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1.
Life Sci ; 274: 119301, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33675895

RESUMO

Tuberculosis is one of the deadliest infectious diseases existing in the world since ancient times and still possesses serious threat across the globe. Each year the number of cases increases due to high drug resistance shown by Mycobacterium tuberculosis (Mtb). Available antimycobacterial drugs have been classified as First line, Second line and Third line antibiotics depending on the time of their discoveries and their effectiveness in the treatment. These antibiotics have a broad range of targets ranging from cell wall to metabolic processes and their non-judicious and uncontrolled usage in the treatment for years has created a significant problem called multi-drug resistant (MDR) tuberculosis. In this review, we have summarized the mechanism of action of all the classified antibiotics currently in use along with the resistance mechanisms acquired by Mtb. We have focused on the new drug candidates/repurposed drugs, and drug in combinations, which are in clinical trials for either treating the MDR tuberculosis more effectively or involved in reducing the time required for the chemotherapy of drug sensitive TB. This information is not discussed very adequately on a single platform. Additionally, we have discussed the recent technologies that are being used to discover novel resistance mechanisms acquired by Mtb and for exploring novel drugs. The story of intrinsic resistance mechanisms and evolution in Mtb is far from complete. Therefore, we have also discussed intrinsic resistance mechanisms of Mtb and their evolution with time, emphasizing the hope for the development of novel antimycobacterial drugs for effective therapy of tuberculosis.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/classificação , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Animais , Antituberculosos/classificação , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
2.
BMC Infect Dis ; 21(1): 238, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33663408

RESUMO

BACKGROUND: The sputum smear bacilliary load is a fundamental indicator of the level of infectiousness in DR-TB patients. However, evidence on DR-TB sputum smear grading and its factors in the study setting is limited. This study was aimed to determine the level of sputum smear grading and associated factors among DR-TB patients in Ethiopia. METHODS: This was an institution based cross-sectional study on 520 bacteriological confirmed pulmonary DR-TB patients from September 2010 to December 2017 in the northwest Ethiopia. Epidata 4.2.00 and SPSS 20 were used for data entry and management, respectively. Ordinary logistic regression was fitted. A cut of p-value less than 0.05 in the multivariable ordinary logistic regression was considered to declare statistically significant variables. RESULTS: Of all 520 bacteriological confirmed pulmonary DR-TB patients; 34.42% had 3+, 15.77% had 2+, 18.27% had 1+, 15.19% had scanty, and 16.35% had negative sputum smear grading results. The odds of having higher sputum smear grades were significantly associated with the patient's educational status of secondary (Adjusted Odds Ratio (AOR) = 0.43, 95% Confidence Interval (CI): 0.21, 0.89), body mass index of 16 to 18.49 kg/m2 (AOR = 1.81, 95%CI: 1.16, 2.84), and TB treatment history of two and more times (AOR = 1.78, 95%CI: 1.24, 2.55). CONCLUSIONS: More than a third of the bacteriological confirmed pulmonary DR-TB patients in the study setting was highly infectious with the highest bacillary load. The odds of having a high bacillary load were significantly associated with the patient's TB treatment history, nutritional, and educational status.


Assuntos
Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Carga Bacteriana , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tuberculose Resistente a Múltiplos Medicamentos/patologia
3.
Lancet Glob Health ; 9(4): e479-e488, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33740409

RESUMO

BACKGROUND: There is little evidence of patient acceptability for drug-resistant tuberculosis (DRTB) care in the context of new treatment regimens and HIV co-infection. We aim to describe experiences of DRTB-HIV care among patients in KwaZulu-Natal province, South Africa. METHODS: In this qualitative study using Bury's framework for chronic illness, we conducted 13 focus groups at a tertiary hospital with 55 patients co-infected with DRTB and HIV (28 women, 27 men) who were receiving new bedaquiline-based treatment for DRTB, concurrent with antiretroviral therapy. Eligible patients were consenting adults (aged >18 years) with confirmed DRTB and HIV who were enrolled into the PRAXIS study within 2 weeks of initiating bedaquiline-based treatment for DRTB. Participants were recruited from the PRAXIS cohort to participate in a focus group based on their time in DRTB treatment: early (2-6 weeks after treatment initiation), middle (2-6 months after discharge or treatment initiation if never hospitalised), and late (>6 months after treatment initiation). Focus groups were carried out in isiZulu language, audio recorded, and translated to English within 4 weeks. Participants were asked about their experiences of DRTB and HIV care and treatment, and qualitative data were coded and thematically analysed. FINDINGS: From March, 2017, to June, 2018, distinctive patient challenges were identified at four critical stages of DRTB care: diagnosis, marked by centralised hospitalisation, renunciation from routine life, systemic stigmatisation and, for patients with longstanding HIV, renewed destabilisation; treatment initiation, marked by side-effects, isolation, and social disconnectedness; discharge, marked by brief respite and resurgent therapeutic and social disruption; and continuity, marked by deepening socioeconomic challenges despite clinical recovery. The periods of diagnosis and discharge into the community were particularly difficult. Treatment information and agency in decision making was a persistent gap. Sources of stigmatisation shifted with movement between the hospital and community. Resilience was built by connecting to peers, self-isolating, financial and material security, and a focus on recovery. INTERPRETATION: People with DRTB and HIV undergo disruptive, life-altering experiences. The lack of information, agency, and social protections in DRTB care and treatment causes wider-reaching challenges for patients compared with HIV. Decentralised, community, peer-support, and differentiated care models for DRTB might be ameliorative and help to maximise the promise of new regimens. FUNDING: US National Institutes of Health. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Coinfecção/tratamento farmacológico , Diarilquinolinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/psicologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Coinfecção/microbiologia , Coinfecção/psicologia , Aconselhamento , Quimioterapia Combinada/métodos , Quimioterapia Combinada/psicologia , Feminino , Grupos Focais , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Estudos Longitudinais , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , Pesquisa Qualitativa , Resiliência Psicológica , África do Sul , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/psicologia , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-33787739

RESUMO

The emergence and spread of extensively drug-resistant tuberculosis (XDR-TB) is a serious threat to global health. Therefore, its rapid diagnosis is crucial. The present study aimed to characterize mutations conferring resistance to second line drugs (SLDs) within multidrug Mycobacterium tuberculosis (MDR-MTB) isolates and to estimate the occurrence of XDR-TB in Casablanca, Morocco. A panel of 200 MDR-TB isolates was collected at the Pasteur Institute between 2015-2018. Samples were subjected to drug susceptibility testing to Ofloxacin (OFX), Kanamycin (KAN) and Amikacin (AMK). The mutational status of gyrA, gyrB, rrs, tlyA and eis was assessed by sequencing these target genes. Drug susceptibility testing for SLDs showed that among the 200 MDR strains, 20% were resistant to OFX, 2.5% to KAN and 1.5% to AMK. Overall, 14.5% of MDR strains harbored mutations in gyrA, gyrB, rrs and tlyA genes. From the 40 OFXR isolates, 67.5% had mutations in QRDR of gyrA and gyrB genes, the most frequent one being Ala90Val in gyrA gene. Of note, none of the isolates harbored simultaneously mutations in gyrA and gyrB genes. In eight out of the 200 MDR-TB isolates resistant either to KAN or AMK, only 25% had A1401G or Lys89Glu change in rrs and tlyA genes respectively. This study is very informative and provides data on the alarming rate of fluoroquinolone resistance which warrants the need to implement appropriate drug regimens to prevent the emergence and spread of more severe forms of Mycobacterium tuberculosis drug resistance.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Marrocos/epidemiologia , Mutação/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase , Polimorfismo Genético , Análise de Sequência de DNA , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia
5.
J Med Microbiol ; 70(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33593474

RESUMO

This study aimed to evaluate whether the antibiotic fidaxomicin has in vitro activity against Mycobacterium tuberculosis (Mtb). 38 fully drug-sensitive Mtb strains and 34 multidrug-resistant tuberculosis (MDR-TB) strains were tested using the microplate alamar blue assay (MABA) method to determine the minimum inhibitory concentrations (MICs) for fidaxomicin and rifampicin. Fidaxomicin has high in vitro activity against Mtb and is a potential drug to treat Mtb, and MDR-TB infections in particular.


Assuntos
Antituberculosos/farmacologia , Fidaxomicina/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/farmacologia , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
6.
BMC Infect Dis ; 21(1): 205, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627075

RESUMO

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. RESULTS: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. CONCLUSIONS: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.


Assuntos
Isoniazida/uso terapêutico , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antituberculosos/uso terapêutico , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
7.
BMC Infect Dis ; 21(1): 183, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596848

RESUMO

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) are unsatisfied to treat, pressing more effective and innovative treatment regimens. New efficient regimens for MDR-TB have obtained high treatment success rates. However, those regimens without drug susceptibility testing (DST) are also likely to contribute to the emergence of resistance. Precision treatments guided by DST might optimize the patients' treatment outcome individually and minimize resistance amplification. METHODS: TB-TRUST is a phase III, multicenter, open-label, randomized controlled clinical trial of non-inferiority comparing the treatment success rate between the World Health Organization (WHO) shorter regimen and the refined ultra-short regimen for fluoroquinolones and second-line injectable drugs susceptible rifampicin-resistant TB. The control arm uses the WHO injectable-containing shorter regimen for 36-44 weeks depending on time of sputum smear conversion. The investigational arm uses a refined ultra-short regimen guided by molecular DST to pyrazinamide via whole-genome sequencing (WGS) to optimize the treatment of pyrazinamide-susceptible patients with levofloxacin, linezolid, cycloserine and pyrazinamide for 24-32 weeks and pyrazinamide-resistant with levofloxacin, linezolid, cycloserine and clofazimine for 36-44 weeks. The primary outcome is the treatment success rate without relapse at 84 weeks after treatment initiation. Secondary outcomes include the time of sputum culture conversion and occurrence of adverse events. Assuming α = 0.025 level of significance (one-sided test), a power of 80%, a < 10% difference in treatment success rate between control arm and investigational (80% vs. 82%), and a 5% lost follow-up rate, the number of participants per arm to show non-inferiority was calculated as 177(354 in total). DISCUSSION: Rapid molecular testing distinguishes patients who are eligible for shorter regimen with fluoroquinolone and the WGS-guided results shorten the treatment to 6 months for pyrazinamide susceptible patients. It's foreseeable that not only novel developed medicines, but also traditional powerful medicines with the susceptibility confirmed by DST are the key factors to ensure the effect of anti-MDR-TB drugs. As a DST-guided precision treatment, TB-TRUST are expected to optimize therapy outcome in more patients who cannot afford the expensive new medicines and minimize and even avoid resistance amplification with the rational use of anti-TB drugs. TRAIL REGISTRATION: ClinicalTrial.gov, NCT03867136 . Registered on March 7, 2019.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Antituberculosos/efeitos adversos , Protocolos Clínicos , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Feminino , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Pirazinamida/efeitos adversos , Pirazinamida/uso terapêutico , Escarro/microbiologia , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Sequenciamento Completo do Genoma , Adulto Jovem
8.
Chem Biol Interact ; 337: 109397, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33508305

RESUMO

One of the leading killer diseases that target the parenchymal tissues of lungs is Tuberculosis. Although antimycobacterial drugs are available, there are increased incidences of drug resistance encountered in Mycobacterium sp. They have been categorized into MDR (Multidrug resistant) and XDR (Extensively drug-resistant) strains exhibiting resistance toward successive treatment regimen. This situation threatens the futuristic containment of TB with the dearth of anti-TB drugs. Nanotechnology, the emerging multidisciplinary science has presented an excellent opportunity for timely and accurate diagnosis and discrimination of Mycobacteria via its unique physio-chemical and optical characteristics. The delayed and misdiagnosis of TB and lack of sensitive diagnostic method(s) has seen a paradigm shift toward nanoparticulate system for improved diagnosis, drug delivery and reduced treatment frequency. This review article highlights the evolution of tuberculosis and its transformation to multidrug resistant strain. Further, the conventional methods for diagnosing TB and the challenges encountered in their analytical performance have been highlighted and the strategies to overcome those challenges have been briefly discussed. Smart approaches encompassing metal nanoparticles, Quantum Dots (QDs) and Field Effect Transistors (FET) based biosensor for accurate diagnosis have been critically reviewed. A decade long state-of-the-art knowledge on TB nanodiagnostics, fabrication concepts and performance characteristics has been reviewed.


Assuntos
Nanopartículas/química , Nanotecnologia/métodos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Antituberculosos/química , Antituberculosos/uso terapêutico , DNA Bacteriano/metabolismo , Portadores de Fármacos/química , Humanos , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Testes Imediatos , Nanomedicina Teranóstica , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia
9.
Int J Mol Sci ; 22(2)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33450990

RESUMO

The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens. Mycobacteriophages are genetically diverse viruses that specifically infect mycobacterial hosts, including members of the M. tuberculosis complex. This review describes general features of mycobacteriophages and their mechanisms of killing M. tuberculosis, as well as their advantages and limitations as therapeutic and prophylactic agents against drug-resistant M. tuberculosis strains. This review also discusses the role of human lung micro-environments in shaping the availability of mycobacteriophage receptors on the M. tuberculosis cell envelope surface, the risk of potential development of bacterial resistance to mycobacteriophages, and the interactions with the mammalian host immune system. Finally, it summarizes the knowledge gaps and defines key questions to be addressed regarding the clinical application of phage therapy for the treatment of drug-resistant tuberculosis.


Assuntos
Micobacteriófagos/fisiologia , Mycobacterium tuberculosis/virologia , Terapia por Fagos , Tuberculose Resistente a Múltiplos Medicamentos/terapia , Tuberculose/terapia , Animais , Carga Bacteriana , Especificidade de Hospedeiro , Interações Hospedeiro-Patógeno/imunologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Pulmão/imunologia , Pulmão/microbiologia , Mycobacterium tuberculosis/imunologia , Terapia por Fagos/métodos , Resultado do Tratamento , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
10.
PLoS One ; 15(12): e0242604, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33347448

RESUMO

BACKGROUND: There are few data on the on the care experiences of pregnant women with rifampicin-resistant TB. OBJECTIVE: To describe the treatment journeys of pregnant women with RR-TB-including how their care experiences shape their identities-and identify areas in which tailored interventions are needed. METHODS: In this qualitative study in-depth interviews were conducted among a convenience sample from a population of pregnant women receiving treatment for RR-TB. This paper follows COREQ guidelines. A thematic network analysis using an inductive approach was performed to analyze the interview transcripts and notes. The analysis was iterative and a coding system developed which focused on the care experiences of the women and how these experiences affected their perceptions of themselves, their children, and the health care system in which treatment was received. RESULTS: Seventeen women were interviewed. The women described multiple challenges in their treatment journeys which required them to demonstrate sustained resilience (i.e. to "be brave"). Care experiences required them to negotiate seemingly contradictory identities as both new mothers-"givers of life"-and RR-TB patients facing a complicated and potentially deadly disease. In terms of their "pregnancy identity" and "RR-TB patient identity" that emerged as part of their care experiences, four key themes were identified that appeared to have elements that were contradictory to one another (contradictory areas). These included: 1) the experience of physical symptoms or changes; 2) the experience of the "mothering" and "patient" roles; 3) the experience of the care they received for their pregnancy and their RR-TB; and 4) the experience of community engagement. There were also three areas that overlapped with both roles and during which identity was negotiated/reinforced and they included: 1) faith; 2) socioeconomic issues; and 3) long-term concerns over the child's health. At times, the health care system exacerbated these challenges as the women were not given the support they needed by health care providers who were ill-informed or angry and treated the women in a discriminatory fashion. Left to negotiate this confusing time period, the women turned to faith, their own mothers, and the fathers of their unborn children. CONCLUSION: The care experiences of the women who participated in this study highlight several gaps in the current health care system that must be better addressed in both TB and perinatal services in order to improve the therapeutic journeys for pregnant women with RR-TB and their children. Suggestions for optimizing care include the provision of integrated services, including specialized counseling as well as training for health care providers; engagement of peer support networks; provision of socioeconomic support; long-term medical care/follow-up for children born to women who were treated for RR-TB; and inclusion of faith-based services in the provision of care.


Assuntos
Mães/psicologia , Gestantes/psicologia , Apoio Social , Tuberculose Resistente a Múltiplos Medicamentos/psicologia , Tuberculose Pulmonar/psicologia , Adulto , Antituberculosos/uso terapêutico , Coragem , Feminino , Humanos , Lactente , Mycobacterium tuberculosis/patogenicidade , Satisfação do Paciente/estatística & dados numéricos , Gravidez , Pesquisa Qualitativa , Rifampina/uso terapêutico , Identificação Social , África do Sul , Inquéritos e Questionários , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
11.
PLoS One ; 15(12): e0244451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33373997

RESUMO

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013-2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.


Assuntos
Coinfecção/tratamento farmacológico , Assistência à Saúde/organização & administração , Infecções por HIV/tratamento farmacológico , Implementação de Plano de Saúde , Hanseníase/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Assistência ao Convalescente/organização & administração , Assistência ao Convalescente/estatística & dados numéricos , Antirretrovirais/uso terapêutico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Quimioprevenção/métodos , Estudos de Coortes , Coinfecção/microbiologia , Assistência à Saúde/métodos , Assistência à Saúde/estatística & dados numéricos , Farmacorresistência Bacteriana Múltipla , Feminino , Infecções por HIV/virologia , Humanos , Hanseníase/microbiologia , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , Mycobacterium leprae/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/estatística & dados numéricos , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Uganda , Adulto Jovem
12.
PLoS One ; 15(12): e0244829, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33382836

RESUMO

Drug resistance (DR) remains a major challenge for tuberculosis (TB) control. Whole-genome sequencing (WGS) provides the highest genetic resolution for genotypic drug-susceptibility tests (DST). We compared DST profiles of 60 Mycobacterium tuberculosis isolates which were drug resistant according to agar proportion tests (one poly DR-TB, 34 multidrug-resistant TB and 25 extensively drug-resistant TB). We additionally performed minimum inhibitory concentration (MIC) tests using Sensititre MYCOTBI plates (MYCOTB) and a WGS-based DST. Agreement between WGS-based DST and MYCOTB was high for all drugs except ethambutol (65%) and ethionamide (62%). Isolates harboring the -15 c/t inhA promoter mutation had a significantly lower MIC for isoniazid than did isolates with the katG Ser315Thr mutation (p < 0.001). Similar patterns were seen for ethambutol (embB Gly406Asp vs. embB Met306Ile), streptomycin (gid Gly73Ala vs. rpsL Lys43Arg), moxifloxacin (gyrA Ala90Val vs. gyrA Asp94Gly) and rifabutin (rpoB Asp435Phe/Tyr/Val vs. rpoB Ser450Leu). For genotypic heteroresistance, isolates with lower proportion of mapped read tended to has lower MIC of anti-TB drugs than those with higher proportion. These results emphasize the high applicability of WGS for determination of DR-TB and the association of particular mutations with MIC levels.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana/genética , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/uso terapêutico , Etambutol/farmacologia , Etambutol/uso terapêutico , Etionamida/farmacologia , Etionamida/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Feminino , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Sequenciamento Completo do Genoma
13.
PLoS Comput Biol ; 16(12): e1008518, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33347430

RESUMO

Tuberculosis disease is a major global public health concern and the growing prevalence of drug-resistant Mycobacterium tuberculosis is making disease control more difficult. However, the increasing application of whole-genome sequencing as a diagnostic tool is leading to the profiling of drug resistance to inform clinical practice and treatment decision making. Computational approaches for identifying established and novel resistance-conferring mutations in genomic data include genome-wide association study (GWAS) methodologies, tests for convergent evolution and machine learning techniques. These methods may be confounded by extensive co-occurrent resistance, where statistical models for a drug include unrelated mutations known to be causing resistance to other drugs. Here, we introduce a novel 'cannibalistic' elimination algorithm ("Hungry, Hungry SNPos") that attempts to remove these co-occurrent resistant variants. Using an M. tuberculosis genomic dataset for the virulent Beijing strain-type (n = 3,574) with phenotypic resistance data across five drugs (isoniazid, rifampicin, ethambutol, pyrazinamide, and streptomycin), we demonstrate that this new approach is considerably more robust than traditional methods and detects resistance-associated variants too rare to be likely picked up by correlation-based techniques like GWAS.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Mutação Puntual , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Algoritmos , Antituberculosos/farmacologia , Genes Bacterianos , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Aprendizado de Máquina , Testes de Sensibilidade Microbiana , Modelos Biológicos , Mycobacterium tuberculosis/efeitos dos fármacos , Filogenia , Polimorfismo de Nucleotídeo Único
14.
BMC Infect Dis ; 20(1): 752, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054726

RESUMO

BACKGROUND: Molecular epidemiological studies of Mycobacterium tuberculosis (MTB) are the core of current research to find out the association of the M. tuberculosis genotypes with its outbreak and transmission. The high prevalence of the Beijing genotype strain among multidrug resistance (MDR) TB has already been reported in various studies around India. The overall objective of this study was to detect the prevalence of Beijing genotype strains of MDR M. tuberculosis and their association with the clinical characteristics of TB patients. METHODS: In this study 381 M. tuberculosis clinical isolates were obtained from sputum samples from 2008 to 2014. The multiplex-PCR and Spoligotyping (n = 131) methods were used to investigate the prevalence of the Beijing genotype strain by targeting the Rv2820 gene and their association with drug resistance and clinical characteristics of TB patients. The drug susceptibility testing of first-line anti-TB drugs was performed by using the proportion method and MGIT960. A collection of isolates having Beijing and non-Beijing strains were also characterized to see if Beijing genotype strains had a higher rate of mutations at codons 516, 526 and 531 of the 81-bp region of the rpoB gene, codon 315 of the katG gene, and codon 306 of the embB gene. RESULTS: The sensitivities and specificities of multiplex-PCR assay compared to that of standard Spoligotyping was detected to be 100%. Further, we observe that the multi drug-resistance was significantly associated with Beijing genotype strains (p = 0.03) and a strong correlation between Beijing genotype strains and specific resistance mutations at the katG315, rpoB531, and embB306 codons (p = < 0.0001, < 0.0001 & 0.0014 respectively) was also found. CONCLUSIONS: This rapid, simple, and cost-effective multiplex PCR assay can effectively be used for monitoring the prevalence of Beijing genotype strains in low resource settings. Findings of this study may provide a scientific basis for the development of new diagnostic tools for detection and effective management of DR-TB in countries with a higher incidence rate of Beijing genotype strains.


Assuntos
Proteínas de Bactérias/genética , Catalase/genética , RNA Polimerases Dirigidas por DNA/genética , Mycobacterium tuberculosis/genética , Pentosiltransferases/genética , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/farmacologia , Criança , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Genótipo , Humanos , Índia/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex/métodos , Taxa de Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto Jovem
15.
PLoS One ; 15(8): e0236362, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32797053

RESUMO

BACKGROUND: Tuberculosis (TB) is among the top 10 causes of mortality and the first killer among infectious diseases worldwide. One of the factors fuelling the TB epidemic is the global rise of multidrug resistant TB (MDR-TB). The aim of this study was to determine the magnitude and factors associated with MDR-TB in the Tigray Region, Ethiopia. METHOD: This study employed a facility-based cross-sectional study design, which was conducted between July 2018 and August 2019. The inclusion criteria for the study participants were GeneXpert-positive who were not under treatment for TB, PTB patients' ≥15 years of age and who provided written informed consent. A total of 300 participants were enrolled in the study, with a structured questionnaire used to collect data on clinical, sociodemographic and behavioral factors. Sputum samples were collected and processed for acid-fast bacilli staining, culture and drug susceptibility testing. Drug susceptibility testing was performed using a line probe assay. Logistic regression was used to analyze associations between outcome and predictor variables. RESULTS: The overall proportion of MDR-TB was 16.7% (11.6% and 32.7% for new and previously treated patients, respectively). Of the total MDR-TB isolates, 5.3% were pre-XDR-TB. The proportion of MDR-TB/HIV co-infection was 21.1%. A previous history of TB treatment AOR 3.75; 95% CI (0.7-2.24), cigarette smoking AOR 6.09; CI (1.65-2.50) and patients who had an intermittent fever (AOR = 2.54, 95% CI = 1.21-5.4) were strongly associated with MDR-TB development. CONCLUSIONS: The magnitude of MDR-TB observed among new and previously treated patients is very alarming, which calls for an urgent need for intervention. The high proportion of MDR-TB among newly diagnosed cases indicates ongoing transmission, which suggests the need for enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to prevent the evolution of drug resistance. Assessing the TB control program performance gaps and an optimal implementation of the WHO recommended priority actions for the management of drug-resistant TB, is imperative to help reduce the current high MDR-TB burden in the study region.


Assuntos
Infecções por HIV/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Estudos Transversais , Etiópia/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/microbiologia , Infecções por HIV/patologia , Humanos , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Rifampina/uso terapêutico , Fatores de Risco , Escarro/efeitos dos fármacos , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/patologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Adulto Jovem
16.
PLoS One ; 15(8): e0236054, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750053

RESUMO

INTRODUCTION: Multi-drug resistance is a major challenge in the control of tuberculosis. Despite newer modalities for diagnosis and treatment, people are still suffering from this disease. Understanding the common gene mutations conferring rifampicin and isoniazid resistance is crucial for the implementation of effective molecular tools at local and national levels. Hence, this study aimed to evaluate the molecular detection of rifampicin and isoniazid-resistant gene mutations in M.tuberculosis isolates in Addis Ababa, Ethiopia. METHOD: Health Center-based cross-sectional study was conducted between January and September 2017 in Addis Ababa, Ethiopia. The collected sputum samples were processed for mycobacterial isolation and Region of difference 9 based polymerase chain reaction for species identification. To characterize the rifampicin and isoniazid-resistant M. tuberculosis isolates, a molecular genetic assay (GenoType MTBDRplus) was used; the assay is based on DNA-STRIP technology. RESULT: Culture positivity was confirmed in 82.6% (190/230) of smear-positive newly diagnosed pulmonary tuberculosis cases enrolled in the study. From 190 isolates 93.2% were sensitive for both rifampicin and isoniazid, and 6.8% of the isolates were resistant to at least one of the tested anti-TB drugs. Gene mutations were observed in all studied multidrug resistance-associated gene loci (rpoB, katG, and inhA). Two isolates exhibited heteroresistance, a mutated, as well as wild type sequences, were detected in the respective strains. MDR-TB case was observed in 1.1% (2/190) of the cases. All the MDR-TB cases were positive for HIV and found to have a history of prior hospital admission. CONCLUSION: In our finding a relatively high prevalence of any drug resistance was observed and the overall prevalence of multidrug-resistant tuberculosis was 1.1%.The majority of drug-resistant isolates demonstrated common mutations. Heteroresistant strains were detected, signaling the existence of an M.tuberculosis population with variable responses to anti-tuberculosis drugs or of mixed infections.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/uso terapêutico , Estudos Transversais , Análise Mutacional de DNA , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Etiópia , Feminino , Genes Bacterianos/genética , Loci Gênicos/genética , Humanos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase , Rifampina/farmacologia , Rifampina/uso terapêutico , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
17.
BMC Infect Dis ; 20(1): 570, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758165

RESUMO

BACKGROUND: In sub-Saharan Africa (SSA), most prisons are overcrowded with poor ventilation and put prisoners disproportionally at risk of exposure to Mycobacterium tuberculosis (TB) and developing TB infection but are mostly missed due to poor access to healthcare. Active case-finding (ACF) of TB in prisons facilitates early diagnosis and treatment of inmates and prevent the spread. We explored literature and described evidence on TB ACF interventions and approaches for prisoners in SSA prisons. METHODS: Guided by the Arksey and O'Malley framework, we searched PubMed, Google Scholar, SCOPUS, Academic search complete, CINAHL and MEDLINE with full text via EBSCOhost for articles on prisoners and ACF from 2000 to May 2019 with no language restriction. Two investigators independently screened the articles at the abstract and full-text stages in parallel guided by the eligibility criteria as well as performed the methodological quality appraisal of the included studies using the latest mixed-method appraisal tool. We extracted all relevant data, organized them into themes and sub-themes, and presented a narrative summary of the results. RESULTS: Of the 391 eligible articles found, 31 met the inclusion criteria. All 31 articles were published between 2006 and 2019 with the highest six (19.4%) in 2015. We found evidence in 11 countries. That is, Burkina Faso, Cameroon, Coˆte d'Ivoire, the Democratic Republic of the Congo, Ethiopia, Ghana, Malawi, Nigeria, South Africa, Uganda, and Zambia with most 41.9% (13/31) recorded in Ethiopia. These intervention studies were conducted in 134 prisons between 2001 and 2018 using either a single or combination of mass, facility-led, entry, peer educators for routine screening, and exit ACF approaches. The majority (74%) of the studies utilized only a mass screening approach. The most (68%) reported study outcome was smear-positive TB cases only (68%). We found no evidence in 16 SSA countries although they are classified among the three high-burden country lists for TB TB/HIV and Multidrug resistant-TB group. CONCLUSION: Our review highlights a dearth of evidence on TB ACF interventions in most SSA countries prisons. Hence, there is the need to scaling-up ACF interventions in SSA prisons, particularly countries included in the three high-burden country lists for TB, TB/HIV, and MDR-TB.


Assuntos
Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/imunologia , Prisioneiros , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , África ao Sul do Saara/epidemiologia , Antibióticos Antituberculose/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Prevalência , Rifampina/uso terapêutico , Escarro/microbiologia , Teste Tuberculínico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
18.
BMC Infect Dis ; 20(1): 576, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758169

RESUMO

BACKGROUND: China ranks second in the world in terms of numbers of tuberculosis (TB) cases and is one of the top three countries with the largest number of multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB). It also has high mortality and low cure rates of human immunodeficiency virus (HIV)-positive TB patients. This study aimed to analyse, under the integrated TB control model, the characteristics of TB patients seeking healthcare in the largest designated TB hospital in Chongqing. METHODS: This was a retrospective study of TB registers in a health facility. Record data of 1827 TB patients who had attended the Chongqing Public Health Medical Center (CPHMC) from 1 January to 31 December 2018 were included. The Statistical Package for Social Science (SPSS 18.0; IBM Corporation, Armonk, NY, USA) was used to analyse the data. Counting data were compared using the chi-square test or Fisher' s exact test. Among the results of the univariate analysis, the variables with statistical significance were included in the binomial stepwise logistic regression, with odds ratio and 95% confidence interval calculated. A two-tailed probability level of P < 0.05 was considered statistically significant. RESULTS: The majority of registered patients were men (1197), of Han ethnicity (1670), aged 21-60 years (1331), farmer/unemployed (1075), and living in county/district (1207). Approximately 24.9% of patients (455/1827) contracted DR-TB, 6% (110/1827) were co-infected with HIV, and 41.0% (749/1827) had drug-related hepatotoxicity. Among those patients, DR-TB was more likely to develop among farmers who received retreatment and had drug-related hepatotoxicity (P < 0.05). Women who received retreatment and lived in county/district were less likely to be HIV positive (P < 0.05). Compared with farmers, patients who were unemployed were more likely to be HIV positive, and those aged 21-60 years had a higher risk of being tested as HIV positive (P < 0.05). CONCLUSION: Farmers who received retreatment and had drug-related hepatotoxicity are more susceptible to DR-TB; young unemployed men have a higher risk of contracting HIV-positive TB. The demographic and clinical characteristics of TB patients should be taken into consideration in DR-TB and HIV-positive TB screening in the future.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Coinfecção/epidemiologia , HIV , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , China/epidemiologia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Fazendeiros , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Desemprego , Adulto Jovem
19.
Cochrane Database Syst Rev ; 8: CD013359, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32853411

RESUMO

BACKGROUND: Every year, at least one million children become ill with tuberculosis and around 200,000 children die. Xpert MTB/RIF and Xpert Ultra are World Health Organization (WHO)-recommended rapid molecular tests that simultaneously detect tuberculosis and rifampicin resistance in adults and children with signs and symptoms of tuberculosis, at lower health system levels. To inform updated WHO guidelines on molecular assays, we performed a systematic review on the diagnostic accuracy of these tests in children presumed to have active tuberculosis. OBJECTIVES: Primary objectives • To determine the diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for (a) pulmonary tuberculosis in children presumed to have tuberculosis; (b) tuberculous meningitis in children presumed to have tuberculosis; (c) lymph node tuberculosis in children presumed to have tuberculosis; and (d) rifampicin resistance in children presumed to have tuberculosis - For tuberculosis detection, index tests were used as the initial test, replacing standard practice (i.e. smear microscopy or culture) - For detection of rifampicin resistance, index tests replaced culture-based drug susceptibility testing as the initial test Secondary objectives • To compare the accuracy of Xpert MTB/RIF and Xpert Ultra for each of the four target conditions • To investigate potential sources of heterogeneity in accuracy estimates - For tuberculosis detection, we considered age, disease severity, smear-test status, HIV status, clinical setting, specimen type, high tuberculosis burden, and high tuberculosis/HIV burden - For detection of rifampicin resistance, we considered multi-drug-resistant tuberculosis burden • To compare multiple Xpert MTB/RIF or Xpert Ultra results (repeated testing) with the initial Xpert MTB/RIF or Xpert Ultra result SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, the WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and the International Standard Randomized Controlled Trials Number (ISRCTN) Registry up to 29 April 2019, without language restrictions. SELECTION CRITERIA: Randomized trials, cross-sectional trials, and cohort studies evaluating Xpert MTB/RIF or Xpert Ultra in HIV-positive and HIV-negative children younger than 15 years. Reference standards comprised culture or a composite reference standard for tuberculosis and drug susceptibility testing or MTBDRplus (molecular assay for detection of Mycobacterium tuberculosis and drug resistance) for rifampicin resistance. We included studies evaluating sputum, gastric aspirate, stool, nasopharyngeal or bronchial lavage specimens (pulmonary tuberculosis), cerebrospinal fluid (tuberculous meningitis), fine needle aspirates, or surgical biopsy tissue (lymph node tuberculosis). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed study quality using the Quality Assessment of Studies of Diagnostic Accuracy - Revised (QUADAS-2). For each target condition, we used the bivariate model to estimate pooled sensitivity and specificity with 95% confidence intervals (CIs). We stratified all analyses by type of reference standard. We assessed certainty of evidence using the GRADE approach. MAIN RESULTS: For pulmonary tuberculosis, 299 data sets (68,544 participants) were available for analysis; for tuberculous meningitis, 10 data sets (423 participants) were available; for lymph node tuberculosis, 10 data sets (318 participants) were available; and for rifampicin resistance, 14 data sets (326 participants) were available. Thirty-nine studies (80%) took place in countries with high tuberculosis burden. Risk of bias was low except for the reference standard domain, for which risk of bias was unclear because many studies collected only one specimen for culture. Detection of pulmonary tuberculosis For sputum specimens, Xpert MTB/RIF pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 64.6% (55.3% to 72.9%) (23 studies, 493 participants; moderate-certainty evidence) and 99.0% (98.1% to 99.5%) (23 studies, 6119 participants; moderate-certainty evidence). For other specimen types (nasopharyngeal aspirate, 4 studies; gastric aspirate, 14 studies; stool, 11 studies), Xpert MTB/RIF pooled sensitivity ranged between 45.7% and 73.0%, and pooled specificity ranged between 98.1% and 99.6%. For sputum specimens, Xpert Ultra pooled sensitivity (95% CI) and specificity (95% CI) verified by culture were 72.8% (64.7% to 79.6%) (3 studies, 136 participants; low-certainty evidence) and 97.5% (95.8% to 98.5%) (3 studies, 551 participants; high-certainty evidence). For nasopharyngeal specimens, Xpert Ultra sensitivity (95% CI) and specificity (95% CI) were 45.7% (28.9% to 63.3%) and 97.5% (93.7% to 99.3%) (1 study, 195 participants). For all specimen types, Xpert MTB/RIF and Xpert Ultra sensitivity were lower against a composite reference standard than against culture. Detection of tuberculous meningitis For cerebrospinal fluid, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 54.0% (95% CI 27.8% to 78.2%) (6 studies, 28 participants; very low-certainty evidence) and 93.8% (95% CI 84.5% to 97.6%) (6 studies, 213 participants; low-certainty evidence). Detection of lymph node tuberculosis For lymph node aspirates or biopsies, Xpert MTB/RIF pooled sensitivity and specificity, verified by culture, were 90.4% (95% CI 55.7% to 98.6%) (6 studies, 68 participants; very low-certainty evidence) and 89.8% (95% CI 71.5% to 96.8%) (6 studies, 142 participants; low-certainty evidence). Detection of rifampicin resistance Xpert MTB/RIF pooled sensitivity and specificity were 90.0% (67.6% to 97.5%) (6 studies, 20 participants; low-certainty evidence) and 98.3% (87.7% to 99.8%) (6 studies, 203 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: We found Xpert MTB/RIF sensitivity to vary by specimen type, with gastric aspirate specimens having the highest sensitivity followed by sputum and stool, and nasopharyngeal specimens the lowest; specificity in all specimens was > 98%. Compared with Xpert MTB/RIF, Xpert Ultra sensitivity in sputum was higher and specificity slightly lower. Xpert MTB/RIF was accurate for detection of rifampicin resistance. Xpert MTB/RIF was sensitive for diagnosing lymph node tuberculosis. For children with presumed tuberculous meningitis, treatment decisions should be based on the entirety of clinical information and treatment should not be withheld based solely on an Xpert MTB/RIF result. The small numbers of studies and participants, particularly for Xpert Ultra, limits our confidence in the precision of these estimates.


Assuntos
Tipagem Molecular/métodos , Tuberculose dos Linfonodos/diagnóstico , Tuberculose Meníngea/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Pulmonar/diagnóstico , Adolescente , Antibióticos Antituberculose/uso terapêutico , Viés , Criança , Fezes/microbiologia , Conteúdo Gastrointestinal/microbiologia , Humanos , Tipagem Molecular/normas , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Rifampina/uso terapêutico , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose dos Linfonodos/tratamento farmacológico , Tuberculose dos Linfonodos/microbiologia , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/tratamento farmacológico , Tuberculose Meníngea/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
20.
Int J Infect Dis ; 98: 420-439, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32645375

RESUMO

OBJECTIVE: To assess poor treatment outcomes and their predictors among drug-resistant tuberculosis patients treated in Ethiopia. METHODS: Data were searched from both electronic databases and other sources. From the whole search, 404 articles were reviewed and 17 articles that fulfilled the inclusion criteria were included in the analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed and Joanna Briggs Institute Critical Appraisal checklist was used for assessing the quality. Risk of bias was assessed using forest plot and Egger's regression test. Data were analyzed using STATA version 15 and Review Manager Software version 5.3. RESULTS: The overall pooled proportion of poor treatment outcome and mortality was 17.86% and 15.13% respectively. The incidence density rate of poor treatment outcome and mortality was 10.41/1000 person-months and 9.28/1000 person-months respectively. Survival status and successful treatment outcomes were 76.97% and 63.82% respectively. HIV positivity, non-HIV comorbidities, clinical complications, extrapulmonary involvement, undernutrition, anemia, treatment delay, lower body weight, and older age were the predictors of poor treatment outcome. CONCLUSION: Better survival and treatment success rates were noted in Ethiopia as compared to the global average. The majority of the poor treatment outcomes occurred within the intensive phase. Early initiation of anti-tuberculosis treatment would be important for successful treatment outcomes.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Etiópia/epidemiologia , Feminino , Humanos , Masculino , Tempo para o Tratamento , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/mortalidade , Adulto Jovem
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