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1.
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
2.
J Assoc Physicians India ; 67(9): 85-86, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561697

RESUMO

Tuberculosis (TB) is an important cause of significant morbidity and mortality, particularly in patients living with human immunodeficiency virus (HIV ) infections. The co-infection of TB and HIV coinfection is further complicated by a relatively higher frequency of extra-pulmonary TB and upsurge of drug resistance. Musculoskeletal TB is a relatively less common form of extrapulmonary TB; involvement of carpometacarpal joint as an initial manifestation is even rarer. We herein present a retro positive patient who presented with low-grade fever, constitutional features and swelling of the base of the left thumb. On evaluation, he was found to have axillary and inguinal lymphadenopathy with lytic destruction of carpometacarpal joint as well as D10-D11 vertebrae. Fine needle aspiration (FNA) of synovial fluid was negative for tuberculosis but geneXpert from FNA of axillary node revealed Mycobacterium tuberculosis with rifampicin resistance. This case highlights the rarity of carpometacarpal joint involvement in TB as the initial manifestation and the importance of meticulous search of alternative sites for sampling in difficult situations such as osteoarticular TB. It also highlights the rising prevalence of drug-resistant TB and a definitive need for microbiological diagnosis wherever feasible.


Assuntos
Articulações Carpometacarpais , Síndrome Inflamatória da Reconstituição Imune/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Osteoarticular/diagnóstico , Infecções por HIV , Humanos , Masculino , Osteomielite
3.
BMC Infect Dis ; 19(1): 817, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533661

RESUMO

BACKGROUND: The emergence of Drug-Resistance Tuberculosis (DR-TB) is an increasing global public health problem. Lost to Follow-up (LTFU) from DR-TB treatment remains a major barrier to tuberculosis epidemic control and better treatment outcome. In Ethiopia, evidences on the incidence and predictors of LTFU are scarce. Thus, this study aimed to determine the incidence and identify the predictors of LTFU among DR-TB patients. METHODS: A retrospective follow-up study was conducted among a total of 332 DR-TB patients at the University of Gondar comprehensive specialized hospital. Data were retrieved from patient records from September 2010 to December 2017 and entered in to Epi-data 4.2.0.0 and analysed using Stata14.1 software. The risk was estimated using the Nelson-Aalen cumulative hazard curve. A log-rank test was used for survival comparisons between categories of independent variables. The Gompertz regression model was fitted, and hazard ratio with a 95% confidence interval (CI) was used to measure the strength of associations. Variables with less than 0.05 p-values in the multivariable model were considered as significantly associated with LTFU. RESULTS: Among a total of 332 patient records reviewed, 206 (62.05%) were male. The median age was 30 years (Inter Quartile Range (IQR): 23-40). Forty-one (12.35%) of the participants had no history of TB treatment, while a quarter of were TB-HIV co-infected. Closely all (92.17%) of the patients had pulmonary tuberculosis. The median follow up time was 20.37 months (IQR: 11.02, 21.80). Thirty-six (10.84%) patients were lost from follow-up with an incidence rate of 6.47 (95% CI: 4.67, 8.97)/1000 Person Months (PM). Homelessness (Adjusted Hazard Ratio (AHR) =2.51, 95%CI: 1.15, 5.45) and treatment enrolment year from 2013 to 2014 (AHR = 3.25, 95% CI: 1.30, 8.13) were significant predictors of LTFU. CONCLUSION: This study indicated that LTFU among DR-TB registered patients was high in the first six months compared to subsequent months. Homelessness and year of treatment enrolment were independent predictors of LTFU, requiring more economic support to patients in order to ensure treatment completion. This result can be generalized to patients who are using DR-TB treatment in similar settings.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto , Etiópia/epidemiologia , Feminino , Hospitais Especializados , Humanos , Incidência , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
4.
Lancet ; 394(10202): 953-966, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31526739

RESUMO

Drug-resistant tuberculosis is a major public health concern in many countries. Over the past decade, the number of patients infected with Mycobacterium tuberculosis resistant to the most effective drugs against tuberculosis (ie, rifampicin and isoniazid), which is called multidrug-resistant tuberculosis, has continued to increase. Globally, 4·6% of patients with tuberculosis have multidrug-resistant tuberculosis, but in some areas, like Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, this proportion exceeds 25%. Treatment for patients with multidrug-resistant tuberculosis is prolonged (ie, 9-24 months) and patients with multidrug-resistant tuberculosis have less favourable outcomes than those treated for drug-susceptible tuberculosis. Individualised multidrug-resistant tuberculosis treatment with novel (eg, bedaquiline) and repurposed (eg, linezolid, clofazimine, or meropenem) drugs and guided by genotypic and phenotypic drug susceptibility testing can improve treatment outcomes. Some clinical trials are evaluating 6-month regimens to simplify management and improve outcomes of patients with multidrug-resistant tuberculosis. Here we review optimal diagnostic and treatment strategies for patients with drug-resistant tuberculosis and their contacts.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/administração & dosagem , Esquema de Medicação , Farmacorresistência Bacteriana Múltipla/genética , Saúde Global , Humanos , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
5.
BMC Infect Dis ; 19(1): 618, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31299893

RESUMO

BACKGROUND: The increased transmission of multidrug-resistant (MDR) tuberculosis (TB) poses a challenge to tuberculosis prevention and control in Sri Lanka. Isoniazid (INH) is a key element of the first line anti tuberculosis treatment regimen. Resistance to INH may lead to development of MDR TB. Therefore, early detection of INH resistance is important to curb spread of resistance. Due to the limited availability of rapid molecular methods for detection of drug resistance in Sri Lanka, this study was aimed at developing a simple and rapid gold nanoparticle (AuNP) based lateral flow strip for the simultaneous detection of the most common INH resistance mutation (katG S315 T, 78.6%) and Mycobacterium tuberculosis (MTb). METHODS: Lateral flow strip was designed on an inert plastic backing layer containing a sample pad, nitrocellulose membrane and an absorption pad. Biotin labeled 4 capture probes which separately conjugated with streptavidin were immobilized on the nitrocellulose. The test sample was prepared by multiplex PCR using primers to amplify codon 315 region of the katG gene and MTb specific IS6110 region. The two detection probes complementary to the 5' end of each amplified fragment was conjugated with gold nanoparticles (20 nm) and coupled with the above amplified PCR products were applied on the sample pad. The hybridization of the amplified target regions to the respective capture probes takes place when the sample moves towards the absorption pad. Positive hybridization is indicated by red colour lines. RESULTS: The three immobilized capture probes on the strip (for the detection of TB, katG wild type and mutation) were 100 and 96.6% specific and 100 and 92.1% sensitive respectively. CONCLUSION: The AuNP based lateral flow assay was capable of differentiating the specific mutation and the wild type along with MTb identification within 3 h.


Assuntos
Doenças Transmissíveis/diagnóstico , Nanotecnologia/métodos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Antituberculosos/uso terapêutico , Proteínas de Bactérias/genética , Catalase/genética , Doenças Transmissíveis/tratamento farmacológico , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Ouro/química , Humanos , Isoniazida/uso terapêutico , Limite de Detecção , Nanopartículas Metálicas/química , Reação em Cadeia da Polimerase Multiplex , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Sri Lanka , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
6.
BMC Infect Dis ; 19(1): 641, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324227

RESUMO

BACKGROUND: The diagnoses of active smear negative PTB, remains difficult. As a result, treatment is often carried out empirically relaying on clinical criteria. The distribution and magnitude of smear negative PTB, smear negative MDR-TB and associated factors in the same day diagnosis strategy are not clearly known in the study area. Therefore, this study aimed to determine the prevalence of TB, MDR-TB and associated risk factors among presumptive smear negative pulmonary tuberculosis patients in Addis Ababa, Ethiopia. METHODS: Analytic cross sectional study design was used. A total of 418 smear negative presumptive pulmonary TB patients were enrolled from selected health facilities since August 01, 2017 to January 5, 2018. Sputum samples were examined by Ziehl Neelsen microscopy, Xpert MTB/RIF assay and Culture. Drug susceptibility testing was performed by line probe assay and BACTEC MGIT 960 system. These laboratory tests were performed in Ethiopian Public Health Institute, National TB Reference Laboratory. Data was analyzed by SPSS Ver.20. RESULTS: From the total of 418 enrolled patients, 27 (6.5%) were Xpert MTB/ RIF and 26 (6.4%) were culture confirmed smear negative PTB patients. The positivity rate among male and female was 10.2 and 3.5% (p = 0.005) respectively. From 26 culture positive isolates 3 (11.54%) were MDR TB; from MDR-TB confirmed isolates 2/23 (8.7%) were among new and 1/3 (33.3%) was among retreatment smear negative presumptive pulmonary TB patients. All Rifampicin resistant smear negative pulmonary TB isolates by Xpert MTB/ RIF assay were found to be MDR TB and 7/26 (26.9%) isolates were INH mono resistant. History of migration found to be a potential factor for developing smear negative pulmonary TB. CONCLUSION: In this study a significant proportion of smear negative pulmonary TB was diagnosed. Furthermore, a high smear negative multi drug resistant (MDR) TB and other mono drug resistant TB prevalence was confirmed. Due to the limitations of smear microscopy which is used as a primary diagnostic tool, these TB strains are missed to be diagnosed and transmission continues in the community.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Comorbidade , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Rifampina/uso terapêutico , Fatores de Risco , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
7.
Pan Afr Med J ; 32: 196, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31312308

RESUMO

Multidrug-resistant tuberculosis is a major challenge for the World Health Organization. Its growing incidence and the diagnostic and therapeutic difficulties make it a public health problem especially in the developing countries. We report two cases of extrapulmonary drug-resistant tuberculosis (nodal and osteo-articular) and five cases of pulmonary tuberculosis and extra-pulmonary tuberculosis (pleural, nodal, anal and neuro-meningeal) in hospitalized patients at the Hopital Moulay Youssef in Rabat. This study reports the issue of drug-resistant TB and highlights the role of genotypic tests in the diagnosis of extrapulmonary tuberculosis.


Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adulto , Antituberculosos/administração & dosagem , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
8.
Medicine (Baltimore) ; 98(26): e16071, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261516

RESUMO

Kazakhstan has a high burden of multidrug-resistant tuberculosis (TB). The patient-centered National Program for the treatment and prevention of TB has been implemented in Kazakhstan. The program is aimed at meeting the needs of patients and expansion of the outpatient treatment of TB in the country.The aim of the study was to compare the efficacy of the outpatient and inpatient treatment of drug-susceptible TB.This study was a retrospective cohort study.A total of 36.926 TB cases were included. The majority of patients were treated as inpatients. The socioeconomic factors, sex, age, HIV status, and other diagnostic factors (e.g., sputum smear results, extrapulmonary disease) may serve as risk factors to estimate the likely TB treatment outcome. The outpatient treatment of drug-susceptible TB seems to be a comparable option to the inpatient treatment in terms of efficacy.The socioeconomic factors are the main modifiable risk factors for treatment failure. The outpatient treatment of drug-susceptible TB is safe and effective.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Adolescente , Adulto , Assistência Ambulatorial , Feminino , Hospitalização , Humanos , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto Jovem
9.
Pan Afr Med J ; 32: 124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31236189

RESUMO

Introduction: hain GenoType MTBDRsl is nucleic acid amplification assay based on reverse hybridization with specific oligonucleotide probes on nitrocellulose strips. MTBDRsl identifies M. tuberculosis complex and detects resistance to fluoroquinolone, second line injectable drugs and ethambutol evident as mutations of gyrA, rrs and embB genes respectively. This study aimed to evaluate the diagnostic performance of the Hain GenoType MTBDRsl Assay using 1% proportion method on LJ medium as gold standard. Methods: a total of 52 rifampicin resistant (RR) isolates were tested for second line drug sensitivity by 1% proportion method and by MTBDRsl assay. Results: two strains were identified as mycobacteria other than tuberculosis MOTT and the rest were Mycobacterium tuberculosis complex MTBC. Five of the MTBC isolates (5/50; 10%) showed resistance to at least one second line drug and one isolate (1/50; 2%) was XDR. XDR strain was concordantly detected by the two methods. One of two Kanamycin-resistant isolates showed discordant results. Ofloxacin showed one false positive and one false negative result. Most discrepancies were detected with Ethambutol. The sensitivity, specificity, positive and negative predictive values were respectively as follows: Ethambutol (63.3.4%, 85.7%, 94.4% and 62%), for Kanamycin (67%, 100%, 100% and 97.9%), for Amikacin and Capreomycin (100%, 100%, 100% and 100%), for Ofloxacin (75%, 97.5%, 75% and 97.8%). For XDR isolate the values were 100%, 100%, 100% and 100% respectively. Conclusion: MTBDRsl showed high specificity and negative predictive values making it acceptable and time-saving for early presumptive detection of resistance to second-line drugs in Sudan.


Assuntos
Antituberculosos/farmacologia , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Tuberculose/diagnóstico , Farmacorresistência Bacteriana Múltipla , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Sudão , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
10.
J Physiol Pharmacol ; 70(1)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31172969

RESUMO

The incidence of tuberculosis (TB) in some countries increases continuously, especially caused by mycobacterial strains resistant to various anti-tuberculotic drugs (AT). The emergence and spread of drug-resistant tuberculosis (multidrug-resistant - MDR-TB, and extensively drug-resistant - XDR-TB) suggest the crucial role of pharmacotherapy protocol tailored to the respective patient with MDR-TB or XDR-TB (a personalized approach) and requirements for fast and precise diagnostics of the degree of resistance. The aim of this study was to characterize a molecular basis of resistance to AT, and to identify the presence of the resistance using conventional susceptibility testing and molecular genetic methods using PCR tests in Slovakia during years 2009 - 2017. Furthermore, we focused on evaluation of the relationship between the level of resistance, the clinical status, and some laboratory markers of patients with drug-resistant TB. Totally 1157 strains isolated from patients in 2009 - 2017 were tested for resistance using classical methods and in resistant strains, the molecular-genetic tests were performed. Increased incidence of recurrence, prolonged time required to culture conversion, increased mortality during treatment, plasma C-reactive protein concentrations and sedimentation rate, broader spectrum of AT used, as well as higher incidence of adverse effects (sufficiently controlled with symptomatic treatment) were observed with higher degree of resistance. Contrary, the number of patients who achieved remission decreased. Rapid and precise identification of MDR-TB or XDR-TB strains using both classical and molecular-genetic testing is an essential tool for personalized drug treatment and prevention of resistance spread and worsening. Both tests should be used for correct diagnosis of resistant TB. Higher level of resistance required more aggressive therapeutic approach, associated with adverse effects and prolongation of the culture conversion time, as well as increased risk of relapse. Effective pharmacotherapy led to significant decrease of CRP levels in all groups of patients. The most frequent adverse effects of ATs - impairment of liver and kidney functions - were effectively managed by symptomatic treatment.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , DNA Bacteriano/análise , Humanos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Fenótipo , Eslováquia/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
11.
BMC Infect Dis ; 19(1): 489, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31151423

RESUMO

BACKGROUND: A delayed initiation of tuberculosis treatment results in high morbidity, mortality, and increased person-to-person transmissions. The aim of this study was to assess treatment delay and its associated factors among adult drug resistant tuberculosis patients in the Amhara Regional State, Ethiopia. METHODS: An institution based cross-sectional study was conducted on all adult drug resistant tuberculosis patients who initiated treatment from September 2010 to December 2017. Data were collected from patient charts, registration books, and computer databases using abstraction sheets. The data were entered using Epi-info version 7 and exported to SPSS version 20 for analysis. Summary statistics, like means, medians, and proportions were used to present it. Binary logistic regression was fitted; Adjusted Odds Ratio (AOR) with a 95% Confidence Interval (CI) was also computed. Variables with p-value < 0.05 in the multi-variable logistic regression model was declared as significantly associated with treatment delay. RESULTS: The median time to commence treatment after drug resistant tuberculosis diagnosis was 8 (IQR: 3-37) days. Being diagnosed by Line probe assay [AOR = 5.59; 95% CI: 3.48-8.98], Culture [AOR = 5.15; 95% CI: 2.53-10.47], and history of injectable anti-TB drugs [AOR = 2.12; 95% CI: 1.41-3.19] were associated with treatment delays. CONCLUSION: Treatment delay was long, especially among patients diagnosed by Culture or LPA and those who had a prior history of injectable anti-TB drugs. That suggested that the need for universal accesses to rapid molecular diagnostic tests, such as Gene Xpert and the PMDT team were needed to promptly decide to minimize unnecessary delays.


Assuntos
Tempo para o Tratamento/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/diagnóstico , Adulto , Estudos Transversais , Diagnóstico Tardio/estatística & dados numéricos , Etiópia/epidemiologia , Feminino , Instalações de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
12.
BMC Infect Dis ; 19(1): 553, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234780

RESUMO

BACKGROUND: Kazakhstan remains a high-burden TB prevalence country with a concomitent high-burden of multi-drug resistant tuberculosis. For this reason, we performed an in depth genetic diversity and population structure characterization of Mycobacterium tuberculosis complex (MTC) genetic diversity in Kazakhstan with both patient and community benefit. METHODS: A convenience sample of 700 MTC DNA cultures extracts from 630 tuberculosis patients recruited from 12 out of 14 regions in Kazakhstan, between 2010 and 2015, was independently studied by high-throughput hybridization-based methods, TB-SPRINT (59-Plex, n = 700), TB-SNPID (50-Plex, n = 543). DNA from 391 clinical isolates was successfully typed by two methods. To resolve the population structure of drug-resistant clades in more detail two complementary assays were run on the L2 isolates: an IS6110-NTF insertion site typing assay and a SigE SNP polymorphism assay. RESULTS: Strains belonged to L2/Beijing and L4/Euro-American sublineages; L2/Beijing prevalence totaled almost 80%. 50% of all samples were resistant to RIF and to INH., Subtyping showed that: (1) all L2/Beijing were "modern" Beijing and (2) most of these belonged to the previously described 94-32 sublineage (Central Asian/Russian), (3) at least two populations of the Central Asian/Russian sublineages are circulating in Kazakhstan, with different evolutionary dynamics. CONCLUSIONS: For the first time, the global genetic diversity and population structure of M. tuberculosis genotypes circulating in Kazakhstan was obtained and compared to previous local studies. Results suggest a region-specific spread of a very limited number of L2/Beijing clonal complexes in Kazakhstan many strongly associated with an MDR phenotype.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , DNA Bacteriano/isolamento & purificação , DNA Bacteriano/metabolismo , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Evolução Molecular , Variação Genética , Genótipo , Humanos , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico/métodos , Fenótipo , Prevalência , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
13.
BMC Infect Dis ; 19(1): 564, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253115

RESUMO

BACKGROUND: The increased incidence of drug-resistant TB is a major challenge for effective TB control. Limited therapeutic options and poor treatment outcomes of DR-TB may increase drug-resistance rates. The objective of the study is to retrospectively compare MDR-TB and pre-XDR-TB treatment regimens and outcomes in two large TB reference centres in Italy from January 2000 to January 2015. METHODS: A retrospective, multicentre study was conducted at the Regional TB Reference Centre Villa Marelli Institute (Milan) and at the Reference Center for MDR-TB and HIV-TB, Eugenio Morelli Hospital (Sondalo). The supra-national Reference Laboratory in Milan performed DST. Inclusion criteria were: age ≥ 18 and culture-confirmed diagnosis of MDR- or pre-XDR TB. Chi-square or Fisher exact test was used to detect differences in the comparison between treatment outcomes, therapeutic regimens, and drug-resistances. Computations were performed with STATA 15. RESULTS: A total of 134 patients were selected. Median (IQR) age at admission was 33 (26-41) years and 90 patients (67.2%) were male. Pulmonary TB was diagnosed in 124 (92.5%) patients. MDR- and pre-XDR-TB cases were 91 (67.9%) and 43 (32.1%), respectively. The WHO shorter MDR-TB regimen could have been prescribed in 16/84 (19.1%) patients. Treatment success was not statistically different between MDR- and pre-XDR-TB (81.3% VS. 81.4%; P = 0.99). Mortality in MDR-TB and pre-XDR-TB groups was 4.4 and 9.3%, respectively (P = 0.2). Median duration of treatment was 18 months and a total of 110 different regimens were administered. Exposure to linezolid, meropenem, and amikacin was associated with a better outcome in both groups (P = 0.001, P < 0.001, and P = 0.004, respectively). CONCLUSIONS: Tailored treatment regimens based on DST results can achieve successful outcomes in patients with pre-XDR-TB.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Amicacina/farmacologia , Amicacina/uso terapêutico , Antituberculosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Feminino , Humanos , Itália , Laboratórios Hospitalares , Linezolida/farmacologia , Linezolida/uso terapêutico , Masculino , Meropeném/farmacologia , Meropeném/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade
14.
BMC Infect Dis ; 19(1): 387, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064332

RESUMO

BACKGROUND: In August 2017, the Uganda Ministry of Health was notified of increased cases of multidrug-resistant tuberculosis (MDR-TB) in Arua District, Uganda during 2017. We investigated to identify the scope of the increase and risk factors for infection, evaluate health facilities' capacity to manage MDR-TB, and recommend evidence-based control measures. METHODS: We defined an MDR-TB case-patient as a TB patient attending Arua Regional Referral Hospital (ARRH) during 2013-2017 with a sputum sample yielding Mycobacterium tuberculosis resistant to at least rifampicin and isoniazid, confirmed by an approved drug susceptibility test. We reviewed clinical records from ARRH and compared the number of MDR-TB cases during January-August 2017 with the same months in 2013-2016. To identify risk factors specific for MDR-TB among cases with secondary infection, we conducted a case-control study using persons with drug-susceptible TB matched by sub-county of residence as controls. We observed infection prevention and control practices in health facilities and community, and assessed health facilities' capacity to manage TB. RESULTS: We identified 33 patients with MDR-TB, of whom 30 were secondary TB infection cases. The number of cases during January-August 2017 was 10, compared with 3-4 cases in January-August from 2013 to 2016 (p = 0.02). Men were more affected than women (6.5 vs 1.6/100,000, p < 0.01), as were cases ≥18 years old compared to those < 18 years (8.7 vs 0.21/100,000, p < 0.01). In the case-control study, poor adherence to first-line anti-TB treatment (aOR = 9.2, 95% CI: 2.3-37) and initiating treatment > 15 months from symptom onset (aOR = 11, 95% CI: 1.5-87) were associated with MDR-TB. All ten facilities assessed reported stockouts of TB commodities. All 15 ambulatory MDR-TB patients we observed were not wearing masks given to them to minimize community infection. The MDR-TB ward at ARRH capacity was 4 patients but there were 11 patients. CONCLUSION: The number of cases during January-August in 2017 was significantly higher than during the same months in 2013-2016. Poor adherence to TB drugs and delayed treatment initiation were associated with MDR-TB infection. We recommended strengthening directly-observed treatment strategy, increasing access to treatment services, and increasing the number of beds in the MDR-TB ward at ARRH.


Assuntos
Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Estudos de Casos e Controles , Criança , Surtos de Doenças , Feminino , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Razão de Chances , Fatores de Risco , Cooperação e Adesão ao Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Uganda/epidemiologia , Adulto Jovem
15.
S Afr Med J ; 109(4): 259-263, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-31084692

RESUMO

BACKGROUND: Xpert MTB/RIF assay rapidly diagnoses rifampicin resistance, enabling early initiation of second-line tuberculosis (TB) treatment. However, the impact of an earlier multidrug-resistant TB (MDR-TB) diagnosis on treatment outcomes is unknown. OBJECTIVES: To compare MDR-TB treatment outcomes in cases diagnosed with smear/culture and Xpert. METHODS: This was a retrospective cohort study with cohorts defined by the diagnostic assay used in presumptive TB cases. Data were extracted from a drug-resistant (DR)-TB register including cases from January 2012 to June 2014. Treatment outcomes were assessed at recorded endpoints or after 2 years for those completing treatment. RESULTS: A total of 718 cases were enrolled into the study. Cure rates were 43.4% (n=158) for the smear/culture cohort and 33.5% (n=118) for the Xpert cohort (p<0.01). Xpert diagnosis (adjusted risk ratio (aRR) 0.65; p=0.02) and male gender (aRR 0.66; p=0.04) were associated with cure outcome. Xpert diagnosis increased time to sputum culture conversion from 4 to 5 months (log-rank test p=0.01). Time to treatment initiation was not associated with treatment success in logistic regression analysis. CONCLUSIONS: Despite rapid treatment initiation, MDR-TB treatment outcomes were poorer in patients diagnosed with Xpert MTB/RIF assay than in the smear/culture cohort, and they were also poorer in men than in women. Additional studies are required to assess possible factors influencing DR-TB outcomes.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Kit de Reagentes para Diagnóstico , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Estudos Retrospectivos , África do Sul , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto Jovem
16.
EBioMedicine ; 43: 356-369, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31047860

RESUMO

BACKGROUND: The diagnosis of multidrug resistant and extensively drug resistant tuberculosis is a global health priority. Whole genome sequencing of clinical Mycobacterium tuberculosis isolates promises to circumvent the long wait times and limited scope of conventional phenotypic antimicrobial susceptibility, but gaps remain for predicting phenotype accurately from genotypic data especially for certain drugs. Our primary aim was to perform an exploration of statistical learning algorithms and genetic predictor sets using a rich dataset to build a high performing and fast predicting model to detect anti-tuberculosis drug resistance. METHODS: We collected targeted or whole genome sequencing and conventional drug resistance phenotyping data from 3601 Mycobacterium tuberculosis strains enriched for resistance to first- and second-line drugs, with 1228 multidrug resistant strains. We investigated the utility of (1) rare variants and variants known to be determinants of resistance for at least one drug and (2) machine and statistical learning architectures in predicting phenotypic drug resistance to 10 anti-tuberculosis drugs. Specifically, we investigated multitask and single task wide and deep neural networks, a multilayer perceptron, regularized logistic regression, and random forest classifiers. FINDINGS: The highest performing machine and statistical learning methods included both rare variants and those known to be causal of resistance for at least one drug. Both simpler L2 penalized regression and complex machine learning models had high predictive performance. The average AUCs for our highest performing model was 0.979 for first-line drugs and 0.936 for second-line drugs during repeated cross-validation. On an independent validation set, the highest performing model showed average AUCs, sensitivities, and specificities, respectively, of 0.937, 87.9%, and 92.7% for first-line drugs and 0.891, 82.0% and 90.1% for second-line drugs. Our method outperforms existing approaches based on direct association, with increased sum of sensitivity and specificity of 11.7% on first line drugs and 3.2% on second line drugs. Our method has higher predictive performance compared to previously reported machine learning models during cross-validation, with higher AUCs for 8 of 10 drugs. INTERPRETATION: Statistical models, especially those that are trained using both frequent and less frequent variants, significantly improve the accuracy of resistance prediction and hold promise in bringing sequencing technologies closer to the bedside.


Assuntos
Aprendizado de Máquina , Modelos Estatísticos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Análise por Conglomerados , Biologia Computacional/métodos , Bases de Dados Genéticas , Evolução Molecular , Tuberculose Extensivamente Resistente a Medicamentos/diagnóstico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Variação Genética , Genoma Bacteriano , Genômica/métodos , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
17.
J Bras Pneumol ; 45(2): e20180128, 2019 Apr 18.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31017225

RESUMO

OBJECTIVE: To evaluate the rapid diagnosis of multidrug-resistant tuberculosis, by using a commercial line probe assay for rifampicin and isoniazid detection (LPA-plus), in the routine workflow of a tuberculosis reference laboratory. METHODS: The LPA-plus was prospectively evaluated on 341 isolates concurrently submitted to the automated liquid drug susceptibility testing system. RESULTS: Among 303 phenotypically valid results, none was genotypically rifampicin false-susceptible (13/13; 100% sensitivity). Two rifampicin-susceptible isolates harboured rpoB mutations (288/290; 99.3% specificity) which, however, were non-resistance-conferring mutations. LPA-plus missed three isoniazid-resistant isolates (23/26; 88.5% sensitivity) and detected all isoniazid-susceptible isolates (277/277; 100% specificity). Among the 38 (11%) invalid phenotypic results, LPA-plus identified 31 rifampicin- and isoniazid-susceptible isolates, one isoniazid-resistant and six as non-Mycobacterium tuberculosis complex. CONCLUSIONS: LPA-plus showed excellent agreement (≥91%) and accuracy (≥99%). Implementing LPA-plus in our setting can speed up the diagnosis of multidrug-resistant tuberculosis, yield a significantly higher number of valid results than phenotypic drug susceptibility testing and provide further information on the drug-resistance level.


Assuntos
Técnicas de Diagnóstico Molecular/métodos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/farmacologia , Criança , Pré-Escolar , DNA Bacteriano , Diagnóstico Precoce , Feminino , Humanos , Lactente , Isoniazida/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Fenótipo , Estudos Prospectivos , Reprodutibilidade dos Testes , Rifampina/farmacologia , Sensibilidade e Especificidade , Fatores de Tempo , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
18.
BMC Infect Dis ; 19(1): 343, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31023267

RESUMO

BACKGROUND: Drug resistant tuberculosis (TB) has become a persistent health threat in Ethiopia. In this respect, baseline data are scarce in many parts of high TB burden regions including the different zones of Ethiopia. METHODS: A total of 111 culture positive M. tuberculosis isolates were recovered from TB patients and identified using region of difference (RD) 9 based polymerase chain reaction (PCR) and spoligotyping. Thereafter, their drug sensitivities to Rifampicin (RIF) and Isoniazid (INH) were evaluated using GenoType MTBDRplus assay. RESULTS: The result showed that 18.0% (20/111) of the isolates were resistant to either RIF or INH. Furthermore, 16.7 and 23.8% of the isolates from new and retreatment cases were resistant to any of the two anti-TB drugs, respectively. Multi-drug resistant (MDR) TB was detected on 1.8% (2/111) of all cases. Significantly higher frequencies of any drug resistance were observed among Euro-American (EA) major lineage (χ2: 9.67; p = 0.046). CONCLUSION: Considerably high proportion of drug resistant M. tuberculosis strains was detected which could suggest a need for an increased effort to strengthen TB control program in the study area.


Assuntos
Tipagem Molecular/métodos , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
19.
BMC Public Health ; 19(1): 395, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971228

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) outcomes are adversely impacted by delay in diagnosis and treatment. METHODS: Mixed qualitative and quantitative approaches were utilized to identify healthcare system related barriers to implementation of molecular diagnostics for MDR-TB. Randomly sampled districts from the 5 highest TB burden regions were enrolled during the 4th quarter of 2016. District TB & Leprosy Coordinators (DTLCs), and District AIDS Coordinators (DACs) were interviewed, along with staff from all laboratories within the selected districts where molecular diagnostics tests for MDR-TB were performed. Furthermore, the 2015 registers were audited for all drug-susceptible but retreatment TB cases and TB collaborative practices in HIV clinics, as these patients were in principal targeted for drug susceptibility testing by rapid molecular diagnostics. RESULTS: Twenty-eight TB districts from the 5 regions had 399 patients reviewed for retreatment with a drug-susceptible regimen. Only 160 (40%) had specimens collected for drug-susceptibility testing, and of those specimens only 120 (75%) had results communicated back to the clinic. MDR-TB was diagnosed in 16 (13.3%) of the 120 specimens but only 12 total patients were ultimately referred for treatment. Furthermore, among the HIV/AIDS clinics served in 2015, the median number of clients with TB diagnosis was 92 cases [IQR 32-157] yet only 2 people living with HIV were diagnosed with MDR-TB throughout the surveyed districts. Furthermore, the districts generated 53 front-line healthcare workers for interviews. DTLCs with intermediate or no knowledge on the clinical application of XpertMTB/RIF were 3 (11%), and 10 (39%), and DACs with intermediate or no knowledge were 0 (0%) and 2 (8%) respectively (p = 0.02). Additionally, 11 (100%) of the laboratories surveyed had only the 4-module XpertMTB/RIF equipment. The median time that XpertMTB/RIF was not functional in the 12 months prior to the investigation was 2 months (IQR 1-4). CONCLUSIONS: Underutilization of molecular diagnostics in high-risk groups was a function of a lack of front-line healthcare workforce empowerment and training, and a lack of equipment access, which likely contributed to the observed delay in MDR-TB diagnosis in Tanzania.


Assuntos
Antituberculosos/uso terapêutico , Pessoal de Saúde/psicologia , Acesso aos Serviços de Saúde/estatística & dados numéricos , Tempo para o Tratamento/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Patologia Molecular/estatística & dados numéricos , Poder (Psicologia) , Tanzânia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
20.
Glob Health Sci Pract ; 7(1): 41-53, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30926737

RESUMO

BACKGROUND: Private physicians in India see and treat more than half of all people with tuberculosis (TB) each year and thus have potential to make significant contributions to TB control. The EQUIP project was designed as a prospective cohort study to assess the potential of private providers to diagnose and appropriately treat drug-resistant TB (DR-TB) in the Central and South districts of Chennai, India. METHODS: The private-sector engagement model consisted of free access to rapid diagnostics; choice of free daily or thrice-weekly treatment regimens; support for notification of patients; and patient support including directly observed therapy through EQUIP centers staffed by a community-based interface agency. Data were collected on provider participation; referral results; treatment regimens prescribed; and treatment outcomes. RESULTS: From October 2015 through June 2017, 227 of the 466 (48.7%) private providers approached referred at least 1 patient to an EQUIP center for evaluation. A total of 2,621 patients received testing and 1,232 (47.0%) were diagnosed with TB. Of those, 727 (59.0%) were bacteriologically confirmed, including 694 (56.3%) using GeneXpert and 33 (2.7%) using smear microscopy. A total of 26 (3.7% of GeneXpert diagnosed) patients were confirmed as rifampicin-resistant cases. EQUIP-related notifications comprised approximately 10% of TB and DR-TB notifications in Chennai during the project period. The project initiated 1,167 (96.8%) drug-sensitive TB patients on treatment. Of those, 691 (59.2%) received standard daily regimens with EQUIP support and 288 (24.7%) received standard intermittent regimens. At the time of writing, 89.4% of 868 drug-susceptible TB patients receiving EQUIP support had treatment success. Of the 26 rifampicin-resistant TB cases notified, 20 (77%) started and continued on second-line treatment; 2 died and 4 were lost to follow-up prior to treatment initiation. CONCLUSION: Private providers can make a substantial contribution to detection and appropriate treatment of patients with TB and DR-TB in India when provided with access to rapid diagnostics, support for notification and patient treatment through interface agencies, and free, quality anti-TB drugs.


Assuntos
Resistência a Múltiplos Medicamentos , Médicos , Prática Privada , Avaliação de Programas e Projetos de Saúde , Saúde Pública/normas , Parcerias Público-Privadas , Tuberculose/terapia , Comunicação , Serviços de Diagnóstico , Revelação , Humanos , Índia , Setor Privado , Estudos Prospectivos , Melhoria de Qualidade , Encaminhamento e Consulta , Rifampina , Tuberculose/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/terapia
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