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2.
BMC Infect Dis ; 19(1): 923, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666021

RESUMO

BACKGROUND: Pulmonary tuberculosis (TB) with detectable Mycobacterium tuberculosis in the sputum is a major source of transmission. In resource limited TB endemic settings, cure is declared through sputum smear examination for acid fast bacilli without performing culture. This may lead to erroneous treatment outcomes as viable bacteria may be missed due to the low sensitivity of direct smear method. The aim of this study was to investigate if sterilizing cure is achieved among the new pulmonary TB cases declared cured by sputum smear conversion and to evaluate the impact of addition of ethambutol in the continuation phase in achieving it. METHODS: New sputum smear-positive pulmonary TB patients registered at a tertiary care hospital in Pakistan from November 2013 to March 2014 were followed under standard Directly Observed Treatment Short Course strategy for 6 months. Half of these patients received ethambutol in addition to isoniazid and rifampicin in the continuation phase. Sputum specimens were examined on microscopy at 2 months and at the end of treatment. Sputa of patients with negative direct smear examination at the end of treatment were cultured. RESULTS: Among 5746 TB suspects, 1595 were new sputum smear positive pulmonary TB cases, and 533 were registered at our hospital. Among these, 504 converted sputum negative at 2 months and 348 converted at the end of 6 months of treatment and were declared cured. Sputa of 204/348 patients were cultured, and 12/204 (6%) were culture-positive. Culture positivity at 6 months was not associated with bacterial load, smoking, diabetes, presence of cavities, history of contact with TB patients, age, sex, socioeconomic status, or addition of ethambutol in the continuation phase. CONCLUSION: Viable cultivable bacilli were detected in 6% of cured patients, which would have significant impact on the control of TB. This highlights the need for an inexpensive and accurate surrogate marker for culture as it is not feasible to perform culture in routine for monitoring treatment response in the low-resource settings. The treatment outcome did not improve by addition of ethambutol emphasizing the need to find the optimal duration of treatment for individual or carefully selected groups of patients.


Assuntos
Antituberculosos/uso terapêutico , Etambutol/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adolescente , Adulto , Idoso , Carga Bacteriana , Testes Diagnósticos de Rotina , Quimioterapia Combinada , Feminino , Humanos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Paquistão , Rifampina/uso terapêutico , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico por imagem , Adulto Jovem
3.
BMC Infect Dis ; 19(1): 851, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615439

RESUMO

BACKGROUND: In Lao People's Democratic Republic (PDR), tuberculosis (TB) prevalence was estimated at 540/100,000 in 2011. Nevertheless, little is known about the genetic characteristics and anti-TB drug resistance of the Mycobacterium tuberculosis population. The main objective of this work was to study the genetic characteristics and drug resistance of M. tuberculosis population collected during the first National TB Prevalence Survey (TBPS) of Lao PDR (2010-2011). METHODS: Two hundred and twenty two isolates collected during TBPS (2010-2011) were analyzed with the GenoType MTBDRplus test for M. tuberculosis identification and drug resistance detection. Then, 206 of the 222 isolates were characterized by spoligotyping and MIRU-VNTR typing. RESULTS: Among the 222 M. tuberculosis isolates, 11 were mono-resistant to isoniazid and 2 were resistant to isoniazid and rifampicin (MDR-TB), using the GenoType MTBDRplus test. Among the 202 genetically characterized isolates, the East African-Indian (EAI) family was predominant (76.7%) followed by the Beijing (14.4%) and T (5.5%) families. EAI isolates came from all the country provinces, whereas Beijing isolates were found mainly in the northern and central provinces. A higher proportion of Beijing isolates was observed in people younger than 35 years compared to EAI. Moreover, the percentage of drug resistance was higher among Beijing (17.2%) than EAI (5.2%) isolates, and the two MDR-TB isolates belonged to the Beijing family. Combined analysis of the MIRU-VNTR and spoligotyping results (n = 202 isolates) revealed an estimated clustering rate of 11% and the occurrence of mini-outbreaks of drug-resistant TB caused by Beijing genotypes. CONCLUSIONS: The EAI family, the ancient and endemic family in Asia, is predominant in Lao PDR whereas the prevalence of Beijing, the most harmful M. tuberculosis family for humans, is still low, differently from neighboring countries. However, its association with drug resistance, its presence in young patients and its potential association with recent transmission suggest that the Beijing family could change TB epidemiological pattern in Lao PDR. Therefore, efficient TB control and surveillance systems must be maintained and reinforced to prevent the emergence of highly transmissible and drug-resistant strains in Lao PDR, as observed in neighboring countries.


Assuntos
Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adolescente , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Análise por Conglomerados , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Genótipo , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Laos/epidemiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/isolamento & purificação , Filogenia , Prevalência , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
4.
BMC Public Health ; 19(1): 1329, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640657

RESUMO

BACKGROUND: Uptake of Isoniazid Preventive Therapy (IPT) among People Living with HIV in Zambia has continued to be low despite various evidence for its added benefit in reducing TB incidence and mortality when taken with antiretroviral therapy. In 2017, only 18% of People Living with HIV newly enrolled in care were initiated on IPT in Zambia. MAIN TEXT: Various challenges including policy and management level factors, supply chain factors, health worker perceptions about IPT, monitoring and evaluation factors and limited demand creation activities have constrained the scale up of IPT in Zambia. Lessons that have been learnt while addressing the above challenges are shared and they can be applied by government ministries, project managers, public health specialists to strengthen IPT activities in their settings. CONCLUSION: Zambia has both a high burden of TB and HIV and without preventing new cases of TB from reactivation of latent TB infection, it will be difficult to control TB. All stakeholders involved in prevention of TB among PLHIV need to commit to addressing the challenges limiting scale up of IPT.


Assuntos
Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Tuberculose/prevenção & controle , Feminino , Infecções por HIV/epidemiologia , Humanos , Incidência , Saúde Pública , Tuberculose/epidemiologia , Zâmbia
5.
Internist (Berl) ; 60(11): 1155-1175, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31641790

RESUMO

Tuberculosis is a bacterial infectious disease that is usually transmitted by inhalation of droplets containing the bacteria. The World Health Organization (WHO) estimates that approximately 10 million patients were newly diagnosed with tuberculosis in 2017. Rapid diagnosis relies on a combination of imaging and microbiological, molecular, and, rarely, immunological tests. Genotypic methods enable early diagnosis and allow highly accurate prediction of drug resistance. Phenotypic (culture-based) methods are the diagnostic gold standard. Standard management of patients with pan drug-susceptible pulmonary tuberculosis includes a combination of rifampicin, isoniazid, ethambutol and pyrazinamide for 2 months followed by rifampicin and isoniazid for additional 4 months, which leads to cure rates of >80%. With individualized treatment schemes, similar cure rates can be achieved for patients with multidrug-resistant tuberculosis.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Etambutol/uso terapêutico , Humanos , Isoniazida/uso terapêutico , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
6.
BMJ ; 367: l5894, 2019 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649017

RESUMO

OBJECTIVE: To measure the association between phenotypic drug resistance and the risk of tuberculosis infection and disease among household contacts of patients with pulmonary tuberculosis. SETTING: 106 district health centers in Lima, Peru between September 2009 and September 2012. DESIGN: Prospective cohort study. PARTICIPANTS: 10 160 household contacts of 3339 index patients with tuberculosis were classified on the basis of the drug resistance profile of the patient: 6189 were exposed to drug susceptible strains of Mycobacterium tuberculosis, 1659 to strains resistant to isoniazid or rifampicin, and 1541 to strains that were multidrug resistant (resistant to isoniazid and rifampicin). MAIN OUTCOME MEASURES: Tuberculosis infection (positive tuberculin skin test) and the incidence of active disease (diagnosed by positive sputum smear or chest radiograph) after 12 months of follow-up. RESULTS: Household contacts exposed to patients with multidrug resistant tuberculosis had an 8% (95% confidence interval 4% to 13%) higher risk of infection by the end of follow-up compared with household contacts of patients with drug sensitive tuberculosis. The relative hazard of incident tuberculosis disease did not differ among household contacts exposed to multidrug resistant tuberculosis and those exposed to drug sensitive tuberculosis (adjusted hazard ratio 1.28, 95% confidence interval 0.9 to 1.83). CONCLUSION: Household contacts of patients with multidrug resistant tuberculosis were at higher risk of tuberculosis infection than contacts exposed to drug sensitive tuberculosis. The risk of developing tuberculosis disease did not differ among contacts in both groups. The evidence invites guideline producers to take action by targeting drug resistant and drug sensitive tuberculosis, such as early detection and effective treatment of infection and disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT00676754.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/transmissão , Tuberculose Pulmonar/transmissão , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Busca de Comunicante/métodos , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Peru/epidemiologia , Estudos Prospectivos , Rifampina/farmacologia , Rifampina/uso terapêutico , Escarro/microbiologia , Teste Tuberculínico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
7.
BMC Infect Dis ; 19(1): 914, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664933

RESUMO

BACKGROUND: Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. METHODS: We estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India. RESULTS: 4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86-5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01-2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02-1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13-2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58-5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen. CONCLUSION: Risk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Tuberculose/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Adolescente , Adulto , Antituberculosos/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Seguimentos , Humanos , Incidência , Índia/epidemiologia , Isoniazida/uso terapêutico , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Tuberculose/prevenção & controle , População Urbana , Adulto Jovem
8.
BMC Public Health ; 19(1): 1407, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664978

RESUMO

BACKGROUND: HIV-associated tuberculosis (TB) is a major cause of death among pregnant women in South Africa. Isoniazid prevention therapy (IPT) strategy was implemented in South Africa concurrently with life-long antiretroviral therapy (ART) to reduce the TB-associated morbidity and mortality in individuals living with HIV. This study assessed the extent of the implementation of IPT and the performance of the Mantoux test by geographic settings of health facilities and residences of pregnant women living with HIV in the Eastern Cape, South Africa. METHODS: We conducted a data analysis of 1709 pregnant women enrolled in the new electronic database of the prevention of mother-to-child transmission programme of the East London Prospective Cohort Study. Relevant data on place of residence and antenatal care, performance of the Mantoux test and subsequent initiation of IPT were obtained. Descriptive and inferential statistics were employed to analyse the geographical variations and accessibility to Mantoux test and IPT. RESULTS: The analysis shows that Mantoux test was performed on 803 pregnant women (47%) with significant geographical variation. After controlling for relevant covariates, pregnant women who resided in rural areas (AOR:0.63; CI: 0.47-0.84) compared to those who resided in urban areas were significantly less likely to receive Mantoux test. The rate of uptake of IPT was 79% with significant geographic variations. In the unadjusted model, rural place of residence (UOR:0.68; CI: 0.49-0.96) was independently associated with lower likelihood of uptake of INH prophylaxis; however, the effect was not significant after controlling for important covariates. CONCLUSIONS: The high uptake rate of isoniazid prevention therapy in pregnant women living with HIV at the study sites is commendable; however, concerted efforts are needed to address the inequality gaps in the roll-out of IPT. Poor performance of Mantoux test is a serious concern and requires the attention of TB programme managers and other relevant authorities.


Assuntos
Infecções por HIV/tratamento farmacológico , Disparidades em Assistência à Saúde , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Teste Tuberculínico/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Estudos Prospectivos , África do Sul , Adulto Jovem
9.
West Afr J Med ; 36(3): 283-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622493

RESUMO

BACKGROUND: Latent Tuberculosis (LTBI) affects approximately a third of the world population. Paediatric health workers caring for adolescent Tuberculosis (TB) patients in high TB endemic regions are particularly susceptible as they are exposed to TB in the community and in the work place. However, there is a paucity of reports on LTBI in paediatric health workers. OBJECTIVES: To identify the factors that could have resulted in latent TB in a paediatric health worker Methods/Results: We present a case of a 38-year old female paediatrician who was diagnosed with LTBI by a positive QuantiFERON-TB gold test during the routine new entry immigrant screening for tuberculosis on arrival in the United Kingdom for postgraduate studies. She was treated with three months course of Rifampicin and Isoniazid (plus pyridoxine). CONCLUSION: Latent TB infection may have been acquired from her involvement in the management of adolescents with adult type TB without the use of personal protective equipment. In this case, routine systematic screening of an at risk individual helped to eliminate TB infection. RECOMMENDATION: Paediatric health workers should use personal protective equipment when managing childhood TB and should also be routinely screened for latent TB.


Assuntos
Antituberculosos/uso terapêutico , Pessoal de Saúde , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Mycobacterium tuberculosis/isolamento & purificação , Piridoxina/uso terapêutico , Rifampina/uso terapêutico , Adolescente , Adulto , Técnicas de Laboratório Clínico , Feminino , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Tuberculose Latente/diagnóstico , Exposição Ocupacional , Resultado do Tratamento
10.
N Engl J Med ; 381(14): 1333-1346, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31577875

RESUMO

BACKGROUND: The safety, efficacy, and appropriate timing of isoniazid therapy to prevent tuberculosis in pregnant women with human immunodeficiency virus (HIV) infection who are receiving antiretroviral therapy are unknown. METHODS: In this multicenter, double-blind, placebo-controlled, noninferiority trial, we randomly assigned pregnant women with HIV infection to receive isoniazid preventive therapy for 28 weeks, initiated either during pregnancy (immediate group) or at week 12 after delivery (deferred group). Mothers and infants were followed through week 48 after delivery. The primary outcome was a composite of treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects. The noninferiority margin was an upper boundary of the 95% confidence interval for the between-group difference in the rate of the primary outcome of less than 5 events per 100 person-years. RESULTS: A total of 956 women were enrolled. A primary outcome event occurred in 72 of 477 women (15.1%) in the immediate group and in 73 of 479 (15.2%) in the deferred group (incidence rate, 15.03 and 14.93 events per 100 person-years, respectively; rate difference, 0.10; 95% confidence interval [CI], -4.77 to 4.98, which met the criterion for noninferiority). Two women in the immediate group and 4 women in the deferred group died (incidence rate, 0.40 and 0.78 per 100 person-years, respectively; rate difference, -0.39; 95% CI, -1.33 to 0.56); all deaths occurred during the postpartum period, and 4 were from liver failure (2 of the women who died from liver failure had received isoniazid [1 in each group]). Tuberculosis developed in 6 women (3 in each group); the incidence rate was 0.60 per 100 person-years in the immediate group and 0.59 per 100 person-years in the deferred group (rate difference, 0.01; 95% CI, -0.94 to 0.96). There was a higher incidence in the immediate group than in the deferred group of an event included in the composite adverse pregnancy outcome (stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery, or congenital anomalies in an infant) (23.6% vs. 17.0%; difference, 6.7 percentage points; 95% CI, 0.8 to 11.9). CONCLUSIONS: The risks associated with initiation of isoniazid preventive therapy during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. (Funded by the National Institutes of Health; IMPAACT P1078 TB APPRISE ClinicalTrials.gov number, NCT01494038.).


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/prevenção & controle , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Isoniazida/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Resultado da Gravidez , Tuberculose/prevenção & controle , Adolescente , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Isoniazida/efeitos adversos , Testes de Função Hepática , Período Pós-Parto , Gravidez , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Adulto Jovem
11.
Medicine (Baltimore) ; 98(41): e17523, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593125

RESUMO

Therapeutic drug monitoring has been employed in anti-tuberculosis (TB) drugs to assess optimal dose for maximum therapeutic effects and minimal toxicity. But the determinants of serum concentration need further evidences.In a retrospective case-control study, clinical and laboratory data were collected from 717 in-patients with TB at Xi'an Chest Hospital, China. Two hours serum concentrations of isoniazid, rifampicin, pyrazinamide as well as ethambutol were obtained and analyzed by liquid chromatography-tandem mass spectrometry.The month 2 culture conversion group had lower concentration of isoniazid, pyrazinamide, and ethambutol than month 1 group. Statistical analysis showed that serum concentrations of isoniazid, rifampicin, pyrazinamide, and ethambutol revealed a positive relationship with dose (mg/kg) (P < .001, P < .001, P < .001, and P = .003, respectively). Furthermore, isoniazid concentration was related to smoking (P = .009) and prior TB (P = .011), while rifampicin and pyrazinamide concentrations were correlated to sex (P = .004 and 0.025, respectively). Ethambutol concentration was associated with creatinine clearance (Ccr, P = .002).It is necessary to optimize drug doses using therapeutic drug monitoring while considering the following determinants: weight, smoking status, prior TB, sex, and Ccr. Furthermore, low 2 hours serum concentrations can be associated with longer culture conversion.


Assuntos
Etambutol/sangue , Isoniazida/sangue , Pirazinamida/sangue , Rifampina/sangue , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/sangue , Antituberculosos/metabolismo , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , China/epidemiologia , Cromatografia Líquida/instrumentação , Creatinina/metabolismo , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Etambutol/metabolismo , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/metabolismo , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirazinamida/metabolismo , Pirazinamida/uso terapêutico , Estudos Retrospectivos , Rifampina/metabolismo , Rifampina/uso terapêutico , Fatores Sexuais , Fumar/efeitos adversos , Tuberculose/sangue , Adulto Jovem
12.
BMC Public Health ; 19(1): 1214, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481046

RESUMO

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) in high-risk groups is an effective strategy for TB control and elimination in low incidence settings. A nine-month course of daily isoniazid (INH) has been the longest prescribed therapy; however, completion rates are suboptimal. We need data to guide TB program outreach efforts to optimize LTBI treatment completion rates. METHODS: We pooled seven (2009-2015) years of LTBI treatment outcome data. We computed the probability of INH treatment disruption over time by patient demographic and clinical risk factors. We used log-rank tests and Cox proportional hazards models to assess the risk factors for treatment disruption. RESULTS: We analyzed data from 12,495 persons with complete data on INH treatment initiation. Pediatric cases (0-17 years), recent contacts of active TB patients, and non-U.S.-born adults living in the United States ≤5 years represented 25.2, 13.0, and 59.2% of the study population, respectively. Overall, 48.4% failed to complete therapy. The median treatment duration was 306 days (95% CI: 297, 315). A significant drop in adherence could be observed around day 30 of treatment initiation. Indeed, by day 30 of treatment, 17.0% (95% CI: 16.4, 17.7) of patients had defaulted on therapy. Pediatric patients (HR = 0.83, 95% CI: 0.78, 0.89), recent contacts (HR = 0.74, 95% CI: 0.68, 0.81), patients with diabetes (HR = 0.77, 95% CI: 0.60, 0.98), and patients with HIV (HR = 0.39, 95% CI: 0.30, 0.51) had a lower risk of treatment default. However, black patients (HR = 1.57, 95% CI: 1.44, 1.70), Hispanic patients (HR = 1.54, 95% CI: 1.43, 1.66), and non-U.S.-born persons living in the United States ≤5 years (HR = 1.25, 95% CI: 1.18, 1.32) were significantly more likely to default on therapy. CONCLUSIONS: In this analysis of INH treatment outcome, we see high levels of treatment discontinuation. On average, patients defaulted on their prescribed nine-month daily INH therapy within 30 days of initiating treatment, and those at increased risk of progression to active disease were most likely to do so. We highlight the need to introduce patient-centered programs to increase treatment adherence in this population.


Assuntos
Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Tuberculose Latente/tratamento farmacológico , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
13.
Brasília; CONITEC; set. 2019. tab.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1024747

RESUMO

CONTEXTO: A TB pode ser causada por qualquer uma das sete espécies que integram o complexo Mycobacterium tuberculosis, a espécie mais importante é a M. tuberculosis, conhecida também como bacilo de Koch. Estima-se que em 2015 cerca de 10,4 milhões de pessoas desenvolveram tuberculose (TB) dos quais 10% correspondem a tuberculose em crianças. TECNOLOGIA: Rifampicina 75 mg + isoniazida 50 mg + pirazinamida 150 mg e Rifampicina 75 mg + isoniazida 50 mg comprimidos dispersíveis. PERGUNTA: O uso do esquema terapêutico dose fixa combinada de rifampicina 75mg + isoniazida 50mg + pirazinamida 150mg seguida de rifampicina 75mg + isoniazida 50mg é eficaz, seguro e custo-efetivo em pacientes com tuberculose menores de 10 anos de idade quando comparado às formulações individualizadas de rifampicina 20 mg/ml (2%), rifampicina + isoniazida 150 mg + 75 mg, Isoniazida 100 mg, Pirazinamida 30 mg/ml (3%) ? EVIDÊNCIAS CIENTÍFICAS: Não foram encontrados estudos em pacientes pediátricos comparando a dose fixa combinada, em sua forma dispersível, com a dose padrão individualizada. Uma revisão sistemática não detectou diferença significativa entre as estratégias farmacológicas em relação à falha de tratamento (RR 1,28, IC95% 0,82 a 2,00), morte (RR 0,96, IC 95% 0,56 a 1,66), eventos adversos (RR 1,45 IC 95% 0,90 a 2,33) e eventos que levassem a descontinuação do tratamento (RR 0,56 IC 95% 0,56 a 1,66). AVALIAÇÃO ECONÔMICA: Assumindo-se que as duas estratégias de tratamento são similares, uma analise de custo-minimização foi realizada. A dose fixa combinada dispersível apresentou um custo de R$ 18,06 reais a menos por tratamento em relação a dose individualizada. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: O impacto em cinco anos da substituição do tratamento individualizado pela dose fixa combinada poderá resultar em uma economia de R$ 118.239,62. Cenários alternativos com a variação da taxa de câmbio em 10% podem variar em uma economia de recursos na ordem de R$ 68.420,88 a 166.936,09 em cinco anos. EXPERIÊNCIA INTERNACIONAL: Há um consenso nas diretrizes internacionais sobre o tratamento da tuberculose infantil. Não há recomendações específicas relacionadas à forma farmacêutica dispersível exceto pela OMS que recomenda formulações em dose fixa como parte das estratégias de combate a tuberculose. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: As pesquisas apontaram não haver medicamentos em fase de desenvolvimento clínico para o tratamento da tuberculose pediátrica. RECOMENDAÇÃO PRELIMINAR: A CONITEC, em sua 78ª reunião ordinária, realizada no dia 05 de junho de 2019, recomendou a incorporação da dose fixa combinada de Rifampicina 75 mg + isoniazida 50 mg + pirazinamida 150 mg e Rifampicina 75 mg + isoniazida 50 mg comprimidos dispersíveis. Considerou que o medicamento já vem sendo utilizado no tratamento da tuberculose pediátrica com sucesso e a nova forma farmacêutica em dose fixa combinada na forma dispersível, por sua melhor aceitabilidade, permitiria a melhor adesão ao tratamento e consequentemente aumento das taxas de curas da doença na população pediátrica. CONSULTA PUBLICA: Foram recebidas 31 contribuições técnico-científicas e 48 contribuições de experiência ou opinião, a maioria em concordância com as recomendações da Conitec. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na 80ª reunião ordinária, no dia 08 de agosto de 2019, deliberaram, por unanimidade, por recomendar a incorporação no SUS da dose fixas pediátricas RHZ (Rifampicina 75 mg + Isoniazida 50 mg + Pirazinamida 150 mg) e RH (Rifampicina 75 mg + Isoniazida 50 mg) comprimidos dispersíveis para tratamento da tuberculose em crianças menores de 10 anos. Foi assinado o Registro de Deliberação nº 463/2019. DECISÃO: Incorporar as doses fixas pediátricas RHZ (rifampicina 75mg + isoniazida 50mg + pirazinamida 150mg) e RH ( rifampicina 75mg + isoniazida 50mg) comprimido dispersíveis para tratamento de turbeculose em crianças menores de 10 anos, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 43, publicada no Diário Oficial da União nº 174, seção 1, página 190, em 09 de setembro de 2019.


Assuntos
Humanos , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Isoniazida/uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
15.
Tuberk Toraks ; 67(2): 92-101, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31414639

RESUMO

Introduction: Tuberculosis (TB) is continuing to be a important public health problem in the undeveloped countries. Drug sensitivity rate should be monitored for the effective treatment and control in the TB. The aim of this study was to determine the rate of resistance to first line TB drugs in the Mycobacterium tuberculosis complex isolates. Materials and Methods: During one-year period, M. tuberculosis complex was isolated in the 1193 samples from 974 patients in the Mycobacterial Laboratory of Yedikule Chest Diseases and Chest Surgery Education and Research Hospital, Istanbul, Turkey. The majority of samples isolated in the M. tuberculosis complex were sputum (n= 897, 92.1%). Anti-TB drug susceptibility testing was performed with Mycobacterium Growth Indicator Tube 960 system. Result: Two hundred and sixty isolat (26.7%) were resistant to at least one of the four first-line anti-TB drugs tested. One hundred ninety seven isolates were resistances to isoniazid (20.2%); 82 to rifampin (8.4%), 63 to ethambutol (6.5%) and 140 to streptomycin (14.4%). Of the 197 isoniazid-resistant isolates, 89 (45.2%) isolates was only isoniazid-resistance, only rifampin-resistance were found 15.9% (n= 13), ethambutol 7.9% (n= 5) and streptomycin 30.7% (n= 43). There were 48 (4.9%) isolates with two drugresistance, 22 (2.3%) isolates with three drug-resistance, and 42 (4.3%) isolates with four drug-resistance. The multidrug resistance rate was 7% (68 of 974). There was no relationship with between the frequency of TB drug resistance and gender or age. The isoniazid--resistance and streptomycin-resistance were seen to tend to increase if together considered the results of this study with outcomes of previously reported studies from Turkey in the 1998-2003, 2004-2007 and 2008-2010 years. Conclusions: Monitoring of drug susceptibility test results can contribute to the management of TB treatment and increase treatment success. Isoniazid-resistance and streptomycin-resistance tend to increase in Turkey. Further clinical studies are needed to investigate regional and global factors affecting the development of resistance to first-line TB drugs.


Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/uso terapêutico , Etambutol/farmacologia , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Saúde Pública , Rifampina/farmacologia , Rifampina/uso terapêutico , Escarro/microbiologia , Estreptomicina/farmacologia , Estreptomicina/uso terapêutico , Centros de Atenção Terciária , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Turquia , Adulto Jovem
16.
Przegl Epidemiol ; 73(2): 211-226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31385679

RESUMO

AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2017 in Poland and to compare with the situation in the EU/EEA countries. METHODS: Analysis of case- based data on TB patients from National TB Register, data on anti-TB drug susceptibility testing results in cases notified in 2017, data from National Institute of Public Health- National Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, data from Central Statistical Office on deaths from tuberculosis based on death certificates, data from ECDC report "European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2019-2017 data. Stockholm: European Centre for Disease Prevention and Control, 2019". RESULTS: In 2017, 5 787 TB cases were reported in Poland. The incidence rate was 15.1 cases per 100 000, with large variability between voivodeships from 8.9 to 21.9 per 100 000. The mean annual decrease of TB incidence in 2013-2017 was 4.2%. In 2017, 5127 cases were newly diagnosed with no history of previous treatment i.e. 13.3 per 100 000. 660 cases i.e. 1.7 per 100 000 ­ 11.4% of all registered subjects were previously treated for tuberculosis. In 2017, the number of all pulmonary tuberculosis cases was 5 531 i.e. 14.4 per 100 000. Pulmonary cases represented 95.6% of all TB cases. In 2017, 256 extrapulmonary TB cases were found. In the whole country there were 68 pediatric cases of tuberculosis. TB in children represented 1.2% of all cases notified in Poland in 2017. The incidence rates of tuberculosis were growing along with the age group from 1.2 per 100 000 among children to 25.6 per 100 000 among subjects in the age group 45-64 years (the highest incidence rate). In 2017, the incidence rate in the age group ≥65 years was 22.6 per 100 000. The TB incidence among men i.e. 22.2 per 100.000 was 2.4 times higher than among women i.e. 8,4 per 100 000. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 45 to 49 years ­ 36.1 vs. 8.1 and in age group 55- 59 years ­ 45.2 vs. 10.7. The TB incidence in rural population was lower than in urban, respectively 14.2 per 100.000 and 15.6 per 100 000. The number of all registered culture positive TB cases was 4 179. Pulmonary tuberculosis was bacteriologically confirmed in 4 057 subjects. Culture-confirmed cases represented 72.2% of all TB cases and 73.4% of all pulmonary TB cases. The number of smear-positive pulmonary TB cases reported in 2017 was 2 472 i.e. 6.4 per 100 000 accounting for 44.7% of all pulmonary TB cases and 60.9% of culture confirmed pulmonary TB cases.. TB was AIDS indicative disease in 16 subjects. In all patients with tuberculosis in Poland in 2017 there were 44 cases with MDR-TB (among them 12 foreigners) and 85 patients with resistance to isoniazid only, representing respectively 1.2% and 2.2% of cases with known DST results (DSTs were available in 90.5% of all cultureconfirmed TB cases). In 2017, there were 108 patients of foreign origin among all cases of tuberculosis in Poland. TUBERCULOSIS MORTALITY: There were 543 deaths due to tuberculosis reported in 2016 ­ 1.4 per 100 000; 526 people died from pulmonary and 17 from extrapulmonary tuberculosis. Mortality among males ­ 2.2 per 100 000 ­ was 3.7 X higher than among females ­ 0.6. 37.9% of all TB deaths were cases 65 years old and older ­ 3.3 per 100 000. In 2016, there was one death from tuberculosis in children and no deaths in adolescents. In 2016, tuberculosis represented 0.14% of total mortality in Poland and 28.1% of mortality from infectious diseases. CONCLUSIONS: In 2017, the incidence of tuberculosis in Poland was lower than in 2016. Despite a continuous decline it is still higher than the average in the EU/EEA countries. The highest incidence rates were observed in older age groups. The incidence in males was more than 2 times higher than in females. The impact of migration on the characteristics of tuberculosis in Poland is not substantial. In Poland, tuberculosis in children, tuberculosis in persons infected with HIV and MDR-TB is less common than the average in the EU/EEA countries.


Assuntos
Sistema de Registros , Tuberculose/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polônia/epidemiologia , População Rural , Distribuição por Sexo , Tuberculose/tratamento farmacológico , Tuberculose/mortalidade , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , População Urbana , Adulto Jovem
17.
BMC Infect Dis ; 19(1): 731, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31429717

RESUMO

BACKGROUND: Isoniazid resistant tuberculosis is the most prevalent type of resistance in Swaziland and over two-thirds of the isoniazid resistant tuberculosis patients are tuberculosis and human immunodeficiency virus co-infected. The study aimed to determine risk factors associated with isoniazid resistant tuberculosis among human immunodeficiency virus positive patients in Swaziland. METHODS: This was a case-control study conducted in nine healthcare facilities across Swaziland. Cases were patients with isoniazid resistant tuberculosis (including 78 patients with isoniazid mono-resistant tuberculosis, 42 with polydrug-resistant tuberculosis, and 77 with multidrug-resistant tuberculosis). Controls were presumed drug-susceptible tuberculosis patients (n = 203). Multinomial logistic regression was used to determine related factors. RESULTS: The median time lag from diagnosis to tuberculosis treatment initiation was 50 days for isoniazid mono or poly drug-resistant tuberculosis, 17 days for multidrug-resistant tuberculosis compared to 1 day for drug-susceptible tuberculosis patients. History of previous tuberculosis treatment was positively associated with either isoniazid mono or poly drug-resistant tuberculosis (OR = 7.91, 95% CI: 4.14-15.11) and multidrug-resistant tuberculosis (OR = 12.20, 95% CI: 6.07-24.54). Isoniazid mono or poly resistant tuberculosis patients were more likely to be from rural areas (OR = 2.05, 95% CI: 1.23-3.32) and current heavy alcohol drinkers compared to the drug-susceptible tuberculosis group. Multi drug-resistant tuberculosis patients were more likely to be non-adherent to tuberculosis treatment compared to drug-susceptible tuberculosis group (OR = 3.01, 95% CI: 1.56-5.82). CONCLUSION: To prevent and control isoniazid resistant tuberculosis among HIV-positive patients in Swaziland, the tuberculosis program should strengthen the use of rapid diagnostic tests, detect resistance early, promptly initiate supervised tuberculosis treatment and decentralize quality tuberculosis services to the rural areas. Adherence to tuberculosis treatment should be improved.


Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/microbiologia , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Rifampina , Fatores de Risco , Fatores Socioeconômicos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
18.
Indian J Med Microbiol ; 37(1): 127-131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31424025

RESUMO

We report here the first case of pulmonary infection due to Mycobacterium kyorinense in a 55-year-old hypertensive woman treated for pulmonary tuberculosis earlier on two occasions. She presented with productive cough, intermittent episode of left-sided chest pain, loss of appetite, low-grade fever, and breathlessness. Sputum cultures revealed non-tuberculous mycobacteria (NTM). She remained persistently symptomatic with sputum cultures positive for acid-fast bacilli even after 6 months of treatment. Hence, a 16SrRNA gene amplification and sequencing were done that revealed M. kyorinense. Based on the guidelines of the American Thoracic Society, she was started on weight-based dosing of clarithromycin, levofloxacin, ethambutol, isoniazid and injection amikacin daily. The patient improved symptomatically and became culture-negative after 3 months of therapy with the above regimen and continued to be culture negative for 12 months of treatment. She continues to remain symptom-free without evidence of any clinical or bacteriological relapse.


Assuntos
Antituberculosos/uso terapêutico , Infecções por Micobactéria não Tuberculosa/diagnóstico , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Mycobacterium/genética , Infecções Respiratórias/diagnóstico , Amicacina/uso terapêutico , Claritromicina/uso terapêutico , Etambutol/uso terapêutico , Feminino , Humanos , Isoniazida/uso terapêutico , Levofloxacino/uso terapêutico , Pessoa de Meia-Idade , Mycobacterium/isolamento & purificação , Infecções por Micobactéria não Tuberculosa/microbiologia , RNA Ribossômico 16S/genética , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/microbiologia
19.
BMC Infect Dis ; 19(1): 689, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382930

RESUMO

BACKGROUND: Isoniazid (INH) represents the cornerstone for the treatment of cases infected with Mycobacterium tuberculosis (MTB) strains. Several molecular mechanisms have been shown to be the major causes for INH resistance, while the dynamic change of mutations conferring INH resistance among MTB strains during the past decade is still unknown in China. METHODS: In this study, we carried out a comparative analysis of the INH minimal inhibitory concentration (MIC) distribution, and investigate the dynamic change of molecular characteristics among INH-resistant MTB strains between 2005 and 2015. RESULTS: The proportion of INH resistance (39.0%, 105/269) in 2015 was significantly higher than in 2005 (30.0%, 82/273; P = 0.03). Among 269 isolates collected in 2015, 76 (28.3%, 76/269) exhibited high-level INH-resistance (MIC≥32 mg/L), which was significantly higher than that in 2005 (20.5%, 56/273, P = 0.04). In addition, a significantly higher percentage of INH-resistant isolates carried inhA promoter mutations in 2015 (26.7%) versus that in 2005 (14.6%, P = 0.04), while no significant difference was observed in the rates of isolates containing katG mutations between 2005 (76.8%) and 2015 (70.5%, P = 0.33). Notably, the proportion of MTB isolates with inhA mutations (26.7%, 28/105) for patients who had previous exposure to protionamide (PTH) was higher than that for patients who had no previous exposure to PTH (21.4%, 6/28). CONCLUSIONS: In conclusion, our results demonstrated that the proportion of INH-resistant MTB isolates significantly increased during the last decade, which was mainly attributed to an increase of high-level INH-resistant MTB. In addition, prior exposure to PTH may be associated with the increased frequency of INH-resistant tuberculosis strains with inhA mutations in China.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/epidemiologia , Adulto , Idoso , Proteínas de Bactérias/genética , China/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Oxirredutases/genética , Prevalência , Regiões Promotoras Genéticas , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Adulto Jovem
20.
Epidemiol Health ; 41: e2019028, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31319659

RESUMO

OBJECTIVES: Tuberculosis (TB) is common in children with human immunodeficiency virus (HIV), but its effect on the survival of HIV-infected children is not well understood. Therefore, the aim of this study was to assess the incidence and predictors of active TB among HIV-positive children at Adama Referral Hospital and Medical College, Oromia, Ethiopia. METHODS: A retrospective study was conducted over 5 years using a checklist to gather data from 428 randomly selected pediatric patient charts. The checklist was adapted from the standardized antiretroviral therapy (ART) follow-up form currently used by the institution's ART clinic. Data were analyzed by bivariate and multivariable analysis using Cox regression proportional hazards models, as appropriate. Survival was calculated and compared using the Kaplan-Meier and log-rank tests. RESULTS: Of the 466 charts reviewed, 428 patient records were included in the analysis. A total of 67 new TB cases were observed during the follow-up period. Hence, the incidence rate in this cohort was found to be 6.03 per 100 child-years of observation. A baseline hemoglobin level <10 g/dL (adjusted hazard ratio [aHR], 7.04; 95% confidence interval [CI], 1.03 to 48.15), moderate wasting (aHR, 2.86; 95% CI, 1.02 to 7.99), and not receiving isoniazid preventive therapy (aHR, 8.23; 95% CI, 2.11 to 32.06) were among the independent predictors of TB occurrence. CONCLUSIONS: The incidence of TB was high, particularly in pre-ART patients receiving chronic care for HIV. Close followup of HIV-positive children is crucial to protect them against the development of TB. Initiating isoniazid preventive therapy, averting malnutrition, and managing anemia are also of significant importance.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Tuberculose/epidemiologia , Antirretrovirais/uso terapêutico , Antituberculosos/uso terapêutico , Criança , Pré-Escolar , Etiópia/epidemiologia , Feminino , Seguimentos , Infecções por HIV/tratamento farmacológico , Humanos , Incidência , Isoniazida/uso terapêutico , Masculino , Encaminhamento e Consulta , Estudos Retrospectivos , Fatores de Risco , Tuberculose/prevenção & controle
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