RESUMO
BACKGROUND: Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB. METHODS: Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992-2014. MIC, pDST, and whole-genome sequencing of the pncA, rpsA, and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses. RESULTS: Of 157 patients with MDR-TB, 56.1% (nâ =â 88) had PZA-resistant strains and 49.7% (nâ =â 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI], .29-.82; P = .007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI, .73-1.31; Pâ =â .89). MIC and gDST for PZA were not associated with treatment outcome. CONCLUSIONS: In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.
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Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Amidoidrolases/genética , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Estudos de Coortes , Humanos , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/genética , Pirazinamida/farmacologia , Pirazinamida/uso terapêutico , Escarro , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
INTRODUCTION: About 90% of active tuberculosis (TB) cases in Sweden are foreign born and are mainly due to latent TB infection (LTBI) reactivation. The aim of this study was to assess the current migrant LTBI screening programme with regards to test results and completion of the care cascade. METHOD: A retrospective cohort of all 14173 individuals attending a health examination was established for the Stockholm Region 2015-2018 through record-linkage of data extracted from the Swedish Migration Authority and medical records. Screening results, referrals to specialist care and treatment initiation were ascertained through automated data extraction for the entire cohort. Detailed cascade steps, including treatment completion, were analysed through manual data extraction for a subsample of all persons referred to specialist care in the period 2016-2017. RESULTS: Of 5470 patients screened with an interferon-gamma release assay (IGRA), 1364 (25%) were positive, of whom 358 (26%) initiated LTBI treatment. An increased trend in IGRA-positivity was seen for increased age and TB-incidence in country of origin. Among the IGRA positive patients, 604 (44%) were referred to specialist care. Lower age was the main referral predictor. In the subsample of 443 patients referred to specialist care in 2016-2017, 386 (87%) were invited, of whom 366 (95%) attended. Of 251 patients (69%) recommended for LTBI treatment, 244 (97%) started such treatment and of those 221 (91%) completed it. CONCLUSION: The low attrition in patient-dependent cascade steps shows that the voluntary approach works well. Low LTBI treatment attainment is due to the current conservative local treatment policy, which means the vast majority are IGRA-tested without an intention to treat for LTBI.
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Tuberculose Latente , Refugiados , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Programas de Rastreamento , Estudos Retrospectivos , Suécia/epidemiologia , Teste TuberculínicoRESUMO
Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy. Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. Results: Of 88â¯159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85â¯836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.
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COVID-19/complicações , Doenças do Recém-Nascido/etiologia , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Adulto , Aleitamento Materno/estatística & dados numéricos , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/mortalidade , Feminino , Idade Gestacional , Mortalidade Hospitalar , Humanos , Hiperbilirrubinemia/epidemiologia , Hiperbilirrubinemia/etiologia , Lactente Extremamente Prematuro , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/mortalidade , Recém-Nascido Prematuro , Tempo de Internação/estatística & dados numéricos , Nascido Vivo/epidemiologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Cuidado Pré-Natal/estatística & dados numéricos , Pontuação de Propensão , Estudos Prospectivos , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/etiologia , Ressuscitação/estatística & dados numéricos , SARS-CoV-2/isolamento & purificação , Suécia/epidemiologiaRESUMO
RATIONALE: Studies investigating the risk of active tuberculosis (TB) in association with pregnancy have not been conclusive. We aimed to investigate this risk in a large retrospective register-based cohort study in Sweden. METHODS: Data from women of 15-49â years of age who had given birth in Sweden between 2005 and 2013 were extracted from the national childbirth register and linked to the national TB register. Cohort time was divided into three exposure periods: during pregnancy, six months (180 days) postpartum and time neither pregnant nor postpartum. We calculated incidence rates (IRs) per 100â000 person-years for each period and incidence rate ratios (IRRs) with IRs neither pregnant nor postpartum as the reference. RESULTS: The cohort included 649â342 women, of whom 553 were registered as cases of active TB, 389 when neither pregnant nor postpartum, 85 during pregnancy and 79 when postpartum. Overall IRs were 9, 12 and 17 cases per 100â000 person-years, respectively, giving IRR 1.4, 95% CI 1.1-1.7 (during pregnancy) and IRR 1.9, 95% CI 1.5-2.5 (when postpartum). Stratification by TB incidence in country of origin showed that the increased risk was concentrated amongst women from countries with a TB incidence of 100 or higher, where IRs per 100â000 person-years were 137 (when neither pregnant nor postpartum), 182 (during pregnancy) and 233 (when postpartum). CONCLUSION: We show a significant increase in risk of active TB during both pregnancy and postpartum in women from high incidence countries and recommend TB screening in pregnant women belonging to this risk group.
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Período Pós-Parto , Tuberculose , Estudos de Coortes , Feminino , Humanos , Incidência , Gravidez , Estudos Retrospectivos , Suécia/epidemiologia , Tuberculose/epidemiologiaRESUMO
BACKGROUND: Minimum inhibitory concentration (MIC) testing, unlike routine drug susceptibility testing (DST) at a single critical concentration, quantifies drug resistance. The association of MICs and treatment outcome in multidrug-resistant (MDR)-tuberculosis patients is unclear. Therefore, we correlated MICs of first- and second-line tuberculosis drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-tuberculosis patients. METHODS: Clinical and demographic data of MDR-tuberculosis patients in Sweden, including DST results, were retrieved from medical records from 1992 to 2014. MIC determinations were performed retrospectively for the stored individual Mycobacterium tuberculosis (Mtb) isolates using broth microdilution in Middlebrook 7H9. We fitted Cox proportional hazard models correlating MICs, DST results, and clinical variables to tSCC and treatment outcome. RESULTS: Successful treatment outcome was observed in 83.5% (132/158) of MDR-tuberculosis patients. Increasing MICs of fluoroquinolones, diabetes, and age >40 years were significantly associated with unsuccessful treatment outcome. Patients treated with pyrazinamide (PZA) had a significantly shorter tSCC compared to patients who were not (median difference, 27 days). CONCLUSIONS: Increasing MICs of fluoroquinolones were correlated with unsuccessful treatment outcome in MDR-tuberculosis patients. Further studies, including MIC testing and clinical outcome data to define clinical Mtb breakpoints, are warranted. PZA treatment was associated with shorter tSCC, highlighting the importance of PZA DST.
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Antituberculosos/farmacologia , Fluoroquinolonas/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Pirazinamida/farmacologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Suécia/epidemiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto JovemRESUMO
The World Health Organization (WHO) recommends that countries implement pharmacovigilance and collect information on active drug safety monitoring (aDSM) and management of adverse events.The aim of this prospective study was to evaluate the frequency and severity of adverse events to anti-tuberculosis (TB) drugs in a cohort of consecutive TB patients treated with new (i.e. bedaquiline, delamanid) and repurposed (i.e. clofazimine, linezolid) drugs, based on the WHO aDSM project. Adverse events were collected prospectively after attribution to a specific drug together with demographic, bacteriological, radiological and clinical information at diagnosis and during therapy. This interim analysis included patients who completed or were still on treatment at time of data collection.Globally, 45 centres from 26 countries/regions reported 658 patients (68.7% male, 4.4% HIV co-infected) treated as follows: 87.7% with bedaquiline, 18.4% with delamanid (6.1% with both), 81.5% with linezolid and 32.4% with clofazimine. Overall, 504 adverse event episodes were reported: 447 (88.7%) were classified as minor (grade 1-2) and 57 (11.3%) as serious (grade 3-5). The majority of the 57 serious adverse events reported by 55 patients (51 out of 57, 89.5%) ultimately resolved. Among patients reporting serious adverse events, some drugs held responsible were discontinued: bedaquiline in 0.35% (two out of 577), delamanid in 0.8% (one out of 121), linezolid in 1.9% (10 out of 536) and clofazimine in 1.4% (three out of 213) of patients. Serious adverse events were reported in 6.9% (nine out of 131) of patients treated with amikacin, 0.4% (one out of 221) with ethionamide/prothionamide, 2.8% (15 out of 536) with linezolid and 1.8% (eight out of 498) with cycloserine/terizidone.The aDSM study provided valuable information, but implementation needs scaling-up to support patient-centred care.
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Antituberculosos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos ProspectivosRESUMO
BACKGROUND: Asylum seekers in Sweden are offered tuberculosis (TB) screening at a voluntary post-arrival health examination. The role of this screening in improving the TB diagnostic pathway has not been previously evaluated. The aim of this study was to determine diagnostic pathways for active TB cases and compare diagnostic delays between different pathways. METHODS: Retrospective review of medical records of patients reported with active TB in Stockholm in 2015, using a structured and pre-coded form. RESULTS: Seventy-one percent of patients actively sought health care due to symptoms. As for source of referral to TB specialist clinic, 15% came from screening of eligible migrants, of whom the majority were asymptomatic. Among asylum seekers, 69% were identified through screening at a health examination (HE). The main sources of referral to TB clinics were emergency departments (27%) and primary health care centers (20%). Median health care provider delay was significantly longer in patients identified through migrant screening in health examination. CONCLUSIONS: Screening at a health examination was the main pathway of active TB detection among mainly asymptomatic and non-contagious asylum seekers but contributed modestly to total overall TB case detection. In these patients TB was diagnosed early in a non-contagious phase of the disease. Further research is required to assess the effectiveness and cost-effectiveness of HE TB screening as well as inclusion of other groups of migrants from high incidence countries in the screening program in terms of impact on delay, transmission and treatment outcomes.
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Diagnóstico Tardio/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Refugiados , Tuberculose/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Refugiados/estatística & dados numéricos , Estudos Retrospectivos , Suécia/epidemiologia , Tuberculose/epidemiologia , Adulto JovemRESUMO
Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30â days, 81.1% and 56.7%, respectively at 60â days; 85.5% and 80.5%, respectively at 90â days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.
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Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Carbapenêmicos/uso terapêutico , Clofazimina/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , Humanos , Linezolida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Retrospectivos , Escarro/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: To estimate the risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) both with and without exposure to biological therapy and to directly compare the risks between therapies. METHODS: Data from the Swedish National Population Registers, Tuberculosis Register and the Swedish Biologics Register were used to conduct a prospective population-based national cohort study (2002-2011). We estimated the rate of incident TB in the general population and in a cohort of biological-naïve and biological-exposed patients diagnosed with RA. Cox models were used to estimate HRs with particular attention to risks by calendar and follow-up time and individual biologics. RESULTS: Compared to the general population, RA patients not exposed to biologicals had a fourfold increased risk of TB (HR 4.2; 95% CI 2.7 to 6.7), which did not decline over calendar time. In contrast, the risk of TB in the biological-exposed RA population decreased since 2002 compared with biological-naïve; from HR=7.9 (95% CI 3.3 to 18.9) in 2002-2006 to HR=2.4 (95% CI 0.9 to 6.1) in 2007-2011. The HRs for most recent exposure to adalimumab and infliximab compared with etanercept were 3.1 (95% CI 0.8 to 12.5) and 2.7 (95% CI 0.7 to 10.9), respectively, and the HR for etanercept compared with biological-naïve RA was 1.7 (95% CI 0.6 to 4.6). CONCLUSIONS: In the past decade, the risk of TB has decreased among biological-exposed RA patients but remains higher than in biological-naïve RA patients. Most cases of TB in RA occur in biological-naïve RA patients, underscoring the elevated risk also in these patients.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Tuberculose/epidemiologia , Adalimumab , Adulto , Idoso , Artrite Reumatoide/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Etanercepte , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Suécia/epidemiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Linezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB). We conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992-2018. Data was collected from medical records. ADRs were classified according to Common Terminology Criteria for Adverse Events (version 5.0). Of all participants (n=132), 43.2% were female and the median age 28 years. The median linezolid treatment was 6.5 months (IQR 3.0-12.7) with a median daily dose of 9.6 mg/kg/day. Any ADR was seen in 58.3% (n=77) of participants, with 35.6% having peripheral neuropathy (n=47), 27.3% anaemia (n=36), 22.0% leukopenia (n=36) while 6.1% (n=8) had optic neuritis. The median time for peripheral neuropathy was 3.6 months (IQR 2.1-5.9) and 8.3 months (6.2-10.7) for optic neuritis. A >2.0 mg/L trough concentration (n=40) was associated with anaemia (p=0.0038) and thrombocytopenia (p=0.009) but not with peripheral neuropathy. In multivariable analysis, a dose ≥12 mg/kg/day was associated with time to peripheral neuropathy (HR 2.89, 95%CI 1.08-7.74, p=0.035), anaemia (HR 6.62, 95%CI 2.22-19.8, p=0.001) and leukopenia (HR 5.23, 95% CI 1.48-18.5, p=0.010). Linezolid ADRs were frequent in a high-resource setting. Structured, regular follow-up for ADRs and adjusting dosing according to body weight followed-up by monitoring of drug concentrations early may reduce toxicity.
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Vaccines against SARS-CoV-2 are highly effective in preventing severe disease and mortality. Although pregnant women are at increased risk of severe COVID-19, vaccination uptake among pregnant women varies. We used the Swedish and Norwegian population-based health registries to identify pregnant women and to investigate background characteristics associated with not being vaccinated. In this study of 164 560 women giving birth between May 2021 and May 2022, 78% in Sweden and 87% in Norway have been vaccinated with at least one dose at delivery. Not being vaccinated while being pregnant was associated with age below 30 years, low education and income level, birth region other than Scandinavia, smoking during pregnancy, not living with a partner, and gestational diabetes. These results can assist health authorities develop targeted vaccination information to diminish vaccination inequality and prevent severe disease in vulnerable groups.
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COVID-19 , Gestantes , Adulto , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Feminino , Humanos , Gravidez , SARS-CoV-2 , Suécia/epidemiologia , VacinaçãoRESUMO
OBJECTIVE: To investigate risk factors and characteristics of active tuberculosis (TB) in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We conducted a population-based case-control study using the Swedish Rheumatology Quality Register, the National Patient Register, and the Tuberculosis Register to identify RA patients with active TB and matched RA controls without TB between 2001-2014. Clinical data were obtained from medical records. TB risk was estimated as adjusted OR (aOR) with 95% CI using univariate and multivariable logistic regression analyses. RESULTS: After validation of diagnoses, the study included 31 RA patients with TB and 122 matched RA controls. All except 3 cases had reactivation of latent TB. Pulmonary TB was most prevalent (84%). Ever use of methotrexate was not associated with increased TB risk (aOR 0.8, 95% CI 0.3-2.0), whereas ever treatment with leflunomide (aOR 6.0, 95% CI 1.5-24.7), azathioprine (aOR 3.8, 95% CI 1.1-13.8), and prednisolone (PSL; aOR 2.4, 95% CI 1.0-6.0) was. There were no significant differences between maximum dose of PSL, treatment duration with PSL before TB, or cumulative dose of PSL the year before TB diagnosis between cases and controls. Obstructive pulmonary disease was associated with an increased TB risk (aOR 3.9, 95% CI 1.5-10.7). CONCLUSION: Several RA-associated factors may contribute to increased TB risk in biologic-naïve patients with RA, making the risk of TB activation difficult to predict in the individual patient. To further decrease TB in patients with RA, the results suggest that screening for latent TB should also be considered in biologic-naïve patients.
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Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Tuberculose , Antirreumáticos/uso terapêutico , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Produtos Biológicos/uso terapêutico , Estudos de Casos e Controles , Humanos , Fatores de Risco , Tuberculose/epidemiologia , Fator de Necrose Tumoral alfaRESUMO
INTRODUCTION: The majority of tuberculosis (TB) cases in Sweden occur among migrants from endemic countries through activation of latent tuberculosis infection (LTBI). Sweden has LTBI-screening policies for migrants that have not been previously evaluated. This study aimed to assess the cost-effectiveness of the current screening strategy in Stockholm. METHODS: A Markov model was developed to predict the costs and effects of the current LTBI-screening program compared to a scenario of no LTBI screening over a 50-year time horizon. Epidemiological and cost data were obtained from local sources when available. The primary outcomes were incremental cost-effectiveness ratio (ICER) in terms of societal cost per quality-adjusted life year (QALY). RESULTS: Screening migrants in the age group 13-19 years had the lowest ICER, 300,082 Swedish Kronor (SEK)/QALY, which is considered cost-effective in Sweden. In the age group 20-34, ICER was 714,527 SEK/QALY (moderately cost-effectives) and in all age groups above 34 ICERs were above 1,000,000 SEK/QALY (not cost-effective). ICER decreased with increasing TB incidence in country of origin. CONCLUSION: Screening is cost-effective for young cohorts, mainly between 13 and 19, while cost-effectiveness in age group 20-34 years could be enhanced by focusing on migrants from highest incidence countries and/or by increasing the LTBI treatment initiation rate. Screening is not cost-effective in older cohorts regardless of the country of origin.
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Tuberculose Latente , Migrantes , Tuberculose , Adolescente , Adulto , Idoso , Análise Custo-Benefício , Humanos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Programas de Rastreamento , Anos de Vida Ajustados por Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: Reports of the outcome of treatment of tuberculosis (TB) disease and infection (TBI) in children are scarce. Since 2010, we routinely use interferon-gamma release assays in addition to clinical history for the exclusion of TBI, although the safety of this approach has been questioned. We present the frequency of recurrent TB or progression to TB after treatment for TB disease or TB infection, respectively, and progression to disease in children considered TB uninfected at our pediatric TB clinic. METHODS: We included 4707 patients from 1990 to 2017. At the initial assessment, 96 (2.0%) had previously received TB treatment, 253 (5.4%) had TB disease, 1625 (35%) had TBI and 2733 (58%) children were considered uninfected. Patients were passively followed at our clinic, at the adult TB clinics in Stockholm and at the Swedish national TB registry. RESULTS: During a median follow-up time of 8.4 years, we found 36 cases of TB disease, with true relapses in 3/243 (1.2%) successfully treated TB patients. Preventive treatment of TBI reduced the risk of progression to TB by 85%, from 4.3% (15/349) to 0.6% (8/1262). In children considered uninfected, the risk of later developing TB was 0.07% (2/2733). CONCLUSIONS: The effectiveness of TB management was acceptable. Our routine procedures for the exclusion of TBI appear safe.
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Antituberculosos/uso terapêutico , Prognóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Recidiva , Suécia/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND AND AIM: Screening for active and latent TB among migrants in low TB incidence countries may constitute an important contribution to TB elimination. E-DETECT TB, a European multi-county collaboration, aims to address the present lack of evidence on effectiveness of migrant TB screening by collating data in an international database and perform cross-country pooled and comparative analyses of screening coverage, results and linkage to care. METHOD: A database was established using migrant TB screening data from participating countries' national screening programs, national screening pilots and local research projects. All partner countries contributed to a common agreed protocol with standardized variables, pooling available numerator and denominator screening data from participating countries and sites. RESULTS: All collaborating members drafted and agreed upon a data sharing accord as well as a protocol that clearly defined responsibilities and data governance principles. The database has been created and data transfer is ongoing. CONCLUSION: By persistence and focus the project has overcome considerable administrative, practical and legal challenges. This international collaboration provides greater power of analysis of harmonized data and thereby a unique opportunity to contribute migrant TB screening evidence. E-DETECT TB has started to invite other countries to contribute data to the database.
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Bases de Dados Factuais , Tuberculose Latente/diagnóstico , Programas de Rastreamento , Migrantes , Tuberculose/diagnóstico , Europa (Continente)/epidemiologia , Humanos , Incidência , Tuberculose Latente/epidemiologia , Tuberculose/epidemiologiaRESUMO
The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries. The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs. Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile. A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019.
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Antituberculosos/efeitos adversos , Diarilquinolinas/efeitos adversos , Nitroimidazóis/efeitos adversos , Oxazóis/efeitos adversos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Diarilquinolinas/administração & dosagem , Quimioterapia Combinada , Estudos de Viabilidade , Feminino , Humanos , Masculino , Nitroimidazóis/administração & dosagem , Oxazóis/administração & dosagem , Projetos Piloto , Tuberculose/tratamento farmacológico , Organização Mundial da SaúdeRESUMO
OBJECTIVE: Rheumatoid arthritis is a risk factor for tuberculosis (TB), particularly following treatment with biologic agents. Since these therapies are increasingly used in ankylosing spondylitis (AS), other types of spondyloarthritis (SpA), and psoriatic arthritis (PsA), we investigated the corresponding TB risks in these patients. METHODS: We identified individuals with AS/SpA/PsA, and non-AS/SpA/PsA comparators by linking Swedish national patient, population, TB, and rheumatology registers, and followed them for TB occurrence. Incidence rates were estimated for biologic-naive and biologic-exposed patients and the comparators. We calculated hazard ratios (HRs), adjusted for age, sex, and country of birth. RESULTS: Included in this study were 38,702 patients with AS/SpA/PsA, and 200,417 persons from the general population. Among the patients, 11 active TB cases were identified, with an incidence rate (per 105 ) of 22 (95% confidence interval [95% CI] 8.3-59.2) for biologic-exposed patients, 2.7 (95% CI 1.3-5.6) for biologic-naive patients, and 2.4 (95% CI 1.8-3.3) for non-AS/SpA/PsA comparators. The adjusted HR comparing biologic-naive patients to the general population was 1.2 (95% CI 0.5-2.7), and 7.5 (95% CI 1.9-29) comparing biologic-exposed to biologic-naive patients. CONCLUSION: Biologic-naive AS/SpA/PsA patients are not at an increased TB risk in Sweden. Following treatment with biologic agents, the risk increased, but the absolute TB risk was low.
Assuntos
Artrite Psoriásica/tratamento farmacológico , Fatores Biológicos/efeitos adversos , Espondilite Anquilosante/tratamento farmacológico , Tuberculose/induzido quimicamente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SuéciaRESUMO
OBJECTIVE: Interferon gamma release assays like Quantiferon Gold In-Tube (QFT) are used to identify individuals infected with Mycobacterium tuberculosis. A dichotomous cut-off (0.35 IU/ml) defines a positive QFT without considering test variability. Our objective was to evaluate the introduction of a borderline range under routine conditions. METHODS: Results of routine QFT samples from Sweden (2009-2014) were collected. A borderline range (0.20-0.99 IU/ml) was introduced in 2010 recommending a follow-up sample. The association between borderline results and incident active TB within 3 to 24 months was investigated through linkage with the national TB-register. RESULTS: Using the recommended QFT cut-off, 75.1% tests were negative, 21.4% positive and 3.5% indeterminate. In total, 9% (3656/40773) were within the borderline range. In follow-up samples, individuals with initial results between 0.20-0.34 IU/ml and 0.35-0.99 IU/ml displayed negative results below the borderline range (<0.20 IU/ml) in 66.1% (230/348) and 42.5% (285/671) respectively, and none developed incident TB. Among 6712 individuals with a positive initial test >0.99 IU/ml, 65 (0.97%) developed incident TB within 3-24 months. CONCLUSIONS: We recommend retesting of subjects with QFT results in the range 0.20-0.99 IU/ml to enhance reliability and validity of the test. Half of the subjects in the borderline range will be negative at a level <0.20 IU/ml when retested and have a very low risk of developing incident active TB.
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Interferon gama/sangue , Tuberculose Latente/diagnóstico , Humanos , Valores de Referência , Reprodutibilidade dos Testes , SuéciaRESUMO
BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) disease remains an important complication of allogeneic stem cell transplantation (SCT). We studied viral load kinetics and correlated the viral load and other transplant factors with the development of CMV disease. DESIGN AND METHODS: We studied 162 consecutive patients who were CMV seropositive or had CMV seropositive donors. Quantification of CMV DNA was performed by real-time polymerase chain reaction. RESULTS: CMV DNA detected was detected in 105 of the 162 patients. The mean peak viral loads were similar at first and subsequent reactivations. The serologic status of the donors and recipients prior to SCT significantly influenced the viral load. The cumulative incidence of CMV disease was 1.8% at 100 days and 6.3% at 365 days after SCT. The peak viral load were higher in patients who developed CMV disease than in patients without CMV disease (log10 3.5; SE +/- 0.26/200,000 cells vs. log10 2.7; SE +/- 0.09/200,000 cells; p=0.02). However, in multivariate analysis, only acute graft-versus-host disease (GVHD) grade II-IV and a graft from a CMV-negative donor to a CMV-positive patient were significant risk factors for CMV disease. In patients who required more than one course of pre-emptive therapy, acute GVHD and the rate of decrease in viral load during first pre-emptive therapy were significant risk factors for subsequent development of CMV disease. INTERPRETATION AND CONCLUSIONS: A decrease in viral load during pre-emptive therapy is an important factor for later development of CMV disease.
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Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Pessoa de Meia-Idade , Infecções Oportunistas , Pré-Medicação , Fatores de Risco , Transplante Homólogo , Carga ViralRESUMO
A real-time TaqMan PCR based on the cytomegalovirus (CMV) polymerase (pol) gene was developed for quantitation of CMV DNA in crude peripheral blood leukocyte (PBL) lysate from stem cell transplantation (SCT) patients. The dynamic range of the assay was between 10 and 4x10(6) copies. Both intra- and inter-assay variability were well within +/-0.25 log10 S.D. Thus, a pooled PBL sample that was used as positive control in 57 consecutive TaqMan PCR runs over 7 months showed a stable CMV quantity (4.12+/-0.13, log10 mean+/-S.D.). The sensitivity of the pol TaqMan PCR was validated by parallel analysis of 177 PBL samples with a nested PCR. The use of crude PBL lysate as PCR input did not cause PCR inhibition. We demonstrated further the clinical utility of the newly developed TaqMan PCR by monitoring changes in CMV levels in eight patients receiving antiviral therapy. This TaqMan PCR was highly sensitive, reproducible, and stable and has served a useful tool for monitoring CMV DNA levels in large number of clinical samples in a routine diagnostic setting for over 1 year.