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Nontuberculous mycobacteria (NTM) are emerging as notable causative agents of opportunistic infections. To examine clinical significance, species distribution, and temporal trends of NTM in Denmark, we performed a nationwide register-based study of all unique persons with NTM isolated in the country during 1991-2022. We categorized patients as having definite disease, possible disease, or isolation by using a previously validated method. The incidence of pulmonary NTM increased throughout the study period, in contrast to earlier findings. Mycobacterium malmoense, M. kansasii, M. szulgai, and M. avium complex were the most clinically significant species based on microbiologic findings; M. avium dominated in incidence. This study shows the need for surveillance for an emerging infection that is not notifiable in most countries, provides evidence to support clinical decision-making, and highlights the importance of not considering NTM as a single entity.
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Infecciones por Mycobacterium no Tuberculosas , Micobacterias no Tuberculosas , Humanos , Relevancia Clínica , Dinamarca/epidemiología , Historia del Siglo XX , Historia del Siglo XXI , Incidencia , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/clasificación , Sistema de RegistrosRESUMEN
BACKGROUND: There is limited knowledge about non-tuberculous mycobacteria (NTM) infections in migrants. We aimed to assess the incidence and clinical significance of NTM among migrants in Denmark. METHOD: Nationwide register-based cohort study of migrants with a positive NTM culture in Denmark from 1991 through 2021, stratified by patient demographics, disease localisation, species, and clinical significance. RESULTS: 433 migrants had a positive NTM culture, resulting in an overall incidence rate (IR) of 3.7 (95%CI 3.3-4.0) per 100,000 migrants. Overall NTM IRs for definite disease were 1.0 (95%CI 0.9-1.2), possible disease 1.0 (95%CI 0.8-1.2), and isolation 1.7 (95%CI 1.4-1.9) per 100,000 migrants. Migrants had considerably higher age- and sex-adjusted NTM IRs of positive cultures (incidence rate ratio [IRR] = 2.1, 95%CI 1.9-2.3, p < 0.001), possible disease (IRR = 2.4, 95%CI 2.0-3.0, p < 0.001), and isolation (IRR = 4.6, 95%CI 3.9-5.4, p < 0.001) compared to Danish-born, but not of definite disease (IRR = 1.1, 95%CI 0.9-1.3, p = 0.562). IRs of migrants with positive NTM cultures did not increase over time (-0.8 %/year, p = 0.133). CONCLUSIONS: Migrants have a higher, but stable, burden of NTM compared with Danish-born. The higher rates likely reflect that more specimens are examined for Mycobacterium tuberculosis. Microbiologically classified definite NTM disease is not substantially more common among migrants.
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INTRODUCTION: The clinical relevance of Mycobacterium malmoense isolation from pulmonary specimens has been considered high compared with other non-tuberculous mycobacteria. In this study, we aimed to analyse all published clinical data of patients with M. malmoense isolation to investigate the clinical spectrum, relevance, and outcomes of infections with this uncommon mycobacterium. METHODS: A systematic review of PubMed, Web of Science, Embase, and Scopus was performed to identify all clinical data about M. malmoense. Random effects meta-analyses of proportions were calculated for clinical relevance, treatment success, and mortality, as well as for other clinical characteristics. A logistic regression analysis, investigating predictors of mortality, as well as Kaplan-Meier survival analyses, were performed. RESULTS: One hundred and eighty eight patients with individual data from 112 articles and 671 patients with pooled data from 12 articles were included in the meta-analyses. Of patients with individual data, pulmonary infection was the most common manifestation (n = 106/188, 56.4%). One third (n = 61/188, 32.4%) suffered from isolated extra-pulmonary and 21/188 (11.2%) from disseminated disease. In 288 patients with pooled data and pulmonary affection, clinical relevance was high with 68% (95% CI 44-85%) of patients fulfilling criteria for clinical disease. Macrolide and rifamycin-containing regimens were associated with improved survival (adjusted OR 0.12, 95% CI 0.03-0.42, p = 0.002, and 0.23, 95% CI 0.04-0.86, p = 0.03, for lethal events, respectively). CONCLUSION: In this study, we provide a detailed clinical description of M. malmoense infections. The pathogen is of high clinical relevance for the individual patient with more than 2 out of 3 patients having relevant disease and >40% of manifestations being extra-pulmonary or disseminated. Macrolide and rifamycin-containing regimens are associated with improved survival.
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Infecciones por Mycobacterium no Tuberculosas , Humanos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/mortalidad , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Antibacterianos/uso terapéutico , Masculino , Femenino , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/efectos de los fármacos , Adulto , Persona de Mediana Edad , Anciano , Mycobacterium/aislamiento & purificación , Mycobacterium/efectos de los fármacos , Mycobacterium/clasificaciónRESUMEN
Infection with Mycobacterium tuberculosis remains one of the biggest causes of death from a single microorganism worldwide, and the continuous emergence of drug resistance aggravates our ability to cure the disease. New improved resistance detection methods are needed to provide adequate treatment, such as whole genome sequencing (WGS), which has been used increasingly to identify resistance-conferring mutations over the last decade. The steadily increasing knowledge of resistance-conferring mutations increases our ability to predict resistance based on genomic data alone. This study evaluates the performance of WGS to predict M. tuberculosis complex resistance. It compares WGS predictions with the phenotypic (culture-based) drug susceptibility results based on 20 years of nationwide Danish data. Analyzing 6,230 WGS-sequenced samples, the sensitivities for isoniazid, rifampicin, ethambutol, and pyrazinamide were 82.5% [78.0%-86.5%, 95% confidence interval (CI)], 97.3% (90.6%-99.7%, 95% CI), 58.0% (43.2%-71.8%, 95% CI), and 60.5% (49.0%-71.2%, 95% CI), respectively, and specificities were 99.8% (99.7%-99.9%, 95% CI), 99.8% (99.7%-99.9%, 95% CI), 99.4% (99.2%-99.6%, 95% CI), and 99.9% (99.7%-99.9%, 95% CI), respectively. A broader range of both sensitivities and specificities was observed for second-line drugs. The results conform with previously reported values and indicate that WGS is reliable for routine resistance detection in resource-rich tuberculosis low-incidence and low-resistance settings such as Denmark.
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Antituberculosos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis , Secuenciación Completa del Genoma , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Dinamarca/epidemiología , Antituberculosos/farmacología , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Isoniazida/farmacología , Etambutol/farmacología , Rifampin/farmacología , Pirazinamida/farmacología , Pirazinamida/uso terapéutico , Mutación , Farmacorresistencia Bacteriana Múltiple/genética , Genoma Bacteriano/genéticaRESUMEN
BackgroundDenmark possesses an exceptional historical data collection on tuberculosis (TB) from 1876 to the present, providing a unique opportunity to assess TB epidemiology over 147 years in Denmark.AimOur aim was to describe the TB disease burden in Denmark in relation to historical events, living conditions and health interventions during the past 147 years.MethodsWe performed a nationwide register-based ecological study including all persons with TB in Denmark from 1876 through 2022, correlating the TB incidence to social, economic and health indicators.ResultsIn Denmark, the overall TB incidence and mortality declined markedly over the past 147 years, only marginally influenced by specific TB interventions such as sanatoria, Bacillus Calmette-Guèrin (BCG) vaccination, mass screenings and antibiotics. Parallel to this decline, the country experienced improved living conditions, as illustrated by decreased infant mortality and increased life expectancy and wealth. In 1978, Denmark became a low-incidence country for TB with risk groups predominantly affected, and with a continuous change in demographics towards fewer Danish-born cases and relatively more migrant cases.ConclusionsThe decline over time in TB incidence and mortality in Denmark preceded specific TB interventions and can, first of all, be attributed to improved living conditions. TB has now become a rare disease in Denmark, predominantly occurring in particular risk groups. Future elimination of TB will require a combination of specific health interventions in these risk groups combined with a continued focus on improving socioeconomic status and living conditions.
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Sistema de Registros , Tuberculosis , Humanos , Dinamarca/epidemiología , Incidencia , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Femenino , Masculino , Historia del Siglo XX , Historia del Siglo XIX , Historia del Siglo XXI , Adulto , Persona de Mediana Edad , Lactante , Factores Socioeconómicos , Tamizaje Masivo , Anciano , Esperanza de Vida , Adolescente , Vacuna BCG/administración & dosificación , Factores de Riesgo , Preescolar , Adulto Joven , Niño , Vigilancia de la PoblaciónRESUMEN
In this case report, we present case reports for two nurses, both working in departments of respiratory medicine, who developed tuberculosis (TB). For each individual case, whole genome sequencing (WGS) revealed only one specific match within a genomic distance of <6 single-nucleotide polymorphisms. The subsequent epidemiological investigations confirmed that both nurses had relevant exposures to their corresponding match 1139 and 1704 days before presenting with TB symptoms, respectively. Twenty-two studies were identified that reported using genotyping to identify occupational transmission of Mycobacterium tuberculosis to healthcare workers. Only two studies applied WGS, both conducted in resource-rich countries, comparable to the present Danish investigation. When comparing the two WGS studies to the other studies that used older genotyping techniques, WGS provided a higher resolution and much more detailed information. Consequently, the epidemiological investigations were more straightforward. In conclusion, WGS is a powerful tool for determining whether M. tuberculosis transmission is occupational as demonstrated for the two cases in this study.
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Mycobacterium tuberculosis , Tuberculosis , Secuenciación Completa del Genoma , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Femenino , Tuberculosis/transmisión , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Tuberculosis/epidemiología , Adulto , Personal de Salud , Polimorfismo de Nucleótido Simple , Persona de Mediana Edad , Masculino , Enfermedades Profesionales/microbiología , Enfermedades Profesionales/diagnóstico , Transmisión de Enfermedad Infecciosa de Paciente a Profesional , Genotipo , Exposición ProfesionalRESUMEN
OBJECTIVES: We evaluated the ability of FluoroType MTBDR version 2 (FTv2; Hain Lifescience), a second-step real-time PCR assay, to simultaneously detect Mycobacterium tuberculosis complex (MTBC) DNA and mutations conferring resistance to rifampicin (RIF) and isoniazid (INH), in pulmonary and extrapulmonary samples from patients and compared them with corresponding cultures. METHODS: FTv2 MTBC was evaluated on 1815 and 432 samples from Denmark (DK) and Germany (DE), respectively. RIF and INH resistance mutations were assessed in the German samples and 110 samples from Sierra Leone and subsequently compared to phenotypic antimicrobial susceptibility testing and a composite reference DNA (CRD) based on the GenoType MTBDR line-probe assay and Sanger sequencing or whole-genome sequencing. RESULTS: Of the 584 (557 smear-negative) Danish and 277 (85 smear-negative) German sputum samples, 42 (16) and 246 (54) were culture positive, and 44 (18) and 222 (35) were FTv2 positive, providing an FTv2 sensitivity and specificity of 0.86 (0.63) and 0.98 (DK), 0.90 (0.65) and 1.00 (DE), respectively. The count, sensitivities, and specificities for all pulmonary samples were 1434, 0.79, and 0.99 (DK) and 347, 0.86, and 1.00 (DE), respectively; for extrapulmonary samples, 381, 0.33, 0.99 (DK) and 83, 0.50, and 1.00 (DE). The valid count, sensitivity, and specificity compared with CRD for detecting resistance mutations were RIF 355, 0.99, 0.96, and INH 340, 1.00, and 0.98, respectively. DISCUSSION: FTv2 reliably detects MTBC DNA in pulmonary and extrapulmonary samples and detects resistance mutations for INH and RIF resistance in inhA promoter, katG, and rpoB genes.
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Isoniazida , Mutación , Mycobacterium tuberculosis , Rifampin , Tuberculosis Resistente a Múltiples Medicamentos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Humanos , Alemania , Dinamarca , Sierra Leona , Rifampin/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Isoniazida/farmacología , Antituberculosos/farmacología , Pruebas de Sensibilidad Microbiana , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/diagnóstico , Proteínas Bacterianas/genética , Sensibilidad y Especificidad , Esputo/microbiología , ARN Polimerasas Dirigidas por ADN/genéticaRESUMEN
BackgroundTuberculosis (TB) elimination requires identifying and treating persons with TB infection (TBI).AimWe estimate the prevalence of positive interferon gamma release assay (IGRA) tests (including TB) and TBI (excluding TB) in Denmark based on TBI screening data from patients with inflammatory bowel disease (IBD) or inflammatory rheumatic disease (IRD).MethodsUsing nationwide Danish registries, we included all patients with IBD or IRD with an IGRA test performed between 2010 and 2018. We estimated the prevalence of TBI and positive IGRA with 95% confidence intervals (CI) in adolescents and adults aged 15-64 years after sample weighting adjusting for distortions in the sample from the background population of Denmark for sex, age group and TB incidence rates (IR) in country of birth.ResultsIn 13,574 patients with IBD or IRD, 12,892 IGRA tests (95.0%) were negative, 461 (3.4%) were positive and 221 (1.6%) were indeterminate, resulting in a weighted TBI prevalence of 3.2% (95% CI: 2.9-3.5) and weighted positive IGRA prevalence of 3.8% (95% CI: 3.5-4.2) among adults aged 15-64 years in the background population of Denmark. Unweighted TBI prevalence increased with age and birthplace in countries with a TB IR higher than 10/100,000 population.ConclusionEstimated TBI prevalence is low in Denmark. We estimate that 200,000 persons have TBI and thus are at risk of developing TB. Screening for TBI and preventive treatment, especially in persons born in high TB incidence countries or immunosuppressed, are crucial to reduce the risk of and eliminate TB.
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Enfermedades Inflamatorias del Intestino , Tuberculosis Latente , Tuberculosis , Adulto , Adolescente , Humanos , Estudios Transversales , Prueba de Tuberculina/métodos , Prevalencia , Estudios Retrospectivos , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Tuberculosis Latente/diagnóstico , Ensayos de Liberación de Interferón gamma/métodos , Dinamarca/epidemiologíaRESUMEN
The number of patients with drug-resistant tuberculosis (DR-TB) is increasing worldwide. This review summarises the global epidemiology of DR-TB and current treatment challenges. Luckily, novel regimens comprising bedaquiline, pretomanid, linezolid, and moxifloxacin have seemingly mitigated the global threat posed by DR-TB. However, emerging resistance against bedaquiline and pretomanid, among other factors, persists as ongoing concerns in the global fight against DR-TB. While the new regimens are groundbreaking, the sustained development of novel drugs targeting the most resistant forms of tuberculosis is of utmost importance for future efforts against DR-TB.
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Nitroimidazoles , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , LinezolidRESUMEN
Background: Poor glycemic control during tuberculosis (TB) treatment is challenging, as the optimum treatment strategy remains unclear. We assessed hyperglycemia severity using glycated hemoglobin (HbA1c) test and predictors of severe hyperglycemia at the time of TB diagnosis in three resources-diverse regions in Tanzania. Methods: This was a substudy from a large cohort study implemented in three regions of Tanzania. TB individuals with diabetes mellitus (DM) (prior history of DM or newly diagnosed DM) were assessed for hyperglycemic levels using HbA1c test and stratified as mild (<53 mmol/mol), moderate (≥53-<86 mmol/mol), and severe (≥86 mmo/mol). Results: From October 2019 to September 2020, 1344 confirmed TB individuals were screened for DM and 105 (7.8%) individuals had dual TB/DM and were assessed for glycemic levels. Of these, 69 (67.7%) had a prior history of DM and 26 (24.8%) were living with human immunodeficiency virus. Their mean age was 49.0 (±15.0) years and 56.2% were male. The majority (77.1%) had pulmonary TB, and 96.2% were newly diagnosed TB individuals. HbA1c test identified 41(39.0%), 37 (35.2%), and 27 (25.7%) individuals with severe, moderate, and mild the hyperglycaemia respectively. Female sex (odds ratio [OR]: 3.55, 95% confidence interval [CI]: 1.06-11.92, P = 0.040) and previous history of DM (OR: 3.71, 95% CI: 1.33-10.33, P = 0.013) were independent risk factors for severe hyperglycemic at the time of TB diagnosis. Conclusion: By integrating early HbA1c testing, a substantial proportion of individuals with severe hyperglycemia were identified. HbA1c testing can be recommended to identify and triage patients requiring personalized intensified DM management in resource-limited programmatic settings.
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Diabetes Mellitus , Hiperglucemia , Tuberculosis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemoglobina Glucada , Sistemas de Atención de Punto , Estudios de Cohortes , Tanzanía/epidemiología , Diabetes Mellitus/diagnóstico , Tuberculosis/complicaciones , Tuberculosis/diagnóstico , Hiperglucemia/diagnósticoRESUMEN
Background: Many evidence-based health interventions, particularly in low-income settings, have failed to deliver the expected impact. We designed an Adaptive Diseases Control Expert Programme in Tanzania (ADEPT) to address systemic challenges in health care delivery and examined the feasibility, acceptability and effectiveness of the model using tuberculosis (TB) and diabetes mellitus (DM) as a prototype. Methods: This was an effectiveness-implementation hybrid type-3 design that was implemented in Dar es Salaam, Iringa and Kilimanjaro regions. The strategy included a stepwise training approach with web-based platforms adapting the Gibbs' reflective cycle. Health facilities with TB services were supplemented with DM diagnostics, including glycated haemoglobin A1c (HbA1c). The clinical audit was deployed as a measure of fidelity. Retrospective and cross-sectional designs were used to assess the fidelity, acceptability and feasibility of the model. Results: From 2019-2021, the clinical audit showed that ADEPT intervention health facilities more often identified median 8 (IQR 6-19) individuals with dual TB and DM, compared with control health facilities, median of 1 (IQR 0-3) (p = 0.02). Likewise, the clinical utility of HbA1c on intervention sites was 63% (IQR:35-75%) in TB/DM individuals compared to none in the control sites at all levels, whereas other components of the standard of clinical management of patients with dual TB and DM did not significantly differ. The health facilities showed no difference in screening for additional comorbidities such as hypertension and malnutrition. The stepwise training enrolled a total of 46 nurse officers and medical doctors/specialists for web-based training and 40 (87%) attended the workshop. Thirty-one (67%), 18 nurse officers and 13 medical doctors/specialists, implemented the second step of training others and yielded a total of 519 additional front-line health care workers trained: 371 nurses and 148 clinicians. Overall, the ADEPT model was scored as feasible by metrics applied to both front-line health care providers and health facilities. Conclusions: It was feasible to use a stepwise training and clinical audit to support the integration of TB and DM management and it was largely acceptable and effective in differing regions within Tanzania. When adapted in the Tanzania health system context, the model will likely improve quality of services.
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Diabetes Mellitus , Enfermedades no Transmisibles , Tuberculosis , Humanos , Estudios Transversales , Hemoglobina Glucada , Estudios Retrospectivos , Tanzanía/epidemiología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Tuberculosis/epidemiología , Tuberculosis/terapia , Instituciones de Salud , Atención a la SaludRESUMEN
INTRODUCTION: Historically, extensively drug-resistant tuberculosis has been notoriously difficult to treat with devasting outcomes. As we are coming to the end of an era where the 2006 extensively drug-resistant tuberculosis definitions and old treatment regimens are being replaced, we aimed to estimate the proportion of extensively drug-resistant tuberculosis patients globally who achieved successful treatment outcomes. METHODS: We conducted a systematic review of PubMed/MEDLINE, Scopus, Web of Science, and Embase from January 1, 2005, through April 3, 2023. Included studies reported WHO treatment outcomes, or adaptions hereof, for pre-extensively and/or extensively drug-resistant tuberculosis patients according to the 2006 WHO definition. Eligible studies included cohorts of at least 10 adults (aged>18 years) that were not pregnant. Using a random-effects model, we calculated pooled proportions of treatment outcomes and performed sensitivity and subgroup analyses. PROSPERO registration number: CRD42022340961. RESULTS: Among 5056 studies reviewed, we identified 94 studies from 26 countries, involving 10,223 extensively drug-resistant tuberculosis patients. The pooled proportion of successful treatment outcomes was 44.2% (95%CI: 38.3-50.3). Sensitivity analyses consistently produced similar estimates. A slight improvement in treatment outcomes was observed after 2013. Furthermore, 25 studies reported outcomes for 3564 individuals with pre-extensively drug-resistant tuberculosis, of which 63.3% achieved successful treatment (95%CI: 43.1-72.5). CONCLUSION: Globally, the success rate of extensively drug-resistant tuberculosis treatment is 44.2%, far below the WHO's target rate of 75%. These results may serve as a reference for future studies assessing extensively drug-resistant tuberculosis treatment outcomes under the 2021 definition treated with better treatment regimens available. Comprehensive surveillance data of extensively drug-resistant tuberculosis outcomes from the whole world are desirable to monitor treatment progress.
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Tuberculosis Extensivamente Resistente a Drogas , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis Pulmonar , Humanos , Adulto , Embarazo , Femenino , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Antituberculosos/uso terapéuticoRESUMEN
OBJECTIVES: This study aimed to analyze mortality, risk factors, and causes of death among people with tuberculosis (TB). METHODS: This is a population-based cohort study with patients with TB ≥18 years notified from 1990 to 2018 in Denmark, compared with sex- and age-matched controls. Mortality was assessed in Kaplan-Meier models and risk factors for death were estimated in Cox proportional hazards models. RESULTS: Overall mortality was twofold higher among people with TB compared with controls up to 15 years after TB diagnosis (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 2.06-2.29, P <0.0001). Danes with TB were three times more likely to die than migrants (adjusted HR: 3.13, 95% CI: 2.84-3.45, P <0.0001). Risk factors for death included living alone, being unemployed, having low income, and comorbidities such as mental illness with substance abuse, lung diseases, hepatitis, and HIV. TB was the most common cause of death (21%), followed by chronic obstructive pulmonary disease (7%), lung cancer (6%), alcoholic liver disease (5%), and mental illness with substance abuse (4%). CONCLUSION: People with TB had substantially inferior survival up to 15 years after TB diagnosis, in particular, socially disadvantaged Danes with TB with specific comorbidities. This may reflect unmet needs for enhanced treatment of other medical/social conditions during TB treatment.
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Tuberculosis , Humanos , Causas de Muerte , Estudios de Cohortes , Tuberculosis/epidemiología , Factores de Riesgo , Comorbilidad , Modelos de Riesgos Proporcionales , Estudios RetrospectivosAsunto(s)
Trastornos Mentales , Trastornos Relacionados con Sustancias , Tuberculosis , Humanos , Trastornos Mentales/complicaciones , Trastornos Mentales/epidemiología , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/epidemiología , Tuberculosis/epidemiologíaRESUMEN
The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization-defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3-81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1-11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity.
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Tuberculosis Extensivamente Resistente a Drogas , Nitroimidazoles , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Antituberculosos/efectos adversos , Diarilquinolinas/efectos adversos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Nitroimidazoles/efectos adversos , Oxazoles/efectos adversos , Resultado del TratamientoRESUMEN
Introduction: Poor quality of health care services remains an important challenge in health care delivery systems. Here, we validate clinical audit tools and describe audit results of selected clinical standards related to communicable disease (CD) and non-communicable disease (NCD) integration at the primary health care level. Methodology: A multi-methods approach, including a retrospective cohort and cross-sectional design, was deployed concurrently at Health Centres. Separate evaluators assessed the Health Centres using an audit tool and the inter-rater/inter-observer reliability was estimated. The extent of adherence to clinical standards was measured in proportions for: infection prevention control, tuberculosis (TB) diagnosis including advanced TB/Human Immunodeficiency Virus (HIV), the diagnosis of chronic lung diseases, and the bidirectional screening and clinical management of TB and Diabetes Mellitus (DM). Results: The inter-rater reliability for the clinical audit tools based on 130 individuals' charts was 99.5% (CI:99-100). The total estimated maximum score for infection prevention control was 114 and on average health centres scored 42 (37%). Only 3 (4%) of 80 individuals' medical charts with unexplained productive cough were evaluated for TB. None of the 24 individuals with HIV infection medical charts had vitals measured and only 6 (25%) patients with advanced HIV had a TB test performed, whereas 4 (17%) had a cryptococcal antigen test, and 1 (4%) had a chest radiograph. Also, 24 patients' chart from documented HIV negative with chronic cough had no records of spirometry or peak flowmeter or a chest radiograph. However, a diagnosis of asthma and chronic obstructive pulmonary disease as made in 17 (71%) and 7 (29%), respectively. TB was confirmed for 102 patients among whom only 12(12%) were screened for DM. The DM clinics had no TB presumptive registers. Patients with TB/DM (n=2) had a glycated haemoglobin (HbA1c) measurement done and received appropriate management. Conclusion and recommendation: The developed clinical audit tools were reliable and could contribute to quality measurement for metrics-related integration of CD and NCD in Tanzania. Further investigations will determine if the clinical audit tools widely used in cycles can improve the quality of care in health care delivery systems.
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BACKGROUND: Diabetes mellitus (DM) is a common comorbidity among people with tuberculosis (TB). Despite the availability of guidelines on how to integrate dual TB/DM in Tanzania, the practice of integration at various healthcare levels is unclear. OBJECTIVE: To explore the participants' experiences and perceptions on the pathway towards clinical management of dual TB/DM. METHOD: The research was carried out in Dar es Salaam, Iringa, and Kilimanjaro regions between January and February 2020. A qualitative, in-depth interview approach was used to collect participants' experiences and perspectives on the acquisition of dual TB/DM services at various levels of healthcare facilities. The information gathered were coded and classified thematically. RESULTS: The participants' perception of TB services within the healthcare facilities was positive due to the support they received from the healthcare providers. On the other hand, participants reported difficulty receiving management in various health facilities for each condition in terms of access to dual TB/DM care and access to DM medication. This was viewed as a significant challenge for the participants with dual TB/DM. CONCLUSIONS: The current disjunction and disruption in healthcare for people with dual TB/DM makes it difficult to access services at various levels of health facilities. For optimal clinical management for people with dual TB/DM, patient-centered strategies and integrated approaches are urgently needed.
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Diabetes Mellitus , Tuberculosis , Humanos , Tanzanía/epidemiología , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/terapia , Instituciones de Salud , Personal de SaludRESUMEN
OBJECTIVES: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease. METHODS: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated. RESULTS: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%). CONCLUSION: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.
Asunto(s)
Enfermedades Pulmonares , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Infección por Mycobacterium avium-intracellulare , Neumonía , Humanos , Micobacterias no Tuberculosas , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/microbiología , Enfermedades Pulmonares/epidemiología , Enfermedades Pulmonares/microbiologíaRESUMEN
Objective: To assess the current Tanzania health facilities readiness in integrating clinical management of dual Tuberculosis (TB) and Diabetes Mellitus (DM) by using the Service Availability and Readiness Assessment (SARA) manual of the World Health Organization prior to implementing an integrated service model. Study design: Cross-sectional study. Methods: A needs assessment survey was conducted at varying levels of health care facilities. The SARA manual evaluated the service delivery outcomes in terms of availability of guidelines, medicines and diagnostic equipment, training of healthcare workers in providing TB and DM care, and patient record review. Data were analyzed using Statistical Package for Social Science version 26. Results: Among 29 health facilities selected, three were regional referral hospitals, eight were district hospitals and eighteen were health centers. Baseline investigations revealed that GeneXpert MTB/RIF machines were present in 10 (34.5%) facilities, and glycated hemoglobin devices were present in two (6.9%) facilities, while all health facilities had a glucometer. The presence of an attending medical doctor in 19 (65.5%) facilities and the presence of operating biochemistry analyzers in 15 (51.7%) facilities were two mandatory variables used to assess readiness. Among the various guidelines observed, none of the facilities had the 2016 DM guidelines. Overall, 15 (51.7%) health facilities were ready to integrate dual TB and DM services. Conclusion: Integrative TB/DM screening and management activities can be achieved only if integration initiatives are prioritized at all levels of health facilities and among health policy makers in Tanzania. At least half of the health facilities were prepared to integrate the management of dual TB/DM. However, there is an urgent need to mobilize significant resources to improve the integration in these facilities, such as management guidelines and diagnostics..
RESUMEN
OBJECTIVE: Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. METHODS: A prospective cohort study recruited TB participants receiving anti-TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre-existing DM or pre-treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6 months of TB treatment. RESULTS: Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co-infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR (p > 0.05). Time to death for participants with and without IGR was 18 versus 28 days (p = 0.870), respectively. Age ≥ 40 years (p = 0.038), bacteriological positive (p = 0.039), HIV (p = 0.009), or recurrent TB (p = 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. CONCLUSION: IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co-management of multi-morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.