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1.
BMC Infect Dis ; 21(1): 2, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397308

RESUMO

BACKGROUND: Acquiring comprehensive insight into the dynamics of Mycobacterium tuberculosis (Mtb) population structure is an essential step to adopt effective tuberculosis (TB) control strategies and improve therapeutic methods and vaccines. Accordingly, we performed this systematic review and meta-analysis to determine the overall prevalence of Mtb genotypes/ sublineages in Iran. METHODS: We carried out a comprehensive literature search using the international databases of MEDLINE and Scopus as well as Iranian databases. Articles published until April 2020 were selected based on the PRISMA flow diagram. The overall prevalence of the Mtb genotypes/sublineage in Iran was determined using the random effects or fixed effect model. The metafor R package and MedCalc software were employed for performing this meta-analysis. RESULTS: We identified 34 studies for inclusion in this study, containing 8329 clinical samples. Based on the pooled prevalence of the Mtb genotypes, NEW1 (21.94, 95% CI: 16.41-28.05%), CAS (19.21, 95% CI: 14.95-23.86%), EAI (12.95, 95% CI: 7.58-19.47%), and T (12.16, 95% CI: 9.18-15.50%) were characterized as the dominant circulating genotypes in Iran. West African (L 5/6), Cameroon, TUR and H37Rv were identified as genotypes with the lowest prevalence in Iran (< 2%). The highest pooled prevalence rates of multidrug-resistant strains were related to Beijing (2.52, 95% CI) and CAS (1.21, 95% CI). CONCLUSIONS: This systematic review showed that Mtb populations are genetically diverse in Iran, and further studies are needed to gain a better insight into the national diversity of Mtb populations and their drug resistance pattern.


Assuntos
Variação Genética , Genótipo , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Humanos , Irã (Geográfico)/epidemiologia , Prevalência , Tuberculose Pulmonar/microbiologia
2.
PLoS One ; 15(12): e0242408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315885

RESUMO

We sought to develop a smooth and low cost sample preparation and DNA extraction protocol, streamlined with a ready-to-use qPCR in a portable instrument to overcome some of the existing hurdles. Several solutions were evaluated as to their ability to liquefy a mucin-based matrix. Each liquefied matrix, supplemented with either Mycobacterium tuberculosis (MTB) H37Rv strain DNA or intact cells, was aliquoted onto a filter paper embedded with solubilizing agents, and was subsequently dried up. Most of the nucleic acids, including genomic DNA from the bacilli and the host, binds to the filter paper. Next, several protocols were evaluated to elute the DNA from the paper, using qPCR to detect the insertion sequence IS6110, a M. tuberculosis complex genomic marker. The limit of detection (LOD) of the best protocol was then evaluated using parallel seeding and colony counting. The protocol was also evaluated using seventeen sputum samples, previously characterized by the GeneXpert or culture. Two instruments (the ABI7500 Standard and the Q3-Plus system) and two reagents storage formats (frozen or ready-to-use) were evaluated. Solutions containing guanidine isothiocyanate exerted the best liquefying effect on the mucin-based matrix extracted from one 6-mm punches, followed by a brief incubation at 95°C. The resulting DNA contained impurities, but a simple 1:10 dilution elicited the detection of MTB and human genomic targets. The described protocol presented an apparent LOD of 02 CFU/mL of MTB. Challenging the protocol with previously characterized samples showed substantial agreement with GeneXpert MTB/RIF results (sensitivity of 90%, agreement of 88.9%, kappa coefficient of 0.77), and moderate agreement with culture results (sensitivity of 100%, agreement of 78.9%, kappa coefficient of 0.58). This work presents a sensitive proof-of-concept protocol for sputum liquefaction and decontamination followed by a simple DNA extraction procedure, in which the extraction steps are streamlined with a ready-to-use qPCR in a portable instrument that can be employed in low infrastructure settings.


Assuntos
Programas de Rastreamento/métodos , Mycobacterium tuberculosis/isolamento & purificação , Sistemas Automatizados de Assistência Junto ao Leito , Manejo de Espécimes/métodos , Tuberculose Pulmonar/diagnóstico , Brasil , DNA Bacteriano/isolamento & purificação , Humanos , Limite de Detecção , Programas de Rastreamento/economia , Programas de Rastreamento/instrumentação , Mycobacterium tuberculosis/genética , Estudo de Prova de Conceito , Reação em Cadeia da Polimerase em Tempo Real/economia , Reação em Cadeia da Polimerase em Tempo Real/instrumentação , Reação em Cadeia da Polimerase em Tempo Real/métodos , Manejo de Espécimes/economia , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia
3.
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
4.
PLoS One ; 15(12): e0240595, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332367

RESUMO

SETTING: Alcohol use increases the risk of tuberculosis (TB) disease and is associated with worse outcomes. OBJECTIVE: To determine whether alcohol use affects TB severity at diagnosis in a high-burden setting. DESIGN: Participants were smear-positive people living with TB (PLWTB) in India. Disease severity was assessed as 1) high versus low smear grade, 2) time to positivity (TTP) on liquid culture, 3) chest radiograph cavitation, and 4) percent lung affected. Alcohol use and being at-risk for alcohol use disorders (AUD) were assessed using the AUDIT-C. Univariable and multivariable analyses were conducted. RESULTS: Of 1166 PLWTB, 691 (59.3%) were drinkers; of those, 518/691 (75.0%) were at-risk for AUD. Drinkers had more lung affected than non-drinkers (adjusted mean difference 10.8%, p<0.0001); this was not significant for those at-risk for AUD (adjusted mean difference 3.7%, p = 0.11). High smear grade (aOR 1.0, 95%CI: 0.7-1.4), cavitation (aOR 0.8, 95%CI 0.4-1.8), and TTP (mean difference 5.2 hours, p = 0.51) did not differ between drinkers and non-drinkers, nor between those at-risk and not at-risk for AUD. CONCLUSIONS: A large proportion of PLWTB were drinkers and were at-risk for AUD. Alcohol drinkers had more lung affected than non-drinkers. Studies are needed to explore mechanisms of this association.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Alcoolismo/epidemiologia , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/complicações , Feminino , Humanos , Índia , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Estudos Prospectivos , Radiografia , Fatores de Risco , Índice de Gravidade de Doença , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
5.
BMC Infect Dis ; 20(1): 924, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276721

RESUMO

BACKGROUND: The presentation of pulmonary tuberculosis (PTB) in young children is often clinically indistinguishable from other common respiratory illnesses, which are frequently infections of viral aetiology. As little is known about the role of viruses in children with PTB, we investigated the prevalence of respiratory viruses in children with suspected PTB at presentation and follow-up. METHODS: In an observational cohort study, children < 13 years were routinely investigated for suspected PTB in Cape Town, South Africa between December 2015 and September 2017 and followed up for 24 weeks. Nasopharyngeal aspirates (NPAs) were tested for respiratory viruses using multiplex PCR at enrolment, week 4 and 8. RESULTS: Seventy-three children were enrolled [median age 22.0 months; (interquartile range 10.0-48.0); 56.2% male and 17.8% HIV-infected. Anti-tuberculosis treatment was initiated in 54.8%; of these 50.0% had bacteriologically confirmed TB. At enrolment, ≥1 virus were detected in 95.9% (70/73) children; most commonly human rhinovirus (HRV) (74.0%). HRV was more frequently detected in TB cases (85%) compared to ill controls (60.6%) (p = 0.02). Multiple viruses were detected in 71.2% of all children; 80% of TB cases and 60.6% of ill controls (p = 0.07). At follow-up, ≥1 respiratory virus was detected in 92.2% (47/51) at week 4, and 94.2% (49/52) at week 8. CONCLUSIONS: We found a high prevalence of viral respiratory co-infections in children investigated for PTB, irrespective of final PTB diagnosis, which remained high during follow up. Future work should include investigating the whole respiratory ecosystem in combination with pathogen- specific immune responses.


Assuntos
Coinfecção/epidemiologia , Infecções por Enterovirus/epidemiologia , Enterovirus/genética , Infecções por HIV/epidemiologia , HIV/genética , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/epidemiologia , Pré-Escolar , Coinfecção/virologia , Infecções por Enterovirus/virologia , Feminino , Seguimentos , Infecções por HIV/virologia , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase Multiplex , Prevalência , África do Sul/epidemiologia , Teste Tuberculínico , Tuberculose Pulmonar/microbiologia
6.
BMC Infect Dis ; 20(1): 937, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33297969

RESUMO

BACKGROUND: There is scarce evidence that tuberculosis (TB) can cause diabetes in those not previously known to be diabetic. Whilst the World Health Organization (WHO) recommends screening for Diabetes Mellitus (DM) at the onset of TB treatment, nevertheless, it remains to be elucidated which patients with TB-associated hyperglycemia are at higher risk for developing DM and stand to benefit from a more regular follow-up. This review aims to firstly quantify the reduction of newly detected hyperglycemia burden in TB patients who are on treatment over time; secondly, determine the burden of TB-associated hyperglycemia after follow-up, and thirdly, synthesize literature on risk factors for unresolved TB-associated hyperglycemia in previously undiagnosed individuals. METHODS: We searched PUBMED, EMBASE, SCOPUS, and Global Health for articles on TB-associated hyperglycemia up to September 30th, 2019. Search terms included Tuberculosis and hyperglycemia/DM, and insulin resistance. We appraised studies, extracted data, and conducted a meta-analysis to assess the change of the burden of hyperglycemia in prospective studies. The review is registered in the PROSPERO database (CRD42019118173). RESULTS: Eleven studies were included in the meta-analysis yielding a total of 677 (27,3%) of patients with newly detected hyperglycemia at baseline. The mean quality score of eligible studies using the Newcastle-Ottawa Quality Assessment Scale was 7.1 out of 9 (range 6-9). The pooled unresolved new cases of hyperglycemia at the end of follow up was 50% (95% CI: 36-64%) and the total pooled burden of hyperglycemia at 3-6 months of follow up was 11% (95% CI: 7-16%), with both estimates displaying a high heterogeneity, which remained significant after performing a sub-analysis by DM diagnostic method and 3 months of follow up. As only 2 studies explored risk factors for unresolved hyperglycemia, no meta-analysis was performed on risk factors. CONCLUSION: Our meta-analysis showed that although in half of the patients with newly observed hyperglycemia at baseline, it remained unresolved at a follow-up of 3 to 6 months, the total burden of hyperglycemia is slightly above 10%, 3 months after initiating TB treatment. Studies are warranted to assess whether risk factors including HIV positivity, smoking, and extensive pulmonary TB disease put patients at higher risk for DM.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Hiperglicemia/epidemiologia , Mycobacterium tuberculosis , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , África ao Sul do Saara/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Estudos Prospectivos , Fatores de Risco , Tuberculose Pulmonar/microbiologia , Adulto Jovem
7.
Nat Commun ; 11(1): 5566, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149141

RESUMO

Tuberculosis (TB) is a leading cause of mortality due to infectious disease, but the factors determining disease progression are unclear. Transcriptional signatures associated with type I IFN signalling and neutrophilic inflammation were shown to correlate with disease severity in mouse models of TB. Here we show that similar transcriptional signatures correlate with increased bacterial loads and exacerbate pathology during Mycobacterium tuberculosis infection upon GM-CSF blockade. Loss of GM-CSF signalling or genetic susceptibility to TB (C3HeB/FeJ mice) result in type I IFN-induced neutrophil extracellular trap (NET) formation that promotes bacterial growth and promotes disease severity. Consistently, NETs are present in necrotic lung lesions of TB patients responding poorly to antibiotic therapy, supporting the role of NETs in a late stage of TB pathogenesis. Our findings reveal an important cytokine-based innate immune effector network with a central role in determining the outcome of M. tuberculosis infection.


Assuntos
Armadilhas Extracelulares/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interferon Tipo I/metabolismo , Pulmão/microbiologia , Mycobacterium tuberculosis/imunologia , Neutrófilos/imunologia , Pneumonia/imunologia , Tuberculose Pulmonar/imunologia , Animais , Bases de Dados Genéticas , Progressão da Doença , Perfilação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Interferon Tipo I/genética , Interferon gama/genética , Interferon gama/metabolismo , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycobacterium tuberculosis/patogenicidade , Pneumonia/genética , Pneumonia/metabolismo , Pneumonia/patologia , RNA-Seq , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/microbiologia
8.
Pan Afr Med J ; 37: 45, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33209172

RESUMO

Introduction: it is unclear what the optimal treatment regimen for previously treated patients with rifampicin-susceptible isoniazid resistant tuberculosis should be. Conflicting evidence exists as to the effectiveness of the WHO standardized category II regimen in these patients. The objectives were to compare treatment outcomes between previously treated rifampicin-susceptible pulmonary tuberculosis patients with and without isoniazid resistance using the category II regimen and determine factors associated with an unfavourable outcome in those with isoniazid resistance in four regions of Cameroon. Methods: we conducted a retrospective review of all bacteriologically confirmed previously treated rifampicin-susceptible patients with and without isoniazid resistance registered in four regions of Cameroon from January 2012 to March 2015. Results: a total of 753 patients with a mean age of 38 ± 12 years including 498(66%) males were registered. Forty seven of the 753 had isoniazid-resistant TB, giving a prevalence of 6.2% (95% CI: 4.7-8.2). Treatment outcomes could only be ascertained for 733 patients as 20 (2.7%) were transferred out to other regions. Twenty-nine percent of patients with isoniazid resistance as against 21% of isoniazid susceptible patients had an unfavourable outcome (p = 0.32). In a multivariate logistic regression analysis, only HIV infection was significantly associated with an unfavourable outcome in isoniazid-resistant patients (p = 0.02). Conclusion: treatment outcomes using WHO category II regimen in previously treated rifampicin -susceptible pulmonary tuberculosis patients with and without isoniazid resistance in four regions of Cameroon are similar. HIV infection is an independent risk factor for an unfavourable outcome in patients with rifampicin-susceptible isoniazid-resistant disease treated with this regimen.


Assuntos
Antituberculosos/administração & dosagem , Isoniazida/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Camarões , Criança , Pré-Escolar , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rifampina/administração & dosagem , Fatores de Risco , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
9.
BMC Infect Dis ; 20(1): 873, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225919

RESUMO

BACKGROUND: Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of death globally. However, little is known about the long-term mortality risk and the timeline of death in those co-infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB). This study sought to understand the long-term mortality risk, factors, and the timeline of death in those with HIV-Mycobacterium tuberculosis (MTB) coinfection, particularly in those with insufficient TB treatment. METHODS: TB-cause specific deaths were classified using a modified 'Coding of Cause of Death in HIV' protocol. A longitudinal cross-registration-system checking approach was used to confirm HIV/MTB co-infection between two observational cohorts. Mortality from the end of TB treatment (6 months) to post-treatment year (PTY) 5 (60 months) was investigated by different TB treatment outcomes. General linear models were used to estimate the mean mortality at each time-point and change between time-points. Cox's proportional hazard regressions measured the mortality hazard risk (HR) at each time-point. The Mantel-Haenszel stratification was used to identify mortality risk factors. Mortality density was calculated by person year of follow-up. RESULTS: At the end point, mortality among patients with HIV/MTB coinfection was 34.7%. From the end of TB treatment to PTY5, mortality and loss of person years among individuals with TB treatment failure, missing, and adverse events (TBFMA) were significantly higher than those who had TB cure (TBC) and TB complete regimen (TBCR). Compared to individuals with TBC and with TBCR, individuals with TBFMA tended to die earlier and their mortality was significantly higher (HRTBFMA-TBC = 3.0, 95% confidence interval: 2.5-3.6, HRTBFMA-TBCR = 2.9, 95% CI: 2.5-3.4, P < 0.0001). Those who were naïve to antiretroviral therapy, were farmers, had lower CD4 counts (≤200 cells/µL) and were ≥ 50 years of age were at the highest risk of mortality. Mortality risk for participants with TBFMA was significantly higher across all stratifications except those with a CD4 count of ≤200 cells/µL. CONCLUSIONS: Earlier and long-term mortality among those with HIV/MTB co-infection is a significant problem when TB treatment fails or is inadequate.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Antituberculosos/uso terapêutico , Coinfecção/mortalidade , HIV/imunologia , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Idoso , China/epidemiologia , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
10.
PLoS One ; 15(11): e0241203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33147240

RESUMO

Tuberculosis prevalence surveys have demonstrated the benefit of screening with chest x-ray (CXR) and sensitive diagnostic tests compared to symptoms and smear microscopy. However, in programmatic practice there is little evidence on the yield of different algorithms. We implemented contact tracing in Chennai, India for adult sputum-positive TB patients registered from January 2015 to March 2016. Patients with symptoms or abnormal X-ray findings further underwent testing using Xpert MTB/RIF (Xpert) and smear microscopy. A retrospective cohort study was done to summarize the key findings. We verbally screened 5553 contacts for symptoms, CXR through private sector collaboration, Xpert, and smear microscopy. Overall, 1312 (23.6%) contacts screened positive. CXR alone identified 531 (40.5%) of them, 679 (51.8%) were symptom-positive only, while 102 (7.8%) were positive on both the symptom and CXR screen. Overall, 35 bacteriologically positive cases were identified (0.7%). A standard approach of symptoms screening followed by microscopy identified only 9 (25.7%) of the total number of bacteriologically positive cases, whereas the combination of a CRX screening followed by microscopy identified 13 (37.1%) of the cases. The algorithm of symptoms screening followed by Xpert testing, detected 20 cases, whereas the combination of symptoms and CXR followed by Xpert increased this number to 35 (75% increase compared to symptoms and Xpert). Optimal use of more sensitive screening tests, better diagnostic tests, and novel private sector engagement can improve diagnostic yield in a programmatic setting.


Assuntos
Busca de Comunicante/métodos , Programas de Rastreamento/métodos , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Antibióticos Antituberculose/farmacologia , Antibióticos Antituberculose/uso terapêutico , Busca de Comunicante/estatística & dados numéricos , Farmacorresistência Bacteriana , Feminino , Humanos , Índia/epidemiologia , Masculino , Programas de Rastreamento/estatística & dados numéricos , Microscopia , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular/estatística & dados numéricos , Radiografia/estatística & dados numéricos , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Estudos Retrospectivos , Rifampina , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
11.
BMC Infect Dis ; 20(1): 789, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097000

RESUMO

BACKGROUND: People successfully completing treatment for tuberculosis remain at elevated risk for recurrent disease, either from relapse or reinfection. Identifying risk factors for recurrent tuberculosis may help target post-tuberculosis screening and care. METHODS: We enrolled 500 patients with smear-positive pulmonary tuberculosis in South Africa and collected baseline data on demographics, clinical presentation and sputum mycobacterial cultures for 24-loci mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. We used routinely-collected administrative data to identify recurrent episodes of tuberculosis occurring over a median of six years after successful treatment completion. RESULTS: Of 500 patients initially enrolled, 333 (79%) successfully completed treatment for tuberculosis. During the follow-up period 35 patients with successful treatment (11%) experienced a bacteriologically confirmed tuberculosis recurrence. In our Cox proportional hazards model, a 3+ AFB sputum smear grade was significantly associated with recurrent tuberculosis with a hazard ratio of 3.33 (95% CI 1.44-7.7). The presence of polyclonal M. tuberculosis infection at baseline had a hazard ratio for recurrence of 1.96 (95% CI 0.86-4.48). CONCLUSION: Our results indicate that AFB smear grade is independently associated with tuberculosis recurrence after successful treatment for an initial episode while the association between polyclonal M. tuberculosis infection and increased risk of recurrence appears possible.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/genética , Escarro/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Recidiva , Fatores de Risco , África do Sul/epidemiologia , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
13.
BMC Infect Dis ; 20(1): 750, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050903

RESUMO

BACKGROUND: Tuberculosis (TB) is caused by Mycobacterium tuberculosis complex (MTBC). Mapping the genetic diversity of MTBC in high TB burden country like Ethiopia is important to understand principles of the disease transmission and to strengthen the regional TB control program. The aim of this study was to investigate the genetic diversity of Mycobacterium tuberculosis complex (MTBC) isolates circulating in the South Omo, southern Ethiopia. METHODS: MTBC isolates (N = 156) were genetically analyzed using spacer oligotyping (spoligotyping) and mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) typing. Major lineages and lineages were identified using MTBC databases. Logistic regression was used to correlate patient characteristics with strain clustering. RESULTS: The study identified Euro-American (EA), East-African-Indian (EAI), Indo-Oceanic (IO), Lineage_7/Aethiops vertus, Mycobacterium bovis and Mycobacterium africanum major lineages in proportions of 67.3% (105/156), 22.4% (35/156), 6.4% (10/156), 1.9% (3/156), 1.3% (2/156) and 0.6% (1/156), respectively. Lineages identified were Delhi/CAS 23.9% (37/155), Ethiopia_2 20.6% (32/155), Haarlem 14.2% (22/155), URAL 14.2%(22/155), Ethiopia_3 8.4% (13/155), TUR 6.5% (10/155), Lineage_7/Aethiops vertus 1.9% (3/155), Bovis 1.3% (2/155), LAM 1.3% (2/155), EAI 0.6% (1/155), X 0.6% (1/155) and Ethiopia H37Rv-like strain 0.6% (1/155). Of the genotyped isolates 5.8% (9/155) remained unassigned. The recent transmission index (RTI) was 3.9%. Orphan strains compared to shared types (AOR: 0.09, 95% CI: 0.04-0.25) were associated with reduced odds of clustering. The dominant TB lineage in pastoral areas was EAI and in non-pastoral areas was EA. CONCLUSION: The epidemiological data, highly diverse MTBC strains and a low RTI in South Omo, provide information contributing to the TB Control Program of the country.


Assuntos
Variação Genética , Mycobacterium bovis/genética , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Etiópia/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições Minissatélites/genética , Epidemiologia Molecular , Reação em Cadeia da Polimerase Multiplex , Mycobacterium bovis/isolamento & purificação , Mycobacterium tuberculosis/isolamento & purificação , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
14.
BMC Infect Dis ; 20(1): 746, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046016

RESUMO

BACKGROUND: Effective active case finding (ACF) activities are essential for early identification of new cases of active tuberculosis (TB) and latent TB infection (LTBI). Accurate diagnostics as well as the ability to identify contacts at high risk of infection are essential for ACF, and have not been systematically reported from Central Asia. The objective was to implement a pilot ACF program to determine the prevalence and risk factors for LTBI and active TB among contacts of individuals with TB in Kyrgyz Republic using Quantiferon-TB Gold plus (QuantiFERON). METHODS: An enhanced ACF project in the Kyrgyz Republic was implemented in which close and household (home) contacts of TB patients from the Issyk-Kul Oblast TB Center were visited at home. QuantiFERON and the tuberculin skin test (TST) alongside clinical and bacteriological examination were used to identify LTBI and active TB cases among contacts. The association for QuantiFERON positivity and risk factors were analysed and compared to TST results. RESULTS: Implementation of ACF with QuantiFERON involved close collaboration with the national sanitary and epidemiological services (SES) and laboratories in the Kyrgyz Republic. From 67 index cases, 296 contacts were enrolled of whom 253 had QuantiFERON or TST results; of those 103 contacts had LTBI (positive TST or IGRA), and four (1.4%) active TB cases were detected. Index case smear microscopy (OR 1.76) and high household density (OR 1.97) were significant risk factors for QuantiFERON positivity for all contacts. When stratified by age, association with smear positivity disappeared for children below 15 years. TST was not associated with any risk factor. CONCLUSIONS: This is the first time that ACF activities have been reported for Central Asia, and provide insight for implementation of effective ACF in the region. These ACF activities using QuantiFERON led to increase in the detection of LTBI and active cases, prior to patients seeking treatment. Household density should be taken into consideration as an important risk factor for the stratification of future ACF activities.


Assuntos
Busca de Comunicante/métodos , Testes de Liberação de Interferon-gama/métodos , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Mycobacterium tuberculosis/imunologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Testes Diagnósticos de Rotina , Características da Família , Feminino , Humanos , Lactente , Recém-Nascido , Quirguistão/epidemiologia , Tuberculose Latente/microbiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prevalência , Fatores de Risco , Teste Tuberculínico/métodos , Tuberculose Pulmonar/microbiologia , Adulto Jovem
15.
BMC Infect Dis ; 20(1): 791, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33096996

RESUMO

BACKGROUND: Tuberculosis (TB) remains a major public health concern in many low-income countries accounting for approximately two-thirds of deaths in people living with human immunodeficiency virus (HIV) infection. With prompt, accurate and appropriate treatment, almost all TB disease can be cured. The present study was to evaluate the diagnostic performance of an in-house duplex PCR (D-PCR) using IS1610 and rpoB specific primers in sputum samples from TB suspected patients. METHODS: A hospital-based cross-sectional study was conducted at the Limbe and Buea Regional Hospitals of the South West Region of Cameroon from June 2016 to April 2017. Sputum samples, decontaminated with hypertonic saline/sodium hydroxide solution were centrifuged and pellets processed for smear microscopy, culture and DNA extraction. Suspected inhibition was resolved by serial dilution of genomic DNA. Results were compared to culture as gold standard as well as a Composite Reference Standard (CRS). RESULTS: A total of 129 participants aged between 5 to 82 years were enrolled in to the study. The median age of the participants was 37 years (interquartile range, IQR: 27-50 years), with 54.3% being male. Forty-seven samples (36.4%) were positive by direct sputum microscopy, 49 (38%) by microscopy after concentration, 51 (39.5%) by culture and 62 (40.1%) by D-PCR. PCR inhibition was resolved in 85.7% (18/21) of the samples that had inhibition. The overall sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and area under the curve AUC) of the D-PCR was 93.5, 94, 94, 94%, 15.6, 0.005 and 89.0% respectively using CRS as reference. The sensitivities of D-PCR observed among different sample categories were 95.7, 87.5 and 87.5% for smear-and culture-positives, smear-negative/culture-positive, and clinically diagnosed cases respectively. CONCLUSION: IS1610 and rpoB duplex PCR using relatively cheap decontamination and DNA extraction methods in addition to simple serial dilutions to resolve PCR inhibition shows high sensitivity in the diagnosis of paucibacillary tuberculosis.


Assuntos
Proteínas de Bactérias/genética , RNA Polimerases Dirigidas por DNA/genética , Genes Bacterianos , Mycobacterium tuberculosis/genética , Reação em Cadeia da Polimerase/métodos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Camarões/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Primers do DNA , Feminino , HIV , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Sensibilidade e Especificidade , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Adulto Jovem
16.
BMC Infect Dis ; 20(1): 797, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109110

RESUMO

BACKGROUND: Delay in the diagnosis of Tuberculosis (TB) remains a major challenge against achieving effective TB prevention and control. Though a number of studies with inconsistent findings were conducted in Ethiopia; unavailability of a nationwide study determining the median time of patient delays to TB diagnosis is an important research gap. Therefore, this study aimed to determine the pooled median time of the patient delay to TB diagnosis and its determinants in Ethiopia. METHODS: We followed PRISMA checklist to present this study. We searched from Google Scholar, PubMed, Science Direct, Web of Science, CINAHL, and Cochrane Library databases for studies. The comprehensive search for relevant studies was done by two of the authors (MA and LY) up to the 10th of October 2019. Risk of bias was assessed using the Newcastle-Ottawa scale adapted for observational studies. Data were pooled and a random effect meta-analysis model was fitted to provide the overall median time of patient delay and its determinants in Ethiopia. Furthermore, subgroup analyses were conducted to investigate how the median time of patient delay varies across different groups of studies. RESULTS: Twenty-four studies that satisfied the eligibility criteria were included. Our meta-analysis showed that the median time of the patient delay was 24.6 (95%CI: 20.8-28.4) days. Living in rural area (OR: 2.19, 95%CI: 1.51-3.18), and poor knowledge about TB (OR: 2.85, 95%CI: 1.49-5.47) were more likely to lead to prolonged delay. Patients who consult non-formal health providers (OR: 5.08, 95%CI: 1.56-16.59) had a prolonged delay in the diagnosis of TB. Moreover, the narrative review of this study showed that age, educational level, financial burden and distance travel to reach the nearest health facility were significantly associated with a patient delay in the diagnosis of TB. CONCLUSIONS: In conclusion, patients are delayed more-than three weeks in the diagnosis of TB. Lack of awareness about TB, consulting non-formal health provider, and being in the rural area had increased patient delay to TB diagnosis. Increasing public awareness about TB, particularly in rural and disadvantaged areas could help to early diagnosis of TB.


Assuntos
Diagnóstico Tardio , Mycobacterium tuberculosis , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia , Fatores Etários , Atitude Frente a Saúde , Conscientização , Etiópia/epidemiologia , Instalações de Saúde , Humanos , Fatores de Risco , População Rural , Fatores de Tempo , Tuberculose Pulmonar/microbiologia
17.
Am J Trop Med Hyg ; 103(6): 2501-2505, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32975178

RESUMO

Gabon carries a high burden of both tuberculosis (TB) and smoking. This study examines the disease characteristics of smoking pulmonary TB patients in Lambaréné. We interviewed adult pulmonary TB patients in Lambaréné, between March 2016 and April 2019. Clinical and biological patient characteristics were collected. Bivariate and logistic regression analyses were performed to assess factors associated with smoking. The mean age of patients included was 31 years (±13). The proportion of smokers in our study was 30% (89/295). Smoking was significantly associated with patient-related diagnostic delay (adjusted odds ratio [AOR] = 8.18; 95% CI = 3.67-19.56), a higher number of pulmonary TB signs and symptoms (AOR = 2.74; 95% CI = 1.18-6.73), and a higher sputum mycobacterial load (AOR = 3.18; 95% CI = 1.33-8.11). The prevalence of smoking among TB patients is high, and leading to aggravated disease as compared with controls. Our study findings suggest that smoking patients should be regularly screened for TB, to reduce diagnostic delay and TB transmission within community. Smoking cessation activities should be included in the national TB control program in Gabon.


Assuntos
Fumar Cigarros/efeitos adversos , Fumar Cigarros/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Adolescente , Adulto , Antituberculosos/uso terapêutico , Estudos Transversais , Feminino , Gabão/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/epidemiologia , Adulto Jovem
18.
PLoS One ; 15(9): e0239289, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32936814

RESUMO

Mycobacterium tuberculosis (Mtb) is the causative agent for tuberculosis, the most extended infectious disease around the world. When Mtb enters inside the pulmonary alveolus it is rapidly phagocytosed by the alveolar macrophage. Although this controls the majority of inhaled microorganisms, in this case, Mtb survives inside the macrophage and multiplies. A posterior chemokine and cytokine cascade generated by the irruption of monocytes, neutrophils and posteriorly, by T-cells, does not necessarily stop the growth of the granuloma. Interestingly, the encapsulation process built by fibroblasts is able to surround the lesion and stop its growing. The success of this last process determines if the host enters in an asymptomatic latent state or continues into a life-threatening and infective active tuberculosis disease (TB). Understanding such dichotomic process is challenging, and computational modeling can bring new ideas. Thus, we have modeled the different stages of the infection, first in a single alveolus (a sac with a radius of 0.15 millimeters) and, second, inside a secondary lobule (a compartment of the lungs of around 3 cm3). We have employed stochastic reaction-diffusion equations to model the interactions among the cells and the diffusive transport to neighboring alveolus. The whole set of equations have successfully described the encapsulation process and determine that the size of the lesions depends on its position on the secondary lobule. We conclude that size and shape of the secondary lobule are the relevant variables to control the lesions, and, therefore, to avoid the evolution towards TB development. As lesions appear near to interlobular connective tissue they are easily controlled and their growth is drastically stopped, in this sense secondary lobules with a more flattened shape could control better the lesion.


Assuntos
Simulação por Computador , Granuloma/patologia , Mycobacterium tuberculosis/patogenicidade , Tuberculose/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Difusão , Granuloma/imunologia , Granuloma/microbiologia , Humanos , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Tuberculose Latente/patologia , Pulmão/imunologia , Pulmão/metabolismo , Macrófagos Alveolares/enzimologia , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Mycobacterium tuberculosis/imunologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagocitose/imunologia , Linfócitos T/imunologia , Linfócitos T/patologia , Tuberculose/microbiologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
19.
Sci Rep ; 10(1): 15537, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968142

RESUMO

This study aimed to investigate the number of persistent bacteria in sputum from tuberculosis patients compared to in vitro and to suggest a model-based approach for accounting for the potential difference. Sputum smear positive patients (n = 25) provided sputum samples prior to onset of chemotherapy. The number of cells detected by conventional agar colony forming unit (CFU) and most probable number (MPN) with Rpf supplementation were quantified. Persistent bacteria was assumed to be the difference between MPNrpf and CFU. The difference in persistent bacteria between in vitro and human sputum prior to chemotherapy was quantified using different model-based approaches. The persistent bacteria in sputum was 17% of the in vitro levels, suggesting a difference in phenotypic resistance, whereas no difference was found for multiplying bacterial subpopulations. Clinical trial simulations showed that the predicted time to 2 log fall in MPNrpf in a Phase 2a setting using in vitro pre-clinical efficacy information, would be almost 3 days longer if drug response was predicted ignoring the difference in phenotypic resistance. The discovered phenotypic differences between in vitro and humans prior to chemotherapy could have implications on translational efforts but can be accounted for using a model-based approach for translating in vitro to human drug response.


Assuntos
Mycobacterium tuberculosis/efeitos dos fármacos , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana , Humanos , Modelos Biológicos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Células-Tronco , Tuberculose Pulmonar/tratamento farmacológico
20.
BMC Infect Dis ; 20(1): 678, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32942990

RESUMO

BACKGROUND: Tuberculosis (TB) control is a primary global health priority but the goal to eliminate TB is being threatened by the increase in incidence of multidrug-resistant tuberculosis (MDR-TB). With this series of seven MDR-TB cases in migrant patients with identical Mycobacterium tuberculosis strains we aim to illustrate the challenges encountered during therapy and follow-up: language barriers, access to care for migrant patients, depression due to isolation, adverse reactions to the treatment, management of pediatric TB, further contact tracing. We also discuss best practices for the management of complex MDR-TB cases in settings with low overall TB incidence focusing on modern diagnostic assays and an individualized and an interdisciplinary therapeutic approach. METHODS: We describe a case series of seven consecutively diagnosed MDR-TB patients, six of them treated at our tertiary care hospital between May 2018 and March 2020. Epidemiologic data was gained by semi-structured patient interviews and reconstruction of the migration route. The origin of the cluster was confirmed by genotyping of the TB-strains. RESULTS: Six related patients were diagnosed with pulmonary MDR-TB between May and August 2018. All had a positive Interferon-Gamma-Release Assay (IGRA), in five patients sputum microscopy was positive for acid-fast bacilli (AFB). The genetic and phenotypical drug susceptibility test did not match with MDR-TB strains from an East-African origin. The index patient was identified through genetical fingerprinting. By changing the therapy to a modern MDR-TB regime and using an interdisciplinary and culture-sensitive approach, all patients improved clinically and radiologically. CONCLUSION: Human migration plays an important role for the global spread of MDR-TB in low incidence countries. Early case detection and adequate treatment are key to prevention of outbreaks. Especially language barriers and complex migration routes make genotyping of TB-strains a crucial tool to identify cases clusters, the potential index patient and transmission dynamics. We are fortunate enough to experience times in which new TB-antibiotics were made available and in which molecular assays revolutionized TB-diagnostics. We need to take advantage of that and develop personalized therapies for patients suffering from drug resistant TB.


Assuntos
Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Pré-Escolar , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Fenótipo , Gravidez , Escarro/microbiologia , Sudão , Migrantes , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Adulto Jovem
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