Immune TB Antibody Phage Display Library as a Tool To Study B Cell Immunity in TB Infections.

PubMed

Hamidon, Nurul Hamizah; Suraiya, Siti; Sarmiento, Maria E; Acosta, Armando; Norazmi, Mohd Nor; Lim, Theam Soon

2018-03-01

B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals. The development of disease-specific antibody libraries or immune libraries is useful to better understand antibody-mediated immune responses against specific disease antigens. This study describes the generation of an immune single-chain variable fragment (scFv) library derived from TB-infected individuals. The immune library with an estimated diversity of 10 9 independent clones was then applied for the identification of monoclonal antibodies against Mycobacterium tuberculosis α-crystalline as a model antigen. Biopanning of the library isolated three monoclonal antibodies with unique gene usage. This strengthens the role of antibodies in TB immunity in addition to the role played by cellular immunity. The developed library can be applied against other TB antigens and aid antibody-derived TB immunity studies in the future.

Hierarchy Low CD4+/CD8+ T-Cell Counts and IFN-γ Responses in HIV-1+ Individuals Correlate with Active TB and/or M.tb Co-Infection.

PubMed

Shao, Lingyun; Zhang, Xinyun; Gao, Yan; Xu, Yunya; Zhang, Shu; Yu, Shenglei; Weng, Xinhua; Shen, Hongbo; Chen, Zheng W; Jiang, Weimin; Zhang, Wenhong

2016-01-01

Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. 164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (<200/μL, 200-500/μL, >500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (P<0.001). Immunologically, HIV-1+ATB group showed significantly lower numbers of ESAT-6-/CFP-10-specific IFN-γ+ T cells than HIV-1+LTB group. Consistently, PPD-specific IFN-γ+CD4+/CD8+ T effector cells in HIV-1+ATB group were significantly lower than those in HIV-1+LTB group (P<0.001). Hierarchy low CD8+ T-cell counts and effector function in HIV-1-infected individuals are correlated with both M.tb co-infection and active TB. Hierarchy low CD4+ T-cell counts and Th1 effector function in HIV-1+ individuals are associated with increased frequencies of active TB, but not M.tb co-infection.

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo.

PubMed

Kaboru, Berthollet Bwira; Ogwang, Brenda A; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-09-01

HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases' control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region.

Mycobacterium tuberculosis thymidylate kinase antigen assays for designating incipient, high-risk latent M.tb infection.

PubMed

Wayengera, Misaki; Kateete, David P; Asiimwe, Benon; Joloba, Moses L

2018-03-16

Precise designation of high risk forms of latent Mycobacterium tuberculosis-M.tb infections (LTBI) is impossible. Delineation of high-risk LTBI can, however, allow for chemoprophylaxis and curtail majority cases of active tuberculosis (ATB). There is epidemiological evidence to support the view that LTBI in context of HIV-1 co-infection is high-risk for progression to ATB relative to LTBI among HIV-ve persons. We recently showed that assays of M.tb thymidylate kinase (TMKmt) antigen and host specific IgG can differentiate ATB from LTBI and or no TB (NTB, or healthy controls). In this study, we aimed to expose the differential levels of TMKmt Ag among HIV+ve co-infected LTBI relative to HIV-ve LTBI as a strategy to advance these assays for designating incipient LTBI. TMKmt host specific IgM and IgG detection Enzyme Immuno-Assays (EIA) were conducted on 40 TB exposed house-hold contacts (22 LTBI vs. 18 no TB (NTB) by QunatiFERON-TB GOLD®); and TMKmt Ag detection EIA done on 82 LTBI (46 HIV+ve vs 36 HIV-ve) and 9 NTB (American donors). Purified recombinant TMKmt protein was used as positive control for the Ag assays. IgM levels were found to be equally low across QuantiFERON-TB GOLD® prequalified NTB and TB exposed house-hold contacts. Higher TMKmt host specific IgG trends were found among TB house-hold contacts relative to NTB controls. TMKmt Ag levels among HIV+ve LTBI were 0.2676 ± 0.0197 (95% CI: 0.2279 to 0.3073) relative to 0.1069 ± 0.01628 (95% CI: 0.07385 to 0.14) for HIV-ve LTBI (supporting incipient nature of LTBI in context of HIV-1 co-infection). NTB had TMKmt Ag levels of 0.1013 ± 0.02505 (5% CI: 0.0421 to 0.1606) (intimating that some were indeed LTBI). TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI.

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo

PubMed Central

Kaboru, Berthollet Bwira; Ogwang, Brenda. A.; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-01-01

Background: HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. Methods: A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Results: Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases’ control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. Conclusion: HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region. PMID:24596866

The prevalence of human immunodeficiency virus infection among TB patients in Port Harcourt Nigeria

PubMed Central

Erhabor, O; Jeremiah, Z A; Adias, T C; Okere, CE

2010-01-01

The joint statement by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America recommends that all patients with tuberculosis (TB) undergo testing for human immunodeficiency virus (HIV) infection after counseling. In this study, we investigated the prevalence of HIV infection among 120 patients diagnosed with microbiologically proven TB aged 18 to 54 years with a mean age of 39.5 years (standard deviation 6.75). The subjects studied were 36 male (30%) and 84 females (70%). Enzyme-linked immunosorbent assay methods were used to screen for HIV infection among the subjects. Of the 120 TB patients tested 30 (25%) were positive for HIV infection. The prevalence of HIV was higher in females 24 (80%) compared to males 6 (20%) and among singles (66.7%) compared to married subjects (33.3%) (χ2 = 83.5 and χ2 = 126.2, respectively P = 0.001). HIV-1 was the predominant viral subtype. HIV prevalence was significantly higher in subjects in the 38–47 year and 28–37 year age groups (both 40%) followed by the 18–28 year age group (20%) (χ2 = 42.6, P = 0.05). The mean CD4 lymphocyte count of the HIV-infected TB subjects was significantly lower (195 ± 40.5 cells/μL) compared to the non-HIV infected (288 ± 35.25 cells/μL P = 0.01). This study has shown a high prevalence of HIV among TB patients. Reactivation of TB among people living with HIV can be reduced by TB preventive therapy and by universal access to antiretroviral therapy. PMID:22096379

Implementation of tuberculosis infection control measures in designated hospitals in Zhejiang Province, China: are we doing enough to prevent nosocomial tuberculosis infections?

PubMed Central

Chen, Bin; Liu, Min; Gu, Hua; Wang, Xiaomeng; Qiu, Wei; Shen, Jian; Jiang, Jianmin

2016-01-01

Objectives Tuberculosis (TB) infection control measures are very important to prevent nosocomial transmission and protect healthcare workers (HCWs) in hospitals. The TB infection control situation in TB treatment institutions in southeastern China has not been studied previously. Therefore, the aim of this study was to investigate the implementation of TB infection control measures in TB-designated hospitals in Zhejiang Province, China. Design Cross-sectional survey using observation and interviews. Setting All TB-designated hospitals (n=88) in Zhejiang Province, China in 2014. Primary and secondary outcome measures Managerial, administrative, environmental and personal infection control measures were assessed using descriptive analyses and univariate logistic regression analysis. Results The TB-designated hospitals treated a median of 3030 outpatients (IQR 764–7094) and 279 patients with confirmed TB (IQR 154–459) annually, and 160 patients with TB (IQR 79–426) were hospitalised in the TB wards. Most infection control measures were performed by the TB-designated hospitals. Measures including regular monitoring of TB infection control in high-risk areas (49%), shortening the wait times (42%), and providing a separate waiting area for patients with suspected TB (46%) were sometimes neglected. N95 respirators were available in 85 (97%) hospitals, although only 44 (50%) hospitals checked that they fit. Hospitals with more TB staff and higher admission rates of patients with TB were more likely to set a dedicated sputum collection area and to conduct annual respirator fit testing. Conclusions TB infection control measures were generally implemented by the TB-designated hospitals. Measures including separation of suspected patients, regular monitoring of infection control practices, and regular fit testing of respirators should be strengthened. Infection measures for sputum collection and respirator fit testing should be improved in hospitals with lower admission

Prevalence of latent TB infection and TB disease among adolescents in high TB burden countries in Africa: a systematic review protocol.

PubMed

Bunyasi, Erick Wekesa; Schmidt, Bey-Marrie; Abdullahi, Leila Hussein; Mulenga, Humphrey; Tameris, Michele; Luabeya, Angelique; Shenje, Justin; Scriba, Thomas; Geldenhuys, Hennie; Wood, Robin; Hatherill, Mark

2017-03-10

Almost a third of the world population has latent tuberculosis (TB) infection (LTBI), ∼10 million of whom develop TB disease annually, despite existence of effective, but lengthy, preventive and curative drug regimens. Although adolescents appear to have a very high force of LTBI, their reported incidence of TB disease is less than that of their corresponding general population. The few available studies on adolescent TB infection and disease prevalence are not sufficient to address the apparent discordance between rates of infection and disease in high TB burden countries in Africa. Therefore, we aim to perform a systematic review to examine the relationship between adolescent LTBI and TB disease, benchmarked against national TB disease burden data. A comprehensive literature search will be performed for cross-sectional studies and screening data in cohort studies to determine the prevalence of LTBI and TB disease among adolescents in high TB burden countries in Africa in the following databases: PubMed , Scopus , Cochrane library , Web of Science , Africa Wide , CINAHL and the Africa Index Medicus . This will be supplemented by a search of reference lists of selected articles for potentially relevant articles. We will restrict our search to articles published in the English language between 1990 and 2016 among adolescents in order to obtain estimates reflective of the mature HIV epidemic in most high TB burden countries in Africa that occurred over this critical period. Primary end points are: prevalence of LTBI and TB disease. We will use the random-effects or fixed-effects modelling for our meta-analysis based on heterogeneity estimates. No ethics approval is required given that this is a systematic review. Findings will be disseminated in a peer-reviewed journal in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). CRD42015023495. Published by the BMJ Publishing Group Limited. For permission to use (where not already

Implementation of tuberculosis infection control measures in designated hospitals in Zhejiang Province, China: are we doing enough to prevent nosocomial tuberculosis infections?

PubMed

Chen, Bin; Liu, Min; Gu, Hua; Wang, Xiaomeng; Qiu, Wei; Shen, Jian; Jiang, Jianmin

2016-03-03

Tuberculosis (TB) infection control measures are very important to prevent nosocomial transmission and protect healthcare workers (HCWs) in hospitals. The TB infection control situation in TB treatment institutions in southeastern China has not been studied previously. Therefore, the aim of this study was to investigate the implementation of TB infection control measures in TB-designated hospitals in Zhejiang Province, China. Cross-sectional survey using observation and interviews. All TB-designated hospitals (n=88) in Zhejiang Province, China in 2014. Managerial, administrative, environmental and personal infection control measures were assessed using descriptive analyses and univariate logistic regression analysis. The TB-designated hospitals treated a median of 3030 outpatients (IQR 764-7094) and 279 patients with confirmed TB (IQR 154-459) annually, and 160 patients with TB (IQR 79-426) were hospitalised in the TB wards. Most infection control measures were performed by the TB-designated hospitals. Measures including regular monitoring of TB infection control in high-risk areas (49%), shortening the wait times (42%), and providing a separate waiting area for patients with suspected TB (46%) were sometimes neglected. N95 respirators were available in 85 (97%) hospitals, although only 44 (50%) hospitals checked that they fit. Hospitals with more TB staff and higher admission rates of patients with TB were more likely to set a dedicated sputum collection area and to conduct annual respirator fit testing. TB infection control measures were generally implemented by the TB-designated hospitals. Measures including separation of suspected patients, regular monitoring of infection control practices, and regular fit testing of respirators should be strengthened. Infection measures for sputum collection and respirator fit testing should be improved in hospitals with lower admission rates of patients with TB. Published by the BMJ Publishing Group Limited. For permission to

Optimal control of a two-strain tuberculosis-HIV/AIDS co-infection model.

PubMed

Agusto, F B; Adekunle, A I

2014-05-01

Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis (TB). The risk for TB infection greatly increases with HIV infection; TB disease occurs in 7-10% of patients with HIV infection each year, increasing the potential for transmission of drug-resistant Mycobacterium tuberculosis strains. In this paper a deterministic model is presented and studied for the transmission of TB-HIV/AIDS co-infection. Optimal control theory is then applied to investigate optimal strategies for controlling the spread of the disease using treatment of infected individuals with TB as the system control variables. Various combination strategies were examined so as to investigate the impact of the controls on the spread of the disease. And incremental cost-effectiveness ratio (ICER) was used to investigate the cost effectiveness of all the control strategies. Our results show that the implementation of the combination strategy involving the prevention of treatment failure in drug-sensitive TB infectious individuals and the treatment of individuals with drug-resistant TB is the most cost-effective control strategy. Similar results were obtained with different objective functionals involving the minimization of the number of individuals with drug-sensitive TB-only and drug-resistant TB-only with the efforts involved in applying the control. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Infection control and the burden of tuberculosis infection and disease in health care workers in china: a cross-sectional study.

PubMed

He, Guang Xue; van denHof, Susan; van der Werf, Marieke J; Wang, Guo Jie; Ma, Shi Wen; Zhao, Dong Yang; Hu, Yuan Lian; Yu, Shi Cheng; Borgdorff, Martien W

2010-10-28

Hospitals with inadequate infection control are risky environments for the emergence and transmission of tuberculosis (TB). We evaluated TB infection control practices, and the prevalence of latent TB infection (LTBI) and TB disease and risk factors in health care workers (HCW) in TB centers in Henan province in China. A cross-sectional survey was conducted in 2005. To assess TB infection control practices in TB centers, checklists were used. HCW were tuberculin skin tested (TST) to measure LTBI prevalence, and were asked for sputum smears and chest X-rays to detect TB disease, and questionnaires to assess risk factors. Differences between groups for categorical variables were analyzed by binary logistic regression. The clustered design of the study was taken into account by using a multilevel logistic model. The assessment of infection control practices showed that only in a minority of the centers the patient consultation areas and X-ray areas were separated from the waiting areas and administrative areas. Mechanical ventilation was not available in any of the TB centers. N95 respirators were not available for HCW and surgical masks were not available for TB patients and suspects. The LTBI prevalence of HCW with and without BCG scar was 55.6% (432/777) and 49.0% (674/1376), respectively (P = 0.003). Older HCW, HCW with longer duration of employment, and HCW who worked in departments with increased contact with TB patients had a higher prevalence of LTBI. HCW who work in TB centers at the prefecture level, or with an inpatient ward also had a higher prevalence of LTBI. Twenty cases of pulmonary TB were detected among 3746 HCW. The TB prevalence was 6.7/1000 among medical staff and 2.5/1000 among administrative/logistic staff. TB infection control in TB centers in Henan, China, appears to be inadequate and the prevalence of LTBI and TB disease among HCW was high. TB infection control practices in TB centers should be strengthened in China, including administrative

Vitamin D status among pulmonary TB patients and non-TB controls: a cross-sectional study from Mwanza, Tanzania.

PubMed

Friis, Henrik; Range, Nyagosya; Changalucha, John; Praygod, George; Jeremiah, Kidola; Faurholt-Jepsen, Daniel; Krarup, Henrik; Mølgaard, Christian; Andersen, Åse Bengaard

2013-01-01

Little is known about vitamin D status in low-income populations burdened with infectious diseases. Hence, there is a need for data on correlates of serum 25-hydroxy vitamin D (S-25(OH)D) and its validity during infections. To assess the role of pulmonary TB (PTB) and HIV as correlates of S-25(OH)D. Age-sex-matched cross-sectional study among PTB patients and non-TB controls. PTB patients were categorized as sputum negative (PTB-) and positive (PTB+) by culture. Non-TB controls were randomly selected among age-sex-matched neighbours to PTB+ patients. Height, weight, arm circumference and triceps skinfold were measured, and body mass index (BMI), arm fat (AFA) and muscle area (AMA) computed. HIV status, and S-25(OH)D, C-reactive protein (S-CRP) and α1-acid glycoprotein (S-AGP) were determined. Linear regression analysis with controls and PTB patients combined was used to identify correlates of S-25(OH)D. S-25(OH)D data were available on 97.8% (1570) of 1605 participants. Mean (SD) S-25(OH)D was 84.4 (25.6) nmol/L with 39.6% <75 nmol/L among 347 non-TB controls. Time of recruitment, sex, PTB and HIV, and elevated S-AGP were correlates of S-25(OH)D. S-25(OH)D was 24.8 (95% CI 18.6;30.9) nmol/L higher in PTB compared to controls among females, but only 9.8 (95% CI:4.5;15.2) nmol/L among males (interaction p<0.0001). Females had 13.8 (95% CI:8.2;21.9) nmol/L lower S-25(OH)D than males, and HIV infected individuals had 8.5 (95% CI:4.9;12.1) higher S-25(OH)D compared to uninfected. Elevated S-AGP was a positive correlate of S-25(OH)D. Low BMI was associated with S-25(OH)D, but not with infections or S-AGP in the model. While S-25(OH)D may decline transiently during a mild acute phase response, it may increase if the acute phase response leads to loss of fat. The validity of S-25(OH)D as a marker of vitamin D status may be affected by infections.

Multiplex analysis of plasma cytokines/chemokines showing different immune responses in active TB patients, latent TB infection and healthy participants.

PubMed

Yao, Xiangyang; Liu, Yongliang; Liu, Yang; Liu, Wei; Ye, Zhizhong; Zheng, Chao; Ge, Shengxiang

2017-12-01

Interferon gamma release assays (IGRAs) have been widely used to diagnose Mycobacterium tuberculosis (MTB) infection. However, IGRAs cannot discriminate between active TB patients and latent TB infection (LTBI), and the sensitivity of IGRAs for MTB infection is suboptimal. Here, we analyzed cytokines/chemokines in MTB antigen-stimulated and -unstimulated plasma samples to identify host biomarkers that are associated with active TB and MTB infection. Active TB patients, subjects with LTBI and healthy participants were recruited. Seventy-one soluble cytokines and chemokines were tested using Luminex liquid array-based multiplexed immunoassays. For the 71 examined factors, our results indicated that the unstimulated levels of IL-8 Nil , IP-10 Nil , MIP-1a Nil , and sIL-2Ra Nil and the antigen stimulated levels of IL-8 (Ag-Nil) , VEGF (Ag-Nil) , and MCP-3 (Ag-Nil) were potential biomarkers for differentiating between active TB and LTBI, with AUCs of 0.8, 0.86, 0.755, 0.845, 0.825, 0.812 and 0.75, respectively. The G-CSF (Ag-Nil) , GM-CSF (Ag-Nil) , IL-1a (Ag-Nil) , IL-2 (Ag-Nil) , IP-10 (Ag-Nil) , BCA-1 (Ag-Nil) and Eotaxin-1 (Ag-Nil) responses were significantly higher in patients with active TB and LTBI compared with healthy participants (p < 0.05), with AUCs of 0.922, 0.902, 0.908, 1.0, 0.937, 0.919 and 0.935, respectively. Our preliminary data suggest that unstimulated or stimulated levels of cytokines and chemokines could be used as host biomarkers for diagnosing active TB as well as additional biomarkers, except IFN-γ, for MTB infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tuberculosis in healthcare workers and infection control measures at primary healthcare facilities in South Africa.

PubMed

Claassens, Mareli M; van Schalkwyk, Cari; du Toit, Elizabeth; Roest, Eline; Lombard, Carl J; Enarson, Donald A; Beyers, Nulda; Borgdorff, Martien W

2013-01-01

Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers. One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained. The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08). The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.

Tuberculosis in Healthcare Workers and Infection Control Measures at Primary Healthcare Facilities in South Africa

PubMed Central

Claassens, Mareli M.; van Schalkwyk, Cari; du Toit, Elizabeth; Roest, Eline; Lombard, Carl J.; Enarson, Donald A.; Beyers, Nulda; Borgdorff, Martien W.

2013-01-01

Background Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers. Methods One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained. Results The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08). Conclusion The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB. PMID:24098461

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

PubMed Central

Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

2012-01-01

Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253.

PubMed

Shiboski, C H; Chen, H; Ghannoum, M A; Komarow, L; Evans, S; Mukherjee, P K; Isham, N; Katzenstein, D; Asmelash, A; Omozoarhe, A E; Gengiah, S; Allen, R; Tripathy, S; Swindells, S

2014-06-01

To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm(3). Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2-4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22-48) and the specificity 85% (95%CI 81-88). We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding.

Performance of the QuantiFERON-TB Gold Assay Among HIV-infected Children With Active Tuberculosis in France.

PubMed

Hormi, Myriam; Guérin-El Khourouj, Valérie; Pommelet, Virginie; Jeljeli, Mohamed; Pédron, Béatrice; Diana, Jean-Sébastien; Faye, Albert; Sterkers, Ghislaine

2018-04-01

Data regarding the use of QuantiFERON to assist the diagnosis of active tuberculosis (TB) in HIV-infected children are limited, especially in countries with low incidence of TB/HIV coinfection. QuantiFERON results were analyzed in 63 HIV-infected children who presented to our hospital in Paris, France. Seventeen HIV-uninfected children with active TB (4 culture-confirmed) were included for comparison. The 63 HIV-infected children (median age: 11 yr) had 113 QuantiFERON tests. Thirty-four (54%) were born in sub-Saharan Africa. Vertical HIV transmission was documented for 50 of 52 (96%) and stage III HIV-infection for 30 of 50 children (60%). Over the study period, active TB was diagnosed in 7 of 63 HIV-infected children (3 culture-confirmed). Additional ongoing or previous opportunistic infections were present in 4 of 7. QuantiFERON results were positive in 2 of 7 HIV-infected children with active TB (sensitivity: 29%) and 16 of 17 HIV-uninfected children with active TB (sensitivity: 94%). At initial QuantiFERON testing of the 63 HIV-infected children, 8 (13%) had positive results (1, active TB; 5, latent TB; 2, previous TB) and 51 (81%) had negative results. Of 33 children with repeat testing after an initially positive or negative result, the only change was one conversion from a negative to a positive result at the onset of active TB. The 4 children (6%) with indeterminate quantiFERON results had a concomitant opportunistic infection. Results of repeat testing after clinical stabilization were negative in all 4. QuantiFERON testing performed poorly for active TB diagnosis in this series of children with advanced HIV infection.

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253

PubMed Central

Shiboski, C. H.; Chen, H.; Ghannoum, M. A.; Komarow, L.; Evans, S.; Mukherjee, P. K.; Isham, N.; Katzenstein, D.; Asmelash, A.; Omozoarhe, A. E.; Gengiah, S.; Allen, R.; Tripathy, S.; Swindells, S.

2014-01-01

SUMMARY OBJECTIVE To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. METHODS Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. RESULTS Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm3. Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2–4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22–48) and the specificity 85% (95%CI 81–88). CONCLUSION We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding. PMID:24903939

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study.

PubMed

Efsen, A M W; Schultze, A; Miller, R F; Panteleev, A; Skrahin, A; Podlekareva, D N; Miro, J M; Girardi, E; Furrer, H; Losso, M H; Toibaro, J; Caylà, J A; Mocroft, A; Lundgren, J D; Post, F A; Kirk, O

2018-01-01

Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5-74.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Latent TB infection and pulmonary TB disease among patients with diabetes mellitus in Bandung, Indonesia.

PubMed

Koesoemadinata, Raspati C; McAllister, Susan M; Soetedjo, Nanny N M; Febni Ratnaningsih, Dwi; Ruslami, Rovina; Kerry, Sarah; Verrall, Ayesha J; Apriani, Lika; van Crevel, Reinout; Alisjahbana, Bachti; Hill, Philip C

2017-02-01

Screening and treatment of latent TB infection (LTBI) and TB disease could reduce diabetes mellitus (DM)-associated TB. We aimed to describe the prevalence of LTBI and pulmonary TB among patients with DM in a TB-endemic setting. Patients with DM attending a hospital and community centres in Bandung, Indonesia, underwent LTBI screening using interferon gamma release assay (IGRA). TB was investigated by sputum smear, culture and x-ray. TB contacts from a parallel study were age- and sex-matched to patients with DM to compare LTBI and TB disease prevalence. Of 682 patients with DM screened, 651 (95.5%) were eligible. Among 'TB disease-free' patients, LTBI prevalence was 38.9% (206/530; 95% CI 34.7-43.2). Patients with DM were less likely to be IGRA positive than TB contacts (38.6%, 54/140; 95% CI 30.5-46.6 vs 68.6%, 96/140; 95% CI 60.9-72.3: p<0.001); but had a higher disease prevalence (4.9%, 8/164; 95% CI 1.6-8.2 vs 1.2%, 2/164; 95% CI -0.5 to 2.9: p=0.054). Patients with DM in crowded households had increased risk of LTBI (AOR 1.71; 95% CI 1.19-2.45). LTBI prevalence in patients with DM was lower than in household contacts, but patients with DM were more likely to have TB disease. Further studies should explore possible benefits of LTBI screening and preventive therapy in patients with DM in TB-endemic settings. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model

PubMed Central

Harrington-Kandt, Rachel; Stylianou, Elena; Eddowes, Lucy A.; Lim, Pei Jin; Stockdale, Lisa; Pinpathomrat, Nawamin; Bull, Naomi; Pasricha, Janet; Ulaszewska, Marta; Beglov, Yulia; Vaulont, Sophie

2018-01-01

Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. PMID:29324800

TB control programmes: the challenges for Africa.

PubMed

Harries, T

1996-11-01

Governmental neglect of tuberculosis (TB), inadequately managed and inaccurately designed TB control programs, population growth, and the HIV epidemic account for the resurgence of TB in sub-Saharan Africa. The World Health Organization and the International Union against TB and Lung Disease have developed a TB control strategy that aims to reduce mortality, morbidity, and transmission of TB. It aims for an 85% cure rate among detected new cases of smear-positive TB and a 70% rate of detecting existing smear-positive TB cases. The strategy involves the provision of short-course chemotherapy (SCC) to all identified smear-positive TB cases through directly observed treatment (DOTS). SCC treatment regimens for smear-positive pulmonary TB recommended for sub-Saharan African countries are: initial phase = daily administration over 2 months of streptomycin, rifampicin, isoniazid, and pyrazinamide; continuation phase = 3 doses over 4 months of isoniazid and rifampicin or daily administration of thiacetazone and isoniazid or of ethambutol and isoniazid. A TB control policy must be implemented to bring about effective TB control. The essential elements of this policy include political commitment, case detection through passive case-finding, SCC, a regular supply of essential drugs, and a monitoring and evaluation system. Political commitment involves establishing a National TB Control Program to be integrated into the existing health structure. Increased awareness of TB in the community and among health workers and a reference laboratory are needed to make case finding successful. A distribution and logistics system is needed to ensure uninterrupted intake of drugs throughout treatment. These regimens have been very successful and cost-effective but pose several disadvantages (e.g., heavy workload of recommended 3 sputum smear tests). A simplified approach involves 1 initial sputum smear for 6 months; 6-months, intermittent rifampicin-based therapy, 100% DOTS throughout

Early morning urine collection to improve urinary lateral flow LAM assay sensitivity in hospitalised patients with HIV-TB co-infection.

PubMed

Gina, Phindile; Randall, Philippa J; Muchinga, Tapuwa E; Pooran, Anil; Meldau, Richard; Peter, Jonny G; Dheda, Keertan

2017-05-12

Urine LAM testing has been approved by the WHO for use in hospitalised patients with advanced immunosuppression. However, sensitivity remains suboptimal. We therefore examined the incremental diagnostic sensitivity of early morning urine (EMU) versus random urine sampling using the Determine® lateral flow lipoarabinomannan assay (LF-LAM) in HIV-TB co-infected patients. Consenting HIV-infected inpatients, screened as part of a larger prospective randomized controlled trial, that were treated for TB, and could donate matched random and EMU samples were included. Thus paired sample were collected from the same patient, LF-LAM was graded using the pre-January 2014, with grade 1 and 2 manufacturer-designated cut-points (the latter designated grade 1 after January 2014). Single sputum Xpert-MTB/RIF and/or TB culture positivity served as the reference standard (definite TB). Those treated for TB but not meeting this standard were designated probable TB. 123 HIV-infected patients commenced anti-TB treatment and provided matched random and EMU samples. 33% (41/123) and 67% (82/123) had definite and probable TB, respectively. Amongst those with definite TB LF-LAM sensitivity (95%CI), using the grade 2 cut-point, increased from 12% (5-24; 5/43) to 39% (26-54; 16/41) with random versus EMU, respectively (p = 0.005). Similarly, amongst probable TB, LF-LAM sensitivity increased from 10% (5-17; 8/83) to 24% (16-34; 20/82) (p = 0.001). LF-LAM specificity was not determined. This proof of concept study indicates that EMU could improve the sensitivity of LF-LAM in hospitalised TB-HIV co-infected patients. These data have implications for clinical practice.

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.

A Systematic Review of the Epidemiology, Immunopathogenesis, Diagnosis, and Treatment of Pleural TB in HIV- Infected Patients

PubMed Central

Aljohaney, A.; Amjadi, K.; Alvarez, G. G.

2012-01-01

Background. High HIV burden countries have experienced a high burden of pleural TB in HIV-infected patients. Objective. To review the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients. Methods. A literature search from 1950 to June 2011 in MEDLINE was conducted. Results. Two-hundred and ninety-nine studies were identified, of which 30 met the inclusion criteria. The immunopathogenesis as denoted by cells and cytokine profiles is distinctly different between HIV and HIV-uninfected pleural TB disease. Adenosine deaminase and interferon gamma are good markers of pleural TB disease even in HIV-infected patients. HIV-uninfected TB suspects with pleural effusions commonly have a low yield of TB organisms however the evidence suggests that in dually infected patients smear and cultures have a higher yield. The Gene Xpert MTB/RIF assay has significant potential to improve the diagnosis of pleural TB in HIV-positive patients. Conclusions. Pleural TB in HIV-infected patients has a different immunopathogenesis than HIV-uninfected pleural TB and these findings in part support the differences noted in this systematic review. Research should focus on developing an interferon gamma-based point of care diagnostic test and expansion of the role of Gene Xpert in the diagnosis of pleural TB. PMID:22474483

Migration, TB control and elimination: Whom to screen and treat.

PubMed

Rendon, A; Centis, R; Zellweger, J-P; Solovic, I; Torres-Duque, C A; Robalo Cordeiro, C; de Queiroz Mello, F C; Manissero, D; Sotgiu, G

Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease. Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Determining Mycobacterium tuberculosis Infection among BCG-Immunised Ugandan Children by T-SPOT.TB and Tuberculin Skin Testing

PubMed Central

Nkurunungi, Gyaviira; Lutangira, Jimreeves E.; Lule, Swaib A.; Akurut, Hellen; Kizindo, Robert; Fitchett, Joseph R.; Kizito, Dennison; Sebina, Ismail; Muhangi, Lawrence; Webb, Emily L.; Cose, Stephen; Elliott, Alison M.

2012-01-01

Background Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population. Methodology/Principal Findings We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens. Conclusions/Significance We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of

Spatial Targeting for Bovine Tuberculosis Control: Can the Locations of Infected Cattle Be Used to Find Infected Badgers?

PubMed

Smith, Catherine M; Downs, Sara H; Mitchell, Andy; Hayward, Andrew C; Fry, Hannah; Le Comber, Steven C

2015-01-01

Bovine tuberculosis is a disease of historical importance to human health in the UK that remains a major animal health and economic issue. Control of the disease in cattle is complicated by the presence of a reservoir species, the Eurasian badger. In spite of uncertainty in the degree to which cattle disease results from transmission from badgers, and opposition from environmental groups, culling of badgers has been licenced in two large areas in England. Methods to limit culls to smaller areas that target badgers infected with TB whilst minimising the number of uninfected badgers culled is therefore of considerable interest. Here, we use historical data from a large-scale field trial of badger culling to assess two alternative hypothetical methods of targeting TB-infected badgers based on the distribution of cattle TB incidents: (i) a simple circular 'ring cull'; and (ii) geographic profiling, a novel technique for spatial targeting of infectious disease control that predicts the locations of sources of infection based on the distribution of linked cases. Our results showed that both methods required coverage of very large areas to ensure a substantial proportion of infected badgers were removed, and would result in many uninfected badgers being culled. Geographic profiling, which accounts for clustering of infections in badger and cattle populations, produced a small but non-significant increase in the proportion of setts with TB-infected compared to uninfected badgers included in a cull. It also provided no overall improvement at targeting setts with infected badgers compared to the ring cull. Cattle TB incidents in this study were therefore insufficiently clustered around TB-infected badger setts to design an efficient spatially targeted cull; and this analysis provided no evidence to support a move towards spatially targeted badger culling policies for bovine TB control.

[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].

PubMed

Zielonka, Tadeusz M

2015-01-01

The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland requires the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, including development, implementation and monitoring of the implementation of procedures into practice, aiming at limiting the dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staff with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include reporting all of the recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as an occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides principles of financing of individual benefits available for the insured TB patients as well as those not insured.

[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].

PubMed

Zielonka, Tadeusz M

2011-01-01

The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland provides for the duty of the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, involving development, implementation and monitoring of practical implementation of procedures aiming at limiting dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staffs with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include notification of all recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides for principles of financing of individual benefits available for the insured TB patients and those not insured.

TB control: challenges and opportunities for India.

PubMed

Pai, Madhukar; Daftary, Amrita; Satyanarayana, Srinath

2016-03-01

India's TB control programme has treated over 19 million patients, but the incidence of TB continues to be high. TB is a major killer and drug-resistant TB is a growing threat. There are several likely reasons, including social conditions and co-morbidities that fuel the TB epidemic: under-investment by the government, weak programme implementation and management, suboptimal quality of care in the private sector, and insufficient advocacy around TB. Fortunately, India possesses the technical know-how, competence and resources to address these challenges. The End TB Strategy by WHO offers India an excellent blueprint to advance the agenda of TB control. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of vitamin A and vitamin C supplementation on oxidative stress in HIV and HIV-TB co-infection at Lagos University Teaching Hospital (LUTH) Nigeria.

PubMed

Makinde, Oluwamayowa; Rotimi, Kunle; Ikumawoyi, Victor; Adeyemo, Titilope; Olayemi, Sunday

2017-06-01

HIV and TB infections are both associated with elevated oxidative stress parameters. Anti-oxidant supplementation may offer beneficial effects in positively modulating oxidative stress parameters in HIV and HIV-TB infected patients. We investigated the effects of vitamin A and C supplementation on oxidative stress in HIV infected and HIV-TB co-infected subjects. 40 HIV/TB co-infected and 50 HIV mono-infected patients were divided into 2 equal groups. Participants provided demographic information and blood was collected to determine oxidative stress parameters before and after vitamin A (5000 IU) and C (2600 mg) supplementation for 1 month. There was a significantly (p < 0.05) higher level of Malondialdehyde (MDA) at baseline for HIV infected subjects compared with HIV-TB co-infected subjects. There was a significantly (p < 0.05) lower level of MDA and higher level of Catalase (CAT) in subjects administered supplementation compared to subjects without supplementation for the HIV infected group. There was a significantly lower level of Reduced Glutathione (GSH), Superoxide Dismutase (SOD) and higher level of MDA after one month of supplementation compared with baseline levels for HIV/TB co infected subjects. A similar result was also obtained for the HIV mono-infected groups which had a significantly lower level of SOD, MDA and CAT compared to the baseline. There was a significantly lower level of GSH and SOD, and higher level of MDA after supplementation compared with the baseline for HIV/TB co-infected subjects. Comparing the indices at baseline and post no-supplementation in HIV/TB co-infection showed no significant differences in the oxidative stress parameters. HIV/TB co-infection and HIV mono-infection seems to diminish the capacity of the anti-oxidant system to control oxidative stress, however exogenous anti-oxidant supplementation appears not to have beneficial roles in positively modulating the associated oxidative stress.

Barriers and outcomes: TB patients co-infected with HIV accessing antiretroviral therapy in rural Zambia.

PubMed

Chileshe, Muatale; Bond, Virginia Anne

2010-01-01

The vulnerabilities that underlie barriers faced by the rural poor whilst trying to access and adhere to "free" antiretroviral treatment (ART) demand more attention. This paper highlights barriers that poor rural Zambians co-infected with tuberculosis (TB) and HIV and their households faced in accessing ART between September 2006 and July 2007, and accounts for patient outcomes by the end of TB treatment and (more sporadically) beyond October 2009. The analysis draws on findings from wider anthropological fieldwork on the converging impact of TB, HIV and food insecurity, focusing for the purpose of this paper on ethnographic case-studies of seven newly diagnosed TB patients co-infected with HIV and their six households (one household had two TB patients). Economic barriers included being pushed into deeper poverty by managing TB, rural location, absence of any external assistance, and mustering time and extended funds for transport and "special food" during and beyond the end of TB. In the case of death, funeral costs were astronomical. Social barriers included translocation, broken marriages, a sub-ordinate household position, gender relations, denial, TB/HIV stigma and the difficulty of disclosure. Health facility barriers involved understaffing, many steps, lengthy procedures and inefficiencies (lost blood samples, electricity cuts). By the end of TB treatment, outcomes were mixed; two co-infected patients had died, three had started ART and two had yet to start ART. The three on ART underwent a striking transformation in the short term. By October 2009, two more had died and three were doing well. The study advocates nutritional support and other material support (especially transport funds) for co-infected TB patients until ART is accessed and livelihood regained. More prompt diagnosis of TB and reducing steps and increasing the reach of the ART programme in rural areas are also recommended.

Prevalence of post-traumatic stress symptoms and associated factors in tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa.

PubMed

Peltzer, Karl; Naidoo, Pamela; Matseke, Gladys; Louw, Julia; McHunu, Gugu; Tutshana, Bomkazi

2013-01-01

High rates of tuberculosis (TB) and TB/HIV co-infection is often linked with mental health issues such as post-traumatic stress disorder (PTSD) symptoms, which is further associated with poor health outcomes. In a country such as South Africa where rates of these infectious diseases are high, it is concerning that there is limited/no data on prevalence rates of mental disorders such as PTSD and its associated factors. Therefore, the aim of this study was to establish the prevalence of PTSD symptoms and associated factors in TB, TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa. Brief screening self-report tools were used to measure: PTSD symptoms, psychological distress (anxiety and depression) and alcohol misuse. Other relevant measures, such as adherence to medication, stressful life events and sexual risk-taking behaviours, were obtained through structured questions. A total of 4900 public primary care adult patients from clinics in high TB burden districts from three provinces in South Africa participated. All the patients screened positive for TB (either new or retreatment cases). The prevalence of PTSD symptoms was 29.6%. Patients who screened positive for PTSD symptoms and psychological distress were more likely to be on antidepressant medication. Factors that predicted PTSD symptoms were poverty, residing in an urban area, psychological distress, suicide attempt, alcohol and/or drug use before sex, unprotected sex, TB-HIV co-infected and the number of other chronic conditions. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of TB and HIV.

Tuberculosis epidemiology, diagnosis and infection control recommendations for dental settings: an update on the Centers for Disease Control and Prevention guidelines.

PubMed

Cleveland, Jennifer L; Robison, Valerie A; Panlilio, Adelisa L

2009-09-01

Although rates of tuberculosis (TB) in the United States have decreased in recent years, disparities in TB incidence still exist between U.S.-born and foreign-born people (people living in the United States but born outside it) and between white people and nonwhite people. In addition, the number of TB outbreaks among health care personnel and patients has decreased since the implementation of the 1994 Centers for Disease Control and Prevention (CDC) guidelines to prevent transmission of Mycobacterium tuberculosis. In this article, the authors provide updates on the epidemiology of TB, advances in TB diagnostic methods and TB infection control guidelines for dental settings. In 2008, 83 percent of all reported TB cases in the United States occurred in nonwhite people and 17 percent occurred in white people. Foreign-born people had a TB rate about 10 times higher than that of U.S.-born people. New blood assays for M. tuberculosis have been developed to diagnose TB infection and disease. Changes from the 1994 CDC guidelines incorporated into CDC's "Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005" include revised risk classifications, new TB diagnostic methods, decreased frequencies of tuberculin skin testing in various settings and changes in terminology. Although the principles of TB infection control have remained the same, the changing epidemiology of TB and the advent of new diagnostic methods for TB led to the development of the 2005 update to the 1994 guidelines. Dental health care personnel should be aware of the modifications that are pertinent to dental settings and incorporate them into their overall infection control programs.

Prevalence and Factors Associated with Tuberculosis Treatment Success among TB/HIV Co-Infection in North-East Malaysia.

PubMed

Jalal, Tengku Mardhiah Tengku; Abdullah, Sarimah; Wahab, Farhanah Abd; Dir, Sharina; Naing, Nyi Nyi

2017-12-01

One of the six strategies developed by WHO, in order to stop Tuberculosis (TB) is addressing TB/HIV high-risk groups. This study aimed to determine the prevalence of successful TB treatment and factors associated with TB treatment success among TB/HIV co-infection patients in North-East Malaysia. A cross-sectional study was carried out in the a-year period from 2003 to 2012 by reviewing TB/HIV records in all hospitals and health clinics. The outcome of interest was treatment success as defined by Ministry of Health (MOH) when the patients was cured or completed TB treatment. Out of 1510 total TB/HIV co-infection cases, 27.9% (95% CI: 25.2, 30.6) of the patients were having treatment success. A majority of TB/HIV co-infection cases were male (91.1%). Fifty-eight percent the patients were drug addicts and 6% were having positive tuberculin tests. The multiple logistic regression revealed that male (OR: 0.39, 95% CI: 0.22, 0.71) and positive tuberculin test result (OR: 2.61, 95% CI: 1.63, 4.19) were significantly associated with the treatment success of TB/HIV co-infection patients. Other factors such as age, comorbid, sputum smear and x-ray findings were not significantly factors in this study. Female patients and those with negative tuberculin test should be emphasised for successful tuberculosis treatment.

The interrelation between intestinal parasites and latent TB infections among newly resettled refugees in Texas.

PubMed

Board, Amy R; Suzuki, Sumihiro

2016-01-01

Previous research has documented that parasite infection may increase vulnerability to TB among certain at risk populations. The purpose of this study was to identify whether an association exists between latent tuberculosis infection (LTBI) and intestinal parasite infection among newly resettled refugees in Texas while controlling for additional effects of region of origin, age and sex. Data for all refugees screened for both TB and intestinal parasites between January 2010 and mid-October 2013 were obtained from the Texas Refugee Health Screening Program and were analyzed using logistic regression. A total of 9860 refugees were included. In multivariable logistic regression analysis, pathogenic and non-pathogenic intestinal parasite infections yielded statistically significant reduced odds of LTBI. However, when individual parasite species were analyzed, hookworm infection indicated statistically significant increased odds of LTBI (OR 1.674, CI: 1.126-2.488). A positive association exists between hookworm infection and LTBI in newly arrived refugees to Texas. More research is needed to assess the nature and extent of these associations. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Expansion and productive HIV-1 infection of Foxp3 positive CD4 T cells at pleural sites of HIV/TB co-infection

PubMed Central

Hirsch, Christina S; Baseke, Joy; Kafuluma, John Lusiba; Nserko, Mary; Mayanja-Kizza, Harriet; Toossi, Zahra

2016-01-01

Background CD4 T-cells expressing Foxp3 are expanded systemically during active tuberculosis (TB) regardless of HIV-1 co-infection. Foxp3+ CD4 T cells are targets of HIV-1 infection. However, expansion of HIV-1 infected Foxp3+ CD4 T cells at sites of HIV/TB co-infection, and whether they contribute to promotion of HIV-1 viral activity is not known. Methods Pleural fluid mononuclear cells (PFMC) from HIV/TB co-infected patients with pleural TB were characterized by immune-staining and FACS analysis for surface markers CD4, CD127, CCR5, CXCR4, HLA-DR and intracellular expression of Foxp3, HIVp24, IFN-γ and Bcl-2. Whole PFMC and bead separated CD4+CD25+CD127− T cells were assessed for HIV-1 LTR strong stop (SS) DNA by real-time PCR, which represents viral DNA post cell entry and initiation of reverse transcription. Results High numbers of HIV-1 p24 positive Foxp3+ and Foxp3+CD127− CD4 T cells were identified in PFMC from HIV/TB co-infected subjects. CD4+Foxp3+CD127− T cells displayed high expression of the cellular activation marker, HLA-DR. Further, expression of the HIV-1 co-receptors, CCR5 and CXCR4, were higher on CD4+Foxp3+T cells compared to CD4+Foxp3− T cells. Purified CD4+CD25+CD127− T cells isolated from PFMC of HIV/TB co-infected patients, were over 90% CD4+Foxp3+T cells, and exhibited higher HIV-1 SS DNA as compared to whole PFMC, and as compared to CD4+CD25+CD127− T cells from an HIV-infected subject with pleural mesothelioma. HIV-1 p24+ Foxp3+ CD4+T cells from HIV/TB patients higher in Bcl-2 expression as compared to both HIV-1 p24+ Foxp3− CD4 T cells, and Foxp3+ CD4+T cells without HIV-p24 expression. Conclusion Foxp3+ CD4 T cells in PFMC from HIV/TB co-infected subjects are predisposed to productive HIV-1 infection and have survival advantage as compared to Foxp3 negative CD4 T cells. PMID:28124031

Tuberculosis infection control practices in a high-burden metro in South Africa: A perpetual bane for efficient primary health care service delivery.

PubMed

Engelbrecht, Michelle C; Kigozi, Gladys; Janse van Rensburg, Andre P; Van Rensburg, Dingie H C J

2018-05-30

Tuberculosis (TB) prevention, including infection control, is a key element in the strategy to end the global TB epidemic. While effective infection control requires all health system components to function well, this is an area that has not received sufficient attention inSouth Africa despite the availability of policy and guidelines. To describe the state of implementation of TB infection control measures in a high-burden metro in South Africa. The research was undertaken in a high TB- and HIV-burdened metropolitan area of South Africa. More specifically, the study sites were primary health care facilities (PHC), thatamong other services also diagnosed TB. A cross-sectional survey, focusing on the World Health Organization levels of infection control, which included structured interviews with nurses providing TB diagnosis and treatment services as well as observations, at all 41 PHC facilities in a high TB-burdened and HIV-burdened metro of South Africa. Tuberculosis infection control was poorly implemented, with few facilities scoring 80% and above on compliance with infection control measures. Facility controls: 26 facilities (63.4%) had an infection control committee and 12 (29.3%) had a written infection control plan. Administrative controls: 26 facilities (63.4%) reported separating coughing and noncoughing patients, while observations revealed that only 11 facilities (26.8%) had separate waiting areas for (presumptive) TB patients. Environmental controls: most facilities used open windows for ventilation (n = 30; 73.2%); however, on the day of the visit, only 12 facilities (30.3%) had open windows in consulting rooms. Personal protective equipment: 9 facilities (22%) did not have any disposable respirators in stock and only 9 respondents (22%) had undergone fit testing. The most frequently reported barrier to implementing good TBinfection control practices was lack of equipment (n = 22; 40%) such as masks and disposable respirators, as well as the structure

FACTORS ASSOCIATED WITH TB/HIV CO-INFECTION AMONG DRUG SENSITIVE TUBERCULOSIS PATIENTS MANAGED IN A SECONDARY HEALTH FACILITY IN LAGOS, NIGERIA.

PubMed

Adejumo, Olusola A; Daniel, Olusoji J; Otesanya, Andrew F; Adegbola, Adebukola A; Femi-Adebayo, Temitope; Bowale, Abimbola; Adesola, Sunday; Kuku, Olugbenga O; Otemuyiwa, Kehinde O; Oladega, Shafaatu N; Johnson, Eze O; Falana, Ayodeji A; Dawodu, Olusola; Owuna, Henry; Osoba, Ganiyat; Dacosta, Adetokunbo

2017-01-01

This study assessed factors associated with TB/HIV co-infection among TB patients managed in a secondary health facility in Lagos Nigeria. A retrospective review of treatment cards of patients seen at a secondary referral hospital between January 1 2014 and December 31 2014 was conducted. Treatment outcomes and factors associated with TB/HIV co-infection were assessed. Of the 334 records of patients reviewed, the proportion of patients with TB/HIV co-infection was 21.6%. The odds of having TB/HIV co-infection was 2.7 times higher among patients above 40 years than patients less than 25 years (AOR 2.7 95% CI 1.1 - 6.5, p =0.030). In addition, the odds of having TB/HIV co-infection was 3.3 higher among extra-pulmonary TB cases (AOR 3.3; 95% CI 1.2 - 9.5; p = 0.026) and 2.1 times higher among retreated patients (AOR 2.1; 95% CI 1.1 - 3.9; p = 0.017) than pulmonary TB and new patients respectively. The chance of having TB/HIV co-infection was 2.7-fold more in patients with poor treatment outcomes than patients with treatment success (AOR 2.7; 95%CI 1.3 - 5.4; p =0.006). TB/HIV co-infection rate was high in the study area. There is need to put measures in place to improve treatment outcomes of TB/HIV co-infected patients.

FACTORS ASSOCIATED WITH TB/HIV CO-INFECTION AMONG DRUG SENSITIVE TUBERCULOSIS PATIENTS MANAGED IN A SECONDARY HEALTH FACILITY IN LAGOS, NIGERIA

PubMed Central

Adejumo, Olusola A.; Daniel, Olusoji J.; Otesanya, Andrew F.; Adegbola, Adebukola A.; Femi-Adebayo, Temitope; Bowale, Abimbola; Adesola, Sunday; Kuku, Olugbenga O.; Otemuyiwa, Kehinde O.; Oladega, Shafaatu N.; Johnson, Eze O.; Falana, Ayodeji A.; Dawodu, Olusola; Owuna, Henry; Osoba, Ganiyat; Dacosta, Adetokunbo

2017-01-01

Background: This study assessed factors associated with TB/HIV co-infection among TB patients managed in a secondary health facility in Lagos Nigeria. Materials and Methods: A retrospective review of treatment cards of patients seen at a secondary referral hospital between January 1 2014 and December 31 2014 was conducted. Treatment outcomes and factors associated with TB/HIV co-infection were assessed. Results: Of the 334 records of patients reviewed, the proportion of patients with TB/HIV co-infection was 21.6%. The odds of having TB/HIV co-infection was 2.7 times higher among patients above 40 years than patients less than 25 years (AOR 2.7 95% CI 1.1 – 6.5, p =0.030). In addition, the odds of having TB/HIV co-infection was 3.3 higher among extra-pulmonary TB cases (AOR 3.3; 95% CI 1.2 – 9.5; p = 0.026) and 2.1 times higher among retreated patients (AOR 2.1; 95% CI 1.1 – 3.9; p = 0.017) than pulmonary TB and new patients respectively. The chance of having TB/HIV co-infection was 2.7-fold more in patients with poor treatment outcomes than patients with treatment success (AOR 2.7; 95%CI 1.3 – 5.4; p =0.006). Conclusion: TB/HIV co-infection rate was high in the study area. There is need to put measures in place to improve treatment outcomes of TB/HIV co-infected patients. PMID:28670643

Assessment of the influence of direct tobacco smoke on infection and active TB management

PubMed Central

Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A.

2017-01-01

Background Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). Objective In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. Methods A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer’s instructions. Results In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs’ false-negative results (aOR: 3.35; 95%CI:1.47–7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02–3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97–22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Conclusions Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke. PMID:28837570

Assessment of the influence of direct tobacco smoke on infection and active TB management.

PubMed

Altet, Neus; Latorre, Irene; Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A; Domínguez, Jose

2017-01-01

Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer's instructions. In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs' false-negative results (aOR: 3.35; 95%CI:1.47-7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02-3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97-22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke.

Virologic and immunologic outcome of HAART in Human Immunodeficiency Virus (HIV)-1 infected patients with and without tuberculosis (TB) and latent TB infection (LTBI) in Addis Ababa, Ethiopia.

PubMed

Kassa, Desta; Gebremichael, Gebremedhin; Alemayehu, Yodit; Wolday, Dawit; Messele, Tsehaynesh; van Baarle, Debbie

2013-01-01

HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB. A total of 232 adults, including 59 HIV patients with clinical TB (HIV + TB+), 125 HIV patients without clinical TB (HIV + TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV + patients (28 TB + and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-γ responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation. The majority of HIV + TB- (70%, 81%, 84%) as well as HIV + TB + patients (60%, 77%, 80%) had virologic success (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4+ T-cell counts at 2 years in HIV + TB + (from 110.3 to 289.9 cells/μl), HIV + TB- patients (197.8 to 332.3 cells/μl), HIV + TST- (199 to 347 cells/μl) and HIV + TST + individuals (195 to 319 cells/μl). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-γ response at baseline was significantly lower in HIV + TB + (3.6 pg/ml) compared to HIV-TB + patients (34.4 pg/ml) and HIV + TST + (46.3 pg/ml) individuals; and in HIV-TB + patients compared to HIV-TST + individuals (491.2 pg/ml). By M18 on HAART, the IFN-γ response remained impaired in HIV + TB + patients (18.1 pg/ml) while it normalized in HIV + TST + individuals (from 46.3 to 414.2 pg/ml). Our data show that

Transmission of drug-susceptible and drug-resistant tuberculosis and the critical importance of airborne infection control in the era of HIV infection and highly active antiretroviral therapy rollouts.

PubMed

Shenoi, Sheela V; Escombe, A Roderick; Friedland, Gerald

2010-05-15

Comprehensive and successful tuberculosis (TB) care and treatment must incorporate effective airborne infection-control strategies. This is particularly and critically important for health care workers and all persons with or at risk of human immunodeficiency virus (HIV) infection. Past and current outbreaks and epidemics of drug-susceptible, multidrug-resistant, and extensively drug-resistant TB have been fueled by HIV infection, with high rates of morbidity and mortality and linked to the absence or limited application of airborne infection-control strategies in both resource-rich and resource-limited settings. Airborne infection-control strategies are available--grouped into administrative, environmental, and personal protection categories--and have been shown to be associated with decreases in nosocomial transmission of TB; their efficacy has not been fully demonstrated, and their implementation is extremely limited, particularly in resource-limited settings. New research and resources are required to fully realize the potential benefits of infection control in the era of TB and HIV epidemics.

Minimum package for cross-border TB control and care in the WHO European region: a Wolfheze consensus statement

PubMed Central

Dara, Masoud; de Colombani, Pierpaolo; Petrova-Benedict, Roumyana; Centis, Rosella; Zellweger, Jean-Pierre; Sandgren, Andreas; Heldal, Einar; Sotgiu, Giovanni; Jansen, Niesje; Bahtijarevic, Rankica; Migliori, Giovanni Battista

2012-01-01

The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants. A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011. Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country. The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support). PMID:22653772

Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial.

PubMed

Ruhwald, Morten; Aggerbeck, Henrik; Gallardo, Rafael Vázquez; Hoff, Søren T; Villate, José I; Borregaard, Bettine; Martinez, José A; Kromann, Ingrid; Penas, Antón; Anibarro, Luis L; de Souza-Galvão, Maria Luiza; Sánchez, Francisca; Rodrigo-Pendás, Jose Ángel; Noguera-Julian, Antoni; Martínez-Lacasa, Xavier; Tuñez, Maria Victoria; Fernández, Virginia Leiro; Millet, Joan P; Moreno, Antonio; Cobos, Nazaret; Miró, José M; Roldan, Llanos; Orcau, Angels; Andersen, Peter; Caylá, Joan A

2017-04-01

Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting. Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain. We compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT] Qiagen, Hilden, Germany) interferon γ release assay (IGRA) and the purified protein derivative (PPD) RT 23 tuberculin skin test ([TST] Statens Serum Institute). All participants older than 5 years were tested with QFT. Some participants in the negative control group received C-Tb without the TST to test for potential interactions between C-Tb and PPD RT 23. The rest were randomly assigned in blocks of ten and tested with both C-Tb and TST, with five in each block receiving injection of C-Tb in the right arm and the TST in the left arm and five vice versa. The primary and safety analyses were done in all participants randomly assigned to a group who received any test. This trial is registered with ClinicalTrials.gov, number NCT01631266, and with EudraCT, number 2011-005617-36. From July 24, 2012, to Oct 2, 2014, 979 participants were enrolled, of whom 263 were negative controls, 299 were occasional contacts, 316 were close contacts, and 101 were patients with tuberculosis. 970 (99%) participants completed the trial. Induration sizes were similar for C-Tb and TST, but TST positivity was affected by BCG vaccination status. We found a strong positive trend towards C-Tb test positivity with increasing risk of infection, from 3% in negative controls to 16% in occasional contacts, to 43% in close contacts. C-Tb and QFT results were concordant in 785 (94%) of 834 participants aged 5 years and older

Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

PubMed Central

Benjamin, Ronald; Banerjee, Atoshi; Sunder, Sharada Ramaseri; Gaddam, Sumanlatha; Valluri, Vijaya Lakshmi; Banerjee, Sharmistha

2013-01-01

Background Cytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy. Methodology/Principal Findings We analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio. Conclusion/Significance With these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse. PMID:23936398

TB & HIV: the deadly intersection.

PubMed

MacDougall, D S

1999-05-01

About 2 billion people worldwide are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB is the leading cause of premature death in less industrialized countries, and 8 million more people become infected every year. The World Health Organization (WHO) declared TB a global emergency in 1993 and launched a series of prevention and vaccination programs. In spite of effective drug therapy and a vaccine, tuberculosis remains a major public health problem. The TB and HIV epidemics are closely intertwined, and the risk of TB disease progression is 100 times greater in HIV-positive individuals. TB is the leading cause of death among HIV-infected people worldwide, and virologic evidence suggests that the host immune response to TB may enhance HIV replication and accelerate the progression of HIV infection. The interaction between the two diseases was the subject of a conference called TB & HIV: Applying Advances to the Clinic, Public Health, and the World. Charts and tables show reported TB cases in the U.S., trends in TB cases among foreign-born persons in the U.S., and the country of origin for foreign-born persons with TB in the U.S. Several poster sessions from the conference are summarized. Strategies for dealing with the TB epidemic are outlined.

Cost-effectiveness of initiating antiretroviral therapy at different points in TB treatment in HIV-TB co-infected ambulatory patients in South Africa

PubMed Central

Naidoo, Kogieleum; Grobler, Anneke C; Deghaye, Nicola; Reddy, Tarylee; Gengiah, Santhanalakshmi; Gray, Andrew; Karim, Salim Abdool

2015-01-01

Objective Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV co-infected patients. In patients with CD4+ counts <50cells/mm3, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost effectiveness of starting ART at various time points during TB treatment in patients with CD4+ counts ≥50cells/mm3. Methods In the SAPiT trial, 642 HIV-TB co-infected patients were randomized to three arms, either receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct healthcare costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. Results For patients with CD4+ count≥50cells/mm3, median monthly variable costs per patient were $116, $113 and $102 in Arms-1, -2 and -3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2 and 19 deaths in 172 patients in Arm-3. While the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Conclusions Initiation of ART after the completion of the intensive phase of TB treatment is cost effective for patients with CD4+ counts≥50cells/mm3. PMID:26167618

Effect of tuberculosis on the survival of HIV-infected men in a country with low TB incidence

PubMed Central

López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP

2010-01-01

Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866

PEPFAR support for the scaling up of collaborative TB/HIV activities.

PubMed

Howard, Andrea A; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L

2012-08-15

The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR's support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy, intensified case finding, and infection control. Issues to be addressed by future programming include accelerating implementation of isoniazid preventive therapy, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation.

PEPFAR Support for the Scaling Up of Collaborative TB/HIV Activities

PubMed Central

Howard, Andrea A.; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D.; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L.

2014-01-01

The US President’s Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR’s TB/HIV programming is based on the World Health Organization 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR’s support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy (IPT), intensified case finding and infection control. Issues to be addressed by future programming include accelerating implementation of IPT, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation. PMID:22797735

Evaluation of the Tuberculosis Infection Control Training Center, Tajikistan, 2014–2015

PubMed Central

Scott, C.; Mangan, J.; Tillova, Z.; Jensen, P. A.; Ahmedov, S.; Ismoilova, J.; Trusov, A.

2017-01-01

SUMMARY SETTING Training center on tuberculosis (TB) infection control (IC) for health care workers in the Central Asian Republics region. OBJECTIVE To assess the effects of TB IC training courses conducted at the Tuberculosis Infection Control Training Center in Machiton, Tajikistan. DESIGN Participants who participated in training (n = 89) during the first year of operation (April 2014–February 2015) were invited to participate in a post-training interview. RESULTS Of the 89 participants, 84 (94%) completed the interview and expressed satisfaction with the training. Eighty (95%) participants reported meeting with workplace leadership to discuss the training. Of these, 69 (85%) reported discussing changes required to meet TB IC standards. Self-reported changes in TB IC practices at work facilities post training included the creation of TB IC committees, designation of a TB IC focal person, TB IC planning, policies to separate infectious patients in waiting rooms, provision of masks for infectious patients, development of cough etiquette policies, improved glove availability, hand hygiene programs, and TB IC posters in waiting rooms. CONCLUSIONS Participant satisfaction and reported changes in TB IC activities illustrate the potential of these training courses to improve TB IC in the region. Future training courses may be tailored to specific audiences using a structured conceptual framework to impact administration, budgeting, and facilities management of TB IC practices. PMID:28399974

Difference Between Latent TB Infection and Active TB Disease

MedlinePlus

... chest x-ray, or positive sputum smear or culture • • Has active TB bacteria in his/her body • • Usually feels sick and may have symptoms such as coughing, fever, and weight loss • • May spread TB bacteria to others • • Needs treatment ...

Targeted screening and treatment for latent tuberculosis infection using QuantiFERON-TB Gold is cost-effective in Mexico.

PubMed

Burgos, J L; Kahn, J G; Strathdee, S A; Valencia-Mendoza, A; Bautista-Arredondo, S; Laniado-Laborin, R; Castañeda, R; Deiss, R; Garfein, R S

2009-08-01

To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective.

The strategic framework of tuberculosis control and prevention in the elderly: a scoping review towards End TB targets.

PubMed

Li, Jun; Chung, Pui-Hong; Leung, Cyrus L K; Nishikiori, Nobuyuki; Chan, Emily Y Y; Yeoh, Eng-Kiong

2017-06-01

With the rapid pace of population ageing, tuberculosis (TB) in the elderly increasingly becomes a public health challenge. Despite the increasing burden and high risks for TB in the elderly, targeted strategy has not been well understood and evaluated. We undertook a scoping review to identify current TB strategies, research and policy gaps in the elderly and summarized the results within a strategic framework towards End TB targets. Databases of Embase, MEDLINE, Global health and EBM reviews were searched for original studies, review articles, and policy papers published in English between January 1990 and December 2015. Articles examining TB strategy, program, guideline or intervention in the elderly from public health perspective were included.Nineteen articles met the inclusion criteria. Most of them were qualitative studies, issued in high- and middle-income countries and after 2000. To break the chain of TB transmission and reactivation in the elderly, infection control, interventions of avoiding delay in diagnosis and containment are essential for preventing transmission, especially in elderly institutions and aged immigrants; screening of latent TB infection and preventive therapy had effective impacts on reducing the risk of reactivation and should be used less reluctantly in older people; optimizing early case-finding with a high index of suspicion, systematic screening for prioritized high-risk groups, initial empirical and adequate follow-up treatment with close monitoring and evaluation, as well as enhanced programmatic management are fundamental pillars for active TB elimination. Evaluation of TB epidemiology, risk factors, impacts and cost-effectiveness of interventions, adopting accurate and rapid diagnostic tools, shorter and less toxic preventive therapy, are critical issues for developing strategy in the elderly towards End TB targets.TB control strategies in the elderly were comprehensively mapped in a causal link pathway. The framework and

Infection control, genetic assessment of drug resistance and drug susceptibility testing in the current management of multidrug/extensively-resistant tuberculosis (M/XDR-TB) in Europe: A tuberculosis network European Trialsgroup (TBNET) study.

PubMed

Bothamley, Graham H; Lange, Christoph

2017-11-01

Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. TBNET is a pan-European clinical research collaboration for tuberculosis. An email survey of TBNET members collected data in relation to infection control, access to molecular tests and basic microbiology with drug sensitivity testing. 68/105 responses gave valid information and were from countries within the WHO European Region. Inpatient beds matched demand, but single rooms with negative pressure were only available in low incidence countries; ultraviolet decontamination was used in 5 sites, all with >10 patients with M/XDR-TB per year. Molecular tests for mutations associated with rifampicin resistance were widely available (88%), even in lower income and especially in high incidence countries. Molecular tests for other first line and second line drugs were less accessible (76 and 52% respectively). A third of physicians considered that drug susceptibility results were delayed by > 2 months. Infection control for inpatients with M/XDR-TB remains a problem in high incidence countries. Rifampicin resistance is readily detected, but tests to plan regimens tailored to the drug susceptibilities of the strain of Mycobacterium tuberculosis are significantly delayed, allowing for further drug resistance to develop. Copyright © 2017 Elsevier Ltd. All rights reserved.

Towards understanding the drivers of policy change: a case study of infection control policies for multi-drug resistant tuberculosis in South Africa.

PubMed

Saidi, Trust; Salie, Faatiema; Douglas, Tania S

2017-05-30

Explaining policy change is one of the central tasks of contemporary policy analysis. In this article, we examine the changes in infection control policies for multi-drug resistant tuberculosis (MDR-TB) in South Africa from the time the country made the transition to democracy in 1994, until 2015. We focus on MDR-TB infection control and refer to decentralised management as a form of infection control. Using Kingdon's theoretical framework of policy streams, we explore the temporal ordering of policy framework changes. We also consider the role of research in motivating policy changes. Policy documents addressing MDR-TB in South Africa over the period 1994 to 2014 were extracted. Literature on MDR-TB infection control in South Africa was extracted from PubMed using key search terms. The documents were analysed to identify the changes that occurred and the factors driving them. During the period under study, five different policy frameworks were implemented. The policies were meant to address the overwhelming challenge of MDR-TB in South Africa, contextualised by high prevalence of HIV infection, that threatened to undermine public health programmes and the success of antiretroviral therapy rollouts. Policy changes in MDR-TB infection control were supported by research evidence and driven by the high incidence and complexity of the disease, increasing levels of dissatisfaction among patients, challenges of physical, human and financial resources in public hospitals, and the ideologies of the political leadership. Activists and people living with HIV played an important role in highlighting the importance of MDR-TB as well as exerting pressure on policymakers, while the mass media drew public attention to infection control as both a cause of and a solution to MDR-TB. The critical factors for policy change for infection control of MDR-TB in South Africa were rooted in the socioeconomic and political environment, were supported by extensive research, and can be framed

Multidrug-Resistant Tuberculosis (MDR TB)

MedlinePlus

... prisons, or homeless shelters. If you work in hospitals or health-care settings where TB patients are likely to be seen, you should consult infection control or occupational health experts. Ask about administrative and ...

Infection control in households of drug-resistant tuberculosis patients co-infected with HIV in Mumbai, India.

PubMed

Albuquerque, T; Isaakidis, P; Das, M; Saranchuk, P; Andries, A; Misquita, D P; Khan, S; Dubois, S; Peskett, C; Browne, M

2014-03-21

Mumbai has a population of 21 million, and an increasingly recognised epidemic of drug-resistant tuberculosis (DR-TB). To describe TB infection control (IC) measures implemented in households of DR-TB patients co-infected with the human immunodeficiency virus (HIV) under a Médecins Sans Frontières programme. IC assessments were carried out in patient households between May 2012 and March 2013. A simplified, standardised assessment tool was utilised to assess the risk of TB transmission and guide interventions. Administrative, environmental and personal protective measures were tailored to patient needs. IC assessments were carried out in 29 houses. Measures included health education, segregating sleeping areas of patients, improving natural ventilation by opening windows, removing curtains and obstacles to air flow, installing fans and air extractors and providing surgical masks to patients for limited periods. Environmental interventions were carried out in 22 houses. TB IC could be a beneficial component of a comprehensive TB and HIV care programme in households and communities. Although particularly challenging in slum settings, IC measures that are feasible, affordable and acceptable can be implemented in such settings using simplified and standardised tools. Appropriate IC interventions at household level may prevent new cases of DR-TB, especially in households of patients with a lower chance of cure.

Malnutrition associated with unfavorable outcome and death among South African MDR-TB and HIV co-infected children.

PubMed

Hicks, R M; Padayatchi, N; Shah, N S; Wolf, A; Werner, L; Sunkari, V B; O'Donnell, M R

2014-09-01

Pediatric multidrug-resistant tuberculosis (MDR-TB) is complicated by difficult diagnosis, complex treatment, and high mortality. In South Africa, these challenges are amplified by human immunodeficiency virus (HIV) co-infection; however, evidence on treatment outcomes among co-infected children is limited. Using conventional and new pediatric definitions, to describe treatment outcomes and identify risk factors for unfavorable outcome and mortality in children aged <15 years with MDR-TB or extensively drug-resistant TB (XDR-TB) in KwaZulu-Natal, South Africa. Retrospective cohort study in a regional TB referral hospital. From January 2009 to June 2010, 84 children (median age 8 years, IQR 4-12) with MDR-TB (n = 78) or XDR-TB (n = 6) initiated treatment. Sixty-four (77%) were HIV-positive and 62 (97%) received antiretroviral therapy. Sixty-six (79%) achieved favorable treatment outcomes. Overall mortality was 11% (n = 9) at 18 months after initiation of treatment. Malnutrition (aOR 27.4, 95%CI 2.7-278.7) and severe radiographic findings (aOR 4.68, 95%CI 1.01-21.9) were associated with unfavorable outcome. New pediatric outcome definitions increased the proportion classified as cured. It is possible to successfully treat pediatric MDR-TB-HIV even in resource-poor settings. Malnutrition is a marker for severe TB-HIV disease, and is a potential target for future interventions in these patients.

Targeted screening and treatment for latent tuberculosis infection using QuantiFERON®-TB Gold is cost-effective in Mexico

PubMed Central

Burgos, J. L.; Kahn, J. G.; Strathdee, S. A.; Valencia-Mendoza, A.; Bautista-Arredondo, S.; Laniado-Laborin, R.; Castañeda, R.; Deiss, R.; Garfein, R. S.

2009-01-01

SUMMARY OBJECTIVE To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON®-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective. PMID:19723375

Barriers and motivators affecting tuberculosis infection control practices of Russian health care workers.

PubMed

Woith, W; Volchenkov, G; Larson, J

2012-08-01

Five in-patient and out-patient tuberculosis (TB) care facilities in two regions of Russia. To identify barriers and motivators to the use of infection control measures among Russian TB health care workers. In this qualitative study, a convenience sample of 96 health care workers (HCWs) was used to generate 15 homogeneous focus groups, consisting of physicians, nurses, and laboratory or support staff. Barriers and motivators related to knowledge, attitudes and beliefs, and practices were identified. The three main barriers were 1) knowledge deficits, including the belief that TB was transmitted by dust, linens and eating utensils; 2) negative attitudes related to the discomfort of respirators; and 3) practices with respect to quality and care of respirators. Education and training, fear of infecting loved ones, and fear of punishment were the main motivators. Our results point to the need for evaluation of current educational programs. Positive health promotion messages that appeal to fear might also be successful in promoting TB infection control. Individualized rewards based on personal motivators or group rewards that build on collectivist theory could be explored.

[Human resource capacity building on TB laboratory work for TB control program--through the experience of international TB laboratory training course for TB control at the Research Institute of Tuberculosis, JATA, Japan].

PubMed

Fujiki, Akiko; Kato, Seiya

2008-06-01

The international training course on TB laboratory work for national tuberculosis program (NTP) has been conducted at the Research Institute of Tuberculosis since 1975 funded by Japan International Cooperation Agency in collaboration with WHO Western Pacific Regional Office. The aim of the course is to train key personnel in TB laboratory field for NTP in resource-limited countries. The course has trained 265 national key personnel in TB laboratory service from 57 resource-limited countries in the last 33 years. The number of participants trained may sound too small in the fight against the large TB problem in resource-limited countries. However, every participant is playing an important role as a core and catalyst for the TB control program in his/her own country when they were back home. The curriculum is composed of technical aspects on TB examination, mainly sputum microscopy in addition since microscopy service is provided at many centers that are deployed in a widely spread area, the managerial aspect of maintaining quality TB laboratory work at the field laboratory is another component of the curriculum. Effective teaching methods using materials such as artificial sputum, which is useful for panel slide preparation, and technical manuals with illustrations and pictures of training procedure have been developed through the experience of the course. These manuals are highly appreciated and widely used by the front line TB workers. The course has also contributed to the expansion of EQA (External Quality Assessment) system on AFB microscopy for the improvement of the quality of TB laboratory service of NTP. The course is well-known for not only having a long history, but also for its unique learning method emphasizing "Participatory Training", particularly for practicum sessions to master the skills on AFB microscopy. The method in learning AFB microscopy, which was developed by the course, was published as a training manual by IUATLD, RIT and USAID. As it is

Cough Due to TB and Other Chronic Infections: CHEST Guideline and Expert Panel Report.

PubMed

Field, Stephen K; Escalante, Patricio; Fisher, Dina A; Ireland, Belinda; Irwin, Richard S

2018-02-01

Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost-effective screening, potentially limiting disease progression and preventing transmission to others. A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks' duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]-endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom-based screening remains low, the negative predictive value of the WHO-endorsed symptom screen in PLWHIV may help to risk-stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource-limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO-endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost-effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost-effective than

Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

PubMed

Takasaki, Jin; Manabe, Toshie; Morino, Eriko; Muto, Yoshikazu; Hashimoto, Masao; Iikura, Motoyasu; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro

2018-03-01

The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Toward a Generation Free of Tuberculosis: TB Disease and Infection in Individuals of College Age in the United States

ERIC Educational Resources Information Center

Shah, N. S.; Flood-Bryzman, A.; Jeffries, C.; Scott, J.

2018-01-01

Objectives: To assess the magnitude of active TB disease and latent TB infection (LTBI) in young adults of college age. Participants: Individuals who were aged 18-24 years in 2011 were used as a proxy for college students. Methods: Active TB cases reported to the 2011 US National TB Surveillance System (NTSS) were included. LTBI prevalence was…

Outbreak column 21: Tuberculosis (TB): Still a nosocomial threat.

PubMed

Curran, Evonne T

2018-05-01

This outbreak column explores the epidemiology and infection prevention guidance on tuberculosis (TB) in the UK. The column finds that, at present, national guidance leaves UK hospitals ill-prepared to prevent nosocomial TB transmission. Reasons for this conclusion are as follows: (1) while TB is predominantly a disease that affects people with 'social ills', it has the potential to infect anyone who is sufficiently exposed; (2) nosocomial transmission is documented throughout history; (3) future nosocomial exposures may involve less treatable disease; and (4) current UK guidance is insufficient to prevent nosocomial transmission and is less than that advocated by the World Health Organization and the Centers for Disease Control and Prevention.

Wind-driven roof turbines: a novel way to improve ventilation for TB infection control in health facilities.

PubMed

Cox, Helen; Escombe, Rod; McDermid, Cheryl; Mtshemla, Yolanda; Spelman, Tim; Azevedo, Virginia; London, Leslie

2012-01-01

Tuberculosis transmission in healthcare facilities contributes significantly to the TB epidemic, particularly in high HIV settings. Although improving ventilation may reduce transmission, there is a lack of evidence to support low-cost practical interventions. We assessed the efficacy of wind-driven roof turbines to achieve recommended ventilation rates, compared to current recommended practices for natural ventilation (opening windows), in primary care clinic rooms in Khayelitsha, South Africa. Room ventilation was assessed (CO₂ gas tracer technique) in 4 rooms where roof turbines and air-intake grates were installed, across three scenarios: turbine, grate and window closed, only window open, and only turbine and grate open, with concurrent wind speed measurement. 332 measurements were conducted over 24 months. For all 4 rooms combined, median air changes per hour (ACH) increased with wind speed quartiles across all scenarios. Higher median ACH were recorded with open roof turbines and grates, compared to open windows across all wind speed quartiles. Ventilation with open turbine and grate exceeded WHO-recommended levels (60 Litres/second/patient) for 95% or more of measurements in 3 of the 4 rooms; 47% in the remaining room, where wind speeds were lower and a smaller diameter turbine was installed. High room ventilation rates, meeting recommended thresholds, may be achieved using wind-driven roof turbines and grates, even at low wind speeds. Roof turbines and air-intake grates are not easily closed by staff, allowing continued ventilation through colder periods. This simple, low-cost technology represents an important addition to our tools for TB infection control.

Wind-Driven Roof Turbines: A Novel Way to Improve Ventilation for TB Infection Control in Health Facilities

PubMed Central

Cox, Helen; Escombe, Rod; McDermid, Cheryl; Mtshemla, Yolanda; Spelman, Tim; Azevedo, Virginia; London, Leslie

2012-01-01

Objective Tuberculosis transmission in healthcare facilities contributes significantly to the TB epidemic, particularly in high HIV settings. Although improving ventilation may reduce transmission, there is a lack of evidence to support low-cost practical interventions. We assessed the efficacy of wind-driven roof turbines to achieve recommended ventilation rates, compared to current recommended practices for natural ventilation (opening windows), in primary care clinic rooms in Khayelitsha, South Africa. Methods Room ventilation was assessed (CO2 gas tracer technique) in 4 rooms where roof turbines and air-intake grates were installed, across three scenarios: turbine, grate and window closed, only window open, and only turbine and grate open, with concurrent wind speed measurement. 332 measurements were conducted over 24 months. Findings For all 4 rooms combined, median air changes per hour (ACH) increased with wind speed quartiles across all scenarios. Higher median ACH were recorded with open roof turbines and grates, compared to open windows across all wind speed quartiles. Ventilation with open turbine and grate exceeded WHO-recommended levels (60 Litres/second/patient) for 95% or more of measurements in 3 of the 4 rooms; 47% in the remaining room, where wind speeds were lower and a smaller diameter turbine was installed. Conclusion High room ventilation rates, meeting recommended thresholds, may be achieved using wind-driven roof turbines and grates, even at low wind speeds. Roof turbines and air-intake grates are not easily closed by staff, allowing continued ventilation through colder periods. This simple, low-cost technology represents an important addition to our tools for TB infection control. PMID:22253742

Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test.

PubMed

Altet-Gómez, N; De Souza-Galvao, M; Latorre, I; Milà, C; Jiménez, M A; Solsona, J; Cantos, A; Zamora, J J; Ruiz-Manzano, J; Ausina, V; Domínguez, J

2011-05-01

The aim of the present study was to compare the performance of the interferon (IFN)-γ tests (QuantiFERON®-TB Gold In-Tube (QFT-G-IT) and T-SPOT®.TB) with the tuberculin skin test (TST) in diagnosing tuberculosis (TB) infection in children, and to analyse discordant results. This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations ≥ 5 mm recruited during public health screenings. Positive IFN-γ tests results were associated with risk of exposure (p<0.0001). T-SPOT.TB was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against Mycobacterium avium were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5-9 mm in diameter and both IFN-γ tests negative. In concordant IFN-γ tests results, a positive correlation was found (p = 0.0001) between the number of responding cells and the amount of IFN-γ released. However, in discordant IFN-γ tests results this correlation was negative (p = 0.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-γ released. The use of IFN-γ tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.

Potential Function of Granulysin, Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

PubMed Central

Pitabut, Nada; Sakurada, Shinsaku; Tanaka, Takahiro; Ridruechai, Chutharut; Tanuma, Junko; Aoki, Takahiro; Kantipong, Pacharee; Piyaworawong, Surachai; Kobayashi, Nobuyuki; Dhepakson, Panadda; Yanai, Hideki; Yamada, Norio; Oka, Shinichi; Okada, Masaji; Khusmith, Srisin; Keicho, Naoto

2013-01-01

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy. Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9+Vδ2+ T cells, CD4+ T cells and CD8+ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection. Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry. Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8+ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed. Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection. PMID:23801887

Mycobacterium tuberculosis Cell Wall released Fragments by the Action of the Human Lung Mucosa modulate Macrophages to Control Infection in a IL-10 Dependent Manner

PubMed Central

Arcos, Jesus; Sasindran, Smitha J.; Moliva, Juan I.; Scordo, Julia M.; Sidiki, Sabeen; Guo, Hui; Venigalla, Poornima; Kelley, Holden V.; Lin, Guoxin; Diangelo, Lauren; Silwani, Sayeed N.; Zhang, Jian; Turner, Joanne; Torrelles, Jordi B.

2016-01-01

Mycobacterium tuberculosis (M.tb) , the causative agent of tuberculosis, is a major public health challenge facing the world. During infection, M.tb is deposited in the lung alveolar space where it comes in contact with the lung mucosa, known as alveolar lining fluid (ALF), an environment that M.tb encounters at different stages of the infection and disease. ALF is abundant in homeostatic and antimicrobial hydrolytic enzymes, also known as hydrolases. Here we demonstrate that ALF hydrolases, at their physiological concentrations and upon contact with M.tb, release M.tb cell envelope fragments into the milieu. These released fragments are bioactive, but non-cytotoxic, regulate the function of macrophages, and thus are capable of modulating the immune response contributing to the control of M.tb infection by human macrophages. Specifically, macrophages exposed to fragments derived from the exposure of M.tb to ALF were able to control the infection primarily by increasing phagosome-lysosome fusion and acidification events. This enhanced control was found to be dependent on fragment induced IL-10 production but also involves the STAT3 signaling pathway in an IL-10 independent manner. Collectively our data indicate that M.tb fragments released upon contact with lung mucosa hydrolases participate in the host immune response to M.tb infection through innate immune modulation. PMID:28000679

Epidemiology of HIV-TB in Asia.

PubMed

Narain, Jai P; Lo, Ying-Ru

2004-10-01

Tuberculosis (TB) has, for centuries, continued to remain a public health problem of enormous importance, particularly in the developing world, taking a heavy toll of those at their prime of life. The emergence of human immunodeficiency virus (HIV infection) and its close association with TB poses an even greater challenge to the health systems in general and TB programmes in particular, in African and Asian countries. HIV is considered to be the most potent risk factor for progression to active TB among those infected both with TB and HIV; as a result, TB is the most common life threatening opportunistic infection associated with HIV, and biggest cause of death among patients with acquired immunodeficiency syndrome (AIDS). In areas hard-hit by HIV, TB is increasing, leading to greater case load, thereby overstretching the already fragile health infrastructure. The deadly relationship between HIV and TB, each potentiating the effect of the other, requires a clearly defined strategy taking into consideration the natural history of the co-infection and its progression to clinical TB (and AIDS). It is clear that the only way to fight this is by bringing the two programmes to join forces and work creatively and innovatively. The strategy should include not only preventing HIV through community-based behavioural interventions and limiting progression to clinical TB through the use of isoniazid preventive therapy, but also early diagnosis and treatment of HIV-associated TB and AIDS using DOTS strategy and combination antiretroviral therapy respectively. The strategy probably would not succeed unless both the programmes are first strengthened before attempting to forge collaboration based on mutual strengths and comparative advantages. In addition, mobilizing national and international response, building partnerships and mobilizing resources will help a great deal in mounting an appropriate and effective response to HIV/TB in the Asian context.

Technology and tuberculosis control: the OUT-TB Web experience.

PubMed

Guthrie, Jennifer L; Alexander, David C; Marchand-Austin, Alex; Lam, Karen; Whelan, Michael; Lee, Brenda; Furness, Colin; Rea, Elizabeth; Stuart, Rebecca; Lechner, Julia; Varia, Monali; McLean, Jennifer; Jamieson, Frances B

2017-04-01

Develop a tool to disseminate integrated laboratory, clinical, and demographic case data necessary for improved contact tracing and outbreak detection of tuberculosis (TB). In 2007, the Public Health Ontario Laboratories implemented a universal genotyping program to monitor the spread of TB strains within Ontario. Ontario Universal Typing of TB (OUT-TB) Web utilizes geographic information system (GIS) technology with a relational database platform, allowing TB control staff to visualize genotyping matches and microbiological data within the context of relevant epidemiological and demographic data. OUT-TB Web is currently available to the 8 health units responsible for >85% of Ontario's TB cases and is a valuable tool for TB case investigation. Users identified key features to implement for application enhancements, including an e-mail alert function, customizable heat maps for visualizing TB and drug-resistant cases, socioeconomic map layers, a dashboard providing TB surveillance metrics, and a feature for animating the geographic spread of strains over time. OUT-TB Web has proven to be an award-winning application and a useful tool. Developed and enhanced using regular user feedback, future versions will include additional data sources, enhanced map and line-list filter capabilities, and development of a mobile app. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Associated factors for treatment delay in pulmonary tuberculosis in HIV-infected individuals: a nested case-control study.

PubMed

Coimbra, Isabella; Maruza, Magda; Militão-Albuquerque, Maria de Fátima Pessoa; Moura, Líbia Vilela; Diniz, George Tadeu Nunes; Miranda-Filho, Demócrito de Barros; Lacerda, Heloísa Ramos; Rodrigues, Laura Cunha; Ximenes, Ricardo Arraes de Alencar

2012-09-07

The delay in initiating treatment for tuberculosis (TB) in HIV-infected individuals may lead to the development of a more severe form of the disease, with higher rates of morbidity, mortality and transmissibility. The aim of the present study was to estimate the time interval between the onset of symptoms and initiating treatment for TB in HIV-infected individuals, and to identify the factors associated to this delay. A nested case-control study was undertaken within a cohort of HIV-infected individuals, attended at two HIV referral centers, in the state of Pernambuco, Brazil. Delay in initiating treatment for TB was defined as the period of time, in days, which was greater than the median value between the onset of cough and initiating treatment for TB. The study analyzed biological, clinical, socioeconomic, and lifestyle factors as well as those related to HIV and TB infection, potentially associated to delay. The odds ratios were estimated with the respective confidence intervals and p-values. From a cohort of 2365 HIV-infected adults, 274 presented pulmonary TB and of these, 242 participated in the study. Patients were already attending 2 health services at the time they developed a cough (period range: 1 - 552 days), with a median value of 41 days. Factors associated to delay were: systemic symptoms asthenia, chest pain, use of illicit drugs and sputum smear-negative. The present study indirectly showed the difficulty of diagnosing TB in HIV-infected individuals and indicated the need for a better assessment of asthenia and chest pain as factors that may be present in co-infected patients. It is also necessary to discuss the role played by negative sputum smear results in diagnosing TB/HIV co-infection as well as the need to assess the best approach for drug users with TB/HIV.

Healthcare workers' challenges in the implementation of tuberculosis infection prevention and control measures in Mozambique.

PubMed

Brouwer, Miranda; Coelho, Eliana; Mosse, Carla das Dores; Brondi, Luciana; Winterton, Laura; van Leth, Frank

2014-01-01

Healthcare Workers (HCWs) have a higher frequency of TB exposure than the general population and have therefore an occupational TB risk that infection prevention and control (IPC) measures aim to reduce. HCWs are crucial in the implementation of these measures. The objective of the study was to investigate Mozambican HCWs' perceptions of their occupational TB risk and the measures they report using to reduce this risk. In addition, we explored the challenges HCWs encounter while using these TBIPC measures. Focus group discussion. Analysis according content method. Four categories of HCWs: auxiliary workers, medical (doctors and clinical officers), nurses and TB program staff. HCWs are aware of their occupational TB risk and use various measures to reduce their risk of infection. HCWs find it challenging to employ measures that minimize such risks and a lack of clear guidelines contributes to these challenges. HCWs' and patient behavior further complicate the use of TBIPC measures. HCWs in Mozambique perceive a high occupational risk of TB infection. They report several challenges using measures to reduce this risk such as shortage of material, lack of clear guidelines, insufficient motivation and inadequate training. Robust training with motivational approaches, alongside supervision and support for HCWs could improve implementation of TBIPC measures. Healthcare management should address the areas for improvement that are beyond the individual HCW's control.

46 CFR 30.10-19a - Control space-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Control space-TB/ALL. 30.10-19a Section 30.10-19a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-19a Control space—TB/ALL. The term control space means an enclosed space in which is located a ship's...

46 CFR 30.10-19a - Control space-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Control space-TB/ALL. 30.10-19a Section 30.10-19a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-19a Control space—TB/ALL. The term control space means an enclosed space in which is located a ship's...

46 CFR 30.10-19a - Control space-TB/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Control space-TB/ALL. 30.10-19a Section 30.10-19a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-19a Control space—TB/ALL. The term control space means an enclosed space in which is located a ship's...

46 CFR 30.10-19a - Control space-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Control space-TB/ALL. 30.10-19a Section 30.10-19a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-19a Control space—TB/ALL. The term control space means an enclosed space in which is located a ship's...

46 CFR 30.10-19a - Control space-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Control space-TB/ALL. 30.10-19a Section 30.10-19a Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-19a Control space—TB/ALL. The term control space means an enclosed space in which is located a ship's...

OSHA TB standard adds teeth to CDC guidelines. Occupational Safety and Health Administration. Centers for Disease Control and Prevention.

PubMed

1997-12-01

The Occupational Safety and Health Administration (OSHA) has published a proposed standard to provide health care workers with more protection against tuberculosis (TB). With one-quarter of new TB cases occurring in HIV-infected people, 5.3 million workers treating AIDS patients and working with at-risk populations need to be aware of the proposed guidelines. OSHA estimates that the new standard could eliminate most work-related TB infections and save up to $116 million in medical costs and lost production. The OSHA standards vary from those of the Centers for Disease Control (CDC) in several ways. CDC guidelines are voluntary, whereas OSHA standards are enforceable and facilities can be fined for violations. Although OSHA standards have incorporated basic elements of the CDC recommendations, OSHA standards also would require employers to conduct exposure assessments, require six-month skin testing, and call for respirator use in more instances. OSHA officials expect broad participation at public hearings on the new standard, scheduled to begin in February 1998.

Effectiveness of TB sensitization initiatives in improving the involvement of self help group members in rural TB control in south India.

PubMed

Thomas, Beena; Priscilla Rebecca, B; Dhanalakshmi, A; Rani, S; Deepa Lakshmi, A; Watson, Basilea; Vijayalakshmi, R; Muniyandi, M; Karikalan, N

2016-12-01

The 'End TB strategy' has highlighted the importance of inter-sectoral collaboration and community mobilization for achieving zero TB deaths by 2020. The aim of the study was to develop and test a model TB sensitization programme involving self help groups (SHGs). This experimental study was conducted in two blocks (intervention and control), in Tiruvallur district. The intervention content included short-lecture, musical story telling activity, role play, short film on TB. The impact was compared at baseline, third and sixth months in terms of SHGs' awareness, promotion of awareness, identification and referral of presumptive TB cases and provision of TB treatment. A total of 764 vs 796 SHGs were enrolled in control and intervention groups, respectively. The knowledge attitude, and practice score (lower score indicated a better attitude and practice), from baseline to 6 months was significantly reduced (29 to 24) in the intervention group. Similarly, a significant difference was observed in identification and referral of chest symptomatics in the intervention group at 3 and 6 months. During the 3 month follow-up a significantly higher proportion of SHG members were involved in TB awareness activities in the intervention (623/748 [83.3%]) vs control group (471/728 [64.7%]; p<0.001). Findings from this study highlight the feasibility of involving SHGs through a model TB sensitization program for strengthening TB prevention and control activities. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

PubMed

Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

2016-01-01

India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A Qualitative Study

PubMed Central

Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.

2014-01-01

Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523

Quantitative genetic analysis of the bTB diagnostic single intradermal comparative cervical test (SICCT).

PubMed

Tsairidou, Smaragda; Brotherstone, Susan; Coffey, Mike; Bishop, Stephen C; Woolliams, John A

2016-11-24

Bovine tuberculosis (bTB) is a disease of significant economic importance and is a persistent animal health problem with implications for public health worldwide. Control of bTB in the UK has relied on diagnosis through the single intradermal comparative cervical test (SICCT). However, limitations in the sensitivity of this test hinder successful eradication and the control of bTB remains a major challenge. Genetic selection for cattle that are more resistant to bTB infection can assist in bTB control. The aim of this study was to conduct a quantitative genetic analysis of SICCT measurements collected during bTB herd testing. Genetic selection for bTB resistance will be partially informed by SICCT-based diagnosis; therefore it is important to know whether, in addition to increasing bTB resistance, this might also alter genetically the epidemiological characteristics of SICCT. Our main findings are that: (1) the SICCT test is robust at the genetic level, since its hierarchy and comparative nature provide substantial protection against random genetic changes that arise from genetic drift and from correlated responses among its components due to either natural or artificial selection; (2) the comparative nature of SICCT provides effective control for initial skin thickness and age-dependent differences; and (3) continuous variation in SICCT is only lowly heritable and has a weak correlation with SICCT positivity among healthy animals which was not significantly different from zero (P > 0.05). These emerging results demonstrate that genetic selection for bTB resistance is unlikely to change the probability of correctly identifying non-infected animals, i.e. the test's specificity, while reducing the overall number of cases. This study cannot exclude all theoretical risks from selection on resistance to bTB infection but the role of SICCT in disease control is unlikely to be rapidly undermined, with any adverse correlated responses expected to be weak and slow, which

Effect of glycemic control and type of diabetes treatment on unsuccessful TB treatment outcomes among people with TB-Diabetes: A systematic review

PubMed Central

Jeyashree, Kathiresan; Mahajan, Preetam; Shah, Amar N.; Kirubakaran, Richard; Rao, Raghuram; Kumar, Ajay M. V.

2017-01-01

Background Stringent glycemic control by using insulin as a replacement or in addition to oral hypoglycemic agents (OHAs) has been recommended for people with tuberculosis and diabetes mellitus (TB-DM). This systematic review (PROSPERO 2016:CRD42016039101) analyses whether this improves TB treatment outcomes. Objectives Among people with drug-susceptible TB and DM on anti-TB treatment, to determine the effect of i) glycemic control (stringent or less stringent) compared to poor glycemic control and ii) insulin (only or with OHAs) compared to ‘OHAs only’ on unsuccessful TB treatment outcome(s). We looked for unfavourable TB treatment outcomes at the end of intensive phase and/or end of TB treatment (minimum six months and maximum 12 months follow up). Secondary outcomes were development of MDR-TB during the course of treatment, recurrence after 6 months and/or after 1 year post successful treatment completion and development of adverse events related to glucose lowering treatment (including hypoglycemic episodes). Methods All interventional studies (with comparison arm) and cohort studies on people with TB-DM on anti-TB treatment reporting glycemic control, DM treatment details and TB treatment outcomes were eligible. We searched electronic databases (EMBASE, PubMed, Google Scholar) and grey literature between 1996 and April 2017. Screening, data extraction and risk of bias assessment were done independently by two investigators and recourse to a third investigator, for resolution of differences. Results After removal of duplicates from 2326 identified articles, 2054 underwent title and abstract screening. Following full text screening of 56 articles, nine cohort studies were included. Considering high methodological and clinical heterogeneity, we decided to report the results qualitatively and not perform a meta-analysis. Eight studies dealt with glycemic control, of which only two were free of the risk of bias (with confounder-adjusted measures of effect). An

Effect of glycemic control and type of diabetes treatment on unsuccessful TB treatment outcomes among people with TB-Diabetes: A systematic review.

PubMed

Shewade, Hemant Deepak; Jeyashree, Kathiresan; Mahajan, Preetam; Shah, Amar N; Kirubakaran, Richard; Rao, Raghuram; Kumar, Ajay M V

2017-01-01

Stringent glycemic control by using insulin as a replacement or in addition to oral hypoglycemic agents (OHAs) has been recommended for people with tuberculosis and diabetes mellitus (TB-DM). This systematic review (PROSPERO 2016:CRD42016039101) analyses whether this improves TB treatment outcomes. Among people with drug-susceptible TB and DM on anti-TB treatment, to determine the effect of i) glycemic control (stringent or less stringent) compared to poor glycemic control and ii) insulin (only or with OHAs) compared to 'OHAs only' on unsuccessful TB treatment outcome(s). We looked for unfavourable TB treatment outcomes at the end of intensive phase and/or end of TB treatment (minimum six months and maximum 12 months follow up). Secondary outcomes were development of MDR-TB during the course of treatment, recurrence after 6 months and/or after 1 year post successful treatment completion and development of adverse events related to glucose lowering treatment (including hypoglycemic episodes). All interventional studies (with comparison arm) and cohort studies on people with TB-DM on anti-TB treatment reporting glycemic control, DM treatment details and TB treatment outcomes were eligible. We searched electronic databases (EMBASE, PubMed, Google Scholar) and grey literature between 1996 and April 2017. Screening, data extraction and risk of bias assessment were done independently by two investigators and recourse to a third investigator, for resolution of differences. After removal of duplicates from 2326 identified articles, 2054 underwent title and abstract screening. Following full text screening of 56 articles, nine cohort studies were included. Considering high methodological and clinical heterogeneity, we decided to report the results qualitatively and not perform a meta-analysis. Eight studies dealt with glycemic control, of which only two were free of the risk of bias (with confounder-adjusted measures of effect). An Indian study reported 30% fewer

Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

PubMed Central

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients. PMID:26075241

Immunoendocrine interactions during HIV-TB coinfection: implications for the design of new adjuvant therapies.

PubMed

Suarez, Guadalupe Veronica; Vecchione, Maria Belen; Angerami, Matias Tomas; Sued, Omar; Bruttomesso, Andrea Claudia; Bottasso, Oscar Adelmo; Quiroga, Maria Florencia

2015-01-01

Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB) and human immunodeficiency virus (HIV). In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.

Optimal Control for TB disease with vaccination assuming endogeneous reactivation and exogeneous reinfection

NASA Astrophysics Data System (ADS)

Anggriani, N.; Wicaksono, B. C.; Supriatna, A. K.

2016-06-01

Tuberculosis (TB) is one of the deadliest infectious disease in the world which caused by Mycobacterium tuberculosis. The disease is spread through the air via the droplets from the infectious persons when they are coughing. The World Health Organization (WHO) has paid a special attention to the TB by providing some solution, for example by providing BCG vaccine that prevent an infected person from becoming an active infectious TB. In this paper we develop a mathematical model of the spread of the TB which assumes endogeneous reactivation and exogeneous reinfection factors. We also assume that some of the susceptible population are vaccinated. Furthermore we investigate the optimal vaccination level for the disease.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project.

PubMed

Merle, Corinne S C; Sismanidis, Charalambos; Sow, Oumou Bah; Gninafon, Martin; Horton, John; Lapujade, Olivier; Lo, Mame Bocar; Mitchinson, Denis A; Perronne, Christian; Portaels, Francoise; Odhiambo, Joseph; Olliaro, Piero; Rustomjee, Roxana; Lienhardt, Christian; Fielding, Katherine

2012-05-18

There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish

TB Is Back.

ERIC Educational Resources Information Center

Natale, Jo Anna

1992-01-01

The reemergence of tuberculosis, particularly of new drug-resistant strains, points up the need for well-coordinated school health programs. Immigration effects, growing populations of HIV-infected persons, and relaxed screening procedures are partly responsible for TB's reemergence. Two sidebars offer advice on coping with TB at school and…

TB Terms

MedlinePlus

... Search Form Controls Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.

PubMed

Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M

2018-04-19

Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug

Unsuccessful TB treatment outcomes with a focus on HIV co-infected cases: a cross-sectional retrospective record review in a high-burdened province of South Africa.

PubMed

Engelbrecht, M C; Kigozi, N G; Chikobvu, P; Botha, S; van Rensburg, H C J

2017-07-10

South Africa did not meet the MDG targets to reduce TB prevalence and mortality by 50% by 2015, and the TB cure rate remains below the WHO target of 85%. TB incidence in the country is largely fuelled by the HIV epidemic, and co-infected patients are more likely to have unsuccessful TB treatment outcomes. This paper analyses the demographic and clinical characteristics of new TB patients with unsuccessful treatment outcomes, as well as factors associated with unsuccessful treatment outcomes for HIV co-infected patients. A cross-sectional retrospective record review of routinely collected data for new TB cases registered in the Free State provincial electronic TB database between 2009 and 2012. The outcome variable, unsuccessful treatment, was defined as cases ≥15 years that 'died', 'failed' or 'defaulted' as the recorded treatment outcome. The data were subjected to descriptive and logistic regression analyses. From 2009 to 2012 there were 66,940 new TB cases among persons ≥15 years (with a recorded TB treatment outcome), of these 61% were co-infected with HIV. Unsuccessful TB treatment outcomes were recorded for 24.5% of co-infected cases and 15.3% of HIV-negative cases. In 2009, co-infected cases were 2.35 times more at risk for an unsuccessful TB treatment outcome (OR: 2.35; CI: 2.06-2.69); this figure decreased to 1.8 times by 2012 (OR: 1.80; CI: 1.63-1.99). Among the co-infected cases, main risk factors for unsuccessful treatment outcomes were: ≥ 65 years (AOR: 1.71; CI: 1.25-2.35); receiving treatment in healthcare facilities in District D (AOR: 1.15; CI 1.05-1.28); and taking CPT (and not ART) (AOR: 1.28; CI: 1.05-1.57). Females (AOR: 0.93; CI: 0.88-0.99) and cases with a CD4 count >350 (AOR: 0.40; CI: 0.36-0.44) were less likely to have an unsuccessful treatment outcome. The importance of TB-HIV/AIDS treatment integration is evident as co-infected patients on both ART and CPT, and those who have a higher CD4 count are less likely to have an

Prevalence and Risk factors for Drug Resistance among Hospitalized TB Patients in Georgia

PubMed Central

Vashakidze, L; Salakaia, A.; Shubladze, N.; Cynamon, M.; Barbakadze, K.; Kikvidze, M.; Papitashvili, L.; Nonikashvili, M.; Solomonia, N.; Bejanishvili, N.; Khurtsilava, I.

2010-01-01

SUMMARY Background Tuberculosis control in Georgia follows the WHO recommended DOTS strategy and has reached Global TB Control targets in treatment of sensitive TB, but the management of drug resistant forms of TB still represents a serious problem. A country-wide Drug Resistance Survey (DRS) found that the prevalence of MDR-TB was 6.8% in new and 27.4% in previously treated TB cases. Objective To determine prevalence and risk factors for drug resistance among TB patients in order to improve DR-TB case management and control. Methods Extensive social, clinical and bacteriological data were collected from hospitalized patients (National Centre for Tuberculosis and Lung Diseases, Georgia, 2005–2007). Results Out of 605 patients DR-TB was found in 491 (81.2%) cases, MDR-TB was observed in 261(43.1%) [51 (23%) out of 222 New cases and 210 (55%) out of 383 Previously treated cases], mono-DR-TB in 130 (21.5%), poly-DR-TB in 67 (11.1%) and XDR-TB in 33 (5.5%) cases. Study showed that female gender, living in densely populated capital, family TB contact and previous TB treatment are associated with risk for having MDR-TB. Conclusions Findings confirm the necessity of improvement of infection control measures and availability of standardized treatment for DR-TB patients. PMID:19723406

Challenges and solutions for a rational vaccine design for TB-endemic regions.

PubMed

Gowthaman, Uthaman; Mushtaq, Khurram; Tan, Amabel C; Rai, Pradeep K; Jackson, David C; Agrewala, Javed N

2015-01-01

Vaccines have been successful for global eradication or control of dreaded diseases such as smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, this success has not been achieved for controlling tuberculosis (TB) worldwide. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered success in the Western world but has failed in TB-endemic areas. In this article, we highlight and discuss the aspects of immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. In addition, we also suggest strategies that contribute toward the development of successful vaccine in protecting populations where BCG has failed.

Antigen-Specific Interferon-Gamma Responses and Innate Cytokine Balance in TB-IRIS

PubMed Central

Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ceulemans, Ann; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

2014-01-01

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB patients receiving antiretroviral therapy (ART). TB-IRIS could be associated with an exaggerated immune response to TB-antigens. We compared the recovery of IFNγ responses to recall and TB-antigens and explored in vitro innate cytokine production in TB-IRIS patients. Methods In a prospective cohort study of HIV-TB co-infected patients treated for TB before ART initiation, we compared 18 patients who developed TB-IRIS with 18 non-IRIS controls matched for age, sex and CD4 count. We analyzed IFNγ ELISpot responses to CMV, influenza, TB and LPS before ART and during TB-IRIS. CMV and LPS stimulated ELISpot supernatants were subsequently evaluated for production of IL-12p70, IL-6, TNFα and IL-10 by Luminex. Results Before ART, all responses were similar between TB-IRIS patients and non-IRIS controls. During TB-IRIS, IFNγ responses to TB and influenza antigens were comparable between TB-IRIS patients and non-IRIS controls, but responses to CMV and LPS remained significantly lower in TB-IRIS patients. Production of innate cytokines was similar between TB-IRIS patients and non-IRIS controls. However, upon LPS stimulation, IL-6/IL-10 and TNFα/IL-10 ratios were increased in TB-IRIS patients compared to non-IRIS controls. Conclusion TB-IRIS patients did not display excessive IFNγ responses to TB-antigens. In contrast, the reconstitution of CMV and LPS responses was delayed in the TB-IRIS group. For LPS, this was linked with a pro-inflammatory shift in the innate cytokine balance. These data are in support of a prominent role of the innate immune system in TB-IRIS. PMID:25415590

The effect of micronutrient supplementation on active TB incidence early in HIV infection in Botswana

PubMed Central

Campa, Adriana; Baum, Marianna K; Bussmann, Hermann; Martinez, Sabrina Sales; Farahani, Mansour; van Widenfelt, Erik; Moyo, Sikhulile; Makhema, Joseph; Essex, Max; Marlink, Richard

2017-01-01

Background Coinfection with active tuberculosis (TB) is one of the leading causes of death in people living with HIV (PLWH) in Africa. This investigation explores the role of micronutrient supplementation in preventing active TB in PLWH. Methods A randomized trial of nutritional supplementation was conducted among antiretroviral- naïve (without previous antiretroviral treatment [ART]) HIV-infected people in Botswana between 2004 and 2009. The study had a factorial design with four arms: the selenium (Se) alone arm, the multivitamins (MVT) alone arm that contained vitamin B complex and vitamins C and E, the combined Se+MVT group and the placebo group. Those participants with prior or current active TB were excluded, as were participants with advanced HIV disease (CD4 <250 cells/μL) or who had already qualified for ART. HIV-positive adults (N=878) were followed monthly for study pill dispensation, every 3 months for CD4 cell count and every 6 months for viral load during 24 months or until they were started on ART. Results The participants' characteristics were not significantly different among the four groups at baseline. Supplementation with Se alone (hazard ratio =0.20, 95% confidence interval: 0.04, 0.95, P=0.043) and the two combined SE groups (Se and Se+MVT) had significantly lower risk of developing incident TB disease compared with placebo in multivariate adjusted models (hazard ratio=0.32, 95% confidence interval: 0.11, 0.93, P=0.036). Multivitamins alone did not affect the incidence of TB. Isoniazid preventive therapy was received by 12.2% of participants, a rate that was not significantly different among the four study arms (P=0.122) and the newly diagnosed cases. Conclusion Se supplementation, alone and with MVT, decreased the incidence of TB disease in PLWH who were ART-naïve. Supplementation with these micronutrients should be considered in HIV infection, prior to ART, in areas where TB and malnutrition are endemic. PMID:29187783

Opportunities and challenges for HIV care in overlapping HIV and TB epidemics.

PubMed

Havlir, Diane V; Getahun, Haileyesus; Sanne, Ian; Nunn, Paul

2008-07-23

Tuberculosis (TB) and the emerging multidrug-resistant TB epidemic represent major challenges to human immunodeficiency virus (HIV) care and treatment programs in resource-limited settings. Tuberculosis is a major cause of mortality among patients with HIV and poses a risk throughout the course of HIV disease, even after successful initiation of antiretroviral therapy (ART). Progress in the implementation of activities directed at reducing TB burden in the HIV population lags far behind global targets. HIV programs designed for longitudinal care are ideally suited to implement TB control measures and have no option but to address TB vigorously to save patient lives, to safeguard the massive investment in HIV treatment, and to curb the global TB burden. We propose a framework of strategic actions for HIV care programs to optimally integrate TB into their services. The core activities of this framework include intensified TB case finding, treatment of TB, isoniazid preventive treatment, infection control, administration of ART, TB recording and reporting, and joint efforts of HIV and TB programs at the national and local levels.

Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB.

PubMed

Luetkemeyer, Anne F; Kendall, Michelle A; Wu, Xingye; Lourenço, Maria Cristina; Jentsch, Ute; Swindells, Susan; Qasba, Sarojini S; Sanchez, Jorge; Havlir, Diane V; Grinsztejn, Beatriz; Sanne, Ian M; Firnhaber, Cynthia

2014-04-01

Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with <7 days of TB treatment had 1 sputum specimen tested with Direct LPA, MTBDR-Plus LPA, smear microscopy, MGIT, biochemical identification of mycobacterial species, and culture-based drug-susceptibility testing (DST). Of 639 participants, 59.3% were MGIT M. tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

HIV screening among TB patients and level of antiretroviral therapy and co-trimoxazole preventive therapy for TB/HIV patients in Hawassa University Referral Hospital: a five year retrospective study.

PubMed

Simieneh, Asnake; Hailemariam, Mengistu; Amsalu, Anteneh

2017-01-01

Initiation of antiretroviral therapy (ART) and co-trimoxazole preventive therapy (CPT) is recommended for tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected patients to prevent opportunistic infection. The aim of this study was to assess the prevalence of HIV among TB patients and initiation of ART and provision of CPT for TB/HIV co-infected patients in Hawassa university referral hospital. A five year document review was done on 1961 TB patients who are registered at TB clinic of Hawassa university referral hospital from September 2009 to august 2014. Data were collected using checklist. Data analysis was done by using SPSS version 20 software. Bivariate and multivariate logistic regression analysis was used to determine the predictors of TB/HIV co-infection. Among 1961 TB patients diagnosed in the hospital, 95% (1765) were screened for HIV. Of these, 13.9% (246) were HIV positive. Out of 246 TB/HIV co-infected patients 31.7% (78/246) and 37.4% (92/246) were enrolled to start ART and CPT respectively. Roughly the trends of TB/HIV co-infection decreased with increased linkage to CPT, while linkage to ART was not regular across the year. The rate of TB/HIV co-infection was significantly associated with type of TB. Although, trend of HIV among TB patients has decreased across the year, only a minority of co-infected patients was linked to start ART and CPT. Therefore, screening of all TB patients for HIV and linkage of co-infected patients to HIV care to start ART and CPT should be strengthened in-line with the national guidelines.

Risk Factors for Bovine Tuberculosis (bTB) in Cattle in Ethiopia.

PubMed

Dejene, Sintayehu W; Heitkönig, Ignas M A; Prins, Herbert H T; Lemma, Fitsum A; Mekonnen, Daniel A; Alemu, Zelalem E; Kelkay, Tessema Z; de Boer, Willem F

2016-01-01

Bovine tuberculosis (bTB) infection is generally correlated with individual cattle's age, sex, body condition, and with husbandry practices such as herd composition, cattle movement, herd size, production system and proximity to wildlife-including bTB maintenance hosts. We tested the correlation between those factors and the prevalence of bTB, which is endemic in Ethiopia's highland cattle, in the Afar Region and Awash National Park between November 2013 and April 2015. A total of 2550 cattle from 102 herds were tested for bTB presence using the comparative intradermal tuberculin test (CITT). Data on herd structure, herd movement, management and production system, livestock transfer, and contact with wildlife were collected using semi-structured interviews with cattle herders and herd owners. The individual overall prevalence of cattle bTB was 5.5%, with a herd prevalence of 46%. Generalized Linear Mixed Models with a random herd-effect were used to analyse risk factors of cattle reactors within each herd. The older the age of the cattle and the lower the body condition the higher the chance of a positive bTB test result, but sex, lactation status and reproductive status were not correlated with bTB status. At herd level, General Linear Models showed that pastoral production systems with transhumant herds had a higher bTB prevalence than sedentary herds. A model averaging analysis identified herd size, contact with wildlife, and the interaction of herd size and contact with wildlife as significant risk factors for bTB prevalence in cattle. A subsequent Structural Equation Model showed that the probability of contact with wildlife was influenced by herd size, through herd movement. Larger herds moved more and grazed in larger areas, hence the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased, enhancing the chances for bTB infection. Therefore, future bTB control strategies in cattle in

Addressing challenges in scaling up TB and HIV treatment integration in rural primary healthcare clinics in South Africa (SUTHI): a cluster randomized controlled trial protocol.

PubMed

Naidoo, Kogieleum; Gengiah, Santhanalakshmi; Yende-Zuma, Nonhlanhla; Padayatchi, Nesri; Barker, Pierre; Nunn, Andrew; Subrayen, Priashni; Abdool Karim, Salim S

2017-11-13

A large and compelling clinical evidence base has shown that integrated TB and HIV services leads to reduction in human immunodeficiency virus (HIV)- and tuberculosis (TB)-associated mortality and morbidity. Despite official policies and guidelines recommending TB and HIV care integration, its poor implementation has resulted in TB and HIV remaining the commonest causes of death in several countries in sub-Saharan Africa, including South Africa. This study aims to reduce mortality due to TB-HIV co-infection through a quality improvement strategy for scaling up of TB and HIV treatment integration in rural primary healthcare clinics in South Africa. The study is designed as an open-label cluster randomized controlled trial. Sixteen clinic supervisors who oversee 40 primary health care (PHC) clinics in two rural districts of KwaZulu-Natal, South Africa will be randomized to either the control group (provision of standard government guidance for TB-HIV integration) or the intervention group (provision of standard government guidance with active enhancement of TB-HIV care integration through a quality improvement approach). The primary outcome is all-cause mortality among TB-HIV patients. Secondary outcomes include time to antiretroviral therapy (ART) initiation among TB-HIV co-infected patients, as well as TB and HIV treatment outcomes at 12 months. In addition, factors that may affect the intervention, such as conditions in the clinic and staff availability, will be closely monitored and documented. This study has the potential to address the gap between the establishment of TB-HIV care integration policies and guidelines and their implementation in the provision of integrated care in PHC clinics. If successful, an evidence-based intervention comprising change ideas, tools, and approaches for quality improvement could inform the future rapid scale up, implementation, and sustainability of improved TB-HIV integration across sub-Sahara Africa and other resource

46 CFR 30.10-5b - Cargo control station-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Cargo control station-TB/ALL. 30.10-5b Section 30.10-5b Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5b Cargo control station—TB/ALL. The term cargo control station means a location that is manned...

46 CFR 30.10-5b - Cargo control station-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Cargo control station-TB/ALL. 30.10-5b Section 30.10-5b Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5b Cargo control station—TB/ALL. The term cargo control station means a location that is manned...

46 CFR 30.10-5b - Cargo control station-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Cargo control station-TB/ALL. 30.10-5b Section 30.10-5b Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5b Cargo control station—TB/ALL. The term cargo control station means a location that is manned...

46 CFR 30.10-5b - Cargo control station-TB/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Cargo control station-TB/ALL. 30.10-5b Section 30.10-5b Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5b Cargo control station—TB/ALL. The term cargo control station means a location that is manned...

46 CFR 30.10-5b - Cargo control station-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Cargo control station-TB/ALL. 30.10-5b Section 30.10-5b Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-5b Cargo control station—TB/ALL. The term cargo control station means a location that is manned...

Framework of behavioral indicators evaluating TB health promotion outcomes: a modified Delphi study of TB policymakers and health workers.

PubMed

Li, Ying; Ehiri, John; Hu, Daiyu; Oren, Eyal; Cao, Jia

2015-12-15

Although TB health promotion directed at policy makers and healthcare workers (HCWs) is considered important to tuberculosis (TB) control, no indicators currently assess the impact of such promotional activities. This article is the second in a series of papers that seek to establish a framework of behavioral indicators for outcome evaluation of TB health promotion, using the Delphi method. In the first article, we sought to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients. The objective of this second article is to present an indicator framework that can be used to assess behavioral outcomes of TB health promotion directed at policy makers and HCWs. A two-round, modified Delphi method was used to establish the indicators. Sixteen experts who were knowledgeable and experienced in the field of TB control were consulted in Delphi surveys. A questionnaire was developed following 4 steps, and involved ranking indicators on a five-point Likert scale. The consensus level was 70 %. Median, mode, and Coefficient of variation (CV) were used to describe expert responses. An authority coefficient (Cr) was used to assess the degree of each expert's authority. Consensus was achieved following the two survey rounds and several iterations among the experts. For TB health-promotion activities directed at policymakers, the experts reached consensus on 2 domains ("Resource inputs" and "Policymaking and monitoring behaviors"), 4 subdomains ("Human resources" among others), and 13 indicators ("Human resources per 100,000 person" among others). For TB health-promotion activities directed at HCWs, the experts reached consensus on 5 domains ("Self-protective behaviors" among others), 6 sub-domains ("Preventing infection" among others), and 15 indicators ("Average hours of daily workplace disinfection by ultraviolet radiation" among others). This study identified a conceptual framework of core behavioral indicators

Clearing the smoke around the TB-HIV syndemic: smoking as a critical issue for TB and HIV treatment and care

PubMed Central

Jackson-Morris, A.; Fujiwara, P. I.; Pevzner, E.

2016-01-01

SUMMARY The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a ‘syndemic’ due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB-HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the ‘MPO-WER’ package recommended by the World Health Organization’s Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking. PMID:26260816

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

Mini epidemic of isoniazide resistant TB in rural TN: a need for supervised preventive therapy.

PubMed

Mehta, Jay; Keith, Rob; Al Hasan, Muhannad; Ryland, Byrd; Roy, Thomas

2009-08-01

With the resurgence of tuberculosis (TB) in the late 1980s, multi-drug-resistant TB (MDR-TB) also became a serious challenge to the TB control programs across the United States (US). While the incidence of TB resumed a downward trend in the mid 1900s, drug-resistant TB continues to be a national and international problem. We reviewed the public health data of drug-resistant TB cases (1996-2002) in Greene County, TN, with a detailed analysis of their contact investigation. Our study included demographic data of age, sex, race, human immunodeficiency virus (HIV) status and other known risk factors for drug-resistant TB. Contact investigation of two patients with isoniazide-resistant active pulmonary TB led to the discovery of two additional cases of active pulmonary tuberculosis, one of them being a 14-month-old child. All four of the patients were U.S. born, had negative HIV tests, and lacked other risk factors for drug-resistant TB. In all four cases, the Mycobacterium tuberculosis isolates were resistant to isoniazide, three were streptomycin resistant, and was ethambutol resistant. A total of 65 close contacts were identified, 11 of whom had a positive purified protein derivative (PPD) skin test indicating latent TB infection. Based on the American Thoracic Society's recommendations, the contacts with a positive PPD were prescribed rifampin for chemo-prevention rather than INH. However, one active case was detected from this infected contact who had failed to comply with chemo-preventive therapy. The second active case was a child who developed active pulmonary TB before chemoprevention could be initiated. Drug culture profile and DNA analysis (RFLP) confirmed the same source for TB transmission. The 11/65 (16.5 percent) infection rate among the contact was comparable to the state average (p < 0.05), but the case rate of 4/65 (6.15 percent) was high. In two out of four active cases, who were family members of the known cases, active infection could have been

Global evidence directing regional preventive strategies in Southeast Asia for fighting TB/HIV.

PubMed

Aung, Myo Nyein; Moolphate, Saiyud; Paudel, Damodar; Jayathunge Ph, Mangalasiri; Duangrithi, Duangjai; Wangdi, Kinley; Aung, Thin Nyein Nyein; Lorga, Thaworn; Higuchi, Kazue

2013-03-14

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-epidemics form a huge burden of disease in the Southeast Asia region. Five out of eleven nations in this region are high TB/HIV burden countries: Myanmar, Thailand, India, Indonesia and Nepal. The trends of TB incidence in these countries have been rising in recent years, in contrast to a falling global trend. Experts in the field of TB control and health service providers have been perplexed by the association of TB and HIV infections which causes a mosaic clinical presentation, a unique course with poor treatment outcomes including death. We conducted a review of contemporary evidence relating to TB/HIV control with the aims of assisting integrated health system responses in Southeast Asia and demystifying current evidence to facilitate translating it into practice.

Tuberculosis Vaccines and Prevention of Infection

PubMed Central

Day, Tracey A.; Scriba, Thomas J.; Hatherill, Mark; Hanekom, Willem A.; Evans, Thomas G.; Churchyard, Gavin J.; Kublin, James G.; Bekker, Linda-Gail; Self, Steven G.

2014-01-01

SUMMARY Tuberculosis (TB) is a leading cause of death worldwide despite the availability of effective chemotherapy for over 60 years. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination protects against active TB disease in some populations, its efficacy is suboptimal. Development of an effective TB vaccine is a top global priority that has been hampered by an incomplete understanding of protective immunity to TB. Thus far, preventing TB disease, rather than infection, has been the primary target for vaccine development. Several areas of research highlight the importance of including preinfection vaccines in the development pipeline. First, epidemiology and mathematical modeling studies indicate that a preinfection vaccine would have a high population-level impact for control of TB disease. Second, immunology studies support the rationale for targeting prevention of infection, with evidence that host responses may be more effective during acute infection than during chronic infection. Third, natural history studies indicate that resistance to TB infection occurs in a small percentage of the population. Fourth, case-control studies of BCG indicate that it may provide protection from infection. Fifth, prevention-of-infection trials would have smaller sample sizes and a shorter duration than disease prevention trials and would enable opportunities to search for correlates of immunity as well as serve as a criterion for selecting a vaccine product for testing in a larger TB disease prevention trial. Together, these points support expanding the focus of TB vaccine development efforts to include prevention of infection as a primary goal along with vaccines or other interventions that reduce the rate of transmission and reactivation. PMID:25428938

Pattern of socio-economic and health aspects among TB patients and controls.

PubMed

Kapoor, A K; Deepani, Vijit; Dhall, Meenal; Kapoor, Satwanti

2016-10-01

Socio-economic and health-related factors have a significant impact on tuberculosis (TB) incidence among population residing in resource-scare settings. To evaluate the pattern of socio-economic and health-related factors among TB patients and control in Delhi, India. The present cross-sectional study was performed among 893 TB patients (or cases) and 333 healthy disease-free controls. The data for the present study was obtained from several district TB centres in north, west and south Delhi. The collected data was edited, coded and statistical analysed with the help of SPSS 20.0 version. Illiteracy and primary education were significant risk factors being associated with a TB. Rented housing condition had an odds ratio (OR) of 1.4 (95% confidence interval [CI]: 1.09-1.89) compared to owned housing condition. 3-5 individuals per room were 3 times more likely to be associated with a case of TB (95% CI: 2.49-4.41). Migrant individuals were 13 times more likely to be associated with a case of TB (95% CI: 8.77-19.78) in comparison to settled population. Daily consumption of non-vegetarian food also significantly contributed to case of TB with an OR of 3.4 (95% CI: 2.51-4.72). Loss of appetite and family TB served as significant health-related factors associated with TB risk. Lower educational status, rented household, individuals per room (as a measure of overcrowding) and migratory status served as prominent risk factors for TB disease. Preference and frequency of non-vegetarian food being consumed, night sweating, weight loss, loss of appetite, earlier TB and family TB were principle health-related risk factors associated with TB disease. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Implementation of Tuberculosis Intensive Case Finding, Isoniazid Preventive Therapy, and Infection Control ("Three I's") and HIV-Tuberculosis Service Integration in Lower Income Countries.

PubMed

Charles, M Katherine; Lindegren, Mary Lou; Wester, C William; Blevins, Meridith; Sterling, Timothy R; Dung, Nguyen Thi; Dusingize, Jean Claude; Avit-Edi, Divine; Durier, Nicolas; Castelnuovo, Barbara; Nakigozi, Gertrude; Cortes, Claudia P; Ballif, Marie; Fenner, Lukas

2016-01-01

World Health Organization advocates for integration of HIV-tuberculosis (TB) services and recommends intensive case finding (ICF), isoniazid preventive therapy (IPT), and infection control ("Three I's") for TB prevention and control among persons living with HIV. To assess the implementation of the "Three I's" of TB-control at HIV treatment sites in lower income countries. Survey conducted between March-July, 2012 at 47 sites in 26 countries: 6 (13%) Asia Pacific, 7 (15%), Caribbean, Central and South America, 5 (10%) Central Africa, 8 (17%) East Africa, 14 (30%) Southern Africa, and 7 (15%) West Africa. ICF using symptom-based screening was performed at 38% of sites; 45% of sites used symptom-screening plus additional diagnostics. IPT at enrollment or ART initiation was implemented in only 17% of sites, with 9% of sites providing IPT to tuberculin-skin-test positive patients. Infection control measures varied: 62% of sites separated smear-positive patients, and healthcare workers used masks at 57% of sites. Only 12 (26%) sites integrated HIV-TB services. Integration was not associated with implementation of TB prevention measures except for IPT provision at enrollment (42% integrated vs. 9% non-integrated; p = 0.03). Implementation of TB screening, IPT provision, and infection control measures was low and variable across regional HIV treatment sites, regardless of integration status.

A pivotal registration phase III, multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project

PubMed Central

2012-01-01

Background There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize

Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study

PubMed Central

Anderson, Suzanne T.; Bangani, Nonzwakazi; Banwell, Claire M.; Brent, Andrew J.; Crampin, Amelia C.; Dockrell, Hazel M.; Eley, Brian; Heyderman, Robert S.; Hibberd, Martin L.; Kern, Florian; Langford, Paul R.; Ling, Ling; Mendelson, Marc; Ottenhoff, Tom H.; Zgambo, Femia; Wilkinson, Robert J.; Coin, Lachlan J.; Levin, Michael

2013-01-01

Background A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. Methods and Findings Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI [80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI [84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our study include the use of

The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

PubMed

Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

2016-01-01

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting.

PubMed

Sharma, Surendra K; Vashishtha, Richa; Chauhan, L S; Sreenivas, V; Seth, Divya

2017-01-01

There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings. 1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases. Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72-1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97-2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients. Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings.

Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

PubMed Central

López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C.; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

2016-01-01

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

Assessment of the QuantiFERON-TB Gold In-Tube test for the detection of Mycobacterium tuberculosis infection in United States Navy recruits.

PubMed

Lempp, Jason M; Zajdowicz, Margan J; Hankinson, Arlene L; Toney, Sean R; Keep, Lisa W; Mancuso, James D; Mazurek, Gerald H

2017-01-01

Immunologic tests such as the tuberculin skin test (TST) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infection, both latent M. tuberculosis infection (LTBI) and infection manifesting as active tuberculosis disease (TB). These tests need high specificity to minimize unnecessary treatment and high sensitivity to allow maximum detection and prevention of TB. Estimate QFT-GIT specificity, compare QFT-GIT and TST results, and assess factor associations with test discordance among U.S. Navy recruits. Among 792 subjects with completed TST and QFT-GIT, 42(5.3%) had TST indurations ≥10mm, 23(2.9%) had indurations ≥15mm, 14(1.8%) had positive QFT-GIT results, and 5(0.6%) had indeterminate QFT-GITs. Of 787 subjects with completed TST and determinate QFT-GIT, 510(64.8%) were at low-risk for infection, 277(35.2%) were at increased risk, and none had TB. Among 510 subjects at low-risk (presumed not infected), estimated TST specificity using a 15mm cutoff, 99.0% (95%CI: 98.2-99.9%), and QFT-GIT specificity, 98.8% (95%CI: 97.9-99.8%), were not significantly different (p>0.99). Most discordance was among recruits at increased risk of infection, and most was TST-positive but QFT-GIT-negative discordance. Of 18 recruits with TST ≥15mm but QFT-GIT negative discordance, 14(78%) were at increased risk. TB prevalence in country of birth was the strongest predictor of positive TST results, positive QFT-GIT results, and TST-positive but QFT-GIT-negative discordance. Reactivity to M. avium purified protein derivative (PPD) was associated with positive TST results and with TST-positive but QFT-GIT-negative discordance using a 10 mm cutoff, but not using a 15 mm cutoff or with QFT-GIT results. M. tuberculosis infection prevalence was low, with the vast majority of infection occurring in recruits with recognizable risks. QFT-GIT and TST specificities were high and not significantly different. Negative QFT-GIT results among subjects

TB-IRIS and remodelling of the T cell compartment in highly immunosuppressed HIV+ patients with TB: the CAPRI T (ANRS-12614) study

PubMed Central

Haridas, V.; Pean, P.; Jasenosky, L.D.; Madec, Y.; Laureillard, D.; Sok, T.; Sath, S.; Borand, L.; Marcy, O.; Chan, S.; Tsitsikov, E.; Delfraissy, J.-F.; Blanc, F.-X.; Goldfeld, A.E.

2015-01-01

Objective To investigate the impact of tuberculosis (TB)-associated immune reconstitution syndrome (IRIS) upon immunological recovery and the T cell compartment after initiation of TB and antiretroviral therapy (ART). Design and methods We prospectively evaluated T cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n=154) of highly immunosuppressed HIV+ patients with TB from the CAMELIA randomized clinical trial. We compared findings from patients who developed TB-IRIS to findings from patients who did not develop TB-IRIS. Data were evaluated with mixed effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank sum tests, and q-values were calculated to control for multiple comparisons. Results Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DR+CD45RO+CD4+, CCR5+CD4+, OX40+CD4+, and Fas+ effector memory (EM) CD8+ T cells, and significantly elevated levels of plasma IL-6, IL-1β, IL-8, and IL-10 and viral load. Post-ART initiation, EM CD4+ and Fas+ EM CD4+ T cell frequencies significantly expanded, and central memory (CM) CD4+ T cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, EM/CM CD4+ T cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients. Conclusions A distinct pattern of pre-ART T cell and cytokine markers appear to poise the immune response to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4+ T cell memory compartment towards an EM-dominated phenotype. We speculate that these pre- and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome. PMID:25486415

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

PubMed Central

Lala, Sanjay G.; Little, Kristen M.; Tshabangu, Nkeko; Moore, David P.; Msandiwa, Reginah; van der Watt, Martin; Chaisson, Richard E.; Martinson, Neil A.

2015-01-01

Background Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. Methods Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. Results Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. Conclusion In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed

Impact of Infection Control Measures to Control an Outbreak of Multidrug-Resistant Tuberculosis in a Human Immunodeficiency Virus Ward, Peru.

PubMed

Ticona, Eduardo; Huaroto, Luz; Kirwan, Daniela E; Chumpitaz, Milagros; Munayco, César V; Maguiña, Mónica; Tovar, Marco A; Evans, Carlton A; Escombe, Roderick; Gilman, Robert H

2016-12-07

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000-56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug-susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB-coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective. © The American Society of Tropical Medicine and Hygiene.

Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection.

PubMed

Dudley, Matthew Z; Sheen, Patricia; Gilman, Robert H; Ticona, Eduardo; Friedland, Jon S; Kirwan, Daniela E; Caviedes, Luz; Rodriguez, Richard; Cabrera, Lilia Z; Coronel, Jorge; Grandjean, Louis; Moore, David A J; Evans, Carlton A; Huaroto, Luz; Chávez-Pérez, Víctor; Zimic, Mirko

2016-12-07

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)-positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58-92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures. © The American Society of Tropical Medicine and Hygiene.

Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection

PubMed Central

Dudley, Matthew Z.; Sheen, Patricia; Gilman, Robert H.; Ticona, Eduardo; Friedland, Jon S.; Kirwan, Daniela E.; Caviedes, Luz; Rodriguez, Richard; Cabrera, Lilia Z.; Coronel, Jorge; Grandjean, Louis; Moore, David A. J.; Evans, Carlton A.; Huaroto, Luz; Chávez-Pérez, Víctor; Zimic, Mirko

2016-01-01

Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)–positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58–92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures. PMID:27928075

Are TB control programmes in South Asia ignoring children with disease? A situational analysis.

PubMed

Shakoor, Sadia; Qamar, Farah Naz; Mir, Fatima; Zaidi, Anita; Hasan, Rumina

2015-02-01

Paediatric tuberculosis (TB) has long been an evasive entity for public health practitioners striving to control the disease. Owing to difficulty in diagnosis of paediatric TB, incidence estimates based on current case detection fall short of actual rates. The four high-burden countries in South Asia (SA-HBC)-Afghanistan, Pakistan, India and Bangladesh-alone account for >75% of missed TB cases worldwide. It follows that these countries are also responsible for a large although unmeasured proportion of missed paediatric cases. In view of current Millennium Development Goals recommending a scale-up of paediatric TB detection and management globally, there is a dire need to improve paediatric TB programmes in these high-burden countries. Inherent problems with diagnosis of paediatric TB are compounded by programmatic and social barriers in SA-HBC. We have reviewed the current situation of TB control programmes in SA-HBC countries based on published statistics and performed a strengths, weaknesses, opportunities and threats situational analysis with a view towards identifying critical issues operant in the region posing barriers to improving paediatric TB control. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Toward a generation free of tuberculosis: TB disease and infection in individuals of college age in the United States.

PubMed

Shah, N S; Flood-Bryzman, A; Jeffries, C; Scott, J

2018-01-01

To assess the magnitude of active TB disease and latent TB infection (LTBI) in young adults of college age. Individuals who were aged 18-24 years in 2011 were used as a proxy for college students. Active TB cases reported to the 2011 US National TB Surveillance System (NTSS) were included. LTBI prevalence was calculated from the 2011-2012 National Health and Nutrition Examination Survey. The 2011 American Community Survey was used to calculate population denominators. Analyses were stratified by nativity. Active TB disease incidence among persons aged 18-24 years was 2.82/100,000, 18.8/100,000 among foreign-born individuals and 0.9/100,000 among US-born individuals. In 2011, 878 TB cases were reported; 629 (71.6%) were foreign-born. LTBI prevalence among persons of 18-24 years was 2.5%: 8.7% and 1.3% among foreign-born and US-born, respectively. Active screening and treatment programs for foreign-born young adults could identify TB cases earlier and provide an opportunity for prevention efforts.

Interleukin 1-beta (IL-1β) production by innate cells following TLR stimulation correlates with TB recurrence in ART-treated HIV infected patients

PubMed Central

Thobakgale, Christina; Naidoo, Kewreshini; McKinnon, Lyle R.; Werner, Lise; Samsunder, Natasha; Karim, Salim Abdool; Ndung’u, Thumbi; Altfeld, Marcus; Naidoo, Kogieleum

2016-01-01

Background Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV co-infection, since immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment. Methods Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time points prior to TB recurrence were stimulated with ligands for Toll like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multi-color flow cytometry and intracellular cytokine staining was used to detect IL-1β, TNF-α, IL-12 and IP10 responses from monocytes and myeloid dendritic cells (mDCs). Results Elevated production of IL-1β from monocytes following TLR-2, TLR-4 and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs respectively). Conclusion Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB. PMID:27654812

46 CFR 39.10-13 - Submission of vapor control system designs-TB/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Submission of vapor control system designs-TB/ALL. 39.10-13 Section 39.10-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.10-13 Submission of vapor control system designs—TB/ALL. (a) Plans, calculations, and...

46 CFR 39.10-13 - Submission of vapor control system designs-TB/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Submission of vapor control system designs-TB/ALL. 39.10-13 Section 39.10-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.10-13 Submission of vapor control system designs—TB/ALL. (a) Plans, calculations, and...

46 CFR 39.10-13 - Submission of vapor control system designs-TB/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Submission of vapor control system designs-TB/ALL. 39.10-13 Section 39.10-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.10-13 Submission of vapor control system designs—TB/ALL. (a) Plans, calculations, and...

Integration of Surveillance for STDs, HIV, Hepatitis, and TB: A Survey of U.S. STD Control Programs.

PubMed

Dowell, Deborah; Gaffga, Nicholas H; Weinstock, Hillard; Peterman, Thomas A

2009-01-01

Integration of surveillance for sexually transmitted diseases (STDs), human immunodeficiency virus (HIV), hepatitis, and tuberculosis (TB) may improve disease prevention and control. We determined the extent of surveillance integration in these programs, the benefits of integration, and barriers to increased integration. We e-mailed a survey to the 58 federally funded local and state STD control programs and followed up with phone interviews of nine program representatives. The response rate was 81%. Many had compared infections by population subgroup for STDs and HIV (89%), STDs and hepatitis (53%), or STDs and TB (28%). Most (74%) had examined co-infections with HIV and STDs at the individual level and entered STD and HIV surveillance data into the same database (54%). All respondents thought some integration would be useful. Many (72%) used integrated data to disseminate information or change program strategies. The most commonly reported barriers to integration were policies preventing work with HIV data (85%) and incompatible databases (59%). Most STD control programs in the United States have some experience integrating surveillance data, but the degree of integration varies widely. Specific barriers to further integration were identified. The Centers for Disease Control and Prevention can help address these barriers by facilitating access to information and sharing technical solutions. Local and state programs can continue advancing surveillance integration by improving understanding of where integrated data are needed, increasing the use of available data, and pressing for appropriate and secure data sharing.

Framework of behavioral indicators for outcome evaluation of TB health promotion: a Delphi study of TB suspects and Tb patients.

PubMed

Li, Ying; Ehiri, John; Hu, Daiyu; Zhang, Yanqi; Wang, Qingya; Zhang, Shun; Cao, Jia

2014-05-16

Health promotion for prevention and control of Tuberculosis (TB) is implemented worldwide because of its importance, but few reports have evaluated its impact on behavior due to a lack of standard outcome indicators. The objective of this study was to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients. A two-round modified Delphi method involving sixteen TB control experts was used to establish a framework of behavioral indicators for outcome evaluation of TB health promotion targeted at TB suspects and patients. Sixteen of seventeen invited experts in TB control (authority score of 0.91 on a 1.0 scale) participated in round 1 survey. All sixteen experts also participated in a second round survey. After two rounds of surveys and several iterations among the experts, there was consensus on a framework of indicators for measuring outcomes of TB health promotion for TB suspects and patients. For TB suspects, the experts reached consensus on 2 domains ("Healthcare seeking behavior" and "Transmission prevention"), 3 subdomains ("Seeking care after onset of TB symptoms", "Pathways of seeking care" and "Interpersonal contact etiquette"), and 8 indicators (including among others, "Length of patient delay"). For TB patients, consensus was reached on 3 domains ("Adherence to treatment", "Healthy lifestyle" and "Transmission prevention"), 8 subdomains (including among others, "Adherence to their medication"), and 14 indicators (including "Percentage of patients who adhered to their medication"). Operational definitions and data sources were provided for each indicator. The findings of this study provide the basis for debate among international experts on a framework for achieving global consensus on outcome indicators for TB health promotion interventions targeted at TB patients and suspects. Such consensus will help to increase effectiveness of TB health promotion, while ensuring international

Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age.

PubMed

Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

2016-01-01

Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30-49 years, 86.5% and 94.7%; 50-69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age.

Latent tuberculosis infection in a Malaysian prison: implications for a comprehensive integrated control program in prisons

PubMed Central

2014-01-01

Background Prisons continue to fuel tuberculosis (TB) epidemics particularly in settings where access to TB screening and prevention services is limited. Malaysia is a middle-income country with a relatively high incarceration rate of 138 per 100,000 population. Despite national TB incidence rate remaining unchanged over the past ten years, data about TB in prisons and its contribution to the overall national rates does not exist. This survey was conducted to address the prevalence of latent TB infection (LTBI) in Malaysia’s largest prison. Methods From July to December 2010, all HIV-infected and a comparative group of HIV-uninfected prisoners housed separately in Kajang prison were asked to participate in the survey after explaining the study protocol. Subjects providing informed consent were interviewed using a structured questionnaire followed by the placement of tuberculin skin test (TST) with 2 TU of PPD RT-23 to subjects not being treated for active TB. TST was read after 48-72 hours and indurations of ≥ 5 mm and ≥ 10 mm were considered positive among HIV-infected and HIV-uninfected subjects, respectively. Additionally, HIV-infected inmates underwent phlebotomy for CD4 lymphocyte count assessment. A logistic regression model was explored to determine factors associated with TST positivity. Results Overall, 286 subjects (138 HIV-infected and 148 HIV-uninfected) had complete data and TST results. The majority were men (95.1%), less than 40 years old (median age 36.0, SD 7.87), and Malaysians (93.3%). Most (82.5%) had been previously incarcerated and more than half (53.1%) reported sharing needles just prior to their incarceration. TST was positive in 88.8% (84.7% among HIV-infected and 92.5% among HIV-uninfected subjects) and was independently associated with being HIV-uninfected (AOR = 2.97, p = 0.01) and with frequent previous incarcerations (AOR = 1.22 for every one previous incarceration, p = 0.01) after adjusting for other

Latent tuberculosis infection in a Malaysian prison: implications for a comprehensive integrated control program in prisons.

PubMed

Al-Darraji, Haider Abdulrazzaq Abed; Kamarulzaman, Adeeba; Altice, Frederick L

2014-01-10

Prisons continue to fuel tuberculosis (TB) epidemics particularly in settings where access to TB screening and prevention services is limited. Malaysia is a middle-income country with a relatively high incarceration rate of 138 per 100,000 population. Despite national TB incidence rate remaining unchanged over the past ten years, data about TB in prisons and its contribution to the overall national rates does not exist. This survey was conducted to address the prevalence of latent TB infection (LTBI) in Malaysia's largest prison. From July to December 2010, all HIV-infected and a comparative group of HIV-uninfected prisoners housed separately in Kajang prison were asked to participate in the survey after explaining the study protocol. Subjects providing informed consent were interviewed using a structured questionnaire followed by the placement of tuberculin skin test (TST) with 2 TU of PPD RT-23 to subjects not being treated for active TB. TST was read after 48-72 hours and indurations of ≥ 5 mm and ≥ 10 mm were considered positive among HIV-infected and HIV-uninfected subjects, respectively. Additionally, HIV-infected inmates underwent phlebotomy for CD4 lymphocyte count assessment. A logistic regression model was explored to determine factors associated with TST positivity. Overall, 286 subjects (138 HIV-infected and 148 HIV-uninfected) had complete data and TST results. The majority were men (95.1%), less than 40 years old (median age 36.0, SD 7.87), and Malaysians (93.3%). Most (82.5%) had been previously incarcerated and more than half (53.1%) reported sharing needles just prior to their incarceration. TST was positive in 88.8% (84.7% among HIV-infected and 92.5% among HIV-uninfected subjects) and was independently associated with being HIV-uninfected (AOR = 2.97, p = 0.01) and with frequent previous incarcerations (AOR = 1.22 for every one previous incarceration, p = 0.01) after adjusting for other potential confounding factors

Tuberculosis infection control practices and associated factors among health care workers in health centers of West Gojjam zone, Northwest Ethiopia: a cross-sectional study.

PubMed

Tamir, Kassahun; Wasie, Belaynew; Azage, Muluken

2016-08-08

Tuberculosis (TB) remains a major global health problem. The emerging epidemic of multi- and extensively drug-resistant (M/XDR) TB further imperils health workers, patients and public health. Health facilities with inadequate infection control are risky environments for the emergence and transmission of TB. There was no study that presented data on infection control practices of health care workers. This study aimed to assess tuberculosis infection control practices and associated factors among health care workers in West Gojjam Zone, Northwest Ethiopia. Institution based quantitative cross-sectional study triangulated with qualitative observation and key informant interview was conducted. Six hundred sixty two health care workers were selected by multistage random sampling method. Self-administered structured questionnaire was used to collect quantitative data. Observation checklists and key informant interview guides were used to collect qualitative data. Quantitative data were entered in to Epi Info version 3.5.3 and analyzed using SPSS version 20. Odds ratio with 95 % confidence interval was used to identify factors associated with TB infection control practice of health care workers. Qualitative data were translated, transcribed, analyzed and triangulated with the quantitative findings. The proportion of proper TB infection control (TBIC) practices was 38 %. Qualitative data showed that administrative, environmental and personal respiratory protection control measures were not practiced well. Knowledge on the presence of TBIC plan [AOR = 4.25, 95 % CI: 2.46 - 7.35], knowledge on the presence of national guideline [AOR = 8.95, 95 % CI: 4.35 - 18.40] and working department of the health care workers were independent predictors of TBIC practices. The proportion of proper TBIC practices of health care workers was low. TBIC practices were determined by knowing the presence of TBIC plan and national guideline and working department. Hence, supportive

Tuberculosis and HIV co-infection-focus on the Asia-Pacific region.

PubMed

Trinh, Q M; Nguyen, H L; Nguyen, V N; Nguyen, T V A; Sintchenko, V; Marais, B J

2015-03-01

Tuberculosis (TB) is the leading opportunistic disease and cause of death in patients with HIV infection. In 2013 there were 1.1 million new TB/HIV co-infected cases globally, accounting for 12% of incident TB cases and 360,000 deaths. The Asia-Pacific region, which contributes more than a half of all TB cases worldwide, traditionally reports low TB/HIV co-infection rates. However, routine testing of TB patients for HIV infection is not universally implemented and the estimated prevalence of HIV in new TB cases increased to 6.3% in 2013. Although HIV infection rates have not seen the rapid rise observed in Sub-Saharan Africa, indications are that rates are increasing among specific high-risk groups. This paper reviews the risks of TB exposure and progression to disease, including the risk of TB recurrence, in this vulnerable population. There is urgency to scale up interventions such as intensified TB case-finding, isoniazid preventive therapy, and TB infection control, as well as HIV testing and improved access to antiretroviral treatment. Increased awareness and concerted action is required to reduce TB/HIV co-infection rates in the Asia-Pacific region and to improve the outcomes of people living with HIV. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Tuberculosis Infection in Zambia: The Association with Relative Wealth

PubMed Central

Boccia, Delia; Hargreaves, James; Ayles, Helen; Fielding, Katherine; Simwinga, Musonda; Godfrey-Faussett, Peter

2013-01-01

This study aimed to assess the association between household socioeconomic position and tuberculosis (TB) infection in two communities of Zambia. For this purpose we implemented a cross-sectional investigation, nested within a larger case control study. Infection was assessed using Quantiferon-TB Gold. A socioeconomic position index was constructed through principal component analysis combining data on human resources, food availability, housing quality, and access to services and infrastructures. In this study, higher socioeconomic position, rather than lower, was associated with significantly higher risk of TB infection. None of the traditional risk factors for TB infection mediated this association, suggesting that in these two communities TB transmission may occur through exposure to as yet undefined risk factors that are associated with higher socioeconomic position. Although further studies are needed, these results suggest emerging new patterns of TB transmission and a role of socioeconomic position on the risk of TB infection opposite to that expected. PMID:19478266

Performance of TB immunodiagnostic tests in Eurasian badgers (Meles meles) of different ages and the influence of duration of infection on serological sensitivity

PubMed Central

2009-01-01

Background In parts of Great Britain and Ireland, Eurasian badgers (Meles meles) constitute a reservoir of Mycobacterium bovis infection and a potential source of infection for cattle. In vitro diagnostic tests for live badgers are an important component of strategies to control TB in this species. Immunological tests have been developed for badgers, although little is known about the influence of the age of the animal on test performance. To address this, we evaluated the performance of three immunological tests for badgers with respect to the age of the animal: the Brock Test and BrockTB STAT-PAK® serological tests and the recently developed interferon-gamma enzyme immunoassay (IFNγ EIA). Data published elsewhere suggested that seropositivity was associated with more progressive forms of TB in the badger. To gain further evidence for this, we used longitudinal data from a well-studied population of badgers to test for an association between the sensitivity of the Brock Test and the duration of TB infection. Results Sensitivity of the two serological tests was approximately 54% for both cubs and adults. Sensitivity of the IFNγ EIA was lower in cubs (57%) compared with adults (85%) when a common cut-off value was used to define test positivity. Taking data from the cubs alone, the IFNγ EIA cut-off value could be adjusted to increase the sensitivity to 71% with no loss in specificity. As a general observation, specificity of all tests was higher in cubs, although only significantly so in the case of the Brock Test. Using logistic regression analysis to adjust for age, sensitivity of the Brock Test was significantly lower at first culture positive event (58%), but increased to >80% as infection progressed. Conclusion These data suggest that serodiagnosis could be a valuable tool for detecting a higher proportion of badgers with the greatest probability of transmitting infection. The age category of the badger appeared to exert little influence on the performance

Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network.

PubMed

Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat

2017-06-01

To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Framework of behavioral indicators for outcome evaluation of TB health promotion: a Delphi study of TB suspects and Tb patients

PubMed Central

2014-01-01

Background Health promotion for prevention and control of Tuberculosis (TB) is implemented worldwide because of its importance, but few reports have evaluated its impact on behavior due to a lack of standard outcome indicators. The objective of this study was to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients. Methods A two-round modified Delphi method involving sixteen TB control experts was used to establish a framework of behavioral indicators for outcome evaluation of TB health promotion targeted at TB suspects and patients. Results Sixteen of seventeen invited experts in TB control (authority score of 0.91 on a 1.0 scale) participated in round 1 survey. All sixteen experts also participated in a second round survey. After two rounds of surveys and several iterations among the experts, there was consensus on a framework of indicators for measuring outcomes of TB health promotion for TB suspects and patients. For TB suspects, the experts reached consensus on 2 domains (“Healthcare seeking behavior” and “Transmission prevention”), 3 subdomains (“Seeking care after onset of TB symptoms”, “Pathways of seeking care” and “Interpersonal contact etiquette”), and 8 indicators (including among others, “Length of patient delay”). For TB patients, consensus was reached on 3 domains (“Adherence to treatment”, “Healthy lifestyle” and “Transmission prevention”), 8 subdomains (including among others, “Adherence to their medication”), and 14 indicators (including “Percentage of patients who adhered to their medication”). Operational definitions and data sources were provided for each indicator. Conclusions The findings of this study provide the basis for debate among international experts on a framework for achieving global consensus on outcome indicators for TB health promotion interventions targeted at TB patients and suspects. Such consensus will help to

When students become patients: TB disease among medical undergraduates in Cape Town, South Africa.

PubMed

Van der Westhuizen, Helene-Mari; Dramowski, Angela

2017-05-24

Medical students acquire latent tuberculosis (TB) infection at a rate of 23 cases/100 person-years. The frequency and impact of occupational TB disease in this population are unknown. A self-administered questionnaire was distributed via email and social media to current medical students and recently graduated doctors (2010 - 2015) at two medical schools in Cape Town. Individuals who had developed TB disease as undergraduate students were eligible to participate. Quantitative and qualitative data collected from the questionnaire and semi-structured interviews were analysed with descriptive statistics and a framework approach to identify emerging themes. Twelve individuals (10 female) reported a diagnosis of TB: pulmonary TB (n=6), pleural TB (n=3), TB lymphadenitis (n=2) and TB spine (n=1); 2/12 (17%) had drug-resistant disease (DR-TB). Mean diagnostic delay post consultation was 8.1 weeks, with only 42% of initial diagnoses being correct. Most consulted private healthcare providers (general practitioners (n=7); pulmonologists (n=4)), and nine underwent invasive procedures (bronchoscopy, pleural fluid aspiration and tissue biopsy). Substantial healthcare costs were incurred (mean ZAR25 000 for drug-sensitive TB, up to  ZAR104 000 for DR-TB). Students struggled to obtain treatment, incurred high transport costs and missed academic time. Students with DR-TB interrupted their studies and experienced severe side-effects (hepatotoxicity, depression and permanent ototoxicity). Most participants cited poor TB infection-control practices at their training hospitals as a major risk factor for occupational TB. Undergraduate medical students in Cape Town are at high risk of occupationally acquired TB, with an unmet need for comprehensive occupational health services and support.

Implementation of tuberculosis infection prevention and control in Mozambican health care facilities.

PubMed

Brouwer, M; Coelho, E; das Dores Mosse, C; van Leth, F

2015-01-01

District and urban health care facilities in three provinces (Manica, Sofala, Tete) in central Mozambique. To assess the level of implementation of selected tuberculosis infection prevention and control (TB-IPC) measures. In a cross-sectional study of TB-IPC implementation in 29 health care facilities, we assessed TB clinics, laboratories, out-patient departments and medical and TB wards. Assessment included selected managerial, administrative and environmental measures and the availability and use of respiratory protective equipment (N95 respirators). Guidelines for diagnosis and treatment of (presumptive) TB patients were not present in all facilities. Staff instructed patients on sputum collection in 91%, but only 4% observed it. Using a pragmatic '20% rule', 52% of the rooms assessed had adequate ventilation. Potentially, this could be increased to 76%. Three quarters of the health care workers had N95 respirators. Only 36% knew how to use it correctly. Implementation of TB-IPC measures showed wide variations within health care facilities. Relatively simple measures to improve TB-IPC include the availability of guidelines, opening doors and windows to improve ventilation, and training and support on correct N95 respirator use. However, even relatively simple measures are challenging to implement, and require careful attention in and evaluation of the implementation process.

Catching the missing million: experiences in enhancing TB & DR-TB detection by providing upfront Xpert MTB/RIF testing for people living with HIV in India.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.

Catching the Missing Million: Experiences in Enhancing TB & DR-TB Detection by Providing Upfront Xpert MTB/RIF Testing for People Living with HIV in India

PubMed Central

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

Background A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. Method The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. Result 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9–29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6–14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. Conclusion The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV. PMID:25658091

Tracking and Treating Mobile Populations. The TB Net System. Migrant Clinicians Network Monograph Series. = El Sistema de Red para la TB.

ERIC Educational Resources Information Center

Migrant Clinicians Network, Inc., Austin, TX.

A comprehensive tracking and referral network that helps provide continuity of care for mobile populations with active tuberculosis (TB) or TB infection is considered essential for effective treatment of TB. However, the interstate referral system that exists between state health departments has been highly inefficient for serving migrant…

Long noncoding RNA derived from CD244 signaling epigenetically controls CD8+ T-cell immune responses in tuberculosis infection

PubMed Central

Wang, Yang; Zhong, Huiling; Xie, Xiaodan; Chen, Crystal Y.; Huang, Dan; Shen, Ling; Zhang, Hui; Chen, Zheng W.; Zeng, Gucheng

2015-01-01

Molecular mechanisms for T-cell immune responses modulated by T cell-inhibitory molecules during tuberculosis (TB) infection remain unclear. Here, we show that active human TB infection up-regulates CD244 and CD244 signaling-associated molecules in CD8+ T cells and that blockade of CD244 signaling enhances production of IFN-γ and TNF-α. CD244 expression/signaling in TB correlates with high levels of a long noncoding RNA (lncRNA)-BC050410 [named as lncRNA-AS-GSTT1(1-72) or lncRNA-CD244] in the CD244+CD8+ T-cell subpopulation. CD244 signaling drives lncRNA-CD244 expression via sustaining a permissive chromatin state in the lncRNA-CD244 locus. By recruiting polycomb protein enhancer of zeste homolog 2 (EZH2) to infg/tnfa promoters, lncRNA-CD244 mediates H3K27 trimethylation at infg/tnfa loci toward repressive chromatin states and inhibits IFN-γ/TNF-α expression in CD8+ T cells. Such inhibition can be reversed by knock down of lncRNA-CD244. Interestingly, adoptive transfer of lncRNA-CD244–depressed CD8+ T cells to Mycobacterium tuberculosis (MTB)-infected mice reduced MTB infection and TB pathology compared with lncRNA-CD244–expressed controls. Thus, this work uncovers previously unidentified mechanisms in which T cell-inhibitory signaling and lncRNAs regulate T-cell responses and host defense against TB infection. PMID:26150504

Prevalence and Risk Factors for Tuberculosis Infection among Hospital Workers in Hanoi, Viet Nam

PubMed Central

Kobayashi, Nobuyuki; Yanai, Hideki; Toyota, Emiko; Sakurada, Shinsaku; Huu Thuong, Pham; Cuong, Vu Cao; Nanri, Akiko; Mizoue, Tetsuya; Matsushita, Ikumi; Harada, Nobuyuki; Higuchi, Kazue; Tuan, Le Anh; Keicho, Naoto

2009-01-01

Background Transmission of tuberculosis (TB) to health care workers (HCWs) is a global issue. Although effective infection control measures are expected to reduce nosocomial TB, HCWs' infection has not been assessed enough in TB high burden countries. We conducted a cross-sectional study to determine the prevalence of TB infection and its risk factors among HCWs in Hanoi, Viet Nam. Methodology/Principal Findings A total of 300 HCWs including all staff members in a municipal TB referral hospital received an interferon-gamma release assay (IGRA), QuantiFERON-TB Gold In-TubeTM, followed by one- and two-step tuberculin skin test (TST) and a questionnaire-based interview. Agreement between the tests was evaluated by kappa statistics. Risk factors for TB infection were analyzed using a logistic regression model. Among the participants aged from 20 to 58 years (median = 40), prevalence of TB infection estimated by IGRA, one- and two-step TST was 47.3%, 61.1% and 66.3% respectively. Although the levels of overall agreement between IGRA and TST were moderate, the degree of agreement was low in the group with BCG history (kappa = 0.29). Working in TB hospital was associated with twofold increase in odds of TB infection estimated by IGRA. Increased age, low educational level and the high body mass index also demonstrated high odds ratios of IGRA positivity. Conclusions/Significance Prevalence of TB infection estimated by either IGRA or TST is high among HCWs in the hospital environment for TB care in Viet Nam and an infection control program should be reinforced. In communities with heterogeneous history of BCG vaccination, IGRA seems to estimate TB infection more accurately than any other criteria using TST. PMID:19710920

Ex-vivo characterization of regulatory T cells in pulmonary tuberculosis patients, latently infected persons, and healthy endemic controls.

PubMed

Zewdie, Martha; Howe, Rawleigh; Hoff, Søren T; Doherty, T Mark; Getachew, Nahom; Tarekegne, Azeb; Tessema, Bamlak; Yamuah, Lawrence; Aseffa, Abraham; Abebe, Markos

2016-09-01

Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB. We isolated PBMC from smear positive TB patients (TB, N = 13) before and after treatment, latent TB infected participants (LTBI, N = 8), and healthy endemic controls (EC, N = 9) and evaluated the frequency of different populations of Tregs and expression of FOXP3 by flowcytometry using six markers. The findings in this study showed that the association of Treg frequency with TB disease depends on the phenotypic markers used. While the frequency of CD4(+)CD25(+/hi) T cells was higher in TB patients compared to LTBI individuals, there was no difference in the frequency of CD4(+)CD25(+)FOXP3(+)CD127(lo) Treg among TB, LTBI, or EC. However, delineation of Tregs into active and naïve subsets revealed a significant increase in FOXP3 expression in active primed Tregs (CD4(+)CD25(+)FOXP3(+)CD127(lo)CD45RO(+)Ki-67(+)) of TB patients compared to LTBI and EC; and a significantly higher frequency of resting primed (CD45RO(+)Ki-67(-)) Treg in QuantiFERON negative EC compared to TB patients. After treatment completion, there was a significant decline in the frequency of active primed Treg, median (IQR) from 12.4% (9.5-21.9) of Tregs to 9.3% (7.0-12.2); P = 0.003 Wilcoxon signed rank test. We conclude that Treg subsets may be differentially regulated and expressed in TB disease, cure, and infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ex-vivo characterization of regulatory T cells in pulmonary tuberculosis patients, latently infected persons, and healthy endemic controls

PubMed Central

Zewdie, Martha; Howe, Rawleigh; Hoff, Søren T.; Doherty, T. Mark; Getachew, Nahom; Tarekegne, Azeb; Tessema, Bamlak; Yamuah, Lawrence; Aseffa, Abraham; Abebe, Markos

2016-01-01

SUMMARY Background Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB. Method We isolated PBMC from smear positive TB patients (TB, N = 13) before and after treatment, latent TB infected participants (LTBI, N = 8), and healthy endemic controls (EC, N = 9) and evaluated the frequency of different populations of Tregs and expression of FOXP3 by flowcytometry using six markers. Results The findings in this study showed that the association of Treg frequency with TB disease depends on the phenotypic markers used. While the frequency of CD4+CD25+/hi T cells was higher in TB patients compared to LTBI individuals, there was no difference in the frequency of CD4+CD25+FOXP3+CD127lo Treg among TB, LTBI, or EC. However, delineation of Tregs into active and naïve subsets revealed a significant increase in FOXP3 expression in active primed Tregs (CD4+CD25+FOXP3+CD127loCD45RO+Ki-67+) of TB patients compared to LTBI and EC; and a significantly higher frequency of resting primed (CD45RO+Ki-67−) Treg in QuantiFERON negative EC compared to TB patients. After treatment completion, there was a significant decline in the frequency of active primed Treg, median (IQR) from 12.4% (9.5–21.9) of Tregs to 9.3% (7.0–12.2); P = 0.003 Wilcoxon signed rank test. We conclude that Treg subsets may be differentially regulated and expressed in TB disease, cure, and infection. PMID:27553411

Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA.

PubMed

van Rensburg, Ilana C; Wagman, Chandre; Stanley, Kim; Beltran, Caroline; Ronacher, Katharina; Walzl, Gerhard; Loxton, Andre G

2017-01-10

Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment).We show that FASLG, IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to healthy controls. The changes in expression levels of CD38 may be due to a reduced activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there was a significant increase in the expression of APRIL and IL5RA in TB cases. Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were upregulated in B-cells from TB cases. The increase in the expression of APRIL and CD19 suggests that there may be restored activation of B-cells following anti-TB treatment. The upregulation of FASLG and IL5RA indicates that B-cells expressing regulatory genes may play an important role in the protective immunity against M.tb infection. Our results show that increased activation of B-cells is present following successful TB treatment, and that the expression of FASLG and IL5RA could potentially be utilised as a signature to monitor treatment response.

Latent tuberculosis infections in hard-to-reach drug using population-detection, prevention and control.

PubMed

Hwang, Lu-Yu; Grimes, Carolyn Z; Beasley, R Palmer; Graviss, Edward A

2009-12-01

Interferon-gamma release assays (IGRAs) need be evaluated for effectiveness as screening tests for tuberculosis (TB) infection in drug users. These tests have demonstrated improved sensitivity and specificity, but have not been studied in drug users. These one step blood tests are intended to replace the tuberculin skin test (TST), which is difficult to use and requires 48 hour follow-up, so they are expected to be particularly suitable for risk groups, like drug users, in whom follow-up is problematic. Drug users have traditionally been identified as being at increased risk for acquiring TB disease. The results of our pilot study using the TST and simpler and more sensitive interferon-gamma release assays showed that about 45% of current drug users in Houston tested have at least one test positive for latent tuberculosis infection (LTBI). These preliminary data suggest that there is an important reservoir of LTBI in drug using populations, and the risk of progression to active TB disease with other infections is great. However, LTBI in drug using populations has not been studied in depth and deserves further investigation. We need to evaluate the validity of IGRAs for detection of latent TB infection, the factors associated with LTBI, the incidence and risk for developing active TB disease in drug users and the effectiveness of early treatment of LTBI. We believe that using better tuberculosis screening tools will allow us to more accurately measure the prevalence of latent TB infection and incidence of active TB disease in drug using populations and develop more effective TB prevention and treatment interventions in the community.

Engagement of the private pharmaceutical sector for TB control: rhetoric or reality?

PubMed

Konduri, Niranjan; Delmotte, Emily; Rutta, Edmund

2017-01-01

Private-sector retail drug outlets are often the first point of contact for common health ailments, including tuberculosis (TB). Systematic reviews on public-private mix (PPM) interventions for TB did not perform in-depth reviews specifically on engaging retail drug outlets and related stakeholders in the pharmaceutical sector. Our objective was to better understand the extent to which the World Health Organization's (WHO) recommendation on engaging retail drug outlets has been translated into programmatic policy, strategy, and intervention in low- and middle-income countries. The study included a content analysis of global-level documents from WHO and the Stop TB Partnership in five phases. A country-level content analysis from four data sources was performed. Global-level findings were tabulated based on key messages related to engaging retail drug outlets. Country-level findings were analyzed based on four factors and tabulated. National strategic plans for TB control from 14 countries with varying TB burdens and a strong private sector were reviewed. 33 global-level documents and 77 full-text articles and Union World Lung Health conference abstracts were included for review. Based on experience of engaging retail drug outlets that has emerged since the mid-2000s, in 2011 WHO and the International Pharmaceutical Federation released a joint statement on promoting the engagement of national pharmacy associations in partnership with national TB programs. Only two of 14 countries' national strategic plans had explicit statements on the need to engage their national pharmacy professional association. The success rate of referrals from retail drug outlets who visited an approved health facility for TB screening ranged from 48% in Vietnam to 86% in Myanmar. Coverage of retail drug outlets ranged from less than 5 to 9% of the universe of retail drug outlets. For WHO's End TB Strategy to be successful, scaling up retail drug outlets to increase national coverage, at

Human Mycobacterium bovis infection in the United Kingdom: Incidence, risks, control measures and review of the zoonotic aspects of bovine tuberculosis.

PubMed

de la Rua-Domenech, Ricardo

2006-03-01

Amongst the members of the Mycobacterium tuberculosis complex (MTBC), M. tuberculosis is mainly a human pathogen, whereas M. bovis has a broad host range and is the principal agent responsible for tuberculosis (TB) in domestic and wild mammals. M. bovis also infects humans, causing zoonotic TB through ingestion, inhalation and, less frequently, by contact with mucous membranes and broken skin. Zoonotic TB is indistinguishable clinically or pathologically from TB caused by M. tuberculosis. Differentiation between the causative organisms may only be achieved by sophisticated laboratory methods involving bacteriological culture of clinical specimens, followed by typing of isolates according to growth characteristics, biochemical properties, routine resistance to pyrazinamide (PZA) and specific non-commercial nucleic acid techniques. All this makes it difficult to accurately estimate the proportion of human TB cases caused by M. bovis infection, particularly in developing countries. Distinguishing between the various members of the MTBC is essential for epidemiological investigation of human cases and, to a lesser degree, for adequate chemotherapy of the human TB patient. Zoonotic TB was formerly an endemic disease in the UK population, usually transmitted to man by consumption of raw cows' milk. Human infection with M. bovis in the UK has been largely controlled through pasteurization of cows' milk and systematic culling of cattle reacting to compulsory tuberculin tests. Nowadays the majority of the 7000 cases of human TB annually reported in the UK are due to M. tuberculosis acquired directly from an infectious person. In the period 1990-2003, between 17 and 50 new cases of human M. bovis infection were confirmed every year in the UK. This represented between 0.5% and 1.5% of all the culture-confirmed TB cases, a proportion similar to that of other industrialized countries. Most cases of zoonotic TB diagnosed in the UK are attributed to (i) reactivation of long

Questions and Answers about TB

MedlinePlus

... Search Form Controls Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

Identifying components for programmatic latent tuberculosis infection control in the European Union

PubMed Central

Sandgren, Andreas; Vonk Noordegraaf-Schouten, Jannigje M; Oordt-Speets, Anouk M; van Kessel, Gerarda B; de Vlas, Sake J; van der Werf, Marieke J

2016-01-01

Individuals with latent tuberculosis infection (LTBI) are the reservoir of Mycobacterium tuberculosis in a population and as long as this reservoir exists, elimination of tuberculosis (TB) will not be feasible. In 2013, the European Centre for Disease Prevention and Control (ECDC) started an assessment of benefits and risks of introducing programmatic LTBI control, with the aim of providing guidance on how to incorporate LTBI control into national TB strategies in European Union/European Economic Area (EU/EEA) Member States and candidate countries. In a first step, experts from the Member States, candidate countries, and international and national organisations were consulted on the components of programmatic LTBI control that should be considered and evaluated in literature reviews, mathematical models and cost-effectiveness studies. This was done through a questionnaire and two interactive discussion rounds. The main components identified were identification and targeting of risk groups, determinants of LTBI and progression to active TB, optimal diagnostic tests for LTBI, effective preventive treatment regimens, and to explore the potential for combining LTBI control with other health programmes. Political commitment, a solid healthcare infrastructure, and favourable economic situation in specific countries were identified as essential to facilitate the implementation of programmatic LTBI control. PMID:27589214

Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting.

PubMed

Penn-Nicholson, Adam; Geldenhuys, Hennie; Burny, Wivine; van der Most, Robbert; Day, Cheryl L; Jongert, Erik; Moris, Philippe; Hatherill, Mark; Ofori-Anyinam, Opokua; Hanekom, Willem; Bollaerts, Anne; Demoitie, Marie-Ange; Kany Luabeya, Angelique Kany; De Ruymaeker, Evi; Tameris, Michele; Lapierre, Didier; Scriba, Thomas J

2015-07-31

Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting

PubMed Central

Penn-Nicholson, Adam; Geldenhuys, Hennie; Burny, Wivine; van der Most, Robbert; Day, Cheryl L.; Jongert, Erik; Moris, Philippe; Hatherill, Mark; Ofori-Anyinam, Opokua; Hanekom, Willem

2018-01-01

Background Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. Methods In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. Results No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. Conclusions The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials. PMID:26072017

Progress and challenges in TB vaccine development

PubMed Central

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H.E.; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development. PMID:29568497

Progress and challenges in TB vaccine development.

PubMed

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H E; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our "failed" trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

Health-care workers' perspectives on workplace safety, infection control, and drug-resistant tuberculosis in a high-burden HIV setting.

PubMed

Zelnick, Jennifer R; Gibbs, Andrew; Loveday, Marian; Padayatchi, Nesri; O'Donnell, Max R

2013-08-01

Drug-resistant tuberculosis (TB) is an occupational hazard for health-care workers (HCWs) in South Africa. We undertook this qualitative study to contextualize epidemiological findings suggesting that HCWs' elevated risk of drug-resistant TB is related to workplace exposure. A total of 55 HCWs and 7 hospital managers participated in focus groups and interviews about infection control (IC). Participants discussed caring for patients with drug-resistant TB, IC measures, occupational health programs, also stigma and support in the workplace. Key themes included: (i) lack of resources that hinders IC, (ii) distrust of IC efforts among HCWs, and (iii) disproportionate focus on individual-level personal protections, particularly N95 masks. IC programs should be evaluated, and the impact of new policies to rapidly diagnose drug-resistant TB and decentralize treatment should be assessed as part of the effort to control drug-resistant TB and create a safe workplace.

Tuberculosis prevention and control in large jails: a challenge to tuberculosis elimination.

PubMed

Roberts, Cheryl A; Lobato, Mark N; Bazerman, Lauri B; Kling, Ryan; Reichard, Audrey A; Hammett, Theodore M

2006-02-01

This study assessed the extent to which 20 large jail systems have implemented national recommendations for tuberculosis (TB) prevention and control in correctional facilities. Data were collected through questionnaires to jail medical directors and TB control directors, observation at the jails, and abstraction of medical records of inmates with TB disease and latent TB infection. Twenty percent of jail systems (4/20) had conducted an assessment of risk for TB transmission in their facilities, and 55% (11/20) monitored tuberculin skin test conversions of inmates and staff. Sixty-five percent (13/20) of jails had an aggregate record-keeping system for tracking TB status and treatment, which was usually paper based. Forty-five percent of jails (9/20) had policies to offer HIV counseling and testing to tuberculin skin test-positive patients, and 75% (15/20) screen HIV-infected inmates with chest radiographs. Three quarters of jails (15/20) had policies to always isolate patients with suspected or confirmed pulmonary TB in an airborne infection isolation room. Half of jails with airborne infection isolation rooms (6/12) conformed to Centers for Disease Control and Prevention (CDC) guidelines for monitoring negative pressure. Improvements are needed in conducting TB risk assessments and evaluations to determine priorities and reduce risk of transmission. Inadequate medical information systems are impeding TB control and evaluation efforts. Although HIV infection is the greatest cofactor for development of TB disease, jails have inadequate information on patients' HIV status to make informed decisions in screening and management of TB and latent TB infection. Jails need to improve the use of environmental controls.

Development of tuberculosis infection control guidelines in a pediatric HIV clinic in sub-Saharan Africa.

PubMed

Carlucci, J G; Jin, L; Sanders, J E; Mohapi, E Q; Mandalakas, A M

2015-03-21

A well-established pediatric human immunodeficiency virus (HIV) clinic in Lesotho with initial infection control (IC) measures prioritizing blood-borne disease. In line with international recommendations, services have been expanded to include the management of patients with tuberculosis (TB). The creation of comprehensive IC guidelines with an emphasis on TB has become a priority. To provide a model for developing and implementing IC guidelines in ambulatory care facilities in limited-resource settings with high HIV and TB prevalence. Activities: An IC plan that includes guidance covering both general IC measures and TB-specific guidelines was created by integrating local and international recommendations and emphasizing the importance of administrative measures, environmental controls, and disease-specific precautions. An interdisciplinary committee was established to oversee its implementation, monitoring, and evaluation. Development and implementation of IC guidelines in resource-limited settings are feasible and should be a priority in high HIV and TB prevalence areas. Education should be the cornerstone of such endeavors. Many interventions can be implemented with minimal expertise and material resources. Administrative support and institutional investment are essential to the sustainability of an effective IC program.

Tuberculosis and latent tuberculosis infection among healthcare workers in Kisumu, Kenya.

PubMed

Agaya, Janet; Nnadi, Chimeremma D; Odhiambo, Joseph; Obonyo, Charles; Obiero, Vincent; Lipke, Virginia; Okeyo, Elisha; Cain, Kevin; Oeltmann, John E

2015-12-01

To assess prevalence and occupational risk factors of latent TB infection and history of TB disease ascribed to work in a healthcare setting in western Kenya. We conducted a cross-sectional survey among healthcare workers in western Kenya in 2013. They were recruited from dispensaries, health centres and hospitals that offer both TB and HIV services. School workers from the health facilities' catchment communities were randomly selected to serve as the community comparison group. Latent TB infection was diagnosed by tuberculin skin testing. HIV status of participants was assessed. Using a logistic regression model, we determined the adjusted odds of latent TB infection among healthcare workers compared to school workers; and among healthcare workers only, we assessed work-related risk factors for latent TB infection. We enrolled 1005 healthcare workers and 411 school workers. Approximately 60% of both groups were female. A total of 22% of 958 healthcare workers and 12% of 392 school workers tested HIV positive. Prevalence of self-reported history of TB disease was 7.4% among healthcare workers and 3.6% among school workers. Prevalence of latent TB infection was 60% among healthcare workers and 48% among school workers. Adjusted odds of latent TB infection were 1.5 times higher among healthcare workers than school workers (95% confidence interval 1.2-2.0). Healthcare workers at all three facility types had similar prevalence of latent TB infection (P = 0.72), but increasing years of employment was associated with increased odds of LTBI (P < 0.01). Healthcare workers at facilities in western Kenya which offer TB and HIV services are at increased risk of latent TB infection, and the risk is similar across facility types. Implementation of WHO-recommended TB infection control measures are urgently needed in health facilities to protect healthcare workers. © 2015 John Wiley & Sons Ltd.

The association between ARV and TB drug resistance on TB treatment outcome among Kazakh TB/HIV patients.

PubMed

Mishkin, Kathryn; Alaei, Kamiar; Alikeyeva, Elmira; Paynter, Christopher; Aringazina, Altyn; Alaei, Arash

2018-02-26

TB drug resistance poses a serious threat to the public health of Kazakhstan. This paper presents findings related to TB treatment outcome and drug resistant status among people coinfected with HIV and TB in Kazakhstan. Cohort study using data were provided by the Kazakhstan Ministry of Health's National Tuberculosis Program for 2014 and 2015. Chi-square and logistical regression were performed to understand factors associated with drug resistant TB status and TB treatment outcome. In bivariate analysis, drug resistant status was significantly associated with year of TB diagnosis (p=0.001) viral load (p=0.03). TB treatment outcome was significantly associated with age at diagnosis (p=01), ARV treatment (p <0.0001), and TB drug resistant status (p=0.02). In adjusted analysis, drug resistance was associated with increased odds of successful completion of treatment with successful result compared to treatment failure (OR 6.94, 95% CI: 1.39-34.44) CONCLUSIONS: Our results suggest that being drug resistant is associated with higher odds of completing treatment with successful outcome, even when controlling for receipt of ARV therapy. Copyright © 2018. Published by Elsevier Ltd.

BUTIMBA: Intensifying the Hunt for Child TB in Swaziland through Household Contact Tracing

PubMed Central

Alonso Ustero, Pilar; Golin, Rachel; Anabwani, Florence; Mzileni, Bulisile; Sikhondze, Welile; Stevens, Robert

2017-01-01

Background Limited data exists to inform contact tracing guidelines in children and HIV-affected populations. We evaluated the yield and additionality of household contact and source case investigations in Swaziland, a TB/HIV high-burden setting, while prioritizing identification of childhood TB. Methods In partnership with 7 local TB clinics, we implemented standardized contact tracing of index cases (IC) receiving TB treatment. Prioritizing child contacts and HIV-affected households, screening officers screened contacts for TB symptoms and to identify risk factors associated with TB. We ascertained factors moderating the yield of contact tracing and measured the impact of our program by additional notifications. Results From March 2013 to November 2015, 3,258 ICs (54% bacteriologically confirmed; 70% HIV-infected; 85% adults) were enrolled leading to evaluation of 12,175 contacts (median age 18 years, IQR 24–42; 45% children; 9% HIV-infected). Among contacts, 196 TB cases (56% bacteriologically confirmed) were diagnosed resulting in a program yield of 1.6% for all forms of TB. The number needed to screen (NNS) to identify a bacteriologically confirmed TB case or all forms TB case traced from a child IC <5 years was respectively 62% and 40% greater than the NNS for tracing from an adult IC. In year one, we demonstrated a 32% increase in detection of bacteriologically confirmed child TB. Contacts were more likely to have TB if <5 years (OR = 2.0), HIV-infected (OR = 4.9), reporting ≥1 TB symptoms (OR = 7.7), and sharing a bed (OR = 1.7) or home (OR = 1.4) with the IC. There was a 1.4 fold increased chance of detecting a TB case in households known to be HIV-affected. Conclusion Contact tracing prioritizing children is not only feasible in a TB/HIV high-burden setting but contributes to overall case detection. Our findings support WHO guidelines prioritizing contact tracing among children and HIV-infected populations while highlighting potential to integrate TB

Knowledge and attitude of key community members towards tuberculosis: mixed method study from BRAC TB control areas in Bangladesh.

PubMed

Paul, Sukanta; Akter, Rahima; Aftab, Afzal; Khan, Antora M; Barua, Mrittika; Islam, Shayla; Islam, Akramul; Husain, Ashaque; Sarker, Malabika

2015-01-31

Bangladesh National Tuberculosis (TB) Control Programme adopted a number of strategies to facilitate TB diagnosis and treatment. 'Advocacy, Communication and Social Mobilization' (ACSM) was one of the key strategies implemented by BRAC (Bangladesh Rural Advancement Committee, a non-governmental development organization) TB control program. The purpose of this study is to assess the knowledge and attitudes of the key community members (KCMs) participated in ACSM in BRAC TB control areas. This study combined quantitative and qualitative methods using a mixed method approach. KCMs in three districts with low TB case detection rates were targeted to assess the ACSM program. The quantitative survey using a multi-stage random-sampling strategy was conducted among 432 participants. The qualitative study included in-depth interviews (IDIs) of a sub sample of 48 respondents. For quantitative analysis, descriptive statistics were reported using frequencies, percentages, and Chi square tests, while thematic analysis was used for qualitative part. Most (99%) of the participants had heard about TB, and almost all knew that TB is a contagious yet curable disease. More than half (53%) of the KCMs had good knowledge regarding TB, but BRAC workers were found to be more knowledgeable compared to other KCMs. However, considerable knowledge gaps were observed among BRAC community health workers. Qualitative results revealed that the majority of the KCMs were aware about the signs, symptoms and transmission pathways of TB and believed that smoking and addiction were the prime causes of transmission of TB. The knowledge about child TB was poor even among BRAC health workers. Stigma associated with TB was not uncommon. Almost all respondents expressed that young girls diagnosed with TB. This study finding has revealed varying levels of knowledge and mixed attitudes about TB among the KCMs. It also provides insight on the poor knowledge regarding child TB and indicate that despite the

Evaluation of the performance of two tuberculosis interferon gamma release assays (IGRA-ELISA and T-SPOT.TB) for diagnosing Mycobacterium tuberculosis infection.

PubMed

Wang, Linchuan; Tian, Xu-Dong; Yu, Yan; Chen, Wei

2018-04-01

The IGRA-ELISA and T-SPOT.TB are widely used in China. The aim of the study was to evaluate the performance of the two assays in diagnosis Mycobacterium tuberculosis infection. Of the 3727 patients in the study, 204 underwent testing using both the T-SPOT.TB and IGRA-ELISA, 1794 were tested using the T-SPOT.TB only, and 1729 were tested using the IGRA-ELISA only. The positive rate and consistency of the two assays were analyzed, and their sensitivity and specificity for diagnosing active tuberculosis were compared. There were no significant differences in the positive rate between the T-SPOT.TB test (25.8%) and IGRA-ELISA (28.6%), p = .065. The two assays were highly consistent, with a kappa value of 0.852 (p < .0001) and a total coincidence rate of 92.7%. For the diagnosis of active tuberculosis, the sensitivity and specificity values of the T-SPOT.TB test were 82.9% (107/129) and 78.6% (1309/1665), respectively, and those of IGRA-ELISA were 81.7% (94/115) and 75.2% (1214/1614), respectively. There were no significant differences in sensitivity (p > .05), but the specificity of the T-SPOT.TB test was slightly higher than that of IGRA-ELISA (p = .023). Both in terms of diagnosing M. tuberculosis infection and ruling out active tuberculosis, the performance of the IGRA-ELISA-a simple, almost labor-free assay that allows simultaneous processing of a very large number of samples-was well-matched with that of T-SPOT.TB test. However, IGRAs cannot be used as the only test to diagnose active tuberculosis. Copyright © 2018 Elsevier B.V. All rights reserved.

The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome

PubMed Central

Manabe, Yukari C.; Kesavan, Anup K.; Lopez-Molina, Javier; Hatem, Christine L.; Brooks, Megan; Fujiwara, Ricardo; Hochstein, Karl; Pitt, M. Louise M.; Tufariello, JoAnn; Chan, John; McMurray, David N.; Bishai, William R.; Dannenberg, Arthur M.; Mendez, Susana

2015-01-01

The large reservoir of human latent tuberculosis (TB) contributes to the global success of the pathogen, Mycobacterium tuberculosis (Mtb). We sought to test whether aerosol infection of rabbits with Mtb H37Rv could model paucibacillary human latent TB. The lung burden of infection peaked at 5 weeks after aerosol infection followed by host containment of infection that was achieved in all rabbits. One-third of rabbits had at least one caseous granuloma with culturable bacilli at 36 weeks after infection suggesting persistent paucibacillary infection. Corticosteroid-induced immunosuppression initiated after disease containment resulted in reactivation of disease. Seventy-two percent of rabbits had culturable bacilli in the right upper lung lobe homogenates compared to none of the untreated controls. Discontinuation of dexamethasone led to predictable lymphoid recovery, with a proportion of rabbits developing multicentric large caseous granuloma. The development and severity of the immune reconstitution inflammatory syndrome (IRIS) was dependent on the antigen load at the time of immunosuppression and subsequent bacillary replication during corticosteroid-induced immunosuppression. Clinically, many aspects were similar to IRIS in severely immunosuppressed HIV-infected patients who have functional restoration of T cells in response to effective (highly active) antiretroviral therapy. This corticosteroid model is the only animal model of the IRIS. Further study of the rabbit model of TB latency, reactivation and IRIS may be important in understanding the immunopathogenesis of these poorly modeled states as well as for improved diagnostics for specific stages of disease. PMID:18068491

Epidemiological Characteristics and Clinical Outcome of HIV-Related Tuberculosis in a Population of TB Patients in South-western Nigeria.

PubMed

Olowe, Olugbenga A; Makanjuola, Olufunmilola B; Adekanmi, Adeniyi S; Adefioye, Olusola J; Olowe, Rita A

2017-06-01

Tuberculosis (TB) is the second leading cause of death from infectious disease globally with its impact more dramatic in resource limited settings. Individuals with human immunodeficiency virus (HIV) infection who also develop tuberculosis represent a significant challenge to TB control. This study was carried out to determine the prevalence of TB-HIV coinfection and pattern of infection among TB patients. We also compared treatment outcome among coinfected patients with those not coinfected. A six-year retrospective review of records of patients managed at the Tuberculosis Treatment Center of the LAUTECH Teaching Hospital, South-Western Nigeria from January 2009 to December 2014 was carried out. One hundred and five (26.3%) of the 399 TB patients seen in the study period were coinfected with HIV. About 10% of the subjects had extrapulmonary tuberculosis. Treatment failure was significantly worse among patients who had both HIV and TB compared with those who had TB only (49.5% vs. 32%, p = 0.001). Death rate was also higher in the coinfected individuals implying a poorer clinical outcome. High prevalence of TB-HIV coinfection and poor treatment outcome in this group of individuals, though predictable, calls for a more concerted effort in the management of TB-HIV coinfection.

Risk Factors for DOTS Treatment Default Among New HIV-TB Coinfected Patients in Nalgonda (Dist.) Telangana (State): A Case Control Study.

PubMed

Reddy Satti, Siva Balaji; Kondagunta, Nagaraj

2016-01-01

The therapeutic regimens as recommended by the Revised National TB Control Programme (RNTCP) have been shown to be highly effective for both preventing and treating tuberculosis, but poor adherence to medication is a major barrier to its global control. The study was conducted to assess the influence of patient related factors for DOTS Treatment Default among HIV-TB Co-infected cases. This was a case control study conducted in Nalgond, Telangana. All new HIV-TB coinfected and DOTS-defaulted patients registered under RNTCP for the period from January 2010 to December 2012 were selected. Of the 154 patients, 23 had died and 11 could not be traced, and these were excluded. Thus the total number of available cases were 120 for those age- and sex-matched controls (HIV-TB coinfected patients and those who had completed the DOTS regimen successfully) were selected. The mean age was 36.5 ± 9 years; the majority (23.3%) of patients defaulted during the second month of treatment. Significant risk factors associated with defaulting included unskilled occupation [adjusted odds ratio (AOR: 3.56; 95% confidence interval (CI): 1.1-11.56], lower middle class socioeconomic status (AOR: 17.16; 95% CI: 3.93-74.82), small family size (AOR: 21.3; 95% CI: 6.4-70.91), marital disharmony (AOR: 6.78; 95% CI: 1.93-23.76), not being satisfied with the conduct of health personnel (AOR: 7.38; 95% CI: 2.32-23.39), smoking (AOR: 8.5; 95% CI: 2.31-31.21), and side effects of drugs (AOR: 4.18; 95% CI: 1.35-12.9). Unskilled occupation, marital disharmony, small family size, lower middle class socioeconomic status, not being satisfied with the conduct of health personnel, smoking, and drug side effects were significantly associated with defaulting. Information on the pattern of tuberculosis (TB), the outcome of anti-tuberculosis treatment (ATT), and the factors associated with it will help in planning interventions to improve adherence to DOTS treatment.

HIV Infection and Geographically Bound Transmission of Drug-Resistant Tuberculosis, Argentina

PubMed Central

López, Beatriz; Ambroggi, Marta; Palmero, Domingo; Salvadores, Bernardo; Gravina, Elida; Mazzeo, Eduardo; Imaz, Susana; Barrera, Lucía

2012-01-01

During 2003–2009, the National Tuberculosis (TB) Laboratory Network in Argentina gave 830 patients a new diagnosis of multidrug-resistant (MDR) TB and 53 a diagnosis of extensively drug- resistant (XDR) TB. HIV co-infection was involved in nearly one third of these cases. Strain genotyping showed that 7 major clusters gathered 56% of patients within restricted geographic areas. The 3 largest clusters corresponded to epidemic MDR TB strains that have been undergoing transmission for >10 years. The indigenous M strain accounted for 29% and 40% of MDR and XDR TB cases, respectively. Drug-resistant TB trends in Argentina are driven by spread of a few strains in hotspots where the rate of HIV infection is high. To curb transmission, the national TB program is focusing stringent interventions in these areas by strengthening infection control in large hospitals and prisons, expediting drug resistance detection, and streamlining information-sharing systems between HIV and TB programs. PMID:23092584

Prevalence of pulmonary TB and spoligotype pattern of Mycobacterium tuberculosis among TB suspects in a rural community in Southwest Ethiopia

PubMed Central

2012-01-01

Background In Ethiopia where there is no strong surveillance system and state of the art diagnostic facilities are limited, the real burden of tuberculosis (TB) is not well known. We conducted a community based survey to estimate the prevalence of pulmonary TB and spoligotype pattern of the Mycobacterium tuberculosis isolates in Southwest Ethiopia. Methods A total of 30040 adults in 10882 households were screened for pulmonary TB in Gilgel Gibe field research centre in Southwest Ethiopia. A total of 482 TB suspects were identified and smear microscopy and culture was done for 428 TB suspects. Counseling and testing for HIV/AIDS was done for all TB suspects. Spoligotyping was done to characterize the Mycobacterium tuberculosis isolates. Results Majority of the TB suspects were females (60.7%) and non-literates (83.6%). Using smear microscopy, a total of 5 new and 4 old cases of pulmonary TB cases were identified making the prevalence of TB 30 per 100,000. However, using the culture method, we identified 17 new cases with a prevalence of 76.1 per 100,000. There were 4.3 undiagnosed pulmonary TB cases for every TB case who was diagnosed through the passive case detection mechanism in the health facility. Eleven isolates (64.7%) belonged to the six previously known spoligotypes: T, Haarlem and Central-Asian (CAS). Six new spoligotype patterns of Mycobacterium tuberculosis, not present in the international database (SpolDB4) were identified. None of the rural residents was HIV infected and only 5 (5.5%) of the urban TB suspects were positive for HIV. Conclusion The prevalence of TB in the rural community of Southwest Ethiopia is low. There are large numbers of undiagnosed TB cases in the community. However, the number of sputum smear-positive cases was very low and therefore the risk of transmitting the infection to others may be limited. Active case finding through health extension workers in the community can improve the low case detection rate in Ethiopia. A large

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

PubMed Central

2011-01-01

Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral

Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination.

PubMed

Diel, Roland; Loddenkemper, Robert; Zellweger, Jean-Pierre; Sotgiu, Giovanni; D'Ambrosio, Lia; Centis, Rosella; van der Werf, Marieke J; Dara, Masoud; Detjen, Anne; Gondrie, Peter; Reichman, Lee; Blasi, Francesco; Migliori, Giovanni Battista

2013-09-01

The introduction of new rapid diagnostic tools for tuberculosis (TB) and the promising TB drugs pipeline together with the development of a new World Health Organization Strategy post 2015 allows new discussions on how to direct TB control. The European Respiratory Society's European Forum for TB Innovation was created to stimulate discussion on how to best take advantage of old and new opportunities, and advances, to improve TB control and eventually progress towards the elimination of TB. While TB control is aimed at reducing the incidence of TB by early diagnosis and treatment of infectious cases of TB, TB elimination requires focus on sterilising the pool of latently infected individuals, from which future TB cases would be generated. This manuscript describes the three core components that are necessary to implement the elimination strategy fully. 1) Improve diagnosis of latent TB infected individuals. 2) Improve regimens to treat latent TB infection. 3) ensure public health commitment to make both 1) and 2) possible. Old and new evidence is critically described, focusing on the European commitment to reach elimination and on the innovative experiences and best practices available.

Pastoralism and delay in diagnosis of TB in Ethiopia

PubMed Central

Gele, Abdi A; Bjune, Gunnar; Abebe, Fekadu

2009-01-01

Background Tuberculosis (TB) is a major public health problem in the Horn of Africa with Ethiopia being the most affected where TB cases increase at the rate of 2.6% each year. One of the main contributing factors for this rise is increasing transmission due to large number of untreated patients, serving as reservoirs of the infection within the communities. Reduction of the time between onset of TB symptoms to diagnosis is therefore a prerequisite to bring the TB epidemic under control. The aim of this study was to measure duration of delay among pastoralist TB patients at TB management units in Somali Regional State (SRS) of Ethiopia. Methods A cross sectional study of 226 TB patients with pastoralist identity was conducted in SRS of Ethiopia from June to September 2007. Patients were interviewed using questionnaire based interview. Time between onset of TB symptoms and first visit to a professional health care provider (patient delay), and the time between first visits to the professional health care provider to the date of diagnosis (medical provider's delay) were analyzed. Both pulmonary and extrapulmonary TB patients were included in the study. Result A total of 226 pastoralist TB patients were included in this study; 93 (41.2%) were nomadic pastoralists and 133 (58.8%) were agro-pastoralists. Median patient delay was found to be 60 days with range of 10–1800 days (83 days for nomadic pastoralists and 57 days for agro-pastoralists). Median health care provider's delay was 6 days and median total delay was 70 days in this study. Patient delay constituted 86% of the total delay. In multivariate logistic regression analysis, nomadic pastoralism (aOR. 2.69, CI 1.47–4.91) and having low biomedical knowledge on TB (aOR. 2.02, CI 1.02–3.98) were significantly associated with prolonged patient delay. However, the only observed risk factor for very long patient delay >120 days was distance to health facility (aOR.4.23, CI 1.32–13.54). Extra-pulmonary TB was

Impact of Infection Control Measures to Control an Outbreak of Multidrug-Resistant Tuberculosis in a Human Immunodeficiency Virus Ward, Peru

PubMed Central

Ticona, Eduardo; Huaroto, Luz; Kirwan, Daniela E.; Chumpitaz, Milagros; Munayco, César V.; Maguiña, Mónica; Tovar, Marco A.; Evans, Carlton A.; Escombe, Roderick; Gilman, Robert H.

2016-01-01

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000—56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug–susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB–coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective. PMID:27621303

A world of cities and the end of TB

PubMed Central

Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

2016-01-01

The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. PMID:26884491

46 CFR 39.1015 - Foreign-flagged tank vessel certification procedures for vapor control system designs-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... vapor control system designs-TB/ALL. 39.1015 Section 39.1015 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.1015 Foreign-flagged tank vessel certification procedures for vapor control system designs—TB/ALL. As an alternative to meeting the requirements...

46 CFR 39.1015 - Foreign-flagged tank vessel certification procedures for vapor control system designs-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... vapor control system designs-TB/ALL. 39.1015 Section 39.1015 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.1015 Foreign-flagged tank vessel certification procedures for vapor control system designs—TB/ALL. As an alternative to meeting the requirements...

Voices of decision makers on evidence-based policy: A case of evolving TB/HIV co-infection policy in India.

PubMed

Reddy, K Srikanth; Sahay, Seema

2016-01-01

This study explores decision makers' perspectives on evidence-based policy (EBP) development using the case of TB/HIV co-infection in India. Twelve in-depth interviews were conducted with purposively selected key national and international policy decision makers in India. Verbatim transcripts were processed and analysed thematically using QSR (NUD*IST 6). The decision makers were unequivocal in recognizing the TB/HIV co-infection as an important public health issue in India and stated the problem to be different than Africa. The need of having a "third programme" for co-infection was not felt. According to them, the public health management of this co-infection must be within the realm of these two programmes. The study also emphasized on decision makers' perspectives on evidence and the process of utilization of evidence for decision-making for co-infection. Study findings showed global evidence was not always accepted by the decision makers and study shows several examples of decision makers demanding local evidence for policy decisions. Decision makers did make interim policies based on global evidence but most of the time their mandate was to get local evidence. Thus, operations research/implementation science especially multi-centric studies emerge as important strategy for EBP development. Researcher-policy maker interface was a gap where role of researcher as aggressive communicator of research findings was expected.

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

PubMed Central

Scordo, Julia M.; Arcos, Jesús; Kelley, Holden V.; Diangelo, Lauren; Sasindran, Smitha J.; Youngmin, Ellie; Wewers, Mark D.; Wang, Shu-Hua; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B.

2017-01-01

In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis (M.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site. PMID:28373877

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection.

PubMed

Scordo, Julia M; Arcos, Jesús; Kelley, Holden V; Diangelo, Lauren; Sasindran, Smitha J; Youngmin, Ellie; Wewers, Mark D; Wang, Shu-Hua; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B

2017-01-01

In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis ( M.tb ) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site.

Multiple intracranial space-occupying lesions in a renal transplant recipient from an area endemic for tuberculosis (TB): TB vs. toxoplasmosis.

PubMed

Bagchi, S; Sachdev, S S; Nalwa, A; Das, C J; Sinha, S; Suri, V; Mahajan, S; Bhowmik, D; Agarwal, S

2014-10-01

Renal transplant recipients may present with intracranial space-occupying lesions (SOLs) due to infections as well as a post-transplant lymphoproliferative disorder (PTLD). Here, we discuss a renal transplant recipient who presented with neurologic symptoms and magnetic resonance imaging (MRI) of the brain showed multiple focal SOLs. Tuberculosis (TB), toxoplasmosis, nocardiosis, fungal infections, and PTLD were considered in the differential diagnosis. MRI spectroscopy was suggestive of an infectious cause, such as toxoplasmosis or TB. Serologic tests using Toxoplasma were negative. A brain biopsy followed by immunohistochemical staining using Toxoplasma antibody demonstrated multiple intravascular cysts of toxoplasma. This case highlights the diagnostic dilemma in an immunocompromised patient with multiple focal brain lesions, especially in areas where TB is endemic. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hit Generation in TB Drug Discovery: From Genome to Granuloma

PubMed Central

2018-01-01

Current tuberculosis (TB) drug development efforts are not sufficient to end the global TB epidemic. Recent efforts have focused on the development of whole-cell screening assays because biochemical, target-based inhibitor screens during the last two decades have not delivered new TB drugs. Mycobacterium tuberculosis (Mtb), the causative agent of TB, encounters diverse microenvironments and can be found in a variety of metabolic states in the human host. Due to the complexity and heterogeneity of Mtb infection, no single model can fully recapitulate the in vivo conditions in which Mtb is found in TB patients, and there is no single “standard” screening condition to generate hit compounds for TB drug development. However, current screening assays have become more sophisticated as researchers attempt to mirror the complexity of TB disease in the laboratory. In this review, we describe efforts using surrogates and engineered strains of Mtb to focus screens on specific targets. We explain model culture systems ranging from carbon starvation to hypoxia, and combinations thereof, designed to represent the microenvironment which Mtb encounters in the human body. We outline ongoing efforts to model Mtb infection in the lung granuloma. We assess these different models, their ability to generate hit compounds, and needs for further TB drug development, to provide direction for future TB drug discovery. PMID:29384369

The prevalence of HIV among adults with pulmonary TB at a population level in Zambia.

PubMed

Chanda-Kapata, Pascalina; Kapata, Nathan; Klinkenberg, Eveline; Grobusch, Martin P; Cobelens, Frank

2017-03-29

Tuberculosis and HIV co-infection is one of the main drivers of poor outcome for both diseases in Zambia. HIV infection has been found to predict TB infection/disease and TB has been reported as a major cause of death among individuals with HIV. Improving case detection of TB/HIV co-infection has the potential to lead to early treatment of both conditions and can impact positively on treatment outcomes. This study was conducted in order to determine the HIV prevalence among adults with tuberculosis in a national prevalence survey setting in Zambia, 2013-2014. A countrywide cross sectional survey was conducted in 2013/2014 using stratified cluster sampling, proportional to population size for rural and urban populations. Each of the 66 countrywide clusters represented one census supervisory area with cluster size averaging 825 individuals. Socio-demographic characteristics were collected during a household visit by trained survey staff. A standard symptom-screening questionnaire was administered to 46,099 eligible individuals across all clusters, followed by chest x-ray reading for all eligible. Those symptomatic or with x-ray abnormalities were confirmed or ruled out as TB case by either liquid culture or Xpert MTBRif performed at the three central reference laboratories. HIV testing was offered to all participants at the survey site following the national testing algorithm with rapid tests. The prevalence was expressed as the proportion of HIV among TB cases with 95% confidence limits. A total of 265/6123 (4.3%) participants were confirmed of having tuberculosis. Thirty-six of 151 TB survey cases who accepted HIV testing were HIV-seropositive (23.8%; 95% CI 17.2-31.4). The mean age of the TB/HIV cases was 37.6 years (range 24-70). The majority of the TB/HIV cases had some chest x-ray abnormality (88.9%); were smear positive (50.0%), and/or had a positive culture result (94.4%). None of the 36 detected TB/HIV cases were already on TB treatment, and 5/36 (13

Tuberculosis: The Connection between TB and HIV (the AIDS Virus)

MedlinePlus

... Task Force Tuberculosis: The Connection between TB and HIV Recommend on Facebook Tweet Share Compartir Order this ... if I am infected with both TB and HIV? If you have HIV, it is important to ...

Risk factors for false-negative T-SPOT.TB assay results in patients with pulmonary and extra-pulmonary TB.

PubMed

Pan, Liping; Jia, Hongyan; Liu, Fei; Sun, Huishan; Gao, Mengqiu; Du, Fengjiao; Xing, Aiying; Du, Boping; Sun, Qi; Wei, Rongrong; Gu, Shuxiang; Zhang, Zongde

2015-04-01

To investigate the risk factors for false-negative T-SPOT.TB results in patients with pulmonary TB (PTB) and extra-pulmonary TB (EPTB). Patients with suspected TB who underwent valid T-SPOT.TB tests were prospectively enrolled at Beijing Chest Hospital between November 2012 and November 2013. Basic characters and clinical laboratory findings were compared between true-positive and false-negative T-SPOT.TB groups. Of 1928 suspected TB patients, 774 (530 PTB and 244 EPTB) microbiologically/histopathogenically-confirmed patients (636 culture-confirmed) were analyzed. Forty-six PTB patients (8.7%) and 32 EPTB patients (13.1%) had negative T-SPOT.TB results. Multivariate analysis showed that increased age [odds radio (OR) 2.26, 95% confidence interval (CI) 1.11-4.58], over-weight (BMI ≥ 25 kg/m(2), OR 2.43, 95% CI 1.05-5.63), and a longer period of illness before hospitalization (>6 months, OR 2.46, 95% CI 1.24-4.92) were independent risk factors for false-negative T-SPOT.TB results in PTB patients. In EPTB patients, increased age (OR 2.42, 95% CI 1.09-5.35) also showed an independent association with false-negative T-SPOT.TB results. Careful interpretation of negative T-SPOT.TB results is necessary in older patients with suspected PTB or EPTB, and in PTB patients who are over-weight or have had longer periods of illness before hospitalization. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Multidrug-resistant tuberculosis: The problem and some priorities in controlling it.

PubMed

Hoffner, Sven

2016-12-01

Multidrug-resistant tuberculosis (MDR-TB), and even more severe forms of drug resistance, cause significant problems and costs for national TB control programs and constitutes an increasing public health concern globally. In parts of the former Soviet Union, the prevalence of MDR-TB is as high as 50% and one third of all newly detected TB patients are infected with MDR strains. Such strains transmit and certain MDR-TB clones constitute an important part of the problem, especially in high MDR-TB burden areas. There are several actions that should be given priority to control this situation. A first important step is timely detection of all patients infected with resistant strains, which makes possible prompt change of standard TB chemotherapy to more effective combinations of drugs. This is important both from the public health and clinical perspectives, since it renders the individual patient noninfectious and subsequently cured. Early detection of MDR-TB also allows infection control to be focused where it is most needed. Strengthened infection control measures are crucial for limiting the ongoing spread of resistant TB in hospitals and elsewhere. In addition, a sustainable drug supply must be ensured to guarantee that all patients are initiated on effective treatment and can avoid interruptions due to drug shortages. An extra focus should be put on vulnerable cases, such as immunosuppressed individuals, prisoners, drug addicts, and migrants, in whom TB is generally more frequent and difficult to control than in the normal population. Finally, political support is needed to ensure necessary infrastructures, human and financial resources to effectively control drug resistant TB. Copyright © 2016.

TB in Children in the United States

MedlinePlus

... Search Form Controls Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

Tuberculosis knowledge, attitudes, and practices among northern Ethiopian prisoners: Implications for TB control efforts.

PubMed

Adane, Kelemework; Spigt, Mark; Johanna, Laturnus; Noortje, Dorscheidt; Abera, Semaw Ferede; Dinant, Geert-Jan

2017-01-01

Although awareness is an important component in tuberculosis (TB) control, we do not know how much Ethiopian prisoners know about TB. This study assessed the level of knowledge, attitudes, and practices (KAP) of prisoners about TB in eight northern Ethiopian prisons. Data were collected cross-sectionally from 615 prisoners using a standardized questionnaire between March and May 2016. The outcome variables were defined considering the basic elements about TB. Out of 615 prisoners, only 37.7% mentioned bacteria as a cause of TB while 21.7% related TB to exposure to cold wind. Eighty-eight per cent correctly mentioned the aerial route of TB transmission and 27.3% had perceived stigma towards TB. The majority (63.7%) was not aware of the possibility of getting multi-drug-resistant strains when they would not adhere to treatment. Overall, only 24% knew the basic elements about TB, 41% had favorable attitudes, and 55% had a good practice. Prisoners who were urban residents were generally more knowledgeable than rural residents (adjusted OR = 2.16; 95% CI = 1.15-4.06). Illiterates were found to be less knowledgeable (adjusted OR = 0.17; 95% CI = 0.06-0.46), less likely to have a favorable attitude (adjusted OR = 0.31; 95% CI = 0.15-0.64), and less good practice (adjusted OR = 0.35; 95% CI = 0.18-0.69). Significant differences were also observed between the different study prisons. Knowledge of prisoners regarding the cause of TB and consequences of non-adherence to TB treatment was low. Knowledge on the transmission, symptoms, and prevention was fairly high. Health education interventions, focused on the cause and the translation of the knowledge to appropriate practices, are needed in all the study prisons. Special attention should be given to less educated prisoners, and to prisons with a high number of prisoners and those in remote areas.

Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research

PubMed Central

2011-01-01

Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes’ performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders. PMID:21967874

Screening of health-care workers for latent tuberculosis infection in a Tertiary Care Hospital.

PubMed

Janagond, Anand Bimari; Ganesan, Vithiya; Vijay Kumar, G S; Ramesh, Arunagiri; Anand, Prem; Mariappan, M

2017-01-01

Health-care workers (HCWs) are at increased risk of acquiring tuberculosis (TB) than the general population. While national-level data on the burden of TB in general population is available from reliable sources, nationally representative data on latent tuberculosis infection (LTBI) burden in HCWs in the high burden countries is lacking. A prospective study was carried out to assess the risk of TB infection among HCWs who directly engage in medical duties. HCWs were recruited between January 2014 and December 2015. A structured questionnaire was used for risk assessment of TB infection among HCWs, including sociodemographic characteristics (e.g., age, gender, period of professional work, and employed position), knowledge of TB prevention and control, and history of professional work. A single-step tuberculin skin test (TST) using 5 international units (IU; 0.1 ml) of tuberculin (purified protein derivative from Mycobacterium bovis Bacillus Calmette-Guérin [BCG]). TB infection was determined using a TST induration ≥10 mm as a cutoff point for TST positivity. TST-positive participants were further subjected to detailed clinical evaluation and chest radiography to rule out active TB. The associations between TB infection and the sociodemographic characteristics, duration of possible exposure to TB while on medical duties, BCG vaccination, and knowledge about TB were estimated using Chi-square test. A two-sided P < 0.05 indicated statistical significance. A total of 206 eligible HCWs signed the informed consent and completed the questionnaires between January 2014 and December 2015. The age of the participants ranged from 18 to 71 years, with a mean age of 27.13 years. TST induration size (mean 6.37 mm) the TST results suggested that 36.8% (76/206) were infected with TB using a TST induration ≥10 mm as a cut-off point. All 76 TST-positive HCWs showed no evidence of active TB in clinical evaluation and chest radiography. However, during the study, two HCWs

46 CFR 39.1013 - U.S.-flagged tank vessel certification procedures for vapor control system designs-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... vapor control system designs-TB/ALL. 39.1013 Section 39.1013 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.1013 U.S.-flagged tank vessel certification procedures for vapor control system designs—TB/ALL. (a) For an existing Coast Guard-approved vapor...

46 CFR 39.1013 - U.S.-flagged tank vessel certification procedures for vapor control system designs-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... vapor control system designs-TB/ALL. 39.1013 Section 39.1013 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.1013 U.S.-flagged tank vessel certification procedures for vapor control system designs—TB/ALL. (a) For an existing Coast Guard-approved vapor...

Impact of external sources of infection on the dynamics of bovine tuberculosis in modelled badger populations.

PubMed

Hardstaff, Joanne L; Bulling, Mark T; Marion, Glenn; Hutchings, Michael R; White, Piran C L

2012-06-27

The persistence of bovine TB (bTB) in various countries throughout the world is enhanced by the existence of wildlife hosts for the infection. In Britain and Ireland, the principal wildlife host for bTB is the badger (Meles meles). The objective of our study was to examine the dynamics of bTB in badgers in relation to both badger-derived infection from within the population and externally-derived, trickle-type, infection, such as could occur from other species or environmental sources, using a spatial stochastic simulation model. The presence of external sources of infection can increase mean prevalence and reduce the threshold group size for disease persistence. Above the threshold equilibrium group size of 6-8 individuals predicted by the model for bTB persistence in badgers based on internal infection alone, external sources of infection have relatively little impact on the persistence or level of disease. However, within a critical range of group sizes just below this threshold level, external infection becomes much more important in determining disease dynamics. Within this critical range, external infection increases the ratio of intra- to inter-group infections due to the greater probability of external infections entering fully-susceptible groups. The effect is to enable bTB persistence and increase bTB prevalence in badger populations which would not be able to maintain bTB based on internal infection alone. External sources of bTB infection can contribute to the persistence of bTB in badger populations. In high-density badger populations, internal badger-derived infections occur at a sufficient rate that the additional effect of external sources in exacerbating disease is minimal. However, in lower-density populations, external sources of infection are much more important in enhancing bTB prevalence and persistence. In such circumstances, it is particularly important that control strategies to reduce bTB in badgers include efforts to minimise such

Impact of external sources of infection on the dynamics of bovine tuberculosis in modelled badger populations

PubMed Central

2012-01-01

Background The persistence of bovine TB (bTB) in various countries throughout the world is enhanced by the existence of wildlife hosts for the infection. In Britain and Ireland, the principal wildlife host for bTB is the badger (Meles meles). The objective of our study was to examine the dynamics of bTB in badgers in relation to both badger-derived infection from within the population and externally-derived, trickle-type, infection, such as could occur from other species or environmental sources, using a spatial stochastic simulation model. Results The presence of external sources of infection can increase mean prevalence and reduce the threshold group size for disease persistence. Above the threshold equilibrium group size of 6–8 individuals predicted by the model for bTB persistence in badgers based on internal infection alone, external sources of infection have relatively little impact on the persistence or level of disease. However, within a critical range of group sizes just below this threshold level, external infection becomes much more important in determining disease dynamics. Within this critical range, external infection increases the ratio of intra- to inter-group infections due to the greater probability of external infections entering fully-susceptible groups. The effect is to enable bTB persistence and increase bTB prevalence in badger populations which would not be able to maintain bTB based on internal infection alone. Conclusions External sources of bTB infection can contribute to the persistence of bTB in badger populations. In high-density badger populations, internal badger-derived infections occur at a sufficient rate that the additional effect of external sources in exacerbating disease is minimal. However, in lower-density populations, external sources of infection are much more important in enhancing bTB prevalence and persistence. In such circumstances, it is particularly important that control strategies to reduce bTB in badgers include

A world of cities and the end of TB.

PubMed

Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

2016-03-01

The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Tuberculosis infection control knowledge and attitudes among health workers in Uganda: a cross-sectional study.

PubMed

Buregyeya, Esther; Kasasa, Simon; Mitchell, Ellen M H

2016-08-15

The World Health Organization recommends TB infection control (TBIC) in health care facilities. In 2008, the Ministry of Health Uganda initiated efforts to implement TBIC by training of health care workers (HCWs). This study was carried out to assess knowledge and attitudes towards TBIC among HCWs. We conducted a cross-sectional study among HCWs in health facilities in the districts of Mukono and Wakiso in Uganda, from October 2010 to February 2011. We assessed HCWs' knowledge of basic standards of TB diagnosis, treatment and TBIC and attitudes towards TBIC measures. Twenty four percent of the participants answered correctly all the basic TB knowledge questions. Overall, 62 % of the HCWs were judged to have adequate basic TB knowledge. At multivariable analysis, non-clinical cadres, were more likely to have poor basic TB knowledge, [adjusted odds ratio (aOR) 0.43; 95 % confidence interval (CI) 0.27-0.68)]. Only 7 % of the respondents answered all the questions on TBIC correctly. Almost all the respondents (98 %; 529/541) knew that TB was transmitted through droplet nuclei, while only a third (34 %; 174/532) knew that masks do not protect the wearer from getting TB. Overall, 69 % (355/512) of the HCWs were judged to have adequate TBIC knowledge. At multivariable analysis, non-clinical cadres (aOR 0.61; 95 % CI 0.38-0.98) and having not attended TBIC training, (aOR 0.65; 95 % CI 0.42-0.99), were more likely to have poor TBIC knowledge. More than three quarters (77 %; 410/530) and 63 % (329/522) of the respondents had a high self-efficacy and perceived threat of acquiring TB at work, respectively. Having not attended a TBIC training was significantly associated with a low self-efficacy (aOR 0.52; 95 % CI 0.33-0.81) and low perceived threat of acquiring TB infection at work, (aOR 0.54; 95 % CI 0.36-0.81). Our study finds moderate number of HCWs with correct knowledge and attitudes towards TBIC. Efforts should be put in place to train all HCWs in TBIC, with

Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial.

PubMed

Kerrigan, Deanna; Tudor, Carrie; Motlhaoleng, Katlego; Lebina, Limakatso; Qomfu, Cokiswa; Variava, Ebrahim; Chon, Sandy; Martinson, Neil; Golub, Jonathan E

2018-04-16

Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa. Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted. Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts. Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics. The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130 , registered 10 April 2014).

Tuberculosis infection testing in HIV-positive men who have sex with men from Xi'an China.

PubMed

Xin, H N; Li, X W; Zhang, L; Li, Z; Zhang, H R; Yang, Y; Li, M F; Feng, B X; Li, H J; Gao, L

2017-02-01

In individuals with latent tuberculosis (TB) infection, those living with human immunodeficiency virus (HIV) had a 20-37 times higher risk of developing active TB compared to those without HIV infection. Systematic testing and treatment of latent TB infection are priorities in HIV-infected persons. In China, the prevalence of HIV infection in men who have sex with men (MSM) has gradually increased in the past decade. However, the prevalence of TB infection has been studied sparsely in HIV-infected MSM. Hence, we conducted a pilot study in MSM living with HIV infection in Xi'an city to evaluate TB infection status by means of interferon-γ release assay (IGRA). A total of 182 HIV-infected MSM were included in this study, the prevalence of IGRA positivity was observed to be 8·79% (16/182). IGRA quantitative results were not statistically influenced by the CD4 cell counts of the study participants. However, IGRA positivity was found to be lower than our previously reported data from the general population. This suggests that immunological deficiency might decrease the sensitivity of IGRA and thus increase the number of false negatives. Our primary results, suggesting systematic testing and treatment of latent TB infection together with active case-finding, were equally important for TB control in persons living with HIV infection.

[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

Risk Factors Associated with MDR-TB at the Onset of Therapy among New Cases Registered with the RNTCP in Mumbai, India

PubMed Central

Atre, Sachin R.; D’Souza, Desiree T. B.; Vira, Tina S.; Chatterjee, Anirvan; Mistry, Nerges F.

2014-01-01

Background Multidrug-resistant TB (MDR-TB) has emerged as a major threat to global TB control efforts in recent years. Facilities for its diagnosis and treatment are limited in many high-burden countries, including India. In hyper-endemic areas like Mumbai, screening for newly diagnosed cases at a higher risk of acquiring MDR-TB is necessary, for initiating appropriate and timely treatment, to prevent its further spread. Objective To assess risk factors associated with MDR-TB among Category I, new sputum smear-positive cases, at the onset of therapy. Materials and Methods The study applied an unmatched case-control design for 514 patients (106 cases with MDR-TB strains and 408 controls with non-MDR-TB strains). The patients were registered with the Revised National Tuberculosis Control Program (RNTCP) in four selected wards of Mumbai during April 2004-January 2007. Data were collected through semi-structured interviews and drug susceptibility test results. Results Multivariate analysis indicated that infection with the Beijing strain (OR = 3.06; 95% C.I. = 1.12-8.38; P = 0.029) and female gender (OR = 1.68; 95% C.I. = 1.02-2.87; P = 0.042) were significant predictors of MDR-TB at the onset of therapy. Conclusion The study provides a starting point to further examine the usefulness of these risk factors as screening tools in identifying individuals with MDR-TB, in settings where diagnostic and treatment facilities for MDR-TB are limited. PMID:21727675

Interdisciplinary Public Health Intervention in a Multigenerational Tuberculosis (TB) Outbreak in Harris County, Texas: A Case Study with Implications for Disease Control Process Improvement and Transmission Cycle Interruption

PubMed Central

Haynie, Aisha; Plasencia, Carlos; Fields, Kimberly; Nesbitt, Elna; Lovings-Clark, Audrey; Scott, Mary; Wiltz-Beckham, Dana; Reed, Brian; Shah, Umair A

2017-01-01

Abstract Background Harris County Public Health (HCPH) is the health department for Harris County, Texas jurisdiction. Harris County as a whole is the nation’s third most populous county, with 4.3 million residents, and a TB case rate more than double that of the USA. (7.6 cases per 100,000 pop). A total, 327 individuals were diagnosed with TB in Harris County during 2015, over two-thirds occurring in foreign-born individuals. In 2016, HCPH treated an immigrant female with active TB. Initial contact investigation (CI) yielded five household contacts (HHC). Two tested positive, but refused subsequent clinical evaluation by HCPH. Two months later, HCPH was notified of a HHC hospitalized with TB. After hospital discharge, the sick HHC moved into a motel in attempts to self-isolate, but refused evaluation of additional HHC in the home, and banned home access, precluding adequate CI. After numerous phone calls, visits to motel and home, and multiple rescheduled appointments, legal action appeared inevitable. Days later, HCPH was notified of another HHC diagnosed with active TB. Methods With alarm regarding the family’s adherence to control orders, TB staff implemented an innovative multidisciplinary team-based intervention in hopes of avoiding legal action. A site visit was paid to the motel by a local health authority, two TB staff, a county public investigator, and a refugee clinic outreach worker fluent in the family’s language. Patients were presented with letters requesting immediate cooperation to avoid court filings. Questions were answered, misinformation corrected, and education provided. Results Intermediary on-site intervention using a compassionate, firm multidisciplinary team approach resulted in 16 additional family members tested, yielding an infant with active TB (Case 4) and 8 with TB Infection (TBI). Isolation breaches were also discovered. Most importantly, TB transmission cycle was interrupted. Cultural and economic barriers hindering

Public-private mix for TB and TB-HIV care in Lagos, Nigeria.

PubMed

Daniel, O J; Adedeji Adejumo, O; Abdur-Razzaq, H A; Ngozi Adejumo, E; Salako, A A

2013-09-01

Private and public tuberculosis (TB) treatment centres in Lagos State, Nigeria. To assess the contribution of private health care providers to TB and TB-HIV (human immunodeficiency virus) case finding in Lagos State. A retrospective review of programme data submitted to the Lagos State TB and Leprosy Control Programme in 2011 by public, private for-profit (PFP) and private not-for-profit (PNFP) health care providers. A total of 8425 TB cases were notified by 31 private (11 PFP and 20 PNFP) and 99 public health facilities in Lagos State. Overall, the private facilities were responsible for 10.3% (866/8425) of the total TB cases notified. The proportion of TB patients tested for HIV was respectively 86.2%, 53.1% and 96.5% among public, PFP and PNFP facilities. Overall, 22.4% of the TB patients were HIV-positive. The HIV positivity rate among public, PFP and PNFP facilities was respectively 23.8%, 7.8% and 9.9%. Uptake of cotrimoxazole preventive therapy was respectively 69.6%, 25% and 38.2% among public, PFP and PNFP facilities, while that of antiretroviral therapy was respectively 23.8%, 8.3% and 9.1% in public, PFP and PNFP facilities. There is a need to scale up collaboration with the private sector, and particularly PNFP health providers.

Snapshot of Quantiferon TB gold testing in Northern Mexico.

PubMed

González-Salazar, F; Vargas-Villarreal, J; Garcialuna-Martínez, F J; Rivera, G; Moreno-Treviño, M G; Montfort-Gardeazabal, J M; Garcialuna-Martínez, E

2011-12-01

Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST outcomes. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an uncommon test due to the higher cost compared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(®) gold in tube (QTB(®)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients (39.7%) compared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(®)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(®)-GIT has better capacity than TST to detect latent tuberculosis infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

HIV screening among TB patients and co-trimoxazole preventive therapy for TB/HIV patients in Addis Ababa: facility based descriptive study.

PubMed

Denegetu, Amenu Wesen; Dolamo, Bethabile Lovely

2014-01-01

Collaborative TB/HIV management is essential to ensure that HIV positive TB patients are identified and treated appropriately, and to prevent tuberculosis (TB) in HIV positive patients. The purpose of this study was to assess HIV case finding among TB patients and Co-trimoxazole Preventive Therapy (CPT) for HIV/TB patients in Addis Ababa. A descriptive cross-sectional, facility-based survey was conducted between June and July 2011. Data was collected by interviewing 834 TB patients from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to summarize and analyze findings. The proportion of TB patients who (self reported) were offered for HIV test, tested for HIV and tested HIV positive during their anti-TB treatment follow-up were; 87.4%, 69.4% and 20.2%; respectively. Eighty seven HIV positive patients were identified, who knew their status before diagnosed for the current TB disease, bringing the cumulative prevalence of HIV among TB patients to 24.5%. Hence, the proportion of TB patients who knew their HIV status becomes 79.9%. The study revealed that 43.6% of those newly identified HIV positives during anti-TB treatment follow-up were actually treated with CPT. However, the commutative proportion of HIV positive TB patients who were ever treated with CPT was 54.4%; both those treated before the current TB disease and during anti-TB treatment follow-up. HIV case finding among TB patients and provision of CPT for TB/HIV co-infected patients needs boosting. Hence, routine offering of HIV test and provision of CPT for PLHIV should be strengthened in-line with the national guidelines.

Infection control and tuberculosis among health care workers in Viet Nam, 2009-2013: a cross-sectional survey.

PubMed

Tiemersma, Edine W; Huong, Nguyen Thien; Yen, Pham Hoang; Tinh, Bui Thi; Thuy, Tran Thi Bich; Van Hung, Nguyen; Mai, Nguyen Thanh; Verver, Suzanne; Gebhard, Agnes; Nhung, Nguyen Viet

2016-11-10

Data on tuberculosis (TB) among health care workers (HCW) and TB infection control (TBIC) indicators are rarely available at national level. We assessed multi-year trends in notification data of TB among HCW and explored possible associations with TBIC indicators. Notified TB incidence among HCW and 3 other TBIC indicators were collected annually from all 64 provincial and 3 national TB facilities in Vietnam. Time trends in TB notification between 2009 and 2013 were assessed using linear regression analysis. Multivariate regression models were applied to assess associations between the facility-specific 5-year notification rate and TBIC indicators. Forty-seven (70 %) of 67 facilities contributed data annually over five years; 15 reported at least one HCW with TB in 2009 compared to six in 2013. The TB notification rate dropped from 593 to 197 per 100,000 HCW (p trend  = 0.02). Among 104 TB cases reported, 30 were employed at TB wards, 24 at other clinical wards, ten in the microbiology laboratory, six at the MDR-TB ward, and 34 in other positions. The proportion of facilities with a TBIC plan and focal person remained relatively stable between 70 % and 84 %. The proportion of facilities providing personal protective equipment (PPE) to their staff increased over time. Facilities with a TBIC focal person were 7.6 times more likely to report any TB cases than facilities without a focal person. The TB notification rates among HCW seemed to decrease over time. Availability of PPE increased over the same period. Appointing a TBIC focal person was associated with reporting of TB cases among HCW. It remains unclear whether TBIC measures helped in reduction of the TB notification rates in HCW.

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

HIV and intestinal parasites in adult TB patients in a teaching hospital in Northwest Ethiopia.

PubMed

Kassu, Afework; Mengistu, Getahun; Ayele, Belete; Diro, Ermias; Mekonnen, Firew; Ketema, Dereje; Moges, Feleke; Mesfin, Tsehay; Getachew, Assefa; Ergicho, Bahiru; Elias, Daniel; Wondmikun, Yared; Aseffa, Abraham; Ota, Fusao

2007-10-01

The level of HIV infection and intestinal parasitoses among TB patients was assessed in a hospital-based cross-sectional study involving 257 patients in Gondar, Ethiopia. In TB patients, our study reported co-infection with HIV (52.1%) and intestinal parasites (40.9%) The high prevalence of HIV and intestinal parasites indicates an increased morbidity inTB patients and emphasized the importance of continued HIV sero-surveillance, stool analysis and treatment.

Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India

PubMed Central

Bapat, Prachi R.; Satav, Ashish R.; Husain, Aliabbas A.; Shekhawat, Seema D.; Kawle, Anuja P.; Chu, Justin J.; Purohit, Hemant J.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S.

2015-01-01

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis. PMID:26241963

Tuberculosis in HIV-infected South African children with complicated severe acute malnutrition.

PubMed

Adler, H; Archary, M; Mahabeer, P; LaRussa, P; Bobat, R A

2017-04-01

Academic tertiary referral hospital in Durban, South Africa. To describe the incidence and diagnostic challenges of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children with severe acute malnutrition (SAM). Post-hoc analysis of a randomised controlled trial that enrolled antiretroviral therapy naïve, HIV-infected children with SAM. Trial records and hospital laboratory results were explored for clinical diagnoses and bacteriologically confirmed cases of TB. Negative binomial regression was used to explore associations with confirmed cases of TB, excluding cases where the clinical diagnosis was not supported by microbiological confirmation. Of 82 children enrolled in the study, 21 (25.6%) were diagnosed with TB, with bacteriological confirmation in 8 cases. Sputum sampling (as opposed to gastric washings) was associated with an increased risk of subsequent diagnosis of TB (adjusted relative risk [aRR] 1.134, 95%CI 1.02-1.26). Culture-proven bacterial infection during admission was associated with a reduced risk of TB (aRR 0.856, 95%CI 0.748-0.979), which may reflect false-negative microbiological tests secondary to empiric broad-spectrum antibiotics. TB is common in HIV-infected children with SAM. While microbiological confirmation of the diagnosis is feasible, empiric treatment remains common, possibly influenced by suboptimal testing and false-negative TB diagnostics. Rigorous microbiological TB investigation should be integrated into the programmatic management of HIV and SAM.

The implementation of isoniazid preventive therapy in HIV clinics: the experience from the TB/HIV in Rio (THRio) study.

PubMed

Durovni, Betina; Cavalcante, Solange C; Saraceni, Valeria; Vellozo, Vitoria; Israel, Giselle; King, Bonnie S; Cohn, Silvia; Efron, Anne; Pacheco, Antonio G; Moulton, Lawrence H; Chaisson, Richard E; Golub, Jonathan E

2010-11-01

The TB/HIV in Rio (THRio) study was launched in September 2005 to assess the impact of integrated tuberculosis (TB) and HIV treatment strategies in 29 HIV clinics in Rio de Janeiro, Brazil. THRio is a cluster-randomized trial (CRT) to determine whether routine screening for and treatment of latent TB in HIV clinic patients with access to antiretroviral therapy will reduce TB incidence at the clinic level. THRio is part of the Consortium to Respond Effectively to AIDS/TB Epidemic that is implementing research studies to assess the impact of bold, new public health paradigms for controlling the AIDS/TB epidemic. Twenty-nine public primary HIV clinics were randomly assigned a date to begin implementing TB screening procedures and provision of isoniazid preventive therapy (IPT) for TB/HIV coinfected patients. Final analysis of the CRT is expected in 2011. Starting at date of tuberculin skin test (TST)/IPT implementation at each clinic through August 2010, 1670 HIV-infected patients initiated IPT, of which 215 are still receiving treatment. Of the remaining 1455 patients, 1230 (85%) completed therapy and only 20 (1.2%) patients initiating IPT reported adverse reactions leading to discontinuation of therapy. IPT completion was higher among HIV-infected patients receiving HAART (87%) than those not yet receiving HAART (79%, P < 0.01). Times to TST and IPT have markedly decreased postintervention, but remain considerably long. The richness of the THRio database has resulted in several analyses of this expansive cohort of HIV-infected patients that are reviewed here. The national implementation of TST and IPT for HIV-positive patients in Brazil has been invigorated partly due to THRio's baseline results. Expanded use of IPT in HIV patients in Rio de Janeiro is achievable with high adherence and low adverse events, although this effort requires a package of activities including training, advocacy and reorganization of services.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

PubMed

Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak

2017-05-09

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

Bovine tuberculosis in Northern Ireland: quantification of the population disease-level effect from cattle leaving herds detected as a source of infection.

PubMed

Doyle, L P; Courcier, E A; Gordon, A W; O'Hagan, M J H; Stegeman, J A; Menzies, F D

2017-12-01

Determination of the proportion of bovine tuberculosis (bTB) breakdowns attributed to a herd purchasing infected animals has not been previously quantified using data from the Animal and Public Health Information System (APHIS) database in Northern Ireland. We used a case-control study design to account for the infection process occurring in the disclosing bTB breakdown herds. Cases (N = 6926) were cattle moving to a future confirmed bTB breakdown where they would disclose as a confirmed bTB reactor or a Lesion at Routine Slaughter (LRS). Controls (N = 303 499) were cattle moving to a future confirmed bTB breakdown where they did not become a bTB reactor or LRS. Our study showed that the cattle leaving herds which disclosed bTB within 450 days had an increased odds of becoming a confirmed bTB reactor or LRS compared with the cattle which left herds that remained free for 450 days (odds ratio (OR) = 2·09: 95% CI 1·96-2·22). Of the 12 060 confirmed bTB breakdowns included in our study (2007-2015 inclusive), 31% (95% CI 29·8-31·5) contained a confirmed bTB reactor(s) or LRS(s) at the disclosing test which entered the herd within the previous 450 days. After controlling for the infection process occurring in the disclosing bTB breakdown herd, our study showed that 6·4% (95% CI 5·9-6·8) of bTB breakdowns in Northern Ireland were directly attributable to the movement of infected animals.

HIV, multidrug-resistant TB and depressive symptoms: when three conditions collide.

PubMed

Das, Mrinalini; Isaakidis, Petros; Van den Bergh, Rafael; Kumar, Ajay M V; Nagaraja, Sharath Burugina; Valikayath, Asmaa; Jha, Santosh; Jadhav, Bindoo; Ladomirska, Joanna

2014-01-01

Management of multidrug-resistant TB (MDR-TB) patients co-infected with human immunodeficiency virus (HIV) is highly challenging. Such patients are subject to long and potentially toxic treatments and may develop a number of different psychiatric illnesses such as anxiety and depressive disorders. A mental health assessment before MDR-TB treatment initiation may assist in early diagnosis and better management of psychiatric illnesses in patients already having two stigmatising and debilitating diseases. To address limited evidence on the baseline psychiatric conditions of HIV-infected MDR-TB patients, we aimed to document the levels of depressive symptoms at baseline, and any alteration following individualized clinical and psychological support during MDR-TB therapy, using the Patient Health Questionnaire-9 (PHQ-9) tool, among HIV-infected patients. This was a retrospective review of the medical records of an adult (aged >15 years) HIV/MDR-TB cohort registered for care during the period of August 2012 through to March 2014. A total of 45 HIV/MDR-TB patients underwent baseline assessment using the PHQ-9 tool, and seven (16%) were found to have depressive symptoms. Of these, four patients had moderate to severe depressive symptoms. Individualized psychological and clinical support was administered to these patients. Reassessments were carried out for all patients after 3 months of follow-up, except one, who died during the period. Among these 44 patients, three with baseline depressive symptoms still had depressive symptoms. However, improvements were observed in all but one after 3 months of follow-up. Psychiatric illnesses, including depressive symptoms, during MDR-TB treatment demand attention. Routine administration of baseline mental health assessments by trained staff has the potential to assist in determining appropriate measures for the management of depressive symptoms during MDR-TB treatment, and help in improving overall treatment outcomes. We recommend

Regulatory T Cells Subvert Mycobacterial Containment in Patients Failing Extensively Drug-resistant TB Treatment.

PubMed

Davids, Malika; Pooran, Anil S; Pietersen, Elize; Wainwright, Helen C; Binder, Anke; Warren, Robin; Dheda, Keertan

2018-02-09

The advent of extensively (XDR-TB) and totally drug-resistant TB, with limited or no treatment options, has facilitated renewed interest in host directed immunotherapy, particularly for therapeutically destitute patients. However, the selection and utility of such approaches depend upon understanding the host immune response in XDR-TB, which hitherto remains unexplored. To determine the host immunological profile in patients with XDR-TB, compared to drug-sensitive TB, using peripheral blood and explanted lung tissue. Blood and explanted lung tissue were obtained from patients with XDR-TB (n=31), drug-sensitive TB (DS-TB, n=20) and presumed latent-TB infection (LTBI, n=20). T-cell phenotype (Th1/Th2/Th17/Tregs) was evaluated in all patient groups, and Treg function assessed in XDR-TB non-responders by co-culturing PPD pre-primed effector T-cells with H37Rv-infected monocyte-derived macrophages, with or without autologous Tregs. Mycobacterial containment was evaluated by counting colony-forming units. Patients failing XDR-TB treatment had an altered immuno-phenotype characterized by a substantial increase in the frequency (median; IQR) of CD4+CD25+FoxP3+ regulatory T-cells (11.5; 5.9-15.2) compared to DS-TB (3.4 %; 1.6-5.73; p < 0.001) and presumed LTBI (1.8 % 1.2-2.3; p < 0.001), which was unrelated to disease duration. Tregs isolated from XDR-TB patients suppressed T-cell proliferation (up to 90%) and subverted containment of H37Rv-infected monocyte-derived macrophages (by 30%; p= 0.03) by impairing effector T-cell function through a mechanism independent of direct cell-to-cell contact, IL-10, TGF-beta and CTLA-4. Collectively, these data suggest that Tregs may be contributing to immune dysfunction, and bacterial persistence, in patients with XDR-TB. The relevant cellular pathways may serve as potential targets for immunotherapeutic intervention.

Multidrug-resistant Mycobacterium tuberculosis in HIV-Infected Persons, Peru

PubMed Central

Campos, Pablo E.; Suarez, Pedro G.; Sanchez, Jorge; Zavala, David; Arevalo, Jorge; Ticona, Eduardo; Nolan, Charles M.; Hooton, Thomas M.

2003-01-01

During 1999 to 2000, we identified HIV-infected persons with new episodes of tuberculosis (TB) at 10 hospitals in Lima-Peru and a random sample of other Lima residents with TB. Multidrug-resistant (MDR)-TB was documented in 35 (43%) of 81 HIV-positive patients and 38 (3.9%)of 965 patients who were HIV-negative or of unknown HIV status (p < 0.001). HIV-positive patients with MDR-TB were concentrated at three hospitals that treat the greatest numbers of HIV-infected persons with TB. Of patients with TB, those with HIV infection differed from those without known HIV infection in having more frequent prior exposure to clinical services and more frequent previous TB therapy or prophylaxis. However, MDR-TB in HIV-infected patients was not associated with previous TB therapy or prophylaxis. MDR-TB is an ongoing problem in HIV-infected persons receiving care in public hospitals in Lima and Callao; they represent sentinel cases for a potentially larger epidemic of nosocomial MDR-TB. PMID:14720398

Tuberculosis infection among young nursing trainees in South India.

PubMed

Christopher, Devasahayam J; Daley, Peter; Armstrong, Lois; James, Prince; Gupta, Richa; Premkumar, Beulah; Michael, Joy Sarojini; Radha, Vedha; Zwerling, Alice; Schiller, Ian; Dendukuri, Nandini; Pai, Madhukar

2010-04-29

Among healthcare workers in developing countries, nurses spend a large amount of time in direct contact with tuberculosis (TB) patients, and are at high risk for acquisition of TB infection and disease. To better understand the epidemiology of nosocomial TB among nurses, we recruited a cohort of young nursing trainees at Christian Medical College, a large, tertiary medical school hospital in Southern India. Among 535 nursing students enrolled in 2007, 468 gave consent to participate, and 436 underwent two-step tuberculin skin testing (TST). A majority (95%) were females, and almost 80% were under 22 years of age. Detailed TB exposure information was obtained using interviews and clinical log books. Prevalence of latent TB infection (LTBI) was estimated using Bayesian latent class analyses (LCA). Logistic regression analyses were done to determine the association between LTBI prevalence and TB exposure and risk factors. 219 of 436 students (50.2%, 95% CI: 45.4-55.0) were TST positive using the 10 mm or greater cut-off. Based on the LCA, the prevalence of LTBI was 47.8% (95% credible interval 17.8% to 65.6%). In the multivariate analysis, TST positivity was strongly associated with time spent in health care, after adjusting for age at entry into healthcare. Our study showed a high prevalence of LTBI even in young nursing trainees. With the recent TB infection control (TBIC) policy guidance from the World Health Organization as the reference, Indian healthcare providers and the Indian Revised National TB Control Programme will need to implement TBIC interventions, and enhance capacity for TBIC at the country level. Young trainees and nurses, in particular, will need to be targeted for TBIC interventions.

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

PubMed Central

2012-01-01

Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection. PMID:23272999

Immune Response to Mycobacterial Infection: Lessons from Flow Cytometry

PubMed Central

Rovina, Nikoletta; Panagiotou, Marios; Koulouris, Nikolaos G.

2013-01-01

Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB) to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response against Mycobacterium tuberculosis (Mtb) at certain stages of infection as revealed by flow cytometry to date. PMID:24376464

Immune response to mycobacterial infection: lessons from flow cytometry.

PubMed

Rovina, Nikoletta; Panagiotou, Marios; Pontikis, Konstantinos; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Koutsoukou, Antonia

2013-01-01

Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB) to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response against Mycobacterium tuberculosis (Mtb) at certain stages of infection as revealed by flow cytometry to date.

Estimation of content of anti-TB drugs supplied at centres of the Revised National TB Control Programme in Tamil Nadu, India.

PubMed

Ramachandran, Geetha; Chandrasekaran, Vedachalam; Hemanth Kumar, Agibothu Kupparam; Dewan, Puneet; Swaminathan, Soumya; Thomas, Aleyamma

2013-09-01

To determine the content of certain antituberculosis (TB) drugs supplied at TB treatment centres of the Revised National TB Control Programme (RNTCP) in the state of Tamil Nadu, India. Eight districts across the state were selected, and the following drugs were collected from five settings (District TB centre, TB unit, designated microscopy centres, DOT providers) in each district: rifampicin (150 and 450 mg), isoniazid (300 mg), pyrazinamide (500 and 750 mg), ethambutol (400 and 600 mg), ethionamide (250 mg), levofloxacin (500 mg) and cycloserine (250 mg). A maximum of 10 tablets/capsules were collected from each setting. The drugs were coded prior to analysis. All drugs were assayed by validated spectrophotometric methods. The acceptable limits for drug content were taken as 90-110% of the stated content. More than 90% of tablets of rifampicin 450 mg, isoniazid 300 mg, pyrazinamide 500 and 750 mg, ethambutol 400 and 600 mg and ethionamide 250 mg were within acceptable limits. Eighty per cent of rifampicin 150 mg, 21% of cycloserine 250 mg and 87% of levofloxacin 500 mg were within acceptable limits. The mean cycloserine content was below the acceptable limit in all districts, the mean drug content being 200 mg (range: 108-245 mg). This systematic study showed that the stated drug content of cycloserine was not reached in all districts. Deterioration of cycloserine could be minimised by storing the drug in refrigerators. The geographical location of the districts had no influence on the drug content. © 2013 John Wiley & Sons Ltd.

Potential Immunological Biomarkers for Detection of Mycobacterium tuberculosis Infection in a Setting Where M. tuberculosis Is Endemic, Ethiopia.

PubMed

Teklu, Takele; Kwon, Keehwan; Wondale, Biniam; HaileMariam, Milkessa; Zewude, Aboma; Medhin, Girmay; Legesse, Mengistu; Pieper, Rembert; Ameni, Gobena

2018-04-01

Accurate diagnosis and early treatment of tuberculosis (TB) and latent TB infection (LTBI) are vital to prevent and control TB. The lack of specific biomarkers hinders these efforts. This study's purpose was to screen immunological markers that discriminate Mycobacterium tuberculosis infection outcomes in a setting where it is endemic, Ethiopia. Whole blood from 90 participants was stimulated using the ESAT-6/CFP-10 antigen cocktail. The interferon gamma (IFN-γ)-based QuantiFERON diagnostic test was used to distinguish between LTBI and uninfected control cases. Forty cytokines/chemokines were detected from antigen-stimulated plasma supernatants (SPSs) and unstimulated plasma samples (UPSs) using human cytokine/chemokine antibody microarrays. Statistical tests allowed us to identify potential biomarkers that distinguish the TB, LTBI, and healthy control groups. As expected, the levels of IFN-γ in SPSs returned a high area under the receiver operating characteristic curve (AUC) value comparing healthy controls and LTBI cases (Z = 0.911; P < 0.001). The SPS data also indicated that interleukin 17 (IL-17) abundance discriminates LTBI from healthy controls (Z = 0.763; P = 0.001). RANTES and MIP-1β were significantly elevated in SPSs of TB-infected compared to healthy controls ( P < 0.05), while IL-12p40 and soluble tumor necrosis factor receptor II (sTNF-RII) were significantly increased in active TB cases compared to the combined LTBI and control groups ( P < 0.05). Interestingly, quantitative changes for RANTES were observed using both SPSs and UPSs, with P values of 0.013 and 0.012, respectively, in active TB versus LTBI cases and 0.001 and 0.002, respectively, in active TB versus healthy controls. These results encourage biomarker verification studies for IL-17 and RANTES. Combinations of these cytokines may complement IFN-γ measurements to diagnose LTBI and distinguish active TB from LTBI cases. Copyright © 2018 American Society for Microbiology.

Analysis of Host Responses to Mycobacterium tuberculosis Antigens in a Multi-Site Study of Subjects with Different TB and HIV Infection States in Sub-Saharan Africa

PubMed Central

Sutherland, Jayne S.; Lalor, Maeve K.; Black, Gillian F.; Ambrose, Lyn R.; Loxton, Andre G.; Chegou, Novel N.; Kassa, Desta; Mihret, Adane; Howe, Rawleigh; Mayanja-Kizza, Harriet; Gomez, Marie P.; Donkor, Simon; Franken, Kees; Hanekom, Willem; Klein, Michel R.; Parida, Shreemanta K.; Boom, W. Henry; Thiel, Bonnie A.; Crampin, Amelia C.; Ota, Martin; Walzl, Gerhard; Ottenhoff, Tom H. M.; Dockrell, Hazel M.; Kaufmann, Stefan H. E.

2013-01-01

Background Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. Methods We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. Results There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST- and TST+ contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST+ contacts (LTBI) compared to TB and TST- contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Conclusions Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

PubMed

Sutherland, Jayne S; Lalor, Maeve K; Black, Gillian F; Ambrose, Lyn R; Loxton, Andre G; Chegou, Novel N; Kassa, Desta; Mihret, Adane; Howe, Rawleigh; Mayanja-Kizza, Harriet; Gomez, Marie P; Donkor, Simon; Franken, Kees; Hanekom, Willem; Klein, Michel R; Parida, Shreemanta K; Boom, W Henry; Thiel, Bonnie A; Crampin, Amelia C; Ota, Martin; Walzl, Gerhard; Ottenhoff, Tom H M; Dockrell, Hazel M; Kaufmann, Stefan H E

2013-01-01

Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy

Public-private mix for control of tuberculosis and TB-HIV in Nairobi, Kenya: outcomes, opportunities and obstacles.

PubMed

Chakaya, J; Uplekar, M; Mansoer, J; Kutwa, A; Karanja, G; Ombeka, V; Muthama, D; Kimuu, P; Odhiambo, J; Njiru, H; Kibuga, D; Sitienei, J

2008-11-01

Nairobi, the capital of Kenya. To promote standardised tuberculosis (TB) care by private health providers and links with the public sector. A description of the results of interventions aimed at engaging private health providers in TB care and control in Nairobi. Participating providers are supported to provide TB care that conforms to national guidelines. The standard surveillance tools are used for programme monitoring and evaluation. By the end of 2006, 26 of 46 (57%) private hospitals and nursing homes were engaged. TB cases reported by private providers increased from 469 in 2002 to 1740 in 2006. The treatment success rate for smear-positive pulmonary TB treated by private providers ranged from 76% to 85% between 2002 and 2005. Of the 1740 TB patients notified by the private sector in 2006, 732 (42%) were tested for human immunodeficiency virus (HIV), of whom 372 (51%) were positive. Of the 372 HIV-positive TB patients, 227 (61%) were provided with cotrimoxazole preventive treatment (CPT) and 136 (37%) with antiretroviral treatment (ART). Private providers can be engaged to provide TB-HIV care conforming to national norms. The challenges include providing diagnostics, CPT and ART and the capacity to train and supervise these providers.

Tuberculosis and HIV co-infection in Vietnam.

PubMed

Trinh, Q M; Nguyen, H L; Do, T N; Nguyen, V N; Nguyen, B H; Nguyen, T V A; Sintchenko, V; Marais, B J

2016-05-01

Tuberculosis (TB) and human immunodeficiency virus (HIV) infection are leading causes of disease and death in Vietnam, but TB/HIV disease trends and the profile of co-infected patients are poorly described. We examined national TB and HIV notification data to provide a geographic overview and describe relevant disease trends within Vietnam. We also compared the demographic and clinical profiles of TB patients with and without HIV infection. During the past 10 years (2005-2014) cumulative HIV case numbers and deaths increased to 298,151 and 71,332 respectively, but access to antiretroviral therapy (ART) improved and new infections and deaths declined. From 2011-2014 routine HIV testing of TB patients increased from 58.9% to 72.5% and of all TB patients diagnosed with HIV in 2014, 2,803 (72.4%) received ART. The number of multidrug resistant (MDR)-TB cases enrolled for treatment increased almost 3-fold (578 to 1,532) from 2011-2014. The rate of HIV co-infection in MDR and non-MDR TB cases (51/1,532; 3.3% vs 3,774/100,555; 3.8%; OR 0.77, 95% CI 0.7-1.2) was similar in 2014. The care of TB/HIV co-infected patients have shown sustained improvement in Vietnam. Rising numbers of MDR-TB cases is a concern, but this is not "driven" by HIV co-infection. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A survey of tuberculosis infection control practices at the NIH/NIAID/DAIDS-supported clinical trial sites in low and middle income countries.

PubMed

Godfrey, Catherine; Tauscher, Gail; Hunsberger, Sally; Austin, Melissa; Scott, Lesley; Schouten, Jeffrey T; Luetkemeyer, Anne F; Benson, Constance; Coombs, Robert; Swindells, Susan

2016-06-10

Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement. A survey was developed that assessed IC activities in three domains: facility level measures, administrative control measures and environmental measures. An external site monitor visited each site in 2013-2014, to complete the audit. A central review committee evaluated the site-level survey and results were tabulated. Fisher's exact test was performed to determine whether there were significant differences in practices at sites that had IC officers versus sites that did not have IC officers. Significance was assessed at pTB IC) elements in place. Sixty-one percent of sites had an IC officer tasked with developing and maintaining TB IC standard operating procedures. Twenty-two (71 %) sites promptly identified and segregated individuals with TB symptoms. Thirty (93 %) sites had a separate waiting area for patients, and 26 (81 %) collected sputum within a specific well-ventilated area that was separate from the general waiting area. Sites with an IC officer were more likely to have standard operating procedures covering TB IC practices (p = 0.02) and monitor those policies (p = 0.02) and perform regular surveillance of healthcare workers (p = 0.02). The presence of an IC officer had a positive impact on performance in most of the TB IC domains surveyed including

Effect of prolonged incubation time on results of the QuantiFERON TB gold in-tube assay for diagnosis of latent tuberculosis infection.

PubMed

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo; Yim, Jae-Joon

2013-09-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.

Effect of Prolonged Incubation Time on Results of the QuantiFERON TB Gold In-Tube Assay for Diagnosis of Latent Tuberculosis Infection

PubMed Central

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo

2013-01-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results. PMID:23825190

Tuberculosis control in Asia and the western Pacific: a role for computer modelling.

PubMed

Brewer, T F; Heymann, S J; Harris, J B

1997-09-01

Despite the availability of effective treatment, tuberculosis (TB) causes more deaths than any other infection. Most of the world's TB cases and deaths occur in Asia and the Western Pacific, and the growing prevalence of multiple drug-resistant TB and the spread of human immunodeficiency virus (HIV) present ever greater obstacles to effective TB control. The management of TB remains difficult, and epidemiologic studies to assess control programmes require significant time and expense and may not be generalizable to other regions. Computer models are powerful and relatively inexpensive tools for rapidly planning and evaluating TB control strategies. Models have demonstrated the value of targeted chemoprophylaxis strategies for the prevention of TB among HIV-infected individuals, and programmes to ensure that all HIV-infected individuals receive TB chemoprophylaxis should be considered in Asia and the Western Pacific. Though directly observed therapy (DOT) is effective when designed to be attractive to patients, modelling has shown that DOT, if poorly accepted by patients, may lead to fewer patients seeking care and thus to paradoxical rises in TB case rates. Models may be used to make accurate predictions of TB morbidity and programme costs using local epidemiologic and demographic inputs. The use of models in Asia and the Western Pacific offers a low-cost way to compare programmes, to improve the evaluation of programmes, to project future cases, and to examine programme needs while providing insights into TB control helpful to countries in and out of the region.

Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity

PubMed Central

Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina

2017-01-01

Background Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Methods Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. Results All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. Conclusion This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB. PMID:28182700

Pilot, double-blind, randomized, placebo-controlled clinical trial of the supplement food Nyaditum resae® in adults with or without latent TB infection: Safety and immunogenicity.

PubMed

Montané, Eva; Barriocanal, Ana Maria; Arellano, Ana Lucía; Valderrama, Angelica; Sanz, Yolanda; Perez-Alvarez, Nuria; Cardona, Paula; Vilaplana, Cristina; Cardona, Pere-Joan

2017-01-01

Nyaditum resae® (NR) is a galenic preparation of heat-killed Mycobacterium manresensis, a new species of the fortuitum complex, that is found in drinkable water, and that has demonstrated to protect against the development of active TB in a murine experimental model that develop human-like lesions. Double-blind, randomized, placebo-controlled Clinical Trial (51 volunteers included). Two different doses of NR and a placebo were tested, the randomization was stratified by Latent Tuberculosis Infection (LTBI)-positive (n = 21) and LTBI-negative subjects (n = 30). Each subject received 14 drinkable daily doses for 2 weeks. All patients completed the study. The 46.3% of the overall reported adverse events (AE) were considered related to the investigational treatment. None of them were severe (94% were mild and 6% moderate). No statistical differences were found when comparing the median number of AE between the placebo group and both treatment groups. The most common AE reported were gastrointestinal events, most frequently mild abdominal pain and increase in stool frequency. Regarding the immunogenic response, both LTBI-negative and LTBI-positive volunteers treated with NR experienced a global increase on the Treg response, showed both in the population of CD25+CD39-, mainly effector Treg cells, or CD25+CD39+ memory PPD-specific Treg cells. This clinical trial demonstrates an excellent tolerability profile of NR linked to a significant increase in the population of specific effector and memory Tregs in the groups treated with NR in both LTBI-positive and negative subjects. NR shows a promising profile to be used to reduce the risk of active TB.

Assessing infection control practices to protect health care workers and patients in Malawi from nosocomial transmission of Mycobacterium tuberculosis

PubMed Central

Simon, Katherine; Hosseinipour, Mina; Kim, Maria H.; Mlauzi, Lameck; Kazembe, Peter N.; Ahmed, Saeed

2017-01-01

Transmission of Mycobacterium tuberculosis (TB) in health settings threatens health care workers and people living with HIV in sub-Saharan Africa. Nosocomial transmission is reduced with implementation of infection control (IC) guidelines. The objective of this study is to describe implementation of TB IC measures in Malawi. We conducted a cross-sectional study utilizing anonymous health worker questionnaires, semi-structured interviews with facility managers, and direct observations at 17 facilities in central Malawi. Of 592 health care workers surveyed, 34% reported that all patients entering the facility were screened for cough and only 8% correctly named the four most common signs and symptoms of TB in adults. Of 33 managers interviewed, 7 (21%) and 1 (3%) provided the correct TB screening questions for use in adults and children, respectively. Of 592 health workers, only 2.4% had been screened for TB in the previous year. Most (90%) reported knowing their HIV status, 53% were tested at their facility of employment, and half reported they would feel comfortable receiving ART or TB treatment at their facility of employment. We conclude that screening is infrequently conducted and knowledge gaps may undercut its effectiveness. Further, health care workers do not routinely access TB and HIV diagnostic and treatment services at their facility of employment. PMID:29211793

Assessing infection control practices to protect health care workers and patients in Malawi from nosocomial transmission of Mycobacterium tuberculosis.

PubMed

Flick, Robert J; Munthali, Adamson; Simon, Katherine; Hosseinipour, Mina; Kim, Maria H; Mlauzi, Lameck; Kazembe, Peter N; Ahmed, Saeed

2017-01-01

Transmission of Mycobacterium tuberculosis (TB) in health settings threatens health care workers and people living with HIV in sub-Saharan Africa. Nosocomial transmission is reduced with implementation of infection control (IC) guidelines. The objective of this study is to describe implementation of TB IC measures in Malawi. We conducted a cross-sectional study utilizing anonymous health worker questionnaires, semi-structured interviews with facility managers, and direct observations at 17 facilities in central Malawi. Of 592 health care workers surveyed, 34% reported that all patients entering the facility were screened for cough and only 8% correctly named the four most common signs and symptoms of TB in adults. Of 33 managers interviewed, 7 (21%) and 1 (3%) provided the correct TB screening questions for use in adults and children, respectively. Of 592 health workers, only 2.4% had been screened for TB in the previous year. Most (90%) reported knowing their HIV status, 53% were tested at their facility of employment, and half reported they would feel comfortable receiving ART or TB treatment at their facility of employment. We conclude that screening is infrequently conducted and knowledge gaps may undercut its effectiveness. Further, health care workers do not routinely access TB and HIV diagnostic and treatment services at their facility of employment.

Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB.

PubMed

Chegou, Novel N; Sutherland, Jayne S; Malherbe, Stephanus; Crampin, Amelia C; Corstjens, Paul L A M; Geluk, Annemieke; Mayanja-Kizza, Harriet; Loxton, Andre G; van der Spuy, Gian; Stanley, Kim; Kotzé, Leigh A; van der Vyver, Marieta; Rosenkrands, Ida; Kidd, Martin; van Helden, Paul D; Dockrell, Hazel M; Ottenhoff, Tom H M; Kaufmann, Stefan H E; Walzl, Gerhard

2016-09-01

User-friendly, rapid, inexpensive yet accurate TB diagnostic tools are urgently needed at points of care in resource-limited settings. We investigated host biomarkers detected in serum samples obtained from adults with signs and symptoms suggestive of TB at primary healthcare clinics in five African countries (Malawi, Namibia, South Africa, The Gambia and Uganda), for the diagnosis of TB disease. We prospectively enrolled individuals presenting with symptoms warranting investigation for pulmonary TB, prior to assessment for TB disease. We evaluated 22 host protein biomarkers in stored serum samples using a multiplex cytokine platform. Using a pre-established diagnostic algorithm comprising of laboratory, clinical and radiological findings, participants were classified as either definite TB, probable TB, questionable TB status or non-pulmonary TB. Of the 716 participants enrolled, 185 were definite and 29 were probable TB cases, 6 had questionable TB disease status, whereas 487 had no evidence of TB. A seven-marker biosignature of C reactive protein, transthyretin, IFN-γ, complement factor H, apolipoprotein-A1, inducible protein 10 and serum amyloid A identified on a training sample set (n=491), diagnosed TB disease in the test set (n=210) with sensitivity of 93.8% (95% CI 84.0% to 98.0%), specificity of 73.3% (95% CI 65.2% to 80.1%), and positive and negative predictive values of 60.6% (95% CI 50.3% to 70.1%) and 96.4% (95% CI 90.5% to 98.8%), respectively, regardless of HIV infection status or study site. We have identified a seven-marker host serum protein biosignature for the diagnosis of TB disease irrespective of HIV infection status or ethnicity in Africa. These results hold promise for the development of a field-friendly point-of-care screening test for pulmonary TB. 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/

Effect of host diversity and species assemblage composition on bovine tuberculosis (bTB) risk in Ethiopian cattle.

PubMed

Sintayehu, Dejene W; Heitkönig, Ignas M A; Prins, Herbert H T; Tessema, Zewdu K; DE Boer, Willem F

2017-05-01

Current theories on diversity-disease relationships describe host species diversity and species identity as important factors influencing disease risk, either diluting or amplifying disease prevalence in a community. Whereas the simple term 'diversity' embodies a set of animal community characteristics, it is not clear how different measures of species diversity are correlated with disease risk. We therefore tested the effects of species richness, Pielou's evenness and Shannon's diversity on bovine tuberculosis (bTB) risk in cattle in the Afar Region and Awash National Park between November 2013 and April 2015. We also analysed the identity effect of a particular species and the effect of host habitat use overlap on bTB risk. We used the comparative intradermal tuberculin test to assess the number of bTB-infected cattle. Our results suggested a dilution effect through species evenness. We found that the identity effect of greater kudu - a maintenance host - confounded the dilution effect of species diversity on bTB risk. bTB infection was positively correlated with habitat use overlap between greater kudu and cattle. Different diversity indices have to be considered together for assessing diversity-disease relationships, for understanding the underlying causal mechanisms. We posit that unpacking diversity metrics is also relevant for formulating disease control strategies to manage cattle in ecosystems characterized by seasonally limited resources and intense wildlife-livestock interactions.

Rolling Out Xpert® MTB/RIF for TB Detection in HIV-Infected Populations:An Opportunity for Systems Strengthening.

PubMed

Pathmanathan, Ishani; Date, Anand; Coggin, William L; Nkengasong, John; Piatek, Amy S; Alexander, Heather

2017-03-31

To eliminate preventable deaths, disease and suffering due to tuberculosis (TB), improved diagnostic capacity is critical. The Cepheid Xpert ® MTB/RIF assay is recommended by the World Health Organization as the initial diagnostic test for people with suspected HIV-associated TB. However, despite high expectations, its scale-up in real-world settings has faced challenges, often due to the systems that support it. In this commentary we discuss needs and opportunities for systems strengthening to support widespread scale-up of Xpert ® MTB/RIF as they relate to each step within the TB diagnostic cascade, from finding presumptive patients, to collecting, transporting and testing sputum specimens, to reporting and receiving results, to initiating and monitoring treatment and, ultimately, to ensuring successful and timely treatment and cure. Investments in evidence-based interventions at each step along the cascade and within the system as a whole will augment not only the utility of Xpert ® MTB/RIF, but also the successful implementation of future diagnostic tests. Xpert ® MTB/RIF will only improve patient outcomes if optimally implemented within the context of strong TB programs and systems. Roll-out of this technology to people living with HIV and others in resource-limited settings offers the opportunity to leverage current TB and HIV laboratory, diagnostic and programmatic investments, while also addressing challenges and strengthening coordination between laboratory systems, laboratory-program interfaces, and TB-HIV program interfaces. If successful, the benefits of this tool could extend beyond progress towards global End TB Strategy goals, to improve system-wide capacity for global disease detection and control.

Cryptosporidiosis and other intestinal parasitic infections in patients with chronic diarrhea.

PubMed

Mahdi, Nadham K; Ali, Naeel H

2004-09-01

To consider the relationship of the parasitic infections including cryptosporidium with chronic diarrhea. Also the effect of chronic disease as pulmonary tuberculosis (TB) and nosocomial infection on the occurrence rate of parasites in cases of chronic diarrhea. Stool samples were collected from 205 patients in teaching, general, child and maternity hospitals in Basrah, Iraq, suffering from chronic diarrhea during 2000. Out of these patients, there were 40 patients with pulmonary TB and 50 inpatients with nosocomial infection. Also 175 apparently healthy individuals who have no episodes of diarrhea for at least 2-months were served as a control group. Direct smear method and then formalin ether sedimentation method were carried out for stool samples to detect intestinal parasites. Fecal smears were prepared from the sediment and stained by the modified Ziehl Neelsen stain for the recovery of red pink oocysts of cryptosporidium. Out of the 205 examined patients, cryptosporidium oocysts were found to be excreted in 20 (9.7%) patients in comparing to 1.1% of the control group. The difference is statistically significant. There were 109 (53.2%) patients found to be positive for intestinal parasitic infections compared to 26 (14.8%) of the control group. The difference is also statistically significant. Out of the 40 TB patients, 2 (5%) were found to excrete cryptosporidium oocysts and also 27 (67.3%) were positive for intestinal parasites. In addition, there were 4 (8%) excreting cryptosporidium oocysts and 23 (46%) infecting by intestinal parasites among the in patients with nosocomial infection. Both acid and non-acid fast parasites should be considered in the differential diagnosis of undiagnosed chronic diarrhea especially among patients with pulmonary TB or nosocomial infection.

Working towards TB elimination the WHO Regional Strategic Plan (2006-2015).

PubMed

Nair, Nani; Cooreman, Erwin

2006-03-01

DOTS has expanded rapidly in the South-East Asia Region over the period of the Partnership's first Global Plan (2001-2005), with almost 100% geographical coverage achieved in 2005. All countries have made impressive progress in improving coverage and quality. This progress has been made possible through strong political commitment and large investments in TB control for improved infrastructure, reliable drug supply, increased staffing, improved laboratory services, and intensified training and supervision. Accomplishing the objectives outlined in this document will require sustaining the progress in all countries and particularly in the five high burden countries for achieving major regional and global impact. National TB programmes will need to be supported to maintain or surpass the 70% case detection and 85% treatment success rates. The achievement of the TB-related targets linked to the MDGs will also depend on how effectively initiatives such as DOTS-Plus, PPM DOTS and interventions for TB/ HIV among others, are implemented. National governments and development partners must fulfill their commitments to mobilizing and sustaining adequate resources to support the full range of activities envisaged. The benefits of full and effective implementation of all the planned interventions would be substantial. These will result in 20 to 25 million TB cases being treated in DOTS program mes and more than 150 000 drug-resistant cases receiving treatment through DOTS-Plus during the period 2006-2015. In addition, at least 250 000 HIV-infected TB patients may also receive anti-retroviral therapy. As a consequence, the prevalence of TB is expected to fall below 175/100 000 and the number of TB deaths is expected to fall to between 100 000 and 150 000 per year. There would also be substantial economic benefits given that TB disproportionately affects adults in their most productive years. Considering these aspects, it is expected that the TB incidence will decline

Targeting the human macrophage with combinations of drugs and inhibitors of Ca2+ and K+ transport to enhance the killing of intracellular multi-drug resistant Mycobacterium tuberculosis (MDR-TB)--a novel, patentable approach to limit the emergence of XDR-TB.

PubMed

Martins, Marta

2011-05-01

The emergence of resistance in tuberculosis has become a serious problem for the control of this disease. For that reason, new therapeutic strategies that can be implemented in the clinical setting are urgently needed. The design of new compounds active against mycobacteria must take into account that tuberculosis is mainly an intracellular infection of the alveolar macrophage and therefore must maintain activity within the host cells. An alternative therapeutic approach will be described in this review, focusing on the activation of the phagocytic cell and the subsequent killing of the internalized bacteria. This approach explores the combined use of antibiotics and phenothiazines, or Ca(2+) and K(+) flux inhibitors, in the infected macrophage. Targeting the infected macrophage and not the internalized bacteria could overcome the problem of bacterial multi-drug resistance. This will potentially eliminate the appearance of new multi-drug resistant tuberculosis (MDR-TB) cases and subsequently prevent the emergence of extensively-drug resistant tuberculosis (XDR-TB). Patents resulting from this novel and innovative approach could be extremely valuable if they can be implemented in the clinical setting. Other patents will also be discussed such as the treatment of TB using immunomodulator compounds (for example: betaglycans).

Prevalence of tuberculous infection and incidence of tuberculosis; a re-assessment of the Styblo rule

PubMed Central

van der Werf, MJ; Borgdorff, MW

2008-01-01

Abstract Objective To evaluate the validity of the fixed mathematical relationship between the annual risk of tuberculous infection (ARTI), the prevalence of smear-positive tuberculosis (TB) and the incidence of smear-positive TB specified as the Styblo rule, which TB control programmes use to estimate the incidence of TB disease at a population level and the case detection rate. Methods Population-based tuberculin surveys and surveys on prevalence of smear-positive TB since 1975 were identified through a literature search. For these surveys, the ratio between the number of tuberculous infections (based on ARTI estimates) and the number of smear-positive TB cases was calculated and compared to the ratio of 8 to 12 tuberculous infections per prevalent smear-positive TB case as part of the Styblo rule. Findings Three countries had national population-based data on both ARTI and prevalence of smear-positive TB for more than one point in time. In China the ratio ranged from 3.4 to 5.8, in the Philippines from 2.6 to 4.4, and in the Republic of Korea, from 3.2 to 4.7. All ratios were markedly lower than the ratio that is part of the Styblo rule. Conclusion According to recent country data, there are typically fewer than 8 to 12 tuberculous infections per prevalent smear-positive TB case, and it remains unclear whether this ratio varies significantly among countries. The decrease in the ratio compared to the Styblo rule probably relates to improvements in the prompt treatment of TB disease (by national TB programmes). A change in the number of tuberculous infections per prevalent smear-positive TB case in population-based surveys makes the assumed fixed mathematical relationship between ARTI and incidence of smear-positive TB no longer valid. PMID:18235886

Mathematical modeling of transmission co-infection tuberculosis in HIV community

NASA Astrophysics Data System (ADS)

Lusiana, V.; Putra, P. S.; Nuraini, N.; Soewono, E.

2017-03-01

TB and HIV infection have the effect of deeply on assault the immune system, since they can afford to weaken host immune respone through a mechanism that has not been fully understood. HIV co-infection is the stongest risk factor for progression of M. tuberculosis to active TB disease in HIV individuals, as well as TB has been accelerated to progression HIV infection. In this paper we create a model of transmission co-infection TB in HIV community, dynamic system with ten compartments built in here. Dynamic analysis in this paper mentioned ranging from disease free equilibrium conditions, endemic equilibrium conditions, basic reproduction ratio, stability analysis and numerical simulation. Basic reproductive ratio were obtained from spectral radius the next generation matrix of the model. Numerical simulations are built to justify the results of the analysis and to see the changes in the dynamics of the population in each compartment. The sensitivity analysis indicates that the parameters affecting the population dynamics of TB in people with HIV infection is parameters rate of progression of individuals from the exposed TB class to the active TB, treatment rate of exposed TB individuals, treatment rate of infectious (active TB) individuals and probability of transmission of TB infection from an infective to a susceptible per contact per unit time. We can conclude that growing number of infections carried by infectious TB in people with HIV infection can lead to increased spread of disease or increase in endemic conditions.

Rapid detection of Mycobacterium tuberculosis complex in sputum Samples using PURE TB-LAMP assay.

PubMed

N'guessan, K; Horo, K; Coulibaly, I; Adegbele, J; Kouame-Adjei, N; Seck-Angu, H; Guei, A; Kouakou, J; Dosso, M

2016-12-01

Lack of rapid and accurate diagnostic testing is a critical obstacle to global tuberculosis (TB) control. Sensitivity of sputum smear microscopy (SSM) is not optimal; however, it remains the most prevalent tool for TB confirmation in poor countries. As a part of passive case finding of TB detection, this study was conducted to determine the clinical performance of PURE TB-LAMP assay using liquid culture medium as the gold standard. Centre Antituberculeux de Yopougon is one of the 17 intermediate Tuberculosis centers in Côte d'Ivoire. A standardized questionnaire was submitted to patients with signs and symptoms consistent with tuberculosis by a trained caregiver. After obtaining signed consent forms, sputum samples were collected according to National TB Control Programme guidelines (spot-morning). SSM after Ziehl-Neelsen staining and TB-LAMP assay were blindly performed on the first sample. Samples transported to Institut Pasteur de Côte d'Ivoire were decontaminated according to the N-acetyl-L-Cystein method. In Mycobacteria Growth Indicator Tube (MGIT), 500mL of pellets were inoculated and incubated in the MGIT 960 system. MPT64 antigen was detected in positive cultures. Of the 500 patients enrolled, 469 (232men and 239 women) patients were included. The mean ages of men and women were 36.9 (15-86) and 37.3 (15-37.3) years, respectively. There were 56 (12.2%) HIV-infected patients, including 14 women. Clinical isolates of M. tuberculosis complex were detected for 157 (33.5%) patients. Compared with culturing, the overall sensitivity and specificity of SSM were 86% (95% confidence interval [CI]=81-91) and 96% (95% CI=94-98), respectively. The overall sensitivity and specificity for TB-LAMP was 92% (95% CI=0.88-0.96) and 94% (95% CI=0.91-0.97), respectively. Positive likelihood ratios for TB-LAMP and SSM were 15.3 and 21.5, respectively, and negative likelihood ratios for TB-LAMP and SSM were 0.09 and 0.15, respectively. Among the 469 patients, active

Relapse, re-infection and mixed infections in tuberculosis disease.

PubMed

McIvor, Amanda; Koornhof, Hendrik; Kana, Bavesh Davandra

2017-04-01

Tuberculosis (TB) disease can be characterized by genotypic and phenotypic complexity in Mycobacterium tuberculosis bacilli within a single patient. This microbiological heterogeneity has become an area of intense study due its perceived importance in drug tolerance, drug resistance and as a surrogate measure of transmission rates. This review presents a descriptive analysis of research describing the prevalence of mixed-strain TB infections in geographically distinct locations. Despite significant variation in disease burden and a rampant human immunodeficiency virus (HIV)-TB co-epidemic, there was no difference in the prevalence range of mixed infections reported in African countries when compared to the rest of the world. The occurrence of recurrent TB was associated with a higher prevalence of mixed-strain infections, but this difference was not reported as statistically significant. These interpretations were limited by differences in the design and overall size of the studies assessed. Factors such as sputum quality, culture media, number of repeated culture steps, molecular typing methods and HIV-infection status can affect the detection of mixed-strain infection. It is recommended that future clinical studies should focus on settings with varying TB burdens, with a common sample processing protocol to gain further insight into these phenomena and develop novel transmission blocking strategies. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Low tuberculosis knowledge among HIV-infected patients in a high HIV prevalence region within southeast India.

PubMed

Arora, Nick; Vadrevu, Ravi; Chandrasekhar, Aditya; Gupta, Amita

2013-01-01

A private multispecialty hospital in Kakinada, Andhra Pradesh, India. A survey of knowledge, attitudes, and perceptions adapted from a pretested questionnaire was administered to 128 HIV-infected adults, from July to August 2008. A total of 31% had not heard of tuberculosis (TB), with 15 (38%) currently receiving anti-TB therapy or had received it in the past. Of those familiar with TB, 70% could not list a method by which it was spread. Low education attainment, female sex, and less frequent television exposure were associated with low TB literacy. HIV-infected patients in southeast India have poor knowledge of TB and the methods by which it is spread. Scale-up of patient-directed educational programs is necessary to help control TB in India.

Tuberculin skin testing and T-SPOT.TB in internationally adopted children.

PubMed

Spicer, Kevin B; Turner, Joanne; Wang, Shu-Hua; Koranyi, Katalin; Powell, Dwight A

2015-06-01

Diagnosis of latent tuberculosis infection is a problem in children because of lack of a diagnostic standard and potential impact of previous Bacille Calmette-Guérin vaccination and exposure to environmental mycobacteria. Effectiveness and usefulness of interferon-gamma release assays in infants and younger children have yet to be clearly demonstrated. Prospective cohort study including 109 children (4 months to 16 years) seen in an international adoption clinic at Nationwide Children's Hospital, Columbus, OH. Children were adopted from 14 countries, mostly (72.5%) from China, Russia and Ethiopia. Correspondence between tuberculin skin test (TST) and the T-SPOT.TB assay was evaluated. Factors associated with positive results on the TST and T-SPOT.TB were determined, and the impact of age on test performance was specifically addressed. TST was positive in 23.4% (25 of 107). T-SPOT.TB was positive in 4.6% (5 of 109). Overall agreement between TST and T-SPOT.TB was 71%, with prevalence-adjusted, bias-adjusted Kappa of 0.68. History of Mycobacterium tuberculosis exposure was associated with positive results on TST (odds ratio: 25.4, 95% confidence interval: 4.8-261.6, exact logistic regression) and T-SPOT.TB (odds ratio: 78.9, 95% confidence interval: 9.7-∞). All 5 children with positive T-SPOT.TB had TST induration ≥15 mm. No patient less than 1 year of age (n = 17) had positive TST or T-SPOT.TB. Positive TST was not associated with Bacille Calmette-Guérin vaccination or scar. TST was positive in a significant percentage of international adoptees. T-SPOT.TB was rarely positive and discordant results reflected negative T-SPOT.TB with positive TST. In this population latent tuberculosis infection may be over-estimated by TST. Regardless, in our context at the time of the study, treatment decisions were based upon TST results, not results of the T-SPOT.TB assay. Age was consistently associated with findings on TST and T-SPOT.TB with no positive result on either

Infection caused by Mycobacterium tuberculosis.

PubMed

Peloquin, C A; Berning, S E

1994-01-01

To update readers on the clinical management of infections caused by Mycobacterium tuberculosis, to provide a general description of the organism, culture and susceptibility testing, and clinical manifestations of the disease, and to provide several aspects of the treatment of the disease, including historical perspective, current approaches, and research opportunities for the future. The current medical literature, including abstracts presented at recent international meetings, is reviewed. References were identified through MEDLINE, MEDLARS II, Current Contents, and published meeting abstracts. Data regarding the epidemiology, clinical manifestations, culture and susceptibility testing, and treatment of tuberculosis are cited. Specific attention has been focused on the clinical management of patients with noncontagious infection and potentially contagious active disease (TB) caused by M. tuberculosis. Information contributing to the discussion of the topics selected by the authors is reviewed. Data supporting and disputing specific conclusions are presented. The incidence of TB is increasing in the US, despite the fact that available technologies are capable of controlling the vast majority of existing cases. Fueling the fire is the problem of coinfection with HIV and M. tuberculosis. Very few drugs are available for the treatment of TB, and few of these approach the potency of isoniazid and rifampin. Preventive therapy of patients exposed to multiple-drug-resistant M. tuberculosis (MDR-TB) is controversial and of unknown efficacy. Treatment of active disease caused by MDR-TB requires up to four times longer, is associated with increased toxicity, and is far less successful than the treatment of drug-susceptible TB. Strategies for the management of such cases are presented. The rising incidence of TB in the US reflects a breakdown in the healthcare systems responsible for controlling the disease, which reflects the past budgetary reductions. Although TB control

Application Values of T-SPOT.TB in Clinical Rapid Diagnosis of Tuberculosis.

PubMed

Zhu, Feng; Ou, Qinfang; Zheng, Jian

2018-01-01

This paper aims to explore the application value of tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB) in the diagnosis of tuberculosis. Fifty one patients with tuberculosis (TB) admitted to Wuxi No.5 People's Hospital, Wuxi, China from June 2015 to June 2017 were selected as the TB group, and 40 patients without tuberculosis admitted in the same period were randomly selected as the non-TB group. Patients in the two groups received T-SPOT.TB, TB antibody (TB-Ab) test and mycobacterium TB deoxyribonucleic acid (TB-DNA) test, and the results were compared. Comparisons of the sensitivity of the three methods showed that the sensitivity of T-SPOT.TB was the highest, followed by TB-DNA from sputum samples, and that of TB-Ab was the lowest. The specificity of TB-Ab was the highest, followed by T-SPOT.TB, and that of TB-DNA from sputum samples was the lowest. In the receiver operating characteristic (ROC) curve analysis, the area under curve (AUC) of T-SPOT.TB (0.896) was the highest, followed by TB-DNA from sputum samples (0.772), and that of sputum smears (0.698) was the lowest. T-SPOT.TB can quickly and accurately determine the presence of tuberculosis infection, and it is a non-invasive examination, which can further assist in the diagnosis and guide the treatment.

Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity.

PubMed

Abate, Ebba; Belayneh, Meseret; Idh, Jonna; Diro, Ermias; Elias, Daniel; Britton, Sven; Aseffa, Abraham; Stendahl, Olle; Schön, Thomas

2015-08-01

The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB. Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively. A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/μl versus 2.4 (1.1-4.0) cells/μl; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients. Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.

Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

PubMed Central

Kammüller, Michael; Tsai, Tsen-Fang; Griffiths, Christopher EM; Kapoor, Nidhi; Kolattukudy, Pappachan E; Brees, Dominique; Chibout, Salah-Dine; Safi Jr, Jorge; Fox, Todd

2017-01-01

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti-tumor necrosis factor-α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three-dimensional microgranuloma model. Auramine-O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro, anti-TNFα treatment showed increased staining for Auramine-O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections. PMID:28868144

Scale-up of collaborative TB/HIV activities in Guyana.

PubMed

Baker, Brian J; Peterson, Brandy; Mohanlall, Jeetendra; Singh, Shanti; Hicks, Collene; Jacobs, Ruth; Ramos, Ruth; Allen, Barbara; Pevzner, Eric

2017-04-20

To assess scale-up of recommended tuberculosis (TB)/HIV activities in Guyana and to identify specific strategies for further expansion. Medical records and clinic registers were reviewed at nine TB clinics and 10 HIV clinics. At TB clinics, data were collected on HIV testing and antiretroviral therapy (ART) for patients with TB/HIV; at HIV clinics, data were collected on intensified case finding (ICF), tuberculin skin test (TST) results, and provision of isoniazid preventive therapy (IPT). At TB clinics, among 461 patients newly diagnosed with TB, 419 (90.9%) had a known HIV status and 121 (28.9%) were HIV-infected. Among the 63 patients with TB/HIV, 33 (52.4%) received ART. Among the 45 patients with TB/HIV for whom dates of HIV diagnosis were available, 38 (84.4%) individuals knew their HIV status prior to TB diagnosis. At HIV clinics, among 127 patients eligible to receive a TST, 87 (68.5%) received a TST, 66 (75.9%) had a TST result, seven (10.6%) had a newly positive result, two had a previously positive result, and six of nine patients with positive results (66.7%) received IPT. ICF could not be assessed because of incomplete or discrepant documentation. An in-depth evaluation of TB/HIV activities successfully identified areas of success and remaining challenges. At TB clinics, HIV testing rates are high; further scale-up of ART for persons with TB/HIV is needed. At HIV clinics, use of TST to focus IPT is a feasible and efficient strategy; improving rates of annual TST screening will allow for further expansion of IPT.

The impact of HIV status and antiretroviral treatment on TB treatment outcomes of new tuberculosis patients attending co-located TB and ART services in South Africa: a retrospective cohort study.

PubMed

Nglazi, Mweete D; Bekker, Linda-Gail; Wood, Robin; Kaplan, Richard

2015-11-19

The implementation of collaborative TB-HIV services is challenging. We, therefore, assessed TB treatment outcomes in relation to HIV infection and antiretroviral therapy (ART) among TB patients attending a primary care service with co-located ART and TB clinics in Cape Town, South Africa. In this retrospective cohort study, all new TB patients aged ≥ 15 years who registered and initiated TB treatment between 1 October 2009 and 30 June 2011 were identified from an electronic database. The effects of HIV-infection and ART on TB treatment outcomes were analysed using a multinomial logistic regression model, in which treatment success was the reference outcome. The 797 new TB patients included in the analysis were categorized as follows: HIV- negative, in 325 patients (40.8 %); HIV-positive on ART, in 339 patients (42.5 %) and HIV-positive not on ART, in 133 patients (16.7 %). Overall, bivariate analyses showed no significant difference in death and default rates between HIV-positive TB patients on ART and HIV-negative patients. Statistically significant higher mortality rates were found among HIV-positive patients not on ART compared to HIV-negative patients (unadjusted odds ratio (OR) 3.25; 95 % confidence interval (CI) 1.53-6.91). When multivariate analyses were conducted, the only significant difference between the patient categories on TB treatment outcomes was that HIV-positive TB patients not on ART had significantly higher mortality rates than HIV-negative patients (adjusted OR 4.12; 95 % CI 1.76-9.66). Among HIV-positive TB patients (n = 472), 28.2 % deemed eligible did not initiate ART in spite of the co-location of TB and ART services. When multivariate analyses were restricted to HIV-positive patients in the cohort, we found that being HIV-positive not on ART was associated with higher mortality (adjusted OR 7.12; 95 % CI 2.95-18.47) and higher default rates (adjusted OR 2.27; 95 % CI 1.15-4.47). There was no significant difference in death and

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

PubMed

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B B; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and

The rural-to-urban migrant population in China: gloomy prospects for tuberculosis control.

PubMed

Tobe, Ruoyan Gai; Xu, Lingzhong; Song, Peipei; Huang, Yong

2011-12-01

The migrant population is a population with a high risk of tuberculosis (TB) infection and transmission. Globally, migration is likely to have a significant impact on TB epidemiology, particularly in countries that receive substantial numbers of migrants from countries with a high infection burden. China, a country with the world's second highest TB burden, faces a considerable increase in the number of rural-to-urban migrants. This population has a significant impact on urban TB epidemics and is specifically targeted by national guidelines for TB control. TB control among the migrant population has had relatively poor outcomes. Barriers to detection and treatment have both financial and non-financial aspects, such as the "migratory" nature of the migrant population, their marginalized working and living environment, poor financial status, little awareness of TB, inadequate referral to TB dispensaries, and potential social stigma in the workplace. Currently, the free TB treatment policy has limited ability to relieve the financial burden on most migrant TB patients as would allow optimal outcomes of TB detection and treatment. Universal health insurance coverage and fostering of personnel in community-based primary health care for the rural-to- urban migrant population represent two pillars of successful TB control.

Risk factors associated with multidrug-resistant tuberculosis (MDR-TB) in a tertiary armed force referral and teaching hospital, Ethiopia.

PubMed

Demile, Biresaw; Zenebu, Amare; Shewaye, Haile; Xia, Siqing; Guadie, Awoke

2018-05-31

MDR-TB was identified in armed force and civilian patients that were significantly associated with category of attendants, HIV infection and TB contact history. Considering armed force society as one segment of population significantly helps to plan a better MDR-TB control management, especially for countries classified as TB high burden country.

More significance of TB-IGRA except for the diagnose of tuberculosis.

PubMed

Xu, Jun-Chi; Li, Ze-Yi; Chen, Xin-Nian; Shi, Cui-Lin; Wu, Mei-Ying; Chen, Hui; Zhu, Xiao-Yan; Song, Hua-Feng; Wu, Min-Juan; Xu, Ping

2018-01-01

Tuberculosis (TB)-interferon gamma release assay (IGRA) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between TB-IGRA test results and body's immune cells, disease progression and prognosis, which is explored in this study. A retrospective study was carried out on positive TB-IGRA patients who were infected with TB and diagnosed at our hospital from January 2014 to June 2015. The TB-IGRA, routine blood test, T-cell subgroup data were collected for statistical analysis. TB-IGRA results were in positive proportion to the lymphocytes, CD4 + T cells and CD4 + CD28 + T cells, whereas negative to the Treg cells. Patient with unilateral pulmonary lesion had higher TB-IGRA than those with bilateral pulmonary lesions. After the stimulation of TB-specific antigen, the proportion of CD4 + IFN-γ + and CD8 + IFN-γ + T Tcells were both increased and the CD4 + IFN-γ + T had positive correlation with the value of TB-IGRA. IFN-γ was tested with TB-IGRA in patients with TB by the specific TB T cells and correlated with the lymphocytes, while the lymphocytes also closely related to the host's anti-TB immunity and disease outcome. Hence the result of TB-IGRA could reflect the specific anti-TB immunity ability of the host, disease progression and prognosis. This study further expands the application scope of TB-IGRA technology in the diagnosis of TB and lays a foundation for clinical practice to understand the immunity state of the patients with TB and the application of auxiliary clinical immunity regulators. © 2017 Wiley Periodicals, Inc.

Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease.

PubMed

Awoniyi, Dolapo O; Teuchert, Andrea; Sutherland, Jayne S; Mayanja-Kizza, Harriet; Howe, Rawleigh; Mihret, Adane; Loxton, Andre G; Sheehama, Jacob; Kassa, Desta; Crampin, Amelia C; Dockrell, Hazel M; Kidd, Martin; Rosenkrands, Ida; Geluk, Annemieke; Ottenhoff, Tom H M; Corstjens, P L A M; Chegou, Novel N; Walzl, Gerhard

2016-09-01

We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB. Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

PubMed Central

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B.B.; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing

46 CFR 39.1001 - Applicability-TB/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Applicability-TB/ALL. 39.1001 Section 39.1001 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.1001 Applicability—TB/ALL. (a) This part applies to tank vessels that use a vapor control system (VCS) to collect...

46 CFR 39.1001 - Applicability-TB/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Applicability-TB/ALL. 39.1001 Section 39.1001 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS VAPOR CONTROL SYSTEMS General § 39.1001 Applicability—TB/ALL. (a) This part applies to tank vessels that use a vapor control system (VCS) to collect...

"The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.

PubMed

Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy

2017-06-14

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. Copyright © 2017.

Treatment of Latent Tuberculosis Infection.

PubMed

Tang, Patrick; Johnston, James

2017-01-01

The treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) elimination in regions that have a low incidence of TB. However, the decision to treat individuals with LTBI must consider the limitations of current diagnostic tests for LTBI, the risk of developing active TB disease, the potential adverse effects from chemoprophylactic therapy, and the importance of treatment adherence. When an individual has been diagnosed with LTBI and active TB has been ruled out, this is followed by an evaluation of the risks and benefits of LTBI treatment within the context of the regional epidemiology of TB and public health priorities. Once the decision to treat LTBI has been reached, and the infection is not suspected to be due to drug-resistant TB, the recommended regimens include isoniazid and/or rifamycin-derivatives, and the choice of regimen will depend upon the clinical considerations for that individual, such as patient preference, concomitant medications, hepatic disease, pregnancy, or immunodeficiency. As the duration of treatment of LTBI therapy is many months, therapy must be offered within a plan that monitors for adverse drug reactions and emphasizes adherence. For latent multidrug-resistant TB (MDR-TB) or extensively drug-resistant TB (XDR-TB) infection, the management is more complicated as there are few options for chemoprophylactic therapy and little evidence regarding the efficacy or risks of these regimens.

Knowledge and perceptions of national and provincial tuberculosis control programme managers in Pakistan about the WHO Stop TB strategy: a qualitative study.

PubMed

Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz; Hassounah, Sondus

2016-01-01

To understand how national and provincial tuberculosis programme managers in Pakistan perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. National and provincial tuberculosis programme managers play an important role in effective implementation of the Stop TB strategy. A qualitative interview study was conducted with 10 national and provincial tuberculosis programme managers to understand how they perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). National and provincial tuberculosis programme managers in Pakistan. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). National and provincial tuberculosis programmes in Pakistan. 1. Knowledge and perceptions of national and provincial tuberculosis programme managers about the Stop TB strategy 2. Progress in implementing the strategy in Pakistan 3. Significant success factors 4. Significant implementation challenges 5. Lessons learnt to scale up successful implementation. The managers reported that most progress had been made in extending DOTS, health systems strengthening, public -private mixed interventions, MDR-TB care and TB/HIV care. The four factors that contributed significantly to progress were the availability of DOTS services, the public-private partnership approach, comprehensive guidance for TB control and government and donor commitment to TB control. This study identified three main challenges as perceived by national and provincial tuberculosis programme managers in terms of implementing the Stop TB strategy: 1. Inadequate political commitment, 2. Issue pertaining to prioritisation of certain components in the TB strategy over others due to external influences and 3. Limitations in the overall

Knowledge and perceptions of national and provincial tuberculosis control programme managers in Pakistan about the WHO Stop TB strategy: a qualitative study

PubMed Central

Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz

2016-01-01

Objective To understand how national and provincial tuberculosis programme managers in Pakistan perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. National and provincial tuberculosis programme managers play an important role in effective implementation of the Stop TB strategy. Design A qualitative interview study was conducted with 10 national and provincial tuberculosis programme managers to understand how they perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). Participants National and provincial tuberculosis programme managers in Pakistan. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). Setting National and provincial tuberculosis programmes in Pakistan Main outcome measures 1. Knowledge and perceptions of national and provincial tuberculosis programme managers about the Stop TB strategy 2. Progress in implementing the strategy in Pakistan 3. Significant success factors 4. Significant implementation challenges 5. Lessons learnt to scale up successful implementation. Results The managers reported that most progress had been made in extending DOTS, health systems strengthening, public -private mixed interventions, MDR-TB care and TB/HIV care. The four factors that contributed significantly to progress were the availability of DOTS services, the public-private partnership approach, comprehensive guidance for TB control and government and donor commitment to TB control. Conclusion This study identified three main challenges as perceived by national and provincial tuberculosis programme managers in terms of implementing the Stop TB strategy: 1. Inadequate political commitment, 2. Issue pertaining to prioritisation of certain components in the TB

PCR-Internal Transcribed Spacer (ITS) genes sequencing and phylogenetic analysis of clinical and environmental Aspergillus species associated with HIV-TB co infected patients in a hospital in Abeokuta, southwestern Nigeria.

PubMed

Shittu, Olufunke Bolatito; Adelaja, Oluwabunmi Molade; Obuotor, Tolulope Mobolaji; Sam-Wobo, Sam Olufemi; Adenaike, Adeyemi Sunday

2016-03-01

Aspergillosis has been identified as one of the hospital acquired infections but the contribution of water and inhouse air as possible sources of Aspergillus infection in immunocompromised individuals like HIV-TB patients have not been studied in any hospital setting in Nigeria. To identify and investigate genetic relationship between clinical and environmental Aspergillus sp. associated with HIV-TB co infected patients. DNA extraction, purification, amplification and sequencing of Internal Transcribed Spacer (ITS) genes were performed using standard protocols. Similarity search using BLAST on NCBI was used for species identification and MEGA 5.0 was used for phylogenetic analysis. Analyses of sequenced ITS genes of selected fourteen (14) Aspergillus isolates identified in the GenBank database revealed Aspergillus niger (28.57%), A. tubingensis (7.14%), A. flavus (7.14%) and A. fumigatus (57.14%). Aspergillus in sputum of HIV patients were Aspergillus niger, A. fumigatus, A. tubingensis and A. flavus. Also, A. niger and A. fumigatus were identified from water and open-air. Phylogenetic analysis of sequences yielded genetic relatedness between clinical and environmental isolates. Water and air in health care settings in Nigeria are important sources of Aspergillus sp. for HIV-TB patients.

Tuberculosis Screening on a Health Science Campus: Use of QuantiFERON-TB Gold Test for Students and Employees

ERIC Educational Resources Information Center

Veeser, Peggy Ingram; Smith, Phillip Karl; Handy, Barry; Martin, Sharon R.

2007-01-01

Detecting and managing "Mycobacterium tuberculosis" (TB) infection in a health-science center population is a clinical dilemma. Tuberculin skin tests are still the preferred method for detecting present or past infection of TB. The authors discuss the performance of whole blood interferon gamma release assay test commercially known as…

Design and use of mouse control DNA for DNA biomarker extraction and PCR detection from urine: Application for transrenal Mycobacterium tuberculosis DNA detection.

PubMed

Bordelon, Hali; Ricks, Keersten M; Pask, Megan E; Russ, Patricia K; Solinas, Francesca; Baglia, Mark L; Short, Philip A; Nel, Andrew; Blackburn, Jonathan; Dheda, Keertan; Zamudio, Carlos; Cáceres, Tatiana; Wright, David W; Haselton, Frederick R; Pettit, April C

2017-05-01

Urine samples are increasingly used for diagnosing infections including Escherichia coli, Ebola virus, and Zika virus. However, extraction and concentration of nucleic acid biomarkers from urine is necessary for many molecular detection strategies such as polymerase chain reaction (PCR). Since urine samples typically have large volumes with dilute biomarker concentrations making them prone to false negatives, another impediment for urine-based diagnostics is the establishment of appropriate controls particularly to rule out false negatives. In this study, a mouse glyceraldehyde 3-phosphate dehydrogenase (GAPDH) DNA target was added to retrospectively collected urine samples from tuberculosis (TB)-infected and TB-uninfected patients to indicate extraction of intact DNA and removal of PCR inhibitors from urine samples. We tested this design on surrogate urine samples, retrospective 1milliliter (mL) urine samples from patients in Lima, Peru and retrospective 5mL urine samples from patients in Cape Town, South Africa. Extraction/PCR control DNA was detectable in 97% of clinical samples with no statistically significant differences among groups. Despite the inclusion of this control, there was no difference in the amount of TB IS6110 Tr-DNA detected between TB-infected and TB-uninfected groups except for samples from known HIV-infected patients. We found an increase in TB IS6110 Tr-DNA between TB/HIV co-infected patients compared to TB-uninfected/HIV-infected patients (N=18, p=0.037). The inclusion of an extraction/PCR control DNA to indicate successful DNA extraction and removal of PCR inhibitors should be easily adaptable as a sample preparation control for other acellular sample types. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and use of mouse control DNA for DNA biomarker extraction and PCR detection from urine: application for transrenal Mycobacterium tuberculosis DNA detection

PubMed Central

Bordelon, Hali; Ricks, Keersten M.; Pask, Megan E.; Russ, Patricia K.; Solinas, Francesca; Baglia, Mark L.; Short, Philip A.; Nel, Andrew; Blackburn, Jonathan; Dheda, Keertan; Zamudio, Carlos; Cáceres, Tatiana; Wright, David W.; Haselton, Frederick R.; Pettit, April C.

2017-01-01

Urine samples are increasingly used for diagnosing infections including Escherichia coli, Ebola virus, and Zika virus. However, extraction and concentration of nucleic acid biomarkers from urine is necessary for many molecular detection strategies such as polymerase chain reaction (PCR). Since urine samples typically have large volumes with dilute biomarker concentrations making them prone to false negatives, another impediment for urine-based diagnostics is the establishment of appropriate controls particularly to rule out false negatives. In this study, a mouse glyceraldehyde 3-phosphate dehydrogenase (GAPDH) DNA target was added to retrospectively collected urine samples from tuberculosis (TB)-infected and TB-uninfected patients to indicate extraction of intact DNA and removal of PCR inhibitors from urine samples. We tested this design on surrogate urine samples, retrospective 1 milliliter (mL) urine samples from patients in Lima, Peru and retrospective 5 mL urine samples from patients in Cape Town, South Africa. Extraction/PCR control DNA was detectable in 97% of clinical samples with no statistically significant differences among groups. Despite the inclusion of this control, there was no difference in the amount of TB IS6110 Tr-DNA detected between TB-infected and TB-uninfected groups except for samples from known HIV-infected patients. We found a increase in TB IS6110 Tr-DNA between TB/HIV co-infected patients compared to TB-uninfected/HIV-infected patients (N=18, p=0.037). The inclusion of an extraction/PCR control DNA to indicate successful DNA extraction and removal of PCR inhibitors should be easily adaptable as a sample preparation control for other acellular sample types. PMID:28285168

Prevalence of latent tuberculosis infection among tuberculosis laboratory workers in Iran.

PubMed

Nasehi, Mahshid; Hashemi-Shahraki, Abdolrazagh; Doosti-Irani, Amin; Sharafi, Saeed; Mostafavi, Ehsan

2017-01-01

The risk of transmission of Mycobacterium tuberculosis from patients to health care workers (HCWs) is a neglected problem in many countries, including Iran. The aim of this study was to estimate the prevalence of latent tuberculosis (TB) infection (LTBI) among TB laboratory staff in Iran, and to elucidate the risk factors associated with LTBI. All TB laboratory staff (689 individuals) employed in the TB laboratories of 50 Iranian universities of medical sciences and a random sample consisting of 317 low-risk HCWs were included in this cross-sectional study. Participants with tuberculin skin test indurations of 10 mm or more were considered to have an LTBI. The prevalence of LTBI among TB laboratory staff and low-risk HCWs was 24.83% (95% confidence interval [CI], 21.31 to 27.74%) and 14.82% (95% CI, 11.31 to 19.20%), respectively. No active TB cases were found in either group. After adjusting for potential confounders, TB laboratory staff were more likely to have an LTBI than low-risk HCWs (prevalence odds ratio, 2.06; 95% CI, 1.35 to 3.17). This study showed that LTBI are an occupational health problem among TB laboratory staff in Iran. This study reinforces the need to design and implement simple, effective, and affordable TB infection control programs in TB laboratories in Iran.

A model of population dynamics of TB in a prison system and application to South Africa.

PubMed

Witbooi, Peter; Vyambwera, Sibaliwe Maku

2017-11-29

Tuberculosis (TB) continues to spread in South African prisons in particular, as prisons are over-capacitated and have poor ventilation. The awaiting trial detainees are not screened on admission and are at high risk of getting infected with TB. We propose a compartmental model to describe the population dynamics of TB disease in prisons. Our model considers the inflow of susceptible, exposed and TB infectives into the prison population. Removal of individuals out of the prison population can be either by death or by being released from prison, as compared to a general population in which removal is only by death. We describe conditions, including non-inflow of infectives into the prison, which will ensure that TB can be eradicated from the prison population. The model is calibrated for the South African prison system, by using data in existing literature. The model can be used to make quantitative projections of TB prevalence and to measure the effect of interventions. Illustrative simulations in this regard are presented. The model can be used for other prison populations too, if data is available to calculate the model parameters. Various simulations generated with our model serve to illustrate how it can be utilized in making future projections of the levels of prevalence of TB, and to quantify the effect of interventions such as screening, treatment or reduction of transmission parameter values through improved living conditions for inmates. This makes it particularly useful as there are various targets set by the World Health Organization and by governments, for reduction of TB prevalence and ultimately its eradication. Towards eradication of TB from a prison system, the theorem on global stability of the disease-free state is a useful indicator.

HIV infection impairs Th1 and Th17 Mycobacterium tuberculosis-specific T cell responses

PubMed Central

Murray, Lyle W; Satti, Iman; Meyerowitz, Jodi; Jones, Matthew; Willberg, Christian B; Ussher, James E; Goedhals, Dominique; Hurst, Jacob; Phillips, Rodney E; McShane, Helen

2018-01-01

Background HIV-infected individuals have a higher risk of developing active tuberculosis than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (M.tb)-specific CD4+ and CD8+ T cell responses contributed to this increased risk. Methods M.tb-specific T cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa were evaluated. Using a whole-blood flow cytometry assay, we measured expression of IFNγ, TNFα, IL-2 and IL-17 in CD4+ and CD8+ T cells in response to M.tb antigens (PPD, ESAT-6/CFP-10 (EC) and DosR regulon-encoded α-crystallin (Rv2031c)). Results Fewer HIV-infected individuals had detectable CD4+ and CD8+ T cell responses to PPD and Rv2031c than HIV-uninfected subjects. M.tb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions HIV-associated impairment of CD4+ and CD8+ M.tb-specific T cell responses is antigen-specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T cell subset may be key to TB susceptibility in HIV-infected individuals. PMID:29546381

Trends in the incidence of tuberculosis in possums and livestock, associated with differing control intensities applied to possum populations.

PubMed

Coleman, J D; Coleman, M C; Warburton, B

2006-04-01

To determine the trap-catch index (an estimate of abundance) of brushtail possum (Trichosurus vulpecula) populations infected with bovine tuberculosis (Tb; Mycobacterium bovis) that must be achieved, and the length of time such an index must be maintained, for Tb to be eliminated from possum populations and adjacent livestock. Between 1997-1998 and 2000-2001, trap-catch surveys of possum populations naturally infected with Tb and subjected to population-control measures were undertaken at four forest sites and two farmland sites. At the same time, possum carcasses were collected at these sites and their Tb status determined, and all contiguous cattle and deer herds were Tb tested and abattoir slaughter data for these herds were interrogated. Trap-catch surveys indicated that numbers of possums on the farmland sites surveyed were usually very low and well below the control targets set (i.e. a 5% trap catch or approximately 0.5-1 possum/ha) for the study. In contrast, trap-catch surveys undertaken in forest sites indicated possum numbers were more variable, and often recovered rapidly from control operations to exceed control targets within 1-3 years. The annual rate of recovery of possum populations in half of the forest population surveys undertaken exceeded published intrinsic rates of increase for possums. The overall prevalence of Tb in possum populations was < or =1.9% at 5/6 sites, and was 6.5% at the sixth site. Juvenile possums infected with Tb were trapped within but near the edge of control zones and appeared to represent an immigrant source of infection. Mature infected possums survived control operations apparently by having home ranges in uncontrolled patches within control areas. Infection in possums appeared to be eliminated from one study site by the intensive control undertaken, but elimination at other sites appeared less likely. Levels of Tb in livestock on or adjacent to the study sites fell by at least 50% during the study, and cattle in one

PrimaTB STAT-PAK Assay, a Novel, Rapid Lateral-Flow Test for Tuberculosis in Nonhuman Primates▿

PubMed Central

Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Greenwald, David; Nacy, Carol A.; Gibson, Susan; Didier, Peter J.; Washington, Marc; Szczerba, Peter; Motzel, Sherri; Handt, Larry; Pollock, John M.; McNair, James; Andersen, Peter; Langermans, Jan A. M.; Verreck, Frank; Ervin, Sean; Ervin, Frank; McCombs, Candace

2007-01-01

Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP. PMID:17652522

Detection of Lipomannan in Cattle Infected with Bovine Tuberculosis

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

Vu, Dung M.; Sakamuri, Rama M.; Waters, W. Ray

Early and rapid detection of bovine tuberculosis (bTB) is critical to controlling the spread of this disease in cattle and other animals. Here in this study, we demonstrate the development of an immunoassay for the direct detection of the bovine bTB biomarker, lipomannan (LM) in serum using a waveguide-based optical biosensor. We apply an ultra-sensitive detection strategy developed by our team, termed lipoprotein capture, that exploits the pull-down of high-density lipoprotein (HDL) nanodiscs from cattle blood that allows for the recovery and detection of associated LM. We also profile the change in the expression of these TB biomarkers as amore » function of time from a small set of samples collected from studies of bovine TB-infected cattle. Lastly, we demonstrate for the first time the direct detection of bovine LM in serum, and clearly show that the biomarker is expressed in detectable concentrations during the entire course of the infection.« less

Detection of Lipomannan in Cattle Infected with Bovine Tuberculosis

DOE PAGES

Vu, Dung M.; Sakamuri, Rama M.; Waters, W. Ray; ...

2017-04-10

Early and rapid detection of bovine tuberculosis (bTB) is critical to controlling the spread of this disease in cattle and other animals. Here in this study, we demonstrate the development of an immunoassay for the direct detection of the bovine bTB biomarker, lipomannan (LM) in serum using a waveguide-based optical biosensor. We apply an ultra-sensitive detection strategy developed by our team, termed lipoprotein capture, that exploits the pull-down of high-density lipoprotein (HDL) nanodiscs from cattle blood that allows for the recovery and detection of associated LM. We also profile the change in the expression of these TB biomarkers as amore » function of time from a small set of samples collected from studies of bovine TB-infected cattle. Lastly, we demonstrate for the first time the direct detection of bovine LM in serum, and clearly show that the biomarker is expressed in detectable concentrations during the entire course of the infection.« less