Profilaxis Antibiótica , Antituberculosos/uso terapéutico , Isoniazida/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & control , Adulto , Antirretrovirales/administración & dosificación , Antituberculosos/administración & dosificación , Antituberculosos/efectos adversos , Recuento de Linfocito CD4 , Coinfección , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Isoniazida/administración & dosificación , Isoniazida/efectos adversos , Masculino , Resultado del Tratamiento
15.
Lancet Infect Dis ; 21(3): 354-365, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33508224

RESUMEN

BACKGROUND: Targeted preventive therapy for individuals at highest risk of incident tuberculosis might impact the epidemic by interrupting transmission. We tested performance of a transcriptomic signature of tuberculosis (RISK11) and efficacy of signature-guided preventive therapy in parallel, using a hybrid three-group study design. METHODS: Adult volunteers aged 18-59 years were recruited at five geographically distinct communities in South Africa. Whole blood was sampled for RISK11 by quantitative RT-PCR assay from eligible volunteers without HIV, recent previous tuberculosis (ie, <3 years before screening), or comorbidities at screening. RISK11-positive participants were block randomised (1:2; block size 15) to once-weekly, directly-observed, open-label isoniazid and rifapentine for 12 weeks (ie, RISK11 positive and 3HP positive), or no treatment (ie, RISK11 positive and 3HP negative). A subset of eligible RISK11-negative volunteers were randomly assigned to no treatment (ie, RISK11 negative and 3HP negative). Diagnostic discrimination of prevalent tuberculosis was tested in all participants at baseline. Thereafter, prognostic discrimination of incident tuberculosis was tested in the untreated RISK11-positive versus RISK11-negative groups, and treatment efficacy in the 3HP-treated versus untreated RISK11-positive groups, during active surveillance through 15 months. The primary endpoint was microbiologically confirmed pulmonary tuberculosis. The primary outcome measures were risk ratio [RR] for tuberculosis of RISK11-positive to RISK11-negative participants, and treatment efficacy. This trial is registered with ClinicalTrials.gov, NCT02735590. FINDINGS: 20 207 volunteers were screened, and 2923 participants were enrolled, including RISK11-positive participants randomly assigned to 3HP (n=375) or no 3HP (n=764), and 1784 RISK11-negative participants. Cumulative probability of prevalent or incident tuberculosis disease was 0·066 (95% CI 0·049 to 0·084) in RISK11-positive (3HP negative) participants and 0·018 (0·011 to 0·025) in RISK11-negative participants (RR 3·69, 95% CI 2·25-6·05) over 15 months. Tuberculosis prevalence was 47 (4·1%) of 1139 versus 14 (0·78%) of 1984 in RISK11-positive compared with RISK11-negative participants, respectively (diagnostic RR 5·13, 95% CI 2·93 to 9·43). Tuberculosis incidence over 15 months was 2·09 (95% CI 0·97 to 3·19) vs 0·80 (0·30 to 1·30) per 100 person years in RISK11-positive (3HP-negative) participants compared with RISK11-negative participants (cumulative incidence ratio 2·6, 95% CI 1·2 to 5·9). Serious adverse events related to 3HP included one hospitalisation for seizures (unintentional isoniazid overdose) and one death of unknown cause (possibly temporally related). Tuberculosis incidence over 15 months was 1·94 (95% CI 0·35 to 3·50) versus 2·09 (95% CI 0·97 to 3·19) per 100 person-years in 3HP-treated RISK11-positive participants compared with untreated RISK11-positive participants (efficacy 7·0%, 95% CI -145 to 65). INTERPRETATION: The RISK11 signature discriminated between individuals with prevalent tuberculosis, or progression to incident tuberculosis, and individuals who remained healthy, but provision of 3HP to signature-positive individuals after exclusion of baseline disease did not reduce progression to tuberculosis over 15 months. FUNDING: Bill and Melinda Gates Foundation, South African Medical Research Council.


Asunto(s)
Antituberculosos/uso terapéutico , Biomarcadores/metabolismo , Isoniazida/uso terapéutico , Rifampin/análogos & derivados , Tuberculosis/prevención & control , Adulto , Esquema de Medicación , Femenino , Seronegatividad para VIH , Humanos , Incidencia , Masculino , Mycobacterium tuberculosis/genética , ARN Bacteriano/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rifampin/uso terapéutico , Sudáfrica/epidemiología , Resultado del Tratamiento , Tuberculosis/epidemiología , Tuberculosis/genética , Tuberculosis/metabolismo , Adulto Joven
17.
Rev Med Suisse ; 17(720-1): 42-49, 2021 Jan 13.
Artículo en Francés | MEDLINE | ID: mdl-33443830

RESUMEN

What's new in infectious diseases in 2020 ? This year has been marked by the COVID-19 pandemic, prompting a review of the current knowledge on SARS-CoV-2 and its management in this article. The results of the Swiss project «â€…PIRATE ¼ indicate non-inferiority between CRP-guided antibiotic durations or fixed 7-day durations and 14-day durations for Gram-negative bacteremia. A Mongolian study did not show any benefit of vitamin D substitution in protecting children from tuberculosis. Baloxavir, a new antiviral against the flu, has been approved by Swissmedic. Finally, new American recommendations for therapeutic monitoring of vancomycin and universal screening for hepatitis C virus have been published.


Asunto(s)
Infectología/tendencias , Antibacterianos/administración & dosificación , Antivirales/uso terapéutico , Proteína C-Reactiva/análisis , Niño , Enfermedades Transmisibles/tratamiento farmacológico , Humanos , Gripe Humana/tratamiento farmacológico , Pandemias , Tuberculosis/prevención & control , Vitamina D/administración & dosificación
18.
Nat Commun ; 12(1): 424, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462224

RESUMEN

There have been notable advances in the development of vaccines against active tuberculosis (TB) disease for adults and adolescents. Using mathematical models, we seek to estimate the potential impact of a post-exposure TB vaccine, having 50% efficacy in reducing active disease, on global rifampicin-resistant (RR-) TB burden. In 30 countries that together accounted for 90% of global RR-TB incidence in 2018, a future TB vaccine could avert 10% (95% credible interval: 9.7-11%) of RR-TB cases and 7.3% (6.6-8.1%) of deaths over 2020-2035, with India, China, Indonesia, Pakistan, and the Russian Federation having the greatest contribution. This impact would increase to 14% (12-16%) and 31% (29-33%) respectively, when combined with improvements in RR-TB diagnosis and treatment relative to a scenario of no vaccine and no such improvements. A future TB vaccine could have important implications for the global control of RR-TB, especially if implemented alongside enhancements in management of drug resistance.


Asunto(s)
Antituberculosos/farmacología , Carga Global de Enfermedades , Profilaxis Posexposición/métodos , Vacunas contra la Tuberculosis/administración & dosificación , Tuberculosis/epidemiología , Adolescente , Adulto , Antituberculosos/uso terapéutico , Simulación por Computador , Farmacorresistencia Bacteriana/inmunología , Humanos , Incidencia , Modelos Estadísticos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Tuberculosis/prevención & control
20.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-33468674

RESUMEN

The global incidence of tuberculosis remains unacceptably high, with new preventative strategies needed to reduce the burden of disease. We describe here a method for the generation of synthetic self-adjuvanted protein vaccines and demonstrate application in vaccination against Mycobacterium tuberculosis Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting adjuvants Pam2Cys-SK4 or Pam3Cys-SK4 These were produced by chemical synthesis using a peptide ligation strategy. The synthetic self-adjuvanting vaccines generated powerful local CD4+ T cell responses against ESAT6 and provided significant protection in the lungs from virulent M. tuberculosis aerosol challenge when administered to the pulmonary mucosa of mice. The flexible synthetic platform we describe, which allows incorporation of adjuvants to multiantigenic vaccines, represents a general approach that can be applied to rapidly assess vaccination strategies in preclinical models for a range of diseases, including against novel pandemic pathogens such as SARS-CoV-2.


Asunto(s)
Mycobacterium tuberculosis/inmunología , Vacunas contra la Tuberculosis/farmacología , Tuberculosis/inmunología , Tuberculosis/prevención & control , Vacunas Conjugadas/farmacología , Adyuvantes Inmunológicos/farmacología , Animales , Antígenos Bacterianos/inmunología , Vacuna BCG/inmunología , Vacuna BCG/farmacología , Proteínas Bacterianas , Linfocitos T CD4-Positivos/inmunología , Modelos Animales de Enfermedad , Femenino , Ratones , Ratones Endogámicos C57BL , Receptor Toll-Like 2/inmunología , Vacunas contra la Tuberculosis/inmunología , Vacunas Conjugadas/inmunología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/farmacología
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