Nano-biosensing approaches on tuberculosis: Defy of aptamers.

PubMed

Golichenari, Behrouz; Nosrati, Rahim; Farokhi-Fard, Aref; Abnous, Khalil; Vaziri, Farzam; Behravan, Javad

2018-06-11

Tuberculosis is a major global health problem caused by the bacterium Mycobacterium tuberculosis (Mtb) complex. According to WHO reports, 53 million TB patients died from 2000 to 2016. Therefore, early diagnosis of the disease is of great importance for global health care programs. The restrictions of traditional methods have encouraged the development of innovative methods for rapid, reliable, and cost-effective diagnosis of tuberculosis. In recent years, aptamer-based biosensors or aptasensors have drawn great attention to sensitive and accessible detection of tuberculosis. Aptamers are small short single-stranded molecules of DNA or RNA that fold to a unique form and bind to targets. Once combined with nanomaterials, nano-scale aptasensors provide powerful analytical platforms for diagnosing of tuberculosis. Various groups designed and studied aptamers specific for the whole cells of M. tuberculosis, mycobacterial proteins and IFN-γ for early diagnosis of TB. Advantages such as high specificity and strong affinity, potential for binding to a larger variety of targets, increased stability, lower costs of synthesis and storage requirements, and lower probability of contamination make aptasensors pivotal alternatives for future TB diagnostics. In recent years, the concept of SOMAmer has opened new horizons in high precision detection of tuberculosis biomarkers. This review article provides a description of the research progresses of aptamer-based and SOMAmer-based biosensors and nanobiosensors for the detection of tuberculosis. Copyright © 2018 Elsevier B.V. All rights reserved.

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

PubMed Central

Scherer, Luciene Cardoso; Sperhacke, Rosa Dea; Jarczewski, Carla; Cafrune, Patrícia I; Minghelli, Simone; Ribeiro, Marta Osório; Mello, Fernanda CQ; Ruffino-Netto, Antonio; Rossetti, Maria LR; Kritski, Afrânio L

2007-01-01

Background Smear-negative pulmonary tuberculosis (SNPTB) accounts for 30% of Pulmonary Tuberculosis (PTB) cases reported annually in developing nations. Polymerase chain reaction (PCR) may provide an alternative for the rapid detection of Mycobacterium tuberculosis (MTB); however little data are available regarding the clinical utility of PCR in SNPTB, in a setting with a high burden of TB/HIV co-infection. Methods To evaluate the performance of the PCR dot-blot in parallel with pretest probability (Clinical Suspicion) in patients suspected of having SNPTB, a prospective study of 213 individuals with clinical and radiological suspicion of SNPTB was carried out from May 2003 to May 2004, in a TB/HIV reference hospital. Respiratory specialists estimated the pretest probability of active disease into high, intermediate, low categories. Expectorated sputum was examined by direct microscopy (Ziehl-Neelsen staining), culture (Lowenstein Jensen) and PCR dot-blot. Gold standard was based on culture positivity combined with the clinical definition of PTB. Results In smear-negative and HIV subjects, active PTB was diagnosed in 28.4% (43/151) and 42.2% (19/45), respectively. In the high, intermediate and low pretest probability categories active PTB was diagnosed in 67.4% (31/46), 24% (6/25), 7.5% (6/80), respectively. PCR had sensitivity of 65% (CI 95%: 50%–78%) and specificity of 83% (CI 95%: 75%–89%). There was no difference in the sensitivity of PCR in relation to HIV status. PCR sensitivity and specificity among non-previously TB treated and those treated in the past were, respectively: 69%, 43%, 85% and 80%. The high pretest probability, when used as a diagnostic test, had sensitivity of 72% (CI 95%:57%–84%) and specificity of 86% (CI 95%:78%–92%). Using the PCR dot-blot in parallel with high pretest probability as a diagnostic test, sensitivity, specificity, positive and negative predictive values were: 90%, 71%, 75%, and 88%, respectively. Among non-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively. Conclusion PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital. PMID:18096069

Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study.

PubMed

Podlekareva, Daria N; Efsen, Anne Marie W; Schultze, Anna; Post, Frank A; Skrahina, Alena M; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F; Losso, Marcelo H; Toibaro, Javier; Miro, Jose M; Vassilenko, Anna; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Lundgren, Jens D; Mocroft, Amanda; Kirk, Ole

2016-03-01

Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study. Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models. Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001). Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe. EU Seventh Framework Programme. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tuberculosis control in the era of the HIV epidemic: risk of tuberculosis infection in Tanzania, 1983-1998.

PubMed

2001-02-01

In Tanzania, a national tuberculosis programme (NTP) was established in 1979 based on the principles currently known as the World Health Organization DOTS strategy. From the period 1983-1987 to 1994-1998, notification rates of smear-positive tuberculosis increased from 32 to 69 per 100,000 population, mainly due to the human immunodeficiency virus (HIV) epidemic. To estimate the trend in the annual risk of tuberculosis infection and to establish to what extent the opposing forces of improved tuberculosis control and HIV have had an impact on tuberculosis transmission. Three national surveys were conducted in Tanzania among primary school children at 5-year intervals. The annual risk of tuberculosis infection and its trend were determined by tuberculin skin testing. The annual risk of infection in children without BCG scar using the criterion '17 mm + 2 x 18 mm' or more was estimated at 1.1% in 1983-1987, 1.0 in 1988-1992, and 0.9% in 1993-1998. There appears to have been little change in the annual risk of infection over the study period, either when using other criteria to define infection or in children with a BCG scar. The estimated number of infections per notified case decreased over time from 36 to 19. Despite strongly increased tuberculosis notification rates in adults, associated with the HIV epidemic, the risk of tuberculosis infection in children appears to have been stable over the past 15 years in Tanzania. This remarkable achievement is probably due to the impact of the NTP on tuberculosis transmission.

Molecular Characteristics of Mycobacterium tuberculosis Strains Isolated from Cutaneous Tuberculosis Patients in China.

PubMed

Jiang, Haiqin; Jin, Yali; Vissa, Varalakshmi; Zhang, Liangfen; Liu, Weijun; Qin, Lianhua; Wan, Kanglin; Wu, Xiaocui; Wang, Hongsheng; Liu, Weida; Wang, Baoxi

2017-04-06

Cutaneous tuberculosis (CTB) is probably underreported due to difficulties in detection and diagnosis. To address this issue, genotypes of Mycobacterium tuberculosis strains isolated from 30 patients with CTB were mapped at multiple loci, namely, RD105 deletions, spacer oligonucleotides, and Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTRs). Fifty-eight strains of pulmonary tuberculosis (PTB) were mapped as experimental controls. Drug resistance-associated gene mutations were determined by amplicon sequencing of target regions within 7 genes. Beijing family isolates were the most prevalent strains in CTB and PTB. MIRU-VNTR typing separated the Beijing strains from the non-Beijing strains, and the majority of CTB could be separated from PTB counterparts. Drug resistance determining regions showed only one CTB strain expressing isomazid resistance. Thus, while the CTB strains belonged to the same phylogenetic lineages and sub-lineages as the PTB strains, they differed at the level of several MIRU-VNTRs and in the proportion of drug resistance.

Interventions to reduce tuberculosis mortality and transmission in low- and middle-income countries.

PubMed Central

Borgdorff, Martien W.; Floyd, Katherine; Broekmans, Jaap F.

2002-01-01

Tuberculosis is among the top ten causes of global mortality and affects low-income countries in particular. This paper examines, through a literature review, the impact of tuberculosis control measures on tuberculosis mortality and transmission, and constraints to scaling-up. It also provides estimates of the effectiveness of various interventions using a model proposed by Styblo. It concludes that treatment of smear-positive tuberculosis using the WHO directly observed treatment, short-course (DOTS) strategy has by far the highest impact. While BCG immunization reduces childhood tuberculosis mortality, its impact on tuberculosis transmission is probably minimal. Under specific conditions, an additional impact on mortality and transmission can be expected through treatment of smear-negative cases, intensification of case-finding for smear-positive tuberculosis, and preventive therapy among individuals with dual tuberculosis-HIV infection. Of these interventions, DOTS is the most cost-effective at around US$ 5-40 per disability-adjusted life year (DALY) gained. The cost for BCG immunization is likely to be under US$ 50 per DALY gained. Treatment of smear-negative patients has a cost per DALY gained of up to US$ 100 in low-income countries, and up to US$ 400 in middle-income settings. Other interventions, such as preventive therapy for HIV-positive individuals, appear to be less cost-effective. The major constraint to scaling up DOTS is lack of political commitment, resulting in shortages of funding and human resources for tuberculosis control. However, in recent years there have been encouraging signs of increasing political commitment. Other constraints are related to involvement of the private sector, health sector reform, management capacity of tuberculosis programmes, treatment delivery, and drug supply. Global tuberculosis control could benefit strongly from technical innovation, including the development of a vaccine giving good protection against smear-positive pulmonary tuberculosis in adults; simpler and shorter drug regimens for treatment of tuberculosis disease and infection; and improved diagnostics for tuberculosis infection and disease. PMID:11984608

Drug resistance of Mycobacterium tuberculosis in Malawi: a cross-sectional survey

PubMed Central

Abouyannis, Michael; Dacombe, Russell; Dambe, Isaias; Mpunga, James; Faragher, Brian; Gausi, Francis; Ndhlovu, Henry; Kachiza, Chifundo; Suarez, Pedro; Mundy, Catherine; Banda, Hastings T; Nyasulu, Ishmael

2014-01-01

Abstract Objective To document the prevalence of multidrug resistance among people newly diagnosed with – and those retreated for – tuberculosis in Malawi. Methods We conducted a nationally representative survey of people with sputum-smear-positive tuberculosis between 2010 and 2011. For all consenting participants, we collected demographic and clinical data, two sputum samples and tested for human immunodeficiency virus (HIV).The samples underwent resistance testing at the Central Reference Laboratory in Lilongwe, Malawi. All Mycobacterium tuberculosis isolates found to be multidrug-resistant were retested for resistance to first-line drugs – and tested for resistance to second-line drugs – at a Supranational Tuberculosis Reference Laboratory in South Africa. Findings Overall, M. tuberculosis was isolated from 1777 (83.8%) of the 2120 smear-positive tuberculosis patients. Multidrug resistance was identified in five (0.4%) of 1196 isolates from new cases and 28 (4.8%) of 581 isolates from people undergoing retreatment. Of the 31 isolates from retreatment cases who had previously failed treatment, nine (29.0%) showed multidrug resistance. Although resistance to second-line drugs was found, no cases of extensive drug-resistant tuberculosis were detected. HIV testing of people from whom M. tuberculosis isolates were obtained showed that 577 (48.2%) of people newly diagnosed and 386 (66.4%) of people undergoing retreatment were positive. Conclusion The prevalence of multidrug resistance among people with smear-positive tuberculosis was low for sub-Saharan Africa – probably reflecting the strength of Malawi’s tuberculosis control programme. The relatively high prevalence of such resistance observed among those with previous treatment failure may highlight a need for a change in the national policy for retreating this subgroup of people with tuberculosis. PMID:25378741

Nutritional supplements for people being treated for active tuberculosis.

PubMed

Sinclair, David; Abba, Katharine; Grobler, Liesl; Sudarsanam, Thambu D

2011-11-09

Tuberculosis and malnutrition are linked in a complex relationship. The infection may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there are no evidence-based nutritional guidance for adults and children being treated for tuberculosis. To assess the effects of oral nutritional supplements (food, protein/energy supplements or micronutrients) on tuberculosis treatment outcomes and recovery in people on antituberculous drug therapy for active tuberculosis. We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, mRCT, and the Indian Journal of Tuberculosis to July 2011, and checked the reference lists of all included studies. Randomized controlled trials comparing any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. Two authors independently selected trials, extracted data, and assessed the risk of bias. Results are presented as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CI). Where appropriate, data from trials with similar interventions and outcomes have been pooled. The quality of evidence was assessed using the GRADE methods. Twenty-three trials, with 6842 participants, were included. Macronutrient supplementation Five trials assessed the provision of free food, or high energy supplements, although none were shown to provide a total daily kilocalorie intake above the current daily recommended intake for the non-infected population.The available trials were too small to reliably prove or exclude clinically important benefits on mortality, cure, or treatment completion. One small trial from India did find a statistically significant benefit on treatment completion, and clearance of the bacteria from the sputum, but these findings have not been confirmed in larger trials elsewhere (VERY LOW quality evidence).The provision of free food or high-energy nutritional products probably does produce a modest increase in weight gain during treatment for active tuberculosis (MODERATE quality evidence). Two small studies provide some evidence that physical function and quality of life may also be improved but the trials were too small to have much confidence in the result (LOW quality evidence). These effects were not seen in the one trial which included only human immunodeficiency virus (HIV)-positive patients.Micronutrient supplementation Five trials assessed multi-micronutrient supplementation in doses up to ten times the dietary reference intake, and 12 trials assessed single or dual micronutrient supplementation.There is insufficient evidence to judge whether multi-micronutrients have a beneficial effect on mortality in HIV- negative patients with tuberculosis (VERY LOW quality evidence), but the available studies show that multi-micronutrients probably have little or no effect on mortality in HIV-positive patients with tuberculosis (MODERATE quality evidence). No studies have assessed the effects of multi-micronutrients on cure, or treatment completion.Multi-micronutrient supplements may have little or no effect on the proportion of tuberculosis patients remaining sputum positive during the first eight weeks (LOW quality evidence), and probably have no effect on weight gain during treatment (MODERATE quality evidence). No studies have assessed quality of life.Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, plasma levels of zinc, vitamin D and E, and selenium may be improved by supplementation during the early stages of tuberculosis treatment, but a consistent benefit on tuberculosis treatment outcomes or nutritional recovery has not been demonstrated. There is insufficient research to know whether routinely providing free food or energy supplements results in better tuberculosis treatment outcomes, or improved quality of life. Further trials, particularly from food insecure settings, should have adequate sample sizes to identify, or exclude, clinically important benefits.Although blood levels of some vitamins may be low in patients starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing at or above recommended daily amounts has clinical benefits.

Can pleural adenosine deaminase (ADA) levels in pleural tuberculosis predict the presence of pulmonary tuberculosis? A CT analysis.

PubMed

Koh, Myung Je; Lee, In Jae; Kim, Joo-Hee

2016-06-01

To assess the relationship between imaging features of pulmonary tuberculosis at computed tomography (CT) and adenosine deaminase (ADA) values via pleural fluid analysis in patients with pleural tuberculosis. This retrospective study enrolled 60 patients who underwent fluid analysis for ADA and chest CT and were diagnosed with tuberculosis by culture or polymerase chain reaction of pleural fluid and sputum. The presence of centrilobular nodules, consolidation, cavitation, and mediastinal lymphadenopathy at CT were evaluated. The relationship between ADA values and the pattern of pulmonary involvement of tuberculosis was analysed. Pulmonary involvement was seen in 42 of the 60 patients. A centrilobular nodular pattern was seen in 37 and consolidation in 22. In 17 patients, both findings were identified. A centrilobular nodular pattern was more common than consolidation or cavitary lesions. When ADA values were high, pulmonary involvement was more frequent (p=0.002). Comparing low and high ADA groups using an obtained cut-off value of 80 IU/l, the high group had more frequent pulmonary involvement (p<0.001). Patients with tuberculous pleurisy who had high ADA values had a higher probability of manifesting pulmonary tuberculosis. High ADA values may help predict contagious pleuroparenchymal tuberculosis. The most common pulmonary involvement of tuberculous pleurisy showed a centrilobular nodular pattern. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Bim is a crucial regulator of apoptosis induced by Mycobacterium tuberculosis

PubMed Central

Aguiló, N; Uranga, S; Marinova, D; Martín, C; Pardo, J

2014-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis, induces apoptosis in infected macrophages in vitro and in vivo. However, the molecular mechanism controlling this process is not known. In order to study the involvement of the mitochondrial apoptotic pathway in M. tuberculosis-induced apoptosis, we analysed cell death in M. tuberculosis-infected embryonic fibroblasts (MEFs) derived from different knockout mice for genes involved in this route. We found that apoptosis induced by M. tuberculosis is abrogated in the absence of Bak and Bax, caspase 9 or the executioner caspases 3 and 7. Notably, we show that MEF deficient in the BH3-only BCL-2-interacting mediator of cell death (Bim) protein were also resistant to this process. The relevance of these results has been confirmed in the mouse macrophage cell line J774, where cell transfection with siRNA targeting Bim impaired apoptosis induced by virulent mycobacteria. Notably, only infection with a virulent strain, but not with attenuated ESX-1-defective strains, such as Bacillus Calmette-Guerin and live-attenuated M. tuberculosis vaccine strain MTBVAC, induced Bim upregulation and apoptosis, probably implicating virulence factor early secreted antigenic target 6-kDa protein in this process. Our results suggest that Bim upregulation and apoptosis is mediated by the p38MAPK-dependent pathway. Our findings show that Bim is a master regulator of apoptosis induced by M. tuberculosis. PMID:25032866

An agent-based computational model of the spread of tuberculosis

NASA Astrophysics Data System (ADS)

de Espíndola, Aquino L.; Bauch, Chris T.; Troca Cabella, Brenno C.; Souto Martinez, Alexandre

2011-05-01

In this work we propose an alternative model of the spread of tuberculosis (TB) and the emergence of drug resistance due to the treatment with antibiotics. We implement the simulations by an agent-based model computational approach where the spatial structure is taken into account. The spread of tuberculosis occurs according to probabilities defined by the interactions among individuals. The model was validated by reproducing results already known from the literature in which different treatment regimes yield the emergence of drug resistance. The different patterns of TB spread can be visualized at any time of the system evolution. The implementation details as well as some results of this alternative approach are discussed.

Mycobacterium tuberculosis Rv1987 induces Th2 immune responses and enhances Mycobacterium smegmatis survival in mice.

PubMed

Sha, Shanshan; Shi, Xiaoxia; Deng, Guoying; Chen, Lina; Xin, Yi; Ma, Yufang

2017-04-01

Mycobacterium tuberculosis can interfere with host immune response and escape clearance through its specific antigens. M. tuberculosis Rv1987 encoded by region of difference (RD)-2 gene is a secretory protein with immunogenic potency. Here, we investigated the impact of Rv1987 on host cytokine responses and T cell polarization in mouse aerosol model. A recombinant M. smegmatis mc 2 155 strain that overexpressed Rv1987 protein (named MS1987) was constructed and used to infect C57BL/6 mice. The mc 2 155 harbored the empty vector (named MSVec) was as a control. The results showed that MS1987 challenged mice promoted Th2-biased cytokine responses with lower secretion of IFN-γ but higher production of IL-4 and Rv1987-specific IgG antibody compared to MSVec infected mice. Neutrophilic inflammation and high bacterial burden were observed in the lung tissues of MS1987 infected mice probably own to the failed Th1 cell immunity. Besides, subcutaneous injection of Rv1987 protein could mediate the Th1 cytokine responses caused by M. bovis BCG in mice. These results indicated that M. tuberculosis Rv1987 protein could modulate host immune response towards Th2 profile, which probably contributed to the immune evasion of bacteria from host elimination. Copyright © 2017 Elsevier GmbH. All rights reserved.

Factors associated with knowledge about tuberculosis and attitudes of relatives of patients with the disease in Ribeirão Preto, São Paulo, Brazil.

PubMed

de Freitas, Isabela Moreira; Popolin, Marcela Paschoal; Touso, Michelle Mosna; Yamamura, Mellina; Rodrigues, Ludmila Barbosa Bandeira; Santos Neto, Marcelino; Crispim, Juliane de Almeida; Arcêncio, Ricardo Alexandre

2015-01-01

To investigate the knowledge regarding tuberculosis among relatives of patients with tuberculosis and the possible factors associated with this event and also to conduct comparative analyses between groups of relatives with or with few knowledge regarding tuberculosis, considering their attitudes in both groups. Cross-sectional study in which the sample was obtained through simple and randomized method. The data were collected by trained interviewers and validated tool. Logistic regression analyses were done using statistical software SPSS, version 22.0. Among the 110 subjects recruited for the study, 85 (87.5%) were women, and the mean age was 49 years. Regarding common symptoms of tuberculosis, 102 relatives (90.9%) pointed the chronic cough; regarding the knowledge about tuberculosis transmission modes, 100 (90.9%) of them pointed symptomatic respiratory as the probable infection source. The relatives also reported other tuberculosis transmission models: sharing of clothes (n = 87; 79.1%) and household utensils (n = 66; 60%); sexual relations (n = 50; 50%). Illiterate relatives (adjusted OR = 4.39; 95%CI 1.11 - 17.36), those who do not watch or watch little television (adjusted OR = 3.99; 95%CI 1.2 - 13.26), and also those who do not have the Internet access (adjusted OR = 5.01; 95%CI 1.29 - 19.38) were more likely to have low knowledge regarding tuberculosis. Regardless the group, with or without tuberculosis knowledge, the attitudes of both were satisfactory. There are evidences that social inequity is associated to the tuberculosis knowledge of patient relatives.

[Cluster of multidrug-resistant tuberculosis cases in a school of the district of Ica, Peru].

PubMed

Torres, Julio; Sardón, Victoria; Soto, Mirtha G; Anicama, Rolado; Arroyo-Hernández, Hugo; Munayco, César V

2011-01-01

We describe the evolution and features of a cluster of Multidrug-resistant tuberculosis (MDR TB) cases that occurred in 2001, in a school located in a sub-urban area of the district of Ica, Peru. We identified 15 students related before becoming infected with tuberculosis. The mean age of the cluster was 15 years. A total of 12 students were MDR-TB cases and 7 were drug-resistant to 5 first-line drugs (RHEZS). Five out of the 15 cases received at least 3 different anti-tuberculosis treatment schemes. The average treatment duration was 37 months (minimum 21 and maximum 59 months). A total of 13 cases recovered and 2 died. This study describes a cluster of MDR -TB cases in an educational facility, which due to the epidemiological link and time presentation, is probably an outbreak of MDR TB with a satisfactory outcome after prolonged treatment.

Tuberculosis transmission of predominant genotypes of Mycobacterium tuberculosis in northern suburbs of Buenos Aires city region.

PubMed

Morcillo, N; Zumarraga, M; Imperiale, B; Di Giulio, B; Chirico, C; Kuriger, A; Alito, A; Kremer, K; Cataldi, A

2007-01-01

In 2003, the incidence of tuberculosis in Argentina showed an increase compared to 2002. The severe national crisis at the end of the 90s has probably strongly contributed to this situation. The goal of this work was to estimate the extent of the spread of the most predominant Mycobacterium tuberculosis strains and to assess the spread of predominant M. tuberculosis clusters as determined by spoligotyping and IS6110 RFLP. The study involved 590 pulmonary, smear-positive TB cases receiving medical attention at health centers and hospitals in Northern Buenos Aires (NBA) suburbs, from October 2001 to December 2002. From a total of 208 clinical isolates belonging to 6 major clusters, 63 (30.2%) isolates had identical spoligotyping and IS6110 RFLP pattern. Only 22.2% were shown to have epidemiological connections with another member of their respective cluster. In these major clusters, 30.2% of the 208 TB cases studied by both molecular techniques and contact tracing could be convincingly attributable to a recently acquired infection. This knowledge may be useful to assess the clonal distribution of predominant M. tuberculosis clusters in Argentina, which may make an impact on TB control strategies.

Relationship between estimated pretest probability and accuracy of automated Mycobacterium tuberculosis assay in smear-negative pulmonary tuberculosis.

PubMed

Lim, T K; Gough, A; Chin, N K; Kumarasinghe, G

2000-09-01

The AMPLICOR assay (Roche; Branchburg, NJ), a rapid direct amplification test for Mycobacterium tuberculosis, has only been licensed for use in smear-positive respiratory specimens. However, many patients with pulmonary tuberculosis (PTB) have smear-negative disease. The clinical utility of this test in patients with smear-negative PTB is unknown. To evaluate the effect of pretest probability of PTB estimated by chest physicians on the accuracy of the AMPLICOR assay in patients with smear-negative PTB. A prospective study of consecutive patients suspected of having smear-negative PTB. Two chest physicians estimated the pretest probability of active disease (high, intermediate, and low categories). Respiratory specimens were examined with radiometric broth medium cultures and with the AMPLICOR assay for M tuberculosis. The decision on a final diagnosis of PTB was blinded to the AMPLICOR results. Active PTB was diagnosed in 25 of 441 patients (5.7%). The AMPLICOR assay had an overall sensitivity of 44% and a specificity of 99%. Results of the assay were negative in seven patients with culture-negative PTB. The proportions of patients in the high, intermediate, and low pretest groups were 4.5%, 19.7%, and 75.7%, respectively. The incidence of PTB for each group was 95%, 3.4%, and 0.9%, respectively. The sensitivities of the AMPLICOR assay in the three groups of patients were 47%, 33%, and 33%, respectively, while the specificities were 100%, 98%, and 99%, respectively. In patients suspected of having smear-negative PTB, the following conclusions were drawn: (1) the incidence of active PTB was low; (2) pretest estimates accurately discriminated between patients with high and low risk of PTB; (3) the risk of PTB was overestimated in the intermediate group; and (4) the utility of the AMPLICOR assay in the intermediate-risk group may be limited by the overestimation of disease prevalence and low test sensitivity. Further studies are needed on the role of the AMPLICOR assay in better selected patients with an intermediate risk of having smear-negative PTB.

Nutritional supplements for people being treated for active tuberculosis

PubMed Central

Grobler, Liesl; Nagpal, Sukrti; Sudarsanam, Thambu D; Sinclair, David

2016-01-01

Background Tuberculosis and malnutrition are linked in a complex relationship. Tuberculosis may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there is no evidence-based nutritional guidance for adults and children being treated for tuberculosis. Objectives To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2016), MEDLINE (from 1946 to 4 February 2016), EMBASE (from 1980 to 4 February 2016), LILACS (from 1982 to 4 February 2016), the metaRegister of Controlled Trials (mRCT), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the Indian Journal of Tuberculosis up to 4 February 2016, and checked the reference lists of all included studies. Selection criteria Randomized controlled trials that compared any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. The primary outcomes of interest were all-cause death, and cure at six and 12 months. Data collection and analysis Two review authors independently selected trials for inclusion, and extracted data and assessed the risk of bias in the included trials. We presented the results as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). Where appropriate, we pooled data from trials with similar interventions and outcomes. We assessed the quality of the evidence using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Main results Thirty-five trials, including 8283 participants, met the inclusion criteria of this review. Macronutrient supplementation Six trials assessed the provision of free food, or high-energy supplements. Only two trials measured total dietary intake, and in both trials the intervention increased calorie consumption compared to controls. The available trials were too small to reliably prove or exclude clinically important benefits on mortality (RR 0.34, 95% CI 0.10 to 1.20; four trials, 567 participants, very low quality evidence), cure (RR 0.91, 95% CI 0.59 to 1.41; one trial, 102 participants, very low quality evidence), or treatment completion (data not pooled; two trials, 365 participants, very low quality evidence). Supplementation probably produces a modest increase in weight gain during treatment for active tuberculosis, although this was not seen consistently across all trials (data not pooled; five trials, 883 participants, moderate quality evidence). Two small studies provide some evidence that quality of life may also be improved but the trials were too small to have much confidence in the result (data not pooled; two trials, 134 participants, low quality evidence). Micronutrient supplementation Six trials assessed multi-micronutrient supplementation in doses up to 10 times the dietary reference intake, and 18 trials assessed single or dual micronutrient supplementation. Routine multi-micronutrient supplementation may have little or no effect on mortality in HIV-negative people with tuberculosis (RR 0.86, 95% CI 0.46 to 1.6; four trials, 1219 participants, low quality evidence), or HIV-positive people who are not taking antiretroviral therapy (RR 0.92, 95% CI 0.69 to 1.23; three trials, 1429 participants, moderate quality evidence). There is insufficient evidence to know if supplementation improves cure (no trials), treatment completion (RR 0.99, 95% CI 0.95 to 1.04; one trial, 302 participants, very low quality evidence), or the proportion of people who remain sputum positive during the first eight weeks (RR 0.92, 95% CI 0.63 to 1.35; two trials, 1020 participants, very low quality evidence). However, supplementation may have little or no effect on weight gain during treatment (data not pooled; five trials, 2940 participants, low quality evidence), and no studies have assessed the effect on quality of life. Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, supplementation probably does improve plasma levels of zinc, vitamin D, vitamin E, and selenium, but this has not been shown to have clinically important benefits. Of note, despite multiple studies of vitamin D supplementation in different doses, statistically significant benefits on sputum conversion have not been demonstrated. Authors' conclusions There is currently insufficient research to know whether routinely providing free food, or energy supplements improves tuberculosis treatment outcomes, but it probably improves weight gain in some settings. Although blood levels of some vitamins may be low in people starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing above recommended daily amounts has clinical benefits. PLAIN LANGUAGE SUMMARY Nutritional supplements for people being treated for active tuberculosis Cochrane researchers conducted a review of the effects of nutritional supplements for people being treated for tuberculosis. After searching for relevant studies up to 4 February 2016, they included 35 relevant studies with 8283 participants. Their findings are summarized below. What is active tuberculosis and how might nutritional supplements work? Tuberculosis is a bacterial infection which most commonly affects the lungs. Most people who get infected never develop symptoms as their immune system manages to control the bacteria. Active tuberculosis occurs when the infection is no longer contained by the immune system, and typical symptoms are cough, chest pain, fever, night sweats, weight loss, and sometimes coughing up blood. Treatment is with a combination of antibiotic drugs, which must be taken for at least six months. People with tuberculosis are often malnourished, and malnourished people are at higher risk of developing tuberculosis as their immune system is weakened. Nutritional supplements could help people recover from the illness by strengthening their immune system, and by improving weight gain, and muscle strength, allowing them to return to an active life. Good nutrition requires a daily intake of macronutrients (carbohydrate, protein, and fat), and micronutrients (essential vitamins and minerals). What the research says Effect of providing nutritional supplements to people being treated for tuberculosis We currently don't know if providing free food to tuberculosis patients, as hot meals or ration parcels, reduces death or improves cure (very low quality evidence). However, it probably does improve weight gain in some settings (moderate quality evidence), and may improve quality of life (low quality evidence). Routinely providing multi-micronutrient supplements may have little or no effect on deaths in HIV-negative people with tuberculosis (low quality evidence), or HIV-positive people who are not taking anti-retroviral therapy (moderate quality evidence). We currently don't know if micronutrient supplements have any effect on tuberculosis treatment outcomes (very low quality evidence), but they may have no effect on weight gain (low quality evidence). No studies have assessed the effect on quality of life. Plasma levels of vitamin A appear to increase after starting tuberculosis treatment regardless of supplementation. In contrast, supplementation probably does improve plasma levels of zinc, vitamin D, vitamin E, and selenium, but this has not been shown to have clinically important benefits. Despite multiple studies of vitamin D supplementation in different doses, statistically significant benefits on sputum conversion have not been demonstrated. Authors' conclusions Food or energy supplements may improve weight gain during recovery from tuberculosis in some settings, but there is currently no evidence that they improve tuberculosis treatment outcomes. There is also currently no reliable evidence that routinely supplementing above recommended daily amounts has clinical benefits. PMID:27355911

Genome-wide characterization of monomeric transcriptional regulators in Mycobacterium tuberculosis.

PubMed

Feng, Lipeng; Chen, Zhenkang; Wang, Zhongwei; Hu, Yangbo; Chen, Shiyun

2016-05-01

Gene transcription catalysed by RNA polymerase is regulated by transcriptional regulators, which play central roles in the control of gene transcription in both eukaryotes and prokaryotes. In regulating gene transcription, many regulators form dimers that bind to DNA with repeated motifs. However, some regulators function as monomers, but their mechanisms of gene expression control are largely uncharacterized. Here we systematically characterized monomeric versus dimeric regulators in the tuberculosis causative agent Mycobacterium tuberculosis. Of the >160 transcriptional regulators annotated in M. tuberculosis, 154 transcriptional regulators were tested, 22 % probably act as monomers and most are annotated as hypothetical regulators. Notably, all members of the WhiB-like protein family are classified as monomers. To further investigate mechanisms of monomeric regulators, we analysed the actions of these WhiB proteins and found that the majority interact with the principal sigma factor σA, which is also a monomeric protein within the RNA polymerase holoenzyme. Taken together, our study for the first time globally classified monomeric regulators in M. tuberculosis and suggested a mechanism for monomeric regulators in controlling gene transcription through interacting with monomeric sigma factors.

PPE Surface Proteins Are Required for Heme Utilization by Mycobacterium tuberculosis

PubMed Central

Mitra, Avishek; Speer, Alexander; Lin, Kan; Ehrt, Sabine

2017-01-01

ABSTRACT Iron is essential for replication of Mycobacterium tuberculosis, but iron is efficiently sequestered in the human host during infection. Heme constitutes the largest iron reservoir in the human body and is utilized by many bacterial pathogens as an iron source. While heme acquisition is well studied in other bacterial pathogens, little is known in M. tuberculosis. To identify proteins involved in heme utilization by M. tuberculosis, a transposon mutant library was screened for resistance to the toxic heme analog gallium(III)-porphyrin (Ga-PIX). Inactivation of the ppe36, ppe62, and rv0265c genes resulted in resistance to Ga-PIX. Growth experiments using isogenic M. tuberculosis deletion mutants showed that PPE36 is essential for heme utilization by M. tuberculosis, while the functions of PPE62 and Rv0265c are partially redundant. None of the genes restored growth of the heterologous M. tuberculosis mutants, indicating that the proteins encoded by the genes have separate functions. PPE36, PPE62, and Rv0265c bind heme as shown by surface plasmon resonance spectroscopy and are associated with membranes. Both PPE36 and PPE62 proteins are cell surface accessible, while the Rv0265c protein is probably located in the periplasm. PPE36 and PPE62 are, to our knowledge, the first proline-proline-glutamate (PPE) proteins of M. tuberculosis that bind small molecules and are involved in nutrient acquisition. The absence of a virulence defect of the ppe36 deletion mutant indicates that the different iron acquisition pathways of M. tuberculosis may substitute for each other during growth and persistence in mice. The emerging model of heme utilization by M. tuberculosis as derived from this study is substantially different from those of other bacteria. PMID:28119467

A review of the interplay between tuberculosis and mental health.

PubMed

Doherty, Anne M; Kelly, John; McDonald, Colm; O'Dywer, Anne Marie; Keane, Joseph; Cooney, John

2013-01-01

Tuberculosis and mental illness share common risk factors including homelessness, HIV positive serology, alcohol/substance abuse and migrant status leading to frequent comorbidity. We sought to generate a comprehensive literature review that examines the complex relationship between tuberculosis and mental illness. A literature search was conducted in MedLine, Ovid and Psychinfo, with further examination of the references of these articles. In total 316 articles were identified. It was not possible to conduct a formal meta-analysis due to the absence of randomised controlled data. Rates of mental illness of up to 70% have been identified in tuberculosis patients. Medications used in the treatment of common mental illnesses, such as depression, may have significant interactions with anti-tuberculosis agents, especially isoniazid and increasingly linezolid. Many medications used in the treatment of tuberculosis can have significant adverse psychiatric effects and some medications such as rifampicin may reduce the effective doses of anti-psychotics y their enzyme induction actions. Treatment with agents such as cycloserine has been associated with depression, and there have been reported cases of psychosis with most anti-tuberculous agents. Mental illness and substance abuse may also affect compliance with treatment, with attendant public health concerns. As a result of the common co-morbidity of mental illness and tuberculosis, it is probable that physicians will encounter previously undiagnosed mental illness among patients with tuberculosis. Similarly, psychiatrists are likely to meet tuberculosis among their patients. It is important that both psychiatrists and physicians are aware of the potential for interactions between the drugs used to treat tuberculosis and psychiatric conditions. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Can penicillins and other beta-lactam antibiotics be used to treat tuberculosis?

PubMed Central

Chambers, H F; Moreau, D; Yajko, D; Miick, C; Wagner, C; Hackbarth, C; Kocagöz, S; Rosenberg, E; Hadley, W K; Nikaido, H

1995-01-01

An increase in the number of tuberculosis cases caused by multiple-drug-resistant strains of Mycobacterium tuberculosis has stimulated search for new antituberculous agents. Beta-lactam antibiotics, traditionally regarded as ineffective against tuberculosis, merit consideration. Four major penicillin-binding proteins (PBPs) with approximate molecular sizes of 94, 82, 52, and 37 kDa were detected by fluorography of [3H]penicillin-radiolabeled membrane proteins prepared from M. tuberculosis H37Ra. The presence of membrane-associated beta-lactamase precluded the use of membranes for assaying the binding affinities of beta-lactam antibiotics. Therefore, ampicillin affinity chromatography was used to purify these four PBPs from crude membranes in order to assay the binding affinities of beta-lactam antibiotics. Ampicillin, amoxicillin, and imipenem, beta-lactam antibiotics previously reported to be active in vitro against M. tuberculosis, bound to M. tuberculosis PBPs at therapeutically achievable concentrations. Binding of the 94-, 82-, and 52-kDa PBPs, but not the 37-kDa PBP, was associated with antibacterial activity, suggesting that these PBPs are the critical targets. Studies of mycobacterial cell wall permeability, which was assayed with a panel of reference cephalosporins and penicillins with different charge positivities, indicated that the rate of penetration of beta-lactam antibiotics to the target PBPs could not account for resistance. Resistance could be reversed with the beta-lactamase inhibitors clavulanate or sulbactam or could be circumvented by the use of a beta-lactamase-stable drug, imipenem, indicating that mycobacterial beta-lactamase, probably in conjunction with slow penetration, is a major determinant of M. tuberculosis resistance to beta-lactam antibiotics. These findings confirm in vitro data that M. tuberculosis is susceptible to some beta-lactam antibiotics. Further evaluation of these drugs for the treatment of tuberculosis in animal models and in clinical trials is warranted. PMID:8592990

Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti.

PubMed

Jacquet, Vary; Morose, Willy; Schwartzman, Kevin; Oxlade, Olivia; Barr, Graham; Grimard, Franque; Menzies, Dick

2006-08-15

Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. Starting in 2003, DOTS expansion in Haiti is anticipated to cost $4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion.

Mycobacterium tuberculosis Contaminant Risk on Bone Marrow Aspiration Material from Iliac Bone Patients with Active Tuberculous Spondylitis.

PubMed

Rahyussalim, Ahmad Jabir; Kurniawati, Tri; Rukmana, Andriansjah

2016-01-01

There was a concern on Mycobacterium tuberculosis spreading to the bone marrow, when it was applied on tuberculous spine infection. This research aimed to study the probability of using autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis. As many as nine patients with tuberculous spondylitis were used as samples. During the procedure, the vertebral lesion material and iliac bone marrow aspirates were obtained for acid fast staining, bacteria culture, and PCR (polymerase chain reaction) tests for Mycobacterium tuberculosis at the Clinical Microbiology Laboratory of Faculty of Medicine Universitas Indonesia. This research showed that there was a relationship between diagnostic confirmation of tuberculous spondylitis based on the PCR test and bacterial culture on the solid vertebral lesion material with the PCR test and bacterial culture from the bone marrow aspirates. If the diagnostic confirmation concluded positive results, then there was a higher probability that there would be a positive result for the bone marrow aspirates, so that it was not recommended to use autologous bone marrow as a source of mesenchymal stem cell for patients with tuberculous spondylitis unless the PCR and culture examination of the bone marrow showed a negative result.

The incubation period distribution of tuberculosis estimated with a molecular epidemiological approach.

PubMed

Borgdorff, Martien W; Sebek, Maruschka; Geskus, Ronald B; Kremer, Kristin; Kalisvaart, Nico; van Soolingen, Dick

2011-08-01

There is limited information on the distribution of incubation periods of tuberculosis (TB). In The Netherlands, patients whose Mycobacterium tuberculosis isolates have identical DNA fingerprints in the period 1993-2007 were interviewed to identify epidemiological links between cases. We determined the incubation period distribution in secondary cases. Survival analysis techniques were used to include secondary cases not yet symptomatic at diagnosis with weighting to adjust for lower capture probabilities of couples with longer time intervals between their diagnoses. In order to deal with missing data, we used multiple imputations. We identified 1095 epidemiologically linked secondary cases, attributed to 688 source cases with pulmonary TB. Of those developing disease within 15 years, the Kaplan-Meier probability to fall ill within 1 year was 45%, within 2 years 62% and within 5 years 83%. The incubation time was shorter in secondary cases who were men, young, those with extra-pulmonary TB and those not reporting previous TB or previous preventive therapy. Molecular epidemiological analysis has allowed a more precise description of the incubation period of TB than was possible in previous studies, including the identification of risk factors for shorter incubation periods.

Transmission of Extensively Drug-Resistant Tuberculosis in South Africa

PubMed Central

Shah, N. Sarita; Auld, Sara C.; Brust, James C.M.; Mathema, Barun; Ismail, Nazir; Moodley, Pravi; Mlisana, Koleka; Allana, Salim; Campbell, Angela; Mthiyane, Thuli; Morris, Natashia; Mpangase, Primrose; van der Meulen, Hermina; Omar, Shaheed V.; Brown, Tyler S.; Narechania, Apurva; Shaskina, Elena; Kapwata, Thandi; Kreiswirth, Barry; Gandhi, Neel R.

2017-01-01

BACKGROUND Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. METHODS We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants’ history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment– length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug-resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission. RESULTS Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%). CONCLUSIONS The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa, an area with a high tuberculosis burden, were probably due to transmission rather than to inadequate treatment of MDR tuberculosis. These data suggest that control of the epidemic of drug-resistant tuberculosis requires an increased focus on interrupting transmission. (Funded by the National Institute of Allergy and Infectious Diseases and others.) PMID:28099825

Estimation of the individual slaughterhouse surveillance sensitivity for bovine tuberculosis in Catalonia (North-Eastern Spain).

PubMed

Garcia-Saenz, A; Napp, S; Lopez, S; Casal, J; Allepuz, A

2015-10-01

The achievement of the Officially Tuberculosis Free (OTF) status in regions with low bovine Tuberculosis (bTB) herd prevalence, as is the case of North-Eastern Spain (Catalonia), might be a likely option in the medium term. In this context, risk-based approaches could be an alternative surveillance strategy to the costly current strategy. However, before any change in the system may be contemplated, a reliable estimate of the sensitivity of the different surveillance components is needed. In this study, we focused on the slaughterhouse component. The probability of detection of a bTB-infected cattle by the slaughterhouses in Catalonia was estimated as the product of three consecutive probabilities: (P1) the probability that a bTB-infected animal arrived at the slaughterhouse presenting Macroscopically Detectable Lesions (MDL); (P2) the probability that MDL were detected by the routine meat inspection process and (P3) the probability that the veterinary officer suspected bTB and sent the sample for laboratory confirmation. The first probability was obtained from data collected through the bTB eradication program carried out in Catalonia between 2005 and 2008, while the last two were obtained through the expert opinion of the veterinary officers working at the slaughterhouses who fulfilled a questionnaire administered during 2014. The bTB surveillance sensitivity of the different cattle slaughterhouses in Catalonia obtained in this study was 31.4% (CI 95%: 28.6-36.2), and there were important differences among them. The low bTB surveillance sensitivity was mainly related with the low probability that a bTB-infected animal arrived at the slaughterhouse presenting MDL (around 44.8%). The variability of the sensitivity among the different slaughterhouses could be explained by significant associations between some variables included in the survey and P2. For instance, factors like attendance to training courses, number of meat technicians and speed of the slaughter chain were significantly related with the probabilities that a MDL was detected by the meat inspection procedure carried out in the slaughterhouse. Technical and policy efforts should be focused on the improvement of these factors in order to maximize the slaughterhouse sensitivity. Copyright © 2015 Elsevier B.V. All rights reserved.

Offer of primary care services and detection of tuberculosis incidence in Brazil

PubMed Central

Pelissari, Daniele Maria; Bartholomay, Patricia; Jacobs, Marina Gasino; Arakaki-Sanchez, Denise; dos Anjos, Davllyn Santos Oliveira; Costa, Mara Lucia dos Santos; Cavalcanti, Pauline Cristine da Silva; Diaz-Quijano, Fredi Alexander

2018-01-01

ABSTRACT OBJECTIVE To evaluate the association between the health services offered by primary care teams and the detection of new tuberculosis cases in Brazil. METHODS This was an ecological study covering all Brazilian municipalities that registered at least one new tuberculosis case (diagnosed between 2012 to 2014 and notified in the Information System of Notifiable Diseases) and with at least one primary care team evaluated by the second cycle of the National Program for Improving Access and Quality of Primary Care (PMAQ-AB). The variables of the PMAQ-AB were classified as proximal or distal, according to their relation with the tuberculosis diagnosis. Then, they were tested hierarchically in multiple models (adjusted by States) using negative binomial regression. RESULTS An increase of 10% in the primary health care coverage was associated with a decrease of 2.24% in the tuberculosis detection rate (95%CI -3.35– -1.11). Regarding the proximal variables in relation to diagnosis, in the multiple model, the detection of tuberculosis was associated with the proportion of teams that conduct contact investigation (increase in Incidence Rate Ratio [IRR] = 2.97%, 95%CI 2.41–3.53), carry out tuberculosis active case finding (increase in IRR = 2.17%, 95%CI 1.48–2.87), and request culture for mycobacteria (increase in IRR = 1.87%, 95%CI 0.98–2.76). CONCLUSIONS The variables related to the search actions were positively associated with the detection of new tuberculosis cases, which suggests a significant contribution to the strengthening of the sensitivity of the surveillance system. On the other hand, primary care coverage was inversely associated with the tuberculosis detection rate, which could represent the overall effect of the primary care on transmission control, probably from the identification and early treatment of cases. PMID:29791528

Phenotypic and genotypic characteristics of drug resistance in Mycobacterium tuberculosis isolates from pediatric population of Chennai, India.

PubMed

Therese, K Lily; Gayathri, R; Balasubramanian, S; Natrajan, S; Madhavan, H N

2012-01-01

Multidrug-resistant TB (MDR-TB) has been reported in almost all parts of the world. Childhood TB is accorded low priority by national TB control programs. Probable reasons include diagnostic difficulties, limited resources, misplaced faith in BCG and lack of data on treatment. Good data on the burden of all forms of TB among children in India are not available. To study the drug sensitivity pattern of tuberculosis in children aged from 3 months to 18 years and the outcome of drug-resistant tuberculosis by BACTEC culture system and PCR-based DNA sequencing technique. This is a retrospective study. One hundred and fifty-nine clinical specimens were processed for Ziehl-Neelsen stain, Mycobacterial culture by BACTEC method, phenotypic DST for first-line drugs for Mycobacterium tuberculosis (M. tuberculosis) isolates and PCR-based DNA sequencing was performed for the M. tuberculosis isolates targeting rpoB, katG, inhA, oxyR-ahpC, rpsL, rrs and pncA. Out of the 159 Mycobacterial cultures performed during the study period, 17 clinical specimens (10.7%) were culture positive for M. tuberculosis. Among the 17 M. tuberculosis isolates, 2 were multidrug-resistant TB. PCR-based DNA sequencing revealed the presence of many novel mutations targeting katG, inhA, oxyR-ahpC and pncA and the most commonly reported mutation Ser531Leu in the rpoB gene. This study underlines the urgent need to take efforts to develop methods for rapid detection and drug susceptibility of tubercle bacilli in the pediatric population.

Posttraumatic Intracranial Tuberculous Subdural Empyema in a Patient with Skull Fracture

PubMed Central

Kim, Jiha; Kim, Choonghyo; Ryu, Young-Joon

2016-01-01

Intracranial tuberculous subdural empyema (ITSE) is extremely rare. To our knowledge, only four cases of microbiologically confirmed ITSE have been reported in the English literature to date. Most cases have arisen in patients with pulmonary tuberculosis regardless of trauma. A 46-year-old man presented to the emergency department after a fall. On arrival, he complained of pain in his head, face, chest and left arm. He was alert and oriented. An initial neurological examination was normal. Radiologic evaluation revealed multiple fractures of his skull, ribs, left scapula and radius. Though he had suffered extensive skull fractures of his cranium, maxilla, zygoma and orbital wall, the sustained cerebral contusion and hemorrhage were mild. Eighteen days later, he suddenly experienced a general tonic-clonic seizure. Radiologic evaluation revealed a subdural empyema in the left occipital area that was not present on admission. We performed a craniotomy, and the empyema was completely removed. Microbiological examination identified Mycobacterium tuberculosis (M. tuberculosis). After eighteen months of anti-tuberculous treatment, the empyema disappeared completely. This case demonstrates that tuberculosis can induce empyema in patients with skull fractures. Thus, we recommend that M. tuberculosis should be considered as the probable pathogen in cases with posttraumatic empyema. PMID:27226867

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, K L; Steele, P T; Bogan, M J

Two similar mycobacteria, Mycobacteria tuberculosis H37Ra and Mycobacteria smegmatis are rapidly detected and identified within samples containing a complex background of respiratory effluents using Single Particle Aerosol Mass Spectrometry (SPAMS). M. tuberculosis H37Ra (TBa), an avirulent strain, is used as a surrogate for virulent tuberculosis (TBv); M. smegmatis (MSm) is utilized as a near neighbor confounder for TBa. Bovine lung surfactant and human exhaled breath condensate are used as first-order surrogates for infected human lung expirations from patients with pulmonary tuberculosis. This simulated background sputum is mixed with TBa or MSm and nebulized to produce conglomerate aerosol particles, single particlesmore » that contain a bacterium embedded within a background respiratory matrix. Mass spectra of single conglomerate particles exhibit ions associated with both respiratory effluents and mycobacteria. Spectral features distinguishing TBa from MSm in pure and conglomerate particles are shown. SPAMS pattern matching alarm algorithms are able to distinguish TBa containing particles from background matrix and MSm for >50% of the test particles, which is sufficient to enable a high probability of detection and a low false alarm rate if an adequate number of such particles are present. These results indicate the potential usefulness of SPAMS for rapid, reagentless tuberculosis screening.« less

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

PubMed Central

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L. C. M.; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M. Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H. M.; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates. PMID:25339944

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis.

PubMed

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L C M; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H M; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

Serological findings in leprosy and tuberculosis with the Wassermann, Meinicke, and VDRL tests.

PubMed

RUGE, H

1955-01-01

In the course of a venereal disease survey in Egypt, 820 cases of leprosy and 720 cases of tuberculosis were serologically examined with the Wassermann, Meinicke (MKR II), and VDRL tests; the results are reported in this paper.On serological and anamnestic evidence, 31 cases of syphilis were discovered among the leprosy cases and 37 among the tuberculosis cases. Apparently false positive reactions were seen in 203 cases of leprosy (25%) and in 38 cases of tuberculosis (5%). The author discusses the probability that a fairly high proportion of these reactions were in fact caused by otherwise undetected syphilis or were non-specific.The Meinicke test proved the most specific of the three, followed, in that order, by the Wassermann and the VDRL tests.It was found that syphilis was more frequent among males with tuberculosis than among those with leprosy; this is attributed to the fact that leprosy patients are kept in greater isolation. Less easily explicable is the fact that more females than males with leprosy were found to have syphilis, whereas in tuberculous persons the difference in syphilis incidence between male and female patients was not very great.

Baseline predictors of sputum culture conversion in pulmonary tuberculosis: importance of cavities, smoking, time to detection and W-Beijing genotype.

PubMed

Visser, Marianne E; Stead, Michael C; Walzl, Gerhard; Warren, Rob; Schomaker, Michael; Grewal, Harleen M S; Swart, Elizabeth C; Maartens, Gary

2012-01-01

Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes. To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis. Between May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable. 113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype. We found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.

Nutritional supplements for people being treated for active tuberculosis: A technical summary.

PubMed

Grobler, L; Durao, S; Van der Merwe, S M; Wessels, J; Naude, C E

2017-12-13

Tuberculosis and nutrition are intrinsically linked in a complex relationship. Altered metabolism and loss of appetite associated with tuberculosis may result in undernutrition, which in turn may worsen the disease or delay recovery. We highlight an updated Cochrane review assessing the effects of oral nutritional supplements in people with active tuberculosis who are receiving antituberculosis drug therapy. The review authors conducted a comprehensive search (February 2016) for all randomised controlled trials comparing any oral nutritional supplement, given for at least 4 weeks, with no nutritional intervention, placebo or dietary advice only in people receiving antituberculosis treatment. Of the 35 trials (N=8 283 participants) included, seven assessed the provision of free food or high-energy supplements, six assessed multi-micronutrient supplementation, and 21 assessed single- or dual-micronutrient supplementation. There is currently insufficient evidence to indicate whether routinely providing free food or high-energy supplements improves antituberculosis treatment outcomes (i.e. reduced death and increased cure rates at 6 and 12 months), but it probably improves weight gain in some settings. Plasma levels of zinc, vitamin D, vitamin E and selenium probably improve with supplementation, but currently no reliable evidence demonstrates that routine supplementation with multi-, single or dual micronutrients above the recommended daily intake has clinical benefits (i.e. reduced death, increased cure rate at 6 and 12 months, improved nutritional status) in patients receiving antituberculosis treatment. In South Africa, most provinces implement a supplementation protocol based on nutritional assessment and classification of individuals rather than on disease diagnosis or treatment status.

Malaria Infections Do Not Compromise Vaccine-Induced Immunity against Tuberculosis in Mice

PubMed Central

Parra, Marcela; Derrick, Steven C.; Yang, Amy; Tian, JinHua; Kolibab, Kristopher; Oakley, Miranda; Perera, Liyanage P.; Jacobs, William R.; Kumar, Sanjai; Morris, Sheldon L.

2011-01-01

Background Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis. Principal Findings Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naïve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-γ, TNF-α, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL. Conclusions Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas. PMID:22205939

The hidden harm of home-based care: pulmonary tuberculosis symptoms among children providing home medical care to HIV/AIDS-affected adults in South Africa.

PubMed

Cluver, Lucie; Orkin, Mark; Moshabela, Mosa; Kuo, Caroline; Boyes, Mark

2013-01-01

Millions of children in sub-Saharan Africa undertake personal and medical care for family members who are unwell with AIDS. To date, no research has investigated whether such care provision places children at heightened risk for pulmonary tuberculosis. This study aimed to address this gap by identifying risk factors for paediatric pulmonary tuberculosis symptomatology. In 2009-2011, 6002 children aged 10-17 years were surveyed using door-to-door household sampling of census enumeration areas. These were randomly sampled from six urban and rural sites with over 30% HIV prevalence, within South Africa's three highest tuberculosis-burden provinces. Validated scales and clinical tuberculosis symptom checklists were modelled in multivariate logistic regressions, controlling for socio-demographic co-factors. Findings showed that, among children, severe pulmonary tuberculosis symptomatology was predicted by primary caregiver HIV/AIDS-illness [odds ratio (OR): 1.63, confidence interval (CI): 1.23-2.15, p<0.001], and AIDS-orphanhood (OR: 1.44, CI: 1.04-2.00, p<0.029). Three-fold increases in severe tuberculosis symptoms were predicted by the child's exposure to body fluids through providing personal or medical care to an ill adult (OR: 3.12, CI: 1.96-4.95, p<0.001). Symptoms were also predicted by socio-economic factors of food insecurity (OR: 1.52, CI: 1.15-2.02, p<0.003) and household overcrowding (OR: 1.35, CI: 1.06-1.72, p<0.017). Percentage probability of severe tuberculosis symptoms rose from 1.4% amongst least-exposed children, to 18.1% amongst those exposed to all above-stated risk factors, independent of biological relationship of primary caregiver-child and other socio-demographics. Amongst symptomatic children, 75% had never been tested for tuberculosis. These findings identify the risk of tuberculosis among children providing home medical care to their unwell caregivers, and suggest that there are gaps in the health system to screen and detect these cases of paediatric tuberculosis. There is a need for effective interventions to reduce childhood risk, as well as further support for community-based contact-tracing, tuberculosis screening and anti-tuberculosis treatment for children caring for ill adults in contexts with a high burden of HIV and tuberculosis.

Hemophagocytic syndrome secondary to tuberculosis at 24-week gestation.

PubMed

Fernández, Alexandra Arteaga; de Velasco Pérez, David Fernández; Fournier, M C Jiménez; Moreno Del Prado, J C; Torras, B Paraíso; Cañete Palomo, M L

2017-01-01

Hemophagocytic syndrome is a life-threatening disease characterized by the uncontrolled activation of macrophages, resulting in hemophagocytosis of blood cells in the bone marrow. A 20-year-old gravida at 23-week and 5-day gestation was admitted to hospital to evaluate fever up to 104°F of unknown origin, moderate cytopenia, and elevated levels of liver enzymes. Bone marrow biopsy confirmed hemophagocytic syndrome, and polymerase chain reaction came back positive for Mycobacterium tuberculosis. Supportive care and tuberculosis treatment resulted in clinical improvement. At 27 weeks and 5 days, premature rupture of the membranes occurred, and because of the high probability of reactivating the hemophagocytic syndrome, a cesarean section was performed at 29-week and 2-day gestation. Hemophagocytic syndrome is an uncommon disease which rarely appears during pregnancy. Early diagnosis and treatment can save both maternal and fetal lives.

The Military Response to Pandemic: The New Global Threat

DTIC Science & Technology

2009-01-28

creeping things and birds of the air, for I am sorry that I have made them.’ —Genesis 6, 71 In the last years, the appearance of incurable diseases...these diseases came from other species, smallpox probably from dogs and cattle , tuberculosis from cattle and birds, AIDS probably from African...biological levels there is astounding parallel between the visible world of the “macrobes”, where some animals feed themselves with others, and the

Characterization of Mycobacterium tuberculosis Complex DNAs from Egyptian Mummies by Spoligotyping

PubMed Central

Zink, Albert R.; Sola, Christophe; Reischl, Udo; Grabner, Waltraud; Rastogi, Nalin; Wolf, Hans; Nerlich, Andreas G.

2003-01-01

Bone and soft tissue samples from 85 ancient Egyptian mummies were analyzed for the presence of ancient Mycobacterium tuberculosis complex DNA (aDNA) and further characterized by spoligotyping. The specimens were obtained from individuals from different tomb complexes in Thebes West, Upper Egypt, which were used for upper social class burials between the Middle Kingdom (since ca. 2050 BC) and the Late Period (until ca. 500 BC). A total of 25 samples provided a specific positive signal for the amplification of a 123-bp fragment of the repetitive element IS6110, indicating the presence of M. tuberculosis DNA. Further PCR-based tests for the identification of subspecies failed due to lack of specific amplification products in the historic tissue samples. Of these 25 positive specimens, 12 could be successfully characterized by spoligotyping. The spoligotyping signatures were compared to those in an international database. They all show either an M. tuberculosis or an M. africanum pattern, but none revealed an M. bovis-specific pattern. The results from a Middle Kingdom tomb (used exclusively between ca. 2050 and 1650 BC) suggest that these samples bear an M. africanum-type specific spoligotyping signature. The samples from later periods provided patterns typical for M. tuberculosis. This study clearly demonstrates that spoligotyping can be applied to historic tissue samples. In addition, our results do not support the theory that M. tuberculosis originated from the M. bovis type but, rather, suggest that human M. tuberculosis may have originated from a precursor complex probably related to M. africanum. PMID:12517873

Idiopathic pulmonary fibrosis misdiagnosed as sputum-negative pulmonary tuberculosis.

PubMed

Isah, Muhammad Danasabe; Abbas, Aminu; Abba, Abdullahi A; Umar, Mohammed

2016-01-01

Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is one of a spectrum of idiopathic interstitial pneumonia. IPF is an increasingly common condition which poses many diagnostic and therapeutic challenges leading to misdiagnosis and mismanagement. We presented a 55-year-old male textile trader who was initially managed as sputum-negative pulmonary tuberculosis before histology report. He presented to our clinic with Breathlessness and cough of 3 years and 2.5 years, respectively. He had commenced anti-tuberculosis two months before presentation without significant relief. General Physical examination and vital signs were essentially normal. SPO2 was 96% on room air. Chest Examination revealed end-inspiratory bi-basal velcro-like crackles. Other systemic examinations were normal. Radiological examination by way of chest X- ray and chest CT showed features suggestive of IPF. The patient also had open Lung biopsy for histology and spirometry which demonstrated restrictive ventilatory function pattern. A diagnosis of Interstitial lung disease probably Idiopathic Pulmonary Fibrosis was entertained. He was commenced on Tab prednisolone, Tab Rabeprazole, with minimal improvement. IPF have often been misdiagnosed and treated as pulmonary tuberculosis with unfavorable outcome.

Protecting health care workers from tuberculosis: a 10-year experience.

PubMed

Welbel, Sharon F; French, Audrey L; Bush, Patricia; DeGuzman, Delia; Weinstein, Robert A

2009-10-01

Cook County Hospital (CCH) is an inner-city, large public hospital. Twenty-five percent of Chicago's tuberculosis (TB) cases are diagnosed at CCH. We wanted to review and analyze interventions implemented over a 10-year period at CCH to prevent TB infection in health care workers. We performed a retrospective review of interventions to prevent health care-associated tuberculosis. We collated and analyzed tuberculin skin test conversions in our employees for the same time period. From 1990 to 2002, we cared for over 1800 in-patients with tuberculosis. During 1992-1997, multiple interventions to eliminate health care-associated spread of tuberculosis were implemented. Tuberculin skin test conversions in our employees decreased markedly from January 1994 through December 2002. Two drops in tuberculin skin test conversion rates occurred: one after introduction of basic administrative and engineering controls and a second after we experienced a decrease in missed TB cases and the introduction of N-95 personal respirators with 1-time qualitative fit testing. Our annual health care worker skin test conversion rate fell significantly when our primary interventions were relatively simple administrative and engineering controls. Educating health care workers to promptly recognize patients with TB and placing exhaust fans to create negative-pressure respiratory isolation rooms were probably our 2 most potent infection control measures.

The fourth national anti-tuberculosis drug resistance survey in Viet Nam.

PubMed

Nhung, N V; Hoa, N B; Sy, D N; Hennig, C M; Dean, A S

2015-06-01

Viet Nam's Fourth National Anti-Tuberculosis Drug Resistance Survey was conducted in 2011. To determine the prevalence of resistance to the four main first-line anti-tuberculosis drugs in Viet Nam. Eighty clusters were selected using a probability proportion to size approach. Drug susceptibility testing (DST) against the four main first-line anti-tuberculosis drugs was performed. A total of 1629 smear-positive tuberculosis (TB) patients were eligible for culture. Of these, DST results were available for 1312 patients, including 1105 new TB cases, 195 previously treated TB cases and 12 cases with an unknown treatment history. The proportion of cases with resistance to any drug was 32.7% (95%CI 29.1-36.5) among new cases and 54.2% (95%CI 44.3-63.7) among previously treated cases. The proportion of multidrug-resistant TB (MDR-TB) cases was 4.0% (95%CI 2.5-5.4) in new cases and 23.3 (95%CI 16.7-29.9) in previously treated cases. The fourth drug resistance survey in Viet Nam found that the proportion of MDR-TB among new and previously treated cases was not significantly different from that in the 2005 survey. The National TB Programme should prioritise the detection and treatment of MDR-TB to reduce transmission of MDR-TB in the community.

Identification of the likely translational start of Mycobacterium tuberculosis GyrB.

PubMed

Karkare, Shantanu; Brown, Amanda C; Parish, Tanya; Maxwell, Anthony

2013-07-15

Bacterial DNA gyrase is a validated target for antibacterial chemotherapy. It consists of two subunits, GyrA and GyrB, which form an A₂B₂ complex in the active enzyme. Sequence alignment of Mycobacterium tuberculosis GyrB with other bacterial GyrBs predicts the presence of 40 potential additional amino acids at the GyrB N-terminus. There are discrepancies between the M. tuberculosis GyrB sequences retrieved from different databases, including sequences annotated with or without the additional 40 amino acids. This has resulted in differences in the GyrB sequence numbering that has led to the reporting of previously known fluoroquinolone-resistance mutations as novel mutations. We have expressed M. tuberculosis GyrB with and without the extra 40 amino acids in Escherichia coli and shown that both can be produced as soluble, active proteins. Supercoiling and other assays of the two proteins show no differences, suggesting that the additional 40 amino acids have no effect on the enzyme in vitro. RT-PCR analysis of M. tuberculosis mRNA shows that transcripts that could yield both the longer and shorter protein are present. However, promoter analysis showed that only the promoter elements leading to the shorter GyrB (lacking the additional 40 amino acids) had significant activity. We conclude that the most probable translational start codon for M. tuberculosis GyrB is GTG (Val) which results in translation of a protein of 674 amino acids (74 kDa).

Burden of Multidrug Resistant Mycobacterium tuberculosis Among New Cases in Al-Madinah Al-Monawarah, Saudi Arabia.

PubMed

Elhassan, Mogahid M; Hemeg, Hassan A; Elmekki, Miskelyemen A; Turkistani, Khalid A; Abdul-Aziz, Ahmed A

2017-01-01

The pattern of Mycobacterium tuberculosis susceptibility to first line drugs and multidrug resistance in Al-Madinah Al-Munawarah, a seasonally overcrowded are during Hajj and Omrah, is not well studied. This study aimed to investigate anti-tuberculosis drug resistance and its distribution among new cases in Al-Madinah Al-Monawarah. Study subjects included 622 patients with first time confirmed TB referred to the central tuberculosis laboratory in Al-Madinah between January 2012 and December 2014. Out of the 622 isolates, 99 (15.9%) were Mycobacteria Other Than Tuberculosis (MOTTS) and 25 (4.0%), three of which (12%) were children under five years of age, revealed multidrug resistance (MDR). Monoresistance to isoniazid (H) was (1.8%), to rifampin (R) was (1.4%), to streptomycin (S) was (1.9 %) to ethambutol (E) was (1.1 %) and to pyrazinamide (Z) was (2.1%). Being among the new cases, multidrug resistant tuberculosis (MDR TB) is supposed to be caused by strains which are originally multidrug resistant. Neither nationality nor gender was found to be associated with MDR TB. Since 12% of MDR cases were among children, a probability of primary infection with MDR strains is to be considered. Moreover, mass gathering during Hajj and Omrah seasons does not seem to increase the burden of MDR in the region. However, further investigation is needed to molecularly characterize MDR isolates and their phylogenetics and geographical origin. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Identification of a novel inhibitor of isocitrate lyase as a potent antitubercular agent against both active and non-replicating Mycobacterium tuberculosis.

PubMed

Liu, Yishuang; Zhou, Shuang; Deng, Qi; Li, Xinghua; Meng, Jianzhou; Guan, Yan; Li, Chuanyou; Xiao, Chunling

2016-03-01

Screen and identify novel inhibitors of isocitrate lyase (ICL) as potent antitubercular agents against Mycobacterium tuberculosis and determine their inhibitory characteristics, antitubercular activities and mechanisms of action. Recombinant ICL of M. tuberculosis was expressed and purified, which was used for high-throughput screening (HTS) and the following experiments. A total of 71,765 compounds were screened to identify ICL inhibitors which were then evaluated for their roles as potent antitubercular agents. To determine the inhibitory characteristics of the agents against latent M. tuberculosis in persistent infections, a macrophage model (mouse J774A.1 cell) infected with Mycobacterium marinum BAA-535 strain was built and assessed. The potent antitubercular agents were identified using the macrophage model. Then, the inhibitory intensity and mode of the agents that exhibit on ICL protein of M. tuberculosis were analyzed, and the interaction mechanisms were preliminarily clarified according to the parameters of enzyme kinetics, circular dichroism experiments, fluorescence quenching assay, and molecular docking. The previously established ICL inhibitor screening model was evaluated to be suitable for HTS assay. Of the 71,765 compounds, 13 of them were identified to inhibit ICL effectively and stably. IMBI-3 demonstrated the most significant inhibitory activity with IC50 of 30.9 μmol/L. Its minimum inhibitory concentration (MIC) for M. tuberculosis, including extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB), were determined in the range of 0.25-1 μg/mL. When IMBI-3 is used in combination with isoniazid, the colony-forming units (CFU) counting of latent M. tuberculosis in J774A.1 macrophage cells decreased significantly as IMBI-3 concentration increased. The inhibition mode of IMBI-3 on ICL was probably competitive inhibition with an inhibition constant (Ki) of approximate 1.85 μmol/L. The interaction between IMBI-3 and ICL of M. tuberculosis was also confirmed by circular dichroism experiments and fluorescence quenching assay. And seven possible active amino acids of ICL of M. tuberculosis were identified in the active site through molecular docking. IMBI-3, a novel potent antitubercular agent targeting ICL of M. tuberculosis, was identified and evaluated. It inhibited both log-phase M. tuberculosis in vitro and dormant M. tuberculosis in macrophages. It was the first representative compound of this family with the ICL enzyme inhibition and antimycobacterial activities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence of drug-resistant tuberculosis and imputed burden in South Africa: a national and sub-national cross-sectional survey.

PubMed

Ismail, Nazir Ahmed; Mvusi, Lindiwe; Nanoo, Ananta; Dreyer, Andries; Omar, Shaheed V; Babatunde, Sanni; Molebatsi, Thabo; van der Walt, Martie; Adelekan, Adeboye; Deyde, Varough; Ihekweazu, Chikwe; Madhi, Shabir A

2018-04-20

Globally, per-capita, South Africa reports a disproportionately high number of cases of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We sought to estimate the prevalence of resistance to tuberculosis drugs in newly diagnosed and retreated patients with tuberculosis provincially and nationally, and compared these with the 2001-02 estimates. A cross-sectional survey was done between June 15, 2012-June 14, 2014, using population proportionate randomised cluster sampling in the nine provinces in South Africa. 343 clusters were included, ranging between 31 and 48 per province. A patient was eligible for inclusion in the survey if he or she presented as a presumptive case during the intake period at a drug resistance survey enrolling facility. Consenting participants (≥18 years old) completed a questionnaire and had a sputum sample tested for resistance to first-line and second-line drugs. Analysis was by logistic regression with robust SEs, inverse probability weighted against routine data, and estimates were derived using a random effects model. 101 422 participants were tested in 2012-14. Nationally, the prevalence of MDR tuberculosis was 2·1% (95% CI 1·5-2·7) among new tuberculosis cases and 4·6% (3·2-6·0) among retreatment cases. The provincial point prevalence of MDR tuberculosis ranged between 1·6% (95% CI 0·9-2·9) and 5·1% (3·7-7·0). Overall, the prevalence of rifampicin-resistant tuberculosis (4·6%, 95% CI 3·5-5·7) was higher than the prevalence of MDR tuberculosis (2·8%, 2·0-3·6; p=0·01). Comparing the current survey with the previous (2001-02) survey, the overall MDR tuberculosis prevalence was 2·8% versus 2·9% and prevalance of rifampicin-resistant tuberculosis was 3·4% versus 1·8%, respectively. The prevalence of isoniazid mono-resistant tuberculosis was above 5% in all provinces. The prevalence of ethionamide and pyrazinamide resistance among MDR tuberculosis cases was 44·7% (95% CI 25·9-63·6) and 59·1% (49·0-69·1), respectively. The prevalence of XDR tuberculosis was 4·9% (95% CI 1·0-8·8). Nationally, the estimated numbers of cases of rifampicin-resistant tuberculosis, MDR tuberculosis, and isoniazid mono-resistant tuberculosis for 2014 were 13 551, 8249, and 17 970, respectively. The overall prevalence of MDR tuberculosis in South Africa in 2012-14 was similar to that in 2001-02; however, prevalence of rifampicin-resistant tuberculosis almost doubled among new cases. Furthermore, the high prevalence of isoniazid mono-resistant tuberculosis, not routinely screened for, and resistance to second-line drugs has implications for empirical management. President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention under the terms of 1U19GH000571. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis.

PubMed

Tonaco, Marcela M; Moreira, Jôsimar D; Nunes, Fernanda F C; Loures, Cristina M G; Souza, Larissa R; Martins, Janaina M; Silva, Henrique R; Porto, Arthur Henrique R; Toledo, Vicente Paulo C P; Miranda, Silvana S; Guimarães, Tânia Mara P D

2017-12-01

The cells T CD4+ T and CD8+ can be subdivided into phenotypes naïve, T of central memory, T of effector memory and effector, according to the expression of surface molecules CD45RO and CD27. The T lymphocytes are cells of long life with capacity of rapid expansion and function, after a new antigenic exposure. In tuberculosis, it was found that specific memory T cells are present, however, gaps remain about the role of such cells in the disease immunology. In this study, the phenotypic profile was analyzed and characterized the functionality of CD4+ T lymphocytes and CD8+ T cells of memory and effector, in response to specific stimuli in vitro, in patients with active pulmonary TB, compared to individuals with latent infection with Mycobacterium tuberculosis the ones treated with pulmonary TB. It was observed that the group of patients with active pulmonary tuberculosis was the one which presented the highest proportion of cells T CD4+ of central memory IFN-ɣ+ e TNF-α+, suggesting that in TB, these T of central memory cells would have a profile of protective response, being an important target of study for the development of more effective vaccines; this group also developed lower proportion of CD8+ T effector lymphocytes than the others, a probable cause of specific and less effective response against the bacillus in these individuals; the ones treated for pulmonary tuberculosis were those who developed higher proportion of T CD4+ of memory central IL-17+ cells, indicating that the stimulation of long duration, with high antigenic load, followed by elimination of the pathogen, contribute to more significant generation of such cells; individuals with latent infection by M. tuberculosis and treated for pulmonary tuberculosis, showed greater response of CD8+ T effector lymphocytes IFN-ɣ+ than the controls, suggesting that these cells, as well as CD4+ T lymphocytes, have crucial role of protection against M. tuberculosis. These findings have contributed to a better understanding of the immunologic changes in M. tuberculosis infection and the development of new strategies for diagnosis and prevention of tuberculosis. Copyright © 2017. Published by Elsevier B.V.

Effect of Antiretroviral Therapy on the Diagnostic Accuracy of Symptom Screening for Intensified Tuberculosis Case Finding in a South African HIV Clinic

PubMed Central

Rangaka, Molebogeng X.; Wilkinson, Robert J.; Glynn, Judith R.; Boulle, Andrew; van Cutsem, Gilles; Goliath, Rene; Mathee, Shaheed; Maartens, Gary

2012-01-01

Background. Current symptom screening algorithms for intensified tuberculosis case finding or prior to isoniazid preventive therapy (IPT) in patients infected with human immunodeficiency virus (HIV) were derived from antiretroviral-naive cohorts. There is a need to validate screening algorithms in patients on antiretroviral therapy (ART). Methods. We performed cross-sectional evaluation of the diagnostic accuracy of symptom screening, including the World Health Organization (WHO) algorithm, to rule out tuberculosis in HIV-infected individuals pre-ART and on ART undergoing screening prior to IPT. Results. A total of 1429 participants, 54% on ART, had symptom screening and a sputum culture result available. Culture-positive tuberculosis was diagnosed in 126 patients (8.8%, 95% confidence interval [CI], 7.4%–10.4%). The WHO symptom screen in the on-ART compared with the pre-ART group had a lower sensitivity (23.8% vs 47.6%), but higher specificity (94.4% vs 79.8%). The effect of ART was independent of CD4+ count in multivariable analyses. The posttest probability of tuberculosis following a negative WHO screen was 8.9% (95% CI, 7.4%–10.8%) and 4.4% (95% CI, 3.7%–5.2%) for the pre-ART and on-ART groups, respectively. Addition of body mass index to the WHO screen significantly improved discriminatory ability in both ART groups, which was further improved by adding CD4 count and ART duration. Conclusions. The WHO symptom screen has poor sensitivity, especially among patients on ART, in a clinic where regular tuberculosis screening is practiced. Consequently, a significant proportion of individuals with tuberculosis would inadvertently be placed on isoniazid monotherapy despite high negative predictive values. Until more sensitive methods of ruling out tuberculosis are established, it would be prudent to do a sputum culture prior to IPT where this is feasible. PMID:22955441

The dynamic of tuberculosis case finding in the era of the public–private mix strategy for tuberculosis control in Central Java, Indonesia

PubMed Central

Reviono, Reviono; Setianingsih, Wahyu; Damayanti, Kusmadewi Eka; Ekasari, Ratna

2017-01-01

ABSTRACT Background: The public–private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown. Objective: We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. Methods: This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. Results: The CDR increased during the initial phase (2000–2005), decreased during the mid-phase (2006–2009), and increased slightly during the late phase (2010–2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. Conclusions: The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator pattern will secure the long-term success of the program. PMID:28766465

The dynamic of tuberculosis case finding in the era of the public-private mix strategy for tuberculosis control in Central Java, Indonesia.

PubMed

Reviono, Reviono; Setianingsih, Wahyu; Damayanti, Kusmadewi Eka; Ekasari, Ratna

2017-01-01

The public-private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown.  We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. The CDR increased during the initial phase (2000-2005), decreased during the mid-phase (2006-2009), and increased slightly during the late phase (2010-2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator pattern will secure the long-term success of the program.

Adding moxifloxacin is associated with a shorter time to culture conversion in pulmonary tuberculosis.

PubMed

Wang, J-Y; Wang, J-T; Tsai, T-H; Hsu, C-L; Yu, C-J; Hsueh, P-R; Lee, L-N; Yang, P-C

2010-01-01

To investigate whether adding moxifloxacin (MXF) to the standard anti-tuberculosis regimen can shorten the time to sputum culture conversion in pulmonary tuberculosis (PTB). Adults with culture-positive PTB were divided into two treatment groups by their choice: standard regimen alone (HERZ group) and standard regimen plus daily 400 mg MXF in the first 2 months (MXF group). Sputum samples were collected thrice weekly in the first 8 weeks. The propensity score was calculated to estimate the conditional probability of entering the MXF group. Factors influencing time to culture conversion were investigated using Cox proportional hazards regression analysis stratified by propensity score. Sixty-two patients were enrolled in the MXF group and 88 in the HERZ group; respectively 51 and 72 completed the study. The regimen was modified before culture conversion in respectively 6 (12%) and 12 (16%; P = 0.47) patients, due to adverse effects. The time to culture conversion was shorter in the MXF group (HR 2.1, 95%CI 1.4-3.2). The culture conversion rate after 6 weeks of treatment was respectively 82% and 61% (P = 0.011, <0.05/4, calculated using the modified Bonferroni method). Adding MXF to the standard anti-tuberculosis regimen in the first 2 months was associated with a shorter time to culture conversion, a higher 6-week culture conversion rate and reduced transmission of tuberculosis.

[Survival analysis of patients with pneumoconiosis from 1956 to 2010 in Changsha].

PubMed

Xue, Jing; Chen, Lizhang

2012-01-01

To investigate the survival rate and life expectancy of patients with pneumoconiosis and influence factors in Changsha from 1956 to 2010. A total of 3685 patients with pneumoconiosis were diagnosed and reported from 1956 to 2010 in Changsha. The fatality rate and life expectancy were analyzed by life table and the cause of death was analyzed by Kaplan-Meier method and Cox regression model. The death rate increased obviously with age. Age and accumulation death probability showed linearity (Ŷ=1.271+0.041X, r=0.989). The life expectancy was 60.12 years. The first cause of death was pulmonary tuberculosis in patients with pneumoconiosis. Ruling out the influence of pulmonary tuberculosis, pneumoconiosis, and lung source heart disease, the life expectancy of patients with pneumoconiosis averagely extended 0.83, 0.99, and 0.02 years. The death rate of pneumoconiosis-tuberculosis had significant difference with that of the pneumoconiosisnontuberculosis (P<0.01). Cox regression analysis revealed that the main risk factors for the survival of patients with pneumoconiosis included type of work (smashing worker), complication with tuberculosis, type of pneumoconiosis (silicosis). The death hazard ratio or relative risk caused by them was 1.927, 1.749, and 1.609, respectively. Prevention of pneumoconiosis should focus on smashing workers in Changsha, while its the treatment primarily attaches importance to complication of tuberculosis and lung infection.

Primary Multidrug Resistant Tuberculosis and Utility of Line Probe Assay for Its Detection in Smear-Positive Sputum Samples in a Tertiary Care Hospital in South India.

PubMed

Yacoob, Fahmiya Leena; Philomina Jose, Beena; Karunakaran Lelitha, Sarada Devi; Sreenivasan, Sreelatha

2016-01-01

In a high tuberculosis burdened country like India, rapid, cost-effective, and reliable diagnostic tools for tuberculosis are an urgent need of the hour to prevent inappropriate treatment strategies and further spread of resistance. This study aimed to estimate the proportion of new smear-positive tuberculosis cases with primary resistance to rifampicin and/or isoniazid as well as identify the common mutations associated with it. Sputum of 200 newly diagnosed smear-positive cases of 1+ score and above was directly subjected to Line Probe Assay using the GenoType MTBDRplus assay kit. All samples were inoculated onto solid media and 61 samples were inoculated in automated liquid culture also. The Line Probe Assay gave hundred percent interpretable results with 2.5% of the study population showing resistant pattern. Only 1% of the cases were primary multidrug resistant tuberculosis and 1.5% showed isoniazid monoresistance. S531L and C15T were the most common genetic mutations seen for rifampicin and isoniazid resistance, respectively. 40% had absent rpoB wild type 8 band indicating probable silent mutation after clinical correlation. The average turnaround time for Line Probe Assay was far less (3.8 days) as compared to solid and liquid cultures (35.6 days and 13.5 days, resp.).

PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

PubMed Central

Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

2014-01-01

Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

Bovine tuberculosis in free-ranging carnivores from Michigan.

PubMed

Bruning-Fann, C S; Schmitt, S M; Fitzgerald, S D; Fierke, J S; Friedrich, P D; Kaneene, J B; Clarke, K A; Butler, K L; Payeur, J B; Whipple, D L; Cooley, T M; Miller, J M; Muzo, D P

2001-01-01

During a survey of carnivores and omnivores for bovine tuberculosis conducted in Michigan (USA) since 1996, Mycobacterium bovis was cultured from lymph nodes pooled from six coyotes (Canis latrans) (four adult female, two adult male), two adult male raccoons (Procyon lotor), one adult male red fox (Vulpes vulpes), and one 1.5-yr-old male black bear (Ursus americanus). One adult, male bobcat (Felis rufus) with histologic lesions suggestive of tuberculosis was negative on culture but positive for organisms belonging to the Mycobacterium tuberculosis complex when tested by polymerase chain reaction. All the tuberculous animals were taken from three adjoining counties where M. bovis is known to be endemic in the free-ranging white-tailed deer (Odocoileus virginianus) population. There were two coyotes, one raccoon, one red fox, and one bobcat infected in Alpena county. Montmorency County had two coyotes and one raccoon with M. bovis. Two coyotes and a bear were infected from Alcona County. These free-ranging carnivores/omnivores probably became infected with M. bovis through consumption of tuberculous deer. Other species included in the survey were opossum (Didelphis virginiana), gray fox (Urocyon cinereoargenteus), and badger (Taxidea taxus); these were negative for M. bovis.

Perspectives on the History of Bovine TB and the Role of Tuberculin in Bovine TB Eradication

PubMed Central

Good, Margaret; Duignan, Anthony

2011-01-01

Tuberculosis remains a significant disease of animals and humans worldwide. Bovine tuberculosis is caused by Mycobacteria with an extremely wide host range and serious, although currently probably underdiagnosed, zoonotic potential. Where bovine tuberculosis controls are effective, human zoonotic TB, due to Mycobacterium bovis or M. caprae, is uncommon and clinical cases are infrequent in cattle. Therefore, the control and ultimate eradication of bovine tuberculosis is desirable. Tuberculin tests are the primary screening tool used in bovine eradication. The choice of tuberculin test is dependent on the environment in which it is to be used. Tuberculin potency is critical to test performance, and the accurate determination of potency is therefore particularly important. The design of a control or eradication programme should take into consideration the fundamental scientific knowledge, the epidemiological profile of disease, the experience of other eradication programmes, and the presence, in the same ecosystem, of maintenance hosts, in which infection is self-sustaining and which are capable of transmitting infection. A control or eradication programme will necessarily require modification as it progresses and must be under constant review to identify the optimal desirable goals, the efficacy of policy, and constraints to progress. PMID:21547209

Nutritional supplements for people being treated for active tuberculosis.

PubMed

Grobler, Liesl; Nagpal, Sukrti; Sudarsanam, Thambu D; Sinclair, David

2016-06-29

Tuberculosis and malnutrition are linked in a complex relationship. Tuberculosis may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there is no evidence-based nutritional guidance for adults and children being treated for tuberculosis. To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2016), MEDLINE (from 1946 to 4 February 2016), EMBASE (from 1980 to 4 February 2016), LILACS (from 1982 to 4 February 2016), the metaRegister of Controlled Trials (mRCT), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the Indian Journal of Tuberculosis up to 4 February 2016, and checked the reference lists of all included studies. Randomized controlled trials that compared any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. The primary outcomes of interest were all-cause death, and cure at six and 12 months. Two review authors independently selected trials for inclusion, and extracted data and assessed the risk of bias in the included trials. We presented the results as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). Where appropriate, we pooled data from trials with similar interventions and outcomes. We assessed the quality of the evidence using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Thirty-five trials, including 8283 participants, met the inclusion criteria of this review. Macronutrient supplementationSix trials assessed the provision of free food, or high-energy supplements. Only two trials measured total dietary intake, and in both trials the intervention increased calorie consumption compared to controls.The available trials were too small to reliably prove or exclude clinically important benefits on mortality (RR 0.34, 95% CI 0.10 to 1.20; four trials, 567 participants, very low quality evidence), cure (RR 0.91, 95% CI 0.59 to 1.41; one trial, 102 participants, very low quality evidence), or treatment completion (data not pooled; two trials, 365 participants, very low quality evidence).Supplementation probably produces a modest increase in weight gain during treatment for active tuberculosis, although this was not seen consistently across all trials (data not pooled; five trials, 883 participants, moderate quality evidence). Two small studies provide some evidence that quality of life may also be improved but the trials were too small to have much confidence in the result (data not pooled; two trials, 134 participants, low quality evidence). Micronutrient supplementationSix trials assessed multi-micronutrient supplementation in doses up to 10 times the dietary reference intake, and 18 trials assessed single or dual micronutrient supplementation.Routine multi-micronutrient supplementation may have little or no effect on mortality in HIV-negative people with tuberculosis (RR 0.86, 95% CI 0.46 to 1.6; four trials, 1219 participants, low quality evidence), or HIV-positive people who are not taking antiretroviral therapy (RR 0.92, 95% CI 0.69 to 1.23; three trials, 1429 participants, moderate quality evidence). There is insufficient evidence to know if supplementation improves cure (no trials), treatment completion (RR 0.99, 95% CI 0.95 to 1.04; one trial, 302 participants, very low quality evidence), or the proportion of people who remain sputum positive during the first eight weeks (RR 0.92, 95% CI 0.63 to 1.35; two trials, 1020 participants, very low quality evidence). However, supplementation may have little or no effect on weight gain during treatment (data not pooled; five trials, 2940 participants, low quality evidence), and no studies have assessed the effect on quality of life.Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, supplementation probably does improve plasma levels of zinc, vitamin D, vitamin E, and selenium, but this has not been shown to have clinically important benefits. Of note, despite multiple studies of vitamin D supplementation in different doses, statistically significant benefits on sputum conversion have not been demonstrated. There is currently insufficient research to know whether routinely providing free food, or energy supplements improves tuberculosis treatment outcomes, but it probably improves weight gain in some settings.Although blood levels of some vitamins may be low in people starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing above recommended daily amounts has clinical benefits.

High Court's TB Ruling Probably Applies to AIDS.

ERIC Educational Resources Information Center

Sendor, Benjamin

1987-01-01

Discusses a United States Supreme Court decision upholding Section 504 protection for an elementary school teacher fired due to recurrent tuberculosis. The school board may need to make reasonable accommodation for employees handicapped by contagious diseases. The Court might also interpret Section 504 as covering AIDS carriers. (MLH)

Detection of interferon-γ response to tuberculosis in blood collected at commencement of exsanguination at slaughter from cattle sensitized with Mycobacterium bovis.

PubMed

Okafor, Chika C; Grooms, Daniel L; Bolin, Steven R; Kaneene, John B

2012-06-01

To determine whether an interferon (IFN)-γ response sufficient to categorize cattle as positive for tuberculosis can be detected in blood collected at commencement of exsanguination at slaughter. 15 Holstein cows. 12 cows were experimentally sensitized by SC injection with inactivated Mycobacterium bovis in mineral oil, which induced an immune response that mimicked natural infection with M bovis. Three nonsensitized control cows were injected SC with mineral oil alone. By 5 weeks after injection, only the 12 sensitized cows had positive results for tuberculosis with whole blood IFN-γ assay. At that time, all 15 cows were sent to slaughter and samples of blood were collected from each cow immediately before stunning and at commencement of exsanguination (within 90 seconds after stunning). A whole blood IFN-γ assay was performed on the samples. Conditional probability and paired t tests were used to analyze changes in the categorical test interpretation and qualitative IFN-γ production, respectively. All 12 sensitized cows had positive results for tuberculosis in samples obtained immediately before stunning, and 9 retained positive results for samples obtained at commencement of exsanguination. There was a significant decrease in the mean background-corrected IFN-γ ELISA optical density values for samples obtained at commencement of exsanguination. IFN-γ response sufficient to classify cattle as positive for tuberculosis could be detected in blood collected at commencement of exsanguination. These findings support further development and use of the IFN-γ assay on blood samples collected at exsanguination as part of a bovine tuberculosis surveillance program.

Tuberculosis in a South African prison – a transmission modelling analysis

PubMed Central

Johnstone-Robertson, Simon; Lawn, Stephen D; Welte, Alex; Bekker, Linda-Gail; Wood, Robin

2015-01-01

Background Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. Methods Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. Results Levels of overcrowding (230%) in communal cells and poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. Conclusions Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently. PMID:22272961

IMPACT OF CIGARETTE SMOKING ON RATES AND CLINICAL PROGNOSIS OF PULMONARY TUBERCULOSIS IN SOUTHERN MEXICO

PubMed Central

Bonacci, Robert A.; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Reynales-Shigematsu, Luz Myriam; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Delgado-Sánchez, Guadalupe; Martínez-Gamboa, Rosa Areli; Cano-Arellano, Bulmaro; Sifuentes-Osornio, José; de León, Alfredo Ponce

2012-01-01

Objectives To examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes. Materials From 1995-2010, we analyzed data from 1062 patients with TB and from 2001-2004, 2951 contacts in Southern Mexico. Patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and mycobacteriological evaluation and received treatment by the local DOTS program. Results Consumers of 1-10 (LS) or 11 or more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS,17.74) smoker-nonsmoker rate ratios were significantly higher for smokers. Smoker population was more likely to experience unfavorable treatment outcomes (HS, adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and 2.37). Contacts that smoked had a higher probability of developing active TB (HR 2.38) during follow up. Conclusions Results indicate the need of incorporating smoking prevention and cessation, especially among men, into international TB control strategies. PMID:22982014

Previous treatment, sputum-smear nonconversion, and suburban living: The risk factors of multidrug-resistant tuberculosis among Malaysians.

PubMed

Mohd Shariff, Noorsuzana; Shah, Shamsul Azhar; Kamaludin, Fadzilah

2016-03-01

The number of multidrug-resistant tuberculosis patients is increasing each year in many countries all around the globe. Malaysia has no exception in facing this burdensome health problem. We aimed to investigate the factors that contribute to the occurrence of multidrug-resistant tuberculosis among Malaysian tuberculosis patients. An unmatched case-control study was conducted among tuberculosis patients who received antituberculosis treatments from April 2013 until April 2014. Cases are those diagnosed as pulmonary tuberculosis patients clinically, radiologically, and/or bacteriologically, and who were confirmed to be resistant to both isoniazid and rifampicin through drug-sensitivity testing. On the other hand, pulmonary tuberculosis patients who were sensitive to all first-line antituberculosis drugs and were treated during the same time period served as controls. A total of 150 tuberculosis patients were studied, of which the susceptible cases were 120. Factors found to be significantly associated with the occurrence of multidrug-resistant tuberculosis are being Indian or Chinese (odds ratio 3.17, 95% confidence interval 1.04-9.68; and odds ratio 6.23, 95% confidence interval 2.24-17.35, respectively), unmarried (odds ratio 2.58, 95% confidence interval 1.09-6.09), living in suburban areas (odds ratio 2.58, 95% confidence interval 1.08-6.19), are noncompliant (odds ratio 4.50, 95% confidence interval 1.71-11.82), were treated previously (odds ratio 8.91, 95% confidence interval 3.66-21.67), and showed positive sputum smears at the 2nd (odds ratio 7.00, 95% confidence interval 2.46-19.89) and 6th months of treatment (odds ratio 17.96, 95% confidence interval 3.51-91.99). Living in suburban areas, positive sputum smears in the 2nd month of treatment, and was treated previously are factors that independently contribute to the occurrence of multidrug-resistant tuberculosis. Those with positive smears in the second month of treatment, have a history of previous treatment, and live in suburban areas are found to have a higher probability of becoming multidrug resistant. The results presented here may facilitate improvements in the screening and detection process of drug-resistant patients in Malaysia in the future. Copyright © 2015 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Bronchoalveolar lavage for diagnosis of tuberculosis infection in elephants.

PubMed

Hermes, R; Saragusty, J; Moser, I; Holtze, S; Nieter, J; Sachse, K; Voracek, T; Bernhard, A; Bouts, T; Göritz, F; Hildebrandt, T B

2018-03-01

Tuberculosis (TB) has been known to affect elephants for thousands of years. It was put into spotlight when few circus elephants were diagnosed carrying Mycobacterium (M.) tuberculosis. Because of the zoonotic risk and high susceptibility to M. tuberculosis, periodic testing was enacted since, in captive breeding programmes. Presently, trunk wash is the recommended diagnostic procedure for TB. Trunk wash, however, puts the operator at risk, has low sensitivity, and is prone to contamination. Here, bronchoalveolar lavage is described for the first time for TB diagnosis in elephants. Bronchial, trunk and mouth fluids were investigated using bacterial culture, M. tuberculosis complex (MTC)-specific real-time quantitative PCR (qPCR) and mycobacterial genus-specific qPCR for overall presence of mycobacteria or mycobacterial DNA including bacteria or DNA of closely related genera, respectively, in 14 elephants. Neither bacteria of the MTC nor their DNA were identified in any of the elephants. Yet, 25% of the cultures grew non-tuberculous mycobacteria (NTM) or closely related bacterial species. Furthermore, 85% of the samples contained DNA of NTM or closely related bacterial genera. This finding might explain continued false-positive results from various serological tests. From a zoonotic point of view, bronchoalveolar lavage is safer for the testing personal, has higher probability of capturing MTC and, through PCR, identifies DNA NTM in elephants. Yet, necessary endoscopic equipment, animal sedation and access to a TB reference laboratory might pose challenging requirements in remote conditions in some elephant range countries.

Widespread Environmental Contamination with Mycobacterium tuberculosis Complex Revealed by a Molecular Detection Protocol

PubMed Central

Santos, Nuno; Santos, Catarina; Valente, Teresa; Gortázar, Christian; Almeida, Virgílio; Correia-Neves, Margarida

2015-01-01

Environmental contamination with Mycobacterium tuberculosis complex (MTC) has been considered crucial for bovine tuberculosis persistence in multi-host-pathogen systems. However, MTC contamination has been difficult to detect due to methodological issues. In an attempt to overcome this limitation we developed an improved protocol for the detection of MTC DNA. MTC DNA concentration was estimated by the Most Probable Number (MPN) method. Making use of this protocol we showed that MTC contamination is widespread in different types of environmental samples from the Iberian Peninsula, which supports indirect transmission as a contributing mechanism for the maintenance of bovine tuberculosis in this multi-host-pathogen system. The proportion of MTC DNA positive samples was higher in the bovine tuberculosis-infected than in presumed negative area (0.32 and 0.18, respectively). Detection varied with the type of environmental sample and was more frequent in sediment from dams and less frequent in water also from dams (0.22 and 0.05, respectively). The proportion of MTC-positive samples was significantly higher in spring (p<0.001), but MTC DNA concentration per sample was higher in autumn and lower in summer. The average MTC DNA concentration in positive samples was 0.82 MPN/g (CI95 0.70–0.98 MPN/g). We were further able to amplify a DNA sequence specific of Mycobacterium bovis/caprae in 4 environmental samples from the bTB-infected area. PMID:26561038

Structural and functional analyses of Mycobacterium tuberculosis Rv3315c-encoded metal-dependent homotetrameric cytidine deaminase.

PubMed

Sánchez-Quitian, Zilpa A; Schneider, Cristopher Z; Ducati, Rodrigo G; de Azevedo, Walter F; Bloch, Carlos; Basso, Luiz A; Santos, Diógenes S

2010-03-01

The emergence of drug-resistant strains of Mycobacterium tuberculosis, the causative agent of tuberculosis, has exacerbated the treatment and control of this disease. Cytidine deaminase (CDA) is a pyrimidine salvage pathway enzyme that recycles cytidine and 2'-deoxycytidine for uridine and 2'-deoxyuridine synthesis, respectively. A probable M. tuberculosis CDA-coding sequence (cdd, Rv3315c) was cloned, sequenced, expressed in Escherichia coli BL21(DE3), and purified to homogeneity. Mass spectrometry, N-terminal amino acid sequencing, gel filtration chromatography, and metal analysis of M. tuberculosis CDA (MtCDA) were carried out. These results and multiple sequence alignment demonstrate that MtCDA is a homotetrameric Zn(2+)-dependent metalloenzyme. Steady-state kinetic measurements yielded the following parameters: K(m)=1004 microM and k(cat)=4.8s(-1) for cytidine, and K(m)=1059 microM and k(cat)=3.5s(-1) for 2'-deoxycytidine. The pH dependence of k(cat) and k(cat)/K(M) for cytidine indicate that protonation of a single ionizable group with apparent pK(a) value of 4.3 abolishes activity, and protonation of a group with pK(a) value of 4.7 reduces binding. MtCDA was crystallized and crystal diffracted at 2.0 A resolution. Analysis of the crystallographic structure indicated the presence of a Zn(2+) coordinated by three conserved cysteines and the structure exhibits the canonical cytidine deaminase fold. (c) 2009 Elsevier Inc. All rights reserved.

Effect of the inoculation site of bovine purified protein derivative (PPD) on the skin fold thickness increase in cattle from officially tuberculosis free and tuberculosis-infected herds.

PubMed

Casal, Carmen; Alvarez, Julio; Bezos, Javier; Quick, Harrison; Díez-Guerrier, Alberto; Romero, Beatriz; Saez, Jose L; Liandris, Emmanouil; Navarro, Alejandro; Perez, Andrés; Domínguez, Lucas; de Juan, Lucía

2015-09-01

The official technique for diagnosis of bovine tuberculosis (bTB) worldwide is the tuberculin skin test, based on the evaluation of the skin thickness increase after the intradermal inoculation of a purified protein derivative (PPD) in cattle. A number of studies performed on experimentally infected or sensitized cattle have suggested that the relative sensitivity of the cervical test (performed in the neck) may vary depending on the exact location in which the PPD is injected. However, quantitative evidence on the variation of the test accuracy associated to changes in the site of inoculation in naturally infected animals (the population in which performance of the test is most critical for disease eradication) is lacking. Here, the probability of obtaining a positive reaction (>2 or 4 millimeters and/or presence of local clinical signs) after multiple inoculations of bovine PPD in different cervical and scapular locations was assessed in animals from five bTB-infected herds (818 cattle receiving eight inoculations) using a hierarchical Bayesian logistic regression model and adjusting for the potential effect of age and sex. The effect of the inoculation site was also assessed qualitatively in animals from four officially tuberculosis free (OTF) herds (two inoculations in 210 animals and eight inoculations in 38 cattle). Although no differences in the qualitative outcome of the test were observed in cattle from OTF herds, a statistically important association between the test outcome and the inoculation site in animals from infected herds was observed, with higher probabilities of positive results when the test was performed in the neck anterior area. Our results suggest that test sensitivity may be maximized by considering the area of the neck in which the test is applied, although lack of effect of the inoculation site in the specificity of the test should be confirmed in a larger sample. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunogenic membrane-associated proteins of Mycobacterium tuberculosis revealed by proteomics.

PubMed

Sinha, Sudhir; Kosalai, K; Arora, Shalini; Namane, Abdelkader; Sharma, Pawan; Gaikwad, Anil N; Brodin, Priscille; Cole, Stewart T

2005-07-01

Membrane-associated proteins of Mycobacterium tuberculosis offer a challenge, as well as an opportunity, in the quest for better therapeutic and prophylactic interventions against tuberculosis. The authors have previously reported that extraction with the detergent Triton X-114 (TX-114) is a useful step in proteomic analysis of mycobacterial cell membranes, and detergent-soluble membrane proteins of mycobacteria are potent stimulators of human T cells. In this study 1-D and 2-D gel electrophoresis-based protocols were used for the analysis of proteins in the TX-114 extract of M. tuberculosis membranes. Peptide mass mapping (using MALDI-TOF-MS, matrix assisted laser desorption/ionization time of flight mass spectrometry) of 116 samples led to the identification of 105 proteins, 9 of which were new to the M. tuberculosis proteome. Functional orthologues of 73 of these proteins were also present in Mycobacterium leprae, suggesting their relative importance. Bioinformatics predicted that as many as 73% of the proteins had a hydrophobic disposition. 1-D gel electrophoresis revealed more hydrophobic/transmembrane and basic proteins than 2-D gel electrophoresis. Identified proteins fell into the following major categories: protein synthesis, cell wall biogenesis/architecture and conserved hypotheticals/unknowns. To identify immunodominant proteins of the detergent phase (DP), 14 low-molecular-mass fractions prepared by continuous-elution gel electrophoresis were subjected to T cell activation assays using blood samples from BCG-vaccinated healthy donors from a tuberculosis endemic area. Analysis of the responses (cell proliferation and IFN-gamma production) showed that the immunodominance of certain DP fractions was most probably due to ribosomal proteins, which is consistent with both their specificity for mycobacteria and their abundance. Other membrane-associated proteins, including transmembrane proteins/lipoproteins and ESAT-6, did not appear to contribute significantly to the observed T cell responses.

Antibacterial activity of selected Cameroonian dietary spices ethno-medically used against strains of Mycobacterium tuberculosis.

PubMed

Tekwu, Emmanuel Mouafo; Askun, Tülin; Kuete, Victor; Nkengfack, Augustin Ephraim; Nyasse, Barthélémy; Etoa, François-Xavier; Beng, Véronique Penlap

2012-07-13

Tuberculosis (TB) is considered as a re-emerging disease and one of the most important public health problems worldwide. The use or (in most cases) misuse of existint anti-tuberculosis drugs over the years has led to an increasing prevalence of resistant strains, establishing an urgent need to search for new effective agents. Spices are largely used ethno-medically across Africa. The present study aimed to evaluate the in vitro antimycobacterial activities of a total of 20 methanol crude extracts prepared from 20 Cameroonian dietary spices for their ability to inhibit the growth of or kill Mycobacterium tuberculosis strains H(37)Rv (ATCC 27294) and H(37)Ra (ATCC 25177). The antituberculosis screening was performed using the Microplate Alamar Blue Assay (MABA) method to determine the minimum inhibitory concentration (MIC) and the minimum mycobactericidal concentration (MBC). Fifteen (15) plant extracts out of 20 showed varied levels of antimycobacterial activity against the strains M. tuberculosis H(37)Rv and H(37)Ra, with MICs in the range of 2.048-0.016 mg/ml. The extract of Echinops giganteus exhibited the most significant activity with a MIC value of 32 μg/ml and 16 μg/ml, respectively against H(37)Ra and H(37)Rv. To the best of our knowledge, the antimycobacterial activity of the tested spices has not been reported before and therefore our results can be evaluated as the first report about the antimycobacterial properties. The results of this study suggest that Echinops giganteus and Piper guineense could be important sources of bactericidal compounds against M. tuberculosis and could probably be promising candidates that can be further investigated. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Mortality in patients with HIV-1 and tuberculosis co-infection in Rio de Janeiro, Brazil - associated factors and causes of death.

PubMed

da Silva Escada, Rodrigo Otavio; Velasque, Luciane; Ribeiro, Sayonara Rocha; Cardoso, Sandra Wagner; Marins, Luana Monteiro Spindola; Grinsztejn, Eduarda; da Silva Lourenço, Maria Cristina; Grinsztejn, Beatriz; Veloso, Valdiléa Gonçalves

2017-05-30

Tuberculosis is the most frequent opportunistic infection and the leading cause of death among persons living with HIV in several low and middle-income countries. Mortality rates during tuberculosis treatment and death causes among HIV-1/TB co-infected patients may differ based on the immunosuppression severity, timing of diagnosis and prompt initiation of tuberculosis and antiretroviral therapy. This was a retrospective observational study conducted in the clinical cohort of patients with HIV-1/Aids of the National Institute of Infectious Diseases Evandro Chagas, Rio de Janeiro, Brazil. All HIV-1 infected patients who started combination antiretroviral therapy up to 30 days before or within 180 days after the start of tuberculosis treatment from 2000 to 2010 were eligible. Causes of death were categorized according to the "Coding Causes of Death in HIV" (CoDe) protocol. The Cox model was used to estimate the hazard ratio (HR) of selected mortality variables. A total of 310 patients were included. Sixty-four patients died during the study period. Mortality rate following tuberculosis treatment initiation was 44 per 100 person-years within the first 30 days, 28.1 per 100 person-years within 31 and 90 days, 6 per 100 person-years within 91 and 365 days and 1.6 per 100 person-years after 365 days. Death probability within one year from tuberculosis treatment initiation was approximately 13%. In the adjusted analysis the associated factors with mortality were: CD4 ≤ 50 cells/mm3 (HR: 3.10; 95% CI: 1.720 to 5.580; p = 0.00); mechanical ventilation (HR: 2.81; 95% CI: 1.170 to 6.760; p = 0.02); and disseminated tuberculosis (HR: 3.70; 95% CI: 1.290 to 10.590, p = 0.01). Invasive bacterial disease was the main immediate cause of death (46.9%). Our results evidence the high morbidity and mortality among patients co-infected with HIV-1 and tuberculosis in Rio de Janeiro, Brazil. During the first year following tuberculosis diagnosis, mortality was the highest within the first 3 months, being invasive bacterial infection the major cause of death. In order to successfully intervene in this scenario, it is utterly necessary to address the social determinants of health contributing to the inequitable health care access faced by this population.

Impact of cigarette smoking on rates and clinical prognosis of pulmonary tuberculosis in Southern Mexico.

PubMed

Bonacci, Robert A; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Reynales-Shigematsu, Luz Myriam; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Mongua-Rodríguez, Norma; Montero-Campos, Rogelio; Delgado-Sánchez, Guadalupe; Martínez-Gamboa, Rosa Areli; Cano-Arellano, Bulmaro; Sifuentes-Osornio, José; Ponce de León, Alfredo

2013-04-01

To examine the relationship between cigarette smoking and incidence and mortality rates of pulmonary tuberculosis (TB) and treatment outcomes. From 1995 to 2010, we analyzed data from 1062 patients with TB and from 2001 to 2004, 2951 contacts in Southern Mexico. Patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and mycobacteriological evaluation and received treatment by the local DOTS program. Consumers of 1-10 (LS) or 11 or more (HS) cigarettes per day incidence (1.75 and 11.79) and mortality (HS, 17.74) smoker-non-smoker rate ratios were significantly higher for smokers. Smoker population was more likely to experience unfavorable treatment outcomes (HS, adjusted OR 2.36) and retreatment (LS and HS, adjusted hazard ratio (HR) 2.14 and 2.37). Contacts that smoked had a higher probability of developing active TB (HR 2.38) during follow up. Results indicate the need of incorporating smoking prevention and cessation, especially among men, into international TB control strategies. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Factors that deregulate the protective immune response in tuberculosis.

PubMed

Hernandez-Pando, Rogelio; Orozco, Hector; Aguilar, Diana

2009-01-01

Tuberculosis (TB) is a chronic infectious disease which essentially affects the lungs and produces profound abnormalities on the immune system. Although most people infected by the tubercle bacillus (90%) do not develop the disease during their lifetime, when there are alterations in the immune system, such as co-infection with HIV, malnutrition, or diabetes, the risk of developing active disease increases considerably. Interestingly, during the course of active disease, even in the absence of immunosuppressive conditions, there is a profound and prolonged suppression of Mycobacterium tuberculosis-specific protective immune responses. Several immune factors can contribute to downregulate the protective immunity, permitting disease progression. In general, many of these factors are potent anti-inflammatory molecules that are probably overproduced with the intention to protect against tissue damage, but the consequence of this response is a decline in protective immunity facilitating bacilli growth and disease progression. Here the most significant participants in protective immunity are reviewed, in particular the factors that deregulate protective immunity in TB. Their manipulation as novel forms of immunotherapy are also briefly commented.

Early detection of the growth of Mycobacterium tuberculosis using magnetophoretic immunoassay in liquid culture.

PubMed

Kim, Jeonghyo; Lee, Kil-Soo; Kim, Eun Bee; Paik, Seungwha; Chang, Chulhun L; Park, Tae Jung; Kim, Hwa-Jung; Lee, Jaebeom

2017-10-15

Tuberculosis (TB) is an often neglected, epidemic disease that remains to be controlled by contemporary techniques of medicine and biotechnology. In this study, a nanoscale sensing system, referred to as magnetophoretic immunoassay (MPI) was designed to capture culture filtrate protein (CFP)-10 antigens effectively using two different types of nanoparticles (NPs). Two specific monoclonal antibodies against CFP-10 antigen were used, including gold NPs for signaling and magnetic particles for separation. These results were carefully compared with those obtained using the commercial mycobacteria growth indicator tube (MGIT) test via 2 sequential clinical tests (with ca. 260 clinical samples). The sensing linearity of MPI was shown in the range of pico- to micromoles and the detection limit was 0.3pM. MPI using clinical samples shows robust and reliable sensing while monitoring Mycobacterium tuberculosis (MTB) growth with monitoring time 3-10 days) comparable to that with the MGIT test. Furthermore, MPI distinguished false-positive samples from MGIT-positive samples, probably containing non-tuberculous mycobacteria. Thus, MPI shows promise in early TB diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis

PubMed Central

Bradley, Phelim; Gordon, N. Claire; Walker, Timothy M.; Dunn, Laura; Heys, Simon; Huang, Bill; Earle, Sarah; Pankhurst, Louise J.; Anson, Luke; de Cesare, Mariateresa; Piazza, Paolo; Votintseva, Antonina A.; Golubchik, Tanya; Wilson, Daniel J.; Wyllie, David H.; Diel, Roland; Niemann, Stefan; Feuerriegel, Silke; Kohl, Thomas A.; Ismail, Nazir; Omar, Shaheed V.; Smith, E. Grace; Buck, David; McVean, Gil; Walker, A. Sarah; Peto, Tim E. A.; Crook, Derrick W.; Iqbal, Zamin

2015-01-01

The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package (‘Mykrobe predictor') that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold-standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n=470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n=1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes. PMID:26686880

Regulating the risk of tuberculosis transmission among health care workers.

PubMed

Nicas, M

2000-01-01

The 1994 Centers for Disease Control and Prevention guidelines on preventing tuberculosis (TB) transmission among health care workers (HCWs), and the 1997 Occupational Safety and Health Administration (OSHA) proposed TB standard, do not address the issue of acceptable risk. Further, many infection control personnel oppose OSHA's promulgating a standard because they believe most TB infections among HCWs are nonoccupational in origin. This article examines the relationship between TB infection and disease rates, and introduces a probability framework to apportion infection risk between occupational and nonoccupational exposure. It is argued that most TB infections among HCWs are work-related. A 0.2% overall annual risk of TB infection (accounting for both workplace and community exposure) is proposed as acceptable, because in the context of an infection surveillance program it limits an HCW's cumulative disease risk close to the value for the general United States population. Based on the probability framework, an estimate of the background community infection rate, and the traditional Wells-Riley risk model, it is shown that a target workplace infection risk value can be derived and expressed in terms of an expected pulmonary dose. The latter target dose informs risk management decision-making.

Breath-based biomarkers for tuberculosis

NASA Astrophysics Data System (ADS)

Kolk, Arend H. J.; van Berkel, Joep J. B. N.; Claassens, Mareli M.; Walters, Elisabeth; Kuijper, Sjoukje; Dallinga, Jan W.; van Schooten, Fredrik-Jan

2012-06-01

We investigated the potential of breath analysis by gas chromatography - mass spectrometry (GC-MS) to discriminate between samples collected prospectively from patients with suspected tuberculosis (TB). Samples were obtained in a TB endemic setting in South Africa where 28% of the culture proven TB patients had a Ziehl-Neelsen (ZN) negative sputum smear. A training set of breath samples from 50 sputum culture proven TB patients and 50 culture negative non-TB patients was analyzed by GC-MS. A classification model with 7 compounds resulted in a training set with a sensitivity of 72%, specificity of 86% and accuracy of 79% compared with culture. The classification model was validated with an independent set of breath samples from 21 TB and 50 non-TB patients. A sensitivity of 62%, specificity of 84% and accuracy of 77% was found. We conclude that the 7 volatile organic compounds (VOCs) that discriminate breath samples from TB and non-TB patients in our study population are probably host-response related VOCs and are not derived from the VOCs secreted by M. tuberculosis. It is concluded that at present GC-MS breath analysis is able to differentiate between TB and non-TB breath samples even among patients with a negative ZN sputum smear but a positive culture for M. tuberculosis. Further research is required to improve the sensitivity and specificity before this method can be used in routine laboratories.

Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000-2012.

PubMed

Delgado-Sánchez, Guadalupe; García-García, Lourdes; Castellanos-Joya, Martín; Cruz-Hervert, Pablo; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Hernández, Andrés; Ortega-Baeza, Victor Manuel; Montero-Campos, Rogelio; Sulca, José Antonio; Martínez-Olivares, Ma de Lourdes; Mongua-Rodríguez, Norma; Baez-Saldaña, Renata; González-Roldán, Jesús Felipe; López-Gatell, Hugo; Ponce-de-León, Alfredo; Sifuentes-Osornio, José; Jiménez-Corona, María Eugenia

2015-01-01

Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM. We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution. In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p<0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p<0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11-1.61) p<0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes. Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure.

Models to understand the population-level impact of mixed strain M. tuberculosis infections.

PubMed

Sergeev, Rinat; Colijn, Caroline; Cohen, Ted

2011-07-07

Over the past decade, numerous studies have identified tuberculosis patients in whom more than one distinct strain of Mycobacterium tuberculosis is present. While it has been shown that these mixed strain infections can reduce the probability of treatment success for individuals simultaneously harboring both drug-sensitive and drug-resistant strains, it is not yet known if and how this phenomenon impacts the long-term dynamics for tuberculosis within communities. Strain-specific differences in immunogenicity and associations with drug resistance suggest that a better understanding of how strains compete within hosts will be necessary to project the effects of mixed strain infections on the future burden of drug-sensitive and drug-resistant tuberculosis. In this paper, we develop a modeling framework that allows us to investigate mechanisms of strain competition within hosts and to assess the long-term effects of such competition on the ecology of strains in a population. These models permit us to systematically evaluate the importance of unknown parameters and to suggest priority areas for future experimental research. Despite the current scarcity of data to inform the values of several model parameters, we are able to draw important qualitative conclusions from this work. We find that mixed strain infections may promote the coexistence of drug-sensitive and drug-resistant strains in two ways. First, mixed strain infections allow a strain with a lower basic reproductive number to persist in a population where it would otherwise be outcompeted if has competitive advantages within a co-infected host. Second, some individuals progressing to phenotypically drug-sensitive tuberculosis from a state of mixed drug-sensitive and drug-resistant infection may retain small subpopulations of drug-resistant bacteria that can flourish once the host is treated with antibiotics. We propose that these types of mixed infections, by increasing the ability of low fitness drug-resistant strains to persist, may provide opportunities for compensatory mutations to accumulate and for relatively fit, highly drug-resistant strains of M. tuberculosis to emerge. Published by Elsevier Ltd.

Cloning, optimization of induction conditions and purification of Mycobacterium tuberculosis Rv1733c protein expressed in Escherichia coli

PubMed Central

Ashayeri-Panah, Mitra; Eftekhar, Fereshteh; Kazemi, Bahram; Joseph, Joan

2017-01-01

Background and Objectives: Rv1733c is a latency antigen from Mycobacterium tuberculosis, a probable integral-membrane protein with promiscuous T-cell and B-cell epitopes, making it a potential vaccine candidate against tuberculosis. This study aimed to clone and optimize the expression of recombinant Rv1733c in Escherichia coli for purification. Materials and Methods: Chemically synthesized rv1733c coding sequence was cloned in pET-23a(+) followed by transforming E. coli BL21 (DE3) cells. To evaluate the induction conditions for optimized expression, factorial design of experiments was employed using four different media as well as four levels of isopropyl-b-D-thiogalactopyranosid [IPTG] concentration and duration of induction. The recombinant protein was then purified using a His-tag purification kit and detected through western blotting. Results: Recombinant Rv1733c (> 24 kDa) was expressed and accumulated in the cytoplasm of the E. coli cells. Medium composition showed the most significant effect on the yield of the recombinant protein (P = 0.000). The highest yield of recombinant Rv1733c occurred in the presence of 0.4 mM of IPTG in Terrific Broth medium (containing 1.2% tryptone, 2.4% yeast extract, 72 mM K 2 HPO 4 , 17 mM KH 2 PO 4 and 0.4% glycerol) after 10 h at 37°C. Under these conditions, the expression level was around 0.5 g/L of culture medium. Purified Rv1733c was detected by an anti-polyhistidine antibody and a tuberculosis patient’s serum. Systematic optimization of induction conditions gave us high yield of recombinant polyhistidine-tagged Rv1733c in E. coli which was successfuly purified. Conclusion: We believe that the purified Rv1733c recombinant protein from M. tuberculosis might be a good candidate for vaccine production against tuberculosis. PMID:29213997

Risk factors for the treatment outcome of retreated pulmonary tuberculosis patients in China: an optimized prediction model.

PubMed

Wang, X-M; Yin, S-H; Du, J; Du, M-L; Wang, P-Y; Wu, J; Horbinski, C M; Wu, M-J; Zheng, H-Q; Xu, X-Q; Shu, W; Zhang, Y-J

2017-07-01

Retreatment of tuberculosis (TB) often fails in China, yet the risk factors associated with the failure remain unclear. To identify risk factors for the treatment failure of retreated pulmonary tuberculosis (PTB) patients, we analyzed the data of 395 retreated PTB patients who received retreatment between July 2009 and July 2011 in China. PTB patients were categorized into 'success' and 'failure' groups by their treatment outcome. Univariable and multivariable logistic regression were used to evaluate the association between treatment outcome and socio-demographic as well as clinical factors. We also created an optimized risk score model to evaluate the predictive values of these risk factors on treatment failure. Of 395 patients, 99 (25·1%) were diagnosed as retreatment failure. Our results showed that risk factors associated with treatment failure included drug resistance, low education level, low body mass index (6 months), standard treatment regimen, retreatment type, positive culture result after 2 months of treatment, and the place where the first medicine was taken. An Optimized Framingham risk model was then used to calculate the risk scores of these factors. Place where first medicine was taken (temporary living places) received a score of 6, which was highest among all the factors. The predicted probability of treatment failure increases as risk score increases. Ten out of 359 patients had a risk score >9, which corresponded to an estimated probability of treatment failure >70%. In conclusion, we have identified multiple clinical and socio-demographic factors that are associated with treatment failure of retreated PTB patients. We also created an optimized risk score model that was effective in predicting the retreatment failure. These results provide novel insights for the prognosis and improvement of treatment for retreated PTB patients.

Computed Tomography-Based Biomarker for Longitudinal Assessment of Disease Burden in Pulmonary Tuberculosis.

PubMed

Gordaliza, P M; Muñoz-Barrutia, A; Via, L E; Sharpe, S; Desco, M; Vaquero, J J

2018-05-29

Computed tomography (CT) images enable capturing specific manifestations of tuberculosis (TB) that are undetectable using common diagnostic tests, which suffer from limited specificity. In this study, we aimed to automatically quantify the burden of Mycobacterium tuberculosis (Mtb) using biomarkers extracted from x-ray CT images. Nine macaques were aerosol-infected with Mtb and treated with various antibiotic cocktails. Chest CT scans were acquired in all animals at specific times independently of disease progression. First, a fully automatic segmentation of the healthy lungs from the acquired chest CT volumes was performed and air-like structures were extracted. Next, unsegmented pulmonary regions corresponding to damaged parenchymal tissue and TB lesions were included. CT biomarkers were extracted by classification of the probability distribution of the intensity of the segmented images into three tissue types: (1) Healthy tissue, parenchyma free from infection; (2) soft diseased tissue, and (3) hard diseased tissue. The probability distribution of tissue intensities was assumed to follow a Gaussian mixture model. The thresholds identifying each region were automatically computed using an expectation-maximization algorithm. The estimated longitudinal course of TB infection shows that subjects that have followed the same antibiotic treatment present a similar response (relative change in the diseased volume) with respect to baseline. More interestingly, the correlation between the diseased volume (soft tissue + hard tissue), which was manually delineated by an expert, and the automatically extracted volume with the proposed method was very strong (R 2  ≈ 0.8). We present a methodology that is suitable for automatic extraction of a radiological biomarker from CT images for TB disease burden. The method could be used to describe the longitudinal evolution of Mtb infection in a clinical trial devoted to the design of new drugs.

Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for tuberculous vertebral osteomyelitis.

PubMed

Choi, Sungim; Jung, Kyung Hwa; Son, Hyo-Ju; Lee, Seung Hyun; Hong, Jung Min; Kim, Min Chul; Kim, Min Jae; Chong, Yong Pil; Sung, Heungsup; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-01

Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis. All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7. A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75-98%), 65% (95% CI, 54-75%), 50% (95% CI, 42-58%), 95% (95% CI, 86-98%), 2.59 (95% CI, 1.89-3.55) and 0.14 (95% CI, 0.05-0.43), respectively. The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

Is systematic screening and treatment for latent tuberculosis infection in HIV patients useful in a low endemic setting?

PubMed

Maniewski, Ula; Payen, Marie-Christine; Delforge, Marc; De Wit, Stephane

2017-08-01

A decreasing incidence of tuberculosis (TB) among HIV patients has been documented in high-income settings and screening for tuberculosis is not systematically performed in many clinics (such as ours). Our objectives are to evaluate whether a same decline of incidence was seen in our Belgian tertiary center and to evaluate whether systematic screening and prophylaxis of tuberculosis should remain part of routine practice. Between 2005 and 2012, the annual incidence of tuberculosis among adult HIV patients was measured. The impact of demographic characteristics and CD 4 nadir on the incidence of active TB was evaluated. Among the 1167 patients who entered the cohort, 42 developed active TB with a significant decrease of annual incidence from 28/1000 patient-years in 2005 to 3/1000 patient-years in 2012. Among the 42 cases, 83% were of sub-Saharan origin. Median CD4 cell count upon HIV diagnosis was significantly lower in TB cases and 60% had a nadir CD4 below 200/μl. Thirty-six percent of incident TB occurred within 14 days after HIV diagnosis. A significant decline of TB incidence in HIV patients was observed. Incident TB occurred mainly in African patients, with low CD4 upon HIV diagnosis. A significant proportion of TB cases were discovered early in follow-up which probably reflects TB already present upon HIV diagnosis. In a low endemic setting, exclusion of active TB upon HIV diagnosis remains a priority and screening for LTBI should focus on HIV patients from high risk groups such as migrants from endemic regions, especially in patients with low CD4 nadir.

Evaluation of Xpert MTB/RIF assay in children with presumed pulmonary tuberculosis in Papua New Guinea.

PubMed

Kasa Tom, Sharon; Welch, Henry; Kilalang, Cornelia; Tefuarani, Nakapi; Vince, John; Lavu, Evelyn; Johnson, Karen; Magaye, Ruth; Duke, Trevor

2018-05-01

The Gene Xpert MTB/ RIF assay (Xpert) is used for rapid, simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin resistance. This study examined the accuracy of Xpert in children with suspected pulmonary tuberculosis (PTB). Children admitted to Port Moresby General Hospital with suspected PTB were prospectively enrolled between September 2014 and March 2015. They were classified into probable, possible and TB-unlikely groups. Sputum or gastric aspirates were tested by Xpert and smear microscopy; mycobacterial culture was undertaken on a subset. Children were diagnosed with TB on the basis of standard criteria which were used as the primary reference standard. Xpert, smear for acid-fast bacilli (AFB) and the Edwards TB score were compared with the primary reference standard. A total of 93 children ≤14 years with suspected PTB were enrolled; 67 (72%) were classified as probable, 21 (22%) possible and 5 (5.4%) TB-unlikely. Eighty were treated for TB based on the primary reference standard. Xpert was positive in 26/93 (28%) MTB cases overall, including 22/67 (33%) with probable TB and 4/21 (19%) with possible TB. Three (13%) samples identified rifampicin resistance. Xpert confirmed more cases of TB than AFB smear (26 vs 13, p = 0.019). The sensitivity of Xpert, AFB smear and an Edwards TB score of ≥7 was 31% (25/80), 16% (13/80) and 90% (72/80), respectively, and the specificity was 92% (12/13), 100% (13/13) and 31% (4/13), respectively, when compared with the primary reference standard. Xpert sensitivity is sub-optimal and cannot be relied upon for diagnosing TB, although a positive result is confirmatory. A detailed history and examination, standardised clinical criteria, radiographs and available tests remain the most appropriate way of diagnosing TB in children in resource-limited countries. Xpert helps confirm PTB better than AFB smear, and identifies rifampicin resistance. Practical guidelines should be used to identify children who will benefit from an Xpert assay.

The effect of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected clients under pre-ART care, Jimma, Ethiopia: a retrospective cohort study.

PubMed

Assebe, Lelisa Fekadu; Reda, Hailemariam Lemma; Wubeneh, Alem Desta; Lerebo, Wondwossen Terefe; Lambert, Saba Maria

2015-04-10

Tuberculosis (TB) is a major public health problem that accounts for almost half a million human immunodeficiency virus (HIV) associated deaths. Provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB in HIV infected individuals. However, in Ethiopia, the coverage and implementation of IPT is limited. The objective of this study is to compare the incidence rate of TB, TB-free survival time and identify factors associated with development TB among HIV-infected individuals on pre-ART follow up. A retrospective cohort study was conducted from January, 2008 to February 31, 2012 in Jimma hospital. Kaplan-Meier survival plots were used to calculate the crude effect in both groups on TB-free survival probabilities and compared using the log rank test. A Cox proportional hazard model was used to identify predictors of TB. A total of 588 patients on pre-ART care (294 IPT and 294 non-IPT group) were followed retrospectively for a median duration of 24.1 months. The median CD4 (+) cell count was 422 cells/μl (IQR 344-589). During the follow up period, 49 individuals were diagnosed with tuberculosis, giving an overall incidence of 3.78 cases per 100 person year (PY). The incidence rate of TB was 5.06 per 100 PY in non-IPT group and 2.22 per 100 PY in IPT user group. Predictors of higher TB risk were: being on clinical WHO stage III/IV (adjusted hazard ratio (AHR = 3.05, 95% confidence interval (CI): 1.61, 5.81); non-IPT user (AHR = 2.02, 95% CI: 1.04, 3.92); having CD4 (+) cell count less than 350 cells/μl (AHR = 3.16, 95% CI: 1.04, 3.92) and between 350-499 cells/μl, (AHR = 2.87; 95% CI: 1.37-6.03) and having episode of opportunistic infection (OI) in the past (AHR = 2.41, 95% CI: 1.33-4.34). IPT use was associated with fifty percent reduction in new cases of tuberculosis and probability of developing TB was higher in non-IPT group. Implementing the widespread use of IPT has the potential to reduce TB rates substantially among HIV-infected individuals in addition to other tuberculosis prevention and control effort in resource limited settings.

Tuberculosis-related stigma leading to an incomplete contact investigation in a low-incidence country.

PubMed

Faccini, M; Cantoni, S; Ciconali, G; Filipponi, M T; Mainardi, G; Marino, A F; Senatore, S; Codecasa, L R; Ferrarese, M; Gesu, G; Mazzola, E; Filia, A

2015-10-01

A contact investigation following a case of infectious tuberculosis (TB) reported in a call centre in Milan (Italy) led to the identification of three additional cases that had occurred in employees of the same workplace during the previous 5 years, one of whom was the probable source case. Thirty-three latent infections were also identified. At the time of diagnosis, the source case, because of fear of stigma related to TB, claimed to be unemployed and a contact investigation was not performed in the workplace. Cases were linked through genotyping of Mycobacterium tuberculosis. TB stigma has been described frequently, mainly in high-incidence settings, and is known to influence health-seeking behaviours and treatment adherence. The findings in this report highlight that TB-associated stigma may also lead to incomplete contact investigations. Little is known about the causes and impact of TB-related stigma in low-incidence countries and this warrants further exploration. Research is also needed to evaluate the effectiveness of specific interviewing techniques and training interventions for staff in reducing feelings of stigma in TB patients. Finally, the outbreak emphasizes the importance of integrating routine contact investigations with genotyping.

Interventions to increase tuberculosis case detection at primary healthcare or community-level services

PubMed Central

Mhimbira, Francis A; Cuevas, Luis E.; Dacombe, Russell; Mkopi, Abdallah; Sinclair, David

2017-01-01

Background Pulmonary tuberculosis is usually diagnosed when symptomatic individuals seek care at healthcare facilities, and healthcare workers have a minimal role in promoting the health-seeking behaviour. However, some policy specialists believe the healthcare system could be more active in tuberculosis diagnosis to increase tuberculosis case detection. Objectives To evaluate the effectiveness of different strategies to increase tuberculosis case detection through improving access (geographical, financial, educational) to tuberculosis diagnosis at primary healthcare or community-level services. Search methods We searched the following databases for relevant studies up to 19 December 2016: the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, Issue 12, 2016; MEDLINE; Embase; Science Citation Index Expanded, Social Sciences Citation Index; BIOSIS Previews; and Scopus. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials. Selection criteria Randomized and non-randomized controlled studies comparing any intervention that aims to improve access to a tuberculosis diagnosis, with no intervention or an alternative intervention. Data collection and analysis Two review authors independently assessed trials for eligibility and risk of bias, and extracted data. We compared interventions using risk ratios (RR) and 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. Main results We included nine cluster-randomized trials, one individual randomized trial, and seven non-randomized controlled studies. Nine studies were conducted in sub-Saharan Africa (Ethiopia, Nigeria, South Africa, Zambia, and Zimbabwe), six in Asia (Bangladesh, Cambodia, India, Nepal, and Pakistan), and two in South America (Brazil and Colombia); which are all high tuberculosis prevalence areas. Tuberculosis outreach screening, using house-to-house visits, sometimes combined with printed information about going to clinic, may increase tuberculosis case detection (RR 1.24, 95% CI 0.86 to 1.79; 4 trials, 6,458,591 participants in 297 clusters, low-certainty evidence); and probably increases case detection in areas with tuberculosis prevalence of 5% or more (RR 1.52, 95% CI 1.10 to 2.09; 3 trials, 155,918 participants, moderate-certainty evidence; prespecified stratified analysis). These interventions may lower the early default (prior to starting treatment) or default during treatment (RR 0.67, 95% CI 0.47 to 0.96; 3 trials, 849 participants, low-certainty evidence). However, this intervention may have may have little or no effect on treatment success (RR 1.07, 95% CI 1.00 to 1.15; 3 trials, 849 participants, low-certainty evidence), and we do not know if there is an effect on treatment failure or mortality. One study investigated long-term prevalence in the community, but with no clear effect due to imprecision and differences in care between the two groups (RR 1.14, 95% CI 0.65 to 2.00; 1 trial, 556,836 participants, very low-certainty evidence). Four studies examined health promotion activities to encourage people to attend for screening, including mass media strategies and more locally organized activities. There was some increase, but this could have been related to temporal trends, with no corresponding increase in case notifications, and no evidence of an effect on long-term tuberculosis prevalence. Two studies examined the effects of two to six nurse practitioner educational sessions in tuberculosis diagnosis, with no clear effect on tuberculosis cases detected. One trial compared mobile clinics every five days with house-to-house screening every six months, and showed an increase in tuberculosis cases. There was also insufficient evidence to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence; this was evaluated in one study, which indicated little or no effect after four years of either contact tracing, extensive health promotion activities, or both (RR 1.31, 95% CI 0.75 to 2.30; 1 study, 405,788 participants in 12 clusters, very low-certainty evidence). Authors' conclusions The available evidence demonstrates that when used in appropriate settings, active case-finding approaches may result in increase in tuberculosis case detection in the short term. The effect of active case finding on treatment outcome needs to be further evaluated in sufficiently powered studies. Interventions to increase the number of tuberculosis cases being diagnosed This review summarized trials evaluating the effects of interventions aiming to increase the diagnosis of tuberculosis and reduce the number of undiagnosed tuberculosis cases in communities. After searching for relevant trials up to 19 December 2016, we included 17 studies conducted in sub-Saharan Africa (nine studies), Asia (six studies), and South America (two studies). Why does tuberculosis go undiagnosed and how might programmes improve this? Tuberculosis is a chronic infectious disease that affects over 10 million people worldwide, with an estimated four million tuberculosis patients remaining undiagnosed each year. Interventions such as outreach tuberculosis screening with or without health promotion that actively screen for tuberculosis among individuals presenting with symptoms of tuberculosis, may increase detection of microbiologically confirmed tuberculosis cases. These interventions may improve treatment outcomes by increasing the number of tuberculosis patients who are cured and complete treatment. However, we do not know if these interventions reduce either tuberculosis treatment failure, or tuberculosis-associated death or long-term tuberculosis burden in moderate- and high-tuberculosis settings. What the research says House-to-house screening for active tuberculosis, and organizing tuberculosis diagnostic clinics nearer to where people live and work, may increase tuberculosis case detection in settings where the prevalence of undiagnosed disease is high (low-certainty evidence). These people may have higher levels of treatment success and lower levels of default from treatment (low-certainty evidence). There was insufficient evidence to determine if health promotion activities alone increase tuberculosis case detection (very low-certainty evidence). There was also insufficient evidence to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence, as the only study to evaluate this found no effect after four years (very low-certainty evidence). PMID:29182800

Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000–2012

PubMed Central

Delgado-Sánchez, Guadalupe; García-García, Lourdes; Castellanos-Joya, Martín; Cruz-Hervert, Pablo; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Hernández, Andrés; Ortega-Baeza, Victor Manuel; Montero-Campos, Rogelio; Sulca, José Antonio; Martínez-Olivares, Ma. de Lourdes; Mongua-Rodríguez, Norma; Baez-Saldaña, Renata; González-Roldán, Jesús Felipe; López-Gatell, Hugo; Ponce-de-León, Alfredo; Sifuentes-Osornio, José; Jiménez-Corona, María Eugenia

2015-01-01

Background Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. Objective To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM. Materials and Methods We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution. Results In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p <0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p <0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11–1.61) p <0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes. Conclusion Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure. PMID:26075393

[The clinical application of quantiferon TB-2G: its usefulness and limitations].

PubMed

Sato, Shigeki; Nagai, Hideaki

2011-02-01

QuantiFERON TB-2G (QFT) is widely used in clinical settings for the identification of tuberculosis infection because of its high level of utility. It is well known that QFT stimulates peripheral blood lymphocytes in vitro by means of M. tuberculosis-specific protein, and that infection is identified by measuring the interferon-gamma released. Interpretation of QFT results is therefore difficult in immunosuppressed subjects in whom the function of immunocompetent cells, including lymphocytes, is suppressed, making it difficult for them to produce interferon-gamma. There is a high incidence of tuberculosis among hemodialysis patients. It has been conjectured that the use of powerful immunosuppressive agents following kidney transplantation results in a high risk of tuberculosis. How QFT results change immediately following kidney transplantation is an extremely interesting question. In recent years, an increasing number of institutions have been using TNF-alpha inhibitors to treat rheumatoid arthritis patients. Is QTF useful for identifying whether patients have latent tuberculosis infection before the administration of anti-TNF antibodies? In particular, many rheumatoid arthritis patients may have been given methotrexate or glucocorticoids, which suppress the immune system, prior to the administration of TNF-alpha inhibitors, possibly making it difficult to interpret the QFT results. We must be aware of this limitation when performing QFT on immunosuppressed patients. It is also important that we understand the clinical parameters influencing QFT results (such as lymphocyte counts). The morbidity rate of tuberculosis is high among healthcare workers, particularly nurses. A number of studies have reported that QFT is useful in hospital infection control for tuberculosis, but the effectiveness of QFT for monitoring the health of healthcare workers is still not fully understood. In this symposium, we will debate how far QFT can be used and the extent of its usefulness under exceptional circumstances. (1) How do we manage kidney transplant recipients with latent tuberculosis infection?: Norihiko GOTO (Transplant Surgery, Nagoya Daini Red Cross Hospital) It is unclear whether QuantiFERON-second generation (QFT-2G) is useful for diagnostic screening and follow up of latent tuberculosis infection (LTBI) in immunosuppressed kidney transplant (KTx) recipients. The QFT-2G assay that included response to mitogen stimulation was performed before and 6 months after KTx. Non responder was 0 (0%) at baseline, 3 (3%) at 6 months. Response to mitogen stimulation was 9.7 +/- 5.3 IU/mL at baseline vs. 10.4 +/- 5.0 IU/mL at 6 months after KTx (p = 0.29). QFT-2G is a useful screening test for LTBI and active tuberculosis (TB) even during maintenance of immunosuppression of KTx. (2) QuantiFERON-TB Gold in Japanese rheumatoid arthritis patients for assessing latent tuberculosis infection prior treatment of anti-tumor necrosis factor antibody: Shogo BANNO (Division of Rheumatology and Nephrology, Department of Internal Medicine, Aichi Medical School of Medicine) To determine the positive rate of LTBI in RA patients using the QFT-2G test, we divided RA patients into two groups: with or without old TB findings by chest CT. With a cutoff level set at 0.35 IU/ml, the positive rate of QFT-2G in LTBI was detected only 5.8%, when setting cutoff at 0.1 IU/ml (lower cutoff level), 23.1% was detected in LTBI patients. The positive TST results were significantly increased in non-LTBI patients compared than in LTBI patients. The QFT-2G test was not affected by the treatment of MTX, and the incidence of indeterminate result was low. The QFT-2G was useful compared to TST before administration of TNF inhibitors in RA patients, because of superior specificity of QFT-2G. (3) Clinical parameters that influence the sensitivity of T-cell assays: Haruyuki ARIGA (National Hospital Organization Tokyo National Hospital) The detection of tuberculosis (TB) infection in compromised hosts is essential for TB control, but T cell assay might be influenced by the degree of cell-mediated immunosuppression. The relationship between immunocompetence and specific interferon (IFN)-gamma response in whole blood QuantiFERON-TB Gold (QFT) is uncertain. Immune-related clinical indicators associated with the degree of antigen-specific IFN-gamma production were analysed using a large immunologically-unselected population with obvious TB infection. The absolute number of blood lymphocyte in TB patients was significantly associated with specific IFN-gamma production in a linear regression model. Sensitivity of 2 IFN-gamma Release Assays, QFT and ELISPOT, partly depends on peripheral lymphocyte counts. At low lymphocyte count conditions, ELISPOT assay is superior to whole blood QFT for detecting tuberculosis infection. (4) QuantiFERON TB-2G among staffs in the hospitals of Nationao Hospital Organization: Susumu OGURI, Chihiro NISHIO, Kensuke SUMI, Masayoshi MINAGUCHI, Tomomasa TSUBOI, Atuo SATOU, Osamu TOKUNAGA, Takeshi MIYAMOMAE, Takuya KURASAWA (National Hospital Organization Minami-Kyoto National Hospital) To investigate the infection rate of tuberculosis among staffs working in the hospitals of NHO. Questionnaires were sent to the hospitals and the responses were analyzed. Among the staffs working in the hospitals with tuberculosis wards, positive rate of QuantiFERON TB-2G was 6.9%, probable positive rate was 5.6%. On the other hand, among the staffs working in the hospitals without tuberculosis wards, positive rate was 4.4%, probable positive rate was 3.9%. It is necessary to monitor the infection rate among hospital staffs.

Diagnostic potential of multi-targeted LAMP (loop-mediated isothermal amplification) for osteoarticular tuberculosis.

PubMed

Sharma, Kusum; Sharma, Megha; Batra, Nitya; Sharma, Aman; Dhillon, Mandeep Singh

2017-02-01

Delay in diagnosing osteoarticular tuberculosis (OATB) contributes significantly to morbidity by causing disfiguration and neurological sequelae. The delay caused by conventional culture and the expertise and expense involved in other nucleic acid based tests, make LAMP (loop-mediated isothermal amplification) assay a favorable middle path. We evaluated LAMP assay using IS6110 and MPB64 for rapid diagnosis of OATB by comparing with IS6110 PCR and culture. LAMP assay was performed on 140 synovial fluid and pus samples (10 culture-positive proven cases, 80 culture-negative probable cases, and 50 negative controls) using three set of primer pairs each for IS6110 and MPB64. LAMP assay, using two-target approach, had an overall sensitivity and specificity of 90% and 100% in detecting OATB. Sensitivity of IS6110 PCR, IS6110 LAMP, and MPB64 LAMP was 80%, 100%, and 100%, respectively, for confirmed cases and 72.5%, 81.75%, and 86.25%, respectively, for probable cases. Six additional cases were picked using two-target approach. LAMP assay utilizing IS6110 and MPB64 is a cost-effective technique for an early and reliable diagnosis of OATB. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:361-365, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Factors associated with default from treatment among tuberculosis patients in nairobi province, Kenya: A case control study

PubMed Central

2011-01-01

Background Successful treatment of tuberculosis (TB) involves taking anti-tuberculosis drugs for at least six months. Poor adherence to treatment means patients remain infectious for longer, are more likely to relapse or succumb to tuberculosis and could result in treatment failure as well as foster emergence of drug resistant tuberculosis. Kenya is among countries with high tuberculosis burden globally. The purpose of this study was to determine the duration tuberculosis patients stay in treatment before defaulting and factors associated with default in Nairobi. Methods A Case-Control study; Cases were those who defaulted from treatment and Controls those who completed treatment course between January 2006 and March 2008. All (945) defaulters and 1033 randomly selected controls from among 5659 patients who completed treatment course in 30 high volume sites were enrolled. Secondary data was collected using a facility questionnaire. From among the enrolled, 120 cases and 154 controls were randomly selected and interviewed to obtain primary data not routinely collected. Data was analyzed using SPSS and Epi Info statistical software. Univariate and multivariate logistic regression analysis to determine association and Kaplan-Meier method to determine probability of staying in treatment over time were applied. Results Of 945 defaulters, 22.7% (215) and 20.4% (193) abandoned treatment within first and second months (intensive phase) of treatment respectively. Among 120 defaulters interviewed, 16.7% (20) attributed their default to ignorance, 12.5% (15) to traveling away from treatment site, 11.7% (14) to feeling better and 10.8% (13) to side-effects. On multivariate analysis, inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3), herbal medication use (OR 5.7; 95% CI 1.37-23.7), low income (OR 5.57, CI 1.07-30.0), alcohol abuse (OR 4.97; 95% CI 1.56-15.9), previous default (OR 2.33; 95% CI 1.16-4.68), co-infection with Human immune-deficient Virus (HIV) (OR 1.56; 95% CI 1.25-1.94) and male gender (OR 1.43; 95% CI 1.15-1.78) were independently associated with default. Conclusion The rate of defaulting was highest during initial two months, the intensive phase of treatment. Multiple factors were attributed by defaulting patients as cause for abandoning treatment whereas several were independently associated with default. Enhanced patient pre-treatment counseling and education about TB is recommended. PMID:21906291

Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries.

PubMed

del Amo, Julia; Moreno, Santiago; Bucher, Heiner C; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Lodi, Sara; van Sighem, Ard; de Wolf, Wolf; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; Miró, José M; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Toulomi, Giota; Gargalianos, Panagiotis; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A

2012-05-01

The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries. The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting. Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL. Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

Estimation of the Rate of Unrecognized Cross-Contamination with Mycobacterium tuberculosis in London Microbiology Laboratories

PubMed Central

Ruddy, M.; McHugh, T. D.; Dale, J. W.; Banerjee, D.; Maguire, H.; Wilson, P.; Drobniewski, F.; Butcher, P.; Gillespie, S. H.

2002-01-01

Isolates from patients with confirmed tuberculosis from London were collected over 2.5 years between 1995 and 1997. Restriction fragment length polymorphism (RFLP) analysis was performed by the international standard technique as part of a multicenter epidemiological study. A total of 2,779 samples representing 2,500 individual patients from 56 laboratories were examined. Analysis of these samples revealed a laboratory cross-contamination rate of between 0.54%, when only presumed cases of cross-contamination were considered, and 0.93%, when presumed and possible cases were counted. Previous studies suggest an extremely wide range of laboratory cross-contamination rates of between 0.1 and 65%. These data indicate that laboratory cross-contamination has not been a common problem in routine practice in the London area, but in several incidents patients did receive full courses of therapy that were probably unnecessary. PMID:12409381

Lack of consensus in the diagnosis and treatment for ocular tuberculosis among uveitis specialists.

PubMed

Lou, Susan M; Larkin, Kelly L; Winthrop, Kevin; Rosenbaum, James T

2015-02-01

To assess the approach of specialists to ocular tuberculosis (TB). The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1-75%) or that a patient with a risk factor for TB had ocular TB (range 0-90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

Prime-boost bacillus Calmette-Guérin vaccination with lentivirus-vectored and DNA-based vaccines expressing antigens Ag85B and Rv3425 improves protective efficacy against Mycobacterium tuberculosis in mice.

PubMed

Xu, Ying; Yang, Enzhuo; Wang, Jianguang; Li, Rui; Li, Guanghua; Liu, Guoyuan; Song, Na; Huang, Qi; Kong, Cong; Wang, Honghai

2014-10-01

To prevent the global spread of tuberculosis (TB), more effective vaccines and vaccination strategies are urgently needed. As a result of the success of bacillus Calmette-Guérin (BCG) in protecting children against miliary and meningeal TB, the majority of individuals will have been vaccinated with BCG; hence, boosting BCG-primed immunity will probably be a key component of future vaccine strategies. In this study, we compared the ability of DNA-, protein- and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 to boost the effects of BCG in the context of immunity and protection against Mycobacterium tuberculosis in C57BL/6 mice. Our results demonstrated that prime-boost BCG vaccination with a lentiviral vector expressing the antigens Ag85B and Rv3425 significantly enhanced immune responses, including T helper type 1 and CD8(+) cytotoxic T lymphocyte responses, compared with DNA- and protein-based vaccines. However, lentivirus-vectored and DNA-based vaccines greatly improved the protective efficacy of BCG against M. tuberculosis, as indicated by a lack of weight loss and significantly reduced bacterial loads and histological damage in the lung. Our study suggests that the use of lentiviral or DNA vaccines containing the antigens Ag85B and Rv3425 to boost BCG is a good choice for the rational design of an efficient vaccination strategy against TB. © 2014 John Wiley & Sons Ltd.

Increasing drug resistance of Mycobacterium tuberculosis in Sinaloa, Mexico, 1997-2005.

PubMed

Zazueta-Beltran, Jorge; León-Sicairos, Nidia; Muro-Amador, Secundino; Flores-Gaxiola, Adrian; Velazquez-Roman, Jorge; Flores-Villaseñor, Hector; Canizalez-Roman, Adrian

2011-04-01

In 1997 the US Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) reported high proportions of drug-resistant Mycobacterium tuberculosis in three Mexican states: Sinaloa, Baja California, and Oaxaca. In 2006, we showed that resistance to anti-tuberculosis drugs remained frequent in Sinaloa. The objectives of this study were to describe drug-resistant tuberculosis (TB) trends and to investigate the probability that patients acquire resistance to first-line anti-TB drugs on recurrence after treatment in Sinaloa. Sputum specimens were collected from patients diagnosed with TB at all the health care institutions of Sinaloa during 1997-2005. Isolates were tested for susceptibility to first-line drugs. Among 671 isolates tested from 1997 to 2002, the overall resistance rate was 34.9% (95% confidence interval (CI) 31.2-38.4) with a 1.2% increase per year (Chi-square=4.258, p=0.03906). The prevalence of multi-drug resistance (MDR) was 17.9% (95% CI 14.9-20.7) with a 1.2% increase per year (Chi-square=8.352, p=0.00385). Of 50 patients registered twice between 1997 and 2005, 15 were fully susceptible at first registration, of whom six (40%) acquired drug resistance. Of 35 cases with any drug resistance at first registration, 21 (60%) came to acquire resistance to at least one other drug. The proportion of drug-resistant TB increased during 1997-2005 in Sinaloa. Major efforts are needed to prevent the further rise and spread of drug-resistant and MDR TB. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011

PubMed Central

Tran, Huong Thi Giang; Bui, Quyen Thi Tu

2016-01-01

Introduction Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Methods Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. Results A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. Conclusion This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance. PMID:27508089

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011.

PubMed

Nguyen, Hoa Binh; Nguyen, Nhung Viet; Tran, Huong Thi Giang; Nguyen, Hai Viet; Bui, Quyen Thi Tu

2016-01-01

Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

National position statement for the management of latent tuberculosis infection.

PubMed

Stock, David

2017-09-01

The primary role of any tuberculosis (TB) control program is to ensure the prompt identification and effective treatment of active disease. The host immune system often succeeds in containing the initial (or primary) infection with Mycobacterium tuberculosis (Mtb), but may fail to eliminate the pathogen. The persistence of viable organisms explains the potential for the development of active disease years or even decades after infection. This is known as latent tuberculosis infection (LTBI) although, rather than a distinct entity, this probably represents part of a dynamic spectrum. Individuals with LTBI are asymptomatic and it is therefore clinically undetectable. The World Health Organization (WHO) estimates that one-third of the global population has been infected with Mtb, with highest prevalence of LTBI in countries/regions with the highest prevalence of active disease. In 2013, 88% of 1322 notifications in Australia were in the overseas-born population (incidence 19.5 per 100,000 v. 1.0 per 100,000), with this proportion rising over the course of the last decade. Combined with epidemiological evidence of low local transmission, this strongly implies that the vast majority resulted from reactivation of latent infection acquired prior to immigration. Contrasting trends in TB incidence in other developed countries probably reflect differences in policy regarding LTBI. The diagnosis and treatment of LTBI represents an important opportunity for intervention by jurisdictional TB control programs. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the Online, Services and External Relations Branch, Department of Health, GPO Box 9848, Canberra ACT 2601, or by email to copyright@health.gov.au.

Identifying multidrug resistant tuberculosis transmission hotspots using routinely collected data12

PubMed Central

Manjourides, Justin; Lin, Hsien-Ho; Shin, Sonya; Jeffery, Caroline; Contreras, Carmen; Cruz, Janeth Santa; Jave, Oswaldo; Yagui, Martin; Asencios, Luis; Pagano, Marcello; Cohen, Ted

2012-01-01

SUMMARY In most countries with large drug resistant tuberculosis epidemics, only those cases that are at highest risk of having MDRTB receive a drug sensitivity test (DST) at the time of diagnosis. Because of this prioritized testing, identification of MDRTB transmission hotspots in communities where TB cases do not receive DST is challenging, as any observed aggregation of MDRTB may reflect systematic differences in how testing is distributed in communities. We introduce a new disease mapping method, which estimates this missing information through probability–weighted locations, to identify geographic areas of increased risk of MDRTB transmission. We apply this method to routinely collected data from two districts in Lima, Peru over three consecutive years. This method identifies an area in the eastern part of Lima where previously untreated cases have increased risk of MDRTB. This may indicate an area of increased transmission of drug resistant disease, a finding that may otherwise have been missed by routine analysis of programmatic data. The risk of MDR among retreatment cases is also highest in these probable transmission hotspots, though a high level of MDR among retreatment cases is present throughout the study area. Identifying potential multidrug resistant tuberculosis (MDRTB) transmission hotspots may allow for targeted investigation and deployment of resources. PMID:22401962

Contact investigation after a fatal case of extensively drug-resistant tuberculosis (XDR-TB) in an aircraft, Germany, July 2013

PubMed Central

an der Heiden, Maria; Hauer, Barbara; Fiebig, Lena; Glaser-Paschke, Gisela; Stemmler, Markus; Simon, Claudia; Rüsch-Gerdes, Sabine; Gilsdorf, Andreas; Haas, Walter

2017-01-01

In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired. PMID:28367796

Short-course chemotherapy for pulmonary tuberculosis with a rifampicin-isoniazid-pyrazinamide combination tablet.

PubMed

Cowie, R L; Brink, B A

1990-04-21

The effectiveness of a tablet containing a combination of rifampicin, isoniazid and pyrazinamide (Rifater; Mer-National) in the treatment of pulmonary tuberculosis was examined by comparing it with a previously evaluated four-drug regimen. Of 150 black goldminers with a first case of pulmonary tuberculosis, 69 were randomly allocated to receive the combination tablet (RHZ), 5 tablets per day on weekdays for 100 treatment-days, and 81 the four-drug regimen (streptomycin, rifampicin, isoniazid and pyrazinamide) (RHZS). Non-compliance was detected in 42% of the RHZ group and in 16% of the RHZS group. Two patients in the RHZ group and 4 in the RHZS group had to have their treatment altered because routine investigations revealed drug-resistant mycobacteria. Treatment was unsuccessful in 10 patients in the RHZ group, with 4 men failing to complete the regimen and being lost to follow-up, 3 cases of failure of conversion of sputum on the regimen, and 3 relapses. The results for the RHZS group were similar, with 4 failures to complete the regimen, 2 treatment failures and 4 relapses. Evaluation of RHZ showed it to be comparable with a previously evaluated, successful short-course regimen (RHZS). The high incidence of non-compliance probably reflects reduced supervision of this wholly oral regimen.

Evolutionary landscape of the Mycobacterium tuberculosis complex from the viewpoint of PhoPR: implications for virulence regulation and application to vaccine development.

PubMed

Broset, Esther; Martín, Carlos; Gonzalo-Asensio, Jesús

2015-10-20

Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC). Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology. Copyright © 2015 Broset et al.

Evolutionary Landscape of the Mycobacterium tuberculosis Complex from the Viewpoint of PhoPR: Implications for Virulence Regulation and Application to Vaccine Development

PubMed Central

Broset, Esther

2015-01-01

ABSTRACT Different members of the Mycobacterium genus have evolved to cause tuberculosis in diverse human populations and in a variety of animal species. Our cumulative knowledge of mycobacterial genomes indicates that mutations in the PhoPR two-component virulence system were acquired not only during the natural evolution of mycobacterial species but also during in vitro subculture, which has given rise to the attenuated reference strain H37Ra or to different daughter strains of Mycobacterium bovis BCG. PhoPR is a well-known regulator of pathogenic phenotypes, including secretion of the virulence factor ESAT-6, biosynthesis of acyltrehalose-based lipids, and modulation of antigen export, in members of the Mycobacterium tuberculosis complex (MTBC). Evolutionarily conserved polymorphisms in PhoPR from Mycobacterium africanum, M. bovis, or M. tuberculosis H37Ra result in loss of functional phenotypes. Interestingly, some members of the MTBC have acquired compensatory mutations to counteract these polymorphisms and, probably, to maintain their pathogenic potential. Some of these compensatory mutations include the insertion of the IS6110 element upstream from phoPR in a particular M. bovis strain that is able to transmit between humans or polymorphisms in M. africanum and M. bovis that affect the regulatory region of the espACD operon, allowing PhoPR-independent ESAT-6 secretion. This review highlights the increasing knowledge of the significance of PhoPR in the evolution of the MTBC and its potential application in the construction of new attenuated vaccines based on phoPR inactivation. In this context, the live attenuated vaccine MTBVAC, based on a phoP fadD26 deletion mutant of M. tuberculosis, is the first vaccine of this kind to successfully enter into clinical development, representing a historic milestone in the field of human vaccinology. PMID:26489860

Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis.

PubMed

Proaño, Alvaro; Bravard, Marjory A; López, José W; Lee, Gwenyth O; Bui, David; Datta, Sumona; Comina, Germán; Zimic, Mirko; Coronel, Jorge; Caviedes, Luz; Cabrera, José L; Salas, Antonio; Ticona, Eduardo; Vu, Nancy M; Kirwan, Daniela E; Loader, Maria-Cristina I; Friedland, Jon S; Moore, David A J; Evans, Carlton A; Tracey, Brian H; Gilman, Robert H

2017-05-01

Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. We prospectively evaluated human immunodeficiency virus-negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2-4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0-1.4) and at the end of the study decreased to 0.18 (IQR, 0.0-0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%-41%). Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Dynamics of Cough Frequency in Adults Undergoing Treatment for Pulmonary Tuberculosis

PubMed Central

Bravard, Marjory A.; López, José W.; Lee, Gwenyth O.; Bui, David; Datta, Sumona; Comina, Germán; Zimic, Mirko; Coronel, Jorge; Caviedes, Luz; Cabrera, José L.; Salas, Antonio; Ticona, Eduardo; Vu, Nancy M.; Kirwan, Daniela E.; Loader, Maria-Cristina I.; Friedland, Jon S.; Moore, David A. J.; Evans, Carlton A.; Tracey, Brian H.; Gilman, Robert H.

2017-01-01

Abstract Background. Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load. Methods. We prospectively evaluated human immunodeficiency virus–negative adults (n = 64) with a new diagnosis of culture-proven, drug-susceptible pulmonary tuberculosis immediately prior to treatment and repeatedly until treatment day 62. At each time point, participant cough was recorded (n = 670) and analyzed using the Cayetano Cough Monitor. Consecutive coughs at least 2 seconds apart were counted as separate cough episodes. Sputum samples (n = 426) were tested with microscopic-observation drug susceptibility broth culture, and in culture-positive samples (n = 252), the time to culture positivity was used to estimate bacillary load. Results. The highest cough frequency occurred from 1 pm to 2 pm, and the lowest from 1 am to 2 am (2.4 vs 1.1 cough episodes/hour, respectively). Cough frequency was higher among participants who had higher sputum bacillary load (P < .01). Pretreatment median cough episodes/hour was 2.3 (interquartile range [IQR], 1.2–4.1), which at 14 treatment days decreased to 0.48 (IQR, 0.0–1.4) and at the end of the study decreased to 0.18 (IQR, 0.0–0.59) (both reductions P < .001). By 14 treatment days, the probability of culture conversion was 29% (95% confidence interval, 19%–41%). Conclusions. Coughs were most frequent during daytime. Two weeks of appropriate treatment significantly reduced cough frequency and resulted in one-third of participants achieving culture conversion. Thus, treatment by 2 weeks considerably diminishes, but does not eliminate, the potential for airborne tuberculosis transmission. PMID:28329268

A predictive scoring instrument for tuberculosis lost to follow-up outcome

PubMed Central

2012-01-01

Background Adherence to tuberculosis (TB) treatment is troublesome, due to long therapy duration, quick therapeutic response which allows the patient to disregard about the rest of their treatment and the lack of motivation on behalf of the patient for improved. The objective of this study was to develop and validate a scoring system to predict the probability of lost to follow-up outcome in TB patients as a way to identify patients suitable for directly observed treatments (DOT) and other interventions to improve adherence. Methods Two prospective cohorts, were used to develop and validate a logistic regression model. A scoring system was constructed, based on the coefficients of factors associated with a lost to follow-up outcome. The probability of lost to follow-up outcome associated with each score was calculated. Predictions in both cohorts were tested using receiver operating characteristic curves (ROC). Results The best model to predict lost to follow-up outcome included the following characteristics: immigration (1 point value), living alone (1 point) or in an institution (2 points), previous anti-TB treatment (2 points), poor patient understanding (2 points), intravenous drugs use (IDU) (4 points) or unknown IDU status (1 point). Scores of 0, 1, 2, 3, 4 and 5 points were associated with a lost to follow-up probability of 2,2% 5,4% 9,9%, 16,4%, 15%, and 28%, respectively. The ROC curve for the validation group demonstrated a good fit (AUC: 0,67 [95% CI; 0,65-0,70]). Conclusion This model has a good capacity to predict a lost to follow-up outcome. Its use could help TB Programs to determine which patients are good candidates for DOT and other strategies to improve TB treatment adherence. PMID:22938040

Reversion and conversion of Mycobacterium tuberculosis IFN-gamma ELISpot results during anti-tuberculous treatment in HIV-infected children.

PubMed

Connell, Tom G; Davies, Mary-Ann; Johannisen, Christine; Wood, Kathryn; Pienaar, Sandy; Wilkinson, Katalin A; Wilkinson, Robert J; Zar, Heather J; Beatty, David; Nicol, Mark P; Curtis, Nigel; Eley, Brian

2010-05-27

Recent interest has focused on the potential use of serial interferon gamma (IFN-gamma) release assay (IGRA) measurements to assess the response to anti-tuberculous (TB) treatment. The kinetics of IFN-gamma responses to Mycobacterium tuberculosis (MTB) antigens in HIV-infected children during treatment have not however been previously investigated. IFN-gamma responses to the MTB antigens, ESAT-6, CFP-10 and PPD were measured by an enzyme-linked immunospot assay (IFN-gamma ELISpot) at presentation and at one, two and six months after starting anti-tuberculous treatment in HIV-infected children with definite or probable TB. Responses at different time points were compared using a Mann-Whitney U test with paired data analysed using the Wilcoxon signed rank test. A Fisher's exact or Chi-squared test was used to compare proportions when test results were analysed as dichotomous outcomes. Of 102 children with suspected TB, 22 (21%) had definite TB and 24 (23%) probable TB. At least one follow up IFN-gamma ELISpot assay result was available for 31 (67%) of the 46 children. In children with definite or probable TB in whom the IFN-gamma ELISpot assay result was positive at presentation, anti-tuberculous treatment was accompanied by a significant decrease in both the magnitude of the IFN-gamma response to individual or combined MTB-specific antigens (ESAT-6 median 110 SFCs/106 PBMC (IQR 65-305) at presentation vs. 15 (10-115) at six months, p = 0.04; CFP-10 177 (48-508) vs. 20 (5-165), p = 0.004, ESAT-6 or CFP-10 median 250 SFCs/106 PBMC (IQR 94-508) vs. 25 (10-165), p = 0.004) and in the proportion of children with a positive IFN-gamma ELISpot assay (Fisher's exact test: ESAT-6 15/0 vs 5/11, p = 0.0002, CFP-10 22/0 vs 8/17, p = 0.0001, ESAT-6 or CFP-10 22/0 vs. 9/17, p= 0.002). However almost half of the children had a positive IFN-gamma ELISpot assay after six months of anti-tuberculous treatment. In addition, there was conversion of the IFN-gamma ELISpot assay result during anti-tuberculous therapy in six of 12 children in whom the initial IFN-gamma ELISpot assay was negative. In HIV-infected children with definite or probable TB, anti-tuberculosis treatment is accompanied by a reduction in the magnitude of the IFN-gamma ELISpot response to MTB-antigens. However, serial IFN-gamma ELISpot measurements appear to have limited clinical utility in assessing a successful response to anti-tuberculous treatment in HIV infected children.

Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection.

PubMed

Gómez-Reino, Juan J; Carmona, Loreto; Angel Descalzo, Miguel

2007-06-15

To evaluate the causes of new cases of active tuberculosis (ATB) in patients treated with tumor necrosis factor (TNF) antagonists included in the national registry BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) after the dissemination of recommendations to prevent reactivation of latent tuberculosis infection (LTBI). Incidence rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were calculated in patients entering BIOBADASER after March 2002 and were stratified by compliance with recommendations (complete or incomplete). ATB rates in BIOBADASER were compared with the background rate and the rate in the rheumatoid arthritis cohort EMECAR (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB among patients treated with adalimumab, etanercept, and infliximab were estimated and compared only for treatments started after September 2003, when all 3 drugs became fully available. Following March 2002, a total of 5,198 patients treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases were noted (rate 172 per 100,000 patient-years, 95% CI 103-285). Recommendations were fully followed in 2,655 treatments. The probability of developing ATB was 7 times higher when recommendations were not followed (incidence rate ratio 7.09, 95% CI 1.60-64.69). Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations. New cases of ATB still occur in patients treated with all available TNF antagonists due to lack of compliance with recommendations to prevent reactivation of LTBI. Continuous evaluation of recommendations is required to improve clinical practice.

Pyrimidin-2(1H)-ones based inhibitors of Mycobacterium tuberculosis orotate phosphoribosyltransferase.

PubMed

Breda, Ardala; Machado, Pablo; Rosado, Leonardo Astolfi; Souto, André Arigony; Santos, Diógenes Santiago; Basso, Luiz Augusto

2012-08-01

Tuberculosis (TB) is an ancient human chronic infectious disease caused mainly by Mycobacterium tuberculosis. The emergence of strains resistant to first and second line anti-TB drugs, associated with the increasing number of TB cases among HIV positive subjects, and the large number of individuals infected with latent bacilli have urged the development of new strategies to treat TB. Enzymes of nucleotide metabolism pathways provide promising molecular targets for the development of drugs, aiming at both active and latent TB. The orotate phosphoribosyltransferase (OPRT) enzyme catalyzes the synthesis of orotidine 5'-monophosphate from 5'-phospho-α-d-ribose 1'-diphosphate and orotic acid, in the de novo pyrimidine synthesis pathway. Based on the kinetic mechanism and molecular properties, here we describe the design, selection and synthesis of substrate analogs with inhibitory activity of M. tuberculosis OPRT (MtOPRT) enzyme. Steady-state kinetic measurements were employed to determine the mode of inhibition of commercially available and chemically derived compounds. The 6-Hydroxy-2-oxo-1,2-dihydropyridine-4-carboxylic acid (6) chemical compound and its derivative, 3-Benzylidene-2,6-dioxo-1,2,3,6-tetrahydropyridine-4-carboxylic acid (13), showed enzyme inhibition constants in the submicromolar range. Isothermal titration calorimetry data indicated that binding of both compounds to MtOPRT have negative enthalpy and favorable Gibbs free energy probably due to their high complementarity to the enzyme's binding pocket. Improvement of compound 13 hydrophobic character by addition of an aromatic ring substituent resulted in entropic optimization, reflected on a thermodynamic discrimination profile characteristic of high affinity ligands. These inhibitors represent lead compounds for further development of MtOPRT inhibitors with increased potency, which may be tested as anti-TB agents. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Indirect supportive evidence for diagnosis of tuberculosis-related uveitis: from the tuberculin skin test to the new interferon gamma release assays.

PubMed

Llorenç, Víctor; González-Martin, Julian; Keller, Johannes; Rey, Amanda; Pelegrín, Laura; Mesquida, Marina; Adán, Alfredo

2013-03-01

To evaluate clinical and paraclinical parameters for the indirect diagnosis of tuberculosis-related uveitis (TRU). Prospective 2-year study in a tertiary referral centre. Patients with clinically suspected TRU were recruited. Demographical and clinical data were recorded. QuantiFERON(®) -TB Gold (QFT), tuberculosis skin test (TST) and pulmonary X-ray were performed, and other possible uveitis aetiologies were ruled out. Further investigations were also performed case by case after consultation. After final assessment, standard antituberculosis therapy was started if TRU was considered highly probable. Finally, diagnosis of TRU was established according to current criteria and set as gold standard. Strength of association for TRU was determined by odds ratio and compared by appropriate tests. Concordance and binary classification tests were also assessed.   The study included 103 patients, 54 men and 49 women. Mean age 45.6 years. Sixty-eight patients were Spanish-born and 35 were foreign-born. Final diagnosis included 33 (32%) cases of TRU and 70 (67%) cases with other diagnoses. Asian origin (OR = 3.50, p = 0.046), previous tuberculosis (TB) contact (OR = 2.61, p = 0.026), TB in the past (OR = 6.18, p = 0.004) and associated retinal vasculitis (OR = 7.85, p < 0.001) were significantly related to TRU. Sensitivity (S) and specificity (Sp) of the TST and QFT did not differ significantly (S 87% versus 90% and Sp 85% versus 82%, respectively) with fair agreement (k = 0.607). In a Western urban multi-ethnic population, patients from Asia, TB history or contact in the past and vasculitis are at higher risk of TRU. TST and QF are complementary providing enough S and Sp to support the diagnosis. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

Two-year population-based molecular epidemiological study of tuberculosis transmission in the metropolitan area of Milan, Italy.

PubMed

Moro, M L; Salamina, G; Gori, A; Penati, V; Sacchetti, R; Mezzetti, F; Infuso, A; Sodano, L

2002-02-01

A 2-year, population-based, molecular epidemiological study was conducted in Milan, Italy, to determine the proportion of tuberculosis (TB) cases attributable to recent transmission. All strains were typed by restriction fragment length polymorphism (RFLP) analysis; clustering was considered indicative of recent transmission. Of the 581 cases, 239 (41.1%) belonged to clusters that consisted of 2 to 11 patients; 28.1% were attributable to recent transmission (number of clustered patients minus 1). Clustering was associated with multidrug-resistant Mycobacterium tuberculosis strains (74.2% of cases), AIDS (60.2%), and a history of incarceration (67.4%). The frequency of multidrug-resistant Mycobacterium tuberculosis was 5.3% overall (15.4% among AIDS patients). Among AIDS patients, infection with a resistant strain was independently associated with clustering (odds ratio, 1.32; 95% confidence interval, 1.07-1.163), while among non-AIDS patients, three factors were associated with clustering: history of incarceration (odds ratio, 2.03; 95% confidence interval, 1.41-2.92), age <30 years (odds ratio, 1.43; 95% confidence interval, 1.05-1.94), and native-born Italian nationality (odds ratio, 1.44; 95% confidence interval, 1.08-1.92). Of the 118 patients who belonged to either the smallest or the largest cluster, 19 (16.1%) reported an epidemiological link with another study patient. The results of this study highlight the need for control programs that focus on selected high-risk groups consisting primarily of HIV-infected individuals and persons with social and lifestyle risks for TB. These programs should be aimed at reducing the probability of transmission of drug-resistant TB through early identification of cases and provision of effective treatment until the individual is cured.

Structural and biophysical characterization of Rv3716c, a hypothetical protein from Mycobacterium tuberculosis.

PubMed

Gopalan, A; Deka, G; Prabhavathi, M; Savithri, H S; Murthy, M R N; Raja, A

2018-01-01

Latent tuberculosis (TB) is the main hurdle in reaching the goal of "Stop TB 2050". Tuberculin skin and Interferon-gamma release assay tests used currently for the diagnosis of TB infection cannot distinguish between active disease and latent tuberculosis infection (LTBI) and hence new and sensitive protein markers need to be identified for the diagnosis. A protein Rv3716c from Mycobacterium tuberculosis (MtbRv3716c) has been identified as a potential surrogate marker for the diagnosis of LTBI. Here, we present characterization of MtbRv3716c (∼13 kDa) using both biophysical and X-Ray crystallographic methods. EMSA study showed that MtbRv3716c binds to double stranded DNA. X-ray diffraction data collected on a crystal of MtbRv3716c at 1.9 Å resolution was used for structure determination using the molecular replacement method. Significant electron density was not observed for the N-terminal 21 and C-terminal 41 residues in the final electron density map. The C- terminal disordered region is proline rich and displays characteristics of intrinsically disordered proteins. Although the crystal asymmetric unit contained a protomer, a tight dimer could be generated by the application of the crystal two-fold symmetry parallel to the b axis. Packing of dimers in the crystal is mediated by a cadmium ion (Cd 2+ ) occurring at the interface of two dimers. Molecular packing analysis reveals large cavities that are probably occupied by the disordered segments of the N- and C-termini. Structural comparison with other homologous hypothetical DNA binding proteins (PDB codes: 1PUG, 1YBX) highlights structural features that might be significant for DNA binding. Copyright © 2017 Elsevier Inc. All rights reserved.

Tuberculous brain abscess and subdural empyema in an immunocompetent child: Significance of AFB staining in aspirated pus

PubMed Central

Vijayakumar, B.; Sarin, K.; Mohan, Girija

2012-01-01

Tuberculous brain abscess and subdural empyema are extremely rare manifestations of central nervous system tuberculosis. Here, we report a case of an 11-year-old immunocompetent child who developed temporal lobe abscess and subdural empyema following chronic otitis media. A right temporal craniotomy was performed and the abscess was excised. The Ziehl Nielsen staining of the aspirated pus from the temporal lobe abscess yielded acid fast bacilli. Prompt administration of antituberculous treatment resulted in complete recovery of the child. Even though the subdural abscess was not drained, we presume that to be of tubercular aetiology. Ours is probably the first case of brain abscess and subdural empyema due to Mycobacterium tuberculosis reported in the same child. This case is being reported because of its rarity and to stress the importance of routine staining for tubercle bacilli in all cases of brain abscess, especially in endemic areas, as it is difficult to differentiate tuberculous from pyogenic abscess clinically as well as histopathologically. PMID:22566728

Tuberculous brain abscess and subdural empyema in an immunocompetent child: Significance of AFB staining in aspirated pus.

PubMed

Vijayakumar, B; Sarin, K; Mohan, Girija

2012-04-01

Tuberculous brain abscess and subdural empyema are extremely rare manifestations of central nervous system tuberculosis. Here, we report a case of an 11-year-old immunocompetent child who developed temporal lobe abscess and subdural empyema following chronic otitis media. A right temporal craniotomy was performed and the abscess was excised. The Ziehl Nielsen staining of the aspirated pus from the temporal lobe abscess yielded acid fast bacilli. Prompt administration of antituberculous treatment resulted in complete recovery of the child. Even though the subdural abscess was not drained, we presume that to be of tubercular aetiology. Ours is probably the first case of brain abscess and subdural empyema due to Mycobacterium tuberculosis reported in the same child. This case is being reported because of its rarity and to stress the importance of routine staining for tubercle bacilli in all cases of brain abscess, especially in endemic areas, as it is difficult to differentiate tuberculous from pyogenic abscess clinically as well as histopathologically.

Fusion of local and global detection systems to detect tuberculosis in chest radiographs.

PubMed

Hogeweg, Laurens; Mol, Christian; de Jong, Pim A; Dawson, Rodney; Ayles, Helen; van Ginneken, Bramin

2010-01-01

Automatic detection of tuberculosis (TB) on chest radiographs is a difficult problem because of the diverse presentation of the disease. A combination of detection systems for abnormalities and normal anatomy is used to improve detection performance. A textural abnormality detection system operating at the pixel level is combined with a clavicle detection system to suppress false positive responses. The output of a shape abnormality detection system operating at the image level is combined in a next step to further improve performance by reducing false negatives. Strategies for combining systems based on serial and parallel configurations were evaluated using the minimum, maximum, product, and mean probability combination rules. The performance of TB detection increased, as measured using the area under the ROC curve, from 0.67 for the textural abnormality detection system alone to 0.86 when the three systems were combined. The best result was achieved using the sum and product rule in a parallel combination of outputs.

Evaluation of New Vaccines in the Mouse and Guinea Pig Model of Tuberculosis

PubMed Central

Baldwin, Susan L.; D’Souza, Celine; Roberts, Alan D.; Kelly, Brian P.; Frank, Anthony A.; Lui, Margaret A.; Ulmer, Jeffrey B.; Huygen, Kris; McMurray, David M.; Orme, Ian M.

1998-01-01

The results of this study provide the first evidence that two completely separate vaccine approaches, one based on a subunit vaccine consisting of a mild adjuvant admixed with purified culture filtrate proteins and enhanced by the cytokine interleukin-2 and the second based on immunization with DNA encoding the Ag85A protein secreted by Mycobacterium tuberculosis, could both prevent the onset of caseating disease, which is the hallmark of the guinea pig aerogenic infection model. In both cases, however, the survival of vaccinated guinea pigs was shorter than that conferred by Mycobacterium bovis BCG, with observed mortality of these animals probably due to consolidation of lung tissues by lymphocytic granulomas. An additional characteristic of these approaches was that neither induced skin test reactivity to commercial tuberculin. These data thus provide optimism that development of nonliving vaccines which can generate long-lived immunity approaching that conferred by the BCG vaccine is a feasible goal. PMID:9596772

Prevalence of tuberculosis infection in healthcare workers of the public hospital network in Medellín, Colombia: a Bayesian approach.

PubMed

Ochoa, J; León, A L; Ramírez, I C; Lopera, C M; Bernal, E; Arbeláez, M P

2017-04-01

A latent tuberculosis infection (LTBI) prevalence survey was conducted using tuberculin skin test (TST) and Quantiferon test (QFT) in 1218 healthcare workers (HCWs) in Medellín, Colombia. In order to improve the prevalence estimates, a latent class model was built using a Bayesian approach with informative priors on the sensitivity and specificity of the TST. The proportion of concordant results (TST+,QFT+) was 41% and the discordant results contributed 27%. The marginal estimate of the prevalence P(LTBI+) was 62·1% [95% credible interval (CrI) 53·0-68·2]. The probability of LTBI+ given positive results for both tests was 99·6% (95% CrI 98·1-99·9). Sensitivity was 88·5 for TST and 74·3 for QFT, and specificity was 87·8 for TST and 97·6 for QFT. A high LTBI prevalence was found in HCWs with time-accumulated exposure in hospitals that lack control plans. In a context of intermediate tuberculosis (TB) incidence it is recommended to use only one test (either QFT or TST) in prevalence surveys or as pre-employment tests. Results will be useful to help implement TB infection control plans in hospitals where HCWs may be repeatedly exposed to unnoticed TB patients, and to inform the design of TB control policies.

Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection.

PubMed

Kim, Ji Yeun; Park, Joung Ha; Kim, Min-Chul; Cha, Hye Hee; Jeon, Na-Young; Park, Seong Yeon; Kim, Min-Jae; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-08

The IFN-γ-release assay (IGRA) cannot differentiate active tuberculosis (TB) from latent TB infection (LTBI). We hypothesized that the TNF-α-release assay (TARA) combined with IGRA might discriminate active TB from not active TB without LTBI. Adult patients with suspected TB, and with unrelated diseases such as herpes zoster as controls, were enrolled in an intermediate TB-burden country. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as those having not active TB with and without LTBI based on IGRA results. The IGRA and TARA by using ELISPOT assays were performed on peripheral mononuclear cells. Thirty six patients with active TB and 53 patients including 18 not active TB with LTBI and 35 not active TB without LTBI were finally included. The sensitivity and specificity of the IGRA for those patients found to have active TB were 94% (CI, 80-99) and 66% (CI 52-78), respectively. Combining the IGRA and the TARA substantially increased the specificity for active TB (93%, CI, 82-98; P = 0.001) compared with the IGRA only, without compromising sensitivity (89%, CI, 73-96; P = 0.67). Combining the IGRA and TARA appears to be useful for diagnosing active TB. Copyright © 2018. Published by Elsevier Ltd.

A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt

PubMed Central

Fiebig, Lena; Kohl, Thomas A; Popovici, Odette; Mühlenfeld, Margarita; Indra, Alexander; Homorodean, Daniela; Chiotan, Domnica; Richter, Elvira; Rüsch-Gerdes, Sabine; Schmidgruber, Beatrix; Beckert, Patrick; Hauer, Barbara; Niemann, Stefan; Allerberger, Franz; Haas, Walter

2017-01-01

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders. PMID:28106529

Proteome analysis of ofloxacin and moxifloxacin induced mycobacterium tuberculosis isolates by proteomic approach.

PubMed

Lata, Manju; Sharma, Divakar; Kumar, Bhavnesh; Deo, Nirmala; Tiwari, Pramod Kumar; Bisht, Deepa; Venkatesan, Krishnamurthy

2015-01-01

Ofloxacin (OFX) and moxifloxacin (MOX) are the most promising second line drugs for tuberculosis treatment. Although the primary mechanism of action of OFX and MOX is gyrase inhibition, other possible mechanisms cannot be ruled out. Being the functional moiety of cell, the proteins act as primary targets for developing drugs, diagnostics and therapeutics. In this study we have investigated the proteomic changes of Mycobacterium tuberculosis isolates induced by OFX and MOX by applying comparative proteomic approaches based on two-dinensional gel electrophoresis (2DE) along with matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI TOF/TOF-MS) and bioinformatic tools. The findings are likely to provide new understanding of OFX and MOX mechanisms that might be helpful in exploring new diagnostics and drug targets. Our study explored eleven proteins (Rv2889c, Rv2623, Rv0952, Rv1827, Rv1932, Rv0054, Rv1080c, Rv3418c, Rv3914, Rv1636 and Rv0009) that were overexpressed in the presence of drugs. Among them, Rv2623, Rv1827 and Rv1636 were identified as proteins with unknown function. InterProScan and molecular docking revealed that the conserved domain of hypothetical proteins interact with OFX and MOX which indicate a probable inhibition/modulation of the functioning of these proteins by both drugs, which might be overexpressed to overcome this effect.

Contact investigation after a fatal case of extensively drug-resistant tuberculosis (XDR-TB) in an aircraft, Germany, July 2013.

PubMed

An der Heiden, Maria; Hauer, Barbara; Fiebig, Lena; Glaser-Paschke, Gisela; Stemmler, Markus; Simon, Claudia; Rüsch-Gerdes, Sabine; Gilsdorf, Andreas; Haas, Walter

2017-03-23

In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired. This article is copyright of The Authors, 2017.

Profile of skin biopsies and patterns of skin cancer in a tertiary care center of Western Nepal.

PubMed

Kumar, Ajay; Shrestha, Prashanna Raj; Pun, Jenny; Thapa, Pratichya; Manandhar, Merina; Sathian, Brijesh

2015-01-01

Skin biopsy is the method to assist clinicians to make definite dermatological diagnosis which further helps in holistic management. Skin cancers are relatively rare clinical diagnosis in developing countries like Nepal, but the prevalence is on rise. To investigate the profile of skin biopsies and frequencies and pattern of skin cancers in a tertiary care centre of Western Nepal. The materials consisted of 434 biopsies (1.37%) out of 31,450 OPD visits performed in the Department of Dermatology, Manipal Teaching Hospital, Pokhara, Nepal, during the period of Dec 2011-Nov 2014. Data were collected and analyzed using SPSS-16 with reference to incidence, age, sex, race and clinical and histopathological features. The commonest disorders observed in biopsies were papulosquamous lesions, skin tuberculosis of different types, benign skin tumors, leprosy, collagen and fungal diseases. Viral diseases were rarely seen, probably due to straight forward clinical diagnosis. Dermatological malignancies accounted for 55/434 (12.67%) of biopsies. Skin disorders in general were commoner in females 280/434 (64%), including malignancies 32/55(58.2%). Mean age of patients with skin cancer was 54.5 years. Facilities for proper laboratory investigation of dermatological disorders will improve the quality of life. The most prevalent lesion in skin biopsies was papulosquamous disorders followed by skin tuberculosis of different types. Dermatological malignancy constituted 55/434 (12.67%) cases. The prevalence of skin malignancy is on rise in Nepalese society probably due to increase in life expectancy and better diagnostic services.

Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area.

PubMed

Ruan, Sheng-Yuan; Chuang, Yu-Chung; Wang, Jann-Yuan; Lin, Jou-Wei; Chien, Jung-Yien; Huang, Chun-Ta; Kuo, Yao-Wen; Lee, Li-Na; Yu, Chong-Jen J

2012-09-01

Tuberculous pleurisy is traditionally indicated by extreme lymphocytosis in pleural fluid and low yield of effusion culture. However, there is considerable inconsistency among previous study results. In addition, these data should be updated due to early effusion studies and advances in culture methods. From January 2004 to June 2009, patients with tuberculous pleurisy were retrospectively identified from the mycobacteriology laboratories and the pathology and tuberculosis registration databases of two hospitals in Taiwan where tuberculosis is endemic. Pleural fluid characteristics and yields of mycobacterial cultures using liquid media were evaluated. A total of 382 patients with tuberculous pleurisy were identified. The median lymphocyte percentage of total cells in pleural fluids was 84% (IQR 64-95%) and 17% of cases had a lymphocyte percentage of <50%. The lymphocyte percentage was negatively associated with the probability of a positive effusion culture (OR 0.97; 95% CI 0.96 to 0.99). The diagnostic yields were 63% for effusion culture, 48% for sputum culture, 79% for the combination of effusion and sputum cultures, and 74% for histological examination of pleural biopsy specimens. The degree of lymphocyte predominance in tuberculous pleurisy was lower than was previously thought. The lymphocyte percentage in pleural fluid was negatively associated with the probability of a positive effusion culture. With the implementation of a liquid culture method, the sensitivity of effusion culture was much higher than has been previously reported, and the combination of effusion and sputum cultures provided a good diagnostic yield.

Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010.

PubMed

Báez-Saldaña, Renata; Delgado-Sánchez, Guadalupe; García-García, Lourdes; Cruz-Hervert, Luis Pablo; Montesinos-Castillo, Marlene; Ferreyra-Reyes, Leticia; Bobadilla-Del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Yanes-Lane, Mercedes; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

2016-01-01

Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables. The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings.

[Longitudinal follow-up of contact subjects of cases of tuberculosis in Paris].

PubMed

Fournier, A; Antoun, F; Charlois Ou, C; Muller, G; Ezri, L; Morin, P; Faure, A; Marteau, D; Keshtmand, H; Quelet, S

2015-09-01

To our knowledge, the proportion of active tuberculosis diagnosed after 12-18 months during a screening tuberculosis process in a specialized centre (centre de lutte antituberculeuse [CLAT]) has not been described in France. The majority of other countries do not have any recommendation to screen at this time. We evaluated the number of treated or not treated latent tuberculosis infections (LTI) identified during tuberculosis screening. We identified the causes of ITL non-treatment, the number of active disease cases and the proportion of subjects lost to follow-up after 12-18 months. Among the 1066 contact subjects, 159 (15 %) had a positive QuantiFERON-TB-Gold In-Tube(®) test. A prophylactic treatment with Rifinah(®) was given to 97 (61 %) subjects, 7 (7.3 %) having developed side effects that led to treatment interruption. A high proportion (56 %) of contact subjects were lost of follow-up and the main reason for no prophylactic treatment (20/52, 38 %) was due to these losses. No active disease cases were identified among the 474 (44 %) contact subjects who had a chest X-ray after 12-18 months follow-up by the CLAT. The low level of positive QuantiFERON-TB-Gold In-Tube(®) tests (15 %) could be explained by the high specificity of this test and the strong proportion of occupational contacts, of whom a probably significant number were not exposed to active disease. The absence of active disease at 12-18 months and a majority (56 %) of contact subjects lost from follow-up at this period let us propose not to recall contact subjects at 12-18 months with the exception of those living under the same roof as the index case and/or those having a cumulative contact time of greater than 100 hours during the theoretical infectious period. This proposal remains to be confirmed by other studies, particularly including possible secondary cases diagnosed outside the screening periods by the CLAT. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Diagnostic Challenges in Chronic Constrictive Pericarditis.

PubMed

Braga, Ana; Oliveira, Afonso; Domingues, Kevin; Andrade, Maria João; Abecacis, Miguel; Neves, José Pedro

2017-01-01

Chronic constrictive pericarditis (CCP) is a disease that has multiple possible causes and is associated with variable clinical findings, depending on its severity. It develops insidiously, and in many cases, particularly in developed countries, no antecedent diagnosis can be found. These cases are termed idiopathic. Tuberculosis is the leading cause of constrictive pericarditis in developing nations but represents only a small minority in developed countries. Here the authors describe two different case reports where tuberculosis was the probable cause of CCP. A 21-year-old man born in Cape Verde living in Europe for 4 years and a 24-year-old man born in Guiné Bissau were both admitted due to intense precordial pain and syncope after exertion. Interestingly both had fatigability, dyspnea, chest discomfort and palpitations on exertion, as well as progressive involuntary weight loss and decubitus cough. On physical examination they had tachycardia, jaundice, cachexia, elevated jugular venous pressure, hepatomegaly and ascites. Both electrocardiograms showed prominent P waves and chest X-ray showed bilateral pulmonary interstitial infiltrates and enlargement of the right cavities. Analytically, elevated bilirubin, leukopenia and thrombocytopenia was also found in both. Echocardiography revealed findings, in both cases, compatible with CCP including less common signs as annulus reversus and annulus paradoxus. Thoraco-abdomino-pelvic CT from both patients revealed chronic liver disease with congestion, pleural effusion, pericardial calcifications, ascites and massive mediastinal and abdominal adenopathies. Blood cultures and IGRA test were negative. However, given the presumptive diagnosis of tuberculosis (TB), anti-TB therapy was started. Despite the diagnosis of "end-stage" CCP with very high operative risk multidisciplinary team decided after informed consent, to perform total anterior pericardiectomy, that occurred without complications. Pericardial and mediastinal biopsies, pericardial/pleural fluid cultures/ immune-phenotyping were inconclusive. Anti- tuberculosis therapy was maintained. After surgery, the patients had a remarkable clinical improvement (NYHA I) that persisted in 6- month follow-up. These two case reports illustrate that despite the markedly elevated operative risk of pericardiectomy in "end-stage" forms of disease after patients informed consent must be a considered option. The other point to consider is that, despite rare, tuberculosis still is a possible diagnosis to consider in CCP in Portugal.

Differentiation of Mycobacterium tuberculosis complex from non-tubercular mycobacteria by nested multiplex PCR targeting IS6110, MTP40 and 32kD alpha antigen encoding gene fragments.

PubMed

Sinha, Pallavi; Gupta, Anamika; Prakash, Pradyot; Anupurba, Shampa; Tripathi, Rajneesh; Srivastava, G N

2016-03-12

Control of the global burden of tuberculosis is obstructed due to lack of simple, rapid and cost effective diagnostic techniques that can be used in resource poor-settings. To facilitate the early diagnosis of TB directly from clinical specimens, we have standardized and validated the use of nested multiplex PCR, targeting gene fragments IS6110, MTP40 and 32kD α-antigen encoding genes specific for Mycobacterium tuberculosis complex and non-tubercular mycobacteria (NTM), in comparison to smear microscopy, solid culture and single step multiplex PCR. The results were evaluated in comparison to a composite reference standard (CRS) comprising of microbiological results (smear and culture), clinical, radiological and cytopathological findings, clinical treatment and response to anti-tubercular therapy. The nested multiplex PCR (nMPCR) assay was evaluated to test its utility in 600 (535 pulmonary and 65 extra-pulmonary specimens) clinically suspected TB cases. All specimens were processed for smear, culture, single step multiplex PCR and nested multiplex PCR testing. Out of 535 screened pulmonary and 65 extra-pulmonary specimens, 329 (61.5%) and 19 (29.2%) cases were culture positive for M. tuberculosis. Based on CRS, 450 patients had "clinical TB" (definitive-TB, probable-TB and possible-TB). Remaining 150 were confirmed "non-TB" cases. For culture, the sensitivity was low, 79.3% for pulmonary and 54.3% for extra-pulmonary cases. The sensitivity and specificity results for nMPCR test were evaluated taken composite reference standard as a gold standard. The sensitivity of the nMPCR assay was 97.1% for pulmonary and 91.4% for extra-pulmonary TB cases with specificity of 100% and 93.3% respectively. Nested multiplex PCR using three gene primers is a rapid, reliable and highly sensitive and specific diagnostic technique for the detection and differentiation of M. tuberculosis complex from NTM genome and will be useful in diagnosing paucibacillary samples. Nested multiplex PCR assay was found to be better than single step multiplex PCR for assessing the diagnosis of TB.

Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010

PubMed Central

Báez-Saldaña, Renata; Delgado-Sánchez, Guadalupe; García-García, Lourdes; Cruz-Hervert, Luis Pablo; Montesinos-Castillo, Marlene; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Yanes-Lane, Mercedes; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

2016-01-01

Background Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. Objective To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. Materials and Methods We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. Results Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15–2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08–6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38–45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00–10.84). All the models were adjusted for socio-demographic and clinical variables. Conclusions The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings. PMID:28030600

Impact of an effective multidrug-resistant tuberculosis control programme in the setting of an immature HIV epidemic: system dynamics simulation model.

PubMed

Atun, Rifat A; Lebcir, Reda; Drobniewski, Francis; Coker, Richard J

2005-08-01

This study sought to determine the impact of an effective programme of multidrug resistant tuberculosis control (MDRTB) on a population that is witnessing an explosive HIV epidemic among injecting drug users (IDUs), where the prevalence of MDRTB is already high. A transmission model was constructed that represents the dynamics of the drug-susceptible tuberculosis (DSTB), MDRTB and HIV spread among the adult population of Samara Oblast, Russia: from official notifications of tuberculosis and of HIV infection, estimates of MDRTB derived from surveillance studies, population data from official regional statistics, data on transmission probabilities from peer-reviewed publications and informed estimates, and policy-makers' estimates of IDU populations. Two scenarios of programme effectiveness for MDRTB were modelled and run over a period of 10 years to predict cumulative deaths. In a population of 3.3 million with a high prevalence of MDRTB, an emerging epidemic of HIV among IDUs, and a functioning directly observed therapy-short course (DOTS) programme, the model predicts that under low cure rates for MDRTB the expected cumulative deaths from tuberculosis will reach 6303 deaths including 1900 deaths from MDRTB at 10 years. Under high cure rate for MDRTB 4465 deaths will occur including 134 deaths from MDRTB. At 10 years there is little impact on HIV-infected populations from the MDRTB epidemic, but as the HIV epidemic matures the impact becomes substantial. When the model is extended to 20 years cumulative deaths from MDRTB become very high if cure rates for MDRTB are low and cumulative deaths in the HIV-infected population, likewise, are profoundly affected. In the presence of an immature HIV epidemic failure to actively control MDRTB may result in approximately a third more deaths than if effective treatment is given. As the HIV epidemic matures then the impact of MDRTB grows substantially if MDRTB control strategies are ineffective. The epidemiological starting point for these scenarios is present in many regions within the former Soviet Union and this analysis suggests control of MDRTB should be an urgent priority.

Influence of health rights discourses and community organizing on equitable access to health: the case of HIV, tuberculosis and cancer in Peru

PubMed Central

2013-01-01

Background The right to health is recognized as a fundamental human right. Social participation is implied in the fulfillment of health rights since Alma Ata posited its relevance for successful health programs, although a wide range of interpretations has been observed for this term. While Peruvian law recognizes community and social participation in health, it was the GFATM requirement of mixed public-civil society participation in Country Coordination Mechanisms (CCM) for proposal submission what effectively led to formal community involvement in the national response to HIV and, to a lesser extent, tuberculosis. This has not been the case, however, for other chronic diseases in Peru. This study aims to describe and compare the role of health rights discourse and community involvement in the national response to HIV, tuberculosis and cancer. Methods Key health policy documents were identified and analyzed. In-depth interviews were conducted with stakeholders, representatives of civil society organizations (CSO), and leaders of organizations of people affected by HIV, cancer and tuberculosis. Results and discussion A health rights discourse, well established in the HIV field, is expanding to general health discussions and to the tuberculosis (TB) field in particular. Both HIV and TB programs have National Multisectoral Strategic Plans and recognize participation of affected communities’ organizations. Similar mechanisms are non-existent for cancer or other disease-focused programs, although other affected patients are starting some organization efforts. Interviewees agreed that reaching the achievements of HIV mobilization is difficult for other diseases, since the HIV response was modeled based on a global movement with strong networks and advocacy mechanisms, eventually succeeding in the establishment of financial sources like the GFATM. Nevertheless, organizations linked to cancer and other diseases are building a National Patient Network to defend health rights. Conclusions There are new efforts to promote and protect health rights in Peru, probably inspired by the achievements of organizations of people living with HIV (PLHA). The public health sector must consolidate the participation of affected communities’ organizations in decision-making processes and implementation of health programs. PLHA organizations have become a key political and social actor in Peruvian public health policy. PMID:23683817

Tuberculosis Reports - UDOH-EPI

Science.gov Websites

Tuberculosis Tuberculosis Reports Tuberculosis Reports Tuberculosis Utah Reports Tuberculosis in Utah - Five (IBIS-PH) Tuberculosis 2015 Monthy Reports January February March April May June Tuberculosis National Reports National TB Data and Statistics Tuberculosis Global Reports TB Incidence Map by country TB

Tuberculosis-related knowledge is associated with patient outcomes in shantytown residents; results from a cohort study, Peru.

PubMed

Westerlund, Emma E; Tovar, Marco A; Lönnermark, Elisabet; Montoya, Rosario; Evans, Carlton A

2015-09-01

Tuberculosis is frequent among poor and marginalized people whose limited tuberculosis-related knowledge may impair healthcare access. We characterised tuberculosis-related knowledge and associations with delayed treatment and treatment outcome. Tuberculosis patients (n = 943), people being tested for suspected tuberculosis (n = 2020), and randomly selected healthy controls (n = 476) in 16 periurban shantytowns were interviewed characterizing: socio-demographic factors; tuberculosis risk-factors; and patients' treatment delay. Principle component analysis was used to generate a tuberculosis-related knowledge score. Patients were followed-up for median 7.7 years. Factors associated with tuberculosis treatment delay, treatment outcome and tuberculosis recurrence were assessed using linear, logistic and Cox regression. Tuberculosis-related knowledge was poor, especially in older people who had not completed schooling and had never been diagnosed with tuberculosis. Tuberculosis treatment delay was median 60 days and was more delayed for patients who were poorer, older, had more severe tuberculosis and in only unadjusted analysis with incomplete schooling and low tuberculosis-related knowledge (all p ≤ 0.03). Lower than median tuberculosis-related knowledge was associated with tuberculosis recurrence (unadjusted hazard ratio = 2.1, p = 0.008), and this association was independent of co-morbidities, disease severity and demographic factors (multiple regression adjusted hazard ratio = 2.6, p = 0.008). Low tuberculosis-related knowledge independently predicted tuberculosis recurrence. Thus health education may improve tuberculosis prognosis. Copyright © 2015. Published by Elsevier Ltd.

A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt.

PubMed

Fiebig, Lena; Kohl, Thomas A; Popovici, Odette; Mühlenfeld, Margarita; Indra, Alexander; Homorodean, Daniela; Chiotan, Domnica; Richter, Elvira; Rüsch-Gerdes, Sabine; Schmidgruber, Beatrix; Beckert, Patrick; Hauer, Barbara; Niemann, Stefan; Allerberger, Franz; Haas, Walter

2017-01-12

Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders. This article is copyright of The Authors, 2017.

MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: A study from the tertiary care hospital in Zanzibar.

PubMed

Jørstad, Melissa Davidsen; Marijani, Msafiri; Dyrhol-Riise, Anne Ma; Sviland, Lisbet; Mustafa, Tehmina

2018-01-01

Extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting. Patients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases. Patients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%). We show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.

[Not Available].

PubMed

Demaeyer, Ph

2016-01-01

Medicine owes many to Hippocrate, but pneumology traces its origin back to antiquity, from Mesopotamia to ancient Rome. Regarding prehistory: if viscera of this period have not been kept, some bones were. Since Neanderthals, it is then possible to study osteoarticular pathologies (often chronic arthrosis). But no evidence of tuberculosis was found (all thoracic kyphosis are not tuberculosis). Tuberculosis probably appears during the Neolithic age, because of high concentration of population. In ancient times, pneumology was of course not a real medical specialty. However, respiratory illness already constituted a big part of antique medical practice. The purpose of the physician in antiquity was to establish a diagnosis, a prognostic and to propose a treatment. Prognostic revealed to be of great importance in ancient times, since therapeutic efficacy was limited. Contemporary physicians often neglect this part of their practice. In ancient times, physicians also tried to gradually eliminate magic-religious aspects in taking care of the patients. This review will propose a journey from Mesopotamia to ancient Egypt (and its medical papyrus). Very few sources are available concerning medicine in pre-Columbian cultures. However, it is well known that shamans had, besides their religious competences, a great pharmacopoeia. Because of these very few sources, this topic will not be added to this article. Little is known in Europa about chinese medicine before the Jesuit mission in China during the 17th and 18th centuries. Yet, chinese medicine grew in parallel with European's one. Some relevant elements of this medicine will hereafter be shown.

High Genetic Diversity Revealed by Variable-Number Tandem Repeat Genotyping and Analysis of hsp65 Gene Polymorphism in a Large Collection of “Mycobacterium canettii” Strains Indicates that the M. tuberculosis Complex Is a Recently Emerged Clone of “M. canettii”

PubMed Central

Fabre, Michel; Koeck, Jean-Louis; Le Flèche, Philippe; Simon, Fabrice; Hervé, Vincent; Vergnaud, Gilles; Pourcel, Christine

2004-01-01

We have analyzed, using complementary molecular methods, the diversity of 43 strains of “Mycobacterium canettii” originating from the Republic of Djibouti, on the Horn of Africa, from 1998 to 2003. Genotyping by multiple-locus variable-number tandem repeat analysis shows that all the strains belong to a single but very distant group when compared to strains of the Mycobacterium tuberculosis complex (MTBC). Thirty-one strains cluster into one large group with little variability and five strains form another group, whereas the other seven are more diverged. In total, 14 genotypes are observed. The DR locus analysis reveals additional variability, some strains being devoid of a direct repeat locus and others having unique spacers. The hsp65 gene polymorphism was investigated by restriction enzyme analysis and sequencing of PCR amplicons. Four new single nucleotide polymorphisms were discovered. One strain was characterized by three nucleotide changes in 441 bp, creating new restriction enzyme polymorphisms. As no sequence variability was found for hsp65 in the whole MTBC, and as a single point mutation separates M. tuberculosis from the closest “M. canettii” strains, this diversity within “M. canettii” subspecies strongly suggests that it is the most probable source species of the MTBC rather than just another branch of the MTBC. PMID:15243089

[Severe tularaemia mimicking glandular tuberculosis during adalimumab therapy].

PubMed

Konstantinou, M-P; Abecassis-Cotta, S; Valeyrie-Allanore, L; Ortonne, N; Maurin, M; Roujeau, J-C; Revuz, J; Bagot, M

2009-10-01

Tularaemia is an anthropozoonosis, transmitted by small mammals (hares) and arthropods (ticks, horseflies). The causative agent is Francisella tularensis, a facultatively intracellular Gram-negative bacillus. We report a case of tularaemia in its ulceroglandular form occurring during methotrexate and adalimumab treatment (Humira) for rheumatoid arthritis. A 58-year-old man with a history of primary tuberculosis receiving adalimumab in combination with methotrexate for rheumatoid arthritis for almost 1 year consulted for a febrile inflammatory plaque on the left leg with a small central necrotic area. An enlarged left inguinal lymph node was present. Doxycycline has previously been prescribed for a tick bite. The lymphadenopathy gradually became enlarged resulting in skin fistulisation. After surgical excision, histopathology revealed epithelioid granulomas accompanied by giant cells and central necrosis. Mycobacterial cultures were negative. Positive tularaemia serology at significant titres suggested a diagnosis of tularaemia, with probable transmission via a tick bite. The diagnosis was confirmed by F. tularensis DNA amplification using PCR on a lymph node biopsy. Doxycycline was continued for a further 6 weeks. One year later, no relapse had occurred. A febrile adenopathy presenting the histological features of necrotic granulomas in a patient receiving anti-TNF alpha treatment initially suggested reactivation of tuberculosis. However, the history of tick bite and failure to isolate mycobacteria from different tissue specimens prompted screening for a tick-borne disease, finally leading to a diagnosis of tularaemia. We discuss the possible relationship between immunosuppression and the clinical course of this rare infection.

New insights on the nature of latent tuberculosis infection and its treatment.

PubMed

Cardona, Pere-Joan

2007-03-01

Nowadays, there is no conclusive theory explaining the latent tuberculosis infection (LTBI). LTBI is reviewed herein as a standard progression of M. tuberculosis in the context of the usual microaerobiosis present in the host's tissues and displaying their main virulent factors: slow metabolism; cell wall thickness and ability to induce intragranulomatous necrosis. Therefore, latent bacilli (LB) would be generated by the irruption of specific immunity forcing bacilli to remain in a stationary phase (SP) inside the necrotic tissue. This tissue is crucial because it maintains a stable LB population and prolongs the production of foamy macrophages which facilitate the LB escape to the alveolar spaces. In the alveolar spaces, LB will regrow and, once freed in this privileged space, they will induce new granulomas -less developed because they are better controlled by immunity. This explains the ability of LB to face the chance to be drained as a consequence of the constant cellular turnover, and to survive for a long time in the lung. This activity also supports the hypothesis that generation of active TB highly depends on the probability of the LB regrowth in a favorable zone (i.e., in the pulmonary apex). This "dynamic" hypothesis faces a more classic one (or "static") essentially based on the presence of a "resuscitation" factor that would reactivate "dormant" bacilli in old lesions in the apex. Current possibilities for LTBI treatment are reviewed according to this "dynamic hypothesis", from the standard chemotherapy to the introduction of therapeutic vaccines and anti-inflammatory treatments.

Economics of United States tuberculosis airline contact investigation policies: a return on investment analysis.

PubMed

Coleman, Margaret S; Marienau, Karen J; Marano, Nina; Marks, Suzanne M; Cetron, Martin S

2014-01-01

In 2011, the Centers for Disease Control and Prevention modified its 2008 protocol for flight-related tuberculosis contact investigation initiation. The 2011 Modified protocol was implemented and replaced the 2008 CDC protocol based on comparative epidemiologic and economic analyses; this publication reports the economic analysis results. A return on investment model compared relative changes in tuberculosis disease treatment costs resulting from expenditures on tuberculosis contact investigations and latent tuberculosis infection treatment for the 2008 CDC and Modified protocols. At moderate/high rates of latent tuberculosis infection and tuberculosis disease, positive returns on investment indicated each $1.00 spent on tuberculosis contact investigations and latent tuberculosis treatment resulted in more than $1.00 of savings from reduced tuberculosis disease treatment costs. Low rates of latent tuberculosis infection and tuberculosis disease resulted in negative returns on investment, indicating economic losses from tuberculosis disease treatment costs. There were smaller economic losses at low latent tuberculosis infection and tuberculosis disease rates with the Modified protocol in comparison to the 2008 CDC protocol, while both identified comparable numbers of persons at risk for tuberculosis. The Modified protocol for conducting flight-related tuberculosis contact investigations represents a better use of resources and protects public health. Published by Elsevier Ltd.

Economics of United States tuberculosis airline contact investigation policies: A return on investment analysis

PubMed Central

Coleman, Margaret S.; Marienau, Karen J.; Marano, Nina; Marks, Suzanne M.; Cetron, Martin S.

2017-01-01

Summary Background In 2011, the Centers for Disease Control and Prevention modified its 2008 protocol for flight-related tuberculosis contact investigation initiation. The 2011 Modified protocol was implemented and replaced the 2008 CDC protocol based on comparative epidemiologic and economic analyses; this publication reports the economic analysis results. Methods A return on investment model compared relative changes in tuberculosis disease treatment costs resulting from expenditures on tuberculosis contact investigations and latent tuberculosis infection treatment for the 2008 CDC and Modified protocols. Results At moderate/high rates of latent tuberculosis infection and tuberculosis disease, positive returns on investment indicated each $1.00 spent on tuberculosis contact investigations and latent tuberculosis treatment resulted in more than $1.00 of savings from reduced tuberculosis disease treatment costs. Low rates of latent tuberculosis infection and tuberculosis disease resulted in negative returns on investment, indicating economic losses from tuberculosis disease treatment costs. There were smaller economic losses at low latent tuberculosis infection and tuberculosis disease rates with the Modified protocol in comparison to the 2008 CDC protocol, while both identified comparable numbers of persons at risk for tuberculosis. Conclusion The Modified protocol for conducting flight-related tuberculosis contact investigations represents a better use of resources and protects public health. PMID:24262643

New Generation IGRA in Immunocompromised Individuals

ClinicalTrials.gov

2016-08-05

Monitoring, Immunologic; Active Tuberculosis; Tuberculosis in Solid Organ Transplant Recipients; Tuberculosis in Marrow Transplant Recipients; Tuberculosis in Rheumatoid Arthritis; Tuberculosis in Chronic Renal Failure; Tuberculosis in HIV-infected Individuals

Evaluating the usefulness of the ICT tuberculosis test kit for the diagnosis of tuberculosis

PubMed Central

Chang, C. L.; Lee, E. Y.; Son, H. C.; Park, S. K.

2000-01-01

Background—Early diagnosis of tuberculosis is crucial, especially in Korea, where tuberculosis is endemic. Aims—To evaluate the validity of the ICT tuberculosis test (ICT) in early diagnosis of tuberculosis. Methods—Sixty eight patients with tuberculosis were tested; 37 had no history of previous tuberculosis (patient group 1), and 31 had reactivated tuberculosis (patient group 2). The control groups comprised 77 subjects: 25 healthy adults, 35 hospital workers, and 17 inpatients with non-tuberculous respiratory diseases. Results—The diagnostic sensitivities of ICT were 73% in patient group 1 and 87.1% in patient group 2. In two patients with extrapulmonary tuberculosis, both tested positive using ICT. The specificities of ICT were 88%, 94%, and 94% in healthy adults, hospital workers, and non-tuberculous patients, respectively. Conclusions—ICT is a useful tool for the diagnosis of tuberculosis. Key Words: serological diagnosis of tuberculosis • ICT tuberculosis test PMID:11041064

Prevalence of Gene Mutations profiles by GenoType MTBDRplus/sl to First Line Antituberculosis Drugs and Clinical Characteristics in Drug Resistant Tuberculosis Patients Referred to the National Institute of Respiratory Diseases in Mexico City

PubMed Central

Martinez-Orozco, Jose Arturo; Nuñez-Luna, Blanca A; Narváez-Diaz, Luis A; Pilar, Mariela Segura-Del; Mujica-Sanchez, Mario; Salazar-Lezama, Miguel Angel; Mireles-Davalos, Christian D

2017-01-01

Abstract Background Drug resistance tuberculosis, specially MDR and XDR are a big challenge for diagnosis and treatment. In Mexico the prevalence of MDR is between 3–5%, a number probably underestimated due to lack of diagnostic tests for susceptibility. The National Institute of Respiratory Diseases in Mexico City is the national referral center for MDR/XDR tuberculosis. In our country there is no data about the gene mutations involved in drug resistance to first line antituberculosis treatment nor the clinical characteristics that accompany these findings. Objective: Evaluate the prevalence of genotyping profiles according to a line probe assay (LPA) in patients with drug resistance tuberculosis and their associated clinical characteristics Methods Retrospective cohort from 2010 to 2014 of M. tuberculosis isolates with any type of resistance to first line antituberculosis drugs identified by MGIT SIRE and in which GenoType MTBDRplus/sl were performed, we evaluate prevalence of genotyping profiles according to the LPA within the isolates and gather data from those with complete medical records to asses clinical characteristics. Results In 52 and 33 isolates phenotyping and genotyping MTBDRplus/sl respectively were performed, 41 resistant to Isoniazid INH with 75% genotypic concordance, 33 resistant to rifampicin RIF with 75.6% concordance, 14 to streptomycin SM with 23% concordance and 10 to ethambutol EMB with 100% concordance, 54% MDR tuberculosis. The genotyping profile for RIF was absence of probes rpoB Wild Type 8 (WT) 57.7%, WT 7 30.8% and presence of rpoB mutation 3 (MUT) 19.2%. For INH absence of InhA WT2 48.1% and InhA WT1 19.2%. For EMB absence of embB WT1 30.8% and for SM absence of rrs WT1 (19%). Absence of InhA WT1 was associated with female (P = 0.01) and DM2 (P = 0.032) patients, other clinical/biochemical characteristics and mortality was not different in patients with o without the genotypic profile for each drug. Cavitary disease by CT was more frequent in patients with WT probe absence in RIF and INH than those who did not have a LPA suggestive of resistance for this drugs. Conclusion Wild Type probe absense is the frequent finding in our isolates according to LPA in RIF, INH, EMB and SM, intrisic host factors and clinical characteristics seem not to be related to a particular resistant gene profile. Disclosures All authors: No reported disclosures.

Examining the social status, risk factors and lifestyle changes of tuberculosis patients in Sri Lanka during the treatment period: a cross-sectional study.

PubMed

Senanayake, Madapathage Gayan Buddhika; Wickramasinghe, Sumudu Indika; Samaraweera, Sudath; De Silva, Pubudu; Edirippulige, Sisira

2018-01-01

Tuberculosis (TB) is a major global health problem, commonly seen in underdeveloped countries. The probability of contracting the disease is significantly higher among the economically vulnerable and the socially disadvantaged. Risk factors associated with TB can also change over time. In the Sri Lankan context, no study has explored how these factors impact patients. Therefore, we aimed to explore social status, associated risk factors and lifestyle changes during the treatment period of TB patients attending a tertiary respiratory center in Colombo, Sri Lanka. The descriptive cross-sectional study was conducted in 2011. The study population consisted of diagnosed tuberculosis patients above the age of 15 years. Patient records were retrieved from the TB patient registry for the Colombo district. Systematic sampling was used to identify patients to be invited to the study. An interviewer-administered questionnaire was used for data collection. Data were collected on social status (example, level of education, employment, and income), associated risk factors (example, smoking and alcohol consumption, contact history, narcotic drug use) and lifestyle changes during treatment (example, employment status, social interactions). The analysis included a logistic regression model to explore the association between social status and risk factors. The total number of patients included in the study was 425. Tuberculosis was found to be strongly prevalent among participants from the lower socio-economic status. It was also common in participants with a low level of education, unemployed, if employed, those who are engaged in unskilled employment and have low levels of income. Risk factors associated with the patients were smoking, alcohol consumptions, narcotic drug use, imprisonment, close contact history with active TB patients and chronic medical conditions. Changes in employment and the reduction of social-interactions were the main lifestyle changes of the participants occurred during the treatment period. The analysis also showed positive correlation between low-level social status and sputum smear infectivity, and use of dangerous drugs. Even after adjusting for confounders, tuberculosis negatively affected social interactions and income levels of participants from the low social status. Low socio-economic status negatively affected the lifestyle and social interactions of patients during the treatment period. Though competent treatment programs exist in Sri Lanka, it is still important to identify and mitigate risk factors associated with tuberculosis patients. A comprehensive multi-disciplinary approach considering patient lifestyle, and the implications of the disease and treatment on social interactions may strengthen the current preventive strategies.

Tuberculosis (TB): Treatment

MedlinePlus

... Education & Training Home Conditions Tuberculosis (TB) Tuberculosis: Treatment Tuberculosis: Treatment Make an Appointment Refer a Patient Ask ... or bones is treated longer. NEXT: Preventive Treatment Tuberculosis: Diagnosis Tuberculosis: History Clinical Trials For more than ...

The Incremental Cost-Effectiveness of Engaging Private Practitioners to Refer Tuberculosis Suspects to DOTS Services in Jogjakarta, Indonesia

PubMed Central

Mahendradhata, Yodi; Probandari, Ari; Ahmad, Riris A.; Utarini, Adi; Trisnantoro, Laksono; Lindholm, Lars; van der Werf, Marieke J.; Kimerling, Michael; Boelaert, Marleen; Johns, Benjamin; Van der Stuyft, Patrick

2010-01-01

We aimed to evaluate the incremental cost-effectiveness of engaging private practitioners (PPs) to refer tuberculosis (TB) suspects to public health centers in Jogjakarta, Indonesia. Effectiveness was assessed for TB suspects notified between May 2004 and April 2005. Private practitioners referred 1,064 TB suspects, of which 57.5% failed to reach a health center. The smear-positive rate among patients reaching a health center was 61.8%. Two hundred eighty (280) out of a total of 1,306 (21.4%) new smear-positive cases were enrolled through the PPs strategy. The incremental cost-effectiveness ratio per smear-positive case successfully treated for the PPs strategy was US$351.66 (95% CI 322.84–601.33). On the basis of an acceptability curve using the National TB control program's willingness-to-pay threshold (US$448.61), we estimate the probability that the PPs strategy is cost-effective at 66.8%. The strategy of engaging PPs was incrementally cost-effective, although under specific conditions, most importantly a well-functioning public directly observed treatment, short-course (DOTS) program. PMID:20519613

Cerebral tuberculomas – A clinical challenge

PubMed Central

Monteiro, Regina; Carneiro, José Carlos; Costa, Claúdia; Duarte, Raquel

2013-01-01

Cerebral tuberculomas are a rare and serious form of tuberculosis (TB) due to the haematogenous spread of Mycobacterium Tuberculosis (MT). Symptoms and radiologic features are nonspecific, leading sometimes to misdiagnosis. Anti-TB drugs are essential for the successful treatment of cerebral tuberculomas but there is no agreement regarding the duration of therapy. The authors present a case of a 55 years old male, presented to the emergency room with sudden onset of diplopia. Cerebral computerized tomography revealed multiple brain lesions, with contrast enhancement and peri-lesional oedema. The patient was HIV negative and because of previous malignancy the first suspicion was metastatic disease. Cultural exam of the bronchial wash showed MT sensitive to all first-line drugs. The patient started antituberculosis treatment with 4 drugs (HRZE) for 2 months, followed by maintenance therapy (HR). Treatment was prolonged for 24 months because at 12th and 18th months of treatment one of the brain lesions, although significantly smaller, still showed contrast enhancement. Even though it is not clear if contrast enhancement lesions represent active lesions or just inflammation, continuing treatment until total resolution of the tuberculomas is probably prudent. PMID:26029627

Molecular and epidemiological population-based integrative analysis of human and animal Mycobacterium bovis infections in a low-prevalence setting.

PubMed

Palacios, Juan José; Navarro, Yurena; Romero, Beatriz; Penedo, Ana; Menéndez González, Ángela; Pérez Hernández, M Dolores; Fernández-Verdugo, Ana; Copano, Francisca; Torreblanca, Aurora; Bouza, Emilio; Domínguez, Lucas; de Juan, Lucía; García-de-Viedma, Darío

2016-11-15

Human Mycobacterium bovis infections are considered to be due to reactivations, when involve elderly people, or to recent transmissions, when exposure is occupational. We determined the cause of M. bovis infections by genotyping M. bovis isolates in a population-based study integrating human and animal databases. Among the 1,586 tuberculosis (TB) cases in Asturias, Northern Spain (1,080,000 inhabitants), 1,567 corresponded to M. tuberculosis and 19 to M. bovis. The number of human isolates sharing genotype with cattle isolates was higher than expected (47%) for a setting with low prevalence of bovine TB and efficient control programs in cattle. The risk of exposure to infected animals was probable/possible in most of these matched cases (77.7%). Recent transmission was the likely explanation of most M. bovis infections in elderly people. A potential human-to-human transmission was found. Our study illustrates a model of collaboration between human and animal health professionals to provide a precise snapshot of the transmission of M. bovis in the human-animal interface. Copyright © 2016 Elsevier B.V. All rights reserved.

Mycobacterium bovis infection at the interface between domestic and wild animals in Zambia.

PubMed

Hang'ombe, Mudenda B; Munyeme, Musso; Nakajima, Chie; Fukushima, Yukari; Suzuki, Haruka; Matandiko, Wigganson; Ishii, Akihiro; Mweene, Aaron S; Suzuki, Yasuhiko

2012-11-14

In Zambia, the presence of bovine tuberculosis in both wild and domestic animals has long been acknowledged and mutual transmission between them has been predicted without any direct evidence. Elucidation of the circulating Mycobacterium bovis strains at wild and domestic animals interphase area in Zambia, where bovine tuberculosis was diagnosed in wildlife seemed to be important. A PCR identified 15 and 37 M. bovis isolates from lechwe and cattle, respectively. Spoligotype analysis revealed that M. bovis strains from lechwe and cattle in Kafue basin clustered into a major node SB0120, where isolates outside the Kafue basin clustered into different nodes of SB0131 and SB0948. The comparatively higher variety of strains in cattle compared to lechwe elucidated by Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeats analyses are consistent with cattle being the probable source of M. bovis in wild and domestic animals interphase area in Zambia. These results provide strong evidence of M. bovis strains transfer between cattle and lechwe, with the latter having developed into a sylvatic reservoir host.

Mycobacterium bovis infection at the interface between domestic and wild animals in Zambia

PubMed Central

2012-01-01

Background In Zambia, the presence of bovine tuberculosis in both wild and domestic animals has long been acknowledged and mutual transmission between them has been predicted without any direct evidence. Elucidation of the circulating Mycobacterium bovis strains at wild and domestic animals interphase area in Zambia, where bovine tuberculosis was diagnosed in wildlife seemed to be important. Results A PCR identified 15 and 37 M. bovis isolates from lechwe and cattle, respectively. Spoligotype analysis revealed that M. bovis strains from lechwe and cattle in Kafue basin clustered into a major node SB0120, where isolates outside the Kafue basin clustered into different nodes of SB0131 and SB0948. The comparatively higher variety of strains in cattle compared to lechwe elucidated by Mycobacterial Interspersed Repetitive Units–Variable Number Tandem Repeats analyses are consistent with cattle being the probable source of M. bovis in wild and domestic animals interphase area in Zambia. Conclusions These results provide strong evidence of M. bovis strains transfer between cattle and lechwe, with the latter having developed into a sylvatic reservoir host. PMID:23151267

Familial transmission of leprosy in post-war Britain--discrimination and dissent.

PubMed

Gill, A L; Gill, G V; Beeching, N J

2008-05-01

A Polish immigrant, who was resident in the United Kingdom (UK), presented with lepromatous leprosy and was detained in two hospitals against his wishes in the late 1940s. The public reaction to his diagnosis was remarkable, with street riots and questions in the Houses of Parliament about 'this leper'. His wife was persecuted and had to change her name. The index patient died of tuberculosis during enforced isolation in hospital, and several years later his daughter (who had never left the UK) presented with a left median nerve palsy and probable lepromatous dactylitis of the left third finger, eventually requiring amputation and prolonged dapsone treatment. Her disease resolved slowly but completely. We believe these two familial cases represent the first documented episode of autochthonous leprosy transmission in the UK since the early 1920s. They also demonstrate the ability of this disease to engender fear, dissent and discrimination amongst the public. Parallels are drawn with reactions to the cholera epidemics in nineteenth century Britain, and to HIV/AIDS, SARS and multi-drug resistant tuberculosis in more recent times.

Lupus and leprosy: beyond the coincidence.

PubMed

Ribeiro, F M; Gomez, V E; Albuquerque, E M N; Klumb, E M; Shoenfeld, Y

2015-02-01

Systemic lupus erythematous (SLE) is an autoimmune disease that presents an increased susceptibility to infections which may trigger reactivation. Disease flares have been mostly associated with parvovirus B19, cytomegalovirus, EBV and Mycobacterium tuberculosis infections, but it is probable that many other agents may also induce innate and adaptive immune system stimulation including the production of autoantibodies as ANA, anti nDNA and anti-ß2-GPI mainly in lepromatous leprosy. Mycobacterium leprae not only may determine symptoms that mimic lupus flares, including autoantibodies production, but could also act as a trigger for lupus reactivation; however, its association is still not fully explored. As demonstrated for tuberculosis, it is quite possible that molecular mimicry may also be involved in the interface of these two diseases. Some studies reported shared epitopes among idiotypes derived from 8E7 and TH9 lepromatous antibodies and those obtained from SLE patients, and it could partially explain the triggering phenomenon of SLE caused by M. leprae. We report and discuss three Brazilian patients whose disease was inactive and presented disease flares concurrently with the diagnosis of leprosy.

Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.

PubMed

Guiastrennec, Benjamin; Ramachandran, Geetha; Karlsson, Mats O; Kumar, A K Hemanth; Bhavani, Perumal Kannabiran; Gangadevi, N Poorana; Swaminathan, Soumya; Gupta, Amita; Dooley, Kelly E; Savic, Radojka M

2017-12-16

This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4-7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P unfavorable ). Model-based simulation of optimized (P unfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure-response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines. © 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

[Efficacy of the treatment for latent tuberculosis infection and delayed reactivation of tuberculosis].

PubMed

Toyota, Makoto

2013-09-01

To evaluate the efficacy of treatment for latent tuberculosis infection and delayed reactivation of tuberculosis. During a large tuberculosis outbreak, 129 individuals who were in close contact with tuberculosis patients and subsequently tested strongly positive by the tuberculin skin test were followed up for 10 years after identification of the source case. Of the 129 individuals, 105 received treatment for latent tuberculosis infection for 6 months as per recommendation, while the remaining 24 did not receive treatment, because most of them were above 30 years of age and were therefore discouraged from receiving treatment, as was done in the earlier times in Japan. Of the 105 individuals, 5 (4.8%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 53 months. Of the 24 individuals who did not receive treatment for latent tuberculosis infection, 6 (25.0%) were newly diagnosed with tuberculosis, and the average duration from identification of the source case to reactivation of tuberculosis was 8.2 months. The risk of active tuberculosis was reduced by 81.0% with treatment for latent tuberculosis infection, compared with that without treatment. Delayed reactivation of tuberculosis was observed among patients treated with isoniazid for latent tuberculosis infection for 6 months.

Mycobacterial peritonitis: difference between non-tuberculous mycobacteria and Mycobacterium tuberculosis.

PubMed

Shu, C-C; Wang, J-T; Wang, J-Y; Yu, C-J; Lee, L-N

2012-03-01

Unlike tuberculous peritonitis, peritonitis due to non-tuberculous mycobacteria (NTM) has unclear clinical manifestations. This study aimed to clarify the clinical manifestations and laboratory results of NTM peritonitis and compare it to tuberculous peritonitis. This retrospective study was conducted from 2000 to 2008 in a medical centre in Taiwan. Patients with mycobacteria isolated from ascites were identified and compared according to causative pathogens (Mycobacterium tuberculosis or NTM). Those with NTM peritonitis were further classified into the 'probable' and 'possible' groups based on diagnostic evidence. Twenty-five patients with NTM peritonitis and 65 with tuberculous peritonitis were reviewed. Mycobacterium avium complex was the most common NTM pathogen (52%). There was no obvious difference between the 'probable' and 'possible' NTM peritonitis groups regarding age and laboratory data. Patients with NTM peritonitis and those with tuberculous peritonitis had no differences in age or gender but varied in symptoms and serum laboratory data. NTM peritonitis was 100% associated with underlying co-morbidities and had lower proportions of lymphocytes and albumin level in ascites. Twelve (48%) NTM peritonitis and 21 (32%) tuberculous peritonitis patients died during the 6-month follow-up. Anti-mycobacterial treatment, but not mycobacterial species, was correlated with better 6-month survival. In Taiwan, NTM is responsible for 28% of mycobacterial peritonitis cases, which have a poor prognosis if untreated. There are some differences in clinical manifestations between NTM and tuberculous peritonitis. NTM peritonitis should be considered in patients with peritonitis but without causative microorganisms identified other than NTM. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Revisiting tuberculous pleurisy: pleural fluid characteristics and diagnostic yield of mycobacterial culture in an endemic area

PubMed Central

Ruan, Sheng-Yuan; Chuang, Yu-Chung; Lin, Jou-Wei; Chien, Jung-Yien; Huang, Chun-Ta; Kuo, Yao-Wen; Lee, Li-Na; Yu, Chong-Jen J

2012-01-01

Background Tuberculous pleurisy is traditionally indicated by extreme lymphocytosis in pleural fluid and low yield of effusion culture. However, there is considerable inconsistency among previous study results. In addition, these data should be updated due to early effusion studies and advances in culture methods. Methods From January 2004 to June 2009, patients with tuberculous pleurisy were retrospectively identified from the mycobacteriology laboratories and the pathology and tuberculosis registration databases of two hospitals in Taiwan where tuberculosis is endemic. Pleural fluid characteristics and yields of mycobacterial cultures using liquid media were evaluated. Results A total of 382 patients with tuberculous pleurisy were identified. The median lymphocyte percentage of total cells in pleural fluids was 84% (IQR 64–95%) and 17% of cases had a lymphocyte percentage of <50%. The lymphocyte percentage was negatively associated with the probability of a positive effusion culture (OR 0.97; 95% CI 0.96 to 0.99). The diagnostic yields were 63% for effusion culture, 48% for sputum culture, 79% for the combination of effusion and sputum cultures, and 74% for histological examination of pleural biopsy specimens. Conclusion The degree of lymphocyte predominance in tuberculous pleurisy was lower than was previously thought. The lymphocyte percentage in pleural fluid was negatively associated with the probability of a positive effusion culture. With the implementation of a liquid culture method, the sensitivity of effusion culture was much higher than has been previously reported, and the combination of effusion and sputum cultures provided a good diagnostic yield. PMID:22436167

Novel Mutations in pncA Gene of Pyrazinamide Resistant Clinical Isolates of Mycobacterium tuberculosis.

PubMed

Kahbazi, Manijeh; Sarmadian, Hossein; Ahmadi, Azam; Didgar, Farshideh; Sadrnia, Maryam; Poolad, Toktam; Arjomandzadegan, Mohammad

2018-04-16

In clinical isolates of Mycobacterium tuberculosis (MTB), resistance to pyrazinamide occurs by mutations in any positions of the pncA gene (NC_000962.3) especially in nucleotides 359 and 374. In this study we examined the pncA gene sequence in clinical isolates of MTB. Genomic DNA of 33 clinical isolates of MTB was extracted by the Chelex100 method. The polymerase chain reactions (PCR) were performed using specific primers for amplification of 744 bp amplicon comprising the coding sequences (CDS) of the pncA gene. PCR products were sequenced by an automated sequencing Bioscience system. Additionally, semi Nested-allele specific (sNASP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods were carried out for verification of probable mutations in nucleotides 359 and 374. Sequencing results showed that from 33 MTB clinical isolates, nine pyrazinamide-resistant isolates have mutations. Furthermore, no mutation was detected in 24 susceptible strains in the entire 561 bp of the pncA gene. Moreover, new mutations of G→A at position 3 of the pncA gene were identified in some of the resistant isolates. Results showed that the sNASP method could detect mutations in nucleotide 359 and 374 of the pncA gene, but the PCR-RFLP method by the SacII enzyme could not detect these mutations. In conclusion, the identification of new mutations in the pncA gene confirmed the probable occurrence of mutations in any nucleotides of the pncA gene sequence in resistant isolates of MTB.

Contribution of microbiology in the diagnosis of tuberculosis in Castile and León (Spain): Findings of the GRUMICALE 2013 study.

PubMed

López-Medrano, Ramiro; Nebreda-Mayoral, Teresa; Brezmes-Valdivieso, M Fé; García-de Cruz, Susana; Nogueira-González, Begoña; Sánchez-Arroyo, Rafael; Tinajas-Puertas, Almudena; Gutiérrez-Zufiaurre, Nieves; Labayru-Echeverría, Cristina; Hernando-Real, Susana; López-Urrutia, Luis; Rivero-Lezcano, Octavio; Ullivarri-Francia, Belén; Rodríguez-Tarazona, Raquel; Antolín-Ayala, Isabel

2018-03-01

A retrospective study was conducted by collecting microbiological tuberculosis (TB) data in Castile and León during the year 2013 in order to determine the incidence and distribution of TB, and resistance to the tuberculostatic drug, and compare them with the epidemiological data provided by the Department of Epidemiological Surveillance (SIVE). Microbiologists of the 14 hospitals of the Castile and León public health network (GRUMICALE) collected epidemiological, microbiological, and management data from the Microbiology laboratories in the community during the year 2013. A single isolate of Mycobacterium tuberculosis complex (MTC) per patient was considered. The study included a total of 270 MTC isolates (an incidence rate of 11.63 cases/100,000 inhab./year). A total of 288 cases of TB (11.43 cases/100,000 inhab. year) were recovered using epidemiological data, which included 243 confirmed, 29 suspected, and 16 as probable cases. Pulmonary TB was predominant, followed a long way off by the pleural TB and the remaining locations. A total of 27,620 samples were processed for mycobacterial detection. Mycobacterial growth was observed in 3.46% of automated fluid cultures, and 50.37% were positive by direct staining of the smear. Resistance to one tuberculostatic drug, mostly to isoniazid, was observed in 16 (5.92%) isolates of Mycobacterium tuberculosis (MT). The province with greater incidence and number of isolates was León (24.23 cases/100,000 inhab./year), with the highest being observed in El Bierzo health area (30.46 cases/100,000 inhab./year). An adequate collection of microbiological information is essential to determine the epidemiology of TB in our region. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

CD4+ CD25high Foxp3+ regulatory T cells downregulate human Vδ2+ T-lymphocyte function triggered by anti-CD3 or phosphoantigen

PubMed Central

Mahan, C Scott; Thomas, Jeremy J; Boom, W Henry; Rojas, Roxana E

2009-01-01

Vδ2+ T cells, the major circulating T-cell receptor-γδ-positive (TCR-γδ+) T-cell subset in healthy adults, are involved in immunity against many microbial pathogens including Mycobacterium tuberculosis. Vδ2+ T cells recognize small phosphorylated metabolites (phosphoantigens), expand in response to whole M. tuberculosis bacilli, and complement the protective functions of CD4+ T cells. CD4+ CD25high Foxp3+ T cells (Tregs) comprise 5–10% of circulating T cells and are increased in patients with active tuberculosis (TB). We investigated whether, in addition to their known role in suppressing TCR-αβ+ lymphocytes, Tregs suppress Vδ2+ T-cell function. We found that depletion of Tregs from peripheral blood mononuclear cells increased Vδ2+ T-cell expansion in response to M. tuberculosis (H37Ra) in tuberculin-skin-test-positive donors. We developed a suppression assay with fluorescence-activated cell sorting-purified Tregs and Vδ2+ T cells by coincubating the two cell types at a 1 : 1 ratio. The Tregs partially suppressed interferon-γ secretion by Vδ2+ T cells in response to anti-CD3 monoclonal antibody plus interleukin-2 (IL-2). In addition, Tregs downregulated the Vδ2+ T-cell interferon-γ responses induced by phosphoantigen (BrHPP) and IL-2. Under the latter conditions there was no TCR stimulus for Tregs and therefore IL-2 probably triggered suppressor activity. Addition of purified protein derivative (PPD) increased the suppression of Vδ2+ T cells, suggesting that PPD activated antigen-specific Tregs. Our study provides evidence that Tregs suppress both anti-CD3 and antigen-driven Vδ2+ T-cell activation. Antigen-specific Tregs may therefore contribute to the Vδ2+ T-cell functional deficiencies observed in TB. PMID:19019089

An Evaluation of Culture Results during Treatment for Tuberculosis as Surrogate Endpoints for Treatment Failure and Relapse

PubMed Central

Phillips, Patrick P. J.; Fielding, Katherine; Nunn, Andrew J.

2013-01-01

It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial. PMID:23667677

An evaluation of culture results during treatment for tuberculosis as surrogate endpoints for treatment failure and relapse.

PubMed

Phillips, Patrick P J; Fielding, Katherine; Nunn, Andrew J

2013-01-01

It is widely acknowledged that new regimens are urgently needed for the treatment of tuberculosis. The primary endpoint in the Phase III trials is a composite outcome of failure at the end of treatment or relapse after stopping treatment. Such trials are usually both long and expensive. Valid surrogate endpoints measured during or at the end of treatment could dramatically reduce both the time and cost of assessing the effectiveness of new regimens. The objective of this study was to evaluate sputum culture results on solid media during treatment as surrogate endpoints for poor outcome. Data were obtained from twelve randomised controlled trials conducted by the British Medical Research Council in the 1970s and 80s in East Africa and East Asia, consisting of 6974 participants and 49 different treatment regimens. The month two culture result was shown to be a poor surrogate in East Africa but a good surrogate in Hong Kong. In contrast, the month three culture was a good surrogate in trials conducted in East Africa but not in Hong Kong. As well as differences in location, ethnicity and probable strain of Mycobacteria tuberculosis, Hong Kong trials more often evaluated regimens with rifampicin throughout and intermittent regimens, and patients in East African trials more often presented with extensive cavitation and were slower to convert to culture negative during treatment. An endpoint that is a summary measure of the longitudinal profile of culture results over time or that is able to detect the presence of M. tuberculosis later in treatment is more likely to be a better endpoint for a phase II trial than a culture result at a single time point and may prove to be an acceptable surrogate. More data are needed before any endpoint can be used as a surrogate in a confirmatory phase III trial.

[Analysis of drug resistance to antituberculosis drugs of the first time retreated pulmonary tuberculosis patients in Shanghai].

PubMed

Fan, Yu-mei; Xiao, He-ping; Mei, Jian

2006-10-01

To investigate antituberculosis drug resistance among the first time retreated pulmonary tuberculosis patients in Shanghai, and therefore to provide evidence for establishing retreatment regimen. Analysis was conducted retrospectively on drug susceptibility tests to isoniazid, rifampin, streptomycin, ethambutol and para-aminosalicylates of the first time retreated pulmonary tuberculosis patients with a positive sputum culture in Shanghai Center for Disease Control from January 2002 to December 2004. The total drug resistance rate was 39.6%. The drug resistance rate in male and female patients was 38.5% and 44.4% respectively, the difference being not significant. The drug resistance rate in the young age group, the middle age group and the old age group were 50.0%, 41.6% and 34.6% respectively, the difference being not significant. The total drug resistance rates in the treatment failure group with standard initial chemotherapy and in the relapse group with standard regimen were both higher than in the relapse group with non-standard regimen (70.0%, 47.5%, 28.2%). So do the drug resistance rates of more than two drugs (70.0%, 18.3%, 6.4%). The multi-drug resistance rate of the failures with standard regimen was 70.0%, much higher than the relapses with standard regimen and the relapses with non-standard regimen. In relapses with non-standard initial therapy, the drug resistance rate of patients who received medications > or = 12 months was 55.0%, significantly higher than those treated for 1 - 5 months (13.0%). The drug resistance rate of patients who were treated with one to two drugs was lower than those treated with > or = 3 drugs, but no significant difference was observed (24.4% and 30.8%). Drug resistance rate varies in different types of the first time retreated pulmonary tuberculosis patients due to the history of drug use, which indicates that the current standard retreatment regimen is probably ineffective for some patients.

RUTI: a new chance to shorten the treatment of latent tuberculosis infection.

PubMed

Cardona, Pere-Joan

2006-01-01

Treatment of latent tuberculosis infection (LTBI) requires a long period of chemotherapy (9 months), which makes treatment-compliance extremely difficult. Current knowledge of latent bacilli and of the lesions with which they are associated suggests that these bacilli survive in granulomas with a central necrotic core and an outermost layer of foamy macrophages (FM) that represent an important immunosuppressive barrier. The presence of FM, which is especially strong in mice, explains not only the kinetics of the drainage of dead bacilli, debris and surfactant, but also how latent bacilli can escape from the granuloma and re-grow in the periphery, particularly in the alveolar spaces where they can disseminate easily. RUTI, a therapeutic vaccine made of detoxified, fragmented Mycobacterium tuberculosis cells, delivered in liposomes, was used to assess its effectiveness in a short period of chemotherapy (1 month). The rationale of this therapy was first to take advantage of the bactericidal properties of chemotherapy to kill active growing bacilli, eliminate the outermost layer of FM and reduce local inflammatory responses so as to avoid the predictable Koch phenomenon caused by M. tuberculosis antigens when given therapeutically. After chemotherapy, RUTI can be inoculated to reduce the probability of regrowth of the remaining latent bacilli. RUTI has already demonstrated its efficacy in controlling LTBI in experimental models of mice and guinea-pigs after a short period of chemotherapy; these experiments in animals showed the induction of a mixed Th1/Th2/Th3, polyantigenic response with no local or systemic toxicity. Local accumulation of specific CD8 T cells and a strong humoral response are characteristic features of RUTI that explain its protective properties; these are particular improvements when compared with BCG, although the regulatory response to RUTI may also be an important advantage. Further experiments using bigger animals (goats and mini-pigs) will provide more data on the efficacy of RUTI before starting phase I clinical trials.

Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs.

PubMed

Zumla, Alimuddin; Abubakar, Ibrahim; Raviglione, Mario; Hoelscher, Michael; Ditiu, Lucica; McHugh, Timothy D; Squire, S Bertel; Cox, Helen; Ford, Nathan; McNerney, Ruth; Marais, Ben; Grobusch, Martin; Lawn, Stephen D; Migliori, Giovanni-Battista; Mwaba, Peter; O'Grady, Justin; Pletschette, Michel; Ramsay, Andrew; Chakaya, Jeremiah; Schito, Marco; Swaminathan, Soumya; Memish, Ziad; Maeurer, Markus; Atun, Rifat

2012-05-15

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.

Tuberculosis of the head and neck – epidemiological and clinical presentation

PubMed Central

Bruzgielewicz, Antoni; Osuch-Wójcikewicz, Ewa; Niemczyk, Kazimierz; Chmielewski, Rafał

2013-01-01

Introduction The aim of our retrospective study was to review the clinical and epidemiological presentation of head and neck tuberculosis. Material and methods We analyzed the history of 73 patients with head and neck tuberculosis hospitalized in the Department of Otolaryngology, Medical University of Warsaw, between 1983 and 2009. Results We found that 26 (35.6%) patients presented with lymph node tuberculosis, 20 (27.4%) with laryngeal tuberculosis, 10 (13.7%) with oropharyngeal tuberculosis, 9 (12.3%) with salivary gland tuberculosis, 3 (4.1%) with tuberculosis of paranasal sinuses, 3 (4.1%) with aural tuberculosis, and 2 (2.7%) with skin tuberculosis in the head and neck region. Within the group of patients with lymph node tuberculosis in 15 cases there were infected lymph nodes of the 2nd and 3rd cervical region and in 11 infected lymph nodes of the 1st cervical region. In 5 cases of laryngeal tuberculosis there was detected coexistence of cancer. Oropharyngeal tuberculosis in 7 cases was localized in tonsils, where in 1 case coexisting cancer was diagnosed. Chest X-ray was performed in all cases and pulmonary tuberculosis was identified in 26 (35.6%) cases. Conclusions We conclude that tuberculosis still remains a problem and must be taken into consideration in the diagnostic process. The coincidence of tuberculosis and cancer is remarkable in the head and neck region. PMID:25624854

Protecting health care workers from tuberculosis in China: a review of policy and practice in China and the United States.

PubMed

Chai, Shua J; Mattingly, Daniel C; Varma, Jay K

2013-01-01

Tuberculosis causes >1.7 million deaths worldwide each year and is frequently transmitted in hospitals. Outbreaks of multidrug-resistant tuberculosis have led to illness and death among health care workers (HCWs) in many countries. Some countries, such as the United States, implemented occupational health policies that substantially reduced tuberculosis rates among HCWs. Inadequate tuberculosis infection control in China may contribute to its high burden of tuberculosis and multidrug-resistant tuberculosis, which are both the second highest worldwide. Occupational health policies in China for tuberculosis control can be strengthened. We reviewed the development and content of tuberculosis infection control policies in the United States and China. Sources included published academic literature, Chinese Ministry of Health policies, US government agency reports, legal databases, personal observations of hospitals, review of internet discussion sites, and discussions with HCWs and health care and law experts. In the United States, slow acceptance of the tuberculosis problem in HCWs resulted in decades of inaction. Tuberculosis infection control policies, based mostly on expert opinion, were implemented only after tuberculosis resurged in the 1980s. Effective evidence-based policies were developed only after multiple cycles of policy implementation, evaluation and revision. These policies have now substantially reduced occupational tuberculosis. In China, tuberculosis has not been formally recognized as an occupational disease, and data regarding the burden in HCWs are sparse. Vagueness of current labour laws and suboptimal alignment of infection control authority and expertise result in varied and sometimes absent protection of HCWs against tuberculosis. Formal evaluations of occupational tuberculosis policies have not been reported. By collecting data on its current HCW tuberculosis burden and infection control practices, refining policies, continually evaluating its policies based on accumulated evidence and rapidly identifying unsuspected tuberculosis cases, China can develop a more comprehensive strategy to ensure the health of HCWs and reduce transmission of tuberculosis and multidrug-resistant tuberculosis.

Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis*

PubMed Central

Rahman, Md. Aejazur; Sobia, Parveen; Dwivedi, Ved Prakash; Bhawsar, Aakansha; Singh, Dhiraj Kumar; Sharma, Pawan; Moodley, Prashini; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

2015-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many Gram-positive bacteria, but its function in M. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild type M. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence. PMID:25847237

What We Know About Tuberculosis Transmission: An Overview.

PubMed

Churchyard, Gavin; Kim, Peter; Shah, N Sarita; Rustomjee, Roxana; Gandhi, Neel; Mathema, Barun; Dowdy, David; Kasmar, Anne; Cardenas, Vicky

2017-11-03

Tuberculosis remains a global health problem with an enormous burden of disease, estimated at 10.4 million new cases in 2015. To stop the tuberculosis epidemic, it is critical that we interrupt tuberculosis transmission. Further, the interventions required to interrupt tuberculosis transmission must be targeted to high-risk groups and settings. A simple cascade for tuberculosis transmission has been proposed in which (1) a source case of tuberculosis (2) generates infectious particles (3) that survive in the air and (4) are inhaled by a susceptible individual (5) who may become infected and (6) then has the potential to develop tuberculosis. Interventions that target these events will interrupt tuberculosis transmission and accelerate the decline in tuberculosis incidence and mortality. The purpose of this article is to provide a high-level overview of what is known about tuberculosis transmission, using the tuberculosis transmission cascade as a framework, and to set the scene for the articles in this series, which address specific aspects of tuberculosis transmission. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Joint modeling of longitudinal data and discrete-time survival outcome.

PubMed

Qiu, Feiyou; Stein, Catherine M; Elston, Robert C

2016-08-01

A predictive joint shared parameter model is proposed for discrete time-to-event and longitudinal data. A discrete survival model with frailty and a generalized linear mixed model for the longitudinal data are joined to predict the probability of events. This joint model focuses on predicting discrete time-to-event outcome, taking advantage of repeated measurements. We show that the probability of an event in a time window can be more precisely predicted by incorporating the longitudinal measurements. The model was investigated by comparison with a two-step model and a discrete-time survival model. Results from both a study on the occurrence of tuberculosis and simulated data show that the joint model is superior to the other models in discrimination ability, especially as the latent variables related to both survival times and the longitudinal measurements depart from 0. © The Author(s) 2013.

Nontuberculous Mycobacteria, Zambia

PubMed Central

van der Sande, Marianne A.B.; de Graaff, Cas S.; Parkinson, Shelagh; Verbrugh, Henri A.; Petit, Pieter L.C.; van Soolingen, Dick

2009-01-01

Clinical relevance of nontuberculous mycobacteria (NTM) isolated from 180 chronically ill patients and 385 healthy controls in Zambia was evaluated to examine the contribution of these isolates to tuberculosis (TB)–like disease. The proportion of NTM-positive sputum samples was significantly higher in the patient group than in controls; 11% and 6%, respectively (p<0.05). NTM-associated lung disease was diagnosed for 1 patient, and a probable diagnosis was made for 3 patients. NTM-positive patients and controls were more likely to report vomiting and diarrhea and were more frequently underweight than the NTM-negative patients and controls. Chest radiographs of NTM-positive patients showed deviations consistent with TB more frequently than those of controls. The most frequently isolated NTM was Mycobacterium avium complex. Multiple, not previously identified mycobacteria (55 of 171 NTM) were isolated from both groups. NTM probably play an important role in the etiology of TB-like diseases in Zambia. PMID:19193268

38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

38 CFR 3.375 - Determination of inactivity (complete arrest) in tuberculosis.

Code of Federal Regulations, 2014 CFR

2014-07-01

... inactivity (complete arrest) in tuberculosis. 3.375 Section 3.375 Pensions, Bonuses, and Veterans' Relief...) in tuberculosis. (a) Pulmonary tuberculosis. A veteran shown to have had pulmonary tuberculosis will...) Nonpulmonary disease. Determination of complete arrest of nonpulmonary tuberculosis requires absence of...

Global fund financing of tuberculosis services delivery in prisons.

PubMed

Lee, Donna; Lal, S S; Komatsu, Ryuichi; Zumla, Alimuddin; Atun, Rifat

2012-05-15

Despite concerted efforts to scale up tuberculosis control with large amounts of international financing in the last 2 decades, tuberculosis continues to be a social issue affecting the world's most marginalized and disadvantaged communities. This includes prisoners, estimated at about 10 million globally, for whom tuberculosis is a leading cause of mortality and morbidity. The Global Fund to Fight AIDS, Tuberculosis and Malaria has emerged as the single largest international donor for tuberculosis control, including funding support in delivering tuberculosis treatment for the confined population. The Global Fund grants database, with an aggregate approved investment of $21.7 billion in 150 countries by the end of 2010, was reviewed to identify tuberculosis and human immunodeficiency virus/tuberculosis grants and activities that monitored the delivery of tuberculosis treatment and support activities in penitentiary settings. The distribution and trend of number of countries with tuberculosis prison support was mapped by year, geographic region, tuberculosis or multidrug-resistant tuberculosis burden, and prison population rate. We examined the types of grant recipients managing program delivery, their performance, and the nature and range of services provided. Fifty-three of the 105 countries (50%) with Global Fund-supported tuberculosis programs delivered services within prison settings. Thirty-two percent (73 of 228) of tuberculosis grants, representing $558 million of all disbursements of Global Fund tuberculosis support by the end of 2010, included output indicators related to tuberculosis services delivered in prisons. Nearly two-thirds (64%) of these grants were implemented by governments, with the remaining by civil society and other partners. In terms of services, half (36 of 73) of grants provided diagnosis and treatment and an additional 27% provided screening and monitoring of tuberculosis for prisoners. The range of services tracked was limited in scope and scale, with 69% offering only 1 type of service and less than one-fifth offering 2 types of service. This study is a preliminary attempt to examine Global Fund investments in the fight against tuberculosis in prison settings. Tuberculosis services delivered in prisons have increased in the last decade, but systematic information on funding levels and gaps, services provided, and cost-effective delivery models for delivering tuberculosis services in prisons are lacking.

A proposed national strategy for tuberculosis vaccine development.

PubMed

Ginsberg, A M

2000-06-01

The global tuberculosis epidemic causes approximately 5% of deaths worldwide. Despite recent concerted and largely successful tuberculosis control efforts, the incidence of tuberculosis in the United States remains 74-fold higher than the stated elimination goal of <1 case per million population by the year 2010. Current bacille Calmette-Guérin vaccines, although efficacious in preventing extrapulmonary tuberculosis in young children, have shown widely variable efficacy in preventing adult pulmonary tuberculosis, confound skin test screening, and are not recommended for use in the United States. The Advisory Council for Elimination of Tuberculosis recently stated that tuberculosis would not be eliminated from the United States without a more effective vaccine. Recent scientific advances have created unprecedented opportunity for tuberculosis vaccine development. Therefore, members of the broad tuberculosis research and control communities have recently created and proposed a national strategy, or blueprint, for tuberculosis vaccine development, which is presented here.

Trends in silicosis prevalence and the healthy worker effect among gold miners in South Africa: a prevalence study with follow up of employment status.

PubMed

Knight, David; Ehrlich, Rodney; Fielding, Katherine; Jeffery, Hannah; Grant, Alison; Churchyard, Gavin

2015-12-18

Given the intimate association between silicosis and tuberculosis, understanding the epidemiology of the South African gold mining industry silicosis epidemic is essential to current initiatives to control both silicosis and tuberculosis in this population, one of the most heavily affected globally. The study's objectives were to compare the prevalence of silicosis among working black gold miners in South Africa during 2004-2009 to that of previous studies, including autopsy series, and to analyse the influence of silicosis and/or tuberculosis on exiting employment. Routine chest radiographs from a cohort of gold miners were read for silicosis by an experienced reader (I), and a subset re-read by a B-trained reader (II). Two methods of presenting the readings were used. Additionally, with baseline status of silicosis and previous or active tuberculosis as predictors, survival analysis examined the probability of exiting the workforce for any reason during 2006-2011. Reader I read 11 557 chest radiographs and reader II re-read 841. Overall, silicosis prevalence (ILO ≥ 1/0: 5.7 and 6.2% depending on reader method) was similar to the age adjusted prevalence found in a large study in 1984 (5.0%). When comparison was restricted to a single mine shaft previously studied in 2000, a decline in prevalence (ILO ≥ 1/1) was suggested for one of the reading methods (duration adjusted 20.5% vs. 13.0% in the current study). These findings are discordant with a long-term rising autopsy prevalence of silicosis over this period. Overall, relative to miners with neither disease, the adjusted hazard ratio for exiting employment during the follow-up period was 1.54 for baseline silicosis [95% confidence interval (CI) 1.17, 2.04], 1.71 for tuberculosis (95% CI 1.51, 1.94) and 1.53 for combined disease (95% CI 1.20, 1.96). This study found, a) there was no significant decline in overall silicosis prevalence among working black miners in the South African gold mining industry between 1984 and 2004-2009, and b) a possible decline at one mine shaft more recently. In the absence of evidence of declining respirable silica concentrations between the 1980s and 2000s, the trends found are plausibly due to a healthy worker survivor effect, which may be accelerating.

First case of sexual transmitted asymptomatic female genital tuberculosis from spousal epididymal tuberculosis diagnosed by active screening.

PubMed

Kimura, Muneyoshi; Araoka, Hideki; Baba, Hiromi; Okada, Chikako; Murase, Yoshiro; Takaki, Akiko; Mitarai, Satoshi; Yoneyama, Akiko

2018-06-04

Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had been infected with active genital tuberculosis via sexual intercourse with her husband who had epididymal tuberculosis. Vaginal swab culture yielded Mycobacterium tuberculosis. Furthermore, whole genome sequencing revealed that the two causative isolates were genetically identical. To the best of our knowledge, this is the first report on sexual transmission of genital tuberculosis from a man to an asymptomatic woman detected by active screening for genital tuberculosis and molecular analysis, including whole-genome-sequencing. Active screening for genital tuberculosis in the female partner should be considered soon after diagnosis of male genital tuberculosis even when the female partner is asymptomatic. Copyright © 2018. Published by Elsevier Ltd.

[Increased IL-4 production in response to virulent Mycobacterium tuberculosis in tuberculosis patients with advanced disease].

PubMed

Ordway, Diane J; Martins, Marta S; Costa, Leonor M; Freire, Mónica S; Arroz, Maria J; Dockrell, Hazel M; Ventura, Fernando A

2005-01-01

The study was designed to compare immune responses to Mycobacterium tuberculosis bacilli and antigens in healthy Portuguese subjects and pulmonary tuberculosis patients (TB), and to correlate immune status with clinical severity of tuberculosis disease. PBMC were cultured and stimulated with live and killed M. tuberculosis H37Rv and purified protein derivative (PPD) and lymphoproliferation and production of IFN-gamma and IL-5/IL-4 by these cultures were evaluated by the use of ELISA and multi-parameter flow cytometry. PBMC from 30 tuberculosis patients demonstrated significantly reduced amounts of proliferation and IFN-gamma when stimulated with live M. tuberculosis compared the control group. Of 15 tuberculosis patients tested for intracellular IL-4 following stimulation with M. tuberculosis, 7 showed greatly increased IL-4 production in CD8+ and gammadelta+ T cells. Tuberculosis patients demonstrated an increase of intracellular IL-4 after PBMC were stimulated with live M. tuberculosis in the CD4+ phenotype, but more notably in CD8+ and gammadelta TCR+ subsets. Increased production of IL-4 in tuberculosis patients was primarily in individuals with advanced involvement of lung parenchymal with high bacterial loads in sputum. These results suggest that an alteration in type 1 and type 2 cytokine balance can occur in patients with tuberculosis at an advanced clinical stage of disease.

[Pachymeningitis].

PubMed

Fain, O; Mekinian, A

2017-09-01

Pachymeningitis is a fibrosing and inflammatory process, which involves the dura mater. Some pachymeningitis are cranial and induce headaches and cranial nerve palsies. Others are spinal and responsible for nerve roots or spinal cord compression. MRI shows contrast enhancement thickening of the dura mater. Etiologies are infectious (syphilis, tuberculosis, etc.) or inflammatory (sarcoidosis, granulomatosis with polyangiitis, IgG4-related disease, idiopathic). Corticosteroids are the main treatment. The use of immunosuppressive drugs or rituximab is yet to be determined and probably adapted to each etiology. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Pulmonary nocardiosis in a 3-year-old child

PubMed Central

Holdaway, M. D.; Kennedy, J.; Ashcroft, T.; Kay-Butler, J. J.

1967-01-01

Until 1960, 179 cases of infection with Nocardia asteroides had been described in the world literature. Seventeen cases in children were reported by 1963. The organism is a common saprophyte in nature with probably a world-wide distribution. Infection can be primary but is more common in patients with underlying malignancy, auto-immune disease or preceding tuberculosis. Sulphonamides, particularly sulphadiazine, are the drugs of choice in treatment; the value of antibiotics is less clearly established. The indications for surgical treatment have not yet been defined. We record a further case of primary pulmonary nocardiosis in a 3-year-old child. Images PMID:6035802

The Socioeconomic Factors and the Indigenous Component of Tuberculosis in Amazonas

PubMed Central

2016-01-01

Despite the availability of tuberculosis prevention and control services throughout Amazonas, high rates of morbidity and mortality from tuberculosis remain in the region. Knowledge of the social determinants of tuberculosis in Amazonas is important for the establishment of public policies and the planning of effective preventive and control measures for the disease. To analyze the relationship of the spatial distribution of the incidence of tuberculosis in municipalities and regions of Amazonas to the socioeconomic factors and indigenous tuberculosis component, from 2007 to 2013. An ecological study was conducted based on secondary data from the epidemiological surveillance of tuberculosis. A linear regression model was used to analyze the relationship of the annual incidence of tuberculosis to the socioeconomic factors, performance indicators of health services, and indigenous tuberculosis component. The distribution of the incidence of tuberculosis in the municipalities of Amazonas was positively associated with the Gini index and the population attributable fraction of tuberculosis in the indigenous peoples, but negatively associated with the proportion of the poor and the unemployment rate. The spatial distribution of tuberculosis in the different regions of Amazonas was heterogeneous and closely related with the socioeconomic factors and indigenous component of tuberculosis. PMID:27362428

Association of tuberculosis with multimorbidity and social networks

PubMed Central

Valenzuela-Jiménez, Hiram; Manrique-Hernández, Edgar Fabian; Idrovo, Alvaro Javier

2017-01-01

ABSTRACT The combination of tuberculosis with other diseases can affect tuberculosis treatment within populations. In the present study, social network analysis of data retrieved from the Mexican National Epidemiological Surveillance System was used in order to explore associations between the number of contacts and multimorbidity. The node degree was calculated for each individual with tuberculosis and included information from 242 contacts without tuberculosis. Multimorbidity was identified in 49.89% of individuals. The node degrees were highest for individuals with tuberculosis + HIV infection (p < 0.04) and lowest for those with tuberculosis + pulmonary edema (p < 0.07). Social network analysis should be used as a standard method for monitoring tuberculosis and tuberculosis-related syndemics. PMID:28125153

Identification of risk factors for extrapulmonary tuberculosis.

PubMed

Yang, Zhenhua; Kong, Ying; Wilson, Frank; Foxman, Betsy; Fowler, Annadell H; Marrs, Carl F; Cave, M Donald; Bates, Joseph H

2004-01-15

The proportion of extrapulmonary tuberculosis cases in the United States has increased from 16% of tuberculosis cases, in 1991, to 20%, in 2001. To determine associations between the demographic, clinical, and life style characteristics of patients with tuberculosis and the occurrence of extrapulmonary tuberculosis, a retrospective case-control study was conducted. This study included 705 patients with tuberculosis, representing 98% of the culture-proven cases of tuberculosis in Arkansas from 1 January 1996 through 31 December 2000. A comparison between 85 patients with extrapulmonary tuberculosis (case patients) and 620 patients with pulmonary tuberculosis (control patients) showed women (OR, 1.98; 95% CI, 1.25-3.13), non-Hispanic blacks (OR, 2.38; 95% CI, 1.42-3.97), and HIV-positive persons (OR, 4.93; 95% CI, 1.95-12.46) to have a significantly higher risk for extrapulmonary tuberculosis than men, non-Hispanic whites, and HIV-negative persons. This study expands the knowledge base regarding the epidemiology of extrapulmonary tuberculosis and enhances our understanding of the relative contribution of host-related factors to the pathogenesis of tuberculosis.

[Education and training for tuberculosis in medical schools and in hospitals].

PubMed

1998-01-01

The recent decrease of the number of tuberculosis patients in Japan, by the economical development and the establishment of standard regimen with INH, RFP, SM/EB and PZA, have brought decrease of concern to tuberculosis not only in the masses but also in the medical personnel, and the worsening of the medical economy by the advancing of the ages in the nations is forcing to close the tuberculosis wards. On the other hand, the recent situation of tuberculosis in Japan, such as the increase of HIV infection, the additional inflow of the foreign tuberculosis patients, the increase of tuberculosis patients in the younger population by the increase of mass-infection, and recent progress of the maldistributions of the tuberculosis patients realized the efforts of the education and training for tuberculosis to the medical students and medical personnel, even in the increase of items that they must learn. The Japanese Society for Tuberculosis set a Symposium "How Tuberculosis be Taught in Medical Education" in 1986. It will be worth to have Round Table Discussion concerning to the education and training for the tuberculosis, after 11 years. Doctor Sato from Nagoya City University reported as follows. To survey the actual condition of tuberculosis education before graduation, a nationwide medical school questionnaire survey was carried out. Answers were received from 80 institutions (100%). It was found that 58 institutions (72%) lacked tuberculosis ward. When the results from this survey, in the area of medical school lecture, were compared to the previous survey of 11 years ago, it showed a decrease in the time and frequency that tuberculosis covered during lecture. This tendency was clearly seen, with the exception of internal medicine, in surgery, in plastic surgery, in urology and in public health. Furthermore, medical schools lacking tuberculosis ward were found to have a lesser percentage of clinical lectures and bed-side teaching when compared to ones with tuberculosis ward. He concluded that in the medical school without tuberculosis ward, the tuberculosis education is virtually impossible, and it is necessary to carry out with hospitals that have tuberculosis ward. Doctor Honda from Sapporo Medical University reported that in the University Hospital, the Third Department of Internal Medicine holds 6 isolation sick-beds for tuberculosis (3 for men and 3 for women) which containing an exclusive day room and bath room, in 52 beds alloted to their department. They always give 2 or 3 lectures about tuberculosis to medical students and also give bed-side teaching using these beds. He concluded education on tuberculosis is necessary for the protection of doctor's delay, and the tuberculosis ward in the university is very useful in the education of tuberculosis to medical students, even the economical efficiency of these beds are low. Doctor Nakabayashi from Sapporo National Hospital reported that his hospital is a general hospital with 513 beds but has no tuberculosis-bed, and that this hospital is combined with Hokkaido Cancer Center and 91.7% of in-patients of pulmonary division are lung cancer and one or two residents are trained in pulmonary division by 6 months rotation. He also reported that in his hospital, 18 mycobacteria positive cases were treated through 1996, however the training for tuberculosis to residents are mainly by the differential diagnosis of tuberculosis with lung cancer through case conferences with staff doctors. Doctor Yosikawa from Daido Hospital reported as follows. In his hospital, tuberculosis-beds and other respiratory-beds are in the same nursing unit managed with the same standard for nursing, although tuberculosis-beds are separated from other respiratory-beds by door and have exclusive toilets and bath-room. The doctors could study general respiratory diseases and tuberculosis at the same time. Thirteen doctors have finished this training, and all of them could deepen their knowledge to tuberculosi

Controlling the Seedbeds of Tuberculosis: Diagnosis and Treatment of Tuberculosis Infection

PubMed Central

Rangaka, Molebogeng X.; Cavalcante, Solange C.; Marais, Ben J.; Thim, Sok; Martinson, Neil A.; Swaminathan, Soumya; Chaisson, Richard E.

2015-01-01

The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a critical opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programs focusing on single strategies rather than comprehensive programs that deliver an integrated arsenal for tuberculosis control may continue to struggle. Tuberculosis preventive therapy is a poorly utilized tool that is essential for controlling the reservoirs of disease that drive the current epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. This paper outlines challenges to implementation of preventive therapy and provides pragmatic suggestions for overcoming them. It further advocates for tuberculosis preventive therapy as the core of a renewed global focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics, and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems, community engagement, and enhance sustainable large scale implementation of preventive therapy programs. PMID:26515679

Biomolecular identification of ancient Mycobacterium tuberculosis complex DNA in human remains from Britain and continental Europe.

PubMed

Müller, Romy; Roberts, Charlotte A; Brown, Terence A

2014-02-01

Tuberculosis is known to have afflicted humans throughout history and re-emerged towards the end of the 20th century, to an extent that it was declared a global emergency in 1993. The aim of this study was to apply a rigorous analytical regime to the detection of Mycobacterium tuberculosis complex (MTBC) DNA in 77 bone and tooth samples from 70 individuals from Britain and continental Europe, spanning the 1st-19th centuries AD. We performed the work in dedicated ancient DNA facilities designed to prevent all types of modern contamination, we checked the authenticity of all products obtained by the polymerase chain reaction, and we based our conclusions on up to four replicate experiments for each sample, some carried out in an independent laboratory. We identified 12 samples that, according to our strict criteria, gave definite evidence for the presence of MTBC DNA, and another 22 that we classified as "probable" or "possible." None of the definite samples came from vertebrae displaying lesions associated with TB. Instead, eight were from ribs displaying visceral new bone formation, one was a tooth from a skeleton with rib lesions, one was taken from a skeleton with endocranial lesions, one from an individual with lesions to the sacrum and sacroiliac joint and the last was from an individual with no lesions indicative of TB or possible TB. Our results add to information on the past temporal and geographical distribution of TB and affirm the suitability of ribs for studying ancient TB. Copyright © 2013 Wiley Periodicals, Inc.

Primary resistence of mycobacteria in tuberculosis patients.

PubMed

Daddi, G; Giobbi, A; Lucchesi, M

1976-03-01

Primary mycobactria resistance especially in some countries may be a serious obstacle to a successful therapy and the number of patients carrier of primary resistant mycobacteria remains almost at the same level in spite of the chemotherapeutic treatments and the usually rapid recover of the newly diagnosed cases. This may probably be attributed to the fact that the number of chronic patients, spitting resistant tubercle bacilli has remained almost the same, because these patients are eliminated little by little. In our country there is a constant regression of the morbidity, but not so rapid as expected, The newly diagnosed patients are generally young and, if well treated, they heal quickly and well; moreover, they are usually not so richly bacillised as they used to be once and the severity of their disease, globally evaluated, appears also reduced. The cultural positivity at the first admission into hospital is also diminishing. From all the above facts it is obvious that in order to eradicate tuberculosis it is necessary: First - to avoid creatin chronic patients; in order to reach this goal the treatment must be the most effective possible from the very beginning: INH and Rifampin. Second - to try to cure the chronic patients and to render them abacillary of, at least, to treat them intensively, with the purpose of inducing in the infecting flora a polyresistance which reners the mycobacteria hypovirulent, especially if it includes a R/AMP resistance over 40-gamma. Third - the role of the primary resistance in the epidemiology and the evolution of tuberculosis in the various countries and in the single patients, may be very different.

Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes.

PubMed

Jiménez-Corona, María Eugenia; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Bobadilla-Del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

2013-03-01

To determine the clinical consequences of pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM). We conducted a prospective study of patients with TB in Southern Mexico. From 1995 to 2010, patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. Annual follow-ups were performed to ascertain treatment outcome, recurrence, relapse and reinfection. The prevalence of DM among 1262 patients with pulmonary TB was 29.63% (n=374). Patients with DM and pulmonary TB had more severe clinical manifestations (cavities of any size on the chest x-ray, adjusted OR (aOR) 1.80, 95% CI 1.35 to 2.41), delayed sputum conversion (aOR 1.51, 95% CI 1.09 to 2.10), a higher probability of treatment failure (aOR 2.93, 95% CI 1.18 to 7.23), recurrence (adjusted HR (aHR) 1.76, 95% CI 1.11 to 2.79) and relapse (aHR 1.83, 95% CI 1.04 to 3.23). Most of the second episodes among patients with DM were caused by bacteria with the same genotype but, in 5/26 instances (19.23%), reinfection with a different strain occurred. Given the growing epidemic of DM worldwide, it is necessary to add DM prevention and control strategies to TB control programmes and vice versa and to evaluate their effectiveness. The concurrence of both diseases potentially carries a risk of global spreading, with serious implications for TB control and the achievement of the United Nations Millennium Development Goals.

Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes

PubMed Central

Jiménez-Corona, María Eugenia; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

2013-01-01

Objective To determine the clinical consequences of pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM). Methods We conducted a prospective study of patients with TB in Southern Mexico. From 1995 to 2010, patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. Annual follow-ups were performed to ascertain treatment outcome, recurrence, relapse and reinfection. Results The prevalence of DM among 1262 patients with pulmonary TB was 29.63% (n=374). Patients with DM and pulmonary TB had more severe clinical manifestations (cavities of any size on the chest x-ray, adjusted OR (aOR) 1.80, 95% CI 1.35 to 2.41), delayed sputum conversion (aOR 1.51, 95% CI 1.09 to 2.10), a higher probability of treatment failure (aOR 2.93, 95% CI 1.18 to 7.23), recurrence (adjusted HR (aHR) 1.76, 95% CI 1.11 to 2.79) and relapse (aHR 1.83, 95% CI 1.04 to 3.23). Most of the second episodes among patients with DM were caused by bacteria with the same genotype but, in 5/26 instances (19.23%), reinfection with a different strain occurred. Conclusions Given the growing epidemic of DM worldwide, it is necessary to add DM prevention and control strategies to TB control programmes and vice versa and to evaluate their effectiveness. The concurrence of both diseases potentially carries a risk of global spreading, with serious implications for TB control and the achievement of the United Nations Millennium Development Goals. PMID:23250998

Protein kinase G confers survival advantage to Mycobacterium tuberculosis during latency-like conditions.

PubMed

Khan, Mehak Zahoor; Bhaskar, Ashima; Upadhyay, Sandeep; Kumari, Pooja; Rajmani, Raju S; Jain, Preeti; Singh, Amit; Kumar, Dhiraj; Bhavesh, Neel Sarovar; Nandicoori, Vinay Kumar

2017-09-29

Protein kinase G (PknG), a thioredoxin-fold-containing eukaryotic-like serine/threonine protein kinase, is a virulence factor in Mycobacterium tuberculosis , required for inhibition of phagolysosomal fusion. Here, we unraveled novel functional facets of PknG during latency-like conditions. We found that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient-limited conditions, suggesting its role in modulating cellular metabolism. Intracellular metabolic profiling revealed that PknG is necessary for efficient metabolic adaptation during hypoxia. Notably, the PknG mutant exhibited a reductive shift in mycothiol redox potential and compromised stress response. Exposure to antibiotics and hypoxic environment resulted in higher oxidative shift in mycothiol redox potential of PknG mutant compared with the wild type. Persistence during latency-like conditions required kinase activity and thioredoxin motifs of PknG and is mediated through phosphorylation of a central metabolic regulator GarA. Finally, using a guinea pig model of infection, we assessed the in vivo role of PknG in manifestation of disease pathology and established a role for PknG in the formation of stable granuloma, hallmark structures of latent tuberculosis. Taken together, PknG-mediated GarA phosphorylation is important for maintenance of both mycobacterial physiology and redox poise, an axis that is dispensable for survival under normoxic conditions but is critical for non-replicating persistence of mycobacteria. In conclusion, we propose that PknG probably acts as a modulator of latency-associated signals. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Definite (microbiologically confirmed) tuberculous meningitis: predictors and prognostic impact.

PubMed

Jha, Sneh Kumar; Garg, Ravindra Kumar; Jain, Amita; Malhotra, Hardeep Singh; Verma, Rajesh; Sharma, Praveen Kumar

2015-12-01

Microbiological confirmation cannot be obtained in approximately two-third patients with tuberculous meningitis. In this study, we sought to identify epidemiological, clinical, cerebrospinal fluid, and imaging parameters that could indicate the possibility of microbiological confirmation among patients with suspected tuberculous meningitis. In this prospective observational study, patients with tuberculous meningitis were evaluated for clinical, laboratory (cerebrospinal fluid microscopy, culture, and polymerase chain reaction), and neuroimaging parameters. All patients received anti-tuberculosis drugs and corticosteroids. The patients were followed for a period of 6 months. Among 118 cases of tuberculous meningitis, there were 43 (36 %) definite (microbiologically confirmed) cases, 59 (50 %) probable and 16 (14 %) possible cases. Among 43 definite cases, tuberculosis polymerase chain reaction (PCR) was positive in 42 (35 %) patients, culture was positive in 1 case and microscopy, after Ziehl-Neelsen staining, was positive in 3 cases. Three factors, modified Barthel index score at admission ≤12 (p = 0.008), cerebrospinal fluid total cell count >100/mm(3) (p = 0.016), and basal exudates on imaging (p = 0.015), were significantly associated with definite tuberculous meningitis. Among 20 patients who died within 6 months, 13 belonged to definite tuberculous meningitis group (p < 0.001). Stage III tuberculous meningitis (p = 0.004), baseline-modified Barthel index score ≤12 (p = 0.013), and positive tuberculosis PCR (p = 0.007) were independently associated with poor outcome on multivariate analysis. Severe disability, cerebrospinal fluid cells >100 mm(3), and basal exudates are significantly related to the presence of microbiologically confirmed definite tuberculous meningitis. Microbiologically confirmed tuberculous meningitis is associated with poorer outcome.

Performance of Xpert MTB/RIF on Ascitic Fluid Samples for Detection of Abdominal Tuberculosis.

PubMed

Rufai, Syed Beenish; Singh, Sarman; Singh, Amit; Kumar, Parveen; Singh, Jitendra; Vishal, Anand

2017-01-01

Diagnosis of abdominal tuberculosis (TB) from ascitic fluid samples using routinely available diagnostic methods is challenging due to its paucibacillary nature. Although performance of Xpert MTB/RIF assay has been evaluated extensively on pulmonary samples, its performance on extrapulmonary samples is still under evaluation. The objective of this study was to find out the performance of Xpert MTB/RIF on ascitic fluid samples obtained from suspected cases of abdominal TB. Performance was compared with Mycobacterium growth indicator tube-960 (MGIT-960) culture and in-house multiplex polymerase chain reaction (PCR). The latter detects and differentiates Mycobacterium tuberculosis and nontuberculous mycobacteria simultaneously. Sixty-seven patients suspected of probable/possible abdominal TB were included in this observational, prospective study. All samples were tested by Ziehl-Neelsen staining, MGIT-960 culture, in-house multiplex PCR, and Xpert MTB/RIF assay. All 67 samples were smear negative. Seventeen (25.4%) were MGIT-960 culture positive while 12 (17.9%) were detected positive by the Xpert MTB/RIF assay and 9 (13.4%) by in-house multiplex PCR. Sensitivity and specificity of the Xpert MTB/RIF assay compared with the MGIT-960 culture were 70.6% (95%, confidence interval [CI]: 44.1-89.7) and 100% (95%, CI: 92.8-100) and that of in-house multiplex PCR were 52.9% (95%, CI: 30.9-73.8) and 100% (95%, CI: 92.8-100), respectively. Diagnostic yield of Xpert MTB/RIF assay on ascitic fluid samples was lower than MGIT-960 culture. We thus emphasize on the need for urgent discovery of new biomarkers for paucibacillary TB.

Analysis and hit filtering of a very large library of compounds screened against Mycobacterium tuberculosis.

PubMed

Ekins, Sean; Kaneko, Takushi; Lipinski, Christopher A; Bradford, Justin; Dole, Krishna; Spektor, Anna; Gregory, Kellan; Blondeau, David; Ernst, Sylvia; Yang, Jeremy; Goncharoff, Nicko; Hohman, Moses M; Bunin, Barry A

2010-11-01

There is an urgent need for new drugs against tuberculosis which annually claims 1.7-1.8 million lives. One approach to identify potential leads is to screen in vitro small molecules against Mycobacterium tuberculosis (Mtb). Until recently there was no central repository to collect information on compounds screened. Consequently, it has been difficult to analyze molecular properties of compounds that inhibit the growth of Mtb in vitro. We have collected data from publically available sources on over 300 000 small molecules deposited in the Collaborative Drug Discovery TB Database. A cheminformatics analysis on these compounds indicates that inhibitors of the growth of Mtb have statistically higher mean logP, rule of 5 alerts, while also having lower HBD count, atom count and lower PSA (ChemAxon descriptors), compared to compounds that are classed as inactive. Additionally, Bayesian models for selecting Mtb active compounds were evaluated with over 100 000 compounds and, they demonstrated 10 fold enrichment over random for the top ranked 600 compounds. This represents a promising approach for finding compounds active against Mtb in whole cells screened under the same in vitro conditions. Various sets of Mtb hit molecules were also examined by various filtering rules used widely in the pharmaceutical industry to identify compounds with potentially reactive moieties. We found differences between the number of compounds flagged by these rules in Mtb datasets, malaria hits, FDA approved drugs and antibiotics. Combining these approaches may enable selection of compounds with increased probability of inhibition of whole cell Mtb activity.

[Clinical and radiological study of Suruí indigenous children and adolescents, Amazon Region, Brazil].

PubMed

Basta, Paulo Cesar; Rios, Diana Patrícia Giraldo; Alves, Luiz Carlos Corrêa; Sant' Anna, Clemax Couto; Coimbra Junior, Carlos Everaldo Alvares

2010-01-01

The average incidence coefficient of tuberculosis in Suruí Indians from Rondônia was 2.500/100.000 inhabitants in 1991-2002. About 50% of these cases were reported in children < 15 years-old. This study aimed to describe the clinical and radiological characteristics of children and adolescents identified as TB case contacts. A score system for the diagnosis of childhood TB was used and the procedures adopted by local health services were in accordance with national guidelines. 52 chest X-rays of 37 indigenous subjects were analyzed; of these, 51.9% were abnormal. Some X-rays showed more than two lesions, making a total of 36 independent events. Infiltrates (38.9%), calcifications (38.9%), cavitations (11.1%) and atelectasis/pleural effusion (11.1%) were observed. Among the abnormal images, 22.2% were probably indicated active TB and 33.3% showed sequelae. Confrontation with the guidelines revealed 52.6% of divergent procedures. The presence of latent tuberculosis infection (LTBI) and active TB between children and adolescents are indicators of active and progressive transmission of Mycobacterium tuberculosis. The X-rays showed high frequencies of infiltrates and calcifications, which are compatible with primary infection in early childhood. However, these lesions are not different from those observed among other groups and do not suggest immune deficiencies. The divergences presented show that the best moment for the treatment of LTBI went unnoticed by local personnel. In conclusion, the use of a score system is fundamental for the correct diagnosis of TB in childhood, as is conducting bacilloscopy and sputum culture in adolescents able to expectorate.

A new trial design to accelerate tuberculosis drug development: the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP).

PubMed

Phillips, Patrick P J; Dooley, Kelly E; Gillespie, Stephen H; Heinrich, Norbert; Stout, Jason E; Nahid, Payam; Diacon, Andreas H; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Hoelscher, Michael

2016-03-23

The standard 6-month four-drug regimen for the treatment of drug-sensitive tuberculosis has remained unchanged for decades and is inadequate to control the epidemic. Shorter, simpler regimens are urgently needed to defeat what is now the world's greatest infectious disease killer. We describe the Phase IIC Selection Trial with Extended Post-treatment follow-up (STEP) as a novel hybrid phase II/III trial design to accelerate regimen development. In the Phase IIC STEP trial, the experimental regimen is given for the duration for which it will be studied in phase III (presently 3 or 4 months) and patients are followed for clinical outcomes of treatment failure and relapse for a total of 12 months from randomisation. Operating characteristics of the trial design are explored assuming a classical frequentist framework as well as a Bayesian framework with flat and sceptical priors. A simulation study is conducted using data from the RIFAQUIN phase III trial to illustrate how such a design could be used in practice. With 80 patients per arm, and two (2.5 %) unfavourable outcomes in the STEP trial, there is a probability of 0.99 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.91 that the proportion of unfavourable outcomes would be less than 8 %. With six (7.5 %) unfavourable outcomes, there is a probability of 0.82 that the proportion of unfavourable outcomes in a potential phase III trial would be less than 12 % and a probability of 0.41 that it would be less than 8 %. Simulations using data from the RIFAQUIN trial show that a STEP trial with 80 patients per arm would have correctly shown that the Inferior Regimen should not proceed to phase III and would have had a high chance (0.88) of either showing that the Successful Regimen could proceed to phase III or that it might require further optimisation. Collection of definitive clinical outcome data in a relatively small number of participants over only 12 months provides valuable information about the likelihood of success in a future phase III trial. We strongly believe that the STEP trial design described herein is an important tool that would allow for more informed decision-making and accelerate regimen development.

Factors determining ethnic differences in the incidence of bacteriologically confirmed genitourinary tuberculosis in south east England.

PubMed

Grange, J M; Yates, M D; Ormerod, L P

1995-01-01

In South East England, genitourinary (GU) tuberculosis is a much less common manifestation of non-respiratory tuberculosis in patients of Indian subcontinent (ISC) ethnic origin than in those of European ethnic origin. When considered in relation to all bacteriologically confirmed cases of tuberculosis, both respiratory and non-respiratory, the ethnic difference in the occurrence of GU tuberculosis is much less evident, while there is a highly significant excess of other forms of non-respiratory tuberculosis among the ethnic ISC patients. Unlike other forms of non-respiratory tuberculosis, GU disease tends to occur in an older age range in the ethnic ISC population and, when stratified for age, the ethnic difference in the occurrence of this form of tuberculosis is not significant while that of lymph node tuberculosis remains significantly high. Thus, after elimination of the confounding factor of age, the occurrence of GU tuberculosis is very similar in the two ethnic groups while other forms of non-respiratory tuberculosis differ considerably.

Clinical management of concurrent diabetes and tuberculosis and the implications for patient services.

PubMed

Riza, Anca Lelia; Pearson, Fiona; Ugarte-Gil, Cesar; Alisjahbana, Bachti; van de Vijver, Steven; Panduru, Nicolae M; Hill, Philip C; Ruslami, Rovina; Moore, David; Aarnoutse, Rob; Critchley, Julia A; van Crevel, Reinout

2014-09-01

Diabetes triples the risk for active tuberculosis, thus the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic. Recommendations have been made for bidirectional screening, but evidence is scarce about the performance of specific tuberculosis tests in individuals with diabetes, specific diabetes tests in patients with tuberculosis, and screening and preventive therapy for latent tuberculosis infections in individuals with diabetes. Clinical management of patients with both diseases can be difficult. Tuberculosis patients with diabetes have a lower concentration of tuberculosis drugs and a higher risk of drug toxicity than tuberculosis patients without diabetes. Good glycaemic control, which reduces long-term diabetes complications and could also improve tuberculosis treatment outcomes, is hampered by chronic inflammation, drug-drug interactions, suboptimum adherence to drug treatments, and other factors. Besides drug treatments for tuberculosis and diabetes, other interventions, such as education, intensive monitoring, and lifestyle interventions, might be needed, especially for patients with newly diagnosed diabetes or those who need insulin. From a health systems point of view, delivery of optimum care and integration of services for tuberculosis and diabetes is a huge challenge in many countries. Experience from the combined tuberculosis and HIV/AIDS epidemic could serve as an example, but more studies are needed that include economic assessments of recommended screening and systems to manage concurrent tuberculosis and diabetes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical management of concurrent diabetes and tuberculosis and the implications for patient services

PubMed Central

Riza, Anca Lelia; Pearson, Fiona; Ugarte-Gil, Cesar; Alisjahbana, Bachti; van de Vijver, Steven; Panduru, Nicolae M; Hill, Philip C; Ruslami, Rovina; Moore, David; Aarnoutse, Rob; Critchley, Julia A; van Crevel, Reinout

2016-01-01

Diabetes triples the risk for active tuberculosis, thus the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic. Recommendations have been made for bidirectional screening, but evidence is scarce about the performance of specific tuberculosis tests in individuals with diabetes, specific diabetes tests in patients with tuberculosis, and screening and preventive therapy for latent tuberculosis infections in individuals with diabetes. Clinical management of patients with both diseases can be difficult. Tuberculosis patients with diabetes have a lower concentration of tuberculosis drugs and a higher risk of drug toxicity than tuberculosis patients without diabetes. Good glycaemic control, which reduces long-term diabetes complications and could also improve tuberculosis treatment outcomes, is hampered by chronic inflammation, drug-drug interactions, suboptimum adherence to drug treatments, and other factors. Besides drug treatments for tuberculosis and diabetes, other interventions, such as education, intensive monitoring, and lifestyle interventions, might be needed, especially for patients with newly diagnosed diabetes or those who need insulin. From a health systems point of view, delivery of optimum care and integration of services for tuberculosis and diabetes is a huge challenge in many countries. Experience from the combined tuberculosis and HIV/AIDS epidemic could serve as an example, but more studies are needed that include economic assessments of recommended screening and systems to manage concurrent tuberculosis and diabetes. PMID:25194887

Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit

PubMed Central

Liu, Qiu-Yue; Han, Fen; Pan, Li-Ping; Jia, Hong-Yan; Li, Qi; Zhang, Zong-De

2018-01-01

Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global problem. Inflammatory responses are the primary characteristics of patients with pulmonary tuberculosis in intensive care units (ICU). The aim of the present study was to investigate the clinical importance of inflammatory cells and factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients with pulmonary tuberculosis in ICU were recruited for the present study. The inflammatory responses in patients with pulmonary tuberculosis in ICU were examined by changes in inflammatory cells and factors in the serum. The results indicated that serum levels of lymphocytes, plasma cells, granulocytes and monocytes were increased in patients with pulmonary tuberculosis in ICU compared with healthy controls. The serum levels of inflammatory factors interleukin (IL)-1, IL-6, IL-10, IL-12, and IL-4 were upregulated in patients with pulmonary tuberculosis in ICU. Lower plasma concentrations of IL-2, IL-15 and interferon-γ were detected in patients with pulmonary tuberculosis compared with healthy controls. It was demonstrated that high mobility group box-1 protein expression levels were higher in the serum of patients with pulmonary tuberculosis compared with healthy controls. Notably, an imbalance of T-helper cell (Th)1/Th2 cytokines was observed in patients with pulmonary tuberculosis. Pulmonary tuberculosis caused by M. tuberculosis also upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-9 in hPMCs. In conclusion, these outcomes demonstrated that inflammatory responses and inflammatory factors are associated with the progression of pulmonary tuberculosis, suggesting that inhibition of inflammatory responses and inflammatory factors may be beneficial for the treatment of patients with pulmonary tuberculosis in ICU. PMID:29456674

Comprehensive definition of human immunodominant CD8 antigens in tuberculosis.

PubMed

Lewinsohn, Deborah A; Swarbrick, Gwendolyn M; Park, Byung; Cansler, Meghan E; Null, Megan D; Toren, Katelynne G; Baseke, Joy; Zalwango, Sarah; Mayanja-Kizza, Harriet; Malone, LaShaunda L; Nyendak, Melissa; Wu, Guanming; Guinn, Kristi; McWeeney, Shannon; Mori, Tomi; Chervenak, Keith A; Sherman, David R; Boom, W Henry; Lewinsohn, David M

2017-01-01

Despite widespread use of the Bacillus Calmette-Guerin vaccine, tuberculosis, caused by infection with Mycobacterium tuberculosis , remains a leading cause of morbidity and mortality worldwide. As CD8 + T cells are critical to tuberculosis host defense and a phase 2b vaccine trial of modified vaccinia Ankara expressing Ag85a that failed to demonstrate efficacy, also failed to induce a CD8 + T cell response, an effective tuberculosis vaccine may need to induce CD8 + T cells. However, little is known about CD8, as compared to CD4, antigens in tuberculosis. Herein, we report the results of the first ever HLA allele independent genome-wide CD8 antigen discovery program. Using CD8 + T cells derived from humans with latent tuberculosis infection or tuberculosis and an interferon-γ ELISPOT assay, we screened a synthetic peptide library representing 10% of the Mycobacterium tuberculosis proteome, selected to be enriched for Mycobacterium tuberculosis antigens. We defined a set of immunodominant CD8 antigens including part or all of 74 Mycobacterium tuberculosis proteins, only 16 of which are previously known CD8 antigens. Immunogenicity was associated with the degree of expression of mRNA and protein. Immunodominant antigens were enriched in cell wall proteins with preferential recognition of Esx protein family members, and within proteins comprising the Mycobacterium tuberculosis secretome. A validation study of immunodominant antigens demonstrated that these antigens were strongly recognized in Mycobacterium tuberculosis -infected individuals from a tuberculosis endemic region in Africa. The tuberculosis vaccine field will likely benefit from this greatly increased known repertoire of CD8 immunodominant antigens and definition of properties of Mycobacterium tuberculosis proteins important for CD8 antigenicity.

Transmission of Mycobacterium tuberculosis in China: A Population-Based Molecular Epidemiologic Study

PubMed Central

Yang, Chongguang; Shen, Xin; Peng, Ying; Lan, Rushu; Zhao, Yuling; Long, Bo; Luo, Tao; Sun, Guomei; Li, Xia; Qiao, Ke; Gui, Xiaohong; Wu, Jie; Xu, Jiying; Li, Fabin; Li, Dingyue; Liu, Feiying; Shen, Mei; Hong, Jianjun; Mei, Jian; DeRiemer, Kathryn; Gao, Qian

2015-01-01

Background. Understanding the transmission of Mycobacterium tuberculosis is essential for the development of efficient tuberculosis control strategies. China has the second-largest tuberculosis burden in the world. Recent transmission and infection with M. tuberculosis, particularly drug-resistant strains, may account for many new tuberculosis cases. Methods. We performed a population-based molecular epidemiologic study of pulmonary tuberculosis in China during 1 July 2009 to 30 June 2012. We defined clusters as cases with identical variable number tandem repeat genotype patterns and identified the risk factors associated with clustering, by logistic regression. Relative transmission rates were estimated by the sputum smear status and drug susceptibility status of tuberculosis patients. Results. Among 2274 culture-positive tuberculosis patients with genotyped isolates, there were 705 (31.0%) tuberculosis patients in 287 clusters. Multidrug-resistant (MDR) tuberculosis (adjusted odds ratio [aOR], 1.86; 95% confidence interval [CI], 1.25–2.63) and infection with a Beijing family strain (aOR, 1.56; 95% CI, 1.23–2.96) were associated with clustering. Eighty-four of 280 (30.0%) clusters had a putative source case that was sputum smear negative, and 30.6% of their secondary cases were attributed to transmission by sputum smear–negative patients. The relative transmission rate for sputum smear negative compared with sputum smear–positive patients was 0.89 (95% CI, .68–1.10), and was 1.51 (95% CI, 1.00–2.24) for MDR tuberculosis vs drug-susceptible tuberculosis. Conclusions. Recent transmission of M. tuberculosis, including MDR strains, contributes substantially to tuberculosis disease in China. Sputum smear–negative cases were responsible for at least 30% of the secondary cases. Interventions to reduce the transmission of M. tuberculosis should be implemented in China. PMID:25829000

Drug-resistant tuberculosis: time for visionary political leadership.

PubMed

Abubakar, Ibrahim; Zignol, Matteo; Falzon, Dennis; Raviglione, Mario; Ditiu, Lucica; Masham, Susan; Adetifa, Ifedayo; Ford, Nathan; Cox, Helen; Lawn, Stephen D; Marais, Ben J; McHugh, Timothy D; Mwaba, Peter; Bates, Matthew; Lipman, Marc; Zijenah, Lynn; Logan, Simon; McNerney, Ruth; Zumla, Adam; Sarda, Krishna; Nahid, Payam; Hoelscher, Michael; Pletschette, Michel; Memish, Ziad A; Kim, Peter; Hafner, Richard; Cole, Stewart; Migliori, Giovanni Battista; Maeurer, Markus; Schito, Marco; Zumla, Alimuddin

2013-06-01

Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans. Copyright © 2013 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.

Tuberculosis

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Antibodies and tuberculosis: finally coming of age?

PubMed

Li, Hao; Javid, Babak

2018-06-05

Are antibodies important for protection against tuberculosis? The jury has been out for more than 100 years. B cell depletion in experimental Mycobacterium tuberculosis infection failed to identify a major role for these cells in immunity to tuberculosis. However, recent identification of naturally occurring antibodies in humans that are protective during M. tuberculosis infection has reignited the debate. Here, we discuss the evidence for a protective role for antibodies in tuberculosis and consider the feasibility of designing novel tuberculosis vaccines targeting humoral immunity.

Trend in case detection rate for all tuberculosis cases notified in Ebonyi, Southeastern Nigeria during 1999-2009.

PubMed

Ukwaja, Kingsley Nnanna; Alobu, Isaac; Ifebunandu, Ngozi Appolonia; Osakwe, Chijioke; Igwenyi, Chika

2013-01-01

Unlike previous annual WHO tuberculosis reports that reported case detection rate for only smear-positive tuberculosis cases, the 2010 report presented case detection rate for all tuberculosis cases notified in line with the current Stop TB strategy. To help us understand how tuberculosis control programmes performed in terms of detecting tuberculosis, there is need to document the trend in case detection rate for all tuberculosis cases notified in high burden countries. This evidence is currently lacking from Nigeria. Therefore, this study aimed to assess the trend in case detection rate for all tuberculosis cases notified from Ebonyi state compared to Nigeria national figures. Reports of tuberculosis cases notified between 1999 and 2009 were reviewed from the Ebonyi State Ministry of Health tuberculosis quarterly reports. Tuberculosis case detection rates were computed according to WHO guidelines. 22, 508 patients with all forms of tuberculosis were notified during the study. Case detection rate for all tuberculosis rose from 27% in 1999 to gradually reach a peak of 40% during 2007 to 2008 before a slight decline in 2009 to 38%. However, the national case detection rate for all tuberculosis cases in Nigeria rose from 7% in 1999 and progressively increased to reach a peak of 19% during 2008 and 2009. Since the introduction of DOTS in Ebonyi, the programme has achieved 40% case detection rate for all tuberculosis cases - about 20% better than national figures. However, with the current low case detection rates, alternative mechanisms are needed to achieve the current global stop- TB targets in Nigeria.

[The present situation, treatment and prognosis of drug-resistant pulmonary tuberculosis. Cooperative Study Unit of Chemotherapy of Tuberculosis of the National Sanitoria in Japan].

PubMed

Sato, K; Nagai, H; Kurashima, A; Mori, M; Katayama, T

1995-10-01

We studied 266 patients with drug-resistant pulmonary tuberculosis at national sanatoria in Japan. The patients included 218 men (mean age, 58 years) and 48 women (mean age, 62 years). The levels of isoniazid and rifampicin resistance were determined at 1 mcg/mL and 50 mcg/mL, respectively. The results were as follows. (1) Most patients with drug-resistant pulmonary tuberculosis were middle-aged or past middle-aged. (2) There were many cases of drug-resistant pulmonary tuberculosis in previously treated tuberculosis patients with active disease and several cases in previously untreated pulmonary tuberculosis patients. However, in some previously untreated patients active tuberculosis was convert relatively easily to inactive tuberculosis. (3) Concerning life style, bachelors who drank heavily were more likely to develop drug-resistant pulmonary tuberculosis. (4) Most cases of drug-resistant pulmonary tuberculosis had at least one cavity on chest radiographs. (5) Several patients with drug-resistant tuberculosis left the hospital against the advice of their attending doctors; therefore, it was difficult to treat their illnesses. (6) In more than half the cases in which Mycobacterium tuberculosis was resistant to isoniazid and rifampicin, tolerance to streptomycin and ethanbutol was also seen. (7) When patients with drug-resistant pulmonary tuberculosis continued to have tuberculous bacilli in their sputum after 3 months of chemotherapy, there was a tendency for them to expectorate tuberculous bacilli in their sputum. For these drug-resistant tuberculosis patients, we must pay attention not only to the medical aspects but also to the social aspects of their disease.

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice.

PubMed

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-04-23

Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective.

Tuberculosis and nutrition

PubMed Central

Gupta, Krishna Bihari; Gupta, Rajesh; Atreja, Atulya; Verma, Manish; Vishvkarma, Suman

2009-01-01

Malnutrition and tuberculosis are both problems of considerable magnitude in most of the underdeveloped regions of the world. These two problems tend to interact with each other. Tuberculosis mortality rates in different economic groups in a community tend to vary inversely with their economic levels. Similarly, nutritional status is significantly lower in patients with active tuberculosis compared with healthy controls. Malnutrition can lead to secondary immunodeficiency that increases the host's susceptibility to infection. In patients with tuberculosis, it leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting. Both, protein-energy malnutrition and micronutrients deficiencies increase the risk of tuberculosis. It has been found that malnourished tuberculosis patients have delayed recovery and higher mortality rates than well-nourished patients. Nutritional status of patients improves during tuberculosis chemotherapy. High prevalence of human immunodeficiency (HIV) infection in the underdeveloped countries further aggravates the problem of malnutrition and tuberculosis. Effect of malnutrition on childhood tuberculosis and tuberculin skin test are other important considerations. Nutritional supplementation may represent a novel approach for fast recovery in tuberculosis patients. In addition, raising nutritional status of population may prove to be an effective measure to control tuberculosis in underdeveloped areas of world. PMID:20165588

Updates on Knowledge, Attitude and Preventive Practices on Tuberculosis among Healthcare Workers.

PubMed

Wahab, Farhanah Abd; Abdullah, Sarimah; Abdullah, Jafri Malin; Jaafar, Hasnan; Noor, Siti Suraiya Md; Mohammad, Wan Mohd Zahiruddin Wan; Yusoff, Abdul Aziz Mohamed; Tharakan, John; Bhaskar, Shalini; Sangu, Muthuraju; Mahmood, Mohd Shah; Kassim, Fauziah; Rafia, Md Hanip; Haspani, Mohammed Safari Mohammed; Alias, Azmi; Pando, Rogelio Hernández

2016-11-01

Ranking as the most communicable disease killer worldwide, tuberculosis, has accounted with a total of 9.6 million new tuberculosis cases with 1.5 million tuberculosis-related deaths reported globally in 2014. Tuberculosis has remain as an occupational hazard for healthcare workers since 1920s and due to several tuberculosis outbreaks in healthcare settings in the early 1990s, the concern about the transmission to both patients and healthcare workers has been raised. Healthcare workers have two to three folds greater the risk of active tuberculosis than the general population. Several studies on knowledge, attitude and practices on tuberculosis among healthcare workers worldwide have revealed that majority of the participated healthcare workers had good knowledge on tuberculosis. Most of the healthcare workers from South India and South Africa also reported to have positive attitude whereas a study in Thailand reported that most of the healthcare providers have negative attitude towards tuberculosis patients. Nevertheless, majority of the healthcare workers have low level of practice on tuberculosis prevention. An improved communication between healthcare workers and the patients as well as their families is the key to better therapeutic outcomes with good knowledge, attitude and preventive practice towards tuberculosis.

The double burden.

PubMed

Faurholt-Jepsen, Daniel

2013-07-01

One third of the world's population is latently infected with Mycobacterium tuberculosis, and with the lifestyle changes succeeding the on-going urbanization, populations already burdened by tuberculosis are experiencing a dramatic increase in chronic diseases, with diabetes being a serious challenge. Tuberculosis and diabetes are not only becoming co-existing diseases. In fact, the diseases interact, and there is evidence to suggest that especially diabetes disease increases the susceptibility for developing active tuberculosis disease. Furthermore, it is plausible that tuberculosis leads to, either transient or permanent, impairment of the glucose metabolism, which ultimately will turn into diabetes. A number of studies from the Americas, Europe, Asia, and, most lately, from sub-Saharan Africa have reported strong association between tuberculosis and diabetes; on average, the estimated risk of active tuberculosis is thrice as high among people with diabetes. The study from sub-Saharan Africa was conducted in Tanzania and is the basis of this thesis. Based on available evidence on the association between tuberculosis and diabetes, the primary aim of the study was to assess the role of diabetes for tuberculosis risk, manifestations, treatment outcomes and survival in a Tanzanian population of tuberculosis patients and non-tuberculosis neighbourhood controls. The study was conducted in Mwanza City in northern Tanzania, with a population exceeding half a million inhabitants, with tuberculosis and HIV being common infections in the region, but with little knowledge about the prevalence of diabetes. We recruited newly diagnosed pulmonary tuberculosis patients from spring 2006 and continuously till the fall 2009, with all participating in a nutritional intervention running in parallel with the medical tuberculosis treatment. All participants underwent diabetes and HIV testing as well as a series of measurements such as anthropometric, clinical and paraclinical parameters. The population was followed up during treatment (2 and 5 months) to assess treatment outcome as well as after one year to assess their survival status. Based on data from 1,250 tuberculosis patients and 350 neighbourhood controls, we found that 38 and 21%, respectively, had impaired glycaemia, and that the prevalence of diabetes was 17 and 9% among tuberculosis patients and controls, respectively. This difference in prevalence between patients and controls was equivalent to an adjusted odds ratio of more than four, indicating a strong association between tuberculosis and diabetes. Furthermore, we found that diabetes was associated with tuberculosis among both participants with or without HIV co-infection. Despite the strong association, diabetes had only moderate clinical implications when the tuberculosis patients initiated the tuberculosis treatment; the patients with diabetes co-morbidity had a minor elevation in the immune response and more frequently reported to have fever. Furthermore, diabetes did not seem to delay time to sputum conversion during treatment. Nevertheless, diabetes co-morbidity led to impaired treatment outcome with slower recovery of weight and haemoglobin and a more than four times higher mortality rate within the initial phase of tuberculosis treatment. In conclusion, in the African region, the double burden of tuberculosis and diabetes is becoming a major health problem. Although the tuberculosis incidence has stabilized during the last decade, the increasing incidence of diabetes will possibly interfere with tuberculosis control and may, consequently, make the tuberculosis incidence increase again. Future research strategies should focus on enhanced diagnostic tools to identify tuberculosis patients with diabetes co-morbidity, and on the role of disease-disease, drug-disease and drug-drug interactions between tuberculosis and diabetes diseases and treatments.

Prevalence and risk factors for latent tuberculosis infection among healthcare workers in Nampula Central Hospital, Mozambique.

PubMed

Belo, Celso; Naidoo, Saloshni

2017-06-08

Healthcare workers in high tuberculosis burdened countries are occupationally exposed to the tuberculosis disease with uncomplicated and complicated tuberculosis on the increase among them. Most of them acquire Mycobacterium tuberculosis but do not progress to the active disease - latent tuberculosis infection. The objective of this study was to assess the prevalence and risk factors associated with latent tuberculosis infection among healthcare workers in Nampula Central Hospital, Mozambique. This cross-sectional study of healthcare workers was conducted between 2014 and 2015. Participants (n = 209) were administered a questionnaire on demographics and occupational tuberculosis exposure and had a tuberculin skin test administered. Multivariate linear and logistic regression tested for associations between independent variables and dependent outcomes (tuberculin skin test induration and latent tuberculosis infection status). The prevalence of latent tuberculosis infection was 34.4%. Latent tuberculosis infection was highest in those working for more than eight years (39.3%), those who had no BCG vaccination (39.6%) and were immunocompromised (78.1%). Being immunocompromised was significantly associated with latent tuberculosis infection (OR 5.97 [95% CI 1.89; 18.87]). Positive but non-significant associations occurred with working in the medical domain (OR 1.02 [95% CI 0.17; 6.37]), length of employment > eight years (OR 1.97 [95% CI 0.70; 5.53]) and occupational contact with tuberculosis patients (OR 1.24 [95% CI 0.47; 3.27]). Personal and occupational factors were positively associated with latent tuberculosis infection among healthcare workers in Mozambique.

Drug therapy in spinal tuberculosis.

PubMed

Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Tuberculosis screening in patients with HIV: An audit against UK national guidelines to assess current practice and the effectiveness of an electronic tuberculosis-screening prompt.

PubMed

Fox-Lewis, A; Brima, N; Muniina, P; Grant, A D; Edwards, S G; Miller, R F; Pett, S L

2016-09-01

A retrospective clinical audit was performed to assess if the British HIV Association 2011 guidelines on routine screening for tuberculosis in HIV are being implemented in a large UK urban clinic, and if a tuberculosis-screening prompt on the electronic patient record for new attendees was effective. Of 4658 patients attending during the inclusion period, 385 were newly diagnosed first-time attendees and routine tuberculosis screening was recommended in 165. Of these, only 6.1% of patients had a completed tuberculosis screening prompt, and 12.1% underwent routine tuberculosis screening. This audit represents the first published UK data on routine screening rates for tuberculosis in HIV and demonstrates low rates of tuberculosis screening despite an electronic screening prompt designed to simplify adherence to the national guideline. Reasons why tuberculosis screening rates were low, and the prompt ineffective, are unclear. A national audit is ongoing, and we await the results to see if our data reflect a lack of routine tuberculosis screening in HIV-infected patients at a national level. © The Author(s) 2016.

Tuberculosis associated chronic obstructive pulmonary disease.

PubMed

Sarkar, Malay; Srinivasa; Madabhavi, Irappa; Kumar, Kushal

2017-05-01

Reviewed the epidemiology, clinical characteristics, mechanisms, and treatment of tuberculosis associated chronic obstructive pulmonary disease. We searched PubMed, EMBASE, and the CINAHL from inception to June 2016. We used the following search terms: Tuberculosis, COPD, Tuberculosis associated COPD, and so forth. All types of study were chosen. Chronic obstructive pulmonary disease (COPD) and tuberculosis are significant public health problems, particularly in developing countries. Although, smoking is the conventional risk factor for COPD, nonsmoking related risk factors such as biomass fuel exposure, childhood lower-respiratory tract infections, chronic asthma, outdoor air pollution, and prior history of pulmonary tuberculosis have become important risk factors of COPD, particularly in developing countries. Past history of tuberculosis as a risk factor of chronic airflow obstruction has been reported in several studies. It may develop during the course of tuberculosis or after completion of tuberculosis treatment. Developing countries with large burden of tuberculosis can contribute significantly to the burden of chronic airflow obstruction. Prompt diagnosis and treatment of tuberculosis should be emphasized to lessen the future burden of chronic airflow obstruction. © 2017 John Wiley & Sons Ltd.

A high resolution computer tomography scoring system to predict culture-positive pulmonary tuberculosis in the emergency department.

PubMed

Yeh, Jun-Jun; Neoh, Choo-Aun; Chen, Cheng-Ren; Chou, Christine Yi-Ting; Wu, Ming-Ting

2014-01-01

This study evaluated the use of high-resolution computed tomography (HRCT) to predict the presence of culture-positive pulmonary tuberculosis (PTB) in adult patients with pulmonary lesions in the emergency department (ED). The study included a derivation phase and validation phase with a total of 8,245 patients with pulmonary disease. There were 132 patients with culture-positive PTB in the derivation phase and 147 patients with culture-positive PTB in the validation phase. Imaging evaluation of pulmonary lesions included morphology and segmental distribution. The post-test probability ratios between both phases in three prevalence areas were analyzed. In the derivation phase, a multivariate analysis model identified cavitation, consolidation, and clusters/nodules in right or left upper lobe (except anterior segment) and consolidation of the superior segment of the right or left lower lobe as independent positive factors for culture-positive PTB, while consolidation of the right or left lower lobe (except superior segment) were independent negative factors. An ideal cutoff point based on the receiver operating characteristic (ROC) curve analysis was obtained at a score of 1. The sensitivity, specificity, positivity predictive value, and negative predictive value from derivation phase were 98.5% (130/132), 99.7% (3997/4008), 92.2% (130/141), and 99.9% (3997/3999). Based on the predicted positive likelihood ratio value of 328.33 in derivation phase, the post-test probability was observed to be 91.5% in the derivation phase, 92.5% in the validation phase, 94.5% in a high TB prevalence area, 91.0% in a moderate prevalence area, and 76.8% in moderate-to-low prevalence area. Our model using HRCT, which is feasible to perform in the ED, can promptly diagnose culture-positive PTB in moderate and moderate-to-low prevalence areas.

Predictive value of C-reactive protein for tuberculosis, bloodstream infection or death among HIV-infected individuals with chronic, non-specific symptoms and negative sputum smear microscopy.

PubMed

Bedell, Richard A; van Lettow, Monique; Meaney, Christopher; Corbett, Elizabeth L; Chan, Adrienne K; Heyderman, Robert S; Anderson, Suzanne T; Åkesson, Ann; Kumwenda, Moses; Zachariah, Rony; Harries, Anthony D; Ramsay, Andrew R

2018-03-01

C-reactive protein (CRP) is an inflammatory biomarker that may identify patients at risk of infections or death. Mortality among HIV-infected persons commencing antiretroviral therapy (ART) is often attributed to tuberculosis (TB) or bloodstream infections (BSI). In two district hospitals in southern Malawi, we recruited HIV-infected adults with one or more unexplained symptoms present for at least one month (weight loss, fever or diarrhoea) and negative expectorated sputum microscopy for TB. CRP determination for 452 of 469 (96%) participants at study enrolment was analysed for associations with TB, BSI or death to 120 days post-enrolment. Baseline CRP was significantly elevated among patients with confirmed or probable TB (52), BSI (50) or death (60) compared to those with no identified infection who survived at least 120 days (269). A CRP value of >10 mg/L was associated with confirmed or probable TB (adjusted odds ratio 5.7; 95% CI 2.6, 14.3; 87% sensitivity) or death by 30 days (adjusted odds ratio 9.2; 95% CI 2.2, 55.1; 88% sensitivity). CRP was independently associated with TB, BSI or death, but the prediction of these endpoints was enhanced by including haemoglobin (all outcomes), CD4 count (BSI, death) and whether ART was started (death) in logistic regression models. High CRP at the time of ART initiation is associated with TB, BSI and early mortality and so has potential utility for stratifying patients for intensified clinical and laboratory investigation and follow-up. They may also be considered for empirical treatment of opportunistic infections including TB. © 2017 John Wiley & Sons Ltd.

Evaluation of the Xpert MTB/RIF assay for the diagnosis of smear-negative pulmonary and extrapulmonary tuberculosis in Madagascar.

PubMed

Rakotoarivelo, R; Ambrosioni, J; Rasolofo, V; Raberahona, M; Rakotosamimanana, N; Andrianasolo, R; Ramanampamonjy, R; Tiaray, M; Razafimahefa, J; Rakotoson, J; Randria, M; Bonnet, F; Calmy, A

2018-04-01

To evaluate the feasibility of the implementation of a commercial rapid molecular diagnostic test (Xpert MTB/RIF) for the routine diagnosis of smear-negative or extrapulmonary tuberculosis (TB) and its diagnostic accuracy, and to assess HIV prevalence in a real-life setting in Madagascar. This study was set in a tertiary care hospital in Madagascar. A prospective cohort study was conducted of all consecutive cases with suspected smear-negative and/or extrapulmonary TB over a 2-year period. Cases were classified as proven, probable, or possible TB cases, or as having an alternative diagnosis. Of the 363 patients included, 183 (50.4%) had suspected smear-negative pulmonary TB and 180 (49.6%) had suspected extrapulmonary TB. For proven cases, the sensitivity, specificity, positive and negative predictive values of Xpert MTB/RIF were 82.4%, 98.8%, 98.3%, and 86.6%, respectively; for proven and probable cases grouped together, these values were 65%, 98.8%, 98.5%, and 64%, respectively. The diagnostic accuracy was slightly lower for extrapulmonary TB compared to smear-negative pulmonary TB. The prevalence of HIV infection was 12.1%, but almost half of these cases did not have TB (alternative diagnosis group). The implementation of a rapid diagnosis programme for TB in a resource-poor setting is feasible. The performance of the Xpert-MTB/RIF was remarkable in this difficult-to-diagnose population. HIV prevalence in this study was much higher than the prevalence reported in the general population in Madagascar, in patients with TB and patients with conditions other than TB. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Risk factors for failure to detect bovine tuberculosis in cattle from infected herds across Northern Ireland (2004-2010).

PubMed

Lahuerta-Marin, Angela; McNair, James; Skuce, Robin; McBride, Stewart; Allen, Michelle; Strain, Sam A J; Menzies, Fraser D; McDowell, Stanley J W; Byrne, Andrew W

2016-08-01

Correctly identifying animals that are truly infected with a pathogen using ante-mortem tests is the cornerstone of any disease eradication programme. Failure to identify all infected animals will impede the progress towards controlling and eradicating disease and may also have unforeseen consequences when specific prevention measures are in place to avoid animal-to-animal transmission. In the case of bovine tuberculosis (bTB), the screening ante-mortem test, the Single Comparative Intradermal Tuberculin Test (SCITT), can exhibit moderate sensitivity which can result in a "hidden burden" of infection residing within the population. Using an animal-level dataset relating to the disclosure of infected cattle with Mycobacterium bovis, the causative agent of bTB within infected herds in Northern Ireland, we investigated what factors influenced the probability of an animal being a false-negative when truly infected (using post-mortem (PM) microbiological culture confirmation results to assess infection status). We found that different risk factors affected the probability of a test-negative outcome on infected animals depending on the ante-mortem test or their combination (SICTT and/or interferon gamma (IFN-ɣ) testing). Using multivariable models, SCITT disclosure performance varied significantly by age, location (region), and production type. The IFN-ɣ tests were significantly affected by region or season, but these effects depended on the cut-off used during interpretation of the test which affected the tests characteristics. Parallel use of SCITT and IFN-ɣ tests resulted in the least number of false-negatives, and their disclosure was affected by season and age-class. Understanding the factors that lead to the non-disclosure of infected animals is essential to optimise large-scale bTB disease eradication programmes. Copyright © 2016. Published by Elsevier Ltd.

Drug targeted virtual screening and molecular dynamics of LipU protein of Mycobacterium tuberculosis and Mycobacterium leprae.

PubMed

Kaur, Gurkamaljit; Pandey, Bharati; Grover, Arbind; Garewal, Naina; Grover, Abhinav; Kaur, Jagdeep

2018-03-30

The lipolytic protein LipU was conserved in mycobacterium sp. including M. tuberculosis (MTB LipU) and M. leprae (MLP LipU). The MTB LipU was identified in extracellular fraction and was reported to be essential for the survival of mycobacterium. Therefore to address the problem of drug resistance in pathogen, LipU was selected as a drug target and the viability of finding out some FDA approved drugs as LipU inhibitors in both the cases was explored. Three-dimensional (3D) model structures of MTB LipU and MLP LipU were generated and stabilized through molecular dynamics (MD). FDA approved drugs were screened against these proteins. The result showed that the top-scoring compounds for MTB LipU were Diosmin, Acarbose and Ouabain with the Glide XP score of -12.8, -11.9 and -11.7 kcal/mol, respectively, whereas for MLP LipU protein, Digoxin (-9.2 kcal/mol), Indinavir (-8.2 kcal/mol) and Travoprost (-8.2 kcal/mol) showed highest affinity. These drugs remained bound in the active site pocket of MTB LipU and MLP LipU structure and interaction grew stronger after dynamics. RMSD, RMSF and Rg were found to be persistent throughout the simulation period. Hydrogen bonds along with large number of hydrophobic interactions stabilized the complex structures. Binding free energies obtained through Prime/MM-GBSA were found in the significant range from -63.85 kcal/mol to -34.57 kcal/mol for MTB LipU and -71.33 kcal/mol to -23.91 kcal/mol for MLP LipU. The report suggested high probability of these drugs to demolish the LipU activity and could be probable drug candidates to combat TB and leprosy disease.

Development of risk-based trading farm scoring system to assist with the control of bovine tuberculosis in cattle in England and Wales.

PubMed

Adkin, A; Brouwer, A; Simons, R R L; Smith, R P; Arnold, M E; Broughan, J; Kosmider, R; Downs, S H

2016-01-01

Identifying and ranking cattle herds with a higher risk of being or becoming infected on known risk factors can help target farm biosecurity, surveillance schemes and reduce spread through animal trading. This paper describes a quantitative approach to develop risk scores, based on the probability of infection in a herd with bovine tuberculosis (bTB), to be used in a risk-based trading (RBT) scheme in England and Wales. To produce a practical scoring system the risk factors included need to be simple and quick to understand, sufficiently informative and derived from centralised national databases to enable verification and assess compliance. A logistic regression identified herd history of bTB, local bTB prevalence, herd size and movements of animals onto farms in batches from high risk areas as being significantly associated with the probability of bTB infection on farm. Risk factors were assigned points using the estimated odds ratios to weight them. The farm risk score was defined as the sum of these individual points yielding a range from 1 to 5 and was calculated for each cattle farm that was trading animals in England and Wales at the start of a year. Within 12 months, of those farms tested, 30.3% of score 5 farms had a breakdown (sensitivity). Of farms scoring 1-4 only 5.4% incurred a breakdown (1-specificity). The use of this risk scoring system within RBT has the potential to reduce infected cattle movements; however, there are cost implications in ensuring that the information underpinning any system is accurate and up to date. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Multiple hepatic lesions in a case of isolated hepatic tuberculosis simulating metastases on 18F-FDG PET/CT imaging.

PubMed

Karunanithi, Sellam; Sharma, Punit; Jain, Tarun Kumar; Vijay, Maneesh Kumar; Kumar, Rakesh

2014-01-01

Hepatic tuberculosis is an unusual form of extrapulmonary tuberculosis and constitutes less than 1% of all cases of tuberculosis. Imaging studies for hepatic tuberculosis are nonspecific and mimic primary or metastatic carcinoma. Here we present ¹⁸F-FDG PET/CT images of a 25-year-old male patient with isolated hepatic tuberculosis.

Anti-Tuberculosis Policy of the Government General of Korea during Japanese-Colonial Period (1910-1945): From Simple Restriction to Active Enlightenment.

PubMed

Choi, Eun Kyung

2013-12-01

In this paper, I tried to examine the characteristic of anti-tuberculosis policy in colonial Korea and find out internal constraint of hygienic administration by Japanese government during Japanese-Colonial Period. Despite of high prevalence of tuberculosis among Japanese in Korea, the Japanese Government General of Korea had done almost nothing until 1936. Japan's hygienic administration was highly dependent upon hygienic police, and mainly with compulsory isolation and disinfection. It was inefficient in tuberculosis problem. In 1918, Japanese Government General enacted 'Ordinance of Prevention of Tuberculosis', solely based upon naive tuberculosis etiology in sputum; consisted of simple crackdown and isolation and had no effect due to the limit of anti-tuberculosis and health budget. Also the ordinance actually set limitation upon the tuberculosis facilities, only a few health care facilities could be affordable for tuberculosis patients. Since 1936, the Japanese Government General of Korea began tuberculosis prevention measures in earnest. Due to the Second Sino- Japanese War and World War II, there was urgent need to make Korean society and population as "safe, and healthy rear area". The Government organized 'Chosen Anti-tuberculosis Association' and highly pursued enlightment campaign. It was almost temporary measures of enlightenment and publicity. Also various types of health screening and tuberculosis prevalence research were introduced to Korean people. But it was not so effective to identify tuberculosis problem in Korea. Mass tuberculin test and X-ray test was introduced, but it was not well organized and scientifically designed. Besides, tuberculosis treatment facility was extremely rare because of strict isolation and high standard policy. Japanese Governemtn set numerous tuberculosis-counseling centers and mobilized public doctor for consulting tuberculosis, but the accessibility of centers was very low. Moreover, there was no source to establish facilities like sanatorium. The Japanese Government General of Korea was constantly suffered from limit of budget and a lot of Japanese in Korea had no inherent motive for installing sanatorium and anti-tuberculosis measures. As the result, the effort made by Japanese Government General of Korea to diminish tuberculosis in Korea failed during the wartime.

Does non-central nervous system tuberculosis increase the risk of ischemic stroke? A population-based propensity score-matched follow-up study.

PubMed

Wu, Chueh-Hung; Chen, Li-Sheng; Yen, Ming-Fang; Chiu, Yueh-Hsia; Fann, Ching-Yuan; Chen, Hsiu-Hsi; Pan, Shin-Liang

2014-01-01

Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73-1.14, P = 0.4299). Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke.

Role of the Health Department in Tuberculosis Prevention and Control-Legal and Public Health Considerations.

PubMed

Jeffries, Carla; Lobue, Phil; Chorba, Terence; Metchock, Beverly; Kashef, Ijaz

2017-03-01

Because tuberculosis is caused by an infectious organism that is spread from person to person through the air, public health measures are essential to control the disease. There are three priority strategies for tuberculosis prevention and control in the United States: (i) identifying and treating persons who have tuberculosis disease; (ii) finding persons exposed to infectious tuberculosis patients, evaluating them for Mycobacterium tuberculosis infection and disease, and providing subsequent treatment, if appropriate; and (iii) testing populations at high risk for latent tuberculosis infection (LTBI) and treating those persons who are infected to prevent progression to disease. These strategies for prevention and control of tuberculosis are discussed in a framework containing the following important topics: historical and epidemiological context of tuberculosis control, organization of public health tuberculosis control programs, legal basis for public health authority, conducting overall planning and development of policy, identifying persons who have clinically active tuberculosis, evaluation of immigrants, managing persons who have or who are suspected of having disease, medical consultation, interjurisdictional referrals, identifying and managing persons infected with Mycobacterium tuberculosis, providing laboratory and diagnostic services, collecting and analyzing data, and providing training and education. This chapter describes the role of the health department in the context of these components. This discussion is primarily applicable to tuberculosis prevention and control programs in the United States.

Relationship between human LTA4H polymorphisms and extra-pulmonary tuberculosis in an ethnic Han Chinese population in Eastern China.

PubMed

Yang, Jinghui; Chen, Jin; Yue, Jun; Liu, Lirong; Han, Min; Wang, Hongxiu

2014-12-01

Two single nucleotide polymorphisms in Leukotriene A4 hydrolase (LTA4H) gene were reported to be associated with protection from pulmonary tuberculosis in Vietnamese population. But these associations were not found in the Russians. To investigate the association of LTA4H polymorphisms with tuberculosis in a Han Chinese population in Eastern China, we genotyped 5 SNPs of LTA4H gene in 743 of pulmonary tuberculosis patients, 372 of extra-pulmonary tuberculosis patients and 888 of healthy controls individuals. The CC and TT homozygotes of rs1978331 and rs2540474 were identified to have higher rates (P < 0.01) and be risk factors in the patients with extra-pulmonary tuberculosis (OR = 1.412; 95% CI = 1.104-1.804 and(OR = 1.380; 95% CI = 1.080-1.764). However, no significant association was found between any of the SNPs and pulmonary tuberculosis. In the extra-pulmonary tuberculosis subgroups. LTA4H gene were significantly associated with tuberculous meningitis, lymph node tuberculosis, bone tuberculosis and other extra-pulmonary tuberculosis except for pleural tuberculosis. The present findings suggest that polymorphisms in the LTA4H gene may affect susceptibility to extra-pulmonary tuberculosis and change the risk of developing the disease in the Han nationality in the East China. Copyright © 2014 Elsevier Ltd. All rights reserved.

Localized hepatic tuberculosis presenting as severe hypercalcemia.

PubMed

Arrais Morais, Matheus; Cardoso Teixeira, Lorena Lane; de Sousa Brandão Torres, Dennyse; da Rocha Klautau Neto, Prócion Barreto; Machado Kahwage, Amanda

2018-04-01

Hypercalcemia might present itself in association with granulomatous diseases such as tuberculosis. We report a rare case of a 62-year-old man with hypercalcemia due to hepatic tuberculosis. The diagnosis was based on laparoscopic and a histopathological examination. After treatment with anti-tuberculosis medication, the patient's serum calcium levels were within normal limits. Tuberculosis needs to be excluded as a diagnosis in any febrile patient with hypercalcemia, especially in countries where tuberculosis is endemic. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Aggressive Regimens for Multidrug-Resistant Tuberculosis Reduce Recurrence

PubMed Central

Franke, Molly F.; Appleton, Sasha C.; Mitnick, Carole D.; Furin, Jennifer J.; Bayona, Jaime; Chalco, Katiuska; Shin, Sonya; Murray, Megan; Becerra, Mercedes C.

2013-01-01

Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2–53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17–0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17–50.60]; P = .004). Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease. PMID:23223591

Clinical evaluation of tuberculosis viability microscopy for assessing treatment response.

PubMed

Datta, Sumona; Sherman, Jonathan M; Bravard, Marjory A; Valencia, Teresa; Gilman, Robert H; Evans, Carlton A

2015-04-15

It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. To assess treatment response, sputum samples (n=124) from unselected patients (n=35) with sputum microscopy-positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS=0.85; P<.0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P<.001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P=.4) or quantitative culture (P=.6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P<.001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P=.6). Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice

PubMed Central

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-01-01

Abstract Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective. PMID:29471332

Decline in tuberculosis among Mexico-born persons in the United States, 2000-2010.

PubMed

Baker, Brian J; Jeffries, Carla D; Moonan, Patrick K

2014-05-01

In 2010, Mexico was the most common (22.9%) country of origin for foreign-born persons with tuberculosis in the United States, and overall trends in tuberculosis morbidity are substantially influenced by the Mexico-born population. To determine the risk of tuberculosis disease among Mexico-born persons living in the United States. Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined tuberculosis case counts and case rates stratified by years since entry into the United States and geographic proximity to the United States-Mexico border. We calculated trends in case rates over time measured by average annual percent change. The total tuberculosis case count (-14.5%) and annual tuberculosis case rate (average annual percent change -5.1%) declined among Mexico-born persons. Among those diagnosed with tuberculosis less than 1 year since entry into the United States (newly arrived persons), there was a decrease in tuberculosis cases (-60.4%), no change in tuberculosis case rate (average annual percent change of 0.0%), and a decrease in population (-60.7%). Among those living in the United States for more than 5 years (non-recently arrived persons), there was an increase in tuberculosis cases (+3.4%), a decrease in tuberculosis case rate (average annual percent change of -4.9%), and an increase in population (+62.7%). In 2010, 66.7% of Mexico-born cases were among non-recently arrived persons, compared with 51.1% in 2000. Although border states reported the highest proportions (>15%) of tuberculosis cases that were Mexico-born, the highest Mexico-born-specific tuberculosis case rates (>20/100,000 population) were in states in the eastern and southeastern regions of the United States. The decline in tuberculosis morbidity among Mexico-born persons may be attributed to fewer newly arrived persons from Mexico and lower tuberculosis case rates among non-recently arrived Mexico-born persons. The extent of the decline was dampened by an unchanged tuberculosis case rate among newly arrived persons from Mexico and a large increase in the non-recently arrived Mexico-born population. If current trends continue, tuberculosis morbidity among Mexico-born persons will be increasingly driven by those who have been living in the United States for more than 5 years.

Decline in Tuberculosis among Mexico-Born Persons in the United States, 2000–2010

PubMed Central

Baker, Brian J.; Jeffries, Carla D.; Moonan, Patrick K.

2016-01-01

Background In 2010, Mexico was the most common (22.9%) country of origin for foreign-born persons with tuberculosis in the United States, and overall trends in tuberculosis morbidity are substantially influenced by the Mexico-born population. Objectives To determine the risk of tuberculosis disease among Mexico-born persons living in the United States. Methods Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined tuberculosis case counts and case rates stratified by years since entry into the United States and geographic proximity to the United States–Mexico border. We calculated trends in case rates over time measured by average annual percent change. Results The total tuberculosis case count (−14.5%) and annual tuberculosis case rate (average annual percent change −5.1%) declined among Mexico-born persons. Among those diagnosed with tuberculosis less than 1 year since entry into the United States (newly arrived persons), there was a decrease in tuberculosis cases (−60.4%), no change in tuberculosis case rate (average annual percent change of 0.0%), and a decrease in population (−60.7%). Among those living in the United States for more than 5 years (non-recently arrived persons), there was an increase in tuberculosis cases (+3.4%), a decrease in tuberculosis case rate (average annual percent change of −4.9%), and an increase in population (+62.7%). In 2010, 66.7% of Mexico-born cases were among non–recently arrived persons, compared with 51.1% in 2000. Although border states reported the highest proportions (>15%) of tuberculosis cases that were Mexico-born, the highest Mexico-born–specific tuberculosis case rates (>20/100,000 population) were in states in the eastern and southeastern regions of the United States. Conclusions The decline in tuberculosis morbidity among Mexico-born persons may be attributed to fewer newly arrived persons from Mexico and lower tuberculosis case rates among non–recently arrived Mexico-born persons. The extent of the decline was dampened by an unchanged tuberculosis case rate among newly arrived persons from Mexico and a large increase in the non–recently arrived Mexico-born population. If current trends continue, tuberculosis morbidity among Mexico-born persons will be increasingly driven by those who have been living in the United States for more than 5 years. PMID:24708206

Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

PubMed

Sharma, Aditya; Hill, Andrew; Kurbatova, Ekaterina; van der Walt, Martie; Kvasnovsky, Charlotte; Tupasi, Thelma E; Caoili, Janice C; Gler, Maria Tarcela; Volchenkov, Grigory V; Kazennyy, Boris Y; Demikhova, Olga V; Bayona, Jaime; Contreras, Carmen; Yagui, Martin; Leimane, Vaira; Cho, Sang Nae; Kim, Hee Jin; Kliiman, Kai; Akksilp, Somsak; Jou, Ruwen; Ershova, Julia; Dalton, Tracy; Cegielski, Peter

2017-07-01

Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study.

PubMed

Pan, Sung-Ching; Ku, Chu-Chang; Kao, Diana; Ezzati, Majid; Fang, Chi-Tai; Lin, Hsien-Ho

2015-05-01

Diabetes increases the risk of tuberculosis incidence and the risk of adverse treatment outcomes in patients with tuberculosis. Because prevalence of diabetes is increasing in low-income and middle-income countries where the burden of tuberculosis is high, prevention of diabetes carries the potential to improve tuberculosis control worldwide. We used dynamic tuberculosis transmission models to analyse the potential effect of diabetes on tuberculosis epidemiology in 13 countries with high tuberculosis burden. We used data for previous diabetes prevalence in each country and constructed scenarios to represent the potential ranges of future diabetes prevalence. The country-specific model was calibrated to the estimated trend of tuberculosis incidence. We estimated the tuberculosis burden that can be reduced by alternative scenarios of diabetes prevention. If the prevalence of diabetes continues to rise as it has been in the past decade in the 13 countries (base case scenario), by 2035, the cumulative reduction in tuberculosis incidence would be 8·8% (95% credible interval [CrI] 4·0-15·8) and mortality would be 34·0% (30·3-39·6). Lowering the prevalence of diabetes by an absolute level of 6·6-13·8% could accelerate the decline of tuberculosis incidence by an absolute level of 11·5-25·2% and tuberculosis mortality by 8·7-19·4%. Compared with the base case scenario, stopping the rise of diabetes would avoid 6·0 million (95% CrI 5·1-6·9) incident cases and 1·1 million (1·0-1·3) tuberculosis deaths in 13 countries during 20 years. If interventions reduce diabetes incidence by 35% by 2025, 7·8 million (6·7-9·0) tuberculosis cases and 1·5 million (1·3-1·7) tuberculosis deaths could be averted by 2035. The diabetes epidemic could substantially affect tuberculosis epidemiology in high burden countries. The communicable disease and non-communicable disease sectors need to move beyond conventional boundaries and link with each other to form a joint response to diabetes and tuberculosis. Taiwan National Science Council. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel

PubMed Central

Gupta, Amita; Mathad, Jyoti S.; Abdel-Rahman, Susan M.; Albano, Jessica D.; Botgros, Radu; Brown, Vikki; Browning, Renee S.; Dawson, Liza; Dooley, Kelly E.; Gnanashanmugam, Devasena; Grinsztejn, Beatriz; Hernandez-Diaz, Sonia; Jean-Philippe, Patrick; Kim, Peter; Lyerly, Anne D.; Mirochnick, Mark; Mofenson, Lynne M.; Montepiedra, Grace; Piper, Jeanna; Sahin, Leyla; Savic, Radojka; Smith, Betsy; Spiegel, Hans; Swaminathan, Soumya; Watts, D. Heather; White, Amina

2016-01-01

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15–44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population. PMID:26658057

[Tuberculosis and malaria global prophylaxis in the light of decisions of the Big Eight].

PubMed

Onishchenko, G G

2008-01-01

At the present time about two million people, one third of the Earth's population, are carriers of tuberculosis agent. Though tuberculosis is curable disease, it continues to take away lives of about 4400 persons; most of them are young and are in the most productive age. The most active incidence rate of tuberculosis occurs in the countries of Africa to the south of Sahara (29% of all cases of tuberculosis per head); half of new cases of tuberculosis fall on Asian countries: Bangladesh, China, India, Indonesia, Pakistan, Philippines. The governments of Big Eight maintain activities that have stabilized morbidity of tuberculosis on a world scale. Over 11 years (1995 - 2006) World Health Organization (WHO) implemented the DOTS strategy (Directly Observed Treatment with Short course of chemotherapy) in 183 countries and tested it on 26 millions patients with tuberculosis. Global data acquisition in 2005 found out morbidity of tuberculosis in 59% (the aim is 70%) and successful cure in 84% cases (the aim is 85 %). In 2006 WHO started realization of the Global Plan "Stop tuberculosis" (2006 - 2012). At the present time Global Fund use about 17% its resources to finance programs against tuberculosis. These funds help to reveal 5 millions extra cases of tuberculosis and cure 3 millions patients in the network of DOTS.

Recurrent tuberculosis in an urban area in China: Relapse or exogenous reinfection?

PubMed

Shen, Xin; Yang, Chongguang; Wu, Jie; Lin, Senlin; Gao, Xu; Wu, Zheyuan; Tian, Jiyun; Gan, Mingyu; Luo, Tao; Wang, Lili; Yu, Chenlei; Mei, Jian; Pan, Qichao; DeRiemer, Kathryn; Yuan, ZhengAn; Gao, Qian

2017-03-01

Recurrent tuberculosis is an important indicator of the effectiveness of tuberculosis control and can occur by relapse or exogenous reinfection. We conducted a retrospective cohort study on all bacteriologically confirmed tuberculosis cases that were successfully treated between 2000 and 2012 in Shanghai, an urban area with a high number but a low prevalence rate of tuberculosis cases and a low prevalence of HIV infection. Genotyping the Mycobacterium tuberculosis from clinical isolates was used to distinguish between relapse and reinfection. In total, 5.3% (710/13,417) of successfully treated cases had a recurrence, a rate of 7.55 (95% CI 7.01-8.13) episodes per 1000 person-years, more than 18 times the rate of tuberculosis in the general population. Patients who were male, age 30-59, retreatment cases, had cavitation, diabetes, drug-resistant or multidrug-resistant tuberculosis in their initial episode of tuberculosis, were at high risk for a recurrence. Among 141 recurrent cases that had paired isolates, 59 (41.8%) had different genotypes, indicating reinfection with a different strain. Patients who completed treatment were still at high risk of another episode of tuberculosis and exogenous reinfection contributed a significant proportion of the recurrent tuberculosis cases. Targeted control strategies are needed to prevent new tuberculosis infections in this setting. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recurrent tuberculosis in an urban area in China: relapse or exogenous reinfection?

PubMed Central

Shen, Xin; Yang, Chongguang; Wu, Jie; Lin, Senlin; Gao, Xu; Wu, Zheyuan; Tian, Jiyun; Gan, Mingyu; Luo, Tao; Wang, Lili; Yu, Chenlei; Mei, Jian; Pan, Qichao; DeRiemer, Kathryn; Yuan, ZhengAn; Gao, Qian

2017-01-01

Recurrent tuberculosis is an important indicator of the effectiveness of tuberculosis control and can occur by relapse or exogenous reinfection. We conducted a retrospective cohort study on all bacteriologically confirmed tuberculosis cases that were successfully treated between 2000 and 2012 in Shanghai, an urban area with a high number but a low prevalence rate of tuberculosis cases and a low prevalence of HIV infection. Genotyping the Mycobacterium tuberculosis from clinical isolates was used to distinguish between relapse and reinfection. In total, 5.3% (710/13,417) of successfully treated cases had a recurrence, a rate of 7.55 (95% CI 7.01–8.13) episodes per 1000 person-years, more than 18 times the rate of tuberculosis in the general population. Patients who were male, age 30–59, retreatment cases, had cavitation, diabetes, drug-resistant or multidrug-resistant tuberculosis in their initial episode of tuberculosis, were at high risk for a recurrence. Among 141 recurrent cases that had paired isolates, 59 (41.8%) had different genotypes, indicating reinfection with a different strain. Patients who completed treatment were still at high risk of another episode of tuberculosis and exogenous reinfection contributed a significant proportion of the recurrent tuberculosis cases. Targeted control strategies are needed to prevent new tuberculosis infections in this setting. PMID:28237039

Knowledge of and attitudes toward tuberculosis of Turkish nursing and midwifery students.

PubMed

Akin, Semiha; Gorak, Gulay; Unsar, Serap; Mollaoglu, Mukadder; Ozdilli, Kursad; Durna, Zehra

2011-11-01

The aim of the study was to describe the level of knowledge and the attitudes of Turkish nursing and midwifery students toward tuberculosis in an attempt to understand and determine whether there is a need for improvement in nursing and midwifery education regarding tuberculosis. The research is a descriptive study conducted at four nursing or midwifery schools in Turkey. The sample was composed of 615 students who were first-, second-, third-, or fourth-year nursing and midwifery students. Data were collected using the Knowledge and Attitudes toward Treatment and Control of Tuberculosis Questionnaire. The level of tuberculosis knowledge was poor [7.22±1.92 (range: 2-9)]. The attitudes of nursing and midwifery students toward tuberculosis were generally negative. Only 5.9% of the sample would prefer to care for patients with tuberculosis. Students who received tuberculosis lectures/education had higher levels of knowledge and more positive attitudes toward tuberculosis than their peers who did not receive such education. In order to fight effectively against tuberculosis, positive attitudes toward tuberculosis must be developed among health care teams, and awareness of tuberculosis via theoretical and practical education, starting from the initial semesters of the professional education, must be increased. Copyright © 2010 Elsevier Ltd. All rights reserved.

Impact of previous ART and of ART initiation on outcome of HIV-associated tuberculosis.

PubMed

Girardi, Enrico; Palmieri, Fabrizio; Angeletti, Claudio; Vanacore, Paola; Matteelli, Alberto; Gori, Andrea; Carbonara, Sergio; Ippolito, Giuseppe

2012-01-01

Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0-16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death.

Invasive Pulmonary Aspergillosis-mimicking Tuberculosis.

PubMed

Kim, Sung-Han; Kim, Mi Young; Hong, Sun In; Jung, Jiwon; Lee, Hyun Joo; Yun, Sung-Cheol; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee

2015-07-01

Pulmonary tuberculosis is occasionally confused with invasive pulmonary aspergillosis (IPA) in transplant recipients, since clinical suspicion and early diagnosis of pulmonary tuberculosis and IPA rely heavily on imaging modes such as computed tomography (CT). We therefore investigated IPA-mimicking tuberculosis in transplant recipients. All adult transplant recipients who developed tuberculosis or IPA at a tertiary hospital in an intermediate tuberculosis-burden country during a 6-year period were enrolled. First, we tested whether experienced radiologists could differentiate pulmonary tuberculosis from IPA. Second, we determined which radiologic findings could help us differentiate them. During the study period, 28 transplant recipients developed pulmonary tuberculosis after transplantation, and 80 patients developed IPA after transplantation. Two experienced radiologists scored blindly 28 tuberculosis and 50 randomly selected IPA cases. The sensitivities of radiologists A and B for IPA were 78% and 68%, respectively (poor agreement, kappa value = 0.25). The sensitivities of radiologists A and B for tuberculosis were 64% and 61%, respectively (excellent agreement, kappa value = 0.77). We then compared the CT findings of the 28 patients with tuberculosis and 80 patients with IPA. Infarct-shaped consolidations and smooth bronchial wall thickening were more frequent in IPA, and mass-shaped consolidations and centrilobular nodules (<10 mm, clustered) were more frequent in tuberculosis. Certain CT findings appear to be helpful in differentiating between IPA and tuberculosis. Nevertheless, the CT findings of about one-third of pulmonary tuberculosis cases in transplant recipients are very close to those of IPA. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease

PubMed Central

Welch, Ryan J.; Lawless, Kathleen M.

2012-01-01

Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients ≥90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies. PMID:22301692

[Abdominal Tuberculosis in children and adolescents. A diagnostic challenge].

PubMed

Reto Valiente, Luz; Pichilingue Reto, Catherina; Pichilingue Prieto, Oscar; Dolores Cerna, Ketty

2015-01-01

To present our experience with abdominal tuberculosis in children and adolescents treated in our hospital from 2003 - 2014. It is a retrospective study. We have collected clinical records of inpatients <20 years old who were admitted at Hipolito Unanue Hospital from January 2003 to July 2014, with diagnosis of abdominal tuberculosis. Among the overall 30 patients, 16 (53.33%) were female and 14 (46.67%) were male. The mean age of all patients was 16.5 years. The most common clinical features were abdominal pain in 29 (96.67%), fever in 26 (86.67%), ascites in 23 (76.67%) and loss of weight in 21 (70%). 63.33% of the patients were eutrophics, 13.34% were overweight or obese and only 23.33% suffered of malnutrition. TB contact was present in 10 (33.33%). Positive tuberculin skin tests were seen in 10%. Extra-abdominal tuberculosis was found in 22 patients (63.32%). 12 cases had coexisting pulmonary tuberculosis and 4 cases had pleural effusion. 12 patients (40%) had tuberculous peritonitis; 12 patients (40%) had intestinal tuberculosis and peritoneal tuberculosis and 4 patients (13.33%) had intestinal tuberculosis. Bacteriological confirmation of tuberculosis was achieved in 10 cases (33.33%). Antituberculous therapy for 6 months was effective in 29 cases. One patient died who multifocal tuberculosis with HIV had associated. Abdominal tuberculosis is seen in 4.37% of children affected with tuberculosis, of which over 63% will have extra abdominal manifestations. Abdominal tuberculosis should be considered in patients with abdominal pain, fever, weight loss and abnormal chest radiography. Imaging can be useful for early diagnosis of abdominal tuberculosis.

Addressing diabetes mellitus as part of the strategy for ending TB

PubMed Central

Harries, Anthony D.; Kumar, Ajay M.V.; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil

2016-01-01

As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID:26884497

Evaluation of Loopamp™MTBC detection kit for diagnosis of pulmonary tuberculosis at a peripheral laboratory in a high burden setting.

PubMed

Nguyen, Van Anh Thi; Nguyen, Hung Van; Dinh, Thuong Van; Du, Ha Hoang; Do, Chinh Nhu; Marks, Guy B; Nguyen, Nhung Viet

2018-03-01

The Loopamp™MTBC detection kit (TB-LAMP) was designed to replace the sputum smear microscopy for the diagnosis of pulmonary tuberculosis. We evaluated its performance at a peripheral laboratory in Vietnam. The sensitivity of TB-LAMP was 45.5% (28.1%-63.6%), which was equal to 3-sputum smear microscopy but lower than that of Xpert MTB/RIF (87.8% [71.8%-96.6%]). In patients with culture-confirmed TB, sensitivity was 80% (51.9%-95.7%) in smear-positive and 16.7% (3.5%-41.4%) in smear-negative cases. The specificity of TB-LAMP was 95.1% (92.7%-96.9%), which was lower than that of smear microscopy (98.9% [97.5%-99.7%]) and Xpert MTB/RIF (99.3% [98.1%-99.9%]) (P<0.05). The probability of TB detection by TB-LAMP was more influenced by sample quality and viscosity than were smear microscopy, Xpert MTB/RIF, and culture. The present data do not support the use of TB-LAMP as a replacement test for smear microscopy in peripheral laboratories. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost-utility analysis of LED fluorescence microscopy in the diagnosis of pulmonary tuberculosis in Indian settings.

PubMed

Kelly, V; Sagili, K D; Satyanarayana, S; Reza, L W; Chadha, S S; Wilson, N C

2015-06-01

With support from the Stop TB Partnership's TB REACH Wave 2 Grant, diagnostic microscopy services for tuberculosis (TB) were upgraded from conventional Ziehl-Neelsen (ZN) based sputum microscopy to light emitting diode technology-based fluorescence microscopy (LED FM) in 200 high-workload microscopy centres in India as a pilot intervention. To evaluate the cost-effectiveness of LED-FM over conventional ZN microscopy to inform further scale-up. A decision-tree model was constructed to assess the cost utility of LED FM over ZN microscopy. The results were summarised using incremental cost-effectiveness ratio (ICER); one-way and probabilistic sensitivity analyses were also conducted to address uncertainty within the model. Data were analysed from 200 medical colleges in 2011 and 2012, before and after the introduction of LED microscopes. A full costing analysis was carried out from the perspective of a national TB programme. The ICER was calculated at US$14.64 per disability-adjusted life-year, with an 82% probability of being cost-effective at a willingness-to-pay threshold equivalent to Indian gross domestic product per capita. LED FM is a cost-effective intervention for detecting TB cases in India at high-workload medical college settings.

[Disease numbers in pneumology - a projection to 2060].

PubMed

Pritzkuleit, R; Beske, F; Katalinic, A

2010-09-01

The demographic change leads to a change in the age-composition of the population. We have calculated a status quo projection of the absolute numbers for five diagnoses of the lung (COPD, CAP, lung cancer, bronchial asthma and tuberculosis) for Germany up to 2060. Based on the 12 (th) coordinated population prediction of the Federal Statistics Office, we transferred age- and sex-specific incidence and prevalence rates, respectively, to the expected population. All described developments are based solely on demographic changes. The absolute numbers of bronchial asthma and tuberculosis will experience a minor decrease. We expect at first increasing and later decreasing case numbers for COPD and lung cancer. A major increase of the case numbers for CAP will be probable. By reason of a decreasing population, the rates (burden of disease for the population) will increase considerably. The demographic change is mainly caused by increasing life expectancy, constantly low birth rates, and the entry of the baby-boom generation into the age of higher disease risks. A discussion about prioritisation of health care is needed because of the rising burdens for the health system, including diseases of the lung. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Plasma contributes to the antimicrobial activity of whole blood against Mycobacterium tuberculosis.

PubMed

López-Medrano, Ramiro; Guerra-Laso, José Manuel; López-Fidalgo, Eduardo; Diez-Tascón, Cristina; García-García, Silvia; Blanco-Conde, Sara; Rivero-Lezcano, Octavio Miguel

2016-10-01

The whole blood model for infection has proven useful to analyze the immunological response to Mycobacterium tuberculosis, because it exerts a significant antimicrobial activity. Although this activity has been generally assumed to be cellular, we have found that the leukocyte fraction of blood from healthy volunteers did not kill the bacilli. We have discovered that plasma was responsible for a large proportion, but not all, of the antimicrobial activity. Furthermore, infected monocytes controlled the mycobacterial multiplication when cultivated in the presence of plasma. Intriguingly, serum from the same donors did not share this activity, although it was able to eliminate the non-pathogenic Mycobacterium gordonae To identify the remaining components that participate in the antimycobacterial activity we fractionated blood in leukocytes, plasma, erythrocytes and platelets, and analyzed the bactericidal power of each fraction and their combinations using a factorial design. We found that erythrocytes, but not platelets, participated and showed by flow cytometry that mycobacteria physically associated with erythrocytes. We propose that in exposed healthy individuals that show 'early clearance' of the mycobacteria, the innate response is predominantly humoral, probably through the effect of antimicrobial peptides and proteins. © The Author(s) 2016.

77 FR 8877 - Advisory Council for the Elimination of Tuberculosis (ACET)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

... Council for the Elimination of Tuberculosis (ACET) In accordance with section 10(a)(2) of the Federal... for Health, and the Director, CDC, regarding the elimination of tuberculosis. Specifically, the... eliminating tuberculosis. Matters to be Discussed: Agenda items include the following topics: (1) Tuberculosis...

Polymorphisms of twenty regulatory proteins between Mycobacterium tuberculosis and Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Mycobacterium tuberculosis and Mycobacterium bovis are responsible for tuberculosis in humans or animals, respectively. Both species are closely related and belong to the Mycobacterium tuberculosis complex (MTC). M. tuberculosis is the most ancient species from which M. bovis and the other members o...

Pulmonary tuberculosis

MedlinePlus

TB; Tuberculosis - pulmonary; Mycobacterium - pulmonary ... Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis) . TB is contagious. This means the bacteria is easily spread from an infected person ...

9 CFR 77.3 - Tuberculosis classifications of States and zones.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Tuberculosis classifications of States... TUBERCULOSIS General Provisions § 77.3 Tuberculosis classifications of States and zones. The Administrator shall classify each State for tuberculosis in accordance with this part. A zone comprising less than an...

76 FR 7855 - Proposed Data Collections Submitted for Public Comment and Recommendations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... Report of Verified Case of Tuberculosis (RVCT), (OMB No.0920-0026 exp. 5/31/2011)--Extension--National... are infected with Mycobacterium tuberculosis and about 10% of these persons will develop tuberculosis... tuberculosis surveillance using the standardized Report of Verified Case of Tuberculosis (RVCT). Data collected...

29 CFR 1904.11 - Recording criteria for work-related tuberculosis cases.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 5 2010-07-01 2010-07-01 false Recording criteria for work-related tuberculosis cases... Forms and Recording Criteria § 1904.11 Recording criteria for work-related tuberculosis cases. (a) Basic... tuberculosis (TB), and that employee subsequently develops a tuberculosis infection, as evidenced by a positive...

75 FR 33316 - Advisory Council for the Elimination of Tuberculosis Meeting (ACET)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

... Council for the Elimination of Tuberculosis Meeting (ACET) In accordance with section 10(a)(2) of the... Health, and the Director, CDC, regarding the elimination of tuberculosis. Specifically, the Council makes... tuberculosis. Matters To Be Discussed: Agenda items include: Issues pertaining to pediatric tuberculosis...

78 FR 28221 - Advisory Council for the Elimination of Tuberculosis Meeting (ACET)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-14

... Council for the Elimination of Tuberculosis Meeting (ACET) In accordance with section 10(a)(2) of the... for Health, and the Director, CDC, regarding the elimination of tuberculosis. Specifically, the... eliminating tuberculosis. Matters To Be Discussed: Agenda items include the following topics: 1) Tuberculosis...

75 FR 15443 - Advancing the Development of Diagnostic Tests and Biomarkers for Tuberculosis; Public Workshop...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

...] Advancing the Development of Diagnostic Tests and Biomarkers for Tuberculosis; Public Workshop; Request for... workshop entitled ``Advancing the Development of Diagnostic Tests and Biomarkers for Tuberculosis (TB... Tuberculosis in the United States, Committee on the Elimination of Tuberculosis in the United States, Division...

9 CFR 77.3 - Tuberculosis classifications of States and zones.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Tuberculosis classifications of States... TUBERCULOSIS General Provisions § 77.3 Tuberculosis classifications of States and zones. The Administrator shall classify each State for tuberculosis in accordance with this part. A zone comprising less than an...

29 CFR 1904.11 - Recording criteria for work-related tuberculosis cases.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 5 2013-07-01 2013-07-01 false Recording criteria for work-related tuberculosis cases... Forms and Recording Criteria § 1904.11 Recording criteria for work-related tuberculosis cases. (a) Basic... tuberculosis (TB), and that employee subsequently develops a tuberculosis infection, as evidenced by a positive...

29 CFR 1904.11 - Recording criteria for work-related tuberculosis cases.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 5 2012-07-01 2012-07-01 false Recording criteria for work-related tuberculosis cases... Forms and Recording Criteria § 1904.11 Recording criteria for work-related tuberculosis cases. (a) Basic... tuberculosis (TB), and that employee subsequently develops a tuberculosis infection, as evidenced by a positive...

29 CFR 1904.11 - Recording criteria for work-related tuberculosis cases.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 5 2014-07-01 2014-07-01 false Recording criteria for work-related tuberculosis cases... Forms and Recording Criteria § 1904.11 Recording criteria for work-related tuberculosis cases. (a) Basic... tuberculosis (TB), and that employee subsequently develops a tuberculosis infection, as evidenced by a positive...

9 CFR 77.3 - Tuberculosis classifications of States and zones.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Tuberculosis classifications of States... TUBERCULOSIS General Provisions § 77.3 Tuberculosis classifications of States and zones. The Administrator shall classify each State for tuberculosis in accordance with this part. A zone comprising less than an...

9 CFR 77.3 - Tuberculosis classifications of States and zones.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Tuberculosis classifications of States... TUBERCULOSIS General Provisions § 77.3 Tuberculosis classifications of States and zones. The Administrator shall classify each State for tuberculosis in accordance with this part. A zone comprising less than an...

9 CFR 77.3 - Tuberculosis classifications of States and zones.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Tuberculosis classifications of States... TUBERCULOSIS General Provisions § 77.3 Tuberculosis classifications of States and zones. The Administrator shall classify each State for tuberculosis in accordance with this part. A zone comprising less than an...

29 CFR 1904.11 - Recording criteria for work-related tuberculosis cases.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 5 2011-07-01 2011-07-01 false Recording criteria for work-related tuberculosis cases... Forms and Recording Criteria § 1904.11 Recording criteria for work-related tuberculosis cases. (a) Basic... tuberculosis (TB), and that employee subsequently develops a tuberculosis infection, as evidenced by a positive...

An Unusual Gross Appearance of Vulval Tuberculosis Masquerading as Tumor

PubMed Central

Arakeri, Surekha U.

2014-01-01

Tuberculosis of the vulva is very rare. It is found in about 0.2% of the cases of genital tract tuberculosis. It usually presents as small shallow ulcers and multiple sinus tracts or rarely as elephantiasis of vulva. Except for very rare cases of primary tuberculosis in the vulva, it is usually associated with tuberculosis elsewhere in the body leading to secondary tuberculosis. Here, we report a case of secondary vulval tuberculosis which presented as a vulval mass in a 40-year-old female patient. The rarity of this presentation in the female genital tract is emphasized. PMID:25298898

An unusual gross appearance of vulval tuberculosis masquerading as tumor.

PubMed

Arakeri, Surekha U; Sinkar, Prachi

2014-01-01

Tuberculosis of the vulva is very rare. It is found in about 0.2% of the cases of genital tract tuberculosis. It usually presents as small shallow ulcers and multiple sinus tracts or rarely as elephantiasis of vulva. Except for very rare cases of primary tuberculosis in the vulva, it is usually associated with tuberculosis elsewhere in the body leading to secondary tuberculosis. Here, we report a case of secondary vulval tuberculosis which presented as a vulval mass in a 40-year-old female patient. The rarity of this presentation in the female genital tract is emphasized.

Cutaneous Tuberculosis

PubMed Central

Frankel, Amylynne; Penrose, Carolin

2009-01-01

Cutaneous tuberculosis occurs rarely, despite a high and increasing prevalence of tuberculosis worldwide. Mycobacterium tuberculosis, Mycobacterrium bovis, and the Bacille Calmette-Guérin vaccine can cause tuberculosis involving the skin. Cutaneous tuberculosis can be acquired exogenously or endogenously and present as a multitude of differing clinical morphologies. Diagnosis of these lesions can be difficult, as they resemble many other dermatological conditions that are often primarily considered. Further, microbiological confirmation is poor, despite scientific advances, such as the more frequent use of polymerase chain reaction. The authors report a case that illustrates the challenges faced by dermatologists when considering a diagnosis of cutaneous tuberculosis. PMID:20725570

New indicators proposed to assess tuberculosis control and elimination in Cuba.

PubMed

González, Edilberto R; Armas, Luisa

2012-10-01

Following 48 years of successful operation of the National Tuberculosis Control Program, Cuban health authorities have placed tuberculosis elimination on the agenda. To this end some tuberculosis control processes and their indicators need redesigned and new ones introduced, related to: number and proportion of suspected tuberculosis cases among vulnerable population groups; tuberculosis suspects with sputum microscopy and culture results useful for diagnosis (interpretable); and number of identified contacts of reported tuberculosis cases who were fully investigated. Such new indicators have been validated and successfully implemented in all provinces (2011-12) and are in the approval pipeline for generalized use in the National Tuberculosis Control Program. These indicators complement existing criteria for quality of case detection and support more comprehensive program performance assessment.

Tuberculosis--triumph and tragedy.

PubMed

Singh, M M

2003-03-01

Tuberculosis has been making havoc worldwide with an 11.9 million cases to be involved by the year 2005. In India, about 2 million cases are infected every year. Regarding triumphs and tragedies in the control of tuberculosis some points as follows are discussed. (1) Tuberculosis Control Programmes from National Tuberculosis Programme (NTP) to Revised National Tuberculosis Control Programme (RNTCP) and Directly Observed Treatment, Short course (DOTS). (2) Problem of multidrug resistance (MDR) tuberculosis and (3) HIV and tuberculosis. DOTS being largely based on Indian research. It is now being applied worldwide. MDR is strictly a man made problem. Poor prescriptions, poor case management, lack of coordinated education and haphazard treatment research result in drug resistance. Treatment of MDR is difficult. The drug acceptability, tolerance and toxicity have to be considered. HIV and tuberculosis form a deadly duo. They mean more cases, more costs and more national losses.

Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis.

PubMed

Mishra, Bibhuti B; Lovewell, Rustin R; Olive, Andrew J; Zhang, Guoliang; Wang, Wenfei; Eugenin, Eliseo; Smith, Clare M; Phuah, Jia Yao; Long, Jarukit E; Dubuke, Michelle L; Palace, Samantha G; Goguen, Jon D; Baker, Richard E; Nambi, Subhalaxmi; Mishra, Rabinarayan; Booty, Matthew G; Baer, Christina E; Shaffer, Scott A; Dartois, Veronique; McCormick, Beth A; Chen, Xinchun; Sassetti, Christopher M

2017-05-15

Nitric oxide contributes to protection from tuberculosis. It is generally assumed that this protection is due to direct inhibition of Mycobacterium tuberculosis growth, which prevents subsequent pathological inflammation. In contrast, we report that nitric oxide primarily protects mice by repressing an interleukin-1- and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes bacterial replication. Using M. tuberculosis mutants as indicators of the pathogen's environment, we inferred that granulocytic inflammation generates a nutrient-replete niche that supports M. tuberculosis growth. Parallel clinical studies indicate that a similar inflammatory pathway promotes tuberculosis in patients. The human 12/15-lipoxygenase orthologue, ALOX12, is expressed in cavitary tuberculosis lesions; the abundance of its products correlates with the number of airway neutrophils and bacterial burden and a genetic polymorphism that increases ALOX12 expression is associated with tuberculosis risk. These data suggest that M. tuberculosis exploits neutrophilic inflammation to preferentially replicate at sites of tissue damage that promote contagion.

Progress on mechanism of ethambutol resistance in Mycobacterium Tuberculosis.

PubMed

Wang, Ting; Jiao, Wei-wei; Shen, A-dong

2016-10-20

The occurance and prevalence of multidrug-resistant tuberculosis poses a serious threat to the global tuberculosis control. Ethambutol (EMB) is one of the first-line anti-tuberculosis drugs, which is usually used in combination with isoniazid and rifampicin for treating pan-sensitive tuberculosis, and it can also be used in drug-resistant tuberculosis. However, the situation of EMB resistance is alarmingly high, especially in multi-drug resistant tuberculosis. In China, EMB resistance rate in the previously treated cases was up to 17.2% and showed an increased tendency. What was worse, 51.3%-66.7% of multidrug-resistant tuberculosis cases were resistant to EMB. Thus, it is important to understand the drug resistance mechanism of EMB, which will help to slow down the drug resistance rate of EMB. In this review, we focus on the current status of EMB resistance, the effects of EMB and the mechanisms of EMB resistance in Mycobacterium tuberculosis.

Detection of lipoarabinomannan as a diagnostic test for tuberculosis.

PubMed Central

Sada, E; Aguilar, D; Torres, M; Herrera, T

1992-01-01

A coagglutination technique was established for the detection of lipoarabinomannan of Mycobacterium tuberculosis in human serum samples and evaluated for its utility in the diagnosis of tuberculosis at the Instituto Nacional de Enfermedades Respiratorias in Mexico City. The test had a sensitivity of 88% in patients with sputum-smear-positive active pulmonary tuberculosis. The sensitivity in patients with active pulmonary tuberculosis negative for acid-fast bacilli in sputum was 67%. Less favorable results were obtained for patients with AIDS and tuberculosis, with a sensitivity of 57%. The specificity in control patients with lung diseases different from tuberculosis and in healthy subjects was 100%. The positive predictive value was 100%, and the negative predictive value for patients with sputum-positive active pulmonary tuberculosis was 97%. The results of this study suggest that the detection of lipoarabinomannan is an accurate test for the diagnosis of pulmonary tuberculosis. PMID:1401008

Polymorphisms of 20 regulatory proteins between Mycobacterium tuberculosis and Mycobacterium bovis.

PubMed

Bigi, María M; Blanco, Federico Carlos; Araújo, Flabio R; Thacker, Tyler C; Zumárraga, Martín J; Cataldi, Angel A; Soria, Marcelo A; Bigi, Fabiana

2016-08-01

Mycobacterium tuberculosis and Mycobacterium bovis are responsible for tuberculosis in humans and animals, respectively. Both species are closely related and belong to the Mycobacterium tuberculosis complex (MTC). M. tuberculosis is the most ancient species from which M. bovis and other members of the MTC evolved. The genome of M. bovis is over >99.95% identical to that of M. tuberculosis but with seven deletions ranging in size from 1 to 12.7 kb. In addition, 1200 single nucleotide mutations in coding regions distinguish M. bovis from M. tuberculosis. In the present study, we assessed 75 M. tuberculosis genomes and 23 M. bovis genomes to identify non-synonymous mutations in 202 coding sequences of regulatory genes between both species. We identified species-specific variants in 20 regulatory proteins and confirmed differential expression of hypoxia-related genes between M. bovis and M. tuberculosis. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

Congenital tuberculosis in an extremely preterm infant conceived after in vitro fertilization: case report.

PubMed

Samedi, Veronica; Field, Stephen K; Al Awad, Essa; Ratcliffe, Gregory; Yusuf, Kamran

2017-02-20

Congenital tuberculosis is a rare manifestation of tuberculosis. The diagnosis is often delayed, especially in preterm neonates because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy. We report a case of congenital tuberculosis in an infant born at 24 weeks of gestation to a mother who presented with uncontrolled seizures during preterm labor. Maternal diagnosis was initially made by placental pathology, and later confirmed by isolation of Mycobacterium tuberculosis in urine, gastric aspirates and sputum. Full screening was performed on the newborn infant, and both mother and infant were successfully treated for tuberculosis with a four drug regimen. Pregnancy can exacerbate latent tuberculosis and women originating from endemic areas are especially susceptible. The best way to prevent congenital tuberculosis is to have a high index of suspicion and identify and treat tuberculosis in pregnant women.

Surgical aspects of pulmonary tuberculosis: an update.

PubMed

Dewan, Ravindra Kumar; Pezzella, A Thomas

2016-10-01

Tuberculosis remains a major global medical challenge and concern. In the world's population of over 7.4 billion people, 8.6 million are estimated to be infected with Mycobacterium tuberculosis; another 2.2 billion have latent tuberculosis. There is an annual incidence of 16,000 new cases in the USA and 7-8 million new cases worldwide, of which 440,000 are multidrug-resistant or extensively multidrug-resistant, mainly in developing countries or emerging economies. According to the World Health Organization, the incidence of tuberculosis is 133 cases per 100,000 of the population; 3.3% new cases are drug resistant and 20% are already treated cases. Of the drug-resistant cases, 9.7% are extensively drug-resistant. The annual global mortality attributable to tuberculosis is over 1.3 million people. The association with HIV/AIDS in 430,000 people has compounded the global concern and challenge. This review presents the historical indications for surgical treatment of tuberculosis, reviews the current literature and clinical experience, and collates this into increased awareness and contemporary understanding of the indications and need for surgery in primary active tuberculosis, adjuvant surgical therapy for multidrug-resistant tuberculosis, and the complications of chronic tuberculosis sequelae or previous tuberculosis surgery. © The Author(s) 2016.

Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

PubMed Central

Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.

2011-01-01

Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732

[USE OF QuantiFERON-TB Gold in Tube AND T-SPOT.TB FOR DIAGNOSING PATIENTS WITH SUSPECTED PULMONARY TUBERCULOSIS].

PubMed

Okimoto, Niro; Kurihara, Takeyuki; Miyashita, Naoyuki

2016-04-01

We analyzed the use of QFT-TB Gold in Tube and T-SPOT.TB in diagnosing patients with suspected pulmonary tuberculosis. We evaluated 122 patients with suspected pulmonary tuberculosis (where chest X-ray showed consolidation or. tumor shadow in predilection sites of pulmonary tuberculosis and through contact investigation). QFT-TB Gold and T-SPOT.TB were performed for all the patients. The positive response rate and history of pulmonary tuberculosis in patients who showed positive results for the tests were evaluated. Ninteen patients showed positive results for QFT-TB Gold, and 9, for T-SPOT.TB. Four patients showed positive results for QFT-TB Gold, and 3, for T-SPOT.TB in 4 patients with active tuberculosis. The patients without active tuberculosis whose IGRAs were positive (old pulmonary tuberculosis, Mycobacterium avium cmplex, pneumonia, lung cancer, pulmonary sequestration, bronchiectasis) had a past history of pulmonary tuberculosis. The positive result rate of QFT?-TB Gold was higher than that of T-SPOT.TB in the subjects with suspected pulmonary tuberculosis. We think that QFT-TB Gold reflected the past history of pulmonary tuberculosis.

Co-evolution of Mycobacterium tuberculosis and Homo sapiens

PubMed Central

Brites, Daniela; Gagneux, Sebastien

2015-01-01

The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future ‘genome-to-genome’ studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines. PMID:25703549

Contact Investigation in Households of Patients with Tuberculosis in Hanoi, Vietnam: A Prospective Cohort Study

PubMed Central

Fox, Gregory James; Nhung, Nguyen Viet; Sy, Dinh Ngoc; Lien, Luu Thi; Cuong, Nguyen Kim; Britton, Warwick John; Marks, Guy Barrington

2012-01-01

Setting Existing tuberculosis control strategies in Vietnam are based on symptomatic patients attending health services for investigation. This approach has not resulted in substantial reductions in the prevalence of tuberculosis disease, despite the National Tuberculosis Program achieving high treatment completion rates. Alternative approaches are being considered. Objective To determine the feasibility and yield of contact investigation in households of patients with smear positive pulmonary tuberculosis among household members of tuberculosis patients in Hanoi, Vietnam. Methods Household contacts of patients with smear positive pulmonary tuberculosis were recruited at four urban and rural District Tuberculosis Units in Hanoi. Clinical and radiological screening was conducted at baseline, six months and 12 months. Sputum microscopy and culture was performed in contacts suspected of having tuberculosis. MIRU-VNTR molecular testing was used to compare the strains of patients and their contacts with disease. Results Among 545 household contacts of 212 patients, four were diagnosed with tuberculosis at baseline (prevalence 734 cases per 100,000 persons, 95% CI 17–1451) and one was diagnosed with tuberculosis during the subsequent 12 months after initial screening (incidence 180 cases per 100,000 person-years, 95% CI 44–131). Two of these cases were culture positive for M. tuberculosis and both had identical or near-identical MIRU-VNTR strain types. Conclusion Household contacts of patients with potentially infectious forms of tuberculosis have a high prevalence of disease. Household contact investigation is feasible in Vietnam. Further research is required to investigate its effectiveness. PMID:23166785

Prevalence of pulmonary tuberculosis among prison inmates: A cross-sectional survey at the Correctional and Detention Facility of Abidjan, Côte d'Ivoire

PubMed Central

Koffi, Ange; Danel, Christine; Ouassa, Timothée; Blehoué, Marcel-Angora; Ouattara, Eric; Assemien, Jeanne-d’Arc; Masumbuko, Jean-Marie; Coffie, Patrick; Cartier, Nathalie; Laurent, Arnaud; Raguin, Gilles; Malvy, Denis; N’Dri-Yoman, Thérèse; Eholié, Serge P.; Domoua, Serge K.

2017-01-01

Background In Côte d’Ivoire, a TB prison program has been developed since 1999. This program includes offering TB screening to prisoners who show up with TB symptoms at the infirmary. Our objective was to estimate the prevalence of pulmonary TB among inmates at the Correctional and Detention Facility of Abidjan, the largest prison of Côte d’Ivoire, 16 years after this TB program was implemented. Methods Between March and September 2015, inmates, were screened for pulmonary TB using systematic direct smear microscopy, culture and chest X-ray. All participants were also proposed HIV testing. TB was defined as either confirmed (positive culture), probable (positive microscopy and/or chest X-ray findings suggestive of TB) or possible (signs or symptoms suggestive of TB, no X-Ray or microbiological evidence). Factors associated with confirmed tuberculosis were analysed using multivariable logistic regression. Results Among the 943 inmates screened, 88 (9.3%) met the TB case definition, including 19 (2.0%) with confirmed TB, 40 (4.2%) with probable TB and 29 (3.1%) with possible TB. Of the 19 isolated TB strains, 10 (53%) were TB drug resistant, including 7 (37%) with multi-resistance. Of the 10 patients with TB resistant strain, only one had a past history of TB treatment. HIV prevalence was 3.1% overall, and 9.6%among TB cases. Factors associated with confirmed TB were age ≥30 years (Odds Ratio 3.8; 95% CI 1.1–13.3), prolonged cough (Odds Ratio 3.6; 95% CI 1.3–9.5) and fever (Odds Ratio 2.7; 95% CI 1.0–7.5). Conclusion In the country largest prison, pulmonary TB is still 10 (confirmed) to 44 times (confirmed, probable or possible) as frequent as in the Côte d’Ivoire general population, despite a long-time running symptom-based program of TB detection. Decreasing TB prevalence and limiting the risk of MDR may require the implementation of annual in-cell TB screening campaigns that systematically target all prison inmates. PMID:28759620

Tuberculosis in the lung (image)

MedlinePlus

Tuberculosis is caused by a group of organisms: Mycobacterium tuberculosis, M bovis , M africanum and a few other rarer subtypes. Tuberculosis usually appears as a lung (pulmonary) infection. However, ...

Material incentives and enablers in the management of tuberculosis.

PubMed

Lutge, Elizabeth E; Wiysonge, Charles Shey; Knight, Stephen E; Volmink, Jimmy

2012-01-18

Patient adherence to medications, particularly for conditions requiring prolonged treatment such as tuberculosis, is frequently less than ideal, and can result in poor treatment outcomes. Material incentives (given as cash, vouchers and tokens), have been used to improve adherence. To assess the effects of material incentives in people undergoing diagnostic testing, or receiving prophylactic or curative therapy, for tuberculosis. We undertook a comprehensive search of the Cochrane Infectious Diseases Group Specialized Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; LILACS; Science Citation Index; and reference lists of relevant publications; to 22 June 2011. Randomized controlled trials of material incentives in patients being investigated for tuberculosis, or on treatment for latent or active disease. At least two authors independently screened and selected studies, extracted data, and assessed the risk of bias. The effects of interventions are compared using risk ratios (RR), and presented with 95% confidence intervals (CI). The quality of the evidence was assessed using GRADE. We identified 11 eligible studies. Ten were conducted in the USA: in adolescents (one trial), in injection drug or cocaine users (four trials), in homeless adults (three trials), and in prisoners (two trials). One additional trial recruited malnourished men receiving active treatment for tuberculosis in Timor-Leste.Material incentives may increase the return rate for reading of tuberculin skin test results compared to normal care (two trials, 1371 participants: RR 2.16, 95% CI 1.41 to 3.29, low quality evidence).Similarly, incentives probably improve clinic re-attendance for initiation or continuation of antituberculosis prophylaxis (three trials, 595 participants: RR 1.58, 95% CI 1.27 to 1.96, moderate quality evidence), and may improve subsequent completion of prophylaxis in some settings (three trials, 869 participants: RR 1.79, 95% CI 0.70 to 4.58, low quality evidence).We currently don't know if incentives can improve long-term adherence and completion of antituberculosis treatment for active disease. Only one trial has assessed this and the incentive, given as a daily hot meal, was not well received by the population due to the inconvenience of attending the clinic at midday (one trial, 265 participants, RR 0.98, 95%CI 0.86 to 1.12, very low quality evidence).Several trials have compared different forms or levels of incentive. These comparisons remain limited to single trials and robust conclusions cannot be made. In summary, cash incentives may be more effective than non-cash incentives (return for test results: one trial, 651 participants: RR 1.13, 95%CI 1.07 to 1.19, low quality evidence, adherence to tuberculosis prophylaxis: one trial, 141 participants: RR 1.26, 95%CI 1.02 to 1.56, low quality evidence) and higher amounts of cash may be more effective than lower amounts (return for test results: one trial, 404 participants: RR 1.08, 95%CI 1.01 to 1.16, low quality evidence).Material incentives may also be more effective than motivational education at improving return for tuberculin skin test results (low quality evidence), but may be no more effective than peer counselling, or structured education at improving continuation or completion of prophylaxis (low quality evidence). There is limited evidence to support the use of material incentives to improve return rates for tuberculosis diagnostic test results and adherence to antituberculosis preventive therapy. The data are currently limited to trials among predominantly male drug users, homeless, and prisoner subpopulations in the USA, and therefore the results are not easily generalised to the wider adult population, or to low- and middle-income countries, where the tuberculosis burden is highest.Further high-quality studies are needed to assess both the costs and effectiveness of incentives to improve adherence to long-term treatment of tuberculosis.

Tuberculosis infection control measures in health care facilities offering tb services in Ikeja local government area, Lagos, South West, Nigeria.

PubMed

Kuyinu, Y A; Mohammed, A S; Adeyeye, O O; Odugbemi, B A; Goodman, O O; Odusanya, O O

2016-03-15

Tuberculosis infection among health care workers is capable of worsening the existing health human resource problems of low--and middle-income countries. Tuberculosis infection control is often weakly implemented in these parts of the world therefore, understanding the reasons for poor implementation of tuberculosis infection control guidelines are important. This study was aimed at assessing tuberculosis infection control practices and barriers to its implementation in Ikeja, Nigeria. A cross-sectional study in 20 tuberculosis care facilities (16 public and 4 private) in Ikeja, Lagos was conducted. The study included a facility survey to assess the availability of tuberculosis infection control guidelines, the adequacy of facilities to prevent transmission of tuberculosis and observations of practices to assess the implementation of tuberculosis infection control guidelines. Four focus group discussions were carried out to highlight HCWs' perceptions on tuberculosis infection control guidelines and barriers to its implementation. The observational study showed that none of the clinics had a tuberculosis infection control plan. No clinic was consistently screening patients for cough. Twelve facilities (60%) consistently provided masks to patients who were coughing. Ventilation in the waiting areas was assessed to be adequate in 60% of the clinics while four clinics (20%) possessed N-95 respirators. Findings from the focus group discussions showed weak managerial support, poor funding, under-staffing, lack of space and not wanting to be seen as stigmatizing against tuberculosis patients as barriers that hindered the implementation of TB infection control measures. Tuberculosis infection control measures were not adequately implemented in health facilities in Ikeja, Nigeria. A multi-pronged approach is required to address the identified barriers to the implementation of tuberculosis infection control guidelines.

CD8+ T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

PubMed Central

Nyendak, Melissa; Kiguli, Sarah; Zalwango, Sarah; Mori, Tomi; Mayanja-Kizza, Harriet; Balyejusa, Stephen; Null, Megan; Baseke, Joy; Mulindwa, Deo; Byrd, Laura; Swarbrick, Gwendolyn; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Mudido-Musoke, Philipa; Boom, W. Henry; Lewinsohn, David M.; Lewinsohn, Deborah A.

2012-01-01

Rationale: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis–specific CD8+ T cells are generated in response to high bacillary loads occurring during tuberculosis. Objectives: To determine if M. tuberculosis–specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis. Methods: Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M. tuberculosis–specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8+ T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62). Measurements and Main Results: The proportion of positive CD8+ T-cell assays and magnitude of CD8+ T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis–specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. Conclusions: Among young children, M. tuberculosis–specific CD8+ T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ–producing M. tuberculosis–specific CD8+ T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease. PMID:22071329

European framework for tuberculosis control and elimination in countries with a low incidence. Recommendations of the World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal Netherlands Tuberculosis Association (KNCV) Working Group.

PubMed

Broekmans, J F; Migliori, G B; Rieder, H L; Lees, J; Ruutu, P; Loddenkemper, R; Raviglione, M C

2002-04-01

As countries approach the elimination phase of tuberculosis, specific problems and challenges emerge, due to the steadily declining incidence in the native population, the gradually increasing importance of the importation of latent tuberculosis infection and tuberculosis from other countries and the emergence of groups at particularly high risk of tuberculosis. Therefore, a Working Group of the World Health Organization (WHO), the International Union Against Tuberculosis and Lung Disease (IUATLD) and the Royal Netherlands Tuberculosis Association (KNCV) have developed a new framework for low incidence countries based on concepts and definitions consistent with those of previous recommendations from WHO/IUATLD Working Groups. In low-incidence countries, a broader spectrum of interventions is available and feasible, including: 1) a general approach to tuberculosis which ensures rapid detection and treatment of all the cases and prevention of unnecessary deaths; 2) an overall control strategy aimed at reducing the incidence of tuberculosis infection (risk-group management and prevention of transmission of infection in institutional settings) and 3) a tuberculosis elimination strategy aimed at reducing the prevalence of tuberculosis infection (outbreak management and provision of preventive therapy for specified groups and individuals). Government and private sector commitment towards elimination, effective case detection among symptomatic individuals together with active case finding in special groups, standard treatment of disease and infection, access to tuberculosis diagnostic and treatment services, prevention (e.g. through screening and bacille Calmette-Guéria immunization in specified groups), surveillance and treatment outcome monitoring are prerequisites to implementing the policy package recommended in this new framework document.

CT-Guided Transthoracic Core Biopsy for Pulmonary Tuberculosis: Diagnostic Value of the Histopathological Findings in the Specimen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukuda, Hozumi, E-mail: fkdhzmrad@mitsuihosp.or.jp; Ibukuro, Kenji; Tsukiyama, Toshitaka

We evaluated the value of CT-guided transthoracic core biopsy for the diagnosis of mycobacterial pulmonary nodules. The 30 subjects in this study had pulmonary nodules that had been either diagnosed histopathologically as tuberculosis or were suspected as tuberculosis based on a specimen obtained by CT-guided transthoracic core biopsy. The histopathological findings, the existence of acid-fast bacilli in the biopsy specimens, and the clinical course of the patients after the biopsy were reviewed retrospectively. Two of the three histological findings for tuberculosis that included epithelioid cells, multinucleated giant cells and caseous necrosis were observed in 21 of the nodules which weremore » therefore diagnosed as histological tuberculosis. Six of these 21 nodules were positive for acid-fast bacilli, confirming the diagnosis of tuberculosis. Thirteen of the 21 nodules did not contain acid-fast bacilli but decreased in size in response to antituberculous treatment and were therefore diagnosed as clinical tuberculosis. Seven nodules with only caseous necrosis were diagnosed as suspected tuberculosis, with a final diagnosis of tuberculosis being made in 4 of the nodules and a diagnosis of old tuberculosis in 2 nodules. Two nodules with only multinucleated giant cells were diagnosed as suspected tuberculosis with 1 of these nodules being diagnosed finally as tuberculosis and the other nodule as a nonspecific granuloma. When any two of the three following histopathological findings - epithelioid cells, multinucleated giant cells or caseous necrosis - are observed in a specimen obtained by CT-guided transthoracic core biopsy, the diagnosis of tuberculosis can be established without the detection of acid-fast bacilli or Mycobacterium tuberculosis.« less

The Capacity of Mycobacterium tuberculosis To Survive Iron Starvation Might Enable It To Persist in Iron-Deprived Microenvironments of Human Granulomas.

PubMed

Kurthkoti, Krishna; Amin, Hamel; Marakalala, Mohlopheni J; Ghanny, Saleena; Subbian, Selvakumar; Sakatos, Alexandra; Livny, Jonathan; Fortune, Sarah M; Berney, Michael; Rodriguez, G Marcela

2017-08-15

This study was conducted to investigate the role of iron deprivation in the persistence of Mycobacterium tuberculosis We present evidence of iron restriction in human necrotic granulomas and demonstrate that under iron starvation M. tuberculosis persists, refractive to antibiotics and capable of restarting replication when iron is made available. Transcriptomics and metabolomic analyses indicated that the persistence of M. tuberculosis under iron starvation is dependent on strict control of endogenous Fe utilization and is associated with upregulation of pathogenicity and intrinsic antibiotic resistance determinants. M. tuberculosis mutants compromised in their ability to survive Fe starvation were identified. The findings of this study advance the understanding of the physiological settings that may underpin the chronicity of human tuberculosis (TB) and are relevant to the design of effective antitubercular therapies. IMPORTANCE One-third of the world population may harbor persistent M. tuberculosis , causing an asymptomatic infection that is refractory to treatment and can reactivate to become potentially lethal tuberculosis disease. However, little is known about the factors that trigger and maintain M. tuberculosis persistence in infected individuals. Iron is an essential nutrient for M. tuberculosis growth. In this study, we show, first, that in human granulomas the immune defense creates microenvironments in which M. tuberculosis likely experiences drastic Fe deprivation and, second, that Fe-starved M. tuberculosis is capable of long-term persistence without growth. Together, these observations suggest that Fe deprivation in the lung might trigger a state of persistence in M. tuberculosis and promote chronic TB. We also identified vulnerabilities of iron-restricted persistent M. tuberculosis , which can be exploited for the design of new antitubercular therapies. Copyright © 2017 Kurthkoti et al.

[Chronic otitis and hearing loss revealing a disseminated tuberculosis in a child].

PubMed

See, H; Aubertin, G; Angoulvant, F; Baculard, F; Soussan, V; Bourrillon, A; Faye, A

2006-09-01

Ear localization is sometimes the first symptom of tuberculosis. We report a case of a teen with a chronic otitis revealing a disseminated tuberculosis. The investigations showed ear, bones and pulmonary localisations. The outcome with treatment showed a persistent hearing loss. Middle ear tuberculosis should be suspected in patients with chronic otitis and risk factors of tuberculosis. A disseminated tuberculosis should be investigated and an early treatment is necessary to prevent hearing loss.

The production of consumption: addressing the impact of mineral mining on tuberculosis in southern Africa

PubMed Central

Basu, Sanjay; Stuckler, David; Gonsalves, Gregg; Lurie, Mark

2009-01-01

Background Miners in southern Africa experience incident rates of tuberculosis up to ten times greater than the general population. Migration to and from mines may be amplifying tuberculosis epidemics in the general population. Discussion Migration to and from mineral mines contributes to HIV risks and associated tuberculosis incidence. Health and safety conditions within mines also promote the risk of silicosis (a tuberculosis risk factor) and transmission of tuberculosis bacilli in close quarters. In the context of migration, current tuberculosis prevention and treatment strategies often fail to provide sufficient continuity of care to ensure appropriate tuberculosis detection and treatment. Reports from Lesotho and South Africa suggest that miners pose transmission risks to other household or community members as they travel home undetected or inadequately treated, particularly with drug-resistant forms of tuberculosis. Reducing risky exposures on the mines, enhancing the continuity of primary care services, and improving the enforcement of occupational health codes may mitigate the harmful association between mineral mining activities and tuberculosis incidence among affected communities. Summary Tuberculosis incidence appears to be amplified by mineral mining operations in southern Africa. A number of immediately-available measures to improve continuity of care for miners, change recruitment and compensation practices, and reduce the primary risk of infection may critically mitigate the negative association between mineral mining and tuberculosis. PMID:19785769

Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study.

PubMed

Onifade, Dami A; Bayer, Angela M; Montoya, Rosario; Haro, Marie; Alva, Jessica; Franco, Jessica; Sosa, Rosario; Valiente, Betty; Valera, Enit; Ford, Carolyn M; Acosta, Colleen D; Evans, Carlton A

2010-06-29

There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns. We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22 semi-structured interviews and in four focus group discussions with 26 tuberculosis patients and 17 healthcare workers. We found that the tuberculosis program was perceived not to be gender discriminatory and provided equal tuberculosis diagnostic and treatment care to men and women. This contrasted with stereotypical gender roles in the broader community context and a commonly expressed belief amongst patients and healthcare workers that female health inherently has a lower priority than male health. This belief was principally associated with men's predominant role in the household economy and limited employment for women in this setting. Women were also generally reported to experience the adverse psychosocial and economic consequences of tuberculosis diagnosis more than men. There was a common perception that women's tuberculosis care was of secondary importance to that of men. This reflected societal gender values and occurred despite apparent gender equality in care provision. The greatest opportunities for improving women's access to tuberculosis care appear to be in improving social, political and economic structures, more than tuberculosis program modification.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges

PubMed Central

Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

2017-01-01

Abstract Background While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. Methods We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)–coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. Results The overall tuberculosis burden was estimated to be 532005 cases (range, 333760–764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Conclusion Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. PMID:29117342

Multidrug-resistant Pulmonary Tuberculosis Among Young Korean Soldiers in a Communal Setting

PubMed Central

Lee, Sei Won; Kim, Kwang Hyun; Min, Kyung Hoon

2009-01-01

The goal of this study was to evaluate the prevalence of first-line anti-tuberculosis drug resistance and risk factors associated with multidrug-resistant tuberculosis (MDR TB) among young soldiers in the Korean military, which has a strict tuberculosis control program. All patients with culture-confirmed pulmonary tuberculosis during their service at the Armed Forces Capital Hospital from January 2001 to December 2006 were enrolled in the study. Drug resistant Mycobacterium tuberculosis was isolated from 18 patients (12.2%) and multidrug-resistant M. tuberculosis was isolated from 12 patients (8.1%). Previous treatment of tuberculosis and the presence of a cavity on the patient's chest computed tomography scan were associated with MDR TB; military rank, smoking habits, and positive acid-fast bacilli smears were not associated with MDR TB. In a multiple logistic regression analysis, previous treatment of tuberculosis was a significant independent risk factor for MDR TB (odds ratio 6.12, 95% confidence interval 1.53-24.46). The prevalence of drug resistant tuberculosis among young soldiers in the Korean military was moderately high and the majority of resistant cases were found in patients who had undergone previous treatment of tuberculosis. Based on our results, we suggest that relapsed tuberculosis cases within communal settings should be cautiously managed until the drug susceptibility tests report is completed, even if previous treatment results were satisfactory. PMID:19654938

Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study

PubMed Central

2010-01-01

Background There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns. Methods We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22 semi-structured interviews and in four focus group discussions with 26 tuberculosis patients and 17 healthcare workers. Results We found that the tuberculosis program was perceived not to be gender discriminatory and provided equal tuberculosis diagnostic and treatment care to men and women. This contrasted with stereotypical gender roles in the broader community context and a commonly expressed belief amongst patients and healthcare workers that female health inherently has a lower priority than male health. This belief was principally associated with men's predominant role in the household economy and limited employment for women in this setting. Women were also generally reported to experience the adverse psychosocial and economic consequences of tuberculosis diagnosis more than men. Conclusions There was a common perception that women's tuberculosis care was of secondary importance to that of men. This reflected societal gender values and occurred despite apparent gender equality in care provision. The greatest opportunities for improving women's access to tuberculosis care appear to be in improving social, political and economic structures, more than tuberculosis program modification. PMID:20587044

Global Tuberculosis Report 2016

MedlinePlus

... Alt+0 Navigation Alt+1 Content Alt+2 Tuberculosis (TB) Menu Tuberculosis Data and statistics Regional Framework Resources Meetings and events Global tuberculosis report 2017 WHO has published a global TB ...

9 CFR 50.6 - Identification of animals to be destroyed because of tuberculosis.

Code of Federal Regulations, 2014 CFR

2014-01-01

... destroyed because of tuberculosis. 50.6 Section 50.6 Animals and Animal Products ANIMAL AND PLANT HEALTH... DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS General Indemnity § 50.6 Identification of animals to be destroyed because of tuberculosis. (a) Livestock to be destroyed because of tuberculosis must be identified...

9 CFR 50.6 - Identification of animals to be destroyed because of tuberculosis.

Code of Federal Regulations, 2012 CFR

2012-01-01

... destroyed because of tuberculosis. 50.6 Section 50.6 Animals and Animal Products ANIMAL AND PLANT HEALTH... DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS General Indemnity § 50.6 Identification of animals to be destroyed because of tuberculosis. (a) Livestock to be destroyed because of tuberculosis must be identified...

9 CFR 50.6 - Identification of animals to be destroyed because of tuberculosis.

Code of Federal Regulations, 2013 CFR

2013-01-01

... destroyed because of tuberculosis. 50.6 Section 50.6 Animals and Animal Products ANIMAL AND PLANT HEALTH... DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS General Indemnity § 50.6 Identification of animals to be destroyed because of tuberculosis. (a) Livestock to be destroyed because of tuberculosis must be identified...

9 CFR 50.6 - Identification of animals to be destroyed because of tuberculosis.

Code of Federal Regulations, 2011 CFR

2011-01-01

... destroyed because of tuberculosis. 50.6 Section 50.6 Animals and Animal Products ANIMAL AND PLANT HEALTH... DISEASES ANIMALS DESTROYED BECAUSE OF TUBERCULOSIS General Indemnity § 50.6 Identification of animals to be destroyed because of tuberculosis. (a) Livestock to be destroyed because of tuberculosis must be identified...

[Treatment of tuberculosis in patients with comorbidities].

PubMed

Abe, Masahiro; Fujita, Akira

2013-12-01

Early detection and appropriate treatment are the keys to tuberculosis control. In particular, providing appropriate treatment for tuberculosis in patients with HIV infection, rheumatoid arthritis (RA), chronic hepatic disease, or renal failure necessitating hemodialysis, and taking appropriate measures against adverse reactions to antituberculosis drugs are issues of critical importance. This mini-symposium, four experts explained the current status of "treatment of tuberculosis in patients with comorbidities" and proposed measures to address these problems. Dr. Aoki talked about "HIV infection complicated by tuberculosis." To the next, Dr. Yoshinaga gave a talk on "treatment of tuberculosis in RA patients receiving biological agents. Further, Dr. Sasaki lectured on "tuberculosis in patients with hepatic disease/impairment". Lastly, Dr. Takamori gave a lecture on "tuberculosis in patients with renal disease and those on hemodialysis. Tuberculosis patients often have some underlying diseases, and adverse reactions caused by antituberculosis drugs, such as hepatic and renal impairments, are matters of concern. I believe that this mini-symposium has provided useful information for physicians engaged in tuberculosis treatment and for many other healthcare professionals as well.

Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis

PubMed Central

Dheda, Keertan; Gumbo, Tawanda; Gandhi, Neel R; Murray, Megan; Theron, Grant; Udwadia, Zarir; Migliori, G B; Warren, Robin

2017-01-01

Extensively drug-resistant tuberculosis is a burgeoning global health crisis mainly affecting economically active young adults, and has high mortality irrespective of HIV status. In some countries such as South Africa, drug-resistant tuberculosis represents less than 3% of all cases but consumes more than a third of the total national budget for tuberculosis, which is unsustainable and threatens to destabilise national tuberculosis programmes. However, concern about drug-resistant tuberculosis has been eclipsed by that of totally and extremely drug-resistant tuberculosis—ie, resistance to all or nearly all conventional first-line and second-line antituberculosis drugs. In this Review, we discuss the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medicolegal aspects of extensively drug-resistant tuberculosis and other resistant strains. Finally, we discuss the emerging problem of functionally untreatable tuberculosis, and the issues and challenges that it poses to public health and clinical practice. The emergence and growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis—and increased funding to strengthen global control efforts, research, and advocacy—even more pressing. PMID:24717628

[Clinical analysis of patients with tuberculosis admitted on an emergency cases].

PubMed

Okada, Toru; Shibuya, Yasuhiro; Saito, Hitoshi; Enomoto, Tatsuji; Nakamura, Seiichi

2008-08-01

A retrospective study was made of 75 patients with tuberculosis and tuberculous pleurisy who received medical care in our hospital from 2002 through 2006. Of the 75 patients, 9 were admitted as tertiary emergency cases, and 12 patients were admitted by ambulance as secondary emergency cases. We studied the reason for their emergency medical admission, and the process of diagnosing 21 patients as tuberculosis. In some cases, the reasons for emergency admission were cardiorespiratory arrest, loss of consciousness, and injury resulting from a traffic accident, not common symptoms of tuberculosis such as dyspnea, hemoptysis and bloody sputum. Chest radiographic findings of most patients showed tuberculosis, and other cases were likely to be diagnosed as tuberculosis from their medical history or back-ground such as being homeless, previous tuberculosis, and receiving for therapy of tuberculosis. It was not so difficult to diagnose our cases as tuberculosis, nevertheless we may have an unconscious patient with normal chest radiograph. These data suggest that any patients visiting the emergency room may possibly have tuberculosis even if they are without respiratory symptoms.

[Tuberculosis incidence and primary drug resistance rates in young soldiers: data from 14 military hospitals in Turkey].

PubMed

Taş, Dilaver; Taşçı, Cantürk; Demirer, Ersin; Sezer, Ogün; Okutan, Oğuzhan; Kartaloğlu, Zafer

2012-01-01

Tuberculosis is an important health care problem worldwide as well as in Turkey and the control programmes are still in progress. Epidemiological data are necessary to conduct control studies related to the disease. Tuberculosis incidence and drug resistance rates are two necessary parameters which should be monitored for the effective establishment of tuberculosis control. In this objective, tuberculosis incidence and drug resistance rates were studied in young subjects performing their compulsory military service in Turkish Armed Forces. The study was performed in 14 military hospitals which served for the country-wide soldier patients. Based on the computerized medical database of these military hospitals, conscripts diagnosed with tuberculosis between January 01, 2009 and December 31, 2009 were retrospectively evaluated. Drug sensitivity tests of the Mycobacterium tuberculosis complex isolates were done prior to the treatment in the two military medical training hospitals of the two big cities of Turkey (Ankara and Istanbul). There were a total of 259 new tuberculosis cases in 2009 and they were all male with a mean age of 22.51 ± 4.63 years. The number of patients with pulmonary, extrapulmonary (pleuresia, lymphadenitis, others) and both pulmonary and extrapulmonary involvements were 175 (67.5%), 72 (27.8%) and 12 (4.6%), respectively. The total rate of pulmonary tuberculosis cases was 72.2% (187/259) and 64.7% (121/187) of them were smear positive. Since the number of soldiers in Turkish army in the midyear was 537.200; total tuberculosis, pulmonary tuberculosis and smear-positive pulmonary tuberculosis incidences were estimated as 48.2/100.000, 34.8/100.000 and 22.5/100.000, respectively. Drug sensitivity tests was performed for the M.tuberculosis complex strains isolated from 104 cases. Primary resistance rate to at least one drug was detected as 16.3% (n= 17), while the rates of resistance for isoniazid, rifampicin, ethambutol and streptomycin were 12.5% (n= 13), 7.7% (n= 8), 5.8% (n= 6) and 0.9% (n= 1), respectively. Multidrug resistant tuberculosis (isoniazid + rifampicin resistance) was detected in 6 (5.8%) patients. Our data indicated that although tuberculosis incidence among young soldiers was moderately high, a decreasing trend was observed when compared to the previous years. However, the rates of primary anti-tuberculosis drug resistance and multi-drug resistance were found to be high in our study. To decrease the incidence of tuberculosis and multidrug resistant tuberculosis, drug sensitivity tests should be performed for each patient and national tuberculosis programme should be established effectively.

[A case of melanoderma erroneously considered to be addisonian].

PubMed

Bertello, P; Ciocca Vasino, M A; Ferrua, F; Lalloni, R; Di Cerbo, M; Rietto, G B

1979-02-04

A case characterized by a dark pigmentation of the skin with an initial hypotension and a lung tuberculosis in the remote anamnesis is described. The skin pigment was formed by lipofuscin and emosiderin, but only the former was found in the liver biopsy. Anyway, the pigment was not melanine and the surrenalic function of the patient was completely normal; therefore, an Addisonism syndrome is excluded. The patient was treated for a very long time with DOCA: this caused hypertension, probably supported by the hypervolemia triggered by the DOCA depending retenction of sodium and water. A sure diagnosis of the case was not made, but an Addisonism syndrome was certainly excluded.

HIV-1 Infection Is Associated with Depletion and Functional Impairment of Mycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

PubMed

Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

2017-09-15

Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

[Morphological signs of inflammatory activity in different clinical forms of drug-resistant pulmonary tuberculosis].

PubMed

Elipashev, A A; Nikolsky, V O; Shprykov, A S

to determine whether the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant pulmonary tuberculosis. The material taken from 310 patients operated on in 2010-2015 were retrospectively examined. The patients underwent economical lung resections of limited extent (typical and atypical ones of up to 3 segments) for circumscribed forms of tuberculosis with bacterial excretion. A study group consisted of 161 (51.9%) patients with drug-resistant variants of pulmonary tuberculosis. A control group included 149 (48.1%) patients with preserved susceptibility of Mycobacterium tuberculosis to anti-TB drugs. The activity of specific changes in tuberculosis was morphologically evaluated in accordance with the classification proposed by B.M. Ariel in 1998. The highest activity of fourth-to-fifth degree specific inflammation, including that outside the primary involvement focus, was obtained in the drug-resistant pulmonary tuberculosis group due to the predominance of patients with cavernous and fibrous-cavernous tuberculosis versus those in whom the susceptibility to chemotherapeutic agents was preserved. A macroscopic study showed that the primary lesion focus had a median size in one-half of the all the examinees; but large tuberculomas, caverns, and fibrous caverns over 4 cm in diameter were multiple and detected in the drug-resistant pulmonary tuberculosis group. Multidrug resistance was observed in more than 60% of the patients with fibrous-cavernous pulmonary tuberculosis, extensive drug resistance was seen in those with cavernous tuberculosis, which is an aggravating factor. The data obtained from the morphological study of the intraoperative material can specify the clinical form of tuberculosis and evaluate the efficiency of preoperative specific therapy. The highest activity of specific inflammation was observed in patients with multiple drug-resistant pulmonary tuberculosis, the prevalence of third-to-fourth degree specific changes was seen in those with multiple and extensively drug-resistant tuberculosis. The findings suggest that the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant tuberculosis and with a spectrum of drug resistance.

Socio-economic status and the duration of pulmonary tuberculosis symptoms in women treated at the Mazovian Treatment Centre of Tuberculosis and Lung Diseases in Otwock.

PubMed

Błachnio, Maria; Zielonka, Tadeusz M; Błachnio, Antoni; Jagodziński, Jacek

2014-01-01

The prevalence of tuberculosis depends on various factors such as migration, homelessness, malnutrition, unemployment, bad life conditions and the aging of a society. The aim of this study was to evaluate tuberculosis in females treated at the Mazovian Treatment Centre of Tuberculosis and Lung Diseases (Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy) in Otwock, regarding the context of demographic, social and professional status of female patients. The duration of the illness and the extent of radiographic changes were also taken into consideration. The study was carried out retrospectively. The medical documentation that was evaluated concerned 100 women, aged between 20 and 92, hospitalized at the Mazovian Treatment Centre of Tuberculosis and Lung Diseases in Otwock in the years 2005 and 2006 due to bacteriologically confirmed tuberculosis. Most women with tuberculosis lived in cities (65%), 32% of the evaluated patients lived in villages and 3% were homeless. 1/3 of females were under 40 years of age, and 1/3 were over 60 years of age. Only 29% of the women were professionally active and 25% were unemployed. 60% of women were not married. 35% of women with tuberculosis were bringing up children and 7% had abandoned their offspring. More than 1/3 of women had had tuberculosis symptoms for more than half a year before tuberculosis was diagnosed. 40% of women with tuberculosis had small radiological changes (1 to 2 lung fields); however, 26% of them had extensive changes covering 4 to 6 lung fields. The majority of women with tuberculosis in the Mazovian district are single, over 40 years old, unemployed inhabitants of cities. 30% of women in the study group had had symptoms for more than 6 months before tuberculosis was diagnosed. 40% of women with tuberculosis had very extensive radiological changes covering 4 to 6 lung fields.

Tuberculosis screening among homeless persons with AIDS living in single-room-occupancy hotels.

PubMed

Layton, M C; Cantwell, M F; Dorsinville, G J; Valway, S E; Onorato, I M; Frieden, T R

1995-11-01

Congregate facilities for homeless persons with the acquired immunodeficiency syndrome (AIDS) are often endemic for tuberculosis. We evaluated tuberculosis screening methods at single-room-occupancy hotels housing persons with AIDS. Residents were screened by cross matching the New York City Tuberculosis Registry, interviewing for tuberculosis history, skin testing, and chest radiography. Cases were classified as either previously or newly diagnosed. Among the 106 participants, 16 (15%) previously diagnosed tuberculosis cases were identified. Participants' tuberculosis histories were identified by the questionnaire (100%) or by registry match (69%). Eight participants (50%) were noncompliant with therapy. These findings prompted the establishment of a directly observed therapy program on site.

Antro-duodenal tuberculosis causing gastric outlet obstruction--a rare presentation of a protean disease.

PubMed

Gheorghe, Liana; Băncilă, Ion; Gheorghe, Cristian; Herlea, Vlad; Vasilescu, Cătălin; Aposteanu, Gabriela

2002-06-01

Gastroduodenal tuberculosis is a rare location of abdominal tuberculosis. It usually occurs secondary to pulmonary tuberculosis. We report a case of a 63-year-old woman admitted to the referral center for symptoms of upper gastrointestinal obstruction caused by ulcerohypertrophic antroduodenal tuberculosis. The lesion was misdiagnosed as malignancy at endoscopy. Even at surgery, the lesion was considered gastric cancer and imposed an oncologic resection. The diagnosis was established in the presence of giant-cell granulomas with caseating necrosis in the surgical resected specimens. In our case, the rare gastroduodenal location of abdominal tuberculosis occurred as primary tuberculosis, in the absence of other identifiable locations.

Drug resistant Skeletal Tuberculosis in a tertiary care centre in South India.

PubMed

Arockiaraj, J; Balaji, G S; Cherian, V M; T S, Jepegnanam; Thomas, B P; Michael, Joy S; Poonnoose, P M

2018-03-01

Drug resistant tuberculosis is alarmingly on the rise especially in developing countries. Skeletal tuberculosis accounts up to 10% of all extra pulmonary tuberculosis. World Health Organisation (WHO) has not formulated guidelines for the management of Multi-drug resistant skeletal tuberculosis. A retrospective analysis of patients treated for musculoskeletal tuberculosis was done, to study drug resistance patterns. The outcome was assessed both clinically and radiologically.898 patients were treated for skeletal tuberculosis during the period of 2006-2013 (96 months). 478 (53.2%) patients were treated for tubercular spondylitis and 420 (46.8%) for extra-spinal skeletal tuberculosis. Ninety two patients (10.2%) had documented resistance to the anti-tubercular drugs. There were 42 mono resistant tuberculosis cases (4.7%), 13 poly resistant cases (1.4%), 33 multi-drug resistant cases (MDR TB) (3.7%) and 4 (0.4%) extremely drug resistant tuberculosis cases (XDR). All the patients were treated medically as per drug susceptibility patterns and protocols. Surgery was performed when indicated in 59 (66%) cases. 85% completed their course of treatment and were successfully healed as per pre-set clinical, biochemical and radiological criteria. The remaining were lost to follow up. One patient died as a result of post op respiratory infection. The prevalence of Multi-drug resistant tuberculosis patients in our centre was 3.7% and that of Extremely drug resistant tuberculosis cases was 0.4%. A Multi-disciplinary approach with drug susceptibility tests, sensitive drugs, and surgery if required is essential. Health education is essential to improve awareness among health care professionals about the danger of drug resistance in tuberculosis.

International standards for tuberculosis care.

PubMed

Hopewell, Philip C; Pai, Madhukar; Maher, Dermot; Uplekar, Mukund; Raviglione, Mario C

2006-11-01

Part of the reason for failing to bring about a more rapid reduction in tuberculosis incidence worldwide is the lack of effective involvement of all practitioners-public and private-in the provision of high quality tuberculosis care. While health-care providers who are part of national tuberculosis programmes have been trained and are expected to have adopted proper diagnosis, treatment, and public-health practices, the same is not likely to be true for non-programme providers. Studies of the performance of the private sector conducted in several different parts of the world suggest that poor quality care is common. The basic principles of care for people with, or suspected of having, tuberculosis are the same worldwide: a diagnosis should be established promptly; standardised treatment regimens should be used with appropriate treatment support and supervision; response to treatment should be monitored; and essential public-health responsibilities must be carried out. Prompt and accurate diagnosis, and effective treatment are essential for good patient care and tuberculosis control. All providers who undertake evaluation and treatment of patients with tuberculosis must recognise that not only are they delivering care to an individual, but they are also assuming an important public-health function. The International Standards for Tuberculosis Care (ISTC) describe a widely endorsed level of care that all practitioners should seek to achieve in managing individuals who have, or are suspected of having, tuberculosis. The document is intended to engage all care providers in delivering high quality care for patients of all ages, including those with smear-positive, smear-negative, and extra-pulmonary tuberculosis, tuberculosis caused by drug-resistant Mycobacterium tuberculosis complex, and tuberculosis combined with HIV infection.

Cigarette smoking and health-promoting behaviours among tuberculosis patients in rural areas.

PubMed

Tsai, Shu-Lan; Lai, Chun-Liang; Chi, Miao-Ching; Chen, Mei-Yen

2016-09-01

To explore cigarette smoking and health-promoting behaviours among disadvantaged adults before their tuberculosis diagnosis and after their tuberculosis treatment. Although tuberculosis infection is associated with impaired immune function, healthy lifestyle habits can play a role in improving the immune system. However, limited research has explored the health-promoting behaviours and cigarette smoking habits among tuberculosis patients in Taiwan. A cross-sectional retrospective study with a convenience sample. This study was conducted between May 2013-June 2014 with 123 patients at a rural district hospital in Chiayi County, Taiwan. Statistical analyses included descriptive statistics, univariate analysis and stepwise regression analysis. Tuberculosis tended to be associated with less education, male sex, malnutrition, cigarette smoking and unhealthy lifestyle habits before the tuberculosis diagnosis. The percentage of smoking decreased from 46·9% before to 30·2% after the tuberculosis diagnosis. Body mass index and health-promoting behaviours also significantly improved after tuberculosis treatment. After controlling for potential confounding factors, multivariate analysis identified chronic disease and completed treatment as significant factors that were associated with current health-promoting behaviours. A high prevalence of cigarette smoking and low levels of health-promoting behaviours were observed before the diagnosis and during or after completing tuberculosis treatment. This study's findings indicate the importance of promoting healthy lifestyle changes among tuberculosis patients; aggressive measures should be implemented immediately after the first diagnosis of tuberculosis. Furthermore, health promotion and smoking cessation programmes should be initiated in the general population to prevent activation of latent tuberculosis infection, and these programmes should specifically target men and rural residents. © 2016 John Wiley & Sons Ltd.

[Tuberculosis and mycobacteriosis important opportunistic disease in AIDS patients].

PubMed

Zalewska-Schönthaler, N; Schönthaler-Humiecka, J; Podlasin, R; Cholewińska, G; Rzeszkowicz, T; Mikuła, T; Horban, A

2001-01-01

The aim of the search was investigation of tuberculosis in AIDS patients. Each year 8-9 mln people fall ill of tuberculosis and one third of them die. To the infection of tuberculosis and fast development into active state are especially exposed people with AIDS. 696 people were examined on tuberculosis most of which were AIDS patients hospitalized and cured in Hospital of Infection Diseases and Prison Hospital. 159 patients were women and 537 were men. The average age was between 25 and 45 (70%). The investigated population was characterized according to age, social and living conditions, using drugs and former contact with tuberculosis. All patients suspected of tuberculosis had chest X-rayed, sputum, BAL and pleural liquor were taken to bacteriological examination when extrapulmonary tuberculosis was suspected. The material was taken adequately to the disease process: CSF, urine, lymph nodes, peritoneal fluids, blood, stool, swabs and other. Bacteriological investigations have been carried out by fast cultivating method since 1998 and rapid genetic method since 1999. Apart from modern, fast diagnostic methods, routine bacteriological procedures were applied in tuberculosis diagnosis. More than 30% of the examined population were from bad social-living conditions, 78% had risk factors, 65% were drug users. The analysis of the tuberculosis illness from 1997 to July 2001 shows growing tendency. Nowadays it is 20% cases proved by bacteriological diagnosis. The structure of falling ill with tuberculosis has changed. Considerable increase of extrapulmonary tuberculosis was observed, 20 patients died due to tuberculosis and 8 patients due to mycobacteriosis. Resistance of M.tub.complex occurred within the range of 10% cases.

Microarray analysis of Mycobacterium tuberculosis-infected monocytes reveals IL26 as a new candidate gene for tuberculosis susceptibility.

PubMed

Guerra-Laso, José M; Raposo-García, Sara; García-García, Silvia; Diez-Tascón, Cristina; Rivero-Lezcano, Octavio M

2015-02-01

Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate genes for tuberculosis susceptibility we infected monocytes from both healthy elderly individuals (a tuberculosis susceptibility group) and elderly tuberculosis patients with M. tuberculosis, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns for these genes, regardless of whether they were obtained from younger or older patients. Only one of the detected genes corresponded to a cytokine: IL26, a member of the interleukin-10 (IL-10) cytokine family which we found to be down-regulated in infected monocytes from tuberculosis patients. Non-infected monocytes secreted IL-26 constitutively but they reacted strongly to M. tuberculosis infection by decreasing IL-26 production. Furthermore, IL-26 serum concentrations appeared to be lower in the tuberculosis patients. When whole blood was infected, IL-26 inhibited the observed pathogen-killing capability. Although lymphocytes expressed IL26R, the receptor mRNA was not detected in either monocytes or neutrophils, suggesting that the inhibition of anti-mycobacterial activity may be mediated by lymphocytes. Additionally, IL-2 concentrations in infected blood were lower in the presence of IL-26. The negative influence of IL-26 on the anti-mycobacterial activity and its constitutive presence in both serum and monocyte supernatants prompt us to propose IL26 as a candidate gene for tuberculosis susceptibility. © 2014 John Wiley & Sons Ltd.

Tuberculosis: evidence review for newly arriving immigrants and refugees

PubMed Central

Greenaway, Christina; Sandoe, Amelia; Vissandjee, Bilkis; Kitai, Ian; Gruner, Doug; Wobeser, Wendy; Pottie, Kevin; Ueffing, Erin; Menzies, Dick; Schwartzman, Kevin

2011-01-01

Background: The foreign-born population bears a disproportionate health burden from tuberculosis, with a rate of active tuberculosis 20 times that of the non-Aboriginal Canadian-born population, and could therefore benefit from tuberculosis screening programs. We reviewed evidence to determine the burden of tuberculosis in immigrant populations, to assess the effectiveness of screening and treatment programs for latent tuberculosis infection, and to identify potential interventions to improve effectiveness. Methods: We performed a systematic search for evidence of the burden of tuberculosis in immigrant populations and the benefits and harms, applicability, clinical considerations, and implementation issues of screening and treatment programs for latent tuberculosis infection in the general and immigrant populations. The quality of this evidence was assessed and ranked using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). Results: Chemoprophylaxis with isoniazid is highly efficacious in decreasing the development of active tuberculosis in people with latent tuberculosis infection who adhere to treatment. Monitoring for hepatotoxicity is required at all ages, but close monitoring is required in those 50 years of age and older. Adherence to screening and treatment for latent tuberculosis infection is poor, but it can be increased if care is delivered in a culturally sensitive manner. Interpretation: Immigrant populations have high rates of active tuberculosis that could be decreased by screening for and treating latent tuberculosis infection. Several patient, provider and infrastructure barriers, poor diagnostic tests, and the long treatment course, however, limit effectiveness of current programs. Novel approaches that educate and engage patients, their communities and primary care practitioners might improve the effectiveness of these programs. PMID:20634392

Developing a customised approach for strengthening tuberculosis laboratory quality management systems toward accreditation

PubMed Central

Trollip, Andre; Erni, Donatelle; Kao, Kekeletso

2017-01-01

Background Quality-assured tuberculosis laboratory services are critical to achieve global and national goals for tuberculosis prevention and care. Implementation of a quality management system (QMS) in laboratories leads to improved quality of diagnostic tests and better patient care. The Strengthening Laboratory Management Toward Accreditation (SLMTA) programme has led to measurable improvements in the QMS of clinical laboratories. However, progress in tuberculosis laboratories has been slower, which may be attributed to the need for a structured tuberculosis-specific approach to implementing QMS. We describe the development and early implementation of the Strengthening Tuberculosis Laboratory Management Toward Accreditation (TB SLMTA) programme. Development The TB SLMTA curriculum was developed by customizing the SLMTA curriculum to include specific tools, job aids and supplementary materials specific to the tuberculosis laboratory. The TB SLMTA Harmonized Checklist was developed from the World Health Organisation Regional Office for Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation checklist, and incorporated tuberculosis-specific requirements from the Global Laboratory Initiative Stepwise Process Towards Tuberculosis Laboratory Accreditation online tool. Implementation Four regional training-of-trainers workshops have been conducted since 2013. The TB SLMTA programme has been rolled out in 37 tuberculosis laboratories in 10 countries using the Workshop approach in 32 laboratories in five countries and the Facility-based approach in five tuberculosis laboratories in five countries. Conclusion Lessons learnt from early implementation of TB SLMTA suggest that a structured training and mentoring programme can build a foundation towards further quality improvement in tuberculosis laboratories. Structured mentoring, and institutionalisation of QMS into country programmes, is needed to support tuberculosis laboratories to achieve accreditation. PMID:28879165

Clinical Diagnostic Utility of IP-10 and LAM Antigen Levels for the Diagnosis of Tuberculous Pleural Effusions in a High Burden Setting

PubMed Central

Dheda, Keertan; Van-Zyl Smit, Richard N.; Sechi, Leonardo A.; Badri, Motasim; Meldau, Richard; Symons, Gregory; Khalfey, Hoosein; Carr, Igshaan; Maredza, Alice; Dawson, Rodney; Wainright, Helen; Whitelaw, Andrew; Bateman, Eric D.; Zumla, Alimuddin

2009-01-01

Background Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid. Methods We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis. Principal Findings Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed ∼20% of TB cases and mis-diagnosed ∼20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful. Conclusion Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings. PMID:19277111

A First Insight on the Population Structure of Mycobacterium tuberculosis Complex as Studied by Spoligotyping and MIRU-VNTRs in Santiago, Chile

PubMed Central

Balcells, María Elvira; García, Patricia; Meza, Paulina; Peña, Carlos; Cifuentes, Marcela; Couvin, David; Rastogi, Nalin

2015-01-01

Tuberculosis (TB) remains a significant public health problem worldwide, but the ecology of the prevalent mycobacterial strains, and their transmission, can vary depending on country and region. Chile is a country with low incidence of TB, that has a geographically isolated location in relation to the rest of South American countries due to the Andes Mountains, but recent migration from neighboring countries has changed this situation. We aimed to assess the genotypic diversity of Mycobacterium tuberculosis complex (MTBC) strains in Santiago, Chile, and compare with reports from other Latin-American countries. We analyzed MTBC isolates from pulmonary tuberculosis cases collected between years 2008 and 2013 in Central Santiago, using two genotyping methods: spoligotyping and 12-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTRs). Data obtained were analyzed and compared to the SITVIT2 database. Mean age of the patients was 47.5 years and 61% were male; 11.6% were migrants. Of 103 strains (1 isolate/patient) included, there were 56 distinct spoligotype patterns. Of these, 16 strains (15.5%) corresponded to orphan strains in the SITVIT2 database, not previously reported. Latin American and Mediterranean (LAM) (34%) and T (33%) lineages were the most prevalent strains, followed by Haarlem lineage (16.5%). Beijing family was scarcely represented with only two cases (1.9%), one of them isolated from a Peruvian migrant. The most frequent clustered spoligotypes were SIT33/LAM3 (10.7%), SIT53/T1 (8.7%), SIT50/H3 (7.8%), and SIT37/T3 (6.8%). We conclude that LAM and T genotypes are the most prevalent genotypes of MTBC in Santiago, Chile, and together correspond to almost two thirds of analyzed strains, which is similar to strain distribution reported from other countries of Latin America. Nevertheless, the high proportion of SIT37/T3, which was rarely found in other Latin American countries, may underline a specific history or demographics of Chile related to probable human migrations and evolutions. PMID:25671320

A first insight on the population structure of Mycobacterium tuberculosis complex as studied by spoligotyping and MIRU-VNTRs in Santiago, Chile.

PubMed

Balcells, María Elvira; García, Patricia; Meza, Paulina; Peña, Carlos; Cifuentes, Marcela; Couvin, David; Rastogi, Nalin

2015-01-01

Tuberculosis (TB) remains a significant public health problem worldwide, but the ecology of the prevalent mycobacterial strains, and their transmission, can vary depending on country and region. Chile is a country with low incidence of TB, that has a geographically isolated location in relation to the rest of South American countries due to the Andes Mountains, but recent migration from neighboring countries has changed this situation. We aimed to assess the genotypic diversity of Mycobacterium tuberculosis complex (MTBC) strains in Santiago, Chile, and compare with reports from other Latin-American countries. We analyzed MTBC isolates from pulmonary tuberculosis cases collected between years 2008 and 2013 in Central Santiago, using two genotyping methods: spoligotyping and 12-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTRs). Data obtained were analyzed and compared to the SITVIT2 database. Mean age of the patients was 47.5 years and 61% were male; 11.6% were migrants. Of 103 strains (1 isolate/patient) included, there were 56 distinct spoligotype patterns. Of these, 16 strains (15.5%) corresponded to orphan strains in the SITVIT2 database, not previously reported. Latin American and Mediterranean (LAM) (34%) and T (33%) lineages were the most prevalent strains, followed by Haarlem lineage (16.5%). Beijing family was scarcely represented with only two cases (1.9%), one of them isolated from a Peruvian migrant. The most frequent clustered spoligotypes were SIT33/LAM3 (10.7%), SIT53/T1 (8.7%), SIT50/H3 (7.8%), and SIT37/T3 (6.8%). We conclude that LAM and T genotypes are the most prevalent genotypes of MTBC in Santiago, Chile, and together correspond to almost two thirds of analyzed strains, which is similar to strain distribution reported from other countries of Latin America. Nevertheless, the high proportion of SIT37/T3, which was rarely found in other Latin American countries, may underline a specific history or demographics of Chile related to probable human migrations and evolutions.

Migration Flow and Its Impact on Tuberculosis Notification in Portugal.

PubMed

Dias, Ana; Gaio, Rita; Sousa, Pedro; Gomes, Marta; Oliveira, Olena; Duarte, Raquel

2018-01-01

Tuberculosis notification in Portugal has decreased in the last few years. As a consequence of the economic crisis, emigration has increased and immigration has decreased. Immigrants are a risk group for tuberculosis. Most emigrants are 20-44 years old and belong to the age group most affected by tuberculosis. To describe the decrease in tuberculosis notification in Portugal over the last years from a demographical point of view. Mathematical analysis was performed to quantify the effect of the migration movements (separately and simultaneously) on tuberculosis notification in Portugal from 2008 to 2014. We calculated the estimated tuberculosis notification for each year during the period of study: 1) fixing immigration rate and tuberculosis rate in immigrants at 2008 values; 2) fixing emigration rate and tuberculosis rate in emigrants at 2008 values; 3) fixing both phenomenons at 2008 values. The differences between the observed and the estimated numbers were small (≤0.5 cases/100000 inhabitants). Impact of the migration movements on tuberculosis notification rate does not seem to be significant when analyzed for each phenomenon individually and simultaneously, by our model. This might mean that we have to concentrate our efforts in other risk factors for tuberculosis. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

[Knowledge and perception about tuberculosis among public transport workers in Lima, Peru].

PubMed

Lukac, Danitza; Garaycochea, Octavio; Taype-Rondan, Alvaro; Luque Bustamante, Laura; Mujica-Vasquez, André; Zamora, Dario

2016-11-23

To describe the level of knowledge and perception of tuberculosis among public transport workers attending Road Safety Education courses in Lima, Peru. An observational, cross-sectional, analytic study was conducted between July and August 2014 in public transport workers attending the courses of Road Safety education. In Lima, such courses are mandatory for workers in the public transport area. An anonymous and voluntary survey was applied to obtain the following variables: sociodemographic characteristics, history of tuberculosis, tuberculosis knowledge and attitudes towards the disease. The factors associated to the risk perception of Tuberculosis infection were analysed using Poisson regression. From 309 attendees, 216 surveys were analysed (69.9%). Of these, 88.4% were males, 3.2% had a history of tuberculosis. The most widely known symptom was cough with phlegm (44.4%), the most popular source of information was television (39.8%), and only 9.7% had any training about tuberculosis. A 41.2% of respondents believed that working in the public transport sector was an occupation with a high risk of tuberculosis infection. No significant association between risk perception of tuberculosis and sociodemographic characteristics was found. A considerable lack of knowledge about tuberculosis symptoms and a low perception of risk for tuberculosis exists among public transport workers in Lima. Education strategies directed to this population need to be implemented.

Tuberculosis screening in patients with HIV: use of audit and feedback to improve quality of care in Ghana

PubMed Central

Bjerrum, Stephanie; Bonsu, Frank; Hanson-Nortey, Nii Nortey; Kenu, Ernest; Johansen, Isik Somuncu; Andersen, Aase Bengaard; Bjerrum, Lars; Jarbøl, Dorte; Munck, Anders

2016-01-01

Background Tuberculosis screening of people living with HIV (PLHIV) can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice is scarce. Objectives To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. Design Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during May and October 2014, before and after a performance feedback intervention in August 2014. The outcomes of interest were overall tuberculosis suspicion rate during consultations and provider adherence to the International Standards for Tuberculosis Care and the World Health Organizations’ guidelines for symptom-based tuberculosis screening among PLHIV. Results Twenty-one healthcare providers registered a total of 2,666 consultations; 1,368 consultations before and 1,298 consultations after the feedback intervention. Tuberculosis suspicion rate during consultation increased from 12.6 to 20.9% after feedback (odds ratio, OR 1.83; 95% confidence interval, CI: 1.09–3.09). Before feedback, sputum smear microscopy was requested for 58.7% of patients with suspected tuberculosis, for 47.2% of patients with cough ≥2 weeks, and for 27.5% of patients with a positive World Health Organization (WHO) symptom screen (any of current cough, fever, weight loss or night sweats). After feedback, patients with a positive WHO symptom screen were more likely to be suspected of tuberculosis (OR 2.21; 95% CI: 1.19–4.09) and referred for microscopy (OR 2.71; 95% CI: 1.25–5.86). Conclusions A simple prospective audit tool identified flaws in clinical practices for tuberculosis screening of PLHIV. There was no systematic identification of people with suspected active tuberculosis. We found low initial tuberculosis suspicion rate compounded by low referral rates of relevant patients for sputum smear microscopy. Adherence to recommended standards and guidelines for tuberculosis screening improved after performance feedback. PMID:27569593

Replication of Mycobacterium tuberculosis in retinal pigment epithelium.

PubMed

Nazari, Hossein; Karakousis, Petros C; Rao, Narsing A

2014-06-01

Mycobacterium tuberculosis is an important cause of posterior uveitis in tuberculosis-endemic regions. Clinical and histopathologic evidence suggests that retinal pigment epithelium (RPE) can harbor M tuberculosis. However, the mechanism of M tuberculosis phagocytosis and its growth in RPE is not clear. To investigate M tuberculosis phagocytosis, replication, and cytopathic effects in RPE cells compared with macrophages. Human fetal RPE and monocytic leukemia macrophage (THP-1) cell lines were cultured, and RPE and THP-1 cells were exposed to avirulent M tuberculosis H37Ra. Mycobacteria were added to RPE and THP-1 cells with a 5:1 multiplicity of infection. Nonphagocytized M tuberculosis was removed after 12 hours of exposure (day 0). Cells were harvested at days 0, 1, and 5 to count live and dead cells and intracellular mycobacteria. Toll-like receptor 2 (TLR2) and TLR4 expression was determined by immunohistochemistry; intracellular bacillary load, following TLR2 and TLR4 blockade. Number of intracellular M tuberculosis, cell survival, and TLR2 and TLR4 expression in RPE and THP-1 cells following exposure to M tuberculosis. At day 0, an equal number of intracellular M tuberculosis was observed per THP-1 and RPE cells (0.45 and 0.35 M tuberculosis per RPE and THP-1 cells, respectively). Mean (SD) number of intracellular M tuberculosis at day 5 was 1.9 (0.03) and 3.3 (0.01) per RPE and THP-1 cells, respectively (P < .001). Viability of infected RPE was significantly greater than that of THP-1 cells at day 5 (viable cells: 17 [8%] THP-1 vs 73% [4%] RPE; P < .05). Expression of TLR2 and TLR4 was detected in both cell types after 12 hours of exposure. Inhibition of TLR2 and TLR4 reduced intracellular M tuberculosis counts in RPE but not in THP-1 cells. Mycobacterium tuberculosis is phagocytized by RPE to a similar extent as in macrophages. However, RPE cells are better able to control bacillary growth and RPE cell survival is greater than that of THP-1 cells following mycobacterial infection, suggesting that RPE can serve as a reservoir for intraocular M tuberculosis infection.

IFNγ Response to Mycobacterium tuberculosis, Risk of Infection and Disease in Household Contacts of Tuberculosis Patients in Colombia

PubMed Central

Marín, Nancy D.; Marín, Diana M.; López, Lucelly; Henao, Hanna M.; Martínez, Teresita; Villa, Liliana; Barrera, Luis F.; Ortiz, Blanca L.; Ramírez, María E.; Montes, Carlos J.; Oquendo, María C.; Arango, Lisandra M.; Riaño, Felipe; Aguirre, Carlos; Bustamante, Alberto; Belisle, John T.; Dobos, Karen; Mejía, Gloria I.; Giraldo, Margarita R.; Brennan, Patrick J.; Robledo, Jaime; Arbeláez, María P.; Rojas, Carlos A.; García, Luis F.

2009-01-01

Objectives Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development. Methods A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. Results Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007). Discussion CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination. PMID:20011589

Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition

DOE PAGES

Wolf, Nina M.; Gutka, Hiten J.; Movahedzadeh, Farahnaz; ...

2018-04-03

The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) from Mycobacterium tuberculosis at 2.6 Å resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme from Thermosynechococcus elongatus . This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII from Escherichia coli and ismore » probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII from M. tuberculosis ( Mt FBPaseII) is conserved and is analogous to that described previously for the E. coli enzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures of Mt FBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for the Synechocystis enzyme. The structural and functional insights derived from the structure of Mt FBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention.« less

Structures of the Mycobacterium tuberculosis GlpX protein (class II fructose-1,6-bisphosphatase): implications for the active oligomeric state, catalytic mechanism and citrate inhibition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wolf, Nina M.; Gutka, Hiten J.; Movahedzadeh, Farahnaz

The crystal structures of native class II fructose-1,6-bisphosphatase (FBPaseII) from Mycobacterium tuberculosis at 2.6 Å resolution and two active-site protein variants are presented. The variants were complexed with the reaction product fructose 6-phosphate (F6P). The Thr84Ala mutant is inactive, while the Thr84Ser mutant has a lower catalytic activity. The structures reveal the presence of a 222 tetramer, similar to those described for fructose-1,6/sedoheptulose-1,7-bisphosphatase from Synechocystis (strain 6803) as well as the equivalent enzyme from Thermosynechococcus elongatus . This homotetramer corresponds to a homologous oligomer that is present but not described in the crystal structure of FBPaseII from Escherichia coli and ismore » probably conserved in all FBPaseIIs. The constellation of amino-acid residues in the active site of FBPaseII from M. tuberculosis ( Mt FBPaseII) is conserved and is analogous to that described previously for the E. coli enzyme. Moreover, the structure of the active site of the partially active (Thr84Ser) variant and the analysis of the kinetics are consistent with the previously proposed catalytic mechanism. The presence of metabolites in the crystallization medium (for example citrate and malonate) and in the corresponding crystal structures of Mt FBPaseII, combined with their observed inhibitory effect, could suggest the existence of an uncharacterized inhibition of this class of enzymes besides the allosteric inhibition by adenosine monophosphate observed for the Synechocystis enzyme. The structural and functional insights derived from the structure of Mt FBPaseII will provide critical information for the design of lead inhibitors, which will be used to validate this target for future chemical intervention.« less

bioA mutant of Mycobacterium tuberculosis shows severe growth defect and imparts protection against tuberculosis in guinea pigs

PubMed Central

Kar, Ritika; Nangpal, Prachi; Mathur, Shubhita; Singh, Swati

2017-01-01

Owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the Bacillus Calmette–Guérin (BCG) vaccine, a more efficient vaccine than BCG is required for the global control of tuberculosis. A number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in de novo biotin biosynthesis. In this study, we demonstrate that a bioA mutant of Mycobacterium tuberculosis (MtbΔbioA) is highly attenuated in the guinea pig model of tuberculosis when administered aerogenically as well as intradermally. Immunization with MtbΔbioA conferred significant protection in guinea pigs against an aerosol challenge with virulent M. tuberculosis, when compared with the unvaccinated animals. Booster immunization with MtbΔbioA offered no advantage over a single immunization. These experiments demonstrate the vaccinogenic potential of the attenuated M. tuberculosis bioA mutant against tuberculosis. PMID:28658275

Risk of tuberculosis in immigrant Asians: culturally acquired immunodeficiency?

PubMed

Finch, P J; Millard, F J; Maxwell, J D

1991-01-01

Study of the 620 Asian immigrants with tuberculosis notified in the Wandsworth area of south London between 1973 and 1988 showed a bimodal pattern of tuberculosis notifications: in 1977 there was a peak among Asians from East Africa, and in 1981 a peak among those from the Indian subcontinent. There was a mean lag time of five years between clinical presentation and immigration. Logit analysis showed that, although overall more men had tuberculosis than women, glandular tuberculosis was more common among women of all groups, and pulmonary tuberculosis was more common among Hindu women than Hindu men. Both subgroups of Asians had a substantially higher incidence of tuberculosis than white people, particularly at extrapulmonary sites. Hindus were also at a significantly greater risk of tuberculosis at all sites than Muslims (Hindu:Muslim risk ratio 5.5 for women and 3.7 for men). The increased susceptibility to tuberculosis of Hindus, particularly Hindu women, may be related to a culturally acquired immunodeficiency caused by vegetarianism and associated vitamin deficiency.

Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis.

PubMed

Collins, Angela C; Cai, Haocheng; Li, Tuo; Franco, Luis H; Li, Xiao-Dong; Nair, Vidhya R; Scharn, Caitlyn R; Stamm, Chelsea E; Levine, Beth; Chen, Zhijian J; Shiloh, Michael U

2015-06-10

Activation of the DNA-dependent cytosolic surveillance pathway in response to Mycobacterium tuberculosis infection stimulates ubiquitin-dependent autophagy and inflammatory cytokine production, and plays an important role in host defense against M. tuberculosis. However, the identity of the host sensor for M. tuberculosis DNA is unknown. Here we show that M. tuberculosis activated cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) in macrophages to produce cGAMP, a second messenger that activates the adaptor protein stimulator of interferon genes (STING) to induce type I interferons and other cytokines. cGAS localized with M. tuberculosis in mouse and human cells and in human tuberculosis lesions. Knockdown or knockout of cGAS in human or mouse macrophages blocked cytokine production and induction of autophagy. Mice deficient in cGAS were more susceptible to lethality caused by infection with M. tuberculosis. These results demonstrate that cGAS is a vital innate immune sensor of M. tuberculosis infection. Copyright © 2015 Elsevier Inc. All rights reserved.

Extended spectrum of antibiotic susceptibility for tuberculosis, Djibouti.

PubMed

Bouzid, Fériel; Astier, Hélène; Osman, Djaltou Aboubaker; Javelle, Emilie; Hassan, Mohamed Osman; Simon, Fabrice; Garnotel, Eric; Drancourt, Michel

2018-02-01

In the Horn of Africa, there is a high prevalence of tuberculosis that is reported to be partly driven by multidrug-resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti, and their in vitro susceptibility to standard anti-tuberculous antibiotics in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M. tuberculosis, five Mycobacterium canettii, one 'Mycobacterium simulans' and one Mycobacterium kansasii were identified. Drug-susceptibility tests performed on the first 78 isolates yielded nine MDR M. tuberculosis isolates. All isolates were fully susceptible to clofazimine, minocycline and chloramphenicol, and 75 of 78 isolates were susceptible to sulfadiazine. In the Horn of Africa, patients with confirmed pulmonary tuberculosis caused by an in vitro susceptible strain may benefit from anti-leprosy drugs, sulfamides and phenicol antibiotics. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Tuberculosis Facts - Exposure to TB

MedlinePlus

Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

Tuberculosis Facts - Testing for TB

MedlinePlus

Tuberculosis (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

PubMed

Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

2017-11-01

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges.

PubMed

Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

2017-11-06

While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)-coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. The overall tuberculosis burden was estimated to be 532005 cases (range, 333760-764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Addison's Disease Caused by Tuberculosis with Atypical Hyperpigmentation and Active Pulmonary Tuberculosis

PubMed Central

Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi

2017-01-01

We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity. PMID:28717080

Childhood tuberculosis and malnutrition.

PubMed

Jaganath, Devan; Mupere, Ezekiel

2012-12-15

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease.

Addison's Disease Caused by Tuberculosis with Atypical Hyperpigmentation and Active Pulmonary Tuberculosis.

PubMed

Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi

2017-01-01

We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.

Tuberculosis screening among homeless persons with AIDS living in single-room-occupancy hotels.

PubMed Central

Layton, M C; Cantwell, M F; Dorsinville, G J; Valway, S E; Onorato, I M; Frieden, T R

1995-01-01

Congregate facilities for homeless persons with the acquired immunodeficiency syndrome (AIDS) are often endemic for tuberculosis. We evaluated tuberculosis screening methods at single-room-occupancy hotels housing persons with AIDS. Residents were screened by cross matching the New York City Tuberculosis Registry, interviewing for tuberculosis history, skin testing, and chest radiography. Cases were classified as either previously or newly diagnosed. Among the 106 participants, 16 (15%) previously diagnosed tuberculosis cases were identified. Participants' tuberculosis histories were identified by the questionnaire (100%) or by registry match (69%). Eight participants (50%) were noncompliant with therapy. These findings prompted the establishment of a directly observed therapy program on site. PMID:7485672

Potential of DosR and Rpf antigens from Mycobacterium tuberculosis to discriminate between latent and active tuberculosis in a tuberculosis endemic population of Medellin Colombia.

PubMed

Arroyo, Leonar; Marín, Diana; Franken, Kees L M C; Ottenhoff, Tom H M; Barrera, Luis F

2018-01-08

Tuberculosis (TB) remains one of the most deadly infectious diseases. One-third to one-fourth of the human population is estimated to be infected with Mycobacterium tuberculosis (Mtb) without showing clinical symptoms, a condition called latent TB infection (LTBI). Diagnosis of Mtb infection is based on the immune response to a mixture of mycobacterial antigens (PPD) or to Mtb specific ESAT-6/CFP10 antigens (IGRA), highly expressed during the initial phase of infection. However, the immune response to PPD and IGRA antigens has a low power to discriminate between LTBI and PTB. The T-cell response to a group of so-called latency (DosR-regulon-encoded) and Resuscitation Promoting (Rpf) antigens of Mtb has been proved to be significantly higher in LTBI compared to active TB across many populations, suggesting their potential use as biomarkers to differentiate latent from active TB. PBMCs from a group LTBI (n = 20) and pulmonary TB patients (PTB, n = 21) from an endemic community for TB of the city of Medellín, Colombia, were in vitro stimulated for 7 days with DosR- (Rv1737c, Rv2029c, and Rv2628), Rpf- (Rv0867c and Rv2389c), the recombinant fusion protein ESAT-6-CFP10 (E6-C10)-, or PPD-antigen. The induced IFNγ levels detectable in the supernatants of the antigen-stimulated cells were then used to calculate specificity and sensitivity in discriminating LTBI from PTB, using different statistical approaches. IFNγ production in response to DosR and Rpf antigens was significantly higher in LTBI compared to PTB. ROC curve analyses of IFNγ production allowed differentiation of LTBI from PTB with areas under the curve higher than 0.70. Furthermore, Multiple Correspondence Analysis (MCA) revealed that LTBI is associated with higher levels of IFNγ in response to the different antigens compared to PTB. Analysis based on decision trees showed that the IFNγ levels produced in response to Rv2029c was the leading variable that best-classified disease status. Finally, logistic regression analysis predicted that IFNγ produced by PBMCs in response to E6-C10, Rv2029c, Rv0867c (RpfA) and Rv2389c (RpfA) antigens correlates best with the probability of being latently infected. The Mtb antigens E6-C10, Rv2029c (PfkB), Rv0867c (RpfA) and Rv2389c (RpfA), may be potential candidates to discriminate LTBI from PTB.

Severe Paradoxical Reaction During Treatment of Disseminated Tuberculosis in a Patient With Neutralizing Anti-IFNγ Autoantibodies

PubMed Central

Xie, Yingda L.; Rosen, Lindsey B.; Sereti, Irini; Barber, Daniel L.; Chen, Ray Y.; Hsu, Denise C.; Qasba, S. Sonia; Zerbe, Christa S.; Holland, Steven M.; Browne, Sarah K.

2016-01-01

Interferon-gamma (IFNγ) neutralizing autoantibodies are associated with disseminated nontuberculous mycobacterial infections. We report a previously healthy Thai woman with disseminated tuberculosis and high-titer IFNγ-neutralizing autoantibodies, who developed a severe inflammatory reaction during anti-tuberculosis treatment. IFNγ contributes to host control of tuberculosis but appears inessential for tuberculosis paradoxical reactions. PMID:26646678

A rare presentation of disseminated tuberculosis: Prostatic abscess.

PubMed

Verma, Ajay; Singh, Anubhuti; Kishore, Kislay; Kant, Surya

2017-10-01

Involvement of the prostate by tuberculosis (TB) occurs rarely and tuberculosis prostate abscess is an even rarer occurrence. It has been reported in immunocompromised patients, mainly human immunodeficiency virus seropositive individuals. We are reporting a case of tuberculosis prostatic abscess in an immunocompetent patient with relapse of TB. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel.

PubMed

Graham, Stephen M; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E; Gale, Marianne; Gie, Robert P; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J; McNeeley, David F; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R; Swaminathan, Soumya; Wingfield, Claire

2012-05-15

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

In vitro infection with Mycobacterium tuberculosis induces a distinct immunological pattern in blood from healthy relatives of tuberculosis patients.

PubMed

Juan-García, Javier; García-García, Silvia; Guerra-Laso, José Manuel; Raposo-García, Sara; Diez-Tascón, Cristina; Nebreda-Mayoral, Teresa; López-Fidalgo, Eduardo; López-Medrano, Ramiro; Fernández-Maraña, Araceli; Rivero-Lezcano, Octavio Miguel

2017-11-30

Part of the susceptibility to tuberculosis has a genetic basis, which is clear in primary immunodeficiencies, but is less evident in apparently immunocompetent subjects. Immune responses were analysed in blood samples from tuberculosis patients and their healthy first-degree relatives who were infected in vitro with mycobacteria (either Mycobacterium tuberculosis or M. bovis BCG). The antimicrobial activity against M. tuberculosis in blood from relatives was significantly lower than that observed in healthy controls. Tuberculosis patients exhibited a higher number of neutrophils, and monocyte phagocytosis was inhibited in both relatives and tuberculosis patients. A remarkable finding was that the production of reactive oxygen species by infected neutrophils was higher in relatives than in healthy controls. A higher production of TNFα in infected blood from relatives was also observed. These results may indicate that relatives display a stronger inflammatory response and that their immune response to M. tuberculosis is different from those of unrelated controls. First-degree relatives may represent a highly informative group for the analysis of tuberculosis susceptibility. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Revisiting the role of phospholipases C in virulence and the lifecycle of Mycobacterium tuberculosis

PubMed Central

Le Chevalier, Fabien; Cascioferro, Alessandro; Frigui, Wafa; Pawlik, Alexandre; Boritsch, Eva C.; Bottai, Daria; Majlessi, Laleh; Herrmann, Jean Louis; Brosch, Roland

2015-01-01

Mycobacterium tuberculosis, the agent of human tuberculosis has developed different virulence mechanisms and virulence-associated tools during its evolution to survive and multiply inside the host. Based on previous reports and by analogy with other bacteria, phospholipases C (PLC) of M. tuberculosis were thought to be among these tools. To get deeper insights into the function of PLCs, we investigated their putative involvement in the intracellular lifestyle of M. tuberculosis, with emphasis on phagosomal rupture and virulence, thereby re-visiting a research theme of longstanding interest. Through the construction and use of an M. tuberculosis H37Rv PLC-null mutant (ΔPLC) and control strains, we found that PLCs of M. tuberculosis were not required for induction of phagosomal rupture and only showed marginal, if any, impact on virulence of M. tuberculosis in the cellular and mouse infection models used in this study. In contrast, we found that PLC-encoding genes were strongly upregulated under phosphate starvation and that PLC-proficient M. tuberculosis strains survived better than ΔPLC mutants under conditions where phosphatidylcholine served as sole phosphate source, opening new perspectives for studies on the role of PLCs in the lifecycle of M. tuberculosis. PMID:26603639

Type 2 diabetes mellitus and its influence in the development of multidrug resistance tuberculosis in patients from southeastern Mexico.

PubMed

Pérez-Navarro, Lucia Monserrat; Fuentes-Domínguez, Francisco Javier; Zenteno-Cuevas, Roberto

2015-01-01

To determine the factors associated with the presence of pulmonary tuberculosis in patients with type 2 diabetes mellitus and the effect in the development of drug and multi-drug resistance, in a population with tuberculosis from the southeast of Mexico. This is a case-control study including 409 individuals, 146 with the binomial tuberculosis-type 2 diabetes mellitus and 263 individuals with tuberculosis. Demographic, epidemiological and outcome variables were collected. Risks were calculated. The factors associated with the presence of type 2 diabetes mellitus were age ≥35years, (OR=9.7; CI: 5.2-17.8), previous contact with a person infected with tuberculosis (OR=1.7; CI: 1.1-3.1). Body mass index ≥25 kg/m(2) (OR=2.2; CI: 1.1-4.3), and inherited family history of diabetes (OR=5.4; CI: 3.2-9.2). It was also found that patients with tuberculosis-type 2 diabetes mellitus presented a 4.7-fold (CI: 1.4-11.3) and 3.5-fold (CI: 1.1-11.1) higher risk of developing drug- and multidrug resistance tuberculosis, respectively. By last, individuals with tuberculosis-type 2 diabetes had a 2.3-fold (CI: 1.5-4.1) greater chance of persisting as tuberculosis-positive by the second month of treatment, delaying the resolution of the tuberculosis infection. Type 2 diabetes exerts a strong influence on the presentation and evolution of tuberculosis within the analyzed population and displays remarkable particularities, necessitating the development of dedicated tuberculosis-diabetes surveillance systems that consider the particular epidemiological characteristics of the population affected. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effect of HIV-Related Immunosuppression on the Risk of Tuberculosis Transmission to Household Contacts

PubMed Central

Huang, Chuan-Chin; Tchetgen, Eric Tchetgen; Becerra, Mercedes C.; Cohen, Ted; Hughes, Katherine C.; Zhang, Zibiao; Calderon, Roger; Yataco, Rosa; Contreras, Carmen; Galea, Jerome; Lecca, Leonid; Murray, Megan

2014-01-01

Background. Coinfection with human immunodeficiency virus (HIV) may modify the risk of transmitting tuberculosis. Some previous investigations suggest that patients coinfected with HIV and tuberculosis are less likely to transmit infection, whereas others do not support this conclusion. Here, we estimated the relative risk of tuberculosis transmission from coinfected patients compared to HIV-negative patients with tuberculosis. Methods. Between September 2009 and August 2012, we identified and enrolled 4841 household contacts of 1608 patients with drug-sensitive tuberculosis in Lima, Peru. We assessed the HIV status and CD4 counts of index patients, as well as other risk factors for infection specific to the index patient, the household, and the exposed individuals. Contacts underwent tuberculin skin testing to determine tuberculosis infection status. Results. After adjusting for covariates, we found that household contacts of HIV-infected tuberculosis patients with a CD4 count ≤250 cells/µL were less likely to be infected with tuberculosis (risk ratio = 0.49 [95% confidence interval, .24–.96]) than the contacts of HIV-negative tuberculosis patients. No children younger than 15 years who were exposed to HIV-positive patients with a CD4 count ≤250 cells/µL were infected with tuberculosis, compared to 22% of those exposed to non-HIV-infected patients. There was no significant difference in the risk of infection between contacts of HIV-infected index patients with CD4 counts >250 cells/µL and contacts of index patients who were not HIV-infected. Conclusions. We found a reduced risk of tuberculosis infection among the household contacts of patients with active tuberculosis who had advanced HIV-related immunosuppression, suggesting reduced transmission from these index patients. PMID:24368620

Cough Aerosols of Mycobacterium tuberculosis in the Prediction of Incident Tuberculosis Disease in Household Contacts

PubMed Central

Jones-López, Edward C.; Acuña-Villaorduña, Carlos; Ssebidandi, Martin; Gaeddert, Mary; Kubiak, Rachel W.; Ayakaka, Irene; White, Laura F.; Joloba, Moses; Okwera, Alphonse; Fennelly, Kevin P.

2016-01-01

Background. Tuberculosis disease develops in only 5%–10% of humans infected with Mycobacterium tuberculosis . The mechanisms underlying this variability remain poorly understood. We recently demonstrated that colony-forming units of M. tuberculosis in cough-generated aerosols are a better predictor of infection than the standard sputum acid-fast bacilli smear. We hypothesized that cough aerosol cultures may also predict progression to tuberculosis disease in contacts. Methods. We conducted a retrospective cohort study of 85 patients with smear-positive tuberculosis and their 369 household contacts in Kampala, Uganda. Index case patients underwent a standard evaluation, and we cultured M. tuberculosis from cough aerosols. Contacts underwent a standard evaluation at enrollment, and they were later traced to determine their tuberculosis status. Results. During a median follow-up of 3.9 years, 8 (2%) of the contacts developed tuberculosis disease. In unadjusted and adjusted analyses, incident tuberculosis disease in contacts was associated with sputum Mycobacterial Growth Indicator Tube culture (odds ratio, 8.2; 95% confidence interval, 1.1–59.2; P = .04), exposure to a high-aerosol tuberculosis case patient (6.0, 1.4–25.2; P = .01), and marginally, human immunodeficiency virus in the contact (6.11; 0.89–41.7; P = .07). We present data demonstrating that sputum and aerosol specimens measure 2 related but different phenomena. Conclusions. We found an increased risk of tuberculosis progression among contacts of high-aerosol case patients. The hypothesis that a larger infectious inoculum, represented by high aerosol production, determines the risk of disease progression deserves evaluation in future prospective studies. PMID:27025837

Control and prevention of tuberculosis in the United Kingdom: Code of Practice 2000

PubMed Central

Joint, T

2000-01-01

BACKGROUND—The guidelines on control and prevention of tuberculosis in the United Kingdom have been reviewed and updated.
METHODS—A subcommittee was appointed by the Joint Tuberculosis Committee (JTC) of the British Thoracic Society to revise the guidelines published in 1994 by the JTC, including representatives of the Royal College of Nursing, Public Health Medicine Environmental Group, and Medical Society for Study of Venereal Diseases. In preparing the revised guidelines the authors took account of new published evidence and graded the strength of evidence for their recommendations. The guidelines have been approved by the JTC and the Standards of Care Committee of the British Thoracic Society.
RECOMMENDATIONS—Tuberculosis services in each district should have staffing and resources to fulfil both the control and prevention recommendations in this document and to ensure adequate treatment monitoring. Notification of tuberculosis is required for surveillance and to initiate contact tracing (where appropriate). The following areas are discussed and recommendations made where appropriate: (1) public health law in relation to tuberculosis; (2) the organisational requirements for tuberculosis services; (3) measures for control of tuberculosis in hospitals, including segregation of patients; (4) the requirements for health care worker protection, including HIV infected health care workers; (5) measures for control of tuberculosis in prisons; (6) protection for other groups with potential exposure to tuberculosis; (7) awareness of the high rates of tuberculosis in the homeless together with local plans for detection and action; (8) detailed advice on contact tracing; (9) contact tracing required for close contacts of bovine tuberculosis; (10) management of tuberculosis in schools; (11) screening of new immigrants and how this should be performed; (12) outbreak contingency investigation; and (13) BCG vaccination and the management of positive reactors found in the schools programme.

 PMID:11050256

Cough Aerosols of Mycobacterium tuberculosis in the Prediction of Incident Tuberculosis Disease in Household Contacts.

PubMed

Jones-López, Edward C; Acuña-Villaorduña, Carlos; Ssebidandi, Martin; Gaeddert, Mary; Kubiak, Rachel W; Ayakaka, Irene; White, Laura F; Joloba, Moses; Okwera, Alphonse; Fennelly, Kevin P

2016-07-01

Tuberculosis disease develops in only 5%-10% of humans infected with Mycobacterium tuberculosis The mechanisms underlying this variability remain poorly understood. We recently demonstrated that colony-forming units of M. tuberculosis in cough-generated aerosols are a better predictor of infection than the standard sputum acid-fast bacilli smear. We hypothesized that cough aerosol cultures may also predict progression to tuberculosis disease in contacts. We conducted a retrospective cohort study of 85 patients with smear-positive tuberculosis and their 369 household contacts in Kampala, Uganda. Index case patients underwent a standard evaluation, and we cultured M. tuberculosis from cough aerosols. Contacts underwent a standard evaluation at enrollment, and they were later traced to determine their tuberculosis status. During a median follow-up of 3.9 years, 8 (2%) of the contacts developed tuberculosis disease. In unadjusted and adjusted analyses, incident tuberculosis disease in contacts was associated with sputum Mycobacterial Growth Indicator Tube culture (odds ratio, 8.2; 95% confidence interval, 1.1-59.2; P = .04), exposure to a high-aerosol tuberculosis case patient (6.0, 1.4-25.2; P = .01), and marginally, human immunodeficiency virus in the contact (6.11; 0.89-41.7; P = .07). We present data demonstrating that sputum and aerosol specimens measure 2 related but different phenomena. We found an increased risk of tuberculosis progression among contacts of high-aerosol case patients. The hypothesis that a larger infectious inoculum, represented by high aerosol production, determines the risk of disease progression deserves evaluation in future prospective studies. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

An Effort to Isolate Mycobacterium bovis from Environmental Substrates during Investigations of Bovine Tuberculosis Transmission Sites (Cattle Farms and Wildlife Areas) in Michigan, USA

PubMed Central

Fine, Amanda E.; O'Brien, Daniel J.; Winterstein, Scott R.; Kaneene, John B.

2011-01-01

Deer movements on cattle farms, wildlife feeding, and livestock management practices in Michigan are thought to create opportunities for indirect transmission of Mycobacterium bovis via environmental substrates. To confirm the presence of viable M. bovis in the environment, substrates were collected from 13 farms with culture-confirmed M. bovis in cattle and 5 sites with high prevalence of M. bovis in free-ranging deer. None of the samples processed for mycobacterial culture were positive for M. bovis. Agent, host, and landscape-level factors decrease the probability of detecting M. bovis in the environment using conventional mycobacterial culture. Molecular techniques that increase the probability of M. bovis detection in environmental substrates should be applied to known sites of M. bovis transmission in Michigan. In the interim, epidemiological investigations informed by experimental studies will be most effective in characterizing M. bovis persistence in the environment and its role in the indirect interspecies transmission of M. bovis. PMID:23738108

Tuberculosis: General Information

MedlinePlus

TB Elimination Tuberculosis: General Information What is TB? Tuberculosis (TB) is a disease caused by germs that are spread from person ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination CS227840_A What Does a Positive Test ...

Tuberculosis Facts - TB and HIV/AIDS

MedlinePlus

Tuberculosis (TB) Facts TB and HIV/AIDS What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

Tuberculosis in the tropics.

PubMed

Krause, V L; Britton, W J

1993-09-20

Until recently tuberculosis was considered a well controlled disease, at least in developed countries. In developing countries, more than seven million people are affected by active tuberculosis. This situation is exacerbated by poor infrastructure to support tuberculosis control measures and the interaction between tuberculosis and infection with the human immunodeficiency virus. The three major strategies for controlling tuberculosis remain BCG vaccination in children, appropriate preventive therapy and, most importantly, reducing the sources of infection through case finding and curative treatment. Research and resources to improve on these strategies should be given high priority by the international health community.

A Rare Case of Ileocecal Tuberculosis with Pulmonary Embolism and Deep Vein Thrombosis

PubMed Central

Henry, Tan Chor Lip; Ho, Choon Aik; Mohamad, Yuzaidi

2017-01-01

Venous thromboembolism in tuberculosis is not a well recognised entity. It is a less frequently reported complication of severe pulmonary tuberculosis. It is exceedingly rare when it complicates extrapulmonary tuberculosis. Here, we present a case of 22-year-old young female with abdominal tuberculosis complicated with reverse ileocecal intussusception, deep vein thrombosis and pulmonary embolism. An emergency vena cava filter was inserted prior to a limited right hemicolectomy. In this article, we discuss the rare association of venous thromboembolism with ileocecal tuberculosis. PMID:28892968

Mutual Impact of Diabetes Mellitus and Tuberculosis in China.

PubMed

Cheng, Jun; Zhang, Hui; Zhao, Yan Lin; Wang, Li Xia; Chen, Ming Ting

2017-05-01

China has a double burden of diabetes mellitus and tuberculosis, and many studies have been carried out on the mutual impact of these two diseases. This paper systematically reviewed studies conducted in China covering the mutual impact of epidemics of diabetes and tuberculosis, the impact of diabetes on multi-drug resistant tuberculosis and on the tuberculosis clinical manifestation and treatment outcome, the yields of bi-directional screening, and economic evaluation for tuberculosis screening among diabetes patients. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Significance of nutrition in pulmonary tuberculosis.

PubMed

Kant, Surya; Gupta, Harshita; Ahluwalia, Savita

2015-01-01

Malnutrition and tuberculosis are both problems mostly of the developing countries. Tuberculosis can lead to malnutrition and malnutrition may predispose to tuberculosis. Poor nutrition leads to protein-energy malnutrition and micronutrients deficiencies which lead to immunodeficiency. This secondary immunodeficiency increases the host's susceptibility to infection and hence increase the risk for developing tuberculosis. Tuberculosis itself leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting and poor nutritional status. Nutritional status and dietary intake and hence nutritional status of patients get improved during antituberculosis treatment.

The tuberculosis hospital in Hohenkrug, Stettin. Department of Genitourinary Tuberculosis.

PubMed

Zajaczkowski, Tadeusz

2012-01-01

Towards the end of the 19th century, Europe turned particular attention to the problem of tuberculosis, at that time the most serious social disease. In the majority of cases, pulmonary tuberculosis had a fatal outcome owing to the lack of effective drugs and methods of treatment. Due to poor sanitary conditions, particularly as regards dwellings, pulmonary tuberculosis was able to spread rapidly. Hospital departments were reluctant to admit patients suffering from tuberculosis. It was only after the discoveries of Robert Koch (bacillus tubercle in 1882) that the cause of the disease became understood and methods of treatment began to be developed. A modern sanatorium and hospital with 270 beds was erected in Hohenkrug (today Szczecin-Zdunowo) between 1915 and 1930. Patients could now be treated with modern methods, surgically in most cases. After the Second World War, pulmonary tuberculosis was still an enormous epidemiologic problem. In 1949, the Polish authorities opened a 400-bed sanatoriumin Zdunowo. The methods of treatment were not much different from pre-war practice and it was only the routine introduction of antituberculotic drugs during the fifties of the past century that brought about a radical change in the fight against tuberculosis. The growing numbers of patients with tuberculosis of the genitourinary system led to the opening in 1958 of a 40-bed specialist ward at the Tuberculosis Sanatorium in Zdunowo. It should be emphasized that the Department of Genitourinary Tuberculosis in Szczecin-Zdunowo was a historical necessity and a salvation for thousands of patients from Northern Poland. The Department totally fulfilled its social duties thanks to the commitment of many outstanding persons dedicated to helping the patients. This unit was finally closed in 1987 because the demand for surgical treatment of tuberculosis was declining concurrently with the advent of new and potent antituberculotics and falling number of new cases of genitourinary tuberculosis. Today, the decision to close the Department of Genitourinary Tuberculosis is deeply regretted by urologists in Stettin.

Safety of Resuming Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis Patients Concomitant with the Treatment of Active Tuberculosis: A Retrospective Nationwide Registry of the Korean Society of Spondyloarthritis Research

PubMed Central

Kim, Hye Won; Kwon, Seong Ryul; Jung, Kyong-Hee; Kim, Seong-Kyu; Baek, Han Joo; Seo, Mi Ryung; Bang, So-Young; Lee, Hye-Soon; Suh, Chang-Hee; Jung, Ju Yang; Son, Chang-Nam; Shim, Seung Cheol; Lee, Sang-Hoon; Lee, Seung-Geun; Lee, Yeon-Ah; Lee, Eun Young; Kim, Tae-Hwan

2016-01-01

Backgrounds Patients who develop an active tuberculosis infection during tumor necrosis factor (TNF) inhibitor treatment typically discontinue TNF inhibitor and receive standard anti-tuberculosis treatment. However, there is currently insufficient information on patient outcomes following resumption of TNF inhibitor treatment during ongoing anti- tuberculosis treatment. Our study was designed to investigate the safety of resuming TNF inhibitors in ankylosing spondylitis (AS) patients who developed tuberculosis as a complication of the use of TNF inhibitors. Methods Through the nationwide registry of the Korean Society of Spondyloarthritis Research, 3929 AS patients who were prescribed TNF inhibitors were recruited between June 2003 and June 2014 at fourteen referral hospitals. Clinical information was analyzed about the patients who experienced tuberculosis after exposure to TNF inhibitors. The clinical features of resumers and non-resumers of TNF inhibitors were compared and the outcomes of tuberculosis were surveyed individually. Findings Fifty-six AS patients were treated for tuberculosis associated with TNF inhibitors. Among them, 23 patients resumed TNF inhibitors, and these patients were found to be exposed to TNF inhibitors for a longer period of time and experienced more frequent disease flare-up after discontinuation of TNF inhibitors compared with those who did not resume. Fifteen patients resumed TNF inhibitors during anti-tuberculosis treatment (early resumers) and 8 after completion of anti-tuberculosis treatment (late resumers). Median time to resuming TNF inhibitor from tuberculosis was 3.3 and 9.0 months in the early and late resumers, respectively. Tuberculosis was treated successfully in all resumers and did not relapse in any of them during follow-up (median 33.8 [IQR; 20.8–66.7] months). Conclusions Instances of tuberculosis were treated successfully in our AS patients, even when given concomitantly with TNF inhibitors. We suggest that early resumption of TNF inhibitors in AS patients could be safe under effective coverage of tuberculosis. PMID:27101309

Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients.

PubMed

Adu-Gyamfi, Clement G; Snyman, Tracy; Hoffmann, Christopher J; Martinson, Neil A; Chaisson, Richard E; George, Jaya A; Suchard, Melinda S

2017-10-15

There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P < .001). Six months before tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P < .001) than controls. After 6 months of tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.

PubMed

Houben, Rein M G J; Menzies, Nicolas A; Sumner, Tom; Huynh, Grace H; Arinaminpathy, Nimalan; Goldhaber-Fiebert, Jeremy D; Lin, Hsien-Ho; Wu, Chieh-Yin; Mandal, Sandip; Pandey, Surabhi; Suen, Sze-Chuan; Bendavid, Eran; Azman, Andrew S; Dowdy, David W; Bacaër, Nicolas; Rhines, Allison S; Feldman, Marcus W; Handel, Andreas; Whalen, Christopher C; Chang, Stewart T; Wagner, Bradley G; Eckhoff, Philip A; Trauer, James M; Denholm, Justin T; McBryde, Emma S; Cohen, Ted; Salomon, Joshua A; Pretorius, Carel; Lalli, Marek; Eaton, Jeffrey W; Boccia, Delia; Hosseini, Mehran; Gomez, Gabriela B; Sahu, Suvanand; Daniels, Colleen; Ditiu, Lucica; Chin, Daniel P; Wang, Lixia; Chadha, Vineet K; Rade, Kiran; Dewan, Puneet; Hippner, Piotr; Charalambous, Salome; Grant, Alison D; Churchyard, Gavin; Pillay, Yogan; Mametja, L David; Kimerling, Michael E; Vassall, Anna; White, Richard G

2016-11-01

The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. Bill and Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Evidence for chronic lung impairment in patients treated for pulmonary tuberculosis.

PubMed

Vecino, Mauricio; Pasipanodya, Jotam G; Slocum, Philip; Bae, Sejong; Munguia, Guadalupe; Miller, Thaddeus; Fernandez, Michel; Drewyer, Gerry; Weis, Stephen E

2011-11-01

Patients with pulmonary tuberculosis are likely to develop pulmonary impairment after tuberculosis (PIAT). The stability of PIAT and the relationship of PIAT to the duration of delay in tuberculosis diagnosis and treatment have not been fully characterized. We performed serial pulmonary function tests (PFTs) in a cohort treated for pulmonary tuberculosis after 20 weeks of tuberculosis therapy and again on or after treatment completion to determine the stability of PIAT. PFTs were compared with the duration of delay in tuberculosis diagnosis and treatment, as well as other demographic variables. The median duration between the first and second tests was 15 (interquartile range 9-34) weeks. The mean change in FVC was -0.02l (95% confidence interval [CI] -0.09, 0.06), and the % predicted was -0.02 (95% CI -2.17, 2.12). FEV1 changes were 0l (95% CI -0.05, 0.06), and the % predicted was -0.11 (95% CI -1.82, 1.60). PIAT was not related to the duration of delay in tuberculosis diagnosis or treatment, age or smoking. PIAT was not associated with the duration of delay in tuberculosis diagnosis and treatment and did not significantly change during follow-up. These data demonstrate that, for many individuals, the completion of tuberculosis treatment is the beginning, not the end, of their tuberculosis illness. Published by Elsevier Ltd.

Clinico-pathological features of tuberculosis due to Mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study.

PubMed

Wamala, Dan; Asiimwe, Benon; Kigozi, Edgar; Mboowa, Gerald; Joloba, Moses; Kallenius, Gunilla

2014-04-02

Tuberculous lymphadenitis is next to pulmonary tuberculosis as the most common cause of tuberculosis. Uganda genotype, one of the sub-lineages of Mycobacterium tuberculosis, is the most prevalent cause of pulmonary tuberculosis in Uganda. We here investigate the clinicopathological characteristics of patients with tuberculous lymphadenitis infected with M. tuberculosis Uganda genotype compared with those infected with M. tuberculosis non-Uganda genotype strains. Between 2010 and 2012, we enrolled 121 patients (mean age 28.5 yrs, male 48%; female 52%) with tuberculous lymphadenitis, and categorized them by their M. tuberculosis genotypes. The clinical features and lymph node cytopathological parameters were compared between patients in the Uganda and non-Uganda categories using a crude and multivariable logistic regression model with adjustment for confounding factors. Of the 121participants, 56 (46%) were infected with strains of Uganda genotype. Patients infected with this genotype had significantly lower frequency of abdominal lymphadenopathy (odds ratio 0.4, p = 0.046) after adjusting for sex, age and HIV. Abdominal lymphadenopathy was also significantly associated with abnormal chest X-ray (p = 0.027). Tuberculous lymphadenitis patients infected with M. tuberculosis Uganda genotype were significantly less prone to have abdominal lymphadenopathy indicating potential reduced ability to disseminate and supporting the concept that differences in M. tuberculosis genotype may have clinical implications.

Women and tuberculosis.

PubMed

Connolly, M; Nunn, P

1996-01-01

Tuberculosis is the leading infectious cause of death in women worldwide. The disease poses a major threat to women's health security. Population growth, the HIV epidemic, increasing poverty and rising levels of drug resistance will inevitably increase the burden of this disease in women. Women are at increased risk of progression to disease during their reproductive years. However, in most low-income countries, twice as many men are notified with tuberculosis as women. Biological mechanisms may account for most of this difference but socioeconomic and cultural factors leading to barriers in accessing health care may cause under-notification in women. Tuberculosis control programmes should be sensitive to the constraints faced by women in accessing health care, in order to empower women to commence and complete treatment. The fear and stigma associated with tuberculosis have a greater impact on women than on men, often leaving them in a more precarious social and economic position. Tuberculosis in women creates orphans, impoverished families and reduces the economic development of society. Tuberculosis is a major cause of preventable suffering and death in women. WHO's recommended tuberculosis control strategy, DOTS, represents a cost-effective response to the problem of tuberculosis in women. Tuberculosis is a major women's health issue. It is a global health priority that tuberculosis treatment be made available to women, particularly to those in low-income countries who are bearing the brunt of this epidemic.

Screening for tuberculosis and testing for human immunodeficiency virus in Zambian prisons

PubMed Central

Maggard, Katie R; Hatwiinda, Sisa; Harris, Jennifer B; Phiri, Winifreda; Krüüner, Annika; Kaunda, Kaunda; Topp, Stephanie M; Kapata, Nathan; Ayles, Helen; Chileshe, Chisela; Henostroza, German

2015-01-01

Abstract Objective To improve the Zambia Prisons Service’s implementation of tuberculosis screening and human immunodeficiency virus (HIV) testing. Methods For both tuberculosis and HIV, we implemented mass screening of inmates and community-based screening of those residing in encampments adjacent to prisons. We also established routine systems – with inmates as peer educators – for the screening of newly entered or symptomatic inmates. We improved infection control measures, increased diagnostic capacity and promoted awareness of tuberculosis in Zambia’s prisons. Findings In a period of 9 months, we screened 7638 individuals and diagnosed 409 new patients with tuberculosis. We tested 4879 individuals for HIV and diagnosed 564 cases of infection. An additional 625 individuals had previously been found to be HIV-positive. Including those already on tuberculosis treatment at the time of screening, the prevalence of tuberculosis recorded in the prisons and adjacent encampments – 6.4% (6428/100 000) – is 18 times the national prevalence estimate of 0.35%. Overall, 22.9% of the inmates and 13.8% of the encampment residents were HIV-positive. Conclusion Both tuberculosis and HIV infection are common within Zambian prisons. We enhanced tuberculosis screening and improved the detection of tuberculosis and HIV in this setting. Our observations should be useful in the development of prison-based programmes for tuberculosis and HIV elsewhere. PMID:25883402

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines.

PubMed

Caccamo, Nadia; Pietra, Gabriella; Sullivan, Lucy C; Brooks, Andrew G; Prezzemolo, Teresa; La Manna, Marco P; Di Liberto, Diana; Joosten, Simone A; van Meijgaarden, Krista E; Di Carlo, Paola; Titone, Lucina; Moretta, Lorenzo; Mingari, Maria C; Ottenhoff, Tom H M; Dieli, Francesco

2015-04-01

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genotype heterogeneity of Mycobacterium tuberculosis within geospatial hotspots suggests foci of imported infection in Sydney, Australia.

PubMed

Gurjav, Ulziijargal; Jelfs, Peter; Hill-Cawthorne, Grant A; Marais, Ben J; Sintchenko, Vitali

2016-06-01

In recent years the State of New South Wales (NSW), Australia, has maintained a low tuberculosis incidence rate with little evidence of local transmission. Nearly 90% of notified tuberculosis cases occurred in people born in tuberculosis-endemic countries. We analyzed geographic, epidemiological and genotypic data of all culture-confirmed tuberculosis cases to identify the bacterial and demographic determinants of tuberculosis hotspot areas in NSW. Standard 24-loci mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-24) typing was performed on all isolates recovered between 2009 and 2013. In total 1692/1841 (91.9%) cases with confirmed Mycobacterium tuberculosis infection had complete MIRU-24 and demographic data and were included in the study. Despite some year-to-year variability, spatio-temporal analysis identified four tuberculosis hotspots. The incidence rate and the relative risk of tuberculosis in these hotspots were 2- to 10-fold and 4- to 8-fold higher than the state average, respectively. MIRU-24 profiles of M. tuberculosis isolates associated with these hotspots revealed high levels of heterogeneity. This suggests that these spatio-temporal hotspots, within this low incidence setting, can represent areas of predominantly imported infection rather than clusters of cases due to local transmission. These findings provide important epidemiological insight and demonstrate the value of combining tuberculosis genotyping and spatiotemporal data to guide better-targeted public health interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

Identifying Hotspots of Multidrug-Resistant Tuberculosis Transmission Using Spatial and Molecular Genetic Data

PubMed Central

Zelner, Jonathan L.; Murray, Megan B.; Becerra, Mercedes C.; Galea, Jerome; Lecca, Leonid; Calderon, Roger; Yataco, Rosa; Contreras, Carmen; Zhang, Zibiao; Manjourides, Justin; Grenfell, Bryan T.; Cohen, Ted

2016-01-01

Background. We aimed to identify and determine the etiology of “hotspots” of concentrated multidrug-resistant tuberculosis (MDR-tuberculosis) risk in Lima, Peru. Methods. From 2009 to 2012, we conducted a prospective cohort study among households of tuberculosis cases from 106 health center (HC) areas in Lima, Peru. All notified tuberculosis cases and their household contacts were followed for 1 year. Symptomatic individuals were screened by microscopy and culture; positive cultures were tested for drug susceptibility (DST) and genotyped by 24-loci mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR). Results. 3286 individuals with culture-confirmed disease, DST, and 24-loci MIRU-VNTR were included in our analysis. Our analysis reveals: (1) heterogeneity in annual per-capita incidence of tuberculosis and MDR-tuberculosis by HC, with a rate of MDR-tuberculosis 89 times greater (95% confidence interval [CI], 54,185) in the most-affected versus the least-affected HC; (2) high risk for MDR-tuberculosis in a region spanning several HCs (odds ratio = 3.19, 95% CI, 2.33, 4.36); and (3) spatial aggregation of MDR-tuberculosis genotypes, suggesting localized transmission. Conclusions. These findings reveal that localized transmission is an important driver of the epidemic of MDR-tuberculosis in Lima. Efforts to interrupt transmission may be most effective if targeted to this area of the city. PMID:26175455

Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis Infectiousness

PubMed Central

Datta, Sumona; Sherman, Jonathan M; Tovar, Marco A; Bravard, Marjory A; Valencia, Teresa; Montoya, Rosario; Quino, Willi; D’Arcy, Nikki; Ramos, Eric S; Gilman, Robert H; Evans, Carlton A

2017-01-01

Abstract Background Sputum from patients with tuberculosis contains subpopulations of metabolically active and inactive Mycobacterium tuberculosis with unknown implications for infectiousness. Methods We assessed sputum microscopy with fluorescein diacetate (FDA, evaluating M. tuberculosis metabolic activity) for predicting infectiousness. Mycobacterium tuberculosis was quantified in pretreatment sputum of patients with pulmonary tuberculosis using FDA microscopy, culture, and acid-fast microscopy. These 35 patients’ 209 household contacts were followed with prevalence surveys for tuberculosis disease for 6 years. Results FDA microscopy was positive for a median of 119 (interquartile range [IQR], 47–386) bacteria/µL sputum, which was 5.1% (IQR, 2.4%–11%) the concentration of acid-fast microscopy–positive bacteria (2069 [IQR, 1358–3734] bacteria/μL). Tuberculosis was diagnosed during follow-up in 6.4% (13/209) of contacts. For patients with lower than median concentration of FDA microscopy–positive M. tuberculosis, 10% of their contacts developed tuberculosis. This was significantly more than 2.7% of the contacts of patients with higher than median FDA microscopy results (crude hazard ratio [HR], 3.8; P = .03). This association maintained statistical significance after adjusting for disease severity, chemoprophylaxis, drug resistance, and social determinants (adjusted HR, 3.9; P = .02). Conclusions Mycobacterium tuberculosis that was FDA microscopy negative was paradoxically associated with greater infectiousness. FDA microscopy–negative bacteria in these pretreatment samples may be a nonstaining, slowly metabolizing phenotype better adapted to airborne transmission. PMID:28510693

Frequency of tuberculosis at autopsies in a large hospital in Zagreb, Croatia: a 10-year retrospective study

PubMed Central

Pavić, Ivana; Radulović, Petra; Bujas, Tatjana; Perić Balja, Melita; Ostojić, Jelena; Baličević, Drinko

2012-01-01

Aim To assess the frequency and forms of pulmonary tuberculosis at autopsy in a high-traffic hospital in the capital city of a country with a low tuberculosis incidence. Methods We performed a retrospective search of autopsy data from the period 2000 to 2009 at Sestre Milosrdnice University Hospital Center, Zagreb, Croatia. We also examined patients’ records and histological slides. Results Of 3479 autopsies, we identified 61 tuberculosis cases, corresponding to a frequency of 1.8%. Active tuberculosis was found in 33 cases (54%), 23 of which (70%) were male. Of the 33 active cases, 25 (76%) were clinically unrecognized and 19 (76%) of these were male. Conclusion Clinically undiagnosed tuberculosis accounted for a substantial proportion of active tuberculosis cases diagnosed at autopsy. Autopsy data may be an important complement to epidemiological data on tuberculosis frequency. PMID:22351578

CD8 T cells and Mycobacterium tuberculosis infection

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2015-01-01

Tuberculosis is primarily a respiratory disease that is caused by Mycobacterium tuberculosis. M. tuberculosis can persist and replicate in macrophages in vivo, usually in organized cellular structures called granulomas. There is substantial evidence for the importance of CD4 T cells in control of tuberculosis, but the evidence for a requirement for CD8 T cells in this infection has not been proven in humans. However, animal model data support a non-redundant role for CD8 T cells in control of M. tuberculosis infection, and in humans, infection with this pathogen leads to generation of specific CD8 T cell responses. These responses include classical (MHC Class I restricted) and non-classical CD8 T cells. Here, we discuss the potential roles of CD8 T cells in defense against tuberculosis, and our current understanding of the wide range of CD8 T cell types seen in M. tuberculosis infection. PMID:25917388

CE: Tuberculosis: A New Screening Recommendation and an Expanded Approach to Elimination in the United States.

PubMed

Parmer, John; Allen, Leeanna; Walton, Wanda

2017-08-01

: Nurses play a critical role in the diagnosis and treatment of tuberculosis and in the prevention of tuberculosis transmission through infection control practices. To eliminate tuberculosis in the United States, however, an expanded approach to testing and treating people with latent tuberculosis infection must be implemented. Recently, the U.S. Preventive Services Task Force (USPSTF) issued a new recommendation statement on latent tuberculosis infection testing that expands nurses' opportunities to identify at-risk populations for tuberculosis prevention. In combination with newer testing methodologies and shorter treatment regimens, implementation of the USPSTF recommendation has the potential to remove previously existing barriers to screening and treatment of both patients and health care providers. This article provides a general overview of tuberculosis transmission, pathogenesis, and epidemiology; presents preventive care recommendations for targeted testing among high-risk groups; and discusses the USPSTF recommendation's applicability to public health and primary care practice in the United States.

Intestinal tuberculosis masquerading as difficult to treat Crohn disease: a case report.

PubMed

Niriella, Madunil A; Kodisinghe, S Kuleesha; De Silva, Arjuna P; Hewavisenthi, Janaki; de Silva, Hithanadura J

2016-08-24

Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment. This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory.

Tuberculosis and mental health in the Asia-Pacific.

PubMed

Mason, Paul H; Sweetland, Annika C; Fox, Greg J; Halovic, Shaun; Nguyen, Thu Anh; Marks, Guy B

2016-12-01

This opinion piece encourages mental health researchers and clinicians to engage with mental health issues among tuberculosis patients in the Asia-Pacific region in a culturally appropriate and ethical manner. The diversity of cultural contexts and the high burden of tuberculosis throughout the Asia-Pacific presents significant challenges. Research into tuberculosis and mental illness in this region is an opportunity to develop more nuanced models of mental illness and treatment, while simultaneously contributing meaningfully to regional tuberculosis care and prevention. We overview key issues in tuberculosis and mental illness co-morbidity, highlight ethical concerns and advocate for a regional approach to tuberculosis and mental health that is consistent with the transnational challenges presented by this airborne infectious disease. Integrating tuberculosis and mental health services will go a long way to addressing the needs of vulnerable populations and stopping the transmission of one of the world's biggest infectious killers. © The Royal Australian and New Zealand College of Psychiatrists 2016.

BCG and New Preventive Tuberculosis Vaccines: Implications for Healthcare Workers

PubMed Central

Hatherill, Mark; Scriba, Thomas J.; Udwadia, Zarir F.; Mullerpattan, Jai B.; Hawkridge, Anthony; Mahomed, Hassan; Dye, Christopher

2016-01-01

Healthcare workers (HCWs) are at high risk of Mycobacterium tuberculosis (Mtb) infection and tuberculosis disease, but also play a crucial role in implementing healthcare. Preexposure tuberculosis vaccination, including revaccination with BCG, might benefit Mtb-uninfected HCWs, but most HCWs in tuberculosis-endemic countries are already sensitized to mycobacteria. A new postexposure tuberculosis vaccine offers greatest potential for protection, in the setting of repeated occupational Mtb exposure. Novel strategies for induction of mycobacteria-specific resident memory T cells in the lung by aerosol administration, or induction of T cells with inherent propensity for residing in mucosal sites, such as CD1-restricted T cells and mucosa-associated innate T cells, should be explored. The need for improved protection of HCWs against tuberculosis disease is clear. However, health systems in tuberculosis-endemic countries would need significantly improved occupational health structures to implement a screening and vaccination strategy for HCWs. PMID:27118856

Chronobiology: relevance for tuberculosis.

PubMed

Santos, Lígia Gabrielle; Pires, Gabriel Natan; Azeredo Bittencourt, Lia Rita; Tufik, Sergio; Andersen, Monica Levy

2012-07-01

Despite the knowledge concerning the pathogenesis of tuberculosis, this disease remains one of the most important causes of mortality worldwide. Several risk factors are well-known, such poverty, HIV infection, and poor nutrition, among others. However, some issues that may influence tuberculosis warrant further investigation. In particular, the chronobiological aspects related to tuberculosis have garnered limited attention. In general, the interface between tuberculosis and chronobiology is manifested in four ways: variations in vitamin D bioavailability, winter conditions, associated infections, and circannual oscillations of lymphocytes activity. Moreover, tuberculosis is related to the following chronobiological factors: seasonality, latitude, photoperiod and radiation. Despite the relevance of these topics, the relationship between them has been weakly reviewed. This review aims to synthesize the studies regarding the association between tuberculosis and chronobiology, as well as urge critical discussion and highlight its applicability to health policies for tuberculosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effect of tuberculosis and tuberculosis contact tracing on school function: an exploratory focus group study.

PubMed

Upshur, R E; Deadman, L; Howorth, P; Shortt, L

1999-01-01

Selected schools in East York, an ethnically diverse municipality of 110,000 people within Toronto. To explore school staff's attitudes and beliefs about the nature of tuberculosis and its possible effect on the function and culture of schools. Four focus groups of 6-8 school staff, lasting from 1 to 1.5 hours, were held in the spring of 1997 at four different schools deemed to be at high risk for tuberculosis contact tracing. The study identified the following dominant themes: fear of tuberculosis and its impact on school, lack of knowledge and the need for education concerning tuberculosis, and issues in multiculturalism. Tuberculosis was perceived by staff of East York schools to be a source of fear. Lack of accurate and reliable information concerning tuberculosis contributes to this situation. Staff identified age-specific and culturally relevant, educational initiatives as means to reduce this fear.

Evaluation of the results of Mycobacterium tuberculosis direct test (MTD) and Mycobacterial culture in urine samples

PubMed Central

Sener, Asli Gamze; Kurultay, Nukhet; Afsar, Ilhan

2008-01-01

Tuberculosis remains a public health problem in Turkey. Rapid detection of Mycobacterium tuberculosis plays a key role in control of infection. In this article, the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) was evaluated for detection of M. tuberculosis in urine samples. The performance of the MTD was very good and appropriate for routine laboratory diagnosis. PMID:24031287

Revisiting Host Preference in the Mycobacterium tuberculosis Complex: Experimental Infection Shows M. tuberculosis H37Rv to Be Avirulent in Cattle

PubMed Central

Whelan, Adam O.; Coad, Michael; Cockle, Paul J.; Hewinson, Glyn; Vordermeier, Martin; Gordon, Stephen V.

2010-01-01

Experiments in the late 19th century sought to define the host specificity of the causative agents of tuberculosis in mammals. Mycobacterium tuberculosis, the human tubercle bacillus, was independently shown by Smith, Koch, and von Behring to be avirulent in cattle. This finding was erroneously used by Koch to argue the converse, namely that Mycobacterium bovis, the agent of bovine tuberculosis, was avirulent for man, a view that was subsequently discredited. However, reports in the literature of M. tuberculosis isolation from cattle with tuberculoid lesions suggests that the virulence of M. tuberculosis for cattle needs to be readdressed. We used an experimental bovine infection model to test the virulence of well-characterized strains of M. tuberculosis and M. bovis in cattle, choosing the genome-sequenced strains M. tuberculosis H37Rv and M. bovis 2122/97. Cattle were infected with approximately 106 CFU of M. tuberculosis H37Rv or M. bovis 2122/97, and sacrificed 17 weeks post-infection. IFN-γ and tuberculin skin tests indicated that both M. bovis 2122 and M. tuberculosis H37Rv were equally infective and triggered strong cell-mediated immune responses, albeit with some indication of differential antigen-specific responses. Postmortem examination revealed that while M. bovis 2122/97–infected animals all showed clear pathology indicative of bovine tuberculosis, the M. tuberculosis–infected animals showed no pathology. Culturing of infected tissues revealed that M. tuberculosis was able to persist in the majority of animals, albeit at relatively low bacillary loads. In revisiting the early work on host preference across the M. tuberculosis complex, we have shown M. tuberculosis H37Rv is avirulent for cattle, and propose that the immune status of the animal, or genotype of the infecting bacillus, may have significant bearing on the virulence of a strain for cattle. This work will serve as a baseline for future studies into the genetic basis of host preference, and in particular the molecular basis of virulence in M. bovis. PMID:20049086

Nonlinear pattern of pulmonary tuberculosis among migrants at entry in Kuwait: 1997–2006

PubMed Central

Akhtar, Saeed; Mohammad, Hameed GHH

2008-01-01

Background There is a paucity of published data on the pattern of pulmonary tuberculosis among migrant workers entering Middle Eastern countries particularly Kuwait. The objectives of this study were to use routine health surveillance data i) to estimate the prevalence of pulmonary tuberculosis among migrant workers at entry in Kuwait and ii) to determine the occurrence of any time trends in the proportions of pulmonary tuberculosis positive workers over the study period. Methods The monthly aggregates of daily number of migrants tested and the number of pulmonary tuberculosis cases detected during routine health examinations of migrant workers from tuberculosis high-prevalence countries were used to generate the monthly series of proportions (per 100,000) of pulmonary tuberculosis cases over 120 months between January 1, 1997 and December 31, 2006 and analysed using time series methods. Results The overall prevalence (per 100,000) of documented pulmonary tuberculosis cases among screened migrants was 198 (4608/2328582). Year-specific prevalence (per 100,000) of tuberculosis cases consistently declined from 456 (95% CI: 424 – 490) in 1997 to 124 (95% CI: 110 – 140) in 2002 before showing a steady increase up to 183 (95% CI: 169–197) in 2006. The second-order polynomial regression model revealed significant (P < 0.001) initial decline, followed by a significant (P < 0.001) increasing trend thereafter in monthly proportions of tuberculosis cases among migrant workers. Conclusion The proportions of documented tuberculosis cases among migrant workers showed a significant nonlinear pattern, with an initial decline followed by a significant increasing trend towards the end of the study period. These findings underscore the need to maintain the current policy of migrants' screening for tuberculosis at entry. The public health authorities in Kuwait and perhaps other countries in the region may consider complementing the current screening protocol with interferon-γ assays to detect migrants with latent Mycobacterium tuberculosis infection. An appropriate curative or preventive chemotherapy of detected tuberculosis cases may help in further minimizing the risk of local transmission of M. tuberculosis, while contributing in global efforts to control this public health menace. PMID:18667057

Assessment of knowledge and practice of health workers towards tuberculosis infection control and associated factors in public health facilities of Addis Ababa, Ethiopia: A cross-sectional study.

PubMed

Demissie Gizaw, Girma; Aderaw Alemu, Zewdie; Kibret, Kelemu Tilahun

2015-01-01

Tuberculosis is the leading causes of mortality among infectious diseases worldwide. The risk of transmission from patients to health workers is doubles that of the general population. The close contact to the infectious case before diagnosis is the major risk for tuberculosis infection. The aim of the study was to assess knowledge and practice of health professionals towards tuberculosis infection control and its associated factors in health facilities of Addis Ababa, Ethiopia. A cross-sectional study was conducted from February 29 to April 15/2014 in selected health facilities in Addis Ababa. Five hundred ninety health workers were included in the study. The sample size was assigned to each health facility proportional to their number of health workers. Study subjects were selected from each stratum by simple random sampling technique. Interviewer administered structured questionnaire was used to collect information. Logistic regression was used to identify factors associated with knowledge and practice of health workers towards tuberculosis infection control. Five hundred eighty two participants with 98.6% response rate were involved in the study. Of these, 36.1% had poor knowledge and 51.7% unsatisfactory practice score towards tuberculosis infection control. Having more than six years working experience in health facility (AOR = 2.51; 95% CI: 1.5-4.1) and tuberculosis related training (AOR = 2.51 95% CI; 1.5, 4.1) were significantly associated with knowledge on tuberculosis infection control. Having experience in tuberculosis clinic (AOR =1.93; 95% CI: 1.12, 3.34) and tuberculosis related training (AOR = 1.48; 95% CI: 1.87, 2.51) were significantly associated with practice on tuberculosis infection control. One third of health workers had relatively poor knowledge and nearly half of them had unsatisfactory practice on tuberculosis infection control. Tuberculosis training and work experiences in health facility are determinant factor to knowledge. Whereas tuberculosis related training and experience in tuberculosis clinic are predictor to practice. So, training of the health professionals, on job orientations of junior health workers, and farther study including private health workers are recommended.

Transmission of multidrug-resistant tuberculosis in the USA: a cross-sectional study.

PubMed

Moonan, Patrick K; Teeter, Larry D; Salcedo, Katya; Ghosh, Smita; Ahuja, Shama D; Flood, Jennifer; Graviss, Edward A

2013-09-01

Multidrug-resistant (MDR) tuberculosis is a potential threat to tuberculosis elimination, but the extent of MDR tuberculosis disease in the USA that is attributable to transmission within the country is unknown. We assessed transmission of MDR tuberculosis and potential contributing factors in the USA. In a cross-sectional study, clinical, demographic, epidemiological, and Mycobacterium tuberculosis genotype data were obtained during routine surveillance of all verified cases of MDR tuberculosis reported from eight states in the USA (California from Jan 1, 2007, to Dec 31, 2009; Texas from Jan 1, 2007, to March 31, 2009; and the states of Colorado, Maryland, Massachusetts, New York, Tennessee, and Washington from Jan 1, 2007 to Dec 31, 2008). In-depth interviews and health-record abstraction were done for all who consented to ascertain potential interpersonal connections. 168 cases of MDR tuberculosis were reported in the eight states during our study period. 92 individuals (55%) consented to in-depth interview. 20 (22%) of these individuals developed MDR tuberculosis as a result of transmission in the USA; a source case was identified for eight of them (9%). 20 individuals (22%) had imported active tuberculosis (ie, culture-confirmed disease within 3 months of entry into the USA). 38 (41%) were deemed to have reactivation of disease, of whom 14 (15%) had a known previous episode of tuberculosis outside the USA. Five individuals (5%) had documented treatment of a previous episode in the USA, and so were deemed to have relapsed. For nine cases (10%), insufficient evidence was available to definitively classify reason for presentation. About a fifth of cases of MDR tuberculosis in the USA can be linked to transmission within the country. Many individuals acquire MDR tuberculosis before entry into the USA. MDR tuberculosis needs to be diagnosed rapidly to reduce potential infectious periods, and clinicians should consider latent tuberculosis infection treatment-tailored to the results of drug susceptibility testing of the putative source case-for exposed individuals. Centers for Disease Control and Prevention. Copyright © 2013 Elsevier Ltd. All rights reserved.

[USE OF QuantiFERON® TB-GOLD IN-TUBE IN A CONTACT INVESTIGATION TO DETERMINE THE ONSET OF TUBERCULOSIS WITH OR WITHOUT LATENT TUBERCULOSIS INFECTION TREATMENT].

PubMed

Matsumoto, Kenji; Komukai, Jun; Tsuda, Yuko; Furukawa, Kanae; Saito, Kazumi; Hirota, Satoshi; Koda, Shinichi; Kasai, Sachi; Shimouchi, Akira

2016-02-01

QuantiFERON® TB-Gold In-Tube (3G) testing was performed on tuberculosis-positive index cases and their contacts. The purpose of this study was to evaluate the relationship between 3G test results and the subsequent development of tuberculosis, and to identify effective strategies to prevent the onset of tuberculosis. Index cases and their contacts were subjected to 3G testing in a contact investigation in Osaka City in 2011-2012. For index cases, sputum smears were tested, and the infecting organism was identified. For the contacts, the following information was collected: age, results of 3G testing, presence or absence of latent tuberculosis infection (LTBI) treatment, and onset of tuberculosis disease within 2 years of follow-up from the last contact with the index cases. (1) There were 830 index cases, including 774 subjects with pulmonary tuberculosis (93.3%) and 3 with laryngeal tuberculosis (0.4%). From sputum smear tests, 726 patients (87.5%) were determined to be 3G positive, and 83 (10.0%) were determined to be 3G negative. (2) In total, 2,644 contacts were subjected to 3G testing. Of these, 2,072 patients (78.4%) tested negative, 196 (7.4%) showed an equivocal result, and 375 (14.2%) tested positive. Their mean ages were 33.7, 38.0, and 38.8 years, respectively, showing significant differences in tuberculosis status according to age (P < 0.001). (3) Among the 2,072 3G-negative contacts, tuberculosis developed in 2 (0.1%) of 2063. None of these contacts was treated for LTBI. Among the 375 3G-positive contacts, tuberculosis developed in 36 (36.0%) of 100 subjects that were not LTBI treated, while tuberculosis developed in 3 (1.1 %) of 275 subjects that were LTBI treated. A significant difference in the incidence of tuberculosis between treated and untreated 3G-positive contacts was observed (P < 0.001). Tuberculosis developed in a high proportion of 3G-positive contacts that were not LTBI treated, suggesting the need for preventive management of 3G-positive contacts.

Tuberculosis: a new vision for the 21st century.

PubMed

Small, Peter M

2009-11-01

Tuberculosis is a global problem that we can't afford to keep ignoring. In 2006, tuberculosis killed 1.7 million people--almost twice as many people as malaria--and it is the leading cause of death among people living with HIV/AIDS. This is all the more tragic because these deaths are preventable. For a long time the world thought that we had defeated tuberculosis, but just because tuberculosis doesn't make headlines doesn't mean it has gone away. The fact is that tuberculosis is getting worse, as complacency and lack of adequate tools and funding fuel the disease and the spread of drug resistance. Drug resistant tuberculosis is the wake-up call, it is an airborne epidemic of increasingly untreatable disease. Drug resistant tuberculosis develops when tuberculosis patients take low-quality drugs, do not finish their full course of treatment, or pass drug resistant tuberculosis from one person to another. In 2007, there were approximately 500,000 cases of drug resistant tuberculosis globally. MDR-TB is resistant to the two most commonly used first-line TB drugs, and requires long, complex and expensive treatment. XDR-TB is resistant to first- and second-line drugs, severely limiting treatment options. While progress is being made, much more is needed. Basic tuberculosis control is one of the most cost-effective interventions in global health. Appropriate treatment can save a life and stop the spread of disease for US$14. It is essential that countries implement the World Health Organization's (WHO) internationally recommended Stop TB strategy, which includes DOTS. But due to outdated tools and methods, DOTS alone is not enough. The remarkable fact is that global control of tuberculosis, a disease that kills someone every 20 seconds, depends upon a 125-year-old test, an 85-year-old vaccine and drugs that take six months to cure and haven't changed in four decades. To successfully treat tuberculosis and prevent resistance, we need to use current tools better and accelerate the development of new tools for the future. Simple improvements in tuberculosis control, such as expanding the use of under-utilized technologies, can have enormous impact. Fixed-dose combinations have existed for over 25 years, and could help ensure that more patients complete treatment; yet globally, only 15 percent of patients are using them. We also need new drugs, vaccines and diagnostics, as well as innovations in tuberculosis control and case management. Better diagnostics are already available, and new drugs and vaccines are coming. But more commitment and resources are needed. Better prevention and control of tuberculosis is the surest way to stop drug resistance. To ensure that drug resistance does not pose a wider threat, we need to employ a number of equally important approaches. These include improved basic tuberculosis control, increased use of underutilized technologies such as fixed-dose combinations, and new technologies and health systems innovations. At the same time, we should expand access to M/XDR-TB treatment and diagnostics for those who already have drug resistant tuberculosis. Some of the most innovative solutions can come from the private sector and through partnerships. An untapped market of two billion people carries the tuberculosis bacterium. Since tuberculosis requires a comprehensive approach, companies should also explore opportunities to work together and pool complementary technologies to ensure new tools are used most effectively. Japan is poised to play a leading role in the discovery, development and delivery of tuberculosis solutions in the 21st century.

Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1.

PubMed

Elkington, Paul T G; Nuttall, Robert K; Boyle, Joseph J; O'Kane, Cecilia M; Horncastle, Donna E; Edwards, Dylan R; Friedland, Jon S

2005-12-15

Pulmonary cavitation is fundamental to the global success of Mycobacterium tuberculosis. However, the mechanisms of this lung destruction are poorly understood. The biochemistry of lung matrix predicts matrix metalloproteinase (MMP) involvement in immunopathology. We investigated gene expression of all MMPs, proteins with a disintegrin and metalloproteinase domain, and tissue inhibitors of metalloproteinases in M. tuberculosis-infected human macrophages by real-time polymerase chain reaction. MMP secretion was measured by zymography and Western analysis, and expression in patients with pulmonary tuberculosis was localized by immunohistochemistry. MMP-1 and MMP-7 gene expression and secretion are potently upregulated by M. tuberculosis, and no increase in tissue inhibitor of metalloproteinase expression occurs to oppose their activity. Dexamethasone completely suppresses MMP-1 but not MMP-7 gene expression and secretion. In patients with active tuberculosis, macrophages express MMP-1 and MMP-7 adjacent to areas of tissue destruction. MMP-1 but not MMP-7 expression and secretion are relatively M. tuberculosis specific, are not upregulated by tuberculosis-associated cytokines, and are prostaglandin dependent. In contrast, the vaccine M. bovis bacillus Calmette-Guérin (BCG) does not stimulate MMP-1 secretion from human macrophages, although M. tuberculosis and BCG do upregulate MMP-7 equally. BCG-infected macrophages secrete reduced prostaglandin E2 concentrations compared with M. tuberculosis-infected macrophages, and prostaglandin pathway supplementation augments MMP-1 secretion from BCG-infected cells. M. tuberculosis specifically upregulates MMP-1 in a cellular model of human infection and in patients with tuberculosis. In contrast, vaccine BCG, which does not cause lung cavitation, does not upregulate prostaglandin E2-dependent MMP-1 secretion.

Molecular epidemiology of tuberculosis in foreign-born persons living in San Francisco.

PubMed

Suwanpimolkul, Gompol; Jarlsberg, Leah G; Grinsdale, Jennifer A; Osmond, Dennis; Kawamura, L Masae; Hopewell, Philip C; Kato-Maeda, Midori

2013-05-01

In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations. To determine the clinical, epidemiological and microbiological characteristics of tuberculosis caused by recent infection and rapid evolution in the major groups of foreign-born and the U.S.-born populations. We analyzed data from a 20-year prospective community-based study of the molecular epidemiology of tuberculosis in San Francisco. We included all culture-positive tuberculosis cases in the City during the study period. We calculated and compared incidence rates, clinical and microbiological characteristics, and risk factors for being a secondary case between the various foreign-born and U.S.-born tuberculosis populations. Between 1991 and 2010, there were 4,058 new cases of tuberculosis, of which 1,226 (30%) were U.S.-born and 2,832 (70%) were foreign-born. A total of 3,278 (81%) were culture positive, of which 2,419 (74%) had complete data for analysis. The incidence rate, including the incidence rate of tuberculosis due to recent infection and rapid evolution, decreased significantly in the U.S.-born and the major foreign-born populations. The clinical and microbiological characteristics and the risk factors for tuberculosis due to recent infection differed among the groups. There are differences in the characteristics and the risk factors for tuberculosis due to recent transmission among the major foreign-born and U.S.-born populations in San Francisco. These differences should be considered for the design of targeted tuberculosis control interventions.

Molecular identification of Mycobacterium tuberculosis in cattle.

PubMed

Sweetline Anne, N; Ronald, B S M; Kumar, T M A Senthil; Kannan, P; Thangavelu, A

2017-01-01

Bovine tuberculosis continued to be a re-emerging problem in some countries especially in endemic areas due to the fact that human and animal health surveillance system is not adopted to diagnose the infection. This crisis can be attributed due to sharing of the same habitat especially in rural areas. In the present study, a total of 148 samples were collected from cattle for isolation over a period of 3 years from cattle with and without lesions, of which 67 isolates were obtained by culture. Fifty one isolates were identified as Mycobacterium tuberculosis complex (MTBC) by IS6110 PCR of which 43 (84.3%) were identified as M. tuberculosis and 08 (15.6%) were identified as M. bovis by using 12.7kb fragment multiplex PCR. Among this, 31 isolates which were positive for IS6110 PCR were subjected to spoligotyping and revealed 28 isolates belonging to MANU1 strain of M. tuberculosis. This study clearly indicates that high prevalence of M. tuberculosis than M. bovis in bovine was identified by means of culture and by molecular methods M. tuberculosis can affect cattle producing lesion in contradiction to the earlier thoughts. This study speculates that M. tuberculosis MANU1 strain infection in cattle could be due to spill over from human or other non specific hosts in tuberculosis endemic areas. Though bovine tuberculosis due to M. tuberculosis in cattle is not considered a serious threat worldwide, in countries where human TB is endemic, M. tuberculosis infection of cattle needs to be considered. Copyright © 2016 Elsevier B.V. All rights reserved.

Delivering Patient-Centered Care in a Fragile State: Using Patient-Pathway Analysis to Understand Tuberculosis-Related Care Seeking in Pakistan.

PubMed

Fatima, Razia; Haq, Mahboob Ul; Yaqoob, Aashifa; Mahmood, Nasir; Ahmad, Khawaja Laeeq; Osberg, Mike; Makayova, Julia; Hymoff, Aaron; Hanson, Christy

2017-11-06

Pakistan has the sixth largest population in the world and boasts the fifth greatest burden of tuberculosis. The Government of Pakistan has set the ambitious goal of zero deaths due to tuberculosis and universal access to tuberculosis care by 2020. Successfully reaching these goals is dependent on the country's capacity to diagnose and successfully treat an estimated 200000 unnotified or missing patients with tuberculosis. A patient-pathway analysis (PPA) was conducted at the national level, as well as for each of the 4 provinces, to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services. Almost 90% of patients initiated care in the private sector, which accounts for only 15% of facilities with the capacity for tuberculosis diagnosis and treatment. Across the country, nearly 50% of tuberculosis microscopy laboratories were located in public-sector-basic health units and regional health centers. However, very few patients initiated care in these facilities. Overall, tuberculosis case detection was high given the low likelihood of patients reaching facilities with the capacity for tuberculosis service delivery during their first visit. Improving the engagement of the informal sector and lower-level clinicians will improve the efficiency and timeliness of tuberculosis diagnosis for patients in Pakistan. Concurrently, the apparent strength of the referral networks connecting community-level workers and private clinicians to the public sector for tuberculosis diagnosis and treatment suggests that strengthening the capacity of the public sector could be valuable. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Delayed and Unreported Drug-Susceptibility Testing Results in the US National Tuberculosis Surveillance System, 1993-2014.

PubMed

Jones, Jefferson Michael; Armstrong, Lori R

Drug-susceptibility testing (DST) of Mycobacterium tuberculosis is necessary for identifying drug-resistant tuberculosis, administering effective treatment regimens, and preventing the spread of drug-resistant tuberculosis. DST is recommended for all culture-confirmed cases of tuberculosis. We examined trends in delayed and unreported DST results in the Centers for Disease Control and Prevention's National Tuberculosis Surveillance System. We analyzed culture-confirmed tuberculosis cases reported to the National Tuberculosis Surveillance System during 1993-2014 for annual trends in initial DST reporting for first-line antituberculosis drugs and trends in on-time, delayed, and unreported results. We defined on-time reporting as DST results received during the same calendar year in which the patient's case was reported or ≤4 months after the calendar year ended and delayed reporting as DST results received after the calendar year. We compared cases with on-time, delayed, and unreported DST results by patient and tuberculosis program characteristics. The proportion of cases with reported results for all first-line antituberculosis drugs increased during 1993-2011. Reporting of pyrazinamide results was lower than reporting of other drugs. However, during 2000-2012, of 134 787 tuberculosis cases reported to the National Tuberculosis Surveillance System, reporting was on time for 125 855 (93.4%) cases, delayed for 5332 (4.0%) cases, and unreported for 3600 (2.7%) cases. Despite increases in the proportion of cases with on-time DST results, delayed and unreported results persisted. Carefully assessing causes for delayed and unreported DST results should lead to more timely reporting of drug-resistant tuberculosis.

Population Aging and Migrant Workers: Bottlenecks in Tuberculosis Control in Rural China

PubMed Central

Lu, Hui; You, Hua; Fan, Hong; Huang, Lifang; Wang, Qungang; Shen, Hongbing; Wang, Jianming

2014-01-01

Background Tuberculosis is a serious global health problem. Its paradigms are shifting through time, especially in rapidly developing countries such as China. Health providers in China are at the forefront of the battle against tuberculosis; however, there are few empirical studies on health providers' perspectives on the challenges they face in tuberculosis control at the county level in China. This study was conducted among health providers to explore their experiences with tuberculosis control in order to identify bottlenecks and emerging challenges in controlling tuberculosis in rural China. Methods A qualitative approach was used. Semi-structured, in-depth interviews were conducted with 17 health providers working in various positions within the health system of one rural county (ZJG) of China. Data were analyzed based on thematic content analysis using MAXQDA 10 qualitative data analysis software. Results Health providers reported several problems in tuberculosis control in ZJG county. Migrant workers and the elderly were repeatedly documented as the main obstacles in effective tuberculosis control in the county. At a personal level, doctors showed their frustration with the lack of new drugs for treating tuberculosis patients, and their opinions varied regarding incentives for referring patients. Conclusion The results suggest that several problems still remain for controlling tuberculosis in rural China. Tuberculosis control efforts need to make reaching the most vulnerable populations a priority and encourage local health providers to adopt innovative practices in the local context based on national guidelines to achieve the best results. Considerable changes in China's National Tuberculosis Control Program are needed to tackle these emerging challenges faced by health workers at the county level. PMID:24498440

Population aging and migrant workers: bottlenecks in tuberculosis control in rural China.

PubMed

Bele, Sumedh; Jiang, Wei; Lu, Hui; You, Hua; Fan, Hong; Huang, Lifang; Wang, Qungang; Shen, Hongbing; Wang, Jianming

2014-01-01

Tuberculosis is a serious global health problem. Its paradigms are shifting through time, especially in rapidly developing countries such as China. Health providers in China are at the forefront of the battle against tuberculosis; however, there are few empirical studies on health providers' perspectives on the challenges they face in tuberculosis control at the county level in China. This study was conducted among health providers to explore their experiences with tuberculosis control in order to identify bottlenecks and emerging challenges in controlling tuberculosis in rural China. A qualitative approach was used. Semi-structured, in-depth interviews were conducted with 17 health providers working in various positions within the health system of one rural county (ZJG) of China. Data were analyzed based on thematic content analysis using MAXQDA 10 qualitative data analysis software. Health providers reported several problems in tuberculosis control in ZJG county. Migrant workers and the elderly were repeatedly documented as the main obstacles in effective tuberculosis control in the county. At a personal level, doctors showed their frustration with the lack of new drugs for treating tuberculosis patients, and their opinions varied regarding incentives for referring patients. The results suggest that several problems still remain for controlling tuberculosis in rural China. Tuberculosis control efforts need to make reaching the most vulnerable populations a priority and encourage local health providers to adopt innovative practices in the local context based on national guidelines to achieve the best results. Considerable changes in China's National Tuberculosis Control Program are needed to tackle these emerging challenges faced by health workers at the county level.

Delivering Patient-Centered Care in a Fragile State: Using Patient-Pathway Analysis to Understand Tuberculosis-Related Care Seeking in Pakistan

PubMed Central

Fatima, Razia; Haq, Mahboob Ul; Yaqoob, Aashifa; Mahmood, Nasir; Ahmad, Khawaja Laeeq; Osberg, Mike; Makayova, Julia; Hymoff, Aaron; Hanson, Christy

2017-01-01

Abstract Background Pakistan has the sixth largest population in the world and boasts the fifth greatest burden of tuberculosis. The Government of Pakistan has set the ambitious goal of zero deaths due to tuberculosis and universal access to tuberculosis care by 2020. Successfully reaching these goals is dependent on the country’s capacity to diagnose and successfully treat an estimated 200000 unnotified or missing patients with tuberculosis. Methods A patient-pathway analysis (PPA) was conducted at the national level, as well as for each of the 4 provinces, to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services. Results Almost 90% of patients initiated care in the private sector, which accounts for only 15% of facilities with the capacity for tuberculosis diagnosis and treatment. Across the country, nearly 50% of tuberculosis microscopy laboratories were located in public-sector–basic health units and regional health centers. However, very few patients initiated care in these facilities. Overall, tuberculosis case detection was high given the low likelihood of patients reaching facilities with the capacity for tuberculosis service delivery during their first visit. Discussion Improving the engagement of the informal sector and lower-level clinicians will improve the efficiency and timeliness of tuberculosis diagnosis for patients in Pakistan. Concurrently, the apparent strength of the referral networks connecting community-level workers and private clinicians to the public sector for tuberculosis diagnosis and treatment suggests that strengthening the capacity of the public sector could be valuable. PMID:29117348

The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis

PubMed Central

Caws, Maxine; Thwaites, Guy; Dunstan, Sarah; Hawn, Thomas R.; Thi Ngoc Lan, Nguyen; Thuong, Nguyen Thuy Thuong; Stepniewska, Kasia; Huyen, Mai Nguyet Thu; Bang, Nguyen Duc; Huu Loc, Tran; Gagneux, Sebastien; van Soolingen, Dick; Kremer, Kristin; van der Sande, Marianne; Small, Peter; Thi Hoang Anh, Phan; Chinh, Nguyen Tran; Thi Quy, Hoang; Thi Hong Duyen, Nguyen; Quang Tho, Dau; Hieu, Nguyen T.; Torok, Estee; Hien, Tran Tinh; Dung, Nguyen Huy; Thi Quynh Nhu, Nguyen; Duy, Phan Minh; van Vinh Chau, Nguyen; Farrar, Jeremy

2008-01-01

The factors that govern the development of tuberculosis disease are incompletely understood. We hypothesized that some strains of Mycobacterium tuberculosis (M. tuberculosis) are more capable of causing disseminated disease than others and may be associated with polymorphisms in host genes responsible for the innate immune response to infection. We compared the host and bacterial genotype in 187 Vietnamese adults with tuberculous meningitis (TBM) and 237 Vietnamese adults with uncomplicated pulmonary tuberculosis. The host genotype of tuberculosis cases was also compared with the genotype of 392 cord blood controls from the same population. Isolates of M. tuberculosis were genotyped by large sequence polymorphisms. The hosts were defined by polymorphisms in genes encoding Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and Toll-like receptor-2 (TLR-2). We found a significant protective association between the Euro-American lineage of M. tuberculosis and pulmonary rather than meningeal tuberculosis (Odds ratio (OR) for causing TBM 0.395, 95% confidence intervals (C.I.) 0.193–0.806, P = 0.009), suggesting these strains are less capable of extra-pulmonary dissemination than others in the study population. We also found that individuals with the C allele of TLR-2 T597C allele were more likely to have tuberculosis caused by the East-Asian/Beijing genotype (OR = 1.57 [95% C.I. 1.15–2.15]) than other individuals. The study provides evidence that M. tuberculosis genotype influences clinical disease phenotype and demonstrates, for the first time, a significant interaction between host and bacterial genotypes and the development of tuberculosis. PMID:18369480

Dispersal of Mycobacterium tuberculosis via the Canadian fur trade

PubMed Central

Pepperell, Caitlin S.; Granka, Julie M.; Alexander, David C.; Behr, Marcel A.; Chui, Linda; Gordon, Janet; Guthrie, Jennifer L.; Jamieson, Frances B.; Langlois-Klassen, Deanne; Long, Richard; Nguyen, Dao; Wobeser, Wendy; Feldman, Marcus W.

2011-01-01

Patterns of gene flow can have marked effects on the evolution of populations. To better understand the migration dynamics of Mycobacterium tuberculosis, we studied genetic data from European M. tuberculosis lineages currently circulating in Aboriginal and French Canadian communities. A single M. tuberculosis lineage, characterized by the DS6Quebec genomic deletion, is at highest frequency among Aboriginal populations in Ontario, Saskatchewan, and Alberta; this bacterial lineage is also dominant among tuberculosis (TB) cases in French Canadians resident in Quebec. Substantial contact between these human populations is limited to a specific historical era (1710–1870), during which individuals from these populations met to barter furs. Statistical analyses of extant M. tuberculosis minisatellite data are consistent with Quebec as a source population for M. tuberculosis gene flow into Aboriginal populations during the fur trade era. Historical and genetic analyses suggest that tiny M. tuberculosis populations persisted for ∼100 y among indigenous populations and subsequently expanded in the late 19th century after environmental changes favoring the pathogen. Our study suggests that spread of TB can occur by two asynchronous processes: (i) dispersal of M. tuberculosis by minimal numbers of human migrants, during which small pathogen populations are sustained by ongoing migration and slow disease dynamics, and (ii) expansion of the M. tuberculosis population facilitated by shifts in host ecology. If generalizable, these migration dynamics can help explain the low DNA sequence diversity observed among isolates of M. tuberculosis and the difficulties in global elimination of tuberculosis, as small, widely dispersed pathogen populations are difficult both to detect and to eradicate. PMID:21464295

Childhood Tuberculosis and Malnutrition

PubMed Central

Jaganath, Devan; Mupere, Ezekiel

2012-01-01

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease. PMID:23033147

High prevalence of multidrug resistant tuberculosis in Djibouti: a retrospective study.

PubMed

Boyer-Cazajous, Géraldine; Martinaud, Christophe; Déhan, Céline; Hassan, Mohammed Osman; Gaas, Yassin; Chenilleau-Vidal, Marie-Caroline; Soler, Charles

2014-02-13

The Republic of Djibouti is an African country that exhibits one of the highest incidence rate of tuberculosis in the world. The aim of this study was to evaluate the prevalence of multidrug-resistant tuberculosis among new cases. We studied retrospectively every tuberculosis case diagnosed over a 12-month period in patients hospitalized at the French Military Hospital of Bouffard. During this period, 1,274 samples from 675 patients were tested. We isolated 266 mycobacteria corresponding to 180 cases of tuberculosis. Thirty-three were fully susceptible and 57% met the tuberculosis criteria, with 46% primary resistance. No extensively-drug-resistant tuberculosis was found. Our results highlight a major concern about the situation in this part of the world.

Congenital Tuberculosis as a Result of Disseminated Maternal Disease: Case Report

PubMed Central

Trujillo-Honeysberg, Mónica; Diazgranados-Cuenca, Lucy

2015-01-01

Although tuberculosis is highly prevalent worldwide, congenital tuberculosis is one of the least common manifestations of the disease. The diagnosis is usually difficult because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy and delivery. We present the case of a preterm neonate with congenital tuberculosis, born to a previously healthy mother who had developed severe disseminated tuberculosis during her pregnancy. Once the diagnosis was confirmed in the mother, the congenital infection was confirmed by isolation of Mycobacterium tuberculosis in gastric aspirates, and positive polymerase chain reaction in a cerebrospinal fluid examination. Treatment for tuberculosis with a four-drug regimen resulted in an adequate clinical response in both the mother and infant. PMID:26508944

Bovine Tuberculosis

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB) in animals and humans may result from exposure to bacilli within the Mycobacterium tuberculosis complex (i.e., M. tuberculosis, M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, or M. canetti). Mycobacterium bovis is the species most often isolated from tuberculous catt...

Bovine tuberculosis

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB) in animals and humans may result from exposure to bacilli within the Mycobacterium tuberculosis complex (i.e., M. tuberculosis, M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, or M. canetti) . Mycobacterium bovis is the species most often isolated from tuberculous cat...

Prevalence of self-reported tuberculosis, knowledge about tuberculosis transmission and its determinants among adults in India: results from a nation-wide cross-sectional household survey.

PubMed

Sreeramareddy, Chandrashekhar T; Harsha Kumar, H N; Arokiasamy, John T

2013-01-17

Knowledge about symptoms and transmission of tuberculosis determines health seeking behavior and helps in prevention of tuberculosis transmission in the community. Such data is useful for policy makers to formulate information, education and communication strategies for tuberculosis control. A secondary data analysis of India demographic and health survey, 2005/6 was carried out. Questions about self-reported tuberculosis, transmission and curability of tuberculosis were analysed. Correct knowledge (without misconceptions) about tuberculosis transmission was used as a dependant variable and the explanatory variables tested were: demographic data, education, wealth quintiles, frequency of exposure to media and the curability of tuberculosis. Determinants of correct knowledge without misconceptions were tested by univariate and multivariate analyses using national weighting factor to adjust for complex sampling design. A total of 109,070 households (response rate of 93.5%) and 198,718 participants (response rate of 91.6%) completed the survey. The samples of men and women interviewed were 74,360 and 124,358 respectively. Prevalence rate of self-reported tuberculosis was 445 per 100,000 usual household residents and 4.60 per 1,000 participants. The number of respondents who had "heard of an illness called tuberculosis" was 177,423 (89.3%). Of these 47,487 (26.8%) participants did not know and 55.5% knew about the correct mode of tuberculosis transmission i.e. "Through the air when coughing or sneezing". The common misconceptions about transmission were "Through food" (32.4%), "Sharing utensils" (18.2%), and "Touching a person with tuberculosis" (12.3%). Only 52,617 (29.7%) participants had correct knowledge without misconceptions. Being male (aOR 1.17, 95% CIs 1.14, 1.21), being a Hindu (aOR 1.20, 95% CIs 1.14, 1.26) or Muslim (aOR 1.26, 95% CIs 1.18, 1.34), listening to radio (aOR 1.08, 95% CIs 1.04, 1.13) and "Tuberculosis can be cured" (aOR 1.47, 95% CIs 1.41, 1.53) were associated with correct knowledge without misconceptions. Knowledge about tuberculosis transmission is very poor and misconceptions still exist. Among the traditional mass media, the frequency of listening to radio was associated with correct knowledge about tuberculosis transmission. Strategies to deliver information, education and communication campaigns could be improved.

[Determinants of tuberculosis diagnosis delay in limited resources countries].

PubMed

Ndeikoundam Ngangro, N; Chauvin, P; Halley des Fontaines, V

2012-02-01

Delayed diagnoses of pulmonary tuberculosis contribute to the spread of the epidemic. This study aims to identify risk factors associated with patient delay (from symptoms onset to the first visit), health system delay (from the first visit to the tuberculosis treatment initiation) and total delay (sum of the patient and the health system delay) in low income and high tuberculosis burden countries. A systematic literature review has been performed using the keywords: "tuberculosis"; "delay", care seeking"; "health care seeking behavior"; "diagnosis" and "treatment". Only quantitative studies showing delays for pulmonary tuberculosis adult cases were included in this review. Low income, gender, rural life, unemployment, ageing and misunderstanding the microbial cause of tuberculosis are associated with delayed diagnoses. Systemic factors including low health care coverage, patient expenditures and entry into the health system by consulting a traditional healer or a non-skilled professional delay the beginning of tuberculosis treatment. Delays can be used as indicators to evaluate tuberculosis control programs. Active case finding in the households of contagious patients can help to diminish diagnostic delays in low-income countries with high endemicity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

[Amendment of tuberculosis prevention law and prospect of tuberculosis control program].

PubMed

Ushio, Mitsuhiro

2005-07-01

Tuberculosis Control Law, which provides a legal basis for national tuberculosis control, was amended in 2004 and entered into force on April 1, 2005. As it is more than half a century since its initial enactment, the law has been drastically amended based on some of the relatively new important ideas such as up-to-date scientific evidence, recent epidemiological conditions of tuberculosis, decentralization and respect for human rights. Japan has once seen a time when considerable part of producing population were affected with tuberculosis which caused severe infliction on the whole Japanese society including economical damage. With progress in medical technology such as development of chemotherapy and improvement of sanitary conditions, there was a major decline in incidence rate and death rate during the 1960s and 1970s. However, the decrease in TB incidence began to stagnate in the 1980s, partly explained by aging of the overall society and worsening of the urban tuberculosis conditions. Since then, there has been a discussion on review of national tuberculosis control program, and the increase in the number of tuberculosis patients in 1997, which happened for the first time in 38 years, precipitated the process. In 1999, 'Tuberculosis Emergency Declaration' was announced by the Minister of Health, which led to emergency national tuberculosis survey in 2000, and based on the result came forward the Recommendation on Comprehensive Review of National Tuberculosis Plan. Main ideas and spirits of the Recommendation were taken full account of during the process of the amendment of the law and were mostly reflected on the final outcome. Five key elements include; Establishment of National Tuberculosis Fundamental Guideline and Prefectural Tuberculosis Prevention Plan, Review on TB screening, Review on BCG vaccination policy, Promotion of a Japanese version of DOTS, Review on Tuberculosis Advisory Committee 1. Establishment of National Tuberculosis Fundamental Guideline and Prefectural Tuberculosis Prevention Plan With a view to establishing a comprehensive plan in the context of local tuberculosis situation, it was deemed to be necessary for both the central government and local governments to set out a detailed and comprehensive plan that may supplement the newly amended law. Prior to the amendment of Tuberculosis Prevention Law, it was made obligatory in the amended Infectious Diseases Control Law for the central government to establish National Fundamental Guideline and for local governments to establish Prefectural Prevention Plan. 2. Review on TB Screening With a view to promoting early detection of tuberculosis, tuberculosis screening system was totally reviewed to be turned into more effective and efficacious means for the purpose. Previously, all people above 19 years of age were to be screened annually for tuberculosis with chest X-ray. By this means, however, only 1,600 tuberculosis patients were detected out of 20,000,000 people screened which means the detection rate is 0.0067%. Thorough analysis was made to identify who would benefit from regular X-ray screening in terms of detection of tuberculosis patients and was decided to be those who have certain risk factors to develop tuberculosis such as the elderly and socio-economically challenged people and those who, once develops tuberculosis, may easily infect others such as school teachers, healthcare workers and such. Also the procedure of contact trace was reviewed and in highly required cases, compulsory examination implemented by health care officers has become a choice. 3. Review on BCG vaccination policy Previously national BCG policy included BCG vaccination for young children who tested negative on tuberculin skin test before they become 4 years old. However due to low sensitivity of tuberculin skin test and resulting too many of false-positive cases, the estimated number of unnecessary chemoprophylaxis was thought to be more than justifiable. Also, as regards the timing for vaccination, it was'thought of as best to give BCG vaccination before one gets infected, which may happen even before 4 years of age. For reasons above, new national BCG policy include direct BCG vaccination for infants younger than 6 months of age. 4. Promotion of a Japanese version of DOTS DOTS (Directly Observed Treatment, Short-course) is, needless to say, a tuberculosis control policy advocated worldwide by World Health Organization (WHO) since early 1990s. Japan has a long history of supporting tuberculosis patients through various activities by health care workers such as home-visit follow-up, although it is worthwhile to note that in a newly amended law there is a reference to having patients take medicine in the law itself as direction by a doctor or a director of the public health care center. 5. Review on Tuberculosis Advisory Committee The Tuberculosis Advisory Committee is a regional commi- ttee that gives advice on issues such as treatment of tuberculosis and hospitalization order based on the law. The amendment includes review on committee members to select at least one committee member from non-medical staff from the perspective of human rights protection. We acknowledge this time's amendment of the law is a significant step forward in the history of national tuberculosis control and it is our sincere hope that this will eventually lead to great improvement of national tuberculosis condition.

9 CFR 77.20 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive Cervids... “Uniform Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less.... A herd of captive cervids that has tested negative to at least two consecutive official tuberculosis...

9 CFR 77.20 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive Cervids... “Uniform Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less.... A herd of captive cervids that has tested negative to at least two consecutive official tuberculosis...

9 CFR 77.20 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive Cervids... “Uniform Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less.... A herd of captive cervids that has tested negative to at least two consecutive official tuberculosis...

9 CFR 77.20 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive Cervids... “Uniform Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less.... A herd of captive cervids that has tested negative to at least two consecutive official tuberculosis...

9 CFR 77.20 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive Cervids... “Uniform Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less.... A herd of captive cervids that has tested negative to at least two consecutive official tuberculosis...

Calvarial tuberculosis presenting as cystic lesion: An unusual presentation in two patients.

PubMed

Khare, Pratima; Gupta, Renu; Chand, Priyanka; Agarwal, Swapnil

2015-01-01

Tuberculosis is a common disease in developing countries such as India, posing a major public health problem. With human immunodeficiency virus (HIV) infection being a global endemic, there has been a resurgence of tuberculosis even in developed countries. Tuberculosis may affect almost any part of the body. However, tuberculosis of the calvarium is very rare. Presentation of tuberculosis as a soft tissue swelling on the scalp poses a diagnostic problem. These two cases are being reported here to convey the utility of fine-needle aspiration cytology (FNAC) in providing the confirmatory diagnosis obviating the need for invasive surgical procedure.

Tuberculosis post-liver transplantation: a rare but complicated disease.

PubMed

Lu, W; Wai, C T; Da Costa, M; Tambyah, P A; Prabhakaran, K; Lee, K H

2005-03-01

Tuberculosis is a rare but serious complication after transplantation. We report a case and discuss its presentation and management. A 60-year-old Indonesian male presented initially with fever, acute confusion and rapidly progressive right upper lobe pneumonia 3.5 months post-liver transplant, and was diagnosed with pulmonary tuberculosis by positive sputum smear for acid-fast bacilli and tuberculosis culture. Standard anti-tuberculosis therapy was administered but was complicated by interaction with cyclosporine and drug-induced cholestasis. A high level of suspicion, prompt antituberculosis treatment and close follow-up are essential in management of post-transplant tuberculosis.

The Social Determinants of Tuberculosis: From Evidence to Action

PubMed Central

Boccia, Delia; Evans, Carlton A.; Adato, Michelle; Petticrew, Mark; Porter, John D. H.

2011-01-01

Growing consensus indicates that progress in tuberculosis control in the low- and middle-income world will require not only investment in strengthening tuberculosis control programs, diagnostics, and treatment but also action on the social determinants of tuberculosis. However, practical ideas for action are scarcer than is notional support for this idea. We developed a framework based on the recent World Health Organization Commission on Social Determinants of Health and on current understanding of the social determinants of tuberculosis. Interventions from outside the health sector—specifically, in social protection and urban planning—have the potential to strengthen tuberculosis control. PMID:21330583

Evaluation of Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case Definitions for Classification of Intrathoracic Tuberculosis Disease. Consensus From an Expert Panel

PubMed Central

Graham, Stephen M.; Ahmed, Tahmeed; Amanullah, Farhana; Browning, Renee; Cardenas, Vicky; Casenghi, Martina; Cuevas, Luis E.; Gale, Marianne; Gie, Robert P.; Grzemska, Malgosia; Handelsman, Ed; Hatherill, Mark; Hesseling, Anneke C.; Jean-Philippe, Patrick; Kampmann, Beate; Kabra, Sushil Kumar; Lienhardt, Christian; Lighter-Fisher, Jennifer; Madhi, Shabir; Makhene, Mamodikoe; Marais, Ben J.; McNeeley, David F.; Menzies, Heather; Mitchell, Charles; Modi, Surbhi; Mofenson, Lynne; Musoke, Philippa; Nachman, Sharon; Powell, Clydette; Rigaud, Mona; Rouzier, Vanessa; Starke, Jeffrey R.; Swaminathan, Soumya; Wingfield, Claire

2012-01-01

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis. PMID:22448023

Multifocal systemic tuberculosis: the many faces of an old nemesis.

PubMed

Al-Tawfiq, Jaffar A

2007-04-01

Tuberculosis continues to be a major health problem, where an estimated 7-8 million new cases are diagnosed each year. Multifocal tuberculosis is characterized by the presence of large multifocal tuberculous areas in the same or different organs. Difficulty in diagnosis of multifocal tuberculosis and consideration of other diseases may lead to a delay in diagnosing this entity. Here the clinical features and characteristics of three patients with multifocal systemic tuberculosis are described. During the period of 1999-2005, a total of 128 confirmed cases of tuberculosis were identified. Three (2.3%) patients had multifocal systemic tuberculosis. The first case had involvement of the lung, psoas muscle, and the vertebral bodies. The second patient had multiple brain lesions with mediastinal and retroperitoneal lymphadenopathy. The third patient had multiple brain lesions, lymphadenopathy, and colonic lesions initially mimicking a metastatic disease. Mycobacterium tuberculosis was grown from pleural fluid in one patient and from lymph node biopsies in another patient. The third patient had histopathologic evidence of tuberculosis. All patients received standard anti-tuberculous treatment, resulting in a full recovery in two patients, while the third patient had residual weakness. Multifocal systemic tuberculosis may pose a diagnostic challenge and may occur in immunocompetent hosts, in whom this entity generally has a good outcome.

The outcome of tuberculosis treatment in subjects with chronic kidney disease in Brazil: a multinomial analysis*

PubMed Central

Reis-Santos, Barbara; Gomes, Teresa; Horta, Bernardo Lessa; Maciel, Ethel Leonor Noia

2013-01-01

OBJECTIVE: To analyze the association between clinical/epidemiological characteristics and outcomes of tuberculosis treatment in patients with concomitant tuberculosis and chronic kidney disease (CKD) in Brazil. METHODS: We used the Brazilian Ministry of Health National Case Registry Database to identify patients with tuberculosis and CKD, treated between 2007 and 2011. The tuberculosis treatment outcomes were compared with epidemiological and clinical characteristics of the subjects using a hierarchical multinomial logistic regression model, in which cure was the reference outcome. RESULTS: The prevalence of CKD among patients with tuberculosis was 0.4% (95% CI: 0.37-0.42%). The sample comprised 1,077 subjects. The outcomes were cure, in 58%; treatment abandonment, in 7%; death from tuberculosis, in 13%; and death from other causes, in 22%. The characteristics that differentiated the ORs for treatment abandonment or death were age; alcoholism; AIDS; previous noncompliance with treatment; transfer to another facility; suspected tuberculosis on chest X-ray; positive results in the first smear microscopy; and indications for/use of directly observed treatment, short-course strategy. CONCLUSIONS: Our data indicate the importance of sociodemographic characteristics for the diagnosis of tuberculosis in patients with CKD and underscore the need for tuberculosis control strategies targeting patients with chronic noncommunicable diseases, such as CKD. PMID:24310632

Assessment of the probability of introduction of bovine tuberculosis to Danish cattle farms via imports of live cattle from abroad and immigrant workers.

PubMed

Foddai, Alessandro; Nielsen, Liza Rosenbaum; Krogh, Kaspar; Alban, Lis

2015-12-01

Denmark has been recognized as officially free (OTF) from bovine tuberculosis (bTB) since 1980. In this study, we estimated the annual probability (PIntro) of introducing Mycobacterium bovis into the Danish cattle population, through (a) imports of cattle and (b) foreign personnel working in Danish cattle herds. Data from 2000 to 2013 with date, number and origin of imported live cattle were obtained from the Danish Cattle Federation. Information on immigrants working in Danish cattle herds was obtained through a questionnaire sent by email to a sample of Danish cattle farmers (N=460). Inputs obtained from data analysis, expert opinion, the questionnaire and literature were fed into three stochastic scenario tree models used to simulate the effect of import trade patterns, and contact between immigrant workers and cattle. We also investigated the opportunity of testing animals imported from OTF countries by tuberculin skin test and animals from non-OTF countries by interferon-γ test (IFN-γ), exemplified by using year 2009 where the number of imported animals was higher than usual. Results showed that PIntro is driven mainly by importation of live cattle. The combined median annual probability of introducing M. bovis into the Danish cattle population by either imported live cattle or infectious immigrant workers, ranged from 0.3% (90% prediction interval (P.I.): 0.04%:1.4%) in 2001 to 4.9% (90% P.I.: 0.6%; 19.2%) in 2009. The median of the median PIntro estimates from the 14 years was 0.7% (median of 90% P.I.: 0.08%; 3.5%). Hence, on average, at least one introduction each 143 years could be expected, if the annual number of imported animals does not change remarkably in the future. If the number of imported animals increases, compared to the years we analyzed, additional testing of imported cattle might be considered. For example, in 2009, PIntro would have been reduced from 4.9% to 0.8% (90% P.I.: 0.1%; 4.7%) if animals from OTF countries had been tested with the tuberculin skin test and animals from non-OTF countries had been tested with the IFN-γ test. The presented model could be used easily in other countries with similar bTB status to Denmark, where wildlife represents a negligible probability of infection for domestic cattle and where the imported live cattle represent the main pathway of bTB introduction into the local cattle population. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of output-based approaches used to substantiate bovine tuberculosis free status in Danish cattle herds.

PubMed

Foddai, Alessandro; Nielsen, Liza Rosenbaum; Willeberg, Preben; Alban, Lis

2015-09-01

We compared two published studies based on different output-based surveillance models, which were used for evaluating the performance of two meat inspection systems in cattle and to substantiate freedom from bovine tuberculosis (bTB) in Denmark. The systems were the current meat inspection methods (CMI) vs. the visual-only inspection (VOI). In one study, the surveillance system sensitivity (SSe) was estimated to substantiate the bTB free status. The other study used SSe in the estimation of the probability of freedom (PFree), based on the epidemiological concept of negative predictive value to substantiate the bTB free status. Both studies found that changing from CMI to VOI would markedly decrease the SSe. However, the two studies reported diverging conclusions regarding the effect on the substantiation of Denmark as a bTB free country, if VOI were to be introduced. The objectives of this work were: (a) to investigate the reasons why conclusions based on the two models differed, and (b) to create a hybrid model based on elements from both studies to evaluate the impact of a change from CMI to VOI. The hybrid model was based on the PFree approach to substantiate freedom from bTB and was parametrized with inputs according to the newest available information. The PFree was updated on an annual basis for each of 42 years of test-negative surveillance data (1995-2037), while assuming a low (<1%) annual probability of introduction of bTB into Danish cattle herds. The most important reasons for the difference between the study conclusions were: the approach chosen to substantiate the bTB free status (SSe vs. PFree) and the number of years of surveillance data considered. With the hybrid model, the PFree reached a level >95% after the first year of surveillance and remained ≥96% with both the CMI and VOI systems until the end of the analyzed period. It is appropriate to use the PFree of the surveillance system to substantiate confidence in bTB free status, when test-negative surveillance results can be documented over an extended period of time, while maintaining a low probability of introduction of bTB into the cattle population. For Denmark, the probability of introduction of bTB should be kept <1% on an annual basis to sustain the high confidence in freedom over time. The results could be considered when deciding if the CMI can be replaced by VOI in cattle abattoirs of countries for which bTB freedom can be demonstrated. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

Bovine tuberculosis: a retrospective study at Jos abattoir, Plateau State, Nigeria.

PubMed

Okeke, Lilian Akudo; Fawole, Olufunmilayo; Muhammad, Maryam; Okeke, Ikenna Osemeka; Nguku, Patrick; Wasswa, Peter; Dairo, David; Cadmus, Simeon

2016-01-01

Nigeria has the thirteenth highest burden of human tuberculosis. The current increasing incidence of tuberculosis in humans, particularly in immune-compromised persons, has given interest in the zoonotic importance of Mycobacterium bovis in developing countries like Nigeria. This study determined the prevalence of bovine tuberculosis as a background information for effective control measures in Plateau State in cattle population. We reviewed surveillance records on cattle slaughtered and suggestive tuberculosis lesions from cattle slaughtered annually from 2007-2012 in Jos abattoir, Plateau State. Bovine tuberculosis cases at post mortem were based on examination of characteristics TB lesion on organs by Veterinary officers. We performed descriptive analysis using Epi info version 3.5.3 and Microsoft Excel 2007. A total of 52, 262 cattle were slaughtered from 2007-2012, out of which 4, 658 (11.2%) had evidence of tuberculosis lesion at post mortem. The average yearly prevalence was 9.1% but varied from a high of 16.3% in 2007 to a low of 3.1% in 2012. Trend analysis showed that bovine tuberculosis had a seasonal variation and peaked mostly in July and August. The number of suggestive Tb lesion cases was highest in the month of August and lowest in the month of January, 2007-2012. This study shows that bovine tuberculosis is endemic in Plateau State. Trend analysis showed that bovine tuberculosis is seasonal and peaked mostly in July and August. Continuous surveillance through meat inspection is required to prevent zoonotic transmission of bovine tuberculosis.

[Ivory Coast physician's knowledge and attitudes about smoking in patients with tuberculosis].

PubMed

Daix, A T J; Bakayoko-Yéo, A S; Koné, Z; Samaké, K; Coulibaly, G; Touhon, O A; Domoua, K M S

2015-05-01

Smoking promotes, among other health problems, the development of tuberculosis and the discovery of a case of tuberculosis can therefore be an opportunity for tobacco control interventions. We conducted a prospective study evaluating the knowledge of 37 Ivorian physicians (32 men and 5 women with 5 active smokers) on the relationship between smoking and tuberculosis and their attitudes to smoking tuberculous patients between February and August 2012 using an anonymous self-administered questionnaire. The response rate to the questionnaire was 88.1%. Among them, 70.3% of Ivorian physicians knew that smoking increased the incidence of tuberculosis, 75.7% said that forms of tuberculosis were more severe in smokers and about 27% thought that the cure rate of tuberculosis was lower in smokers. No significant difference was observed according to respondents' smoking status, or gender. Patients' smoking status was always assessed by 64.9% of physicians and by 78.4% in patients with tuberculosis, again not differing by physicians' smoking status or gender. The risks of smoking were always explained to patients with active pulmonary tuberculosis by 43.2% and benefits of stopping smoking ware always described in 35.1%. An intervention for smoking cessation was systematically offered to smokers having tuberculosis by 59.4% of physicians and 8.1% offered medication for smoking cessation. These results strongly support the need to reinforce physician behaviors to address smoking in patients with tuberculosis in Ivory Coast. Copyright © 2014 SPLF. Published by Elsevier Masson SAS. All rights reserved.

A Review of Moxifloxacin for the Treatment of Drug-Susceptible Tuberculosis.

PubMed

Naidoo, Anushka; Naidoo, Kogieleum; McIlleron, Helen; Essack, Sabiha; Padayatchi, Nesri

2017-11-01

Moxifloxacin, an 8-methoxy quinolone, is an important drug in the treatment of multidrug-resistant tuberculosis and is being investigated in novel drug regimens with pretomanid, bedaquiline, and pyrazinamide, or rifapentine, for the treatment of drug-susceptible tuberculosis. Early results of these studies are promising. Although current evidence does not support the use of moxifloxacin in treatment-shortening regimens for drug-susceptible tuberculosis, it may be recommended in patients unable to tolerate standard first-line drug regimens or for isoniazid monoresistance. Evidence suggests that the standard 400-mg dose of moxifloxacin used in the treatment of tuberculosis may be suboptimal in some patients, leading to worse tuberculosis treatment outcomes and emergence of drug resistance. Furthermore, a drug interaction with the rifamycins results in up to 31% reduced plasma concentrations of moxifloxacin when these are combined for treatment of drug-susceptible tuberculosis, although the clinical relevance of this interaction is unclear. Moxifloxacin exhibits extensive interindividual pharmacokinetic variability. Higher doses of moxifloxacin may be needed to achieve drug exposures required for improved clinical outcomes. Further study is, however, needed to determine the safety of proposed higher doses and clinically validated targets for drug exposure to moxifloxacin associated with improved tuberculosis treatment outcomes. We discuss in this review the evidence for the use of moxifloxacin in drug-susceptible tuberculosis and explore the role of moxifloxacin pharmacokinetics, pharmacodynamics, and drug interactions with rifamycins, on tuberculosis treatment outcomes when used in first-line tuberculosis drug regimens. © 2017, The American College of Clinical Pharmacology.

Forecast Model Analysis for the Morbidity of Tuberculosis in Xinjiang, China

PubMed Central

Zheng, Yan-Ling; Zhang, Li-Ping; Zhang, Xue-Liang; Wang, Kai; Zheng, Yu-Jian

2015-01-01

Tuberculosis is a major global public health problem, which also affects economic and social development. China has the second largest burden of tuberculosis in the world. The tuberculosis morbidity in Xinjiang is much higher than the national situation; therefore, there is an urgent need for monitoring and predicting tuberculosis morbidity so as to make the control of tuberculosis more effective. Recently, the Box-Jenkins approach, specifically the autoregressive integrated moving average (ARIMA) model, is typically applied to predict the morbidity of infectious diseases; it can take into account changing trends, periodic changes, and random disturbances in time series. Autoregressive conditional heteroscedasticity (ARCH) models are the prevalent tools used to deal with time series heteroscedasticity. In this study, based on the data of the tuberculosis morbidity from January 2004 to June 2014 in Xinjiang, we establish the single ARIMA (1, 1, 2) (1, 1, 1)12 model and the combined ARIMA (1, 1, 2) (1, 1, 1)12-ARCH (1) model, which can be used to predict the tuberculosis morbidity successfully in Xinjiang. Comparative analyses show that the combined model is more effective. To the best of our knowledge, this is the first study to establish the ARIMA model and ARIMA-ARCH model for prediction and monitoring the monthly morbidity of tuberculosis in Xinjiang. Based on the results of this study, the ARIMA (1, 1, 2) (1, 1, 1)12-ARCH (1) model is suggested to give tuberculosis surveillance by providing estimates on tuberculosis morbidity trends in Xinjiang, China. PMID:25760345

A 10-year experience of tuberculosis in solid-organ transplant recipients.

PubMed

Ulubay, Gaye; Kupeli, Elif; Duvenci Birben, Ozlem; Seyfettin, Emine Pinar; Dogrul, Mustafa Ilgaz; Ozsancak Ugurlu, Aylin; Oner Eyuboglu, Fusun; Haberal, Mehmet

2015-04-01

Tuberculosis remains an important problem in solid-organ transplant patients due to their immunocompromised state. The objective of the present study was to report the incidence, demographic characteristics, and various presentations of tuberculosis in solid-organ transplant recipients. We evaluated a total of 999 patients (male/female = 665/334, 661 renal and 338 liver transplants) who underwent solid-organ transplant between 2003 and 2013. The medical records of all patients were retrospectively reviewed. Patients' demographics, transplant type, primary site of tuberculosis specimen culture and pathology results, chest radiograph, and thoracic computed tomography findings, total blood count and chemistry were all recorded. Among the 999 subjects, 19 patients (1.9%) (male/female: 15/4, mean ± SD age, 42 ± 18.5 y) were diagnosed with tuberculosis. The majority of patients (85%) were diagnosed with tuberculosis within 6 months after transplant, and 15% were diagnosed within 3 months. Most diagnoses of tuberculosis were based on histopathologic examination of biopsy material. Of these patients, 9 were diagnosed with pulmonary tuberculosis, 8 had extrapulmonary tuberculosis, and 2 had both. Nontuberculosis mycobacteria infections were detected in 3 patients. Even with a negative exposure history, tuberculosis can manifest as different clinic presentations in solid-organ transplant patients on immunosuppressive drugs, particularly in the first 6 months after transplant. Therefore, clinicians should always consider tuberculosis as the potential cause of an infectious disease with unknown cause to successfully diagnose and manage solid-organ transplant recipients.

Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis Infectiousness.

PubMed

Datta, Sumona; Sherman, Jonathan M; Tovar, Marco A; Bravard, Marjory A; Valencia, Teresa; Montoya, Rosario; Quino, Willi; D'Arcy, Nikki; Ramos, Eric S; Gilman, Robert H; Evans, Carlton A

2017-09-01

Sputum from patients with tuberculosis contains subpopulations of metabolically active and inactive Mycobacterium tuberculosis with unknown implications for infectiousness. We assessed sputum microscopy with fluorescein diacetate (FDA, evaluating M. tuberculosis metabolic activity) for predicting infectiousness. Mycobacterium tuberculosis was quantified in pretreatment sputum of patients with pulmonary tuberculosis using FDA microscopy, culture, and acid-fast microscopy. These 35 patients' 209 household contacts were followed with prevalence surveys for tuberculosis disease for 6 years. FDA microscopy was positive for a median of 119 (interquartile range [IQR], 47-386) bacteria/µL sputum, which was 5.1% (IQR, 2.4%-11%) the concentration of acid-fast microscopy-positive bacteria (2069 [IQR, 1358-3734] bacteria/μL). Tuberculosis was diagnosed during follow-up in 6.4% (13/209) of contacts. For patients with lower than median concentration of FDA microscopy-positive M. tuberculosis, 10% of their contacts developed tuberculosis. This was significantly more than 2.7% of the contacts of patients with higher than median FDA microscopy results (crude hazard ratio [HR], 3.8; P = .03). This association maintained statistical significance after adjusting for disease severity, chemoprophylaxis, drug resistance, and social determinants (adjusted HR, 3.9; P = .02). Mycobacterium tuberculosis that was FDA microscopy negative was paradoxically associated with greater infectiousness. FDA microscopy-negative bacteria in these pretreatment samples may be a nonstaining, slowly metabolizing phenotype better adapted to airborne transmission. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Tuberculosis Facts - TB Can Be Treated

MedlinePlus

Tuberculosis (TB) Facts TB Can Be Treated What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination Page 1 of 2 TB Facts: TB ...

75 FR 60586 - Tuberculosis in Cattle and Bison; State and Zone Designations; Minnesota

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

.... APHIS-2010-0097] Tuberculosis in Cattle and Bison; State and Zone Designations; Minnesota AGENCY: Animal... are amending the bovine tuberculosis regulations regarding State and zone classifications by... . FOR FURTHER INFORMATION CONTACT: Dr. Alecia Naugle, Coordinator, National Tuberculosis Eradication...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

Tuberculosis Facts - You Can Prevent TB

MedlinePlus

Tuberculosis (TB) Facts You Can Prevent TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination TB Facts: You Can Prevent TB What ...

Tuberculosis: A Problem for Lifeguards?

ERIC Educational Resources Information Center

Skaros, Susan

1996-01-01

Lifeguards run the risk of workplace infection by tuberculosis-carrying swimmers. Even if they work in ventilated, sunlit areas (which reduces risk), they can contract tuberculosis when performing respiratory resuscitation. Without appropriate precautions, lifeguards may be unnecessarily exposed. A tuberculosis infection control plan is needed in…

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

Tuberculosis-resistant transgenic cattle

USDA-ARS?s Scientific Manuscript database

Tuberculosis is a devastating disease that affects humans and many animal species. In humans, tuberculosis (TB) is mainly caused by Mycobacterium tuberculosis, while most cases in cattle are caused by Mycobacterium bovis. However, Mb can also cause, albeit rarely, human TB. In this issue, Wu et al. ...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

9 CFR 381.81 - Tuberculosis.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned. ...

New antituberculous drugs derived from natural products: current perspectives and issues in antituberculous drug development.

PubMed

Igarashi, Masayuki; Ishizaki, Yoshimasa; Takahashi, Yoshiaki

2017-11-01

Tuberculosis is one of the most common and challenging infectious diseases worldwide. Especially, the lack of effective chemotherapeutic drugs for tuberculosis/human immunodeficiency virus co-infection and prevalence of multidrug-resistant and extensively drug-resistant tuberculosis remain to be serious clinical problems. Development of new drugs is a potential solution to fight tuberculosis. In this decade, the development status of new antituberculous drugs has been greatly advanced by the leading role of international organizations such as the Global Alliance for Tuberculosis Drug Development, Stop Tuberculosis Partnership and Global Health Innovative Technology Fund. In this review, we introduce the development status of new drugs for tuberculosis, focusing on those derived from natural products.The Journal of Antibiotics advance online publication, 1 November 2017; doi:10.1038/ja.2017.126.

[Advances in the research of an animal model of wound due to Mycobacterium tuberculosis infection].

PubMed

Chen, Ling; Jia, Chiyu

2015-12-01

Tuberculosis ranks as the second deadly infectious disease worldwide. The incidence of tuberculosis is high in China. Refractory wound caused by Mycobacterium tuberculosis infection ranks high in misdiagnosis, and it is accompanied by a protracted course, and its pathogenic mechanism is still not so clear. In order to study its pathogenic mechanism, it is necessary to reproduce an appropriate animal model. Up to now the study of the refractory wound caused by Mycobacterium tuberculosis infection is just beginning, and there is still no unimpeachable model for study. This review describes two models which may reproduce a wound similar to the wound caused by Mycobacterium tuberculosis infection, so that they could be used to study the pathogenesis and characteristics of a tuberculosis wound in an animal.

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study.

PubMed

Saunders, Matthew J; Wingfield, Tom; Tovar, Marco A; Baldwin, Matthew R; Datta, Sumona; Zevallos, Karine; Montoya, Rosario; Valencia, Teresa R; Friedland, Jon S; Moulton, Larry H; Gilman, Robert H; Evans, Carlton A

2017-11-01

Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Molecular Epidemiology of Tuberculosis in Foreign-Born Persons Living in San Francisco

PubMed Central

Suwanpimolkul, Gompol; Jarlsberg, Leah G.; Grinsdale, Jennifer A.; Osmond, Dennis; Kawamura, L. Masae; Hopewell, Philip C.

2013-01-01

Rationale: In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations. Objectives: To determine the clinical, epidemiological and microbiological characteristics of tuberculosis caused by recent infection and rapid evolution in the major groups of foreign-born and the U.S.-born populations. Methods: We analyzed data from a 20-year prospective community-based study of the molecular epidemiology of tuberculosis in San Francisco. We included all culture-positive tuberculosis cases in the City during the study period. Measurements and Main Results: We calculated and compared incidence rates, clinical and microbiological characteristics, and risk factors for being a secondary case between the various foreign-born and U.S.-born tuberculosis populations. Between 1991 and 2010, there were 4,058 new cases of tuberculosis, of which 1,226 (30%) were U.S.-born and 2,832 (70%) were foreign-born. A total of 3,278 (81%) were culture positive, of which 2,419 (74%) had complete data for analysis. The incidence rate, including the incidence rate of tuberculosis due to recent infection and rapid evolution, decreased significantly in the U.S.-born and the major foreign-born populations. The clinical and microbiological characteristics and the risk factors for tuberculosis due to recent infection differed among the groups. Conclusions: There are differences in the characteristics and the risk factors for tuberculosis due to recent transmission among the major foreign-born and U.S.-born populations in San Francisco. These differences should be considered for the design of targeted tuberculosis control interventions. PMID:23471470

National policies on the management of latent tuberculosis infection: review of 98 countries

PubMed Central

Jagger, Ann; Reiter-karam, Silke; Getahun, Haileyesus

2018-01-01

Abstract Objective To review policies on management of latent tuberculosis infection in countries with low and high burdens of tuberculosis. Methods We divided countries reporting data to the World Health Organization (WHO) Global Tuberculosis Programme into low and high tuberculosis burden, based on WHO criteria. We identified national policy documents on management of latent tuberculosis through online searches, government websites, WHO country offices and personal communication with programme managers. We made a descriptive analysis with a focus on policy gaps and deviations from WHO policy recommendations. Findings We obtained documents from 68 of 113 low-burden countries and 30 of 35 countries with the highest burdens of tuberculosis or human immunodeficiency virus (HIV)-associated tuberculosis. Screening and treatment of latent tuberculosis infection in people living with HIV was recommended in guidelines of 29 (96.7%) high-burden and 54 (79.7%) low-burden countries. Screening for children aged < 5 years with household tuberculosis contact was the policy of 25 (83.3%) high- and 28 (41.2%) low-burden countries. In most high-burden countries the recommendation was symptom screening alone before treatment, whereas in all low-burden countries it was testing before treatment. Some low-burden countries’ policies did not comply with WHO recommendations: nine (13.2%) recommended tuberculosis preventive treatment for travellers to high-burden countries and 10 (14.7%) for patients undergoing abdominal surgery. Conclusion Lack of solid evidence on certain aspects of management of latent tuberculosis infection results in national policies which vary considerably. This highlights a need to advance research and develop clear, implementable and evidence-based WHO policies. PMID:29531416

High prevalence and low cure rate of tuberculosis among patients with HIV in Xinjiang, China.

PubMed

Maimaiti, Rena; Zhang, Yuexin; Pan, Kejun; Mijiti, Peierdun; Wubili, Maimaitiali; Musa, Maimaitijiang; Andersson, Rune

2017-01-05

Tuberculosis and HIV co-epidemics are problems in many parts of the world. Xinjiang is a high tuberculosis and HIV prevalence area in China. We aimed to investigate the prevalence and cure rate of tuberculosis among HIV positive patients in Xinjiang. In a retrospective study between 2006 and 2011, clinical and laboratory data on 333 patients with HIV and tuberculosis were compared to 2668 patients with HIV only. There were 31 HIV positive patients with no data on tuberculosis. The prevalence of tuberculosis co-infection among the HIV positive patients was 11% (95% CI 10-12%), significantly higher than the national figure in China of 2%. In most cases HIV was diagnosed late, with advanced immunodeficiency. The use of isoniazid preventive therapy was only 57.9% in patients without tuberculosis who fulfilled the criteria for receiving this prevention. The cure rate one year after diagnosis was 69.2%, which was lower than the officially reported 91.4% in all tuberculosis cases in Xinjiang in 2011. The hazard of not surviving over the five years was significantly higher in patients with HIV + tuberculosis compared to HIV only after adjusting for sex and Intravenous drug use with HR = 1.84 (95% CI 1.43-2.35; p < 0.0001). The prevalence of tuberculosis among HIV positive patients in Xinjiang was higher than in China taken as a whole, and HIV was diagnosed late, with underuse of isoniazid preventive therapy. The low cure rate and reduced survival can be due to late diagnosis of HIV and no testing for antibiotic resistance, together with insufficient control of adherence to the treatment regimens for tuberculosis and HIV.

Multiscale Model of Mycobacterium tuberculosis Infection Maps Metabolite and Gene Perturbations to Granuloma Sterilization Predictions

PubMed Central

Pienaar, Elsje; Matern, William M.; Linderman, Jennifer J.

2016-01-01

Granulomas are a hallmark of tuberculosis. Inside granulomas, the pathogen Mycobacterium tuberculosis may enter a metabolically inactive state that is less susceptible to antibiotics. Understanding M. tuberculosis metabolism within granulomas could contribute to reducing the lengthy treatment required for tuberculosis and provide additional targets for new drugs. Two key adaptations of M. tuberculosis are a nonreplicating phenotype and accumulation of lipid inclusions in response to hypoxic conditions. To explore how these adaptations influence granuloma-scale outcomes in vivo, we present a multiscale in silico model of granuloma formation in tuberculosis. The model comprises host immunity, M. tuberculosis metabolism, M. tuberculosis growth adaptation to hypoxia, and nutrient diffusion. We calibrated our model to in vivo data from nonhuman primates and rabbits and apply the model to predict M. tuberculosis population dynamics and heterogeneity within granulomas. We found that bacterial populations are highly dynamic throughout infection in response to changing oxygen levels and host immunity pressures. Our results indicate that a nonreplicating phenotype, but not lipid inclusion formation, is important for long-term M. tuberculosis survival in granulomas. We used virtual M. tuberculosis knockouts to predict the impact of both metabolic enzyme inhibitors and metabolic pathways exploited to overcome inhibition. Results indicate that knockouts whose growth rates are below ∼66% of the wild-type growth rate in a culture medium featuring lipid as the only carbon source are unable to sustain infections in granulomas. By mapping metabolite- and gene-scale perturbations to granuloma-scale outcomes and predicting mechanisms of sterilization, our method provides a powerful tool for hypothesis testing and guiding experimental searches for novel antituberculosis interventions. PMID:26975995

Infection Control for Drug-Resistant Tuberculosis: Early Diagnosis and Treatment Is the Key

PubMed Central

van Cutsem, Gilles; Isaakidis, Petros; Farley, Jason; Nardell, Ed; Volchenkov, Grigory; Cox, Helen

2016-01-01

Multidrug-resistant (MDR) tuberculosis, “Ebola with wings,” is a significant threat to tuberculosis control efforts. Previous prevailing views that resistance was mainly acquired through poor treatment led to decades of focus on drug-sensitive rather than drug-resistant (DR) tuberculosis, driven by the World Health Organization's directly observed therapy, short course strategy. The paradigm has shifted toward recognition that most DR tuberculosis is transmitted and that there is a need for increased efforts to control DR tuberculosis. Yet most people with DR tuberculosis are untested and untreated, driving transmission in the community and in health systems in high-burden settings. The risk of nosocomial transmission is high for patients and staff alike. Lowering transmission risk for MDR tuberculosis requires a combination approach centered on rapid identification of active tuberculosis disease and tuberculosis drug resistance, followed by rapid initiation of appropriate treatment and adherence support, complemented by universal tuberculosis infection control measures in healthcare facilities. It also requires a second paradigm shift, from the classic infection control hierarchy to a novel, decentralized approach across the continuum from early diagnosis and treatment to community awareness and support. A massive scale-up of rapid diagnosis and treatment is necessary to control the MDR tuberculosis epidemic. This will not be possible without intense efforts toward the implementation of decentralized, ambulatory models of care. Increasing political will and resources need to be accompanied by a paradigm shift. Instead of focusing on diagnosed cases, recognition that transmission is driven largely by undiagnosed, untreated cases, both in the community and in healthcare settings, is necessary. This article discusses this comprehensive approach, strategies available, and associated challenges. PMID:27118853

Critical role of toll-like receptor 9 in morphine and Mycobacterium tuberculosis-Induced apoptosis in mice.

PubMed

Chen, Lin; Shi, Wanliang; Li, Hui; Sun, Xiuli; Fan, Xionglin; Lesage, Gene; Li, Hui; Li, Yi; Zhang, Yi; Zhang, Xiumei; Zhang, Ying; Yin, Deling

2010-02-19

Although it is established that opioid and Mycobacterium tuberculosis are both public health problems, the mechanisms by which they affect lung functions remain elusive. We report here that mice subjected to chronic morphine administration and M. tuberculosis infection exhibited significant apoptosis in the lung in wild type mice as demonstrated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. Morphine and M. tuberculosis significantly induced the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, deficiency in TLR9 significantly inhibited the morphine and M. tuberculosis induced apoptosis in the lung. In addition, chronic morphine treatment and M. tuberculosis infection enhanced the levels of cytokines (TNF-alpha, IL-1beta, and IL-6) in wild type mice, but not in TLR9 knockout (KO) mice. The bacterial load was much lower in TLR9 KO mice compared with that in wild type mice following morphine and M. tuberculosis treatment. Morphine alone did not alter the bacterial load in either wild type or TLR9 KO mice. Moreover, administration of morphine and M. tuberculosis decreased the levels of phosphorylation of Akt and GSK3beta in the wild type mice, but not in TLR9 KO mice, suggesting an involvement of Akt/GSK3beta in morphine and M. tuberculosis-mediated TLR9 signaling. Furthermore, administration of morphine and M. tuberculosis caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type mice, but not in TLR9 KO mice, indicating a role of Bcl-2 family in TLR9-mediated apoptosis in the lung following morphine and M. tuberculosis administration. These data reveal a role for TLR9 in the immune response to opioids during M. tuberculosis infection.

High prevalence of Mycobacterium tuberculosis DNA in biopsies from sarcoidosis patients from Catalonia, Spain.

PubMed

Fité, E; Fernández-Figueras, M T; Prats, R; Vaquero, M; Morera, J

2006-01-01

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The presence of mycobacterial nucleic acid components in patients with sarcoidosis has been demonstrated with varying degrees of success. The aim of this study was to estimate the presence of Mycobacterium tuberculosis DNA in tissues from sarcoidosis patients, in Catalonia, Spain, as well as to assess the long-term clinical course in these patients. Fifty-eight paraffin-embedded tissue biopsies corresponding to cases of sarcoidosis (n = 23), lung neoplasm (n = 23), and lung tuberculosis (n = 12) available in 1996 were analyzed in a retrospective study by means of a nested polymerase chain reaction using primers corresponding to the insertion element IS6110 of M. tuberculosis complex. For greater sensitivity, Southern blot hybridization was performed. Clinical data were recorded prior to and after PCR analysis (follow-up reported until 2002). M. tuberculosis DNA was present in 9 out of 23 sarcoidosis biopsies (39%), in 1 out of 23 control patients (4%) (p < 0.01), and in all tissue samples from the 12 control patients with tuberculosis. To date, none of these sarcoidosis patients has developed tuberculosis over a mean (+/-SD) follow-up period of 11 (+/-3.4) years. In our setting, M. tuberculosis DNA is present in tissue biopsies of significantly more sarcoidosis patients than controls. However, these results do not demonstrate causality, although they may suggest a link between M. tuberculosis infection and sarcoidosis in some cases. Follow-up of these patients suggests that M. tuberculosis-DNA-positive sarcoidosis patients are not at greater risk of developing tuberculosis than M. tuberculosis-DNA-negative patients. Copyright 2006 S. Karger AG, Basel.

Occupational Risk Factors for Tuberculosis Among Healthcare Workers in KwaZulu-Natal, South Africa

PubMed Central

Tudor, Carrie; Van der Walt, Martie L.; Margot, Bruce; Dorman, Susan E.; Pan, William K.; Yenokyan, Gayane; Farley, Jason E.

2016-01-01

Background. Tuberculosis is a known occupational hazard for healthcare workers (HCWs), especially in countries with a high burden of tuberculosis. It is estimated that HCWs have a 2- to 3-fold increased risk of developing tuberculosis compared with the general population. The objective of this study was to identify occupational risk factors for tuberculosis among HCWs in 3 district hospitals with specialized multidrug-resistant tuberculosis wards in KwaZulu-Natal, South Africa. Methods. We conducted a case-control study of HCWs diagnosed with tuberculosis between January 2006 and December 2010. Cases and controls were asked to complete a self-administered questionnaire regarding potential risk factors for tuberculosis. Results. Of 307 subjects selected, 145 (47%) HCWs responded to the questionnaire; 54 (37%) tuberculosis cases and 91 (63%) controls. Cases occurred more frequently among clinical staff 46% (n = 25) and support staff 35% (n = 19). Thirty-two (26% [32/125]) HCWs were known to be infected with human immunodeficiency virus (HIV), including 45% (21/54) of cases. HCWs living with HIV (odds ratio [OR], 6.35; 95% confidence interval [CI], 3.54–11.37) and those who spent time working in areas with patients (OR, 2.24; 95% CI, 1.40–3.59) had significantly greater odds of developing tuberculosis, controlling for occupation, number of wards worked in, and household crowding. Conclusions. HIV was the major independent risk factor for tuberculosis among HCWs in this sample. These findings support the need for HCWs to know their HIV status, and for HIV-infected HCWs to be offered antiretroviral therapy and isoniazid preventive therapy. Infection prevention and control should also be improved to prevent transmission of tuberculosis in healthcare settings to protect both HCWs and patients. PMID:27118855

Diagnostic Performance of Tuberculosis-Specific IgG Antibody Profiles in Patients with Presumptive Tuberculosis from Two Continents.

PubMed

Broger, Tobias; Basu Roy, Robindra; Filomena, Angela; Greef, Charles H; Rimmele, Stefanie; Havumaki, Joshua; Danks, David; Schneiderhan-Marra, Nicole; Gray, Christen M; Singh, Mahavir; Rosenkrands, Ida; Andersen, Peter; Husar, Gregory M; Joos, Thomas O; Gennaro, Maria L; Lochhead, Michael J; Denkinger, Claudia M; Perkins, Mark D

2017-04-01

Development of rapid diagnostic tests for tuberculosis is a global priority. A whole proteome screen identified Mycobacterium tuberculosis antigens associated with serological responses in tuberculosis patients. We used World Health Organization (WHO) target product profile (TPP) criteria for a detection test and triage test to evaluate these antigens. Consecutive patients presenting to microscopy centers and district hospitals in Peru and to outpatient clinics at a tuberculosis reference center in Vietnam were recruited. We tested blood samples from 755 HIV-uninfected adults with presumptive pulmonary tuberculosis to measure IgG antibody responses to 57 M. tuberculosis antigens using a field-based multiplexed serological assay and a 132-antigen bead-based reference assay. We evaluated single antigen performance and models of all possible 3-antigen combinations and multiantigen combinations. Three-antigen and multiantigen models performed similarly and were superior to single antigens. With specificity set at 90% for a detection test, the best sensitivity of a 3-antigen model was 35% (95% confidence interval [CI], 31-40). With sensitivity set at 85% for a triage test, the specificity of the best 3-antigen model was 34% (95% CI, 29-40). The reference assay also did not meet study targets. Antigen performance differed significantly between the study sites for 7/22 of the best-performing antigens. Although M. tuberculosis antigens were recognized by the IgG response during tuberculosis, no single antigen or multiantigen set performance approached WHO TPP criteria for clinical utility among HIV-uninfected adults with presumed tuberculosis in high-volume, urban settings in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Knowledge about tuberculosis transmission and prevention and perceptions of health service utilization among index cases and contacts in Brazil: Understanding losses in the latent tuberculosis cascade of care.

PubMed

Salame, Flavia Matos; Ferreira, Márcia Danielle; Belo, Marcia Teresa; Teixeira, Eleny Guimarães; Cordeiro-Santos, Marcelo; Ximenes, Ricardo Arraes; de Albuquerque, Maria de Fátima Militão; Hill, Philip C; Menzies, Dick; Trajman, Anete

2017-01-01

Tuberculosis contacts are candidates for active and latent tuberculosis infection screening and eventual treatment. However, many losses occur in the different steps of the contacts' cascade of care. Reasons for this are poorly understood. To describe the different steps where losses in the contact cascade occur and to explore knowledge and attitudes regarding tuberculosis transmission/prevention and perceptions about tuberculosis services in order to understand the reasons for losses from the tuberculosis service users' perspective. We collected routine data from the index case and contact registry books and from patients' records to build the cascade of care of contacts in 12 health facilities in three Brazilian cities with high tuberculosis incidence rates. During a knowledge, attitudes and practices (KAP) survey, trained interviewers administered a semi-structured questionnaire to 138 index cases and 98 contacts. Most of the losses in the cascade occurred in the first two steps (contact identification, 43% and tuberculin skin testing placement, 91% of the identified contacts). Among KAP-interviewed contacts, 67% knew how tuberculosis is transmitted, 87% knew its key symptoms and 81% declared they would take preventive therapy if prescribed. Among KAP-interviewed index cases, 67% knew they could spread tuberculosis, 70% feared for the health of their families and 88% would like their family to be evaluated in the same services. Only a small proportion of contacts are evaluated for active and latent tuberculosis, despite their-and their index cases'-reasonable knowledge, positive attitudes towards prevention and satisfaction with tuberculosis services. In these services, education of service users would not be a sufficient solution. Healthcare workers' and managers' perspective, not explored in this study, may bring more light to this subject.

Mycobacterium tuberculosis Complex and HIV Co-Infection among Extrapulmonary Tuberculosis Suspected Cases at the University of Gondar Hospital, Northwestern Ethiopia.

PubMed

Fanosie, Alemu; Gelaw, Baye; Tessema, Belay; Tesfay, Wogahta; Admasu, Aschalew; Yitayew, Gashaw

2016-01-01

Extrapulmonary Tuberculosis (EPTB) and Human Immunodeficiency Virus (HIV) infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients. An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of < 0.05 was taken as statistically significant. A total of 141 extrapulmonary suspected patients were enrolled in this study. The overall prevalence of culture confirmed extrapulmonary tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37). Tuberculosis lymphadenitis was the predominant (78.4%) type of EPTB infection followed by tuberculosis cold abscess (10.7%). Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013). The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed.

Tuberculosis and HIV at the national level in Kenya: results from the Second Kenya AIDS Indicator Survey.

PubMed

Mbithi, Agneta; Gichangi, Anthony; Kim, Andrea A; Katana, Abraham; Weyenga, Herman; Williamson, John; Robinson, Katherine; Oluoch, Tom; Maina, William K; Kellogg, Timothy A; De Cock, Kevin M

2014-05-01

Co-morbidity with tuberculosis and HIV is a common cause of mortality in sub-Saharan Africa. In the second Kenya AIDS Indicator Survey, we collected data on knowledge and experience of HIV and tuberculosis, as well as on access to and coverage of relevant treatment services and antiretroviral therapy (ART) in Kenya. A national, population-based household survey was conducted from October 2012 to February 2013. Information was collected through household questionnaires, and blood samples were taken for HIV, CD4 cell counts, and HIV viral load testing at a central laboratory. Overall, 13,720 persons aged 15-64 years participated; 96.7% [95% confidence interval (CI): 96.3 to 97.1] had heard of tuberculosis, of whom 2.0% (95% CI: 1.7 to 2.2) reported having prior tuberculosis. Among those with laboratory-confirmed HIV infection, 11.6% (95% CI: 8.9 to 14.3) reported prior tuberculosis. The prevalence of laboratory-confirmed HIV infection in persons reporting prior tuberculosis was 33.2% (95% CI: 26.2 to 40.2) compared to 5.1% (95% CI: 4.5 to 5.8) in persons without prior tuberculosis. Among those in care, coverage of ART for treatment-eligible persons was 100% for those with prior tuberculosis and 88.6% (95% CI: 81.6 to 95.7) for those without. Among all HIV-infected persons, ART coverage among treatment-eligible persons was 86.9% (95% CI: 74.2 to 99.5) for persons with prior tuberculosis and 58.3% (95% CI: 47.6 to 69.0) for those without. Morbidity from tuberculosis and HIV remain major health challenges in Kenya. Tuberculosis is an important entry point for HIV diagnosis and treatment. Lack of knowledge of HIV serostatus is an obstacle to access to HIV services and timely ART for prevention of HIV transmission and HIV-associated disease, including tuberculosis.

Ambient air pollution and risk of tuberculosis: a cohort study.

PubMed

Lai, Ting-Chun; Chiang, Chen-Yuan; Wu, Chang-Fu; Yang, Shiang-Lin; Liu, Ding-Ping; Chan, Chang-Chuan; Lin, Hsien-Ho

2016-01-01

Several respirable hazards, including smoking and indoor air pollution from biomass, were suggested to increase the risk of tuberculosis. Few studies have been conducted on ambient air pollution and tuberculosis. We investigated the association between exposure to ambient air pollution and incidence of active tuberculosis. We conducted a cohort study using 106,678 participants of a community-based screening service in Taiwan, 2005-2012. We estimated individual exposure to air pollution using data from the nearest air quality monitoring station and the road intensity within a 500 m buffer zone. The incidence of tuberculosis was ascertained from the national tuberculosis registry. After a median follow-up of 6.7 years, 418 cases of tuberculosis occurred. Exposure to fine particulate matter (PM2.5) was associated with increased risk of active tuberculosis (adjusted HR: 1.39/10 μg/m3 (95% CI 0.95 to 2.03)). In addition, traffic-related air pollution including nitrogen dioxide (adjusted HR: 1.33/10 ppb; 95% CI 1.04 to 1.70), nitrogen oxides (adjusted HR: 1.21/10 ppb; 95% CI 1.04 to 1.41) and carbon monoxide (adjusted HR: 1.89/ppm; 95% CI 0.78 to 4.58) was associated with tuberculosis risk. There was a non-significant trend between the length of major roads in the neighbourhood and culture-confirmed tuberculosis (adjusted HR: 1.04/km; 95% CI 0.995 to 1.09). Our study revealed a possible link between ambient air pollution and risk of active tuberculosis. Since people from developing countries continue to be exposed to high levels of ambient air pollution and to experience high rates of tuberculosis, the impact of worsening air pollution on global tuberculosis control warrants further investigation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

[Immigrants treated for tuberculosis in Mazovian Center for Treatment of Lung Diseases and Tuberculosis in Otwock].

PubMed

Jagodziński, Jacek; Zielonka, Tadeusz M

2010-01-01

Migration of population contributes to the transmission of tuberculosis (TB), particularly multidrug-resistant tuberculosis. In the countries of Western Europe, the immigrants' inflow contributes to the deterioration of the epidemiological situation. Majority of newly detected TB cases in some countries were affirmed among immigrant and foreign born population. In Poland, this problem has not been investigated up to 2005. The aim of the study was the assessment of the occurrence of tuberculosis in foreigners treated in the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis in Otwock. This work had a retrospective character. The number of cases of tuberculosis in foreigners admitted between 2002 and 2007 was calculated from the data base of the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis; 125 patients, whose basic demographic data, bacteriological status and the radiological changes suggested TB, were included in the study. The foreigners made up to 0.5-1.7% all tuberculosis cases treated in Mazovian Centre for Treatment of Lung Diseases and Tuberculosis. Among confirmed cases, twenty four nationalities were seen. Nationals of the Russian Federation (coming from the Republic of Chechnya) formed the biggest group (24%), followed by the Vietnamese (21%) and the Ukrainians (12%). Most of all cases were young men (77%; average age - 34 years). Children made up to 12% of all cases. Tuberculosis of lungs was predominating, and there were culture confirmed extrapulmonary locations in 13.6% of cases. Bacteriological confirmation was achieved in 53% of cases, but up to 22.7% cases were resistant to one of the antituberculosis medicines and 13.6% was multidrug-resistant. Despite the fact, that foreigners made up a small proportion among all the patient treated for tuberculosis in Mazovia, their number systematically increases. High proportion of multidrug-resistant tuberculosis reported in foreign-born cases is a concern.

Why wait? The social determinants underlying tuberculosis diagnostic delay

PubMed Central

Saunders, Matthew James; Zegarra, Roberto; Evans, Carlton; Alegria-Flores, Kei; Guio, Heinner

2017-01-01

Background Early detection and diagnosis of tuberculosis remain major global priorities for tuberculosis control. Few studies have used a qualitative approach to investigate the social determinants contributing to diagnostic delay and none have compared data collected from individual, community, and health-system levels. We aimed to characterize the social determinants that contribute to diagnostic delay among persons diagnosed with tuberculosis living in resource-constrained settings. Methods/Principle findings Data were collected in public health facilities with high tuberculosis incidence in 19 districts of Lima, Peru. Semi-structured interviews with persons diagnosed with tuberculosis (n = 105) and their family members (n = 63) explored health-seeking behaviours, community perceptions of tuberculosis and socio-demographic circumstances. Focus groups (n = 6) were conducted with health personnel (n = 35) working in the National Tuberculosis Program. All interview data were transcribed and analysed using a grounded theory approach. The median delay between symptom onset and the public health facility visit that led to the first positive diagnostic sample was 57 days (interquartile range 28–126). The great majority of persons diagnosed with tuberculosis distrusted the public health system and sought care at public health facilities only after exhausting other options. It was universally agreed that persons diagnosed with tuberculosis faced discrimination by public and health personnel. Self-medication with medicines bought at local pharmacies was reported as the most common initial health-seeking behaviour due to the speed and low-cost of treatment in pharmacies. Most persons diagnosed with tuberculosis initially perceived their illness as a simple virus. Conclusions Diagnostic delay was common and prolonged. When individuals reached a threshold of symptom severity, they addressed their health with the least time-consuming, most economically feasible, and well-known healthcare option available to them. In high-burden settings, more human and material resources are required to promote tuberculosis case-finding initiatives, reduce tuberculosis associated stigma and address the social determinants underlying diagnostic delay. PMID:28945782

The rate of sputum smear-positive tuberculosis after treatment default in a high-burden setting: a retrospective cohort study.

PubMed

Marx, Florian M; Dunbar, Rory; Enarson, Donald A; Beyers, Nulda

2012-01-01

High rates of recurrent tuberculosis after successful treatment have been reported from different high burden settings in Sub-Saharan Africa. However, little is known about the rate of smear-positive tuberculosis after treatment default. In particular, it is not known whether or not treatment defaulters continue to be or become again smear-positive and thus pose a potential for transmission of infection to others. To investigate, in a high tuberculosis burden setting, the rate of re-treatment for smear-positive tuberculosis among cases defaulting from standardized treatment compared to successfully treated cases. Retrospective cohort study among smear-positive tuberculosis cases treated between 1996 and 2008 in two urban communities in Cape Town, South Africa. Episodes of re-treatment for smear-positive tuberculosis were ascertained via probabilistic record linkage. Survival analysis and Poisson regression were used to compare the rate of smear-positive tuberculosis after treatment default to that after successful treatment. A total of 2,136 smear-positive tuberculosis cases were included in the study. After treatment default, the rate of re-treatment for smear-positive tuberculosis was 6.86 (95% confidence interval [CI]: 5.59-8.41) per 100 person-years compared to 2.09 (95% CI: 1.81-2.41) after cure (adjusted Hazard Ratio [aHR]: 3.97; 95% CI: 3.00-5.26). Among defaulters, the rate was inversely associated with treatment duration and sputum conversion prior to defaulting. Smear grade at start of the index treatment episode (Smear3+: aHR 1.61; 95%CI 1.11-2.33) was independently associated with smear-positive tuberculosis re-treatment, regardless of treatment outcome. In this high-burden setting, there is a high rate of subsequent smear-positive tuberculosis after treatment default. Treatment defaulters are therefore likely to contribute to the pool of infectious source cases in the community. Our findings underscore the importance of preventing treatment default, as a means of successful tuberculosis control in high-burden settings.

Evaluation of tuberculosis cases occurring in ten outlying cities and reported in the Entorno region of the state of Goiás and reported in the neighboring Federal District: analysis of the incidence of tuberculosis in those cites.

PubMed

Moreira, Maria Auxiliadora Carmo; Bello, Aline Sampaio; Alves, Maristela dos Reis Luz; Silva, Miramar Vieira da; Lorusso, Vincenza

2007-01-01

To evaluate tuberculosis cases occurring in the greater metropolitan area of the Distrito Federal (MADF, encompassing the Federal District, i.e., the national capital of Brasília, located in the state of Goiás) but reported in Brasília itself and to analyze the influence that this has on the effectiveness of the tuberculosis control program, as well as on the collection of socioeconomic and demographic data related to tuberculosis incidence rates. Rates of tuberculosis incidence, cure, noncompliance, treatment failure, mortality, and referral, as well as socioeconomic and demographic data, were reviewed for patients from ten MADF cities. From 2000 to 2004, 714 new cases of tuberculosis were reported in the cities studied, 436 (61%) of which were treated in Brasília and were therefore not included in the Goiás database. Among patients treated only in the MADF cities studied, the mean incidence of tuberculosis ranged from 4.40 to 10.02/100,000 inhabitants. When those treated in Brasília were included, the incidence significantly increased, ranging from 15.16 to 20.54/100,000 inhabitants (p < 0.001). The rate at which contacts of tuberculosis patients were investigated was low, and treatment outcomes were unsatisfactory in the MADF cities studied and in Brasília. Socioeconomic and demographic data were consistent with the tuberculosis incidence. The number of tuberculosis patients treated in the city in which they resided was lower than expected. Treatment in another city might impair tuberculosis control. The recalculated tuberculosis incidence is consistent with the socioeconomic and demographic profile of the region. A federal surveillance system could be efficiently optimized, improving the control of this disease.

Why wait? The social determinants underlying tuberculosis diagnostic delay.

PubMed

Bonadonna, Lily Victoria; Saunders, Matthew James; Zegarra, Roberto; Evans, Carlton; Alegria-Flores, Kei; Guio, Heinner

2017-01-01

Early detection and diagnosis of tuberculosis remain major global priorities for tuberculosis control. Few studies have used a qualitative approach to investigate the social determinants contributing to diagnostic delay and none have compared data collected from individual, community, and health-system levels. We aimed to characterize the social determinants that contribute to diagnostic delay among persons diagnosed with tuberculosis living in resource-constrained settings. Data were collected in public health facilities with high tuberculosis incidence in 19 districts of Lima, Peru. Semi-structured interviews with persons diagnosed with tuberculosis (n = 105) and their family members (n = 63) explored health-seeking behaviours, community perceptions of tuberculosis and socio-demographic circumstances. Focus groups (n = 6) were conducted with health personnel (n = 35) working in the National Tuberculosis Program. All interview data were transcribed and analysed using a grounded theory approach. The median delay between symptom onset and the public health facility visit that led to the first positive diagnostic sample was 57 days (interquartile range 28-126). The great majority of persons diagnosed with tuberculosis distrusted the public health system and sought care at public health facilities only after exhausting other options. It was universally agreed that persons diagnosed with tuberculosis faced discrimination by public and health personnel. Self-medication with medicines bought at local pharmacies was reported as the most common initial health-seeking behaviour due to the speed and low-cost of treatment in pharmacies. Most persons diagnosed with tuberculosis initially perceived their illness as a simple virus. Diagnostic delay was common and prolonged. When individuals reached a threshold of symptom severity, they addressed their health with the least time-consuming, most economically feasible, and well-known healthcare option available to them. In high-burden settings, more human and material resources are required to promote tuberculosis case-finding initiatives, reduce tuberculosis associated stigma and address the social determinants underlying diagnostic delay.

The number of privately treated tuberculosis cases in India: an estimation from drug sales data.

PubMed

Arinaminpathy, Nimalan; Batra, Deepak; Khaparde, Sunil; Vualnam, Thongsuanmung; Maheshwari, Nilesh; Sharma, Lokesh; Nair, Sreenivas A; Dewan, Puneet

2016-11-01

Understanding the amount of tuberculosis managed by the private sector in India is crucial to understanding the true burden of the disease in the country, and thus globally. In the absence of quality surveillance data on privately treated patients, commercial drug sales data offer an empirical foundation for disease burden estimation. We used a large, nationally representative commercial dataset on sales of 189 anti-tuberculosis products available in India to calculate the amount of anti-tuberculosis treatment in the private sector in 2013-14. We corrected estimates using validation studies that audited prescriptions against tuberculosis diagnosis, and estimated uncertainty using Monte Carlo simulation. To address implications for numbers of patients with tuberculosis, we explored varying assumptions for average duration of tuberculosis treatment and accuracy of private diagnosis. There were 17·793 million patient-months (95% credible interval 16·709 million to 19·841 million) of anti-tuberculosis treatment in the private sector in 2014, twice as many as the public sector. If 40-60% of private-sector tuberculosis diagnoses are correct, and if private-sector tuberculosis treatment lasts on average 2-6 months, this implies that 1·19-5·34 million tuberculosis cases were treated in the private sector in 2014 alone. The midpoint of these ranges yields an estimate of 2·2 million cases, two to three times higher than currently assumed. India's private sector is treating an enormous number of patients for tuberculosis, appreciably higher than has been previously recognised. Accordingly, there is a re-doubled need to address this burden and to strengthen surveillance. Tuberculosis burden estimates in India and worldwide require revision. Bill & Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Risk factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil

PubMed Central

Fregona, Geisa; Cosme, Lorrayne Belique; Moreira, Cláudia Maria Marques; Bussular, José Luis; Dettoni, Valdério do Valle; Dalcolmo, Margareth Pretti; Zandonade, Eliana; Maciel, Ethel Leonor Noia

2017-01-01

ABSTRACT OBJECTIVE To analyze the prevalence and factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil. METHODS This is a cross-sectional study of cases of tuberculosis tested for first-line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espírito Santo between 2002 and 2012. We have used laboratory data and registration of cases of tuberculosis – from the Sistema Nacional de Agravos de Notificação and Sistema para Tratamentos Especiais de Tuberculose. Individuals have been classified as resistant and non-resistant and compared in relation to the sociodemographic, clinical, and epidemiological variables. Some variables have been included in a logistic regression model to establish the factors associated with resistance. RESULTS In the study period, 1,669 individuals underwent anti-tuberculosis drug susceptibility testing. Of these individuals, 10.6% showed resistance to any anti-tuberculosis drug. The rate of multidrug resistance observed, that is, to rifampicin and isoniazid, has been 5%. After multiple analysis, we have identified as independent factors associated with resistant tuberculosis: history of previous treatment of tuberculosis [recurrence (OR = 7.72; 95%CI 4.24–14.05) and re-entry after abandonment (OR = 3.91; 95%CI 1.81–8.43)], smoking (OR = 3.93; 95%CI 1.98–7.79), and positive culture for Mycobacterium tuberculosis at the time of notification of the case (OR = 3.22; 95%CI 1.15–8.99). CONCLUSIONS The partnership between tuberculosis control programs and health teams working in the network of Primary Health Care needs to be strengthened. This would allow the identification and monitoring of individuals with a history of previous treatment of tuberculosis and smoking. Moreover, the expansion of the offer of the culture of tuberculosis and anti-tuberculosis drug susceptibility testing would provide greater diagnostic capacity for the resistant types in Espírito Santo. PMID:28489185

45 CFR 96.127 - Requirements regarding tuberculosis.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Requirements regarding tuberculosis. 96.127... Substance Abuse Prevention and Treatment Block Grant § 96.127 Requirements regarding tuberculosis. (a... Department of Health/Tuberculosis Control Officer, which address how the program— (1) Will, directly or...

9 CFR 77.5 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Cattle and Bison § 77.5... Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less than 0.5... the provisions of the “Uniform Methods and Rules—Bovine Tuberculosis Eradication,” has zero percent...

Is TB in Your Curriculum?

ERIC Educational Resources Information Center

Kerr, Joanne; Elwell, Jack

2002-01-01

Points out the importance of effective health education to fight against tuberculosis (TB) which is the number one fatal infectious disease around the world. Describes a science curriculum on tuberculosis that includes information on the facts about tuberculosis, a forum on tuberculosis, and evaluation. (Contains 17 references.) (YDS)

76 FR 38602 - Bovine Tuberculosis and Brucellosis; Program Framework

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

...] Bovine Tuberculosis and Brucellosis; Program Framework AGENCY: Animal and Plant Health Inspection Service... framework being developed for the bovine tuberculosis and brucellosis programs in the United States. This... proposed revisions to its programs regarding bovine tuberculosis (TB) and bovine brucellosis in the United...

9 CFR 77.5 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Cattle and Bison § 77.5... Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less than 0.5... the provisions of the “Uniform Methods and Rules—Bovine Tuberculosis Eradication,” has zero percent...

45 CFR 96.127 - Requirements regarding tuberculosis.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Requirements regarding tuberculosis. 96.127... Substance Abuse Prevention and Treatment Block Grant § 96.127 Requirements regarding tuberculosis. (a... Department of Health/Tuberculosis Control Officer, which address how the program— (1) Will, directly or...

45 CFR 96.127 - Requirements regarding tuberculosis.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Requirements regarding tuberculosis. 96.127... Substance Abuse Prevention and Treatment Block Grant § 96.127 Requirements regarding tuberculosis. (a... Department of Health/Tuberculosis Control Officer, which address how the program— (1) Will, directly or...

45 CFR 96.127 - Requirements regarding tuberculosis.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Requirements regarding tuberculosis. 96.127... Substance Abuse Prevention and Treatment Block Grant § 96.127 Requirements regarding tuberculosis. (a... Department of Health/Tuberculosis Control Officer, which address how the program— (1) Will, directly or...

9 CFR 77.34 - Official tuberculosis tests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Official tuberculosis tests. 77.34... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive Cervids § 77.34 Official tuberculosis tests. (a) Primary tests. (1) Single cervical tuberculin (SCT) test...

9 CFR 77.5 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Cattle and Bison § 77.5... Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less than 0.5... the provisions of the “Uniform Methods and Rules—Bovine Tuberculosis Eradication,” has zero percent...

45 CFR 96.127 - Requirements regarding tuberculosis.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Requirements regarding tuberculosis. 96.127... Substance Abuse Prevention and Treatment Block Grant § 96.127 Requirements regarding tuberculosis. (a... Department of Health/Tuberculosis Control Officer, which address how the program— (1) Will, directly or...

9 CFR 77.5 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Cattle and Bison § 77.5... Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less than 0.5... the provisions of the “Uniform Methods and Rules—Bovine Tuberculosis Eradication,” has zero percent...

9 CFR 77.5 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Cattle and Bison § 77.5... Methods and Rules—Bovine Tuberculosis Eradication” and in which tuberculosis is prevalent in less than 0.5... the provisions of the “Uniform Methods and Rules—Bovine Tuberculosis Eradication,” has zero percent...

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations

PubMed Central

Choi, Rihwa; Jeong, Byeong-Ho

2017-01-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response. PMID:28028995

Drug resistant Mycobacterium tuberculosis in Mexico.

PubMed

Zazueta-Beltran, Jorge; León-Sicairos, Claudia; Canizalez-Roman, Adrián

2009-04-30

Tuberculosis (TB) remains a serious public health problem, worsened by an increased frequency of multidrug-resistant (MDR) Mycobacterium tuberculosis strains. The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) launched the Global Project on Anti-Tuberculosis Drug Resistance Surveillance to measure the prevalence of drug resistance. Data from the global reports on resistance to anti-tuberculosis (anti-TB) drugs have shown that drug resistance still presents worldwide and that MDR-TB is present in almost all the world. Though the Global Project (WHO) has been operating since 1994, very few countries and states have reported new information. Data from repeated surveys employing comparable methodologies over several years are essential to determine with any certainty in which direction the prevalence of drug resistance is moving. Drug-resistant tuberculosis and MDR-TB have been identified in Mexico, even with the existence of a National Tuberculosis Program based on Directly Observed Treatment, Short-course (DOTS). This review discusses available surveillance data on drug susceptibility data for TB in different states of Mexico.

Modelling of Cerebral Tuberculosis: Hope for Continuous Research in Solving the Enigma of the Bottom Billion’s Disease

PubMed Central

Hernández Pando, Rogelio

2011-01-01

Cerebral tuberculosis is a severe type of extrapulmonary disease that is highly predominant in children. It is thought that meningeal tuberculosis, the most common form of cerebral tuberculosis, begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. Host genetic susceptibility factors and specific mycobacteria substrains could be involved in the development of this serious form of tuberculosis. In this editorial the different animal models of cerebral tuberculosis are commented, highlighting a recently described murine model in which BALB/c mice were infected by the intratracheal route with clinical isolates, which exhibited rapid dissemination and brain infection. These strains were isolated from the cerebrospinal fluid of patients with meningeal tuberculosis; they showed specific genotype and induced a peculiar immune response in the infected brain. This model could be a useful tool to study host and bacilli factors involved in the pathogenesis of the most severe form of tuberculosis. PMID:22135568

Molecular detection of Mycobacterium tuberculosis in cattle and buffaloes: a cause for public health concern.

PubMed

Abdel-Moein, Khaled A; Hamed, Osman; Fouad, Heba

2016-12-01

Tuberculosis is a re-emerging disease causing a growing public health burden. The current study was conducted to investigate the occurrence of Mycobacterium tuberculosis among cattle and buffaloes with tuberculous lesions. Typical tuberculous lesions were collected from 34 cattle and 34 buffaloes (Bubalus bubalis) through postmortem examination of slaughtered animals in abattoirs. DNAs were extracted from samples, and M. tuberculosis was identified by PCR. Positive samples were examined for resistance against rifampicin and isoniazid using GenoType MTBDRplus. Moreover, sera from 90 slaughterhouse workers, butchers, or meat inspectors were examined for the presence of M. tuberculosis antibodies using ELISA. Five cattle (14.7 %) and three buffaloes (8.8 %) tested positive. M. tuberculosis from one cattle was resistant to rifampicin and another was resistant to isoniazid. In addition, the seroprevalence of M. tuberculosis IgG among examined humans was 5.6 %. The occurrence of M. tuberculosis in cattle and buffaloes is a public health concern.

Type I interferons in tuberculosis: Foe and occasionally friend.

PubMed

Moreira-Teixeira, Lúcia; Mayer-Barber, Katrin; Sher, Alan; O'Garra, Anne

2018-05-07

Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis. Since then, additional studies in human tuberculosis and experimental mouse models of M. tuberculosis infection support the concept that type I IFN promotes both bacterial expansion and disease pathogenesis. More recently, studies in a different setting have suggested a putative protective role for type I IFN. In this study, we discuss the mechanistic and contextual factors that determine the detrimental versus beneficial outcomes of type I IFN induction during M. tuberculosis infection, from human disease to experimental mouse models of tuberculosis. © 2018 Moreira-Teixeira et al.

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

PubMed Central

Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

2016-01-01

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

Driving the Way to Tuberculosis Elimination: The Essential Role of Fundamental Research

PubMed Central

Lienhardt, Christian; Kraigsley, Alison M.; Sizemore, Christine F.

2016-01-01

Tuberculosis has impacted human health for millennia. The World Health Organization estimated that, in 2014, 9.6 million people developed tuberculosis and 1.5 million people died from the disease. In May 2014, the World Health Assembly endorsed the new “End TB Strategy” that presents a pathway to tuberculosis elimination. The strategy outlines 3 areas of emphasis, one of which is intensified research and innovation. In this article we highlight the essential role for fundamental tuberculosis research in the future of tuberculosis diagnostics, treatment, and prevention. To maximize the impact of fundamental research, we must foster collaboration among all stakeholders engaged in tuberculosis research and control to facilitate open dialogue to assure that critical gaps in outcome-oriented science are identified and addressed. We present here a framework for future discussions among scientists, physicians, research and development specialists, and public health managers for the reinforcement of national and international strategies toward tuberculosis elimination. PMID:27270671

Systems Biology-Based Identification of Mycobacterium tuberculosis Persistence Genes in Mouse Lungs

PubMed Central

Dutta, Noton K.; Bandyopadhyay, Nirmalya; Veeramani, Balaji; Lamichhane, Gyanu; Karakousis, Petros C.; Bader, Joel S.

2014-01-01

ABSTRACT Identifying Mycobacterium tuberculosis persistence genes is important for developing novel drugs to shorten the duration of tuberculosis (TB) treatment. We developed computational algorithms that predict M. tuberculosis genes required for long-term survival in mouse lungs. As the input, we used high-throughput M. tuberculosis mutant library screen data, mycobacterial global transcriptional profiles in mice and macrophages, and functional interaction networks. We selected 57 unique, genetically defined mutants (18 previously tested and 39 untested) to assess the predictive power of this approach in the murine model of TB infection. We observed a 6-fold enrichment in the predicted set of M. tuberculosis genes required for persistence in mouse lungs relative to randomly selected mutant pools. Our results also allowed us to reclassify several genes as required for M. tuberculosis persistence in vivo. Finally, the new results implicated additional high-priority candidate genes for testing. Experimental validation of computational predictions demonstrates the power of this systems biology approach for elucidating M. tuberculosis persistence genes. PMID:24549847

Extensively drug-resistant tuberculosis in a young child after travel to India.

PubMed

Salazar-Austin, Nicole; Ordonez, Alvaro A; Hsu, Alice Jenh; Benson, Jane E; Mahesh, Mahadevappa; Menachery, Elizabeth; Razeq, Jafar H; Salfinger, Max; Starke, Jeffrey R; Milstone, Aaron M; Parrish, Nicole; Nuermberger, Eric L; Jain, Sanjay K

2015-12-01

Extensively drug-resistant (XDR) tuberculosis is becoming increasingly prevalent worldwide, but little is known about XDR tuberculosis in young children. In this Grand Round we describe a 2-year-old child from the USA who developed pneumonia after a 3 month visit to India. Symptoms resolved with empirical first-line tuberculosis treatment; however, a XDR strain of Mycobacterium tuberculosis grew in culture. In the absence of clinical or microbiological markers, low-radiation exposure pulmonary CT imaging was used to monitor treatment response, and guide an individualised drug regimen. Management was complicated by delays in diagnosis, uncertainties about drug selection, and a scarcity of child-friendly formulations. Treatment has been successful so far, and the child is in remission. This report of XDR tuberculosis in a young child in the USA highlights the risks of acquiring drug-resistant tuberculosis overseas, and the unique challenges in management of tuberculosis in this susceptible population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

PubMed

Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

2017-03-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

Genomic epidemiology of Lineage 4 Mycobacterium tuberculosis subpopulations in New York City and New Jersey, 1999-2009.

PubMed

Brown, Tyler S; Narechania, Apurva; Walker, John R; Planet, Paul J; Bifani, Pablo J; Kolokotronis, Sergios-Orestis; Kreiswirth, Barry N; Mathema, Barun

2016-11-21

Whole genome sequencing (WGS) has rapidly become an important research tool in tuberculosis epidemiology and is likely to replace many existing methods in public health microbiology in the near future. WGS-based methods may be particularly useful in areas with less diverse Mycobacterium tuberculosis populations, such as New York City, where conventional genotyping is often uninformative and field epidemiology often difficult. This study applies four candidate strategies for WGS-based identification of emerging M. tuberculosis subpopulations, employing both phylogenomic and population genetics methods. M. tuberculosis subpopulations in New York City and New Jersey can be distinguished via phylogenomic reconstruction, evidence of demographic expansion and subpopulation-specific signatures of selection, and by determination of subgroup-defining nucleotide substitutions. These methods identified known historical outbreak clusters and previously unidentified subpopulations within relatively monomorphic M. tuberculosis endemic clone groups. Neutrality statistics based on the site frequency spectrum were less useful for identifying M. tuberculosis subpopulations, likely due to the low levels of informative genetic variation in recently diverged isolate groups. In addition, we observed that isolates from New York City endemic clone groups have acquired multiple non-synonymous SNPs in virulence- and growth-associated pathways, and relatively few mutations in drug resistance-associated genes, suggesting that overall pathoadaptive fitness, rather than the acquisition of drug resistance mutations, has played a central role in the evolutionary history and epidemiology of M. tuberculosis subpopulations in New York City. Our results demonstrate that some but not all WGS-based methods are useful for detection of emerging M. tuberculosis clone groups, and support the use of phylogenomic reconstruction in routine tuberculosis laboratory surveillance, particularly in areas with relatively less diverse M. tuberculosis populations. Our study also supports the use of wider-reaching phylogenomic and population genomic methods in tuberculosis public health practice, which can support tuberculosis control activities by identifying genetic polymorphisms contributing to epidemiological success in local M. tuberculosis populations and possibly explain why certain isolate groups are apparently more successful in specific host populations.