Testing for TB Infection

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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.

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

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

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

Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

PubMed

Gupta, S; Granich, R; Date, A; Lepere, P; Hersh, B; Gouws, E; Samb, B

2014-10-01

Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virus-tuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I's for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count ⩿500 cells/mm(3) for asymptomatic persons. Nineteen (83%) countries are consistent with WHO 2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world's HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries.

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/

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.

Hypovitaminosis D increases TB co-infection risk on HIV patients

NASA Astrophysics Data System (ADS)

Gayatri, Y. A. A. A.; Sukmawati, D. D.; Utama, S. M.; Somia, I. K. A.; Merati, T. P.

2018-03-01

Tuberculosis is causes of mortality and morbidity in patients with HIV. Hypovitaminosis D, a defective cell-mediated immune response to Mycobacterium tuberculosis infection has been extensively described in HIV patients, but studies assessing the role of vitamin D in TB-HIV co-infection are lacking. We, therefore, conducted a 1:1 pair- matched case-control study to verify hypovitaminosis D possible risk factor of TB- HIV co- infection. Consecutive HIV patients starting ARV and sex, age and CD4 cell count matched were by recruiting. Tuberculosis has confirmed by thepresence of acid-fast bacilli in sputum or mycobacterium detected in specimens culture/Gene Xpert/PCR. Vitamin D levels were by measuring direct chemiluminescent immunoassay on a LIAISON®25OH analyzer. The study comprised 25 cases and 25 controls, median (interquartile range) 25(OH)D3 serum concentration were 19.80 (12.15-27.45) ng/mL in cases and 33.30 (27.2-39.4) ng/mL in controls (P<0.001). After adjustment for potential confounders included anemia, smoking,and low BMI, with multivariate logistic regression analysis, hypovitaminosis Dindependently associated with the development of active tuberculosis in HIV patients.(OR 26.154 (90% CI: 4.371-156.541); p <0.001). The finding indicates that hypovitaminosis D was a risk factor of TB-HIV co-infection.

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.

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.

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

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

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.

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.

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

TB infection prevention and control experiences of South African nurses - a phenomenological study

PubMed Central

2011-01-01

Background The tuberculosis (TB) epidemic in South Africa is characterised by one of the highest levels of TB/HIV co-infection and growing multidrug-resistant TB worldwide. Hospitals play a central role in the management of TB. We investigated nurses' experiences of factors influencing TB infection prevention and control (IPC) practices to identify risks associated with potential nosocomial transmission. Methods The qualitative study employed a phenomenological approach, using semi-structured interviews with a quota sample of 20 nurses in a large tertiary academic hospital in Cape Town, South Africa. The data was subjected to thematic analysis. Results Nurses expressed concerns about the possible risk of TB transmission to both patients and staff. Factors influencing TB-IPC, and increasing the potential risk of nosocomial transmission, emerged in interconnected overarching themes. Influences related to the healthcare system included suboptimal IPC provision such as the lack of isolation facilities and personal protective equipment, and the lack of a TB-IPC policy. Further influences included inadequate TB training for staff and patients, communication barriers owing to cultural and linguistic differences between staff and patients, the excessive workload of nurses, and a sense of duty of care. Influences related to wider contextual conditions included TB concerns and stigma, and the role of traditional healers. Influences related to patient behaviour included late uptake of hospital care owing to poverty and the use of traditional medicine, and poor adherence to IPC measures by patients, family members and carers. Conclusions Several interconnected influences related to the healthcare system, wider contextual conditions and patient behavior could increase the potential risk of nosocomial TB transmission at hospital level. There is an urgent need for the implementation and evaluation of a comprehensive contextually appropriate TB IPC policy with the setting and

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

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.

Sensory polyneuropathy in human immunodeficiency virus-infected patients receiving tuberculosis treatment.

PubMed

Centner, C M; Carrara, H; Harrison, T B; Benatar, M; Heckmann, J M

2014-01-01

Human immunodeficiency virus (HIV) infection and treatments for HIV infection and tuberculosis (TB) are associated with the risk of developing sensory polyneuropathy (SPN). Vitamin B6 and genetically determined slow isoniazid (INH) acetylation are believed to play key roles in the development of SPN in a TB treatment setting. To investigate slow acetylation and risk factors for SPN in HIV-infected patients receiving TB treatment, and establish vitamin B6 status and its association with SPN. HIV-infected in-patients were prospectively assessed after initiating TB treatment and vitamin B6 supplementation, and monthly during hospitalisation. SPN was defined as ≥1 symptom plus ≥1 sign. NAT2 genotyping predicted acetylation status, and plasma high performance liquid chromatography estimated vitamin B6 status. A survival analysis estimated hazard ratios (HRs) for SPN during TB treatment. Of 116 participants, 56% had SPN at study entry. Participants developed SPN at a rate of 26/100 person-months (95%CI 18-35) during TB treatment, which was independently associated with slow acetylation (HR 2.5; 95%CI 1.1-5.9), as well as black race, previous TB and extra-pulmonary/disseminated TB. Vitamin B6 status was normal, irrespective of SPN. Risk factors for SPN suggest a multi-factorial pathogenesis related to INH and other potential nervous system insults. SPN developed despite normal vitamin B6 status, suggesting other mechanisms of injury.

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

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.

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

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 ...

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.

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

Evaluation of a TB infection control implementation initiative in out-patient HIV clinics in Zambia and Botswana.

PubMed

Emerson, C; Lipke, V; Kapata, N; Mwananyambe, N; Mwinga, A; Garekwe, M; Lanje, S; Moshe, Y; Pals, S L; Nakashima, A K; Miller, B

2016-07-01

Out-patient human immunodeficiency virus (HIV) care and treatment clinics in Zambia and Botswana, countries with a high burden of HIV and TB infection. To develop a tuberculosis infection control (TB IC) training and implementation package and evaluate the implementation of TB IC activities in facilities implementing the package. Prospective program evaluation of a TB IC training and implementation package using a standardized facility risk assessment tool, qualitative interviews with facility health care workers and measures of pre- and post-test performance. A composite measure of facility performance in TB IC improved from 32% at baseline to 50% at 1 year among eight facilities in Zambia, and from 27% to 80% at 6 months among 10 facilities in Botswana. Although there was marked improvement in indicators of managerial, administrative and environmental controls, key ongoing challenges remained in ensuring access to personal protective equipment and implementing TB screening in health care workers. TB IC activities at out-patient HIV clinics in Zambia and Botswana improved after training using the implementation package. Continued infrastructure support, as well as monitoring and evaluation, are needed to support the scale-up and sustainability of TB IC programs in facilities in low-resource countries.

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.

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.

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

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.

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

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

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.

Differences in IgG responses against infection phase related Mycobacterium tuberculosis (Mtb) specific antigens in individuals exposed or not to Mtb correlate with control of TB infection and progression.

PubMed

Coppola, Mariateresa; Arroyo, Leonar; van Meijgaarden, Krista E; Franken, Kees Lmc; Geluk, Annemieke; Barrera, Luis F; Ottenhoff, Tom H M

2017-09-01

Tuberculosis (TB) occurs in only 3-10% of Mycobacterium tuberculosis (Mtb) infected individuals, suggesting that natural immunity can contain Mtb infection, although this remains poorly understood. Next to T-cells, a potentially protective role for B-cells and antibodies has emerged recently. However, the Mtb antigens involved remain ill-defined. Here, we investigated in a TB-endemic setting IgG levels against 15 Mtb antigens, representing various phases of Mtb infection and known to be potent human T-cell antigens. IgG levels against ESAT6/CFP10, Rv0440, Rv0867c, Rv1737c, Rv2029c, Rv2215, Rv2389c, Rv3616c and Mtb purified protein derivative (PPD) were higher in TB patients than in endemic and non-endemic controls. The only exception was Rv1733c that was preferentially recognized by antibodies from endemic controls compared to TB patients and non-endemic controls, suggesting a potential correlation with control of TB infection and progression. In patients, IgG levels against Ag85B and Rv2029c correlated with Mtb loads, while immunoglobulins against Rv0440 differed between genders. Our results support the potential role of certain Mtb antigen-(Rv1733c) specific antibodies in the control of TB infection and progression, while other Mtb antigen-specific antibodies correlate with TB disease activity and bacillary loads. The findings for Rv1733c agree with previous T-cell results and have implications for including antibody-mediated immunity in designing new strategies to control TB. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prisoners co-infected with tuberculosis and HIV: a systematic review

PubMed Central

Edge, Chantal L; King, Emma J; Dolan, Kate; McKee, Martin

2016-01-01

Introduction Almost from the beginning of the HIV epidemic in 1981, an association with tuberculosis (TB) was recognized. This association between HIV and TB co-infection has been particularly evident amongst prisoners. However, despite this, few studies of TB in prisons have stratified results by HIV status. Given the high prevalence of HIV-positive persons and TB-infected persons in prisons and the documented risk of TB in those infected with HIV, it is of interest to determine how co-infection varies amongst prison populations worldwide. For this reason we have undertaken a systematic review of studies of co-infected prisoners to determine the incidence and/or prevalence of HIV/TB co-infection in prisons, as well as outcomes in this group, measured as treatment success or death. Methods A literature search was undertaken using the online databases PubMed, Embase, IBSS, Scopus, Web of Science, Global Health and CINAHL Plus. No restrictions were set on language or publication date for article retrieval, with articles included if indexed up to 18 October 2015. A total of 1975 non-duplicate papers were identified. For treatment and outcome data all eligible papers were appraised for inclusion; for incidence/prevalence estimates papers published prior to 2000 were excluded from full text review. After full text appraisal, 46 papers were selected for inclusion in the review, 41 for incidence/prevalence estimates and nine for outcomes data, with four papers providing evidence for both outcomes and prevalence/incidence. Results Very few studies estimated the incidence of TB in HIV positive prisoners, with most simply reporting prevalence of co-infection. Co-infection is rarely explicitly measured, with studies simply reporting HIV status in prisoners with TB, or a cross-sectional survey of TB prevalence amongst prisoners with HIV. Estimates of co-infection prevalence ranged from 2.4 to 73.1% and relative risks for one, given the other, ranged from 2.0 to 10.75, although

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

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…

Tuberculin status, socioeconomic differences and differences in all-cause mortality: experience from Norwegian cohorts born 1910-49.

PubMed

Liestøl, Knut; Tretli, Steinar; Tverdal, Aage; Maehlen, Jan

2009-04-01

From 1948 to 1975, Norway had a mandatory tuberculosis (TB) screening programme with Pirquet testing, X-ray examinations and BCG vaccination. Electronic data registration in 1963-75 enabled the current study aimed at revealing (i) the relations between socioeconomic factors and tuberculosis infection and (ii) differences in later all-cause mortality according to TB infection status. TB screening data were linked to information from the Norwegian Cause of Death Registry (1975-98) and the National Population and Housing Censuses (1960, 1970 and 1980). Analyses were done for 10 years cohorts born 1910-49, separately for men (approximately 534,000 individuals) and women (608,000), using logistic and Cox regressions. TB infection and X-ray data confirmed the strong regional pattern seen for TB mortality, with the highest rates in the three northernmost counties and higher rates in urban than rural areas. High socioeconomic status relates to lower odds both for TB infection and TB-related chest X-ray findings (odds ratios 0.6-0.7 for highest vs lowest educational groups). Those infected by TB, and especially those with chest X-ray findings, have increased all-cause mortality in at least a 20 years period following determination of tuberculin status (hazard ratios approximately 1.15 and 1.30, respectively, higher for late than early cohorts). TB particularly affected lower socioeconomic strata, but even those in higher strata were at high risk. The differences in all-cause mortality could partly be attributed to socioeconomic factors, but we hypothesize that developing TB infection may also indicate biological frailness.

Factors associated with good TB infection control practices among primary healthcare workers in the Free State Province, South Africa.

PubMed

Engelbrecht, Michelle; Janse van Rensburg, André; Kigozi, Gladys; van Rensburg, Hcj Dingie

2016-11-04

Despite the availability of TB infection control guidelines, and good levels of healthcare worker knowledge about infection control, often these measures are not well implemented. This study sought to determine the factors associated with healthcare workers' good TB infection control practices in primary health care facilities in the Free State Province, South Africa. A cross-sectional self-administered survey among nurses (n = 202) and facility-based community healthcare workers (n = 34) as well as facility observations were undertaken at all 41 primary health care facilities in a selected district of the Free State Province. The majority of respondents were female (n = 200; 87.7 %) and the average age was 44.19 years (standard deviation ±10.82). Good levels of knowledge were recorded, with 42.8 % (n = 101) having an average score (i.e. 65-79 %) and 31.8 % (n = 75) a good score (i.e. ≥ 80 %). Most respondents (n = 189; 80.4 %) had positive attitudes towards TB infection control practices (i.e. ≥ 80 %). While good TB infection control practices were reported by 72.9 % (n = 161) of the respondents (i.e. ≥75 %), observations revealed this to not necessarily be the case. For every unit increase in attitudes, good practices increased 1.090 times (CI:1.016-1.169). Respondents with high levels of knowledge (≥80 %) were 4.029 (CI: 1.550-10.469) times more likely to have good practices when compared to respondents with poor levels of knowledge (<65 %). The study did not find TB/HIV-related training to be a predictor of good practices. Positive attitudes and good levels of knowledge regarding TB infection control were the main factors associated with good infection control practices. Although many respondents reported good infection control practices - which was somewhat countered by the observations - there are areas that require attention, particularly those related to administrative controls and the use of personal

Infection control in home-based care for people living with HIV/AIDS/TB in South Africa: an exploratory study.

PubMed

Akintola, Olagoke; Hangulu, Lydia

2014-01-01

The majority of HIV and AIDS patients in sub-Saharan African countries receive health care services at home. Yet research on infection control in home-based care settings is virtually non-existent. This study explored infection control practices in home-based care in a South African province with a high HIV/TB prevalence. We conducted interviews with 10 managers of home-based care organizations and 10 focus group discussions with 80 volunteer caregivers working in high HIV/TB prevalent communities in South Africa. Findings show that volunteers had insufficient training on infection control. Materials necessary for the maintenance of hygiene and protective equipment were in short supply and the protective equipment supplied was of poor quality. Home-based care patients lived in crowded and poor conditions, and family members were negatively disposed to the use of protective devices. Together, these factors put volunteers and family caregivers at risk of infection with HIV and TB. Health policy should address the training of volunteer caregivers and the regular supply of good quality materials to ensure effective infection control. It is also important to educate families on infection control. Finally, there is a need to integrate HIV and TB control at the community level.

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.

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

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.

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

.9%) had a previous history of TB treatment. The proportion of TB/HIV was higher in urban than in the rural clusters. The HIV status was unknown for 114/265 (43.0%) of the TB cases. The TB/HIV prevalence in the general population was found to be lower than what is routinely reported as incident TB/HIV cases at facility level. However; the TB/HIV co-infection was higher in areas with higher TB prevalence. Innovative and effective strategies for ensuring TB/HIV co-infected individuals are detected and treated early are required.

Nutritional Status and Tuberculosis Risk in Adult and Pediatric Household Contacts.

PubMed

Aibana, Omowunmi; Acharya, Xeno; Huang, Chuan-Chin; Becerra, Mercedes C; Galea, Jerome T; Chiang, Silvia S; Contreras, Carmen; Calderon, Roger; Yataco, Rosa; Velásquez, Gustavo E; Tintaya, Karen; Jimenez, Judith; Lecca, Leonid; Murray, Megan B

2016-01-01

Studies show obesity decreases risk of tuberculosis (TB) disease. There is limited evidence on whether high body mass index also protects against TB infection; how very high body mass indices influence TB risk; or whether nutritional status predicts this risk in children. We assessed the impact of body mass index on incident TB infection and disease among adults and children. We conducted a prospective cohort study among household contacts of pulmonary TB cases in Lima, Peru. We determined body mass index at baseline and followed participants for one year for TB infection and disease. We used Cox proportional regression analyses to estimate hazard ratios for incident TB infection and disease. We enrolled 14,044 household contacts, and among 6853 negative for TB infection and disease at baseline, 1787 (26.1%) became infected. A total of 406 contacts developed secondary TB disease during follow-up. Body mass index did not predict risk of TB infection but overweight household contacts had significantly decreased risk of TB disease (HR 0.48; 95% CI 0.37-0.64; p <0.001) compared to those with normal weight. Among adults, body mass index ≥ 35 kg/m2 continued to predict a lower risk of TB disease (HR 0.30; 95% CI 0.12-0.74; p 0.009). We found no association between high body mass index and TB infection or disease among children under 12 years of age. High body mass index protects adults against TB disease even at levels ≥ 35 kg/m2. This protective effect does not extend to TB infection and is not seen in children.

Health care workers' knowledge, attitudes and practices on tuberculosis infection control, Nepal.

PubMed

Shrestha, Anita; Bhattarai, Dipesh; Thapa, Barsha; Basel, Prem; Wagle, Rajendra Raj

2017-11-17

Infection control remains a key challenge for Tuberculosis (TB) control program with an increased risk of TB transmission among health care workers (HCWs), especially in settings with inadequate TB infection control measures. Poor knowledge among HCWs and inadequate infection control practices may lead to the increased risk of nosocomial TB transmission. An institution-based cross-sectional survey was conducted in 28 health facilities providing TB services in the Kathmandu Valley, Nepal. A total of 190 HCWs were assessed for the knowledge, attitudes and practices on TB infection control using a structured questionnaire. The level of knowledge on TB infection control among almost half (45.8%) of the HCWs was poor, and was much poorer among administration and lower level staff. The knowledge level was significantly associated with educational status, and TB training and/or orientation received. The majority (73.2%) of HCWs had positive attitude towards TB infection control. Sixty-five percent of HCWs were found to be concerned about being infected with TB. Use of respirators among the HCWs was limited and triage of TB suspects was also lacking. Overall knowledge and practices of HCWs on TB infection control were not satisfactory. Effective infection control measures including regular skill-based training and/or orientation for all categories of HCWs can improve infection control practices in health facilities.

Latent tuberculosis infection among close contacts of multidrug-resistant tuberculosis patients in central Taiwan.

PubMed

Huang, Y-W; Shen, G-H; Lee, J-J; Yang, W-T

2010-11-01

Both the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) may be used to detect Mycobacterium tuberculosis infection. A positive reaction to either test can indicate latent tuberculosis infection (LTBI). These tests can be used to study the rate of infection in contacts of multidrug-resistant tuberculosis (MDR-TB) patients. To evaluate the transmission status of MDR-TB patients in Taiwan by examining their close contacts and to compare the efficiency of TST and QFT-GIT. Chest radiographs, TST and QFT-GIT were performed in household contacts of confirmed MDR-TB patients to determine their infection status. A total of 78 close contacts of confirmed MDR-TB patients were included in the study. The majority of the MDR-TB patients were parents of the close contacts and lived in the same building; 46% of the subjects were TST-positive and 19% were QFT-GIT-positive, indicating LTBI that was likely to develop into active MDR-TB. There was a lack of consistency between TST and QFT-GIT results in subjects with previous bacille Calmette-Guérin vaccination. Household contacts of MDR-TB patients are likely to develop LTBI; thus, follow-up and monitoring are mandatory to provide treatment and reduce the occurrence of active infection.

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.

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

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

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.

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

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…

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

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

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

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.

[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.

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 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.

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

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

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

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.

Anaemia in patients with HIV-associated TB: relative contributions of anaemia of chronic disease and iron deficiency.

PubMed

Kerkhoff, A D; Meintjes, G; Opie, J; Vogt, M; Jhilmeet, N; Wood, R; Lawn, S D

2016-02-01

Anaemia commonly complicates both human immunodeficiency virus (HIV) infection and tuberculosis (TB), contributing substantially to morbidity and mortality. The mechanisms underlying anaemia and corresponding treatments in co-infected patients are poorly defined. To determine the relative contributions of anaemia of chronic disease (ACD) and iron deficiency to anaemia in patients with HIV-associated TB. Consecutively recruited hospitalised (n = 102) and matched ambulatory patients (n = 51) with microbiologically confirmed HIV-associated TB in Cape Town, South Africa, were included. Haemoglobin levels, iron status markers, hepcidin and pro-inflammatory cytokines in blood were measured. We determined the prevalence of ACD and iron-deficiency anaemia (IDA) using seven different published definitions of IDA. More than 80% of enrolled HIV-associated TB patients were anaemic, and anaemia was more severe among in-patients. Over 95% of anaemic HIV-associated TB patients had ACD, whereas the proportion with IDA using a range of seven different definitions was low overall (median <3%, range 0-32.6) in both patient groups. The proportion with IDA and hepcidin concentration ⩿ 20.0 ng/ml (predictive of responsiveness to oral iron supplementation) was also very low (median <3%, range 0-15.1). ACD was the predominant cause underlying anaemia in HIV-associated TB patients, and IDA was very uncommon in this setting. The majority of anaemic HIV-associated TB patients were unlikely to benefit from oral iron supplementation.

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.

Age, Sex & Nutritional Status Modify CD4+T-Cell Recovery Rate in HIV/Tuberculosis Co-infected Patients on cART

PubMed Central

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-01-01

Background We examined baseline age and combination antiretroviral therapy (cART) as determinants of CD4+T-cell recovery during six months of tuberculosis (TB) therapy with/without cART. We determined whether this association was modified by patient sex and nutritional status. Methods This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+T-cell count was measured using flow cytometry. Age was defined as ≤24, 25–29, 30–34, 35–39 vs. ≥ 40 years. Nutritional status was defined as normal (>18.5kg/m2) vs. underweight (≤18.5kg/m2) using body mass index (BMI). Multivariate random-effects linear mixed models were fitted to estimate differences in CD4+T-cell recovery in relation to specified determinants. Results cART was associated with a monthly rise of 15.7 cells/μL (p<0.001). Overall, age was not associated with CD4+T-cell recovery during TB therapy (p=0.655). However, among patients on cART, age-associated CD4+T-cell recovery rate varied by sex and nutritional status such that age <40 vs. ≥ 40 years predicted superior absolute CD4+T-cell recovery among females (p=0.006) and among patients with BMI≥18.5kg/m2 (p<0.001). Conclusions TB infected HIV-positive patients ≥ 40 years have a slower rate of immune restoration given cART-particularly if BMI>18.5kg/m2 or female. They may benefit from increased monitoring and nutritional support during cART. PMID:25910854

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.

Effect of HIV infection on tolerability and bacteriologic outcomes of tuberculosis treatment.

PubMed

Bliven-Sizemore, E E; Johnson, J L; Goldberg, S; Burman, W J; Villarino, M E; Chaisson, R E

2012-04-01

Two international, multicenter Phase 2 clinical trials examining fluoroquinolone-containing regimens in adults with smear-positive pulmonary tuberculosis (TB), conducted from July 2003 to March 2007. Both trials enrolled human immunodeficiency virus (HIV) infected participants who were not receiving antiretroviral therapy (ART) at TB treatment initiation. To assess the impact of HIV infection on TB treatment outcomes in Phase 2 clinical trials. Cross-protocol analysis comparing the safety, tolerability and outcomes of anti-tuberculosis treatment by HIV status. Of 750 participants who received at least one dose of study treatment, 123 (16%) were HIV-infected. Treatment completion rates were similar by HIV status (81% infected vs. 85% non-infected), as were rates of week 8 culture conversion (66% infected vs. 63% non-infected), and treatment failure (5% infected vs. 3% non-infected). Among HIV-infected participants, treatment failure detected using liquid media was more frequent in those treated thrice weekly (14% thrice weekly vs. 2% daily, P = 0.03). HIV-infected participants more frequently experienced an adverse event during the intensive phase treatment than non-HIV-infected participants (30% vs. 15%, P < 0.01). HIV-infected persons not receiving ART had more adverse events during the intensive phase of anti-tuberculosis treatment, but tolerated treatment well. Failure rates were higher among HIV-infected persons treated with thrice-weekly intensive phase therapy.

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.

HIV-TB Coinfection among 57 Million Pregnant Women, Obstetric Complications, Alcohol Use, Drug Abuse, and Depression.

PubMed

Fernandez, Dorian; Salami, Imoleayo; Davis, Janelle; Mbah, Florence; Kazeem, Aisha; Ash, Abreah; Babino, Justin; Carter, Laquiesha; Salemi, Jason L; Spooner, Kiara K; Olaleye, Omonike A; Salihu, Hamisu M

2018-01-01

HIV and tuberculosis represent diseases of major public health importance worldwide. Very little is known about HIV-TB coinfection among pregnant women, especially from industrialized settings. In this study, we examined the association between TB, HIV, and HIV-TB coinfection among pregnant mothers and obstetric complications, alcohol use, drug abuse, and depression. We examined inpatient hospital discharges in the United States from January 1, 2002, through December 31, 2014. We employed multivariable survey logistic regression to generate adjusted estimates for the association between infection status and study outcomes. We analyzed approximately 57 million records of pregnant women and their delivery information. HIV-TB coinfection was associated with the highest risks for several obstetric complications, alcohol use, and drug abuse. The risk for alcohol abuse was more than twice as high among HIV-monoinfected as compared to TB-monoinfected mothers. That risk gap more than doubled with HIV-TB coinfection. Both HIV-monoinfected and HIV-TB coinfected mothers experienced similarly increased risks for depression. Mothers with HIV-TB coinfection experienced relatively heightened risks for obstetric complications, alcohol use, and drug abuse. The findings of this study underscore the importance of augmenting and enhancing social and structural support systems for HIV-TB coinfected pregnant women.

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…

Optimal treatment interruptions control of TB transmission model

NASA Astrophysics Data System (ADS)

Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

2018-03-01

A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

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

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

Tuberculosis and infection control.

PubMed

Karim, Kelvin

Against a background of rising tuberculosis (TB) rates, increasing incidence of TB and human immunodeficiency virus (HIV) co-infection, coupled with the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), the need for effective TB infection control has never been more vital (World Health Organization (WHO), 2009). TB infection control has been defined as 'a combination of measures aimed at minimizing the risk of TB transmission within populations' (WHO, 2009: p.ix). Health professionals are frequently confused about appropriate infection control measures when caring for patients affected by infectious respiratory tuberculosis (Mohandas and Cunniffe, 2009). This article aims to address the key infection control measures required to optimize patient care and reduce the risk of TB transmission within hospital and community settings.

Pulmonary tuberculosis in severely-malnourished or HIV-infected children with pneumonia: a review.

PubMed

Chisti, Mohammod Jobayer; Ahmed, Tahmeed; Pietroni, Mark A C; Faruque, Abu S G; Ashraf, Hasan; Bardhan, Pradip K; Hossain, Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus

2013-09-01

Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/ very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies

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.

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

Invariant NKT cells from HIV-1 or Mycobacterium tuberculosis-infected patients express an activated phenotype.

PubMed

Montoya, Carlos J; Cataño, Juan C; Ramirez, Zoraida; Rugeles, Maria T; Wilson, S Brian; Landay, Alan L

2008-04-01

The frequency, subsets and activation status of peripheral blood invariant NKT (iNKT) cells were evaluated in pulmonary tuberculosis (TB) patients and in chronically HIV-1-infected subjects. The absolute numbers of iNKT cells were significantly decreased in TB patients and in HIV-1+ individuals who were antiretroviral therapy naive or had detectable viremia despite receiving HAART. iNKT cell subset analysis demonstrated a decreased percentage of CD4(+) iNKT cells in HIV-1+ subjects, and a decreased percentage of double negative iNKT cells in TB patients. Peripheral blood iNKT cells from HIV-1+ and TB patients had significantly increased expression of CD69, CD38, HLA-DR, CD16, CD56, and CD62L. The expression of CD25 was significantly increased only on iNKT cells from TB patients. These findings indicate that peripheral blood iNKT cells in these two chronic infections show an up-regulated expression of activation markers, suggesting their role in the immune response to infection.

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.

Quality control in QuantiFERON-TB gold in-tube for screening latent tuberculosis infection in health care workers.

PubMed

Igari, Hidetoshi; Watanabe, Akira; Ichimura, Yasunori; Sakurai, Takayuki; Taniguchi, Toshibumi; Ishiwada, Naruhiko

2017-04-01

QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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.

Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy.

PubMed

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-06-01

Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status. This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants. cART was associated with a monthly rise of 15.7 cells/μl (p<0.001). Overall, age was not associated with CD4+ T-cell recovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age <40 vs. ≥40 years predicted superior absolute CD4+ T-cell recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p<0.001). TB-infected HIV-positive patients aged ≥40 years have a slower rate of immune restoration given cART, particularly if BMI is >18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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

Pulmonary Tuberculosis in Severely-malnourished or HIV-infected Children with Pneumonia: A Review

PubMed Central

Ahmed, Tahmeed; Pietroni, Mark A.C.; Faruque, Abu S.G.; Ashraf, Hasan; Bardhan, Pradip K.; Hossain, Md. Iqbal; Das, Sumon Kumar; Salam, Mohammed Abdus

2013-01-01

Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies

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

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.

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

Reported health, lifestyle and clinical manifestations associated with HIV status in people from rural and urban communities in the Free State Province, South Africa.

PubMed

Pienaar, Michélle; van Rooyen, Francois C; Walsh, Corinna M

2017-01-01

HIV infection impacts heavily on the infected individual's overall health status. To determine significant health, lifestyle (smoking and alcohol use) and independent clinical manifestations associated with HIV status in rural and urban communities. Adults aged between 25 and 64 years completed a questionnaire in a structured interview with each participant. Blood specimens were analysed in an accredited laboratory using standard techniques and controls. Anthropometric measurements were determined using standardised methods. Of the 567 rural participants, 97 (17.1%) were HIV-infected, and 172 (40.6%) of the 424 urban participants. More than half of HIV-infected rural participants used alcohol and more than 40% smoked. Median body mass index (BMI) of HIV-infected participants was lower than that of uninfected participants. Significantly more HIV-infected participants reported experiencing cough (rural), skin rash (urban), diarrhoea (rural and urban), vomiting (rural), loss of appetite (urban) and involuntary weight loss (rural). Significantly more HIV-uninfected participants reported diabetes mellitus (urban) and high blood pressure (rural and urban). In rural areas, HIV infection was positively associated with losing weight involuntarily (odds ratio 1.86), ever being diagnosed with tuberculosis (TB) (odds ratio 2.50) and being on TB treatment (odds ratio 3.29). In the urban sample, HIV infection was positively associated with having diarrhoea (odds ratio 2.04) and ever being diagnosed with TB (odds ratio 2.49). Involuntary weight loss and diarrhoea were most likely to predict the presence of HIV. In addition, present or past diagnosis of TB increased the odds of being HIV-infected. Information related to diarrhoea, weight loss and TB is easy to obtain from patients and should prompt healthcare workers to screen for HIV.

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 ...

HIV and tuberculosis co-infection among migrants in Europe: A systematic review on the prevalence, incidence and mortality

PubMed Central

Fronteira, Inês; Couto, Isabel; Machado, Diana; Viveiros, Miguel; Abecasis, Ana B.; Dias, Sónia

2017-01-01

Background International human migration has been rapidly growing. Migrants coming from low and middle income countries continue to be considerably vulnerable and at higher risk for infectious diseases, namely HIV (Human Immunodeficiency Virus) and tuberculosis (TB). In Europe, the number of patients with HIV-TB co-infection has been increasing and migration could be one of the potential driving forces. Objective This systematic review aims to improve the understanding on the burden of HIV-TB co-infection among migrants in Europe and to assess whether these populations are particularly vulnerable to this co-infection compared to nationals. Design MEDLINE®, Web of Science® and Scopus® databases were searched from March to April 2016 using combinations of keywords. Titles and abstracts were screened and studies meeting the inclusion criteria proceeded for full-text revision. These articles were then selected for data extraction on the prevalence, incidence and mortality. Results The majority of HIV-TB prevalence data reported in the analysed studies, including extrapulmonary/disseminated TB forms, was higher among migrant vs. nationals, some of the studies even showing increasing trends over time. Additionally, while HIV-TB incidence rates have decreased among migrants and nationals, migrants are still at a higher risk for this co-infection. Migrants with HIV-TB co-infection were also more prone to unsuccessful treatment outcomes, death and drug resistant TB. However, contradicting results also showed lower mortality compared to nationals. Conclusions Overall, a disproportionate vulnerability of migrants to acquire the HIV-TB co-infection was observed across studies. Such vulnerability has been associated to low socioeconomic status, poor living conditions and limited access to healthcare. Adequate social support, early detection, appropriate treatment, and adequate access to healthcare are key improvements to tackle HIV-TB co-infection among these populations

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 ...

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.

[Development of antituberculous drugs: current status and future prospects].

PubMed

Tomioka, Haruaki; Namba, Kenji

2006-12-01

latently infected with MTB. Unfortunately, no new drugs except rifabutin and rifapentine has been marketed for TB in the US and other countries during the 40 years after release of rifampicin. There are a number of constraints that have deterred companies from investing in new anti-TB drugs. The research is expensive, slow and difficult, and requires specialized facilities for handling MTB. There are few animal models that closely mimic the human TB disease. Development time of any anti-TB drug will be long. In fact, clinical trials will require the minimum six-month therapy, with a follow-up period of one year or more. In addition, it is hard to demonstrate obvious benefit of a new anti-TB agents over pre-existing drugs, since clinical trials involve multidrug combination therapy using highly effective ordinary anti-TB drugs. Finaly, there is the perceived lack of commercial return to companies engaged in the development of new anti-TB drugs, because over 95% of TB cases worldwide are in developing countries. In this symposium, we reviewed the following areas. 1. Critical new information on the entire genome of MTB recently obtained and increasing knowledge of various mycobacterial virulence genes are greatly promoting the identification of genes that code for new drug targets. In this context, Dr. Namba reviewed the status of new types of compounds which are being developed as anti-TB drug. He also discussed the development of new antimycobacterial drugs according to new and potential pharmacological targets and the best clinical development plans for new-TB drugs in relation to corporate strategy. 2. Using such findings for mycobacterial genomes, bioinformatics/genomics/proteomics-based drug design and drug development using quantitative structure-activity relationships may be possible in the near future. In this context, Dr. Suwa and Dr. Suzuki reviewed the usefulness of chemical genomics in searching novel drug targets for development of new antituberculous drugs. The

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.

Determinants of unsuccessful tuberculosis treatment outcomes in Malaysian HIV-infected patients.

PubMed

Ismail, Ismawati; Bulgiba, Awang

2013-01-01

To determine predictors of unsuccessful treatment in HIV-infected tuberculosis (TB) patients. We reviewed medical records at the time of TB diagnosis and subsequent follow-up of all registered TB patients with HIV co-infection at TB clinics in the Institute of Respiratory Medicine and three public hospitals in Malaysia between January 2010 and September 2010. We reviewed these medical records again twelve months after their initial diagnosis to determine treatment outcomes. Multiple logistic regression was conducted to identify risk factors for unsuccessful TB treatment. Among the 219 patients analyzed, 53.4% achieved successful outcomes (cure, completed treatment) while 46.6% of patients had unsuccessful outcomes (default, treatment failure, died). After adjusting for other factors, unsuccessful outcome was associated with intravenous drug use (OR 2.72; 95% CI 1.44-5.16), not receiving antiretroviral therapy (OR 5.10; 95% CI 2.69-9.69), lymphadenopathy (OR 2.01; 95% CI 1.09-3.72) and low serum albumin (OR 4.61; 95% CI 1.73-12.27). Anti-retroviral treatment must be provided to all HIV-infected tuberculosis patients. Good immune and nutritional status needs to be assured in all HIV-infected tuberculosis patients. More studies are required in intravenous drug users to understand why tuberculosis treatment outcomes are poor in this group. Copyright © 2013 Elsevier Inc. All rights reserved.

Factors associated with linkage to HIV care and TB treatment at community-based HIV testing services in Cape Town, South Africa.

PubMed

Meehan, Sue-Ann; Sloot, Rosa; Draper, Heather R; Naidoo, Pren; Burger, Ronelle; Beyers, Nulda

2018-01-01

Diagnosing HIV and/or TB is not sufficient; linkage to care and treatment is conditional to reduce the burden of disease. This study aimed to determine factors associated with linkage to HIV care and TB treatment at community-based services in Cape Town, South Africa. This retrospective cohort study utilized routinely collected data from clients who utilized stand-alone (fixed site not attached to a health facility) and mobile HIV testing services in eight communities in the City of Cape Town Metropolitan district, between January 2008 and June 2012. Clients were included in the analysis if they were ≥12 years and had a known HIV status. Generalized estimating equations (GEE) logistic regression models were used to assess the association between determinants (sex, age, HIV testing service and co-infection status) and self-reported linkage to HIV care and/or TB treatment. Linkage to HIV care was 3 738/5 929 (63.1%). Linkage to HIV care was associated with the type of HIV testing service. Clients diagnosed with HIV at mobile services had a significantly reduced odds of linking to HIV care (aOR 0.7 (CI 95%: 0.6-0.8), p<0.001. Linkage to TB treatment was 210/275 (76.4%). Linkage to TB treatment was not associated with sex and service type, but was associated with age. Clients in older age groups were less likely to link to TB treatment compared to clients in the age group 12-24 years (all, p-value<0.05). A large proportion of clients diagnosed with HIV at mobile services did not link to care. Almost a quarter of clients diagnosed with TB did not link to treatment. Integrated community-based HIV and TB testing services are efficient in diagnosing HIV and TB, but strategies to improve linkage to care are required to control these epidemics.

Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study

PubMed Central

2013-01-01

Background Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB. Methods Archived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility. Results Hemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses. Conclusions Evidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia

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.

Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: a cross sectional study.

PubMed

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

2013-04-26

Despite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs. A cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART. The majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use. A comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated for TB patients (with and without HIV

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

A Pilot Study Assessing the Impact of a Fortified Supplementary Food on the Health and Well-Being of Crèche Children and Adult TB Patients in South Africa

PubMed Central

Rudolph, Michael; Kroll, Florian; Beery, Moira; Marinda, Edmore; Sobiecki, Jean-Francois; Douglas, Geoffrey; Orr, Gary

2013-01-01

The South African population faces many of the global concerns relating to micronutrient deficiency and the impact this has on health and well-being. Moreover, there is a high prevalence of HIV infection, compounded by a high level of co-infection with TB. This pilot study evaluates the impact of a fortified supplementary food on the health and well-being of a cohort of crèche children, aged 3 to 6, and adult TB patients drawn from the Presidential Node of Alexandra, Johannesburg, South Africa. A further aim of this study was to evaluate the sensitivity and validity of non-invasive indicators of nutritional status in a field-based population sample. The investigational product, e’Pap, is supported by extensive anecdotal evidence that whole grain cereals with food-style nutrients constitute an effective supplementary food for those suffering from the effects of food insecurity, poor health and well-being, and coping with TB and HIV infection. The results indicate a beneficial effect of e’Pap for both study populations, and particularly for adult TB patients, whose baseline data reflected severe food insecurity and malnutrition in the majority of cases. There is evidence to suggest statistically significant improvements in key micronutrient levels, well-being and energy, hand-grip strength, the Bioelectrical Impedance Analysis (BIA) Illness Marker, and certain clinical indicators. Although Body Mass Index (BMI) and Mid Upper Arm Circumference (MUAC) are frequently used as standard measures to evaluate the efficacy of nutritional interventions, these indicators were not sufficiently sensitive in this study. Nor does weight gain necessarily indicate improved nutritional status. Hand-grip strength, lean body mass, and the BIA Illness Marker seem to be more useful indicators of change in nutritional status. PMID:23383220

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).

Influence of age and nutritional status on the performance of the tuberculin skin test and QuantiFERON-TB gold in-tube in young children evaluated for tuberculosis in Southern India.

PubMed

Jenum, Synne; Selvam, Sumithra; Mahelai, Diana; Jesuraj, Nelson; Cárdenas, Vicky; Kenneth, John; Hesseling, Anneke C; Doherty, Timothy Mark; Vaz, Mario; Grewal, Harleen M S

2014-10-01

Reliable identification of Mycobacterium tuberculosis infection or tuberculosis (TB) disease in young children is vital to assure adequate preventive and curative treatment. The tuberculin skin test (TST) and IFNγ-release assays may supplement the diagnosis of pediatric TB as cases are typically bacteriologically unconfirmed. However, it is unclear to what extent the performance of TST and QuantiFERON-TB Gold In-Tube (QFT; Cellestis' IFNγ-release assay test) depends on the demographic, clinical and nutritional characteristics of children in whom they are tested. During a 2-year prospective observational study of 4382 neonates in Southern India, children with suspected TB were investigated and classified by a standard TB diagnostic algorithm. Clinical TB was diagnosed in 13 of 705 children referred for case verification with suspected TB. TST and QFT had a susceptibility for clinical TB of 31% and 23%, respectively, in this group. Children <2 years were more likely to test QFT indeterminate. A height-for-age Z score within the lowest quartile increased the odds ratio (OR) for a positive or indeterminate QFT result [OR 2.46 (1.19-5.06), OR 3.08 (1.10-8.58)], whereas the OR for a positive TST was reduced with a weight-for-height Z score within the lowest quartile [OR 0.17 (0.06-0.47)]. The sensitivities of the TST and QFT for clinical TB in children <3 years of age were equally poor in this population. Stunted children were more susceptible to Mycobacterium tuberculosis infection and more prone to indeterminate QFT results. TST was less reliable in children with wasting.

Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar.

PubMed

Wai, Pyae Phyo; Shewade, Hemant Deepak; Kyaw, Nang Thu Thu; Thein, Saw; Si Thu, Aung; Kyaw, Khine Wut Yee; Aye, Nyein Nyein; Phyo, Aye Mon; Maung, Htet Myet Win; Soe, Kyaw Thu; Aung, Si Thu

2018-01-01

The Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support. To assess whether CBMDR-TBC project's support improved treatment initiation. In this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as "receiving support" if date of project initiation in patient's township was before the date of diagnosis and "not receiving support", if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation. Of 456 patients, 57% initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among patients "not receiving support". After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients "receiving support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients "not receiving support". In addition, age 15-54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation. Receiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also

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

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.

Knowledge of tuberculosis (TB) and human immunodeficiency virus (HIV) and perception about provider initiated HIV testing and counselling among TB patients attending health facilities in Harar town, Eastern Ethiopia.

PubMed

Seyoum, Ayichew; Legesse, Mengistu

2013-02-08

Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infection is one of the major health problems in Ethiopia. The national TB and HIV control guideline in Ethiopia recommends provider initiated HIV testing and counselling (PITC) as a routine care for TB patients. However, the impact of this approach on the treatment seeking of TB patients has not been well studied. In this study, we assessed knowledge of TB and HIV, and perception about PITC among TB patients attending health facilities in Harar town, Eastern Ethiopia. In a health facilities based cross-sectional study, a total of 415 study participants were interviewed about knowledge of TB and HIV as well as the impact of HIV testing on their treatment seeking behavior using a semi-structured questionnaires. Multivariable logistic regression analysis showed the association of distance > 10 km from health facility [adjusted odds ratio (AOR)=0.48, 95% CI: 0.24 - 0.97, P=0.042] with low knowledge of TB. Distance > 10 km from health facility (AOR= 0.12, 95% CI: 0.06 -0.23, P < 0.001) was also associated with low knowledge of HIV testing. Delay in treatment seeking was associated with female participants (AOR = 0.11, 95% CI: 0.05-0.25, <0.001), single marital status (AOR =0.001, 95% CI: 0.00 - 0.01, P< 0.001) and distance > 10 km from health facility (AOR =0.46, 95% CI: 0.28 - 0.75, P=0.002). Most of the study participants (70%) believed that there is no association between TB and HIV/AIDS. On the other hand, two thirds (66.5%) of the participants thought that HIV testing has importance for TB patients. However, the majority (81.6%) of the study participants in the age category less than 21 years believed that fear of PITC could cause delay in treatment seeking. The study showed the association of low knowledge of the study participants about TB and HIV testing with distance > 10 km from health facility. Study participants in the age category less than 21 years thought that fear of PITC could cause treatment

Using a mathematical model to evaluate the efficacy of TB control measures.

PubMed Central

Gammaitoni, L.; Nucci, M. C.

1997-01-01

We evaluated the efficacy of recommended tuberculosis (TB) infection control measures by using a deterministic mathematical model for airborne contagion. We examined the percentage of purified protein derivative conversions under various exposure conditions, environmental controlstrategies, and respiratory protective devices. We conclude that environmental control cannot eliminate the risk for TB transmission during high-risk procedures; respiratory protective devices, and particularly high-efficiency particulate air masks, may provide nearly complete protection if used with air filtration or ultraviolet irradiation. Nevertheless, the efficiency of these control measures decreases as the infectivity of the source case increases. Therefore, administrative control measures (e.g., indentifying and isolating patients with infectious TB) are the most effective because they substantially reduce the rate of infection. PMID:9284378

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

HIV-TB coinfection impairs CD8(+) T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses.

PubMed

Suarez, Guadalupe V; Angerami, Matías T; Vecchione, María B; Laufer, Natalia; Turk, Gabriela; Ruiz, Maria J; Mesch, Viviana; Fabre, Bibiana; Maidana, Patricia; Ameri, Diego; Cahn, Pedro; Sued, Omar; Salomón, Horacio; Bottasso, Oscar A; Quiroga, María F

2015-09-01

Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8(+) T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8(+) T cells, and their modulation by DHEA during HIV-TB coinfection. CD8(+) T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8(+) T cells. Notably, CD8(+) T cells from HIV-TB patients displayed higher Terminal Effector (TTE ) CD45RA(dim) proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8(+) T cells from HIV-TB patients increased although restricted to the CD27(+) population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8(+) T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8(+) T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8(+) T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8(+) T-cell functions during HIV-TB coinfection. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Influence of Age and Nutritional Status on the Performance of the Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube in Young Children Evaluated for Tuberculosis in Southern India

PubMed Central

Jenum, Synne; Selvam, Sumithra; Mahelai, Diana; Jesuraj, Nelson; Cárdenas, Vicky; Kenneth, John; Hesseling, Anneke C.; Doherty, Timothy Mark; Vaz, Mario

2014-01-01

Background: Reliable identification of Mycobacterium tuberculosis infection or tuberculosis (TB) disease in young children is vital to assure adequate preventive and curative treatment. The tuberculin skin test (TST) and IFNγ-release assays may supplement the diagnosis of pediatric TB as cases are typically bacteriologically unconfirmed. However, it is unclear to what extent the performance of TST and QuantiFERON-TB Gold In-Tube (QFT; Cellestis’ IFNγ-release assay test) depends on the demographic, clinical and nutritional characteristics of children in whom they are tested. Methods: During a 2-year prospective observational study of 4382 neonates in Southern India, children with suspected TB were investigated and classified by a standard TB diagnostic algorithm. Results: Clinical TB was diagnosed in 13 of 705 children referred for case verification with suspected TB. TST and QFT had a susceptibility for clinical TB of 31% and 23%, respectively, in this group. Children <2 years were more likely to test QFT indeterminate. A height-for-age Z score within the lowest quartile increased the odds ratio (OR) for a positive or indeterminate QFT result [OR 2.46 (1.19–5.06), OR 3.08 (1.10–8.58)], whereas the OR for a positive TST was reduced with a weight-for-height Z score within the lowest quartile [OR 0.17 (0.06–0.47)]. Conclusion: The sensitivities of the TST and QFT for clinical TB in children <3 years of age were equally poor in this population. Stunted children were more susceptible to Mycobacterium tuberculosis infection and more prone to indeterminate QFT results. TST was less reliable in children with wasting. PMID:24797993

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

developed pulmonary TB (both TST baseline test negative). Statistical analysis suggested that age, duration of employment as a health-care professional, literacy status, and working in medical wards/OP/Intensive Care Unit were significantly associated with TB infection. Many studies propose serial tests of LTBI as effective occupational protection strategies. However, practically, it is not feasible because it has to be done at frequent intervals, but how frequently to be done is not clear. Another concern is even if found to have LTBI, there are no clear consensus guidelines about the treatment in high prevalence settings. The prevalence of LTBI is so high in countries like India that affected HCWs could not be exempted from working in high-risk areas. The depth of knowledge of TB prevention and control among HCWs should be improved by regular infection control training.

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

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.

The sensitivity of the QuantiFERON®-TB Gold Plus assay in Zambian adults with active tuberculosis.

PubMed

Telisinghe, L; Amofa-Sekyi, M; Maluzi, K; Kaluba-Milimo, D; Cheeba-Lengwe, M; Chiwele, K; Kosloff, B; Floyd, S; Bailey, S-L; Ayles, H

2017-06-01

To investigate the sensitivity of the new interferon-gamma release assay (IGRA), QuantiFERON®-TB Gold Plus (QFT-Plus), for active TB (used as a surrogate for latent tuberculous infection) in a Zambian TB clinic. Consecutive smear or Xpert® MTB/RIF-positive adult (age 18 years) pulmonary TB patients were recruited between June 2015 and March 2016. Venous blood was tested using QFT-Plus. The sensitivity was defined as the number positive divided by the total number tested. Using logistic regression, factors associated with positive QFT-Plus results were explored. Of 108 patients (median age 32 years, interquartile range 27-38; 73% male; 63% human immunodeficiency virus [HIV] positive), 90 were QFT-Plus-positive, 11 were negative and seven had indeterminate results; sensitivity was 83% (95%CI 75-90). There was no difference in sensitivity by HIV status (HIV-positive 85%, 95%CI 75-93; n = 68 vs. HIV-negative 80%, 95%CI 64-91; n = 40; P = 0.59). In models adjusted for age alone, CD4 cell count <100 cells/μl (OR 0.15, 95%CI 0.02-0.96; P = 0.05) and body mass index <18.5 kg/m2 (OR 0.27, 95%CI 0.08-0.91; P = 0.02) were associated with decreased odds of positive QFT-Plus results. Overall, the sensitivity of QFT-Plus is similar to that of the tuberculin skin test and other IGRAs. While overall sensitivity is not affected by HIV status, QFT-Plus sensitivity was lower among people living with HIV/acquired immune-deficiency syndrome with severe immunosuppression.

The effects of socioeconomic status, clinical factors, and genetic ancestry on pulmonary tuberculosis disease in northeastern Mexico.

PubMed

Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

The Effects of Socioeconomic Status, Clinical Factors, and Genetic Ancestry on Pulmonary Tuberculosis Disease in Northeastern Mexico

PubMed Central

Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.

2014-01-01

Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB

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.

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 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

Trends in, and factors associated with, HIV infection amongst tuberculosis patients in the era of anti-retroviral therapy: a retrospective study in England, Wales and Northern Ireland.

PubMed

Winter, Joanne R; Stagg, Helen R; Smith, Colette J; Lalor, Maeve K; Davidson, Jennifer A; Brown, Alison E; Brown, James; Zenner, Dominik; Lipman, Marc; Pozniak, Anton; Abubakar, Ibrahim; Delpech, Valerie

2018-06-07

HIV increases the progression of latent tuberculosis (TB) infection to active disease and contributed to increased TB in the UK until 2004. We describe temporal trends in HIV infection amongst patients with TB and identify factors associated with HIV infection. We used national surveillance data of all TB cases reported in England, Wales and Northern Ireland from 2000 to 2014 and determined HIV status through record linkage to national HIV surveillance. We used logistic regression to identify associations between HIV and demographic, clinical and social factors. There were 106,829 cases of TB in adults (≥ 15 years) reported from 2000 to 2014. The number and proportion of TB patients infected with HIV decreased from 543/6782 (8.0%) in 2004 to 205/6461 (3.2%) in 2014. The proportion of patients diagnosed with HIV > 91 days prior to their TB diagnosis increased from 33.5% in 2000 to 60.2% in 2013. HIV infection was highest in people of black African ethnicity from countries with high HIV prevalence (32.3%), patients who misused drugs (8.1%) and patients with miliary or meningeal TB (17.2%). There has been an overall decrease in TB-HIV co-infection and a decline in the proportion of patients diagnosed simultaneously with both infections. However, high rates of HIV remain in some sub-populations of patients with TB, particularly black Africans born in countries with high HIV prevalence and people with a history of drug misuse. Whilst the current policy of testing all patients diagnosed with TB for HIV infection is important in ensuring appropriate management of TB patients, many of these TB cases would be preventable if HIV could be diagnosed before TB develops. Improving screening for both latent TB and HIV and ensuring early treatment of HIV in these populations could help prevent these TB cases. British HIV Association guidelines on latent TB testing for people with HIV from sub-Saharan Africa remain relevant, and latent TB screening for people with HIV with

Low Serum Concentrations of Rifampicin and Pyrazinamide Associated with Poor Treatment Outcomes in Children with Tuberculosis Related to HIV Status.

PubMed

Ramachandran, Geetha; Kumar, A K Hemanth; Kannan, T; Bhavani, P K; Kumar, S Ramesh; Gangadevi, N Poorana; Banurekha, V V; Sudha, V; Venkatesh, S; Ravichandran, N; Kalpana, S; Mathevan, G; Sanjeeva, G N; Agarwal, Dipti; Swaminathan, Soumya

2016-05-01

To compare the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between HIV-infected and HIV-uninfected children with tuberculosis (TB) and correlate it with TB treatment outcome. HIV-uninfected (n = 84) and HIV-infected (n = 77) children with TB receiving standard thrice weekly treatment were recruited from 6 hospitals in India. Semi-intensive pharmacokinetic sampling was performed during intensive phase of TB treatment after directly observed administration of drugs. Drug concentrations were measured by high performance liquid chromatography. INH acetylator status was determined, and nutritional assessment was done. Children were followed-up and treatment outcomes noted. Children with HIV and TB had significantly lower RMP peak concentration (Cmax) (2.6 vs. 5.1 μg/mL; P < 0.001) and exposure [area under the time-concentration curve (AUC0-8); 10.4 vs. 23.4 μg/mL h; P < 0.001] than those with TB. Among HIV-infected children, a significantly higher proportion had stunting (77% vs. 29%; P < 0.001) and underweight (73% vs. 38%; P < 0.001) compared with children with TB. Combining both groups, RMP Cmax (P = 0.001; adjusted odds ratio = 1.437; 95% confidence interval: 1.157-1.784) and PZA Cmax (P = 0.027; adjusted odds ratio = 1.041; 95% confidence interval: 1.005-1.079) significantly influenced treatment outcome. HIV infection was associated with lower Cmax of RMP and INH and AUC0-8 of RMP. Over 90% of children in both groups had subtherapeutic RMP Cmax. Cmax of RMP and PZA significantly influenced TB treatment outcome in children with TB. The findings have important clinical implications and suggest the need to increase anti-TB drug doses in children with HIV and TB.

Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar

PubMed Central

Shewade, Hemant Deepak; Kyaw, Nang Thu Thu; Thein, Saw; Si Thu, Aung; Kyaw, Khine Wut Yee; Aye, Nyein Nyein; Phyo, Aye Mon; Maung, Htet Myet Win; Soe, Kyaw Thu; Aung, Si Thu

2018-01-01

Background The Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support. Objectives To assess whether CBMDR-TBC project’s support improved treatment initiation. Methods In this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as “receiving support” if date of project initiation in patient’s township was before the date of diagnosis and “not receiving support”, if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation. Results Of 456 patients, 57% initiated treatment: 64% and 56% among patients “receiving support (n = 208)” and “not receiving support (n = 228)” respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients “receiving support” and 50 (26,101) among patients “not receiving support”. After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients “receiving support” had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients “not receiving support”. In addition, age 15–54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation. Conclusion Receiving support under CBMDR-TBC project

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.

Alcohol and drug use disorders, HIV status and drug resistance in a sample of Russian TB patients

PubMed Central

Fleming, M. F.; Krupitsky, E.; Tsoy, M.; Zvartau, E.; Brazhenko, N.; Jakubowiak, W.; E. McCaul, M.

2006-01-01

SUMMARY SETTING: Alcohol use, tuberculosis (TB) drug resistance and human immunodeficiency virus (HIV) risk behavior are of increasing concern in Russian TB patients. DESIGN: A prevalence study of alcohol use and HIV risk behavior was conducted in a sample of 200 adult men and women admitted to TB hospitals in St Petersburg and Ivanovo, Russia. RESULTS: Of the subjects, 72% were men. The mean age was 41. Active TB was diagnosed using a combination of chest X-ray, sputum smears and sputum cultures. Sixty-two per cent met DSM-IV criteria for current alcohol abuse or dependence. Drug use was uncommon, with only two patients reporting recent intravenous heroin use. There was one case of HIV infection. The mean total risk assessment battery score was 3.4. Depression was present in 60% of the sample, with 17% severely depressed. Alcohol abuse/dependence was associated with an eight-fold increase in drug resistance (OR 8.58; 95% CI 2.09-35.32). Patients with relapsing or chronic TB were more likely to meet the criteria for alcohol abuse/dependence (OR 2.56; 95% CI 1.0-6.54). CONCLUSION: Alcohol use disorders are common in patients being treated for active TB, and are associated with significant morbidity. Additional surveys are needed to examine the relationship between alcohol use disorders and anti-tuberculosis drug resistance. CONTEXTE: Chezles patients tuberculeux russes, l’utilisation d’alcool, la résistance aux médicaments antituberculeux et un comportement à risque pour le virus de l’immunodéficience humaine (VIH) sont des sujets croissants d’inquiétude. SCHÉMA: Une étude: de prévalence de l’utilisation d’alcool et du comportement à risque pour le VIH a été menée sur un échantillon de 200 hommes et femmes adultes, admis dans des hôpitaux pour la tuberculose (TB) de Saint-Pétersbourg et d’Ivanovo en Russie. RÉSULTATS: Il y avait 72% d’hommes dans l’échantillon. L’âge moyen est de 41 ans. On a diagnostiqué la TB active par l�

Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Newly Diagnosed Pulmonary TB Patients in Tanzania

PubMed Central

Chigutsa, Emmanuel; Faurholt-Jepsen, Daniel; PrayGod, George; Range, Nyagosya; Castel, Sandra; Wiesner, Lubbe; Hagen, Christian Munch; Christiansen, Michael; Changalucha, John; McIlleron, Helen; Friis, Henrik; Andersen, Aase Bengaard

2015-01-01

Exposure to lower-than-therapeutic levels of anti-tuberculosis drugs is likely to cause selection of resistant strains of Mycobacterium tuberculosis and treatment failure. The first-line anti-tuberculosis (TB) regimen consists of rifampicin, isoniazid, pyrazinamide, and ethambutol, and correct management reduces risk of TB relapse and development of drug resistance. In this study we aimed to investigate the effect of standard of care plus nutritional supplementation versus standard care on the pharmacokinetics of isoniazid, pyrazinamide and ethambutol among sputum smear positive TB patients with and without HIV. In a clinical trial in 100 Tanzanian TB patients, with or without HIV infection, drug concentrations were determined at 1 week and 2 months post initiation of anti-TB medication. Data was analysed using population pharmacokinetic modelling. The effect of body size was described using allometric scaling, and the effects of nutritional supplementation, HIV, age, sex, CD4+ count, weight-adjusted dose, NAT2 genotype, and time on TB treatment were investigated. The kinetics of all drugs was well characterised using first-order elimination and transit compartment absorption, with isoniazid and ethambutol described by two-compartment disposition models, and pyrazinamide by a one-compartment model. Patients with a slow NAT2 genotype had higher isoniazid exposure and a lower estimate of oral clearance (15.5 L/h) than rapid/intermediate NAT2 genotype (26.1 L/h). Pyrazinamide clearance had an estimated typical value of 3.32 L/h, and it was found to increase with time on treatment, with a 16.3% increase after the first 2 months of anti-TB treatment. The typical clearance of ethambutol was estimated to be 40.7 L/h, and was found to decrease with age, at a rate of 1.41% per year. Neither HIV status nor nutritional supplementations were found to affect the pharmacokinetics of these drugs in our cohort of patients. PMID:26501782

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.

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

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

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.

The sensitivity of the QuantiFERON®-TB Gold Plus assay in Zambian adults with active tuberculosis

PubMed Central

Amofa-Sekyi, M.; Maluzi, K.; Kaluba-Milimo, D.; Cheeba-Lengwe, M.; Chiwele, K.; Kosloff, B.; Floyd, S.; Bailey, S-L.; Ayles, H.

2017-01-01

SUMMARY SETTING AND OBJECTIVE: To investigate the sensitivity of the new interferon-gamma release assay (IGRA), QuantiFERON®-TB Gold Plus (QFT-Plus), for active TB (used as a surrogate for latent tuberculous infection) in a Zambian TB clinic. DESIGN: Consecutive smear or Xpert® MTB/RIF-positive adult (age ⩾18 years) pulmonary TB patients were recruited between June 2015 and March 2016. Venous blood was tested using QFT-Plus. The sensitivity was defined as the number positive divided by the total number tested. Using logistic regression, factors associated with positive QFT-Plus results were explored. RESULTS: Of 108 patients (median age 32 years, interquartile range 27–38; 73% male; 63% human immunodeficiency virus [HIV] positive), 90 were QFT-Plus-positive, 11 were negative and seven had indeterminate results; sensitivity was 83% (95%CI 75–90). There was no difference in sensitivity by HIV status (HIV-positive 85%, 95%CI 75–93; n = 68 vs. HIV-negative 80%, 95%CI 64–91; n = 40; P = 0.59). In models adjusted for age alone, CD4 cell count <100 cells/μl (OR 0.15, 95%CI 0.02–0.96; P=0.05) and body mass index <18.5 kg/m2 (OR 0.27, 95%CI 0.08–0.91; P = 0.02) were associated with decreased odds of positive QFT-Plus results. CONCLUSION: Overall, the sensitivity of QFT-Plus is similar to that of the tuberculin skin test and other IGRAs. While overall sensitivity is not affected by HIV status, QFT-Plus sensitivity was lower among people living with HIV/acquired immune-deficiency syndrome with severe immunosuppression. PMID:28482964

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.

Human Immunodeficiency Viral Infection and Status Epilepticus in United States (2002-2009).

PubMed

Chaudhry, Saqib A; Afzal, Mohammad Rauf; Rodriguez, Gustavo J; Majidi, Shahram; Bundlie, Scott; Hassan, Ameer E; Suri, M Fareed K; Qureshi, Adnan I

2015-07-01

To determine the association between human immunodeficiency virus (HIV) infection and status epilepticus and compare the outcomes of patients with status epilepticus with or without underlying HIV infection. Patients with primary diagnosis of status epilepticus (cases) and status asthmaticus (controls) were identified from the 2002-2009 Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. We performed logistic regression analysis adjusting for age, gender, co-morbid conditions, including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and opportunistic infections. We compared the in hospital outcomes among patients admitted with status epilepticus in strata defined by underlying HIV infection. The rate of concurrent status epilepticus and HIV has increased over the last 7 years in hospitalized patients with status epilepticus in United States (0.14%-0.27% p<0.0001). The HIV infection was significantly associated with status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8-2.6; p<0.0001)) after adjusting for age, gender, opportunistic infections, and cardiovascular risk factors. The in-hospital mortality was significantly higher while discharge with none or minimal disability was significantly lower in status epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and (50.4% vs. 63.3%, p<0.0001), respectively. Our study suggests that there is a direct association between HIV infection and status epilepticus. The proportion of patients admitted with concurrent status epilepticus and HIV infections is increasing and such patients have higher rates of poor discharge outcomes.

Febrile status epilepticus due to respiratory syncytial virus infection.

PubMed

Uda, Kazuhiro; Kitazawa, Katsuhiko

2017-08-01

Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.

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

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.

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

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.

Improving the diagnosis of pulmonary tuberculosis in HIV-infected individuals in Ho Chi Minh City, Viet Nam.

PubMed

Nguyen, D T M; Hung, N Q; Giang, L T; Dung, N H; Lan, N T N; Lan, N N; Yen, N T B; Bang, N D; Ngoc, D V; Trinh, L T T; Beasley, R P; Ford, C E; Hwang, L-Y; Graviss, E A

2011-11-01

District 6, An Hoa Clinic in Ho Chi Minh City (HCMC), Viet Nam. To evaluate the performance of various algorithms in tuberculosis (TB) screening and diagnosis in a human immunodeficiency virus (HIV) infected population in HCMC, Viet Nam. A cross-sectional study of 397 consecutive HIV-infected patients seeking care at the An Hoa Clinic from August 2009 to June 2010. Data on participant demographics, clinical status, chest radiography (CXR) and laboratory results were collected. A multiple logistic regression model was developed to assess the association of covariates and pulmonary TB (PTB). The prevalence of sputum culture-confirmed PTB, acid-fast bacilli (AFB) positive TB, and multidrugresistant TB among the 397 HIV-infected patients was respectively 7%, 2%, and 0.3%. Adjusted odds ratios for low CD4+ cell count, positive sputum smear, and CXR to positive sputum culture were respectively 3.17, 32.04 and 4.28. Clinical findings alone had poor sensitivity, but combining CD4+ cell count, AFB sputum smear and CXR had a more accurate diagnostic performance. Results suggest that symptom screening had poor clinical performance, and support the routine use of sputum culture to improve the detection of TB disease in HIV-infected individuals in Viet Nam. However, when routine sputum culture is not available, an algorithm combining CD4+ cell count, AFB sputum smear and CXR is recommended for diagnosing PTB.

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

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

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.

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 ...

Knowledge and acceptability of patient-specific infection control measures for pulmonary tuberculosis.

PubMed

Gonzalez-Angulo, Yulieth; Geldenhuys, Hennie; Van As, Danelle; Buckerfield, Norma; Shea, Jawaya; Mahomed, Hassan; Hanekom, Willem; Hatherill, Mark

2013-08-01

Effective infection control measures are essential to reduce tuberculosis (TB) transmission in domestic, workplace, and health care settings. Acceptability of infection control measures is key to patient adherence. We used a prospective questionnaire study to determine knowledge and acceptability of potential patient-specific TB infection control measures in a rural South African community. Fifty adult TB suspects were interviewed at investigation, and 50 newly diagnosed TB patients were interviewed at the start and at the end of TB treatment. TB patients and TB suspects had similar knowledge of infection control measures at baseline. Fifty-seven percent of all participants reported knowing the cause of TB, but only 25% correctly identified microbial etiology. Basic cough hygiene was accepted by 98% of participants. Most participants (89%) accepted wearing of face masks in health facilities, but only 42% of TB suspects and 66% of TB patients (P = .016) would accept wearing face masks at home. Only 68% of participants accepted separate cohorting in health facilities and avoidance of co-sleeping with uninfected household members. At the end of treatment, TB patients demonstrated increased knowledge of TB and increased acceptability of certain household infection control measures. Acceptability of patient-specific infection control measures within households increases with acquired knowledge of TB. National control programs should maximize early TB education to improve adherence to infection control measures. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

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.

Spatial overlap links seemingly unconnected genotype-matched TB cases in rural Uganda

PubMed Central

Kato-Maeda, Midori; Emperador, Devy M.; Wandera, Bonnie; Mugagga, Olive; Crandall, John; Janes, Michael; Marquez, Carina; Kamya, Moses R.; Charlebois, Edwin D.; Havlir, Diane V.

2018-01-01

Introduction Incomplete understanding of TB transmission dynamics in high HIV prevalence settings remains an obstacle for prevention. Understanding where transmission occurs could provide a platform for case finding and interrupting transmission. Methods From 2012–2015, we sought to recruit all adults starting TB treatment in a Ugandan community. Participants underwent household (HH) contact investigation, and provided names of social contacts, sites of work, healthcare and socializing, and two sputum samples. Mycobacterium tuberculosis culture-positive specimens underwent 24-loci MIRU-VNTR and spoligotyping. We sought to identify epidemiologic links between genotype-matched cases by analyzing social networks and mapping locations where cases reported spending ≥12 hours over the one-month pre-treatment. Sites of spatial overlap (≤100m) between genotype-matched cases were considered potential transmission sites. We analyzed social networks stratified by genotype clustering status, with cases linked by shared locations, and compared network density by location type between clustered vs. non-clustered cases. Results Of 173 adults with TB, 131 (76%) were enrolled, 108 provided sputum, and 84/131 (78%) were MTB culture-positive: 52% (66/131) tested HIV-positive. Of 118 adult HH contacts, 105 (89%) were screened and 3 (2.5%) diagnosed with active TB. Overall, 33 TB cases (39%) belonged to 15 distinct MTB genotype-matched clusters. Within each cluster, no cases shared a HH or reported shared non-HH contacts. In 6/15 (40%) clusters, potential epidemiologic links were identified by spatial overlap at specific locations: 5/6 involved health care settings. Genotype-clustered TB social networks had significantly greater network density based on shared clinics (p<0.001) and decreased density based on shared marketplaces (p<0.001), compared to non-clustered networks. Conclusions In this molecular epidemiologic study, links between MTB genotype-matched cases were only

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

Higher serum 25-hydroxyvitamin D concentrations are associated with active pulmonary tuberculosis in hospitalised HIV infected patients in a low income tropical setting: a cross sectional study.

PubMed

Musarurwa, Cuthbert; Zijenah, Lynn Sodai; Mhandire, Doreen Zvipo; Bandason, Tsitsi; Mhandire, Kudakwashe; Chipiti, Maria Mary; Munjoma, Marshall Wesley; Mujaji, Witmore Bayayi

2018-05-08

The inherent risk of developing tuberculosis (TB) in HIV- infected individuals is further enhanced by hypovitaminosis D. Interventions that offset HIV-associated immune deterioration potentially arrest disease progression and incidence of opportunistic infections including TB. Despite conflicting reports on association between vitamin D deficiency (VDD) and risk of TB, vitamin D (VD) supplementation remains a promising intervention. We conducted a comparative cross-sectional study on 145 HIV + /pulmonary TB + (PTB) and 139 HIV + /PTB - hospitalised patients to investigate association of vitamin D status and risk of PTB. Stratified random sampling was used to select archived serum specimens from participants enrolled in a randomised controlled trial (RCT) conducted to investigate the impact of using a point-of-care urine lipoarabinomannan strip test for TB diagnosis. PTB status was confirmed using sputum smear microscopy, culture or GeneXpert MTB/RIF. Serum 25-hydroxyvitamin D [25(OH) D] concentrations were assayed by competitive chemiluminescent immunoassay prior to commencement of anti-TB treatment. Effect of VD status on duration of hospital stay and patient outcomes on follow up at 8 weeks were also investigated. Median serum 25(OH) D concentrations were compared using Mann-Whitney test and covariates of serum VD status were assessed using logistic regression analysis. Overall VDD prevalence in the cohort was 40.9% (95% CI: 35.1-46.8). Median serum 25(OH)D concentrations were significantly higher in HIV + /PTB + group (25.3 ng/ml, IQR:18.0-33.7) compared to the HIV + /PTB - group (20.4 ng/ml, IQR:14.6-26.9), p = 0.0003. Patients with serum 25(OH) D concentration ≥ 30 ng/ml were 1.9 times more likely to be PTB + compared to those with serum 25(OH) D concentrations < 30 ng/ml (odds ratio (OR) 1.91; 95% CI 1.1-3.2). PTB-related death was associated with higher odds of having 25(OH) D levels≥30 ng/ml. Age, gender, CD4 + count, combination

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

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.

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

"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.

Human Immunodeficiency Viral Infection and Status Epilepticus in United States (2002–2009)

PubMed Central

Chaudhry, Saqib A.; Afzal, Mohammad Rauf; Rodriguez, Gustavo J.; Majidi, Shahram; Bundlie, Scott; Hassan, Ameer E.; Suri, M. Fareed K.; Qureshi, Adnan I.

2015-01-01

Objective To determine the association between human immunodeficiency virus (HIV) infection and status epilepticus and compare the outcomes of patients with status epilepticus with or without underlying HIV infection. Methods Patients with primary diagnosis of status epilepticus (cases) and status asthmaticus (controls) were identified from the 2002–2009 Nationwide Inpatient Sample (NIS) which is representative of all admissions in the United States. We performed logistic regression analysis adjusting for age, gender, co-morbid conditions, including hypertension, diabetes mellitus (DM), renal failure, alcohol use, and opportunistic infections. We compared the in hospital outcomes among patients admitted with status epilepticus in strata defined by underlying HIV infection. Results The rate of concurrent status epilepticus and HIV has increased over the last 7 years in hospitalized patients with status epilepticus in United States (0.14%–0.27% p<0.0001). The HIV infection was significantly associated with status epilepticus (odds ratio [OR]: 2.2; 95% confidence interval [CI]: 1.8–2.6; p<0.0001)) after adjusting for age, gender, opportunistic infections, and cardiovascular risk factors. The in-hospital mortality was significantly higher while discharge with none or minimal disability was significantly lower in status epilepticus patients with underlying HIV infection (17.5% vs. 9.9%, p<0.0001) and (50.4% vs. 63.3%, p<0.0001), respectively. Conclusions Our study suggests that there is a direct association between HIV infection and status epilepticus. The proportion of patients admitted with concurrent status epilepticus and HIV infections is increasing and such patients have higher rates of poor discharge outcomes. PMID:26301033

Text messaging to decrease tuberculosis treatment attrition in TB-HIV coinfection in Uganda

PubMed Central

Hermans, Sabine M; Elbireer, Sawsan; Tibakabikoba, Harriet; Hoefman, Bas J; Manabe, Yukari C

2017-01-01

Background Low tuberculosis (TB) treatment completion rates in sub-Saharan Africa are an important driver of multidrug resistance. Mobile technology-based interventions have been shown to improve adherence to antiretroviral therapy in sub-Saharan Africa. We aimed to test the effect of a short-message service (SMS) intervention on loss to follow-up (LFU). Materials and methods In this quasi-experimental study, all adult, literate, HIV-infected patients with mobile phone access diagnosed with TB between November 2010 and October 2011 in an urban clinic in Uganda were eligible to receive adherence and appointment reminders and educational quizzes during the first 8 weeks of TB treatment. Their risk of LFU in the first 8 weeks of treatment was compared with that of patients starting treatment between March 2009 and August 2010 using logistic regression. Results One of 183 (0.5%) enrolled patients was lost to FU during the intervention compared to six of 302 (2.0%) in the preintervention control group (RR 0.27, 95% CI 0.03–2.07; P=0.22). The SMS intervention was rated as very helpful by 96%. Barriers identified included interrupted phone access (26%, median 14 days) and difficulties responding by SMS. The response rate to educational quizzes was below 10%. There were no unintentional disclosures of TB or HIV status due to the intervention. Conclusion An SMS reminder service did not show a clear effect on short-term risk of LFU in this study, which was underpowered due to a lower baseline risk in the control group than expected. The SMS-reminder service was rated highly, and there were no breaches of confidentiality. Important technological barriers have implications for larger-scale implementation, not only for TB but also other disease modalities. PMID:28919720

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.

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.

The magnitude and risk factors of intestinal parasitic infection in relation to Human Immunodeficiency Virus infection and immune status, at ALERT Hospital, Addis Ababa, Ethiopia.

PubMed

Taye, Biruhalem; Desta, Kassu; Ejigu, Selamawit; Dori, Geme Urge

2014-06-01

Human Immunodeficiency Virus (HIV) and intestinal parasitic infections are among the main health problems in developing countries like Ethiopia. Particularly, co-infections of these diseases would worsen the progression of HIV to Acquired Immunodeficiency Syndrome (AIDS). The purpose of this study was to determine the magnitude and risk factors for intestinal parasites in relation to HIV infection and immune status. The study was conducted in (1) HIV positive on antiretroviral therapy (ART) and (2) ART naïve HIV positive patients, and (3) HIV-negative individuals, at All African Leprosy and Tuberculosis (TB) Eradication and Rehabilitation Training Center (ALERT) hospital in Addis Ababa, Ethiopia. Study participants were interviewed using structured questionnaires to obtain socio-demographic characteristics and assess risk factors associated with intestinal parasitic infection. Intestinal parasites were identified from fecal samples by direct wet mount, formol ether concentration, and modified Ziehl-Neelsen staining techniques. The immune status was assessed by measuring whole blood CD4 T-cell count. The overall magnitude of intestinal parasite was 35.08%. This proportion was different among study groups with 39.2% (69/176), 38.83% (40/103) and 27.14% (38/140) in ART naïve HIV positives patients, in HIV negatives, and in HIV positive on ART patients respectively. HIV positive patients on ART had significantly lower magnitude of intestinal parasitic infection compared to HIV negative individuals. Intestinal helminths were significantly lower in HIV positive on ART and ART naïve patients than HIV negatives. Low monthly income, and being married, divorced or widowed were among the socio-demographic characteristics associated with intestinal parasitic infection. No association was observed between the magnitude of intestinal parasites and CD4 T-cell count. However, Cryptosporidium parvum, and Isospora belli were exclusively identified in individuals with CD4 T

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…

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

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania

PubMed Central

Kawai, Kosuke; Villamor, Eduardo; Mugusi, Ferdinand M; Saathoff, Elmar; Urassa, Willy; Bosch, Ronald J; Spiegelman, Donna; Fawzi, Wafaie W

2012-01-01

BACKGROUND Patients with tuberculosis (TB) often suffer from profound malnutrition. OBJECTIVE To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. METHODS A total of 471 HIV-positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months TB treatment following enrollment. RESULTS About 40% of HIV-positive and 47% of HIV-negative TB patients had BMI <18.5 kg/m2 at baseline. About 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV-positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Female sex, older age, low CD4 cell counts, previous TB infection, and less money spent on food were independently associated with a smaller improvement in hemoglobin among HIV-positive patients during treatment. CONCLUSION HIV- positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment. PMID:22283899

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania.

PubMed

Kawai, K; Villamor, E; Mugusi, F M; Saathoff, E; Urassa, W; Bosch, R J; Spiegelman, D; Fawzi, W W

2011-10-01

Patients with tuberculosis (TB) often suffer from profound malnutrition. To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. A total of 471 human immunodeficiency virus (HIV) positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months' TB treatment following enrollment. About 40% of HIV-positive and 47% of HIV-negative TB patients had body mass index (BMI) < 18.5 kg/m 2 at baseline, while about 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV- positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Fe- male sex, older age, low CD4 cell counts, previous TB infection and less money spent on food were independently associated with a smaller improvement in hemoglobin levels among HIV-positive patients during treatment. HIV-positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment.

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.

Addressing knowledge gaps and prevention for tuberculosis-infected Indian adults: a vital part of elimination.

PubMed

DeLuca, Andrea; Dhumal, Gauri; Paradkar, Mandar; Suryavanshi, Nishi; Mave, Vidya; Kohli, Rewa; Shivakumar, Shri Vijay Bala Yogendra; Hulyolkar, Vidula; Gaikwad, Archana; Nangude, Ashwini; Pardeshi, Geeta; Kadam, Dileep; Gupta, Amita

2018-05-02

India plans to eliminate tuberculosis (TB) by 2025, and has identified screening and prevention as key activities. Household contacts (HHCs) of index TB cases are a high-risk population that would benefit from rapid implementation of these strategies. However, best practices for TB prevention and knowledge gaps among HHCs have not been studied. We evaluated TB knowledge and understanding of prevention among tuberculin skin-test (TST) positive HHCs. While extensive information is available in other high-burden settings regarding TB knowledge gaps, identifying how Indian adult contacts view their transmission risk and prevention options may inform novel screening algorithms and education efforts that will be part of the new elimination plan. We approached adult HHC to administer a questionnaire on TB knowledge and understanding of infection. Over 1 year, 100 HHC were enrolled at a tertiary hospital in Pune, India. The study population was 61% (n = 61) female, with a mean age of 36.6 years (range 18-67, SD = 12). Education levels were high, with 78 (78%) having at least a high school education, and 23 (24%) had at least some college education. Four (4%) of our participants were HIV-infected. General TB knowledge among HHC was low, with a majority of participants believing that you can get TB from sharing dishes (70%) or touching something that has been coughed on (52%). Understanding of infection was also low, with 42% believing that being skin-test positive means you have disease. To assess readiness for preventive therapy, we asked participants whether they are at a higher risk of progressing to active disease because of their LTBI status. Fifty-four (55%) felt that they are at higher risk. Only 8% had heard of preventive therapy. Our TB knowledge survey among HHCs with evidence of recent exposure found that knowledge is poor and families are confused about transmission in the household. It is imperative that the Indian program develop tools and incentives

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

Tuberculosis and non-tuberculous mycobacteria among HIV-infected individuals in Ghana.

PubMed

Bjerrum, Stephanie; Oliver-Commey, Joseph; Kenu, Ernest; Lartey, Margaret; Newman, Mercy Jemima; Addo, Kennedy Kwasi; Hilleman, Doris; Andersen, Aase Bengaard; Johansen, Isik Somuncu

2016-09-01

To assess the prevalence and clinical importance of previously unrecognised tuberculosis (TB) and isolation of non-tuberculous mycobacteria (NTM) among HIV-infected individuals in a teaching hospital in Ghana. Intensified mycobacterial case finding was conducted among HIV-positive individuals before initiation of antiretroviral therapy (ART). Data were collected on socio-demographic characteristics, medical history and TB-related signs and symptoms, and participants were followed for six months to determine treatment and vital status. Two sputum samples were obtained and examined for mycobacteria with smear microscopy, culture and Xpert MTB/RIF assay. NTM species were identified with the GenoType Mycobacterium CM/AS or sequence analysis of 16S rRNA gene. Of 473 participants, 60 (12.7%) had confirmed pulmonary TB, and 38 (8.0%) had positive cultures for NTM. Mycobacterium avium complex was identified in 9/38 (23.7%) of NTM isolates. Participants with NTM isolated were more likely to have CD4 cell count< 100 cells/μL (aOR 2.37; 95% CI: 1.10-5.14), BMI<18.5kg/m(2) (aOR 2.51; 95% CI: 1.15-5.51) and fever ≥2 weeks (aOR 2.76; 95% CI: 1.27-6.03) at baseline than participants with no mycobacteria. By six months, 76 (16.1%) participants had died; 20 (33.3%) with confirmed TB and 9 (23.7%) with NTM-positive culture. Mortality at six months was independently associated with TB diagnosis at enrolment (aHR 1.97; 95% CI 1.09-3.59), but not with NTM isolation after controlling for age, sex, CD4 cell count, BMI, prolonged fever and ART initiation. Intensified mycobacterial screening of HIV-infected individuals revealed a high burden of unrecognised pulmonary TB before ART initiation, which increased risk of death within six months. NTM were frequently isolated and associated with signs of poor clinical status but not with increased mortality. © 2016 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

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.

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

Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

PubMed Central

Sara, Chandy; Elsa, Heylen; Baijayanti, Mishra; Lennartsdotter, Ekstrand Maria

2016-01-01

Objectives To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline. PMID:27708985

Gene mutations in Mycobacterium tuberculosis: multidrug-resistant TB as an emerging global public health crisis.

PubMed

Mishra, Rahul; Shukla, Priyanka; Huang, Wei; Hu, Ning

2015-01-01

Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. TB poses formidable challenges to the global health at the public health and scientific level by acquiring gene mutation into anti TB drugs specially rifampin and isoniazid which leads resistant to drug regime and treatment forms. Our tools to combat MDR (multidrug resistant) TB are dangerously out of date and ineffective. Besides new tools (TB drugs, vaccines, diagnostics), we also need new strategies to identify key Mycobacterium tuberculosis and human host interaction. It is all equally important that we build up high quality clinical trial capacity and bio banks for TB biomarkers identification. But most important is global commitment at all levels to roll back TB before it expose us again. Rapid development of drug resistance caused by M. tuberculosis has lead to measure resistance accurately and easily. This knowledge will certainly help us to understand how to prevent the occurrence of drug resistance as well as identifying genes associated with new drug resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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.

Prevalence, patterns, and correlates of HIV disclosure among TB-HIV patients initiating antiretroviral therapy in Lesotho.

PubMed

Hayes-Larson, Eleanor; Hirsch-Moverman, Yael; Saito, Suzue; Frederix, Koen; Pitt, Blanche; Maama, Bridget Llang; Howard, Andrea A

2017-08-01

Disclosure of HIV-positive status has important implications for patient outcomes and preventing HIV transmission, but has been understudied in TB-HIV patients. We assessed disclosure patterns and correlates of non-disclosure among adult TB-HIV patients initiating ART enrolled in the START Study, a mixed-methods cluster-randomized trial conducted in Lesotho, which evaluated a combination intervention package (CIP) versus standard of care. Interviewer-administered questionnaire data were analyzed to describe patterns of disclosure. Patient-related factors were assessed for association with non-disclosure to anyone other than a health-care provider and primary partners using generalized linear mixed models. Among 371 participants, 95% had disclosed their HIV diagnosis to someone other than a health-care provider, most commonly a spouse/primary partner (76%). Age, TB knowledge, not planning to disclose TB status, greater perceived TB stigma, and CIP were associated with non-disclosure in unadjusted models (p < .1). In adjusted models, all point estimates were similar and greater TB knowledge (adjusted odds ratio [aOR] 0.59, 95% confidence interval [CI] 0.39-0.90) and CIP (aOR 0.20, 95% CI 0.05-0.79) remained statistically significant. Among 220 participants with a primary partner, 76% had disclosed to that partner. Significant correlates of partner non-disclosure (p < .1) in unadjusted analyses included being female, married/cohabitating, electricity at home, not knowing if partner was HIV-positive, and TB knowledge. Adjusted point estimates were largely similar, and being married/cohabitating (aOR 0.03, 95% CI 0.01-0.12), having electricity at home (aOR 0.38, 95% CI 0.17-0.85) and greater TB knowledge (aOR 0.76, 95% CI 0.59-0.98) remained significant. In conclusion, although nearly all participants reported disclosing their HIV status to someone other than a health-care provider at ART initiation, nearly a quarter of participants with a primary partner had

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

Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial.

PubMed

Cox, Helen S; Mbhele, Slindile; Mohess, Neisha; Whitelaw, Andrew; Muller, Odelia; Zemanay, Widaad; Little, Francesca; Azevedo, Virginia; Simpson, John; Boehme, Catharina C; Nicol, Mark P

2014-11-01

Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33-0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32-1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06-1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63-0.92, p = 0.005) and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53-0.85, p = 0

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.

Evaluation of FASTPlaqueTB to diagnose smear-negative tuberculosis in a peripheral clinic in Kenya.

PubMed

Bonnet, M; Gagnidze, L; Varaine, F; Ramsay, A; Githui, W; Guerin, P J

2009-09-01

To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no response to 1 week of amoxicillin and abnormal chest X-ray were defined as smear-negative suspects. One sputum sample was collected, decontaminated and divided into two: half was tested with FASTPlaqueTB in the clinic laboratory and the other half was cultured on Löwenstein-Jensen medium in the Kenyan Medical Research Institute. Test sensitivity and specificity were evaluated in all patients and in human immunodeficiency virus (HIV) infected patients. Feasibility was assessed by the contamination rate and the resources required to upgrade the laboratory. Of 208 patients included in the study, 56.2% were HIV-infected. Of 203 FASTPlaqueTB tests, 95 (46.8%) were contaminated, which interfered with result interpretation and led to the interruption of the study. Sensitivity and specificity were respectively 31.2% (95%CI 12.1-58.5) and 94.9% (95%CI 86.8-98.4) in all patients and 33.3% (95%CI 9.9-65.1) and 93.9% (95%CI 83.1-98.7) in HIV-infected patients. Upgrading the laboratory cost euro 20,000. FASTPlaqueTB did not perform satisfactorily in this setting. If contamination can be reduced, in addition to laboratory upgrading, its introduction in peripheral clinics would require further assessment in smear-negative and HIV co-infected patients and test adaptation for friendlier use.

Within-Subject Interlaboratory Variability of QuantiFERON-TB Gold In-Tube Tests

DTIC Science & Technology

2012-09-06

QuantiFERONH-TB Gold In-Tube test (QFT-GIT) is a viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection...viable alternative to the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. However, within-subject variability may limit test...release assays (IGRAs) are designed to detect both latent Mycobacterium tuberculosis infection (LTBI) and infections manifesting as active

Establishment of a Neonatal Rhesus Macaque Model to Study Mycobacterium tuberculosis Infection

PubMed Central

Cepeda, Magdalena; Salas, Mary; Folwarczny, Jessica; Leandro, Ana C.; Hodara, Vida L.; de la Garza, Melissa A.; Dick, Edward J.; Owston, Michael; Armitige, Lisa Y.; Gauduin, Marie-Claire

2014-01-01

Summary Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4–6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS. PMID:24388650

Prevalence of latent tuberculosis infection among foreign students in Lübeck, Germany tested with QuantiFERON-TB Gold In-Tube and QuantiFERON-TB Gold Plus.

PubMed

Gallegos Morales, Elia Noemi; Knierer, Johannes; Schablon, Anja; Nienhaus, Albert; Kersten, Jan Felix

2017-01-01

The tuberculosis (TB) incidence rate in foreign-born individuals has been increasing in Germany in recent years. Foreign students may be an important source of latent tuberculosis infection (LTBI) in low-incidence countries. In Germany, there are no guidelines for LTBI screening of foreign students. The aim of the study was to estimate LTBI prevalence and evaluate associated risk factors among foreign students in Germany. The second purpose of our study was to compare the results of the new generation of QuantiFERON-TB Gold Plus (QFT-Plus) to those of its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT). This cross - sectional study was conducted between February 2016 and March 2016. Foreign students and young professionals attending the university and higher education institutes in Lübeck, Germany were tested with QFT-Plus and QFT-GIT. Participants filled out a questionnaire for the purpose of LTBI risk assessment and analysis. Variables associated with a positive test result were analyzed using logistic regression. One hundred thirty four students participated in the study. The overall prevalence as regards positive results from both tests, QFT-Plus and QFT-GIT, was 9.7%, and the prevalence of positive QFT-Plus results was 8.2%. The main independent variables associated with a positive QFT-Plus result were a) being born in a high-incidence country (OR = 6.7, 95% CI: 1.3-34.3) and b) previous contact with a person with active TB (OR = 4.5, 95% CI: 1.1-18.3). Higher age (OR = 2.8, 95% CI: 0.7-11.3) and male gender (OR = 1.6, 95% CI: 0.4-6.7) showed a tendency toward positive QFT-Plus results but this was not statistically significant. Agreement between QFT-Plus and QFT-GIT results was κ = 0.85, p  < 0.001. The LTBI prevalence among foreign students was about 10%. We recommend implementing a policy whereby all foreign students are screened by means of a questionnaire about LTBI risk factors, so that only students with present risk factors are tested

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.

Routinely detected indicators in plasma have a predictive effect on the identification of HIV-infected patients with non-tuberculous mycobacterial and tuberculous infections.

PubMed

Cai, Ren-Tian; Yu, Feng-Xue; Tao, Zhen; Qian, Xue-Qin; Chen, Jun; Lu, Hong-Zhou

2017-11-02

It is difficult to quickly distinguish non-tuberculous mycobacterial (NTM) infection from tuberculosis (TB) infection in human immunodeficiency virus (HIV)-infected patients because of many similarities between these diseases. A simple and effective way to determine the differences using routine blood tests is necessary in developing countries. A retrospective cohort study was conducted to recruit HIV-infected patients with either NTM infection or TB infection diagnosed for the first time according to mycobacterial culture and microscopic identification from May 2010 to March 2016. These data included the analysis of blood cells, liver function, renal function, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), and were compared between the HIV/TB and HIV/NTM groups. A total of 240 patients were enrolled. The number of HIV/TB and HIV/NTM patients was 113 and 127, respectively. There were no significant differences in the CD4 T-cell count, age, sex, percentage of patients initiating antiretroviral therapy (ART) before the explicit diagnosis of TB or NTM infection. NTM infection was more likely to be restricted in the pulmonary while TB infection also involves extra-pulmonary sites. Both the leukocyte count(5.60 × 10 9 /L) and the proportion of neutrophils in the leukocyte count (76.70%) in the HIV/TB group were significantly higher than those in the HIV/NTM group (4.40 × 10 9 /L [P = 0.0014] and 69.30% [P < 0.001]. The analysis of liver function markers indicated that the concentration of albumin but not ALT and AST was significantly lower in the HIV/TB group than in the HIV/NTM group (P < 0.001). The creatinine and urea levels were not significantly different between the two groups. The ESR (84.00 mm/h) and the concentration of CRP (59.60 mg/L) were significantly higher in the HIV/TB group than in the HIV/NTM group (52.00 mm/h and 19.60 mg/L, respectively) (P < 0.001). To distinguish TB infection from NTM infection, the best cut

[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

Poor agreement between interferon-gamma release assays and the tuberculin skin test among HIV-infected individuals in the country of Georgia.

PubMed

Chkhartishvili, Nikoloz; Kempker, Russell R; Dvali, Natia; Abashidze, Lela; Sharavdze, Lali; Gabunia, Pati; Blumberg, Henry M; Del Rio, Carlos; Tsertsvadze, Tengiz

2013-11-01

Improved tests to diagnose latent TB infection (LTBI) are needed. We sought to evaluate the performance of two commercially available interferon-gamma release assays (IGRAs) compared to the tuberculin skin test (TST) for the diagnosis of LTBI and to identify risk factors for LTBI among HIV-infected individuals in Georgia, a country with high rates of TB. HIV-patients were enrolled from the National AIDS Center in Tbilisi, Georgia. After providing informed consent, each participant completed a questionnaire, had blood drawn for QuantiFERON-TB Gold in-Tube (QFT-GIT) and T-SPOT.TB testing and had a TST placed. The TST was read at 48-72 hrs with ≥ 5 mm induration considered positive. Between 2009-2011, 240 HIV-infected persons (66% male) with a median age of 38 years and a median CD4 count of 255 cells/μl (IQR: 124-412) had diagnostic testing for LTBI performed. 94% had visible evidence of a BCG scar. The TST was positive in 41 (17%) patients; QFT-GIT in 70 (29%); and T-SPOT.TB in 56 (24%). At least one diagnostic test was positive in 109 (45%) patients and only among 13 (5%) patients were all three tests positive. Three (1%) QFT-GIT and 19 (8%) T-SPOT.TB test results were indeterminate. The agreement among all pairs of tests was poor: QFT-GIT vs. T-SPOT.TB (κ = 0.18, 95% CI .07-.30), QFT-GIT vs. TST (κ = 0.29, 95% CI .16-.42), and TST vs. T-SPOT.TB (κ = 0.22, 95% CI .07-.29). Risk factors for LTBI varied by diagnostic test and none showed associations between positive test results and well-known risk factors for TB, such as imprisonment, drug abuse and immunological status. A high proportion of HIV patients had at least one positive diagnostic test for LTBI; however, there was very poor agreement among all tests. This lack of agreement makes it difficult to know which test is superior and most appropriate for LTBI testing among HIV-infected patients. While further follow-up studies will help determine the predictive ability of different LTBI tests, improved

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

Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.

PubMed

Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V; Mondal, Debasis; Nair, Madhavan

2015-01-01

Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

Computational and empirical studies predict Mycobacterium tuberculosis-specific T cells as a biomarker for infection outcome

DOE PAGES

Marino, Simeone; Gideon, Hannah P.; Gong, Chang; ...

2016-04-11

Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2-year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identifiedmore » T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. As a result, we emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery.« less

Computational and empirical studies predict Mycobacterium tuberculosis-specific T cells as a biomarker for infection outcome

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

Marino, Simeone; Gideon, Hannah P.; Gong, Chang

Identifying biomarkers for tuberculosis (TB) is an ongoing challenge in developing immunological correlates of infection outcome and protection. Biomarker discovery is also necessary for aiding design and testing of new treatments and vaccines. To effectively predict biomarkers for infection progression in any disease, including TB, large amounts of experimental data are required to reach statistical power and make accurate predictions. We took a two-pronged approach using both experimental and computational modeling to address this problem. We first collected 200 blood samples over a 2-year period from 28 non-human primates (NHP) infected with a low dose of Mycobacterium tuberculosis. We identifiedmore » T cells and the cytokines that they were producing (single and multiple) from each sample along with monkey status and infection progression data. Machine learning techniques were used to interrogate the experimental NHP datasets without identifying any potential TB biomarker. In parallel, we used our extensive novel NHP datasets to build and calibrate a multi-organ computational model that combines what is occurring at the site of infection (e.g., lung) at a single granuloma scale with blood level readouts that can be tracked in monkeys and humans. We then generated a large in silico repository of in silico granulomas coupled to lymph node and blood dynamics and developed an in silico tool to scale granuloma level results to a full host scale to identify what best predicts Mycobacterium tuberculosis (Mtb) infection outcomes. The analysis of in silico blood measures identifies Mtb-specific frequencies of effector T cell phenotypes at various time points post infection as promising indicators of infection outcome. As a result, we emphasize that pairing wetlab and computational approaches holds great promise to accelerate TB biomarker discovery.« less

Mycobacterium tuberculosis and non-tuberculous mycobacteria isolates from HIV-infected patients in Guangxi, China.

PubMed

Lan, R; Yang, C; Lan, L; Ou, J; Qiao, K; Liu, F; Gao, Q

2011-12-01

Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV) infected persons. The prevalence of infection with Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) in HIV-infected patients in China is unknown. To estimate the prevalence of M. tuberculosis and NTM in HIV-infected patients in Guangxi Province, determine their drug resistance profiles, and evaluate the genotype patterns of M. tuberculosis strains. Samples were collected from two HIV designated hospitals in Guangxi Province between 2005 and 2008. HIV-infected patients who were culture-positive for mycobacteria were included. Drug susceptibility testing was performed for mycobacterial isolates. NTM species was identified by sequencing, and M. tuberculosis isolates were genotyped using the variable number of tandem repeats method. M. tuberculosis and NTM were identified in respectively 117 (53%) and 102 (47%) HIV-infected patients. Drug resistance was found in 27% and multi-drug-resistant TB (MDR-TB) in 11% of the patients with TB. Previous treatment for TB was significantly associated with MDR-TB. Twenty (17%) TB patients belonged to eight VNTR-defined clusters. The high frequency of NTM among HIV-infected patients raises concerns about accurate species identification before the determination of appropriate treatment. The potential for TB transmission exists among HIV-infected patients. Intensified screening and effective treatment of TB-HIV co-infected patients is urgently needed.

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

Serum prolidase activity and oxidative status in Helicobacter pylori infection.

PubMed

Aslan, Mehmet; Nazligul, Yasar; Horoz, Mehmet; Bolukbas, Cengiz; Bolukbas, Fusun F; Aksoy, Nurten; Celik, Hakim; Erel, Ozcan

2007-01-01

During the course of Helicobacter pylori infection, increased oxidative stress plays an important role in the pathogenesis of gastroduodenal mucosal inflammation, which can cause gastric mucosal atrophy that characterized by the replacement of the gastric mucosal glands by collagen fibers. In the present study, we aimed to determine serum prolidase activity and oxidative status, and to find out if there is any association between serum prolidase activity and oxidative status in H. pylori infection. Forty H. pylori-positive and 32 H. pylori-negative subjects were enrolled. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total antioxidant capacity and total oxidant status measurement and calculation of oxidative stress index. Total antioxidant capacity level was lower in H. pylori-positive group than H. pylori-negative group (p<0.001), whereas total oxidant status, oxidative stress index and prolidase activity were higher (all p<0.05). Significant correlation was observed between serum prolidase activity, and total antioxidant capacity, total oxidant status and oxidative stress index (p<0.01, r=-0.367; p<0.05, r=0.283; p<0.01, r=0.379; respectively) in H. pylori-positive subjects. H. pylori infection may be associated with increased oxidative stress and increased serum prolidase activity. Increased oxidative stress seems to be associated with increased serum prolidase activity and this association may help to provide a better understanding about the pathogenesis of H. pylori infection.

Oxidative Stress in Wild Boars Naturally and Experimentally Infected with Mycobacterium bovis

PubMed Central

Gassó, Diana; Vicente, Joaquín; Mentaberre, Gregorio; Soriguer, Ramón; Jiménez Rodríguez, Rocío; Navarro-González, Nora; Tvarijonaviciute, Asta; Lavín, Santiago; Fernández-Llario, Pedro; Segalés, Joaquim; Serrano, Emmanuel

2016-01-01

Reactive oxygen and nitrogen species (ROS-RNS) are important defence substances involved in the immune response against pathogens. An excessive increase in ROS-RNS, however, can damage the organism causing oxidative stress (OS). The organism is able to neutralise OS by the production of antioxidant enzymes (AE); hence, tissue damage is the result of an imbalance between oxidant and antioxidant status. Though some work has been carried out in humans, there is a lack of information about the oxidant/antioxidant status in the presence of tuberculosis (TB) in wild reservoirs. In the Mediterranean Basin, wild boar (Sus scrofa) is the main reservoir of TB. Wild boar showing severe TB have an increased risk to Mycobacterium spp. shedding, leading to pathogen spreading and persistence. If OS is greater in these individuals, oxidant/antioxidant balance in TB-affected boars could be used as a biomarker of disease severity. The present work had a two-fold objective: i) to study the effects of bovine TB on different OS biomarkers (namely superoxide dismutase (SOD), catalasa (CAT), glutathione peroxidase (GPX), glutathione reductase (GR) and thiobarbituric acid reactive substances (TBARS)) in wild boar experimentally challenged with Mycobacterium bovis, and ii) to explore the role of body weight, sex, population and season in explaining the observed variability of OS indicators in two populations of free-ranging wild boar where TB is common. For the first objective, a partial least squares regression (PLSR) approach was used whereas, recursive partitioning with regression tree models (RTM) were applied for the second. A negative relationship between antioxidant enzymes and bovine TB (the more severe lesions, the lower the concentration of antioxidant biomarkers) was observed in experimentally infected animals. The final PLSR model retained the GPX, SOD and GR biomarkers and showed that 17.6% of the observed variability of antioxidant capacity was significantly correlated with

Impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009-2011).

PubMed

Kaplan, Richard; Caldwell, Judy; Middelkoop, Keren; Bekker, Linda-Gail; Wood, Robin

2014-08-15

To identify determinants of tuberculosis (TB) case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients aged ≥15 years. Multivariable Cox proportional hazard models were used to determine the risk factors for TB case fatality in these patients. In 2009, 2010, and 2011, 25,841, 26,104, and 25,554 newly registered adult TB patients were treated in primary health care clinics in Cape Town, of whom 49.7%, 50.4%, and 50.9% were HIV positive. ART uptake increased over 3 years from 43% to 64.9%, and case fatality of the HIV-positive patients decreased from 7.0% to 5.8% (P < 0.001). Female gender, increasing age, retreatment TB, low CD4 counts, and extrapulmonary TB were associated with increased case fatality, whereas patients on ART had a substantial decrease in case fatality. The difference in case fatality between patients on ART and not on ART was most pronounced at low CD4 counts with the positive influence of ART noted up to a CD4 count threshold of 350 cells per cubic millimeter (P < 0.001). Despite improvements in ART uptake, in 2011, 21% of the patients with CD4 counts <350 cells per cubic millimeter did not start ART during TB treatment. This study showed a relatively poor uptake of ART among severely immune-compromised TB patients. Patients with CD4 counts <350 cells per cubic millimeter were shown to clearly benefit from ART during TB treatment, and ART initiation should be prioritized for this category of patients.

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.

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.

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.

Impact of Xpert MTB/RIF for TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa: A Pragmatic Randomised Trial

PubMed Central

Cox, Helen S.; Mbhele, Slindile; Mohess, Neisha; Whitelaw, Andrew; Muller, Odelia; Zemanay, Widaad; Little, Francesca; Azevedo, Virginia; Simpson, John; Boehme, Catharina C.; Nicol, Mark P.

2014-01-01

Background Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. Methods and Findings A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33–0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32–1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06–1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63–0.92, p = 0.005) and among HIV-infected participants

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

Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection.

PubMed

Vecchione, María Belén; Eiras, Javier; Suarez, Guadalupe Verónica; Angerami, Matías Tomás; Marquez, Cecilia; Sued, Omar; Ben, Graciela; Pérez, Héctor Miguel; Gonzalez, Diego; Maidana, Patricia; Mesch, Viviana; Quiroga, María Florencia; Bruttomesso, Andrea Claudia

2018-04-27

An estimated one third of the world's population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.

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

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

Tuberculosis in HIV-infected Tanzanian children below 14 years.

PubMed

Njau, J C; Aboud, S

2010-09-01

Tuberculosis (TB)-human immunodeficiency virus (HIV) co-infection is an important public health problem. Diagnosis of TB in children usually follows discovery of an adult case, and relies on clinical presentation, sputum examination and chest radiograph. However, clinical features are non-specific, chest radiographs are difficult to interpret, and routine laboratory tests are not helpful. The aim of the current study was to determine the prevalence of TB in HIV-infected children below 14 years attending a tertiary hospital. A cross-sectional study was conducted in HIV-infected children below 14 years of age at Muhimbili National Hospital, in Dar es Salaam, Tanzania, between July 2008 and January 2009. Information on socio-demographic and anthropometric characteristics was collected using a structured questionnaire. Following assessment of clinical presentation, physical examination, tuberculin skin test, and chest radiograph were performed for each child. Two consecutive sputum specimens and blopd sample were collected for microscopy and culture, and CD4 T-lymphocyte percentage test, respectively. Chi-square test was used to compare differences in proportions. Odds ratio (OR) and their 95% confidence interval (CI) are presented as the risk estimator. Of 182 HIV-infected children enrolled in the study, 104 (57.1%) were males. Overall, thirty-seven (20.3%) children had TB. The prevalence of TB was highest in males (78.4%) compared to females (p = 0.003). There was a higher proportion of TB (45.9%) in the age group below 24 months compared to other age groups (p = 0.001). Male gender, history of positive TB contact and severe immunosuppression were found to be significant risk factors for TB while use of antiretroviral therapy was found to be associated with decreased risk for TB. One-fifth of children had TB/HIV co-infection. Presence of four or more clinical manifestations and a low CD4+ T-lymphocyte percentage can be used to predict active TB in HIV-infected

Clinical research in the treatment of tuberculosis: current status and future prospects.

PubMed

Chang, K-C; Yew, W-W; Sotgiu, G

2015-12-01

To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens. Our review was restricted to Phase II/III clinical trials, cohort and case-control studies, and systematic reviews of clinical studies. TB programmatic and patient behavioural factors, non-TB drugs, adjunctive surgery, new vaccines, immunotherapy, antiretroviral therapy and management of latent tuberculous infection are outside the scope of this review. An algorithm was used to systematically search PubMed for relevant articles published in English from 1 January 2005 to 31 December 2014. Articles without evaluated factors (drugs, dosing factors and regimens) or comparative analysis of specified anti-tuberculosis treatment outcomes were excluded. Of the 399 articles initially identified, 294 were excluded. The main findings of the remaining 105 articles are described under two categories: presumed drug-susceptible TB and MDR-TB. Fifty-nine articles included under drug-susceptible TB were divided into 12 subcategories: isoniazid, rifampicin, pyrazinamide, fluoroquinolones, fixed-dose combination drugs, dosing frequency, treatment phases, treatment duration, experimental regimens for pulmonary (surrogate markers vs. clinical outcomes) and extra-pulmonary TB. Forty-nine articles included under MDR-TB were divided into seven subcategories: fluoroquinolones, pyrazinamide, second-line injectable drugs, World Health Organization Group 4 and Group 5 drugs, MDR-TB regimens and novel drugs. Clinical research in the last decade and ongoing trials might furnish new paradigms for improving the treatment of this recalcitrant ancient disease.

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.

Detection of antibodies to tuberculosis antigens in free-ranging lions (Panthera leo) infected with Mycobacterium bovis in Kruger National Park, South Africa.

PubMed

Miller, Michele; Joubert, Jennifer; Mathebula, Nomkhosi; De Klerk-Lorist, Lin-Marie; Lyashchenko, Konstantin P; Bengis, Roy; van Helden, Paul; Hofmeyr, Markus; Olea-Popelka, Francisco; Greenwald, Rena; Esfandiari, Javan; Buss, Peter

2012-06-01

Bovine tuberculosis (TB), caused by Mycobacterium bovis, has become established in Kruger National Park, South Africa, in the cape buffalo (Syncerus caffer) population and in other species. TB in prey species has resulted in infection and morbidity in the resident lion (Panthera leo) prides. The only validated live animal test currently available for lions is the intradermal tuberculin test. Because this test requires capture twice, 72 hr apart, of free-ranging lions to read results, it is logistically difficult to administer in a large ecosystem. Therefore, development of a rapid animal-side screening assay would be ideal in providing information for wildlife managers, veterinarians, and researchers working with free-living lion prides. This study reports preliminary descriptive results from an ongoing project evaluating two serologic tests for M. bovis (ElephantTB Stat-Pak and dual path platform VetTB). Disease status was determined by postmortem culture and presence of pathologic lesions in 14 free-ranging lions. Seropositivity was found to be associated with M. bovis infection. Extended field studies are underway to validate these rapid animal-side immunoassays for antemortem screening tests for TB in lions.

MHC-I affects infection intensity but not infection status with a frequent avian malaria parasite in blue tits.

PubMed

Westerdahl, Helena; Stjernman, Martin; Råberg, Lars; Lannefors, Mimi; Nilsson, Jan-Åke

2013-01-01

Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load) and infection status (infected or not). It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts.

MHC-I Affects Infection Intensity but Not Infection Status with a Frequent Avian Malaria Parasite in Blue Tits

PubMed Central

Westerdahl, Helena; Stjernman, Martin; Råberg, Lars; Lannefors, Mimi; Nilsson, Jan-Åke

2013-01-01

Host resistance against parasites depends on three aspects: the ability to prevent, control and clear infections. In vertebrates the immune system consists of innate and adaptive immunity. Innate immunity is particularly important for preventing infection and eradicating established infections at an early stage while adaptive immunity is slow, but powerful, and essential for controlling infection intensities and eventually clearing infections. Major Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and studies on parasite resistance and MHC in wild animals have found effects on both infection intensity (parasite load) and infection status (infected or not). It seems MHC can affect both the ability to control infection intensities and the ability to clear infections. However, these two aspects have rarely been considered simultaneously, and their relative importance in natural populations is therefore unclear. Here we investigate if MHC class I genotype affects infection intensity and infection status with a frequent avian malaria infection Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We found a significant negative association between a single MHC allele and infection intensity but no association with infection status. Blue tits that carry a specific MHC allele seem able to suppress H. majoris infection intensity, while we have no evidence that this allele also has an effect on clearance of the H. majoris infection, a result that is in contrast with some previous studies of MHC and avian malaria. A likely explanation could be that the clearance rate of avian malaria parasites differs between avian malaria lineages and/or between avian hosts. PMID:24023631

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

Helminth Infections Coincident with Active Pulmonary Tuberculosis Inhibit Mono- and Multifunctional CD4+ and CD8+ T Cell Responses in a Process Dependent on IL-10

PubMed Central

George, Parakkal Jovvian; Anuradha, Rajamanickam; Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash

2014-01-01

Tissue invasive helminth infections and tuberculosis (TB) are co-endemic in many parts of the world and can trigger immune responses that might antagonize each other. We have previously shown that helminth infections modulate the Th1 and Th17 responses to mycobacterial-antigens in latent TB. To determine whether helminth infections modulate antigen-specific and non-specific immune responses in active pulmonary TB, we examined CD4+ and CD8+ T cell responses as well as the systemic (plasma) cytokine levels in individuals with pulmonary TB with or without two distinct helminth infections—Wuchereria bancrofti and Strongyloides stercoralis infection. By analyzing the frequencies of Th1 and Th17 CD4+ and CD8+ T cells and their component subsets (including multifunctional cells), we report a significant diminution in the mycobacterial–specific frequencies of mono- and multi–functional CD4+ Th1 and (to a lesser extent) Th17 cells when concomitant filarial or Strongyloides infection occurs. The impairment in CD4+ and CD8+ T cell cytokine responses was antigen-specific as polyclonal activated T cell frequencies were equivalent irrespective of helminth infection status. This diminution in T cell responses was also reflected in diminished circulating levels of Th1 (IFN-γ, TNF-α and IL-2)- and Th17 (IL-17A and IL-17F)-associated cytokines. Finally, we demonstrate that for the filarial co-infections at least, this diminished frequency of multifunctional CD4+ T cell responses was partially dependent on IL-10 as IL-10 blockade significantly increased the frequencies of CD4+ Th1 cells. Thus, co-existent helminth infection is associated with an IL-10 mediated (for filarial infection) profound inhibition of antigen-specific CD4+ T cell responses as well as protective systemic cytokine responses in active pulmonary TB. PMID:25211342

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis

PubMed Central

Schnippel, Kathryn; Sharp, Alana

2016-01-01

Objective Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. Methods We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Findings Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis.

PubMed

McLaren, Zoë M; Schnippel, Kathryn; Sharp, Alana

2016-01-01

Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (β1 = -0

In vitro pharmacokinetic/pharmacodynamic models in anti-infective drug development: focus on TB

PubMed Central

Vaddady, Pavan K; Lee, Richard E; Meibohm, Bernd

2011-01-01

For rapid anti-tuberculosis (TB) drug development in vitro pharmacokinetic/pharmacodynamic (PK/PD) models are useful in evaluating the direct interaction between the drug and the bacteria, thereby guiding the selection of candidate compounds and the optimization of their dosing regimens. Utilizing in vivo drug-clearance profiles from animal and/or human studies and simulating them in an in vitro PK/PD model allows the in-depth characterization of antibiotic activity of new and existing antibacterials by generating time–kill data. These data capture the dynamic interplay between mycobacterial growth and changing drug concentration as encountered during prolonged drug therapy. This review focuses on important PK/PD parameters relevant to anti-TB drug development, provides an overview of in vitro PK/PD models used to evaluate the efficacy of agents against mycobacteria and discusses the related mathematical modeling approaches of time–kill data. Overall, it provides an introduction to in vitro PK/PD models and their application as critical tools in evaluating anti-TB drugs. PMID:21359155

The impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009–2011)

PubMed Central

Kaplan, Richard; Caldwell, Judy; Middelkoop, Keren; Bekker, Linda-Gail; MMed, Robin Wood

2014-01-01

Objective To identify determinants of TB case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. Methods Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients ≥15 yrs. Multivariable Cox proportional hazard models were used to determine risk factors for TB case fatality in these patients. Results In 2009, 2010 and 2011, 25,841, 26,104 and 25,554 newly registered adult TB patients were treated in primary health care clinics in Cape Town, of whom 49.7%, 50.4% and 50.9% were HIV-positive. ART uptake increased over the three years from 43% to 64.9% and case fatality of the HIV-positive patients decreased from 7.0% to 5.8% (p<0.001). Female gender, increasing age, retreatment TB, low CD4 counts and extrapulmonary TB (EPTB) were associated with increased case fatality while patients on ART had a substantial decrease in case fatality. The difference in case fatality between patients on ART and not on ART was most pronounced at low CD4 counts with the positive influence of ART noted up to a CD4 count threshold of 350 cells/mm3 (p<0.001). Despite improvements in ART uptake, in 2011, 21% of patients with CD4 counts <350 cells/mm3 did not start ART during TB treatment. Conclusion This study showed a relatively poor uptake of ART among severely immune-compromised TB patients. Patients with CD4 counts <350 cells/mm3 were shown to clearly benefit from ART during TB treatment and ART initiation should be prioritised for this category of patients. PMID:24820105

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

The prevalence and determinants of active tuberculosis among diabetes patients in Cape Town, South Africa, a high HIV/TB burden setting.

PubMed

Berkowitz, Natacha; Okorie, Adaeze; Goliath, Rene; Levitt, Naomi; Wilkinson, Robert J; Oni, Tolu

2018-04-01

Studies addressing the association between diabetes mellitus (DM) and tuberculosis (TB) in sub-Saharan Africa are limited. We assessed the prevalence of active TB among DM patients at a primary care clinic, and identified risk factors for prevalent TB. A cross-sectional study was conducted in adult DM patients attending a clinic in Khayelitsha, Cape Town. Participants were screened for active TB (symptom screening and microbiological diagnosis) and HIV. Among 440 DM patients screened, the active TB prevalence was 3.0% (95% CI 1.72-5.03). Of the 13 prevalent TB cases, 53.9% (n = 7; 95% CI 27.20-78.50) had no TB symptoms, and 61.5% (n = 8; 95% CI 33.30-83.70) were HIV-1 co-infected. There were no significant differences in either fasting plasma glucose or HbA 1c levels between TB and non-TB participants. On multivariate analysis, HIV-1 infection (OR 11.3, 95% CI 3.26-39.42) and hemoptysis (OR 31.4, 95% CI 3.62-273.35) were strongly associated with prevalent active TB, with no differences in this association by age or gender. The prevalence of active TB among DM patients was 4-fold higher than the national prevalence; suggesting the need for active TB screening, particularly if hemoptysis is reported. Our results highlight the importance of HIV screening in this older population group. The high prevalence of sub-clinical TB among those diagnosed with TB highlights the need for further research to determine how best to screen for active TB in high-risk TB/HIV population groups and settings. Copyright © 2018. Published by Elsevier B.V.

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.

Factors associated with tuberculosis treatment default among HIV-infected tuberculosis patients in Thailand.

PubMed

Kittikraisak, Wanitchaya; Burapat, Channawong; Kaewsa-ard, Samroui; Watthanaamornkiet, Wanpen; Sirinak, Chawin; Sattayawuthipong, Wanchai; Jittimanee, Suksont; Pobkeeree, Vallerut; Varma, Jay K

2009-01-01

Ensuring completion of tuberculosis (TB) treatment remains a major public health problem. In HIV-infected patients, TB is the most common severe opportunistic infection. Few studies have evaluated risk factors for TB treatment default in HIV-infected patients. We conducted a prospective, observational study of HIV-infected TB patients in Thailand. Patients underwent standardised evaluations at the beginning of TB treatment, at the end of the intensive phase and at the end of TB treatment. TB treatment outcomes were assessed according to WHO guidelines. The analysis was limited to patients who defaulted or who had treatment success. Of the 554 patients analysed, 61 (11%) defaulted. In multivariate analysis, factors associated with TB treatment default included incarceration history [adjusted odds ratio (AOR) 2.0, 95% CI 1.1-3.7), smoking (AOR 2.3, 95% CI 1.3-4.1) and having a symptom complaint score >15 (AOR 3.4, 95% CI 1.4-8.0); one marker of wealth, namely owning a refrigerator, was protective (AOR 0.4, 95% CI 0.2-0.8). Default during TB treatment was a significant problem in HIV-infected patients. Reducing default may require enhancing services for patients with a history of incarceration or smoking and designing patient-centred systems to address poverty and patient wellness.

Role of routine abdominal ultrasonography in intensified tuberculosis case finding algorithms at HIV clinics in high TB burden settings.

PubMed

Spalgais, Sonam; Agarwal, Upasna; Sarin, Rohit; Chauhan, Devesh; Yadav, Anita; Jaiswal, Anand

2017-05-18

High proportion of TB in people living with HIV (PLHIV) is undiagnosed. Due to this active TB case finding is recommended for HIV clinics in high TB burden countries. Presently sputum examination and chest radiography are frontline tests recommended for HIV infected TB presumptives. Abdominal TB which occurs frequently in PLHIV may be missed even by existing programmatic intensified case finding protocols. This study evaluated the routine use of ultrasonography (USG) for active case finding of abdominal TB in HIV clinics. Retrospective analysis of eight years' data from an HIV Clinic in a TB hospital in India. Patients underwent chest x-ray, sputum examination, USG abdomen and routine blood tests at entry to HIV care. Case forms were scrutinized for diagnosis of TB, USG findings and CD4 cell counts. Abdominal TB was classified as probable or possible TB. Probable TB was based on presence of two major USG (abdomen) findings suggestive of active TB, or one major USG finding with at least two minor USG findings or at least two symptoms, or any USG finding with microbiologically confirmed active TB at another site. Possible TB was based on the presence of one major USG finding, or the presence of two minor USG findings with at least two symptoms. Bacteriological confirmation was not obtained. Eight hundred and eighty-nine people PLHIV underwent a baseline USG abdomen. One hundred and thirteen of 340 cases already diagnosed with TB and 87 of the 91 newly diagnosed with TB at time of HIV clinic registration had abdominal TB. Non-abdominal symptoms like weight loss, fever and cough were seen in 53% and 22% cases had no symptoms at all. Enlarged abdominal lymph nodes with central caseation, ascitis, splenic microabsesses, bowel thickening and hepatosplenomegaly were the USG findings in these cases. Abdominal TB is a frequent TB site in PLHIV presenting with non-abdominal symptoms. It can be easily detected on basis of features seen on a simple abdominal ultrasound

Associations between Mycobacterium paratuberculosis sero-status, milk quality parameters, and reproduction in dairy cows.

PubMed

Pesqueira, María N; Factor, Camino; Mato, Ivan; Sanjuán, María L; Macias, Laura; Eiras, Carmen; Arnaiz, Ignacio; Camino, Fernando; Yus, Eduardo; Diéguez, Francisco J

2015-01-01

The objective of this study was to investigate the influence of Mycobocterium avium subsp. paratuberculosis (MAP) sero-status of dairy cows on different milk production variables and reproductive traits. The study was carried out on 40 herds from the region of Galicia (North-West Spain). These herds were randomly selected from a larger group that had taken part in a voluntary paratuberculosis control program since 2005, which involves regular serum sampling of every adult animal to run antibody-ELISA tests. Milk production and reproductive data were obtained from the "Dairy Herd Improvement Program (DHIP) of Galicia". All the gathered data were processed following a linear regression model. Results indicated that there was no significant effect of MAP sero-status on individual milk production variables. However, a significant difference was observed at the calving-to-first-insemination interval, with an average increase of 14 days in positive animals compared to negatives. It has to be taken into consideration that the paratuberculosis status was only defined by the serological status. Since para tb-infected animals may have antbodies or may not, para tb-positive animals can also be included in the sero-negative group of animals, which may bias the results.

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.

[Riddles in human tuberculous infection].

PubMed

Tsuyuguchi, I

2000-10-01

Tuberculosis is indeed an infectious disease caused by Mycobacterium tuberculosis. However, only a small percentage of individuals infected develops overt disease, tuberculosis whereas the infected bacilli persist alive years long within the vast majority of persons infected but remained healthy. There are several riddles or enigmas in the natural history of M. tuberculosis infection in humans. Some of them are as follows: 1. What is the virulence of M. tuberculosis? 2. How does M. tuberculosis persist dormant within the host? 3. What determines the development of disease from remaining healthy after infection with M. tuberculosis? 4. What is the mechanism of "endogenous reactivation" of dormant M. tuberculosis within the host? 5. Can we expect more potent anti-TB vaccine than BCG in near future? Most of these issues cited above remain unsolved. What is urgently needed today to answer correctly to these questions is the production of appropriate animal model of tuberculosis infection which mimics human tuberculosis. Murine TB does not reflect human TB at all. What characterizes the mycobacterial organism is its armour-plated unique cell wall structure which is rich in lipid and carbohydrate. Cord factor or trehalose dimycolate (TDM), the main component of cell wall, has once been regarded as the virulence factor of mycobacteria. Cord factor is responsible for the pathogenesis of TB and cachexia or even death of the patients infected. However, cord factor in itself is not toxic but exerts its detrimental effect to the host through the excessive stimulation of the host's immune system to produce abundant varied cytokines including TNF-alpha. How to evade this embarrassing effect of mycobacterial cell wall component on the host immune system seems very important for the future development of better TB vaccine than the currently used BCG.

Increased mortality associated with treated active tuberculosis in HIV-infected adults in Tanzania

PubMed Central

Kabali, Conrad; Mtei, Lillian; Brooks, Daniel R.; Waddell, Richard; Bakari, Muhammad; Matee, Mecky; Arbeit, Robert D.; Pallangyo, Kisali; von Reyn, C. Fordham; Horsburgh, C. Robert

2013-01-01

SUMMARY Active tuberculosis (TB) among HIV-infected patients, even when successfully treated, may be associated with excess mortality. We conducted a prospective cohort study nested in a randomized TB vaccine trial to compare mortality between HIV-infected patients diagnosed and treated for TB (TB, n=77) and HIV-infected patients within the same CD4 range, who were not diagnosed with or treated for active TB (non-TB, n=308) in the period 2001–2008. Only twenty four subjects (6%) were on antiretroviral therapy at the beginning of this study. After accounting for covariate effects including use of antiretroviral therapy, isoniazid preventive therapy, and receipt of vaccine, we found a four-fold increase in mortality in TB patients compared with non-TB patients (adjusted Hazard Ratio 4.61; 95% Confidence Interval (CI): 1.63, 13.05). These findings suggest that treatment for TB alone is not sufficient to avert the excess mortality associated with HIV-related TB and that prevention of TB may provide a mortality benefit. PMID:23523641

Depressive symptoms and hazardous/harmful alcohol use are prevalent and correlate with stigma among TB-HIV patients in Lesotho.

PubMed

Hayes-Larson, E; Hirsch-Moverman, Y; Saito, S; Frederix, K; Pitt, B; Maama-Maime, L; Howard, A A

2017-11-01

Limited data exist on the prevalence and correlates, including stigma, of mental health conditions, including depressive symptoms and alcohol use, among patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) in sub-Saharan Africa, despite their negative impact on health outcomes. To assess the prevalence and correlates of depressive symptoms and hazardous/harmful alcohol use among TB-HIV patients in the Start TB patients on ART and Retain on Treatment (START) study. START, a mixed-methods cluster-randomized trial, evaluated a combination intervention package vs. standard of care (SOC) to improve treatment outcomes in TB-HIV co-infected patients in Lesotho. Moderate/severe depressive symptoms and hazardous/harmful alcohol use were measured using baseline questionnaire data collected from April 2013 to March 2015. Demographic, psychosocial, and TB- and HIV-related knowledge and attitudes, including stigma, were assessed for association with both conditions using generalized linear mixed models. Among 371 participants, 29.8% reported moderate/severe depressive symptoms, and 24.7% reported hazardous/harmful alcohol use; 7% reported both. Depressive symptoms were significantly associated with less education, more difficulty understanding written medical information, non-disclosure of TB, greater TB stigma, and the SOC study arm. Hazardous/harmful alcohol use was significantly associated with male sex, as well as greater TB and external HIV stigma. Prevalence of depressive symptoms and hazardous/harmful alcohol use were high, suggesting a need for routine screening for, and treatment of, mental health disorders in TB-HIV patients.

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.

A case of Manila type Mycobacterium tuberculosis infection in Japan

PubMed Central

Usami, Osamu; Nakajima, Chie; Endo, Shiro; Inomata, Shinya; Kanamori, Hajime; Hirakata, Yoichi; Uchiyama, Bine; Kaku, Mitsuo; Suzuki, Yasuhiko; Hattori, Toshio

2015-01-01

Key Clinical Message A 76-year-old Japanese woman contracted a Mycobacterium tuberculosis (TB, Manila type) infection in Japan, despite never having traveled. However, her son was treated for TB in the Philippines 3 years before he stayed at her house. Spoligotyping allows us to identify the TB genotype and identify the route of infection. PMID:26273455

Tuberculosis Facts - Exposure to TB

MedlinePlus

Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

Tuberculosis Facts - Testing for TB

MedlinePlus

Tuberculosis (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

Comparison of TB-LAMP, GeneXpert MTB/RIF and culture for diagnosis of pulmonary tuberculosis in The Gambia.

PubMed

Bojang, Adama L; Mendy, Francis S; Tientcheu, Leopold D; Otu, Jacob; Antonio, Martin; Kampmann, Beate; Agbla, Schadrac; Sutherland, Jayne S

2016-03-01

Diagnosis of tuberculosis (TB) remains difficult, particularly in resource-limited settings. The development of nucleic acid-based tests for detection of Mycobacterium tuberculosis complex (MTBC) has significantly increased sensitivity compared to conventional smear microscopy and provides results within a matter of hours compared to weeks for the current gold-standard, liquid culture. In this study we performed side-by-side comparison of mycobacterial detection assays on sputum samples from 285 subjects presenting with symptoms suggestive of TB in The Gambia and a cross-sectional cohort of 156 confirmed TB patients with a median of 2 months of treatment. A novel assay, Loop-Mediated Amplification test for TB (TB-LAMP), was compared to smear microscopy, MGIT culture and GeneXpert MTB/RIF for all samples. When culture was used as the reference standard, we found an overall sensitivity for TB-LAMP of 99% (95% CI: 94.5-99.8) and specificity of 94% (95% CI: 89.3-96.7). When latent class analysis was performed, TB-LAMP had 98.6% (95% CI: 95.9-100) sensitivity and 99% (95% CI: 98.2-100) specificity compared to 91.1% (95% CI: 86.1-96) sensitivity and 100% (95% CI: 98.2-100) specificity for MGIT culture. GeneXpert had the highest sensitivity 99.1% (95% CI: 97.1-100) but the lowest specificity 96% (95% CI: 92.6-98.3). Both TB-LAMP and GeneXpert showed high sensitivity and specificity regardless of age or strain of infection. Our findings show the diagnostic utility of both GeneXpert and TB-LAMP in The Gambia. Whilst TB-LAMP requires less infrastructure, it is unable to detect drug-resistant patterns and therefore would be most suitable as a screening test for new TB cases in peripheral health clinics. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011.

PubMed

Izumi, Kiyohiko; Ohkado, Akihiro; Uchimura, Kazuhiro; Murase, Yoshiro; Tatsumi, Yuriko; Kayebeta, Aya; Watanabe, Yu; Ishikawa, Nobukatsu

2015-01-01

Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of "activity space", a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots. Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran's I and Getis-Ord Gi* statistics) identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients' characteristics in these hotspots were assessed. Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2%) were general inhabitants, 42 (6.5%) were foreign-born people, and 184 were homeless people (28.6%). The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households. Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further comprehension of TB transmission dynamics in an

Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?

PubMed

Scordo, Julia M; Knoell, Daren L; Torrelles, Jordi B

2016-01-01

Tuberculosis (TB) is a disease that kills one person every 18 s. TB remains a global threat due to the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following seroconversion, and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure, which influence the extent of infection. We further discuss how the M.tb-alveolar epithelium interaction instigates cell-to-cell crosstalk that regulates the immune balance between a proinflammatory and an immunoregulatory state, thereby prohibiting or allowing the establishment of infection. We propose that consideration of alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. © 2015 S. Karger AG, Basel.

Alveolar epithelial cells in Mycobacterium tuberculosis infection: Active Players or Innocent Bystanders

PubMed Central

Scordo, Julia M.; Knoell, Daren L.; Torrelles, Jordi B.

2015-01-01

Tuberculosis (TB) is a disease that kills one person every 18 seconds. TB remains a global threat due to the emergence of drug resistance Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following sero-conversion and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure that influence the extent of infection. We further discuss how the M.tb-alveolar epithelia interaction instigate cell to cell crosstalk that regulates immune balance between a pro-inflammatory or immunoregulatory state thereby prohibiting or allowing the establishment of infection. We propose that consideration of the alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. PMID:26384325

Impact of Euro-American sublineages of Mycobacterium tuberculosis on new infections among named contacts.

PubMed

Feng, J-Y; Jarlsberg, L G; Rose, J; Grinsdale, J A; Janes, M; Higashi, J; Osmond, D H; Nahid, P; Hopewell, P C; Kato-Maeda, M

2017-05-01

The impact of demographic, clinical, and bacterial factors on new infection by Euro-American lineage Mycobacterium tuberculosis among contacts of patients with tuberculosis (TB) has not been evaluated. To describe the risk factors for new infection by Euro-American M. tuberculosis sublineages in San Francisco, California. We included contacts of patients with TB due to Euro-American M. tuberculosis. Sublineages were determined by large-sequence polymorphisms. We used tuberculin skin testing or QuantiFERON®-TB Gold In-Tube to identify contacts with new infection. Regression models with generalized estimating equations were used to determine the risk factors for new infection. We included 1488 contacts from 134 patients with TB. There were 79 (5.3%) contacts with new infection. In adjusted analyses, contacts of patients with TB due to region of difference 219 M. tuberculosis sublineage were less likely to have new infection (OR 0.23, 95%CI 0.06-0.84) than those with other sublineages. Other risk factors for new infection were contacts exposed to more than one patient with TB, contacts exposed for 30 days, or contacts with a history of smoking or excessive alcohol consumption. In addition to well-known exposure and clinical characteristics, bacterial characteristics independently contribute to the transmissibility of TB in San Francisco.

TB in healthcare workers in the UK: a cohort analysis 2009-2013.

PubMed

Davidson, Jennifer A; Lalor, Maeve K; Anderson, Laura F; Tamne, Surinder; Abubakar, Ibrahim; Thomas, H Lucy

2017-07-01

To describe the burden of TB in healthcare workers (HCWs) in the UK and determine whether HCWs are at increased risk of TB due to occupational exposure. Retrospective cohort analysis of national UK TB surveillance and genotyping data between 2009 and 2013. The rate of TB in HCWs compared with non-HCWs to calculate incidence rate ratios stratified by country of birth. 2320 cases of TB in HCWs were notified in the study period, 85% were born abroad. The TB rate in HCWs was 23.4 (95% CI 22.5 to 24.4) per 100 000 compared with 16.2 (95% CI 16.0 to 16.3) per 100 000 in non-HCWs. After stratifying by country of birth, there was not an increased TB incidence in HCWs for the majority of countries of birth, including in the UK-born. Using combined genotyping and epidemiological data, only 10 confirmed nosocomial transmission events involving HCWs were identified between 2010 and 2012. Of these, only two involved transmission to patients. The lack of an increased risk of TB after stratifying by country of birth, and the very few transmission events involving nosocomial transmission in the UK suggests that TB in HCWs in the UK is not generally acquired through UK occupational exposure. The majority of cases in foreign-born HCWs are likely to result from reactivation of latent TB infection (LTBI) acquired abroad, and is not likely to be prevented by BCG vaccination in the UK. Testing and treatment of LTBI in HCWs with exposure to high TB burden countries should be the focus of occupational health prevention activities. 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/.

Detection of circulating Mycobacterium tuberculosis-specific DNA by droplet digital PCR for vaccine evaluation in challenged monkeys and TB diagnosis.

PubMed

Song, Neng; Tan, Yang; Zhang, Lingyun; Luo, Wei; Guan, Qing; Yan, Ming-Zhe; Zuo, Ruiqi; Liu, Weixiang; Luo, Feng-Ling; Zhang, Xiao-Lian

2018-04-24

Mycobacterium tuberculosis (M. tb) is emerging as a more serious pathogen due to the increased multidrug-resistant TB and co-infection of human immunodeficiency virus (HIV). The development of an effective and sensitive detection method is urgently needed for bacterial load evaluation in vaccine development, early TB diagnosis, and TB treatment. Droplet digital polymerase chain reaction (ddPCR) is a newly developed sensitive PCR method for the absolute quantification of nucleic acid concentrations. Here, we used ddPCR to quantify the circulating virulent M. tb-specific CFP10 (10-kDa culture filtrate protein, Rv3874) and Rv1768 DNA copy numbers in the blood samples from Bacille Calmette-Guerin (BCG)-vaccinated and/or virulent M. tb H37Rv-challenged rhesus monkeys. We found that ddPCR was more sensitive compared to real-time fluorescence quantitative PCR (qPCR), as the detection limits of CFP10 were 1.2 copies/μl for ddPCR, but 15.8 copies/μl for qPCR. We demonstrated that ddPCR could detect CFP10 and Rv1768 DNA after 3 weeks of infection and at least two weeks earlier than qPCR in M.tb H37Rv-challenged rhesus monkey models. DdPCR could also successfully quantify CFP10 and Rv1768 DNA copy numbers in clinical TB patients' blood samples (active pulmonary TB, extrapulmonary TB (EPTB), and infant TB). To our knowledge, this study is the first to demonstrate that ddPCR is an effective and sensitive method of measuring the circulating CFP10 and Rv1768 DNA for vaccine development, bacterial load evaluation in vivo, and early TB (including EPTB and infant TB) diagnosis as well.

Tuberculosis incidence in a cohort of individuals infected with human T-lymphotropic virus type 1 (HTLV-1) in Salvador, Brazil.

PubMed

Grassi, Maria Fernanda Rios; Dos Santos, Normeide Pedreira; Lírio, Monique; Kritski, Afrânio Lineu; Chagas Almeida, Maria da Conceição; Santana, Leonardo Pereira; Lázaro, Noilson; Dias, Juarez; Netto, Eduardo Martins; Galvão-Castro, Bernardo

2016-09-19

Few reports have investigated the association between human T-lymphotropic virus type 1 (HTLV-1) and tuberculosis (TB) in countries where both infections are endemic. This study estimates the incidence of TB in a cohort infected with HTLV-1, compared with non-infected individuals, over a ten-year period. Retrospective cohort study involving the cross-matching of records of individuals for whom a HTLV serology was performed at a referral center for HTLV (CHTLV) with a database of TB cases from Sinan-the Information System on Diseases of Compulsory Declaration between 2002 and 2012. From a cohort of 6,495 individuals, 1,711 were infected with HTLV-1. A total of 73 TB cases occurred during the study period: 33 HTLV-1-infected patients and 40 uninfected individuals. The incidence density for TB in the HTLV-1 infected group was 3.3 person-years per 1,000 individuals and 1.1 person-years per 1,000 individuals in the group HTLV-1 uninfected group. The relative risk of developing TB in the group of patients infected with HTLV-1 was 2.6 (CI 95 % 1.6-4.2) in comparison with HTLV-1 uninfected group. Compared to individuals with isolated TB, those in the HTLV-1 infected group who had TB were older (p = 0.005) and had lower education levels (p = 0.02). No differences were observed with respect to the clinical/radiological presentation, nor in the outcome of TB and prevalence of HIV infection, when comparing among the HTLV-1-infected and uninfected groups. Patients infected with HTLV-1 are more susceptible to TB. The epidemiological characteristics of HTLV-1/TB subjects and those infected with TB overlap.

Usefulness of Chinese Herbal Medicines as Host-Directed Therapeutics against Mycobacterial Infections: A Review.

PubMed

Tomioka, Haruaki

2017-01-01

The high incidence of tuberculosis (TB) in developing countries, the resurgence of TB in industrialized countries, and the worldwide increase in the prevalence of Mycobacterium avium complex infections have prompted the quest for new antimycobacterial drugs. However, the development of such chemotherapeutics is currently making very slow progress. It therefore appears that devising improved administration protocols for clinical treatment against intractable mycobacteriosis using existing chemotherapeutics is more practical than awaiting the development of novel antimycobacterial drugs. The modulation of host immune responses using immunoadjunctive agents may increase the efficacy of antimicrobial treatment against mycobacteriosis. Particularly, the mild and long-term up-regulation of host immune reactions against mycobacterial pathogens using Chinese herbal medicines (CHMs) may be beneficial for immunoadjunctive therapy. This review focuses on the current status and future prospects regarding the development of CHMs that can be useful for the clinical control of intractable mycobacterial infections.

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

PubMed

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

2018-03-01

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

Adverse events and treatment interruption in tuberculosis patients with and without HIV co‐infection

PubMed Central

Breen, R A M; Miller, R F; Gorsuch, T; Smith, C J; Schwenk, A; Holmes, W; Ballinger, J; Swaden, L; Johnson, M A; Cropley, I; Lipman, M C I

2006-01-01

Background Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co‐infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti‐TB treatment in the era of effective antiretroviral therapy. Methods The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co‐infected with HIV. Results 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti‐TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co‐infected patients (p<0.001; p = 0.006), although all cause interruption of anti‐TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re‐treatment. Conclusion Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti‐TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals. PMID:16844730

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.

Tuberculosis Facts - TB Can Be Treated

MedlinePlus

Tuberculosis (TB) Facts TB Can Be Treated What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination Page 1 of 2 TB Facts: TB ...

Tuberculosis Facts - You Can Prevent TB

MedlinePlus

Tuberculosis (TB) Facts You Can Prevent TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination TB Facts: You Can Prevent TB What ...

Tuberculosis 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.

Application of a whole blood mycobacterial growth inhibition assay to study immunity against Mycobacterium tuberculosis in a high tuberculosis burden population

PubMed Central

Smit, Erica; Erasmus, Mzwandile; Day, Jonathan; Makhethe, Lebohang; de Kock, Marwou; Hughes, E. Jane; van Rooyen, Michele; Stone, Lynnett; Hanekom, Willem; Brennan, Michael J.; Wallis, Robert S.; Hatherill, Mark; Scriba, Thomas J.

2017-01-01

The determinants of immunological protection against Mycobacterium tuberculosis (M.tb) infection in humans are not known. Mycobacterial growth inhibition assays have potential utility as in vitro surrogates of in vivo immunological control of M.tb. We evaluated a whole blood growth inhibition assay in a setting with high burden of TB and aimed to identify immune responses that correlate with control of mycobacterial growth. We hypothesized that individuals with underlying M.tb infection will exhibit greater M.tb growth inhibition than uninfected individuals and that children aged 4 to 12 years, an age during which TB incidence is curiously low, will also exhibit greater M.tb growth inhibition than adolescents or adults. Neither M.tb infection status, age of the study participants, nor M.tb strain was associated with differential control of mycobacterial growth. Abundance and function of innate or T cell responses were also not associated with mycobacterial growth. Our data suggest that this assay does not provide a useful measure of age-associated differential host control of M.tb infection in a high TB burden setting. We propose that universally high levels of mycobacterial sensitization (through environmental non-tuberculous mycobacteria and/or universal BCG vaccination) in persons from high TB burden settings may impart broad inhibition of mycobacterial growth, irrespective of M.tb infection status. This sensitization may mask the augmentative effects of mycobacterial sensitization on M.tb growth inhibition that is typical in low burden settings. PMID:28886145

Developing a point-of-care electronic medical record system for TB/HIV co-infected patients: experiences from Lighthouse Trust, Lilongwe, Malawi.

PubMed

Tweya, Hannock; Feldacker, Caryl; Gadabu, Oliver Jintha; Ng'ambi, Wingston; Mumba, Soyapi L; Phiri, Dave; Kamvazina, Luke; Mwakilama, Shawo; Kanyerere, Henry; Keiser, Olivia; Mwafilaso, Johnbosco; Kamba, Chancy; Egger, Matthias; Jahn, Andreas; Simwaka, Bertha; Phiri, Sam

2016-03-05

Implementation of user-friendly, real-time, electronic medical records for patient management may lead to improved adherence to clinical guidelines and improved quality of patient care. We detail the systematic, iterative process that implementation partners, Lighthouse clinic and Baobab Health Trust, employed to develop and implement a point-of-care electronic medical records system in an integrated, public clinic in Malawi that serves HIV-infected and tuberculosis (TB) patients. Baobab Health Trust, the system developers, conducted a series of technical and clinical meetings with Lighthouse and Ministry of Health to determine specifications. Multiple pre-testing sessions assessed patient flow, question clarity, information sequencing, and verified compliance to national guidelines. Final components of the TB/HIV electronic medical records system include: patient demographics; anthropometric measurements; laboratory samples and results; HIV testing; WHO clinical staging; TB diagnosis; family planning; clinical review; and drug dispensing. Our experience suggests that an electronic medical records system can improve patient management, enhance integration of TB/HIV services, and improve provider decision-making. However, despite sufficient funding and motivation, several challenges delayed system launch including: expansion of system components to include of HIV testing and counseling services; changes in the national antiretroviral treatment guidelines that required system revision; and low confidence to use the system among new healthcare workers. To ensure a more robust and agile system that met all stakeholder and user needs, our electronic medical records launch was delayed more than a year. Open communication with stakeholders, careful consideration of ongoing provider input, and a well-functioning, backup, paper-based TB registry helped ensure successful implementation and sustainability of the system. Additional, on-site, technical support provided

Polyclonal Pulmonary Tuberculosis Infections and Risk for Multidrug Resistance, Lima, Peru

PubMed Central

Shi, Cynthia X.; Chindelevitch, Leonid; Calderon, Roger; Zhang, Zibiao; Galea, Jerome T.; Contreras, Carmen; Yataco, Rosa; Lecca, Leonid; Becerra, Mercedes C.; Murray, Megan B.; Cohen, Ted

2017-01-01

Because within-host Mycobacterium tuberculosis diversity complicates diagnosis and treatment of tuberculosis (TB), we measured diversity prevalence and associated factors among 3,098 pulmonary TB patients in Lima, Peru. The 161 patients with polyclonal infection were more likely than the 115 with clonal or the 2,822 with simple infections to have multidrug-resistant TB. PMID:29048297

Advocacy, partnership and political commitment for TB vaccine research.

PubMed

Olesen, Ole F; Chan, Sharon; Chappell, Janice; Guo, Yan; Leite, Luciana C C

2016-08-01

The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Advancing the Pipeline: A Vision for the Next Decade, Engaging the BRICS: Basic Research to Manufacturing, and Regulatory and Access Issues for New TB Vaccines. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30]. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Influence of helminth infections on childhood nutritional status in lowland Bolivia.

PubMed

Tanner, S; Leonard, W R; McDade, T W; Reyes-Garcia, V; Godoy, R; Huanca, T

2009-01-01

Infectious disease, such as diarrheal disease, respiratory infections, and parasitic infections, are an important source of nutritional and energetic stress in many populations. Inspired by the research and methodological innovations of A. Roberto Frisancho, this work considers the impact of childhood environment and local disease ecology on child health and nutritional patterns among an indigenous group in lowland Bolivia. Specifically, we examine the association between soil-transmitted helminth infection, especially hookworm species, and anthropometric markers of short- and long-term nutritional status. Fecal samples, anthropometric dimensions, and health interviews were collected for 92 children ranging in age from 2.0 to 10.9 years. Microscopic examination revealed high levels of parasitic infection, with 76% of children positive for hookworm species infections (77% of girls and 74% of boys). Less common infections included Ascaris lumbricoides, Trichurius trichiura, and Strongyloides stercoralis with only 15% of children positive for multiple-species infections. After adjusting for sex and age, no statistically significant associations were observed between helminth infections and the frequency of reported illness or anthropometric measures of nutritional status. These data demonstrate the difficulty of assessing nutritional impacts of endemic infections.

Farm-level risk factors for the occurrence, new infection or persistence of tuberculosis in cattle herds from South-Central Spain.

PubMed

Martínez-López, B; Barasona, J A; Gortázar, C; Rodríguez-Prieto, V; Sánchez-Vizcaíno, J M; Vicente, J

2014-10-01

Eradication of tuberculosis (TB) in cattle is a priority in the EU. However, and despite the resources invested, TB eradication is still a goal yet to be accomplished. As a consequence, the identification of risk factors contributing to TB transmission and persistence is key to a better understand and, ultimately, more cost-effectively control and eradicate this complex zoonotic disease worldwide. This study aimed to identify the factors contributing to the TB occurrence, new infection, and persistence in one of the most TB-prevalent regions in the South-Central part of Spain (SCS), Ciudad Real (CR), and for which high quality and detailed information on cattle and wild ungulate demographics, management, and sanitary status was available for up to 5 years (2007-2011). Multilevel logistic modeling was used for this purpose. Results of this study revealed that the risk for TB (occurrence, new infection, and/or persistence) in cattle herds from CR is related to TB-persistence on farm in previous years, extensive production systems (beef and bullfighting being more risky that dairy) and large farm in terms of cattle number. Also, the presence and proximity of fenced hunting estates (which are usually intensively managed) significantly contributed to the risk of TB occurrence and persistence in CR. This association suggests that wild ungulates may play a role as TB-reservoirs and transmit TB to cattle in the CR, a region where TB is endemic and is associated with extensive farming of beef cattle. To the best of author's knowledge this is the first study to (i) evaluate the wild ungulate-domestic interface at a farm level using detailed information over an extensive region and period of time (2007-2011) and (ii) to identify a direct association between TB in cattle and the proximity and management practices of wild ungulates. Methods and results presented here may support policies to better prevent and control TB in the SCS and in other regions/countries with similar

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.

Stratification by interferon-γ release assay level predicts risk of incident TB.

PubMed

Winje, Brita Askeland; White, Richard; Syre, Heidi; Skutlaberg, Dag Harald; Oftung, Fredrik; Mengshoel, Anne Torunn; Blix, Hege Salvesen; Brantsæter, Arne Broch; Holter, Ellen Kristine; Handal, Nina; Simonsen, Gunnar Skov; Afset, Jan Egil; Bakken Kran, Anne Marte

2018-04-05

Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Thai health education program for improving TB migrant's compliance.

PubMed

Khortwong, Pornsak; Kaewkungwal, Jaranit

2013-03-01

Investigate the effectiveness of health education programs by using the PRECEDE-PROCEED Model to improve non-Thai migrant TB patient's compliance during treatment. This quasi-intervention study was conducted in three targeted hospitals, between August 2009 and December 2010. The study sample consisted of 100 cases, 50 cases who registered in Samutsakorn Province served as the intervention group and 50 cases who registered in Samutprakarn Province served as the control group. At the end of the health education intervention, the intervention group showedsignificantly improved health-behavior scores in nine domains-health promotion, health education, predisposing, reinforcing, enabling factors, behavior and lifestyle, environment, and health status, which were also significantly higher than the control group (p < 0.001). The percentage of patients achieving successful treatment outcomes was 76% in the intervention group and 62% in the control group. The tuberculosis treatment and care program, and the associated health education interventions enabled migrants to complete the treatment regimen and achieve treatment success. It could also help TB staff develop an appropriate program and clear understanding of TB control among migrants. It is recommended that this type of information and health education program be used in other hospitals and healthcare settings providing TB services for migrants throughout the nation.

Spatial and temporal analyses of metrics of tuberculosis infection in badgers (Meles meles) from the Republic of Ireland: Trends in apparent prevalence.

PubMed

Byrne, A W; Kenny, K; Fogarty, U; O'Keeffe, J J; More, S J; McGrath, G; Teeling, M; Martin, S W; Dohoo, I R

2015-12-01

Badgers are a wildlife host of Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), and an important contributor to the epidemiology of bTB in cattle in Ireland and Britain. Repeated culling of badgers in high prevalence cattle bTB areas has been used in the Republic of Ireland as one tool to reduce intra- and interspecific transmission of M. bovis. We assessed factors that influenced infection prevalence of culled badgers from 2009 to 2012 (n=4948) where spatial, temporal and intrinsic factor data were available using multivariable modelling. Prevalence appeared higher in western areas than eastern areas of Ireland and badgers were more likely to be test-positive if caught at a sett (burrow system) which was close to other infected setts (spatial clustering of infection). There was a significant positive association between badger test-status and cattle prevalence of M. bovis infection at a spatial scale of 1km around setts. Badgers were more likely to be deemed test positive if they were male (OR: 1.9) or a parous female (OR: 1.7), compared to a female who had never conceived. Our results are consistent with different groups within badger populations having differential exposures and therefore infection risk (for example, parous vs. non-parous females). Furthermore, bTB clusters within the badger population, with greater risk to badgers in setts that are closest to other infected setts. The effective scale of the association of bTB risk between badger and cattle populations may be relatively large in Ireland. Our data indicate that the overall trend in prevalence of M. bovis infection in badgers has decreased in Ireland (P<0.001) while controlling for significant confounders over the study period, and follows a longer temporal trend from 2007 to 2013, where unadjusted apparent prevalence declined from 26% to 11% during 2007 to mid-2011, followed by a stable trend between 9 and 11% thereafter (n=10,267). Copyright © 2015 Elsevier B.V. All rights

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 ...

Integrated, Home-based Treatment for MDR-TB and HIV in Rural South Africa: An Alternate Model of Care

PubMed Central

Brust, James C.M.; Shah, N. Sarita; Scott, Michelle; Chaiyachati, Krisda; Lygizos, Melissa; van der Merwe, Theo L.; Bamber, Sheila; Radebe, Zanele; Loveday, Marian; Moll, Anthony P.; Margot, Bruce; Lalloo, Umesh G.; Friedland, Gerald H.; Gandhi, Neel R.

2012-01-01

SUMMARY Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, inpatient treatment programs struggle to cope with rising prevalence and HIV co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. We describe the design and preliminary results of an integrated, home-based MDR-TB/HIV treatment program created in rural KwaZulu-Natal. In 2008, a decentralized center was established to provide outpatient MDR-TB and HIV treatment. Nurses, community health workers, and family supporters have been trained to administer injections, provide adherence support, and monitor adverse reactions in patients’ homes. Physicians assess clinical response, adherence, and adverse reaction severity to MDR-TB and HIV therapy at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. Eighty patients initiated MDR-TB therapy from 2/2008–4/2010; 66 were HIV co-infected. Retention has been high (only 5% defaults, 93% of visits attended) and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%), or died (6%). Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor, and high-HIV prevalent settings. PMID:22668560

Cognitive Performance and Iron Status are Negatively Associated with Hookworm Infection in Cambodian Schoolchildren.

PubMed

Kuong, Khov; Fiorentino, Marion; Perignon, Marlene; Chamnan, Chhoun; Berger, Jacques; Sinuon, Muth; Molyden, Vann; Burja, Kurt; Parker, Megan; Ly, Sou Chheng; Friis, Henrik; Roos, Nanna; Wieringa, Frank T

2016-10-05

Soil-transmitted helminth (STH) infection has been associated with lower cognitive performance of schoolchildren. To identify pathways through which STH infection might affect school performance, baseline data from a large rice-fortification trial in Cambodian schoolchildren were used to investigate associations between STH infection, micronutrient status, anemia, and cognitive performance. Complete data on anthropometry, cognitive performance, and micronutrient status were available for 1,760 schoolchildren, 6-16 years of age. STH infection was identified using Kato-Katz, whereas cognitive performance was assessed using Raven's Colored Progressive Matrices (RCPM), block design, and picture completion. STH infection was found in 18% of the children; almost exclusively hookwork infection. After adjusting for age and gender, raw cognitive test scores were significantly lower in hookworm-infected children (-0.65; -0.78; -2.03 points for picture completion, RCPM, and block design, respectively; P < 0.05 for all). Hookworm infection was associated with iron status (total body iron), but not with vitamin A and zinc status, nor with inflammation or anthropometry. Body iron was negatively associated with increased intensity of hookworm infection (R = 0.22, P < 0.001). Hookworm infection in Cambodian schoolchildren was associated with lower cognitive performance, an effect most likely mediated through lower body iron. Interventions that are more effective against hookworm infection are needed to contribute to better health and improvement of cognitive performance. © The American Society of Tropical Medicine and Hygiene.

Risk factors for latent tuberculosis infection in close contacts of active tuberculosis patients in South Korea: a prospective cohort study.

PubMed

Lee, Seung Jun; Lee, Seung Hun; Kim, You Eun; Cho, Yu Ji; Jeong, Yi Yeong; Kim, Ho Cheol; Lee, Jong Deog; Kim, Jang Rak; Hwang, Young Sil; Kim, Hee Jin; Menzies, Dick

2014-11-18

The diagnosis and treatment of latent tuberculosis infection (LTBI) have become mandatory to reduce the burden of tuberculosis worldwide. Close contacts of active TB patients are at high risk of both active and LTBI. The aim of this study is to identify the predominant risk factors of contracting LTBI, persons in close contact with TB patients were recruited. This study also aimed to compare the efficacy of the tuberculin skin test (TST) and QuantiFERON(®)-TB GOLD (QFT-G) to diagnose LTBI. Close contacts of active pulmonary TB patients visiting a hospital in South Korea were diagnosed for LTBI using TST and/or QFT-G. The association of positive TST and/or QFT-G with the following factors was estimated: age, gender, history of Bacillius Calmette-Guerin (BCG) vaccination, history of pulmonary TB, cohabitation status, the acid-fast bacilli smear status, and presence of cough in source cases. Of 308 subjects, 38.0% (116/305) were TST positive and 28.6% (59/206) were QFT-G positive. TST positivity was significantly associated with male gender (OR: 1.734; 95% CI: 1.001-3.003, p =0.049), history of pulmonary TB (OR: 4.130; 95% CI: 1.441-11.835, p =0.008) and household contact (OR: 2.130; 95% CI: 1.198-3.786, p =0.01) after adjustment for confounding variables. The degree of concordance between TST and QFT-G was fair (70.4%, κ =0.392). A prevalence of LTBI among close contacts of active pulmonary TB patients was high, and prior TB history and being a household contact were risk factors of LTBI in the study population.

HIV and Tuberculosis (TB)

MedlinePlus

... or brain. If not treated, TB disease can cause death. HIV weakens the immune system , increasing the risk ... spine, or brain. If not treated, TB can cause death. How does TB spread from person to person? ...

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

Metronidazole prevents reactivation of latent Mycobacterium tuberculosis infection in macaques

PubMed Central

Lin, Philana Ling; Dartois, Veronique; Johnston, Paul J.; Janssen, Christopher; Via, Laura; Goodwin, Michael B.; Klein, Edwin; Barry, Clifton E.; Flynn, JoAnne L.

2012-01-01

Targeting Mycobacterium tuberculosis bacilli in low-oxygen microenvironments, such as caseous granulomas, has been hypothesized to have the potential to shorten therapy for active tuberculosis (TB) and prevent reactivation of latent infection. We previously reported that upon low-dose M. tuberculosis infection, equal proportions of cynomolgus macaques develop active disease or latent infection and that latently infected animals reactivated upon neutralization of TNF. Using this model we now show that chemoprophylaxis of latently infected cynomolgus macaques with 6 mo of isoniazid (INH) effectively prevented anti-TNF antibody-induced reactivation. Similarly, 2-mo treatment of latent animals with a combination of INH and rifampicin (RIF) was highly effective at preventing reactivation disease in this model. Metronidazole (MTZ), which has activity only against anaerobic, nonreplicating bacteria, was as effective as either of these treatments in preventing reactivation of latent infection. Because hypoxic lesions also occur during active TB, we further showed that addition of MTZ to INH/RIF effectively treated animals with active TB within 2 mo. Healing lesions were associated with distinct changes in cellular pathology, with a shift toward increasingly fibrotic and calcified lesions. Our data in the nonhuman primate model of active and latent TB supports targeting bacteria in hypoxic environments for preventing reactivation of latent infection and possibly shortening the duration of therapy in active TB. PMID:22826237

Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa

PubMed Central

Govindasamy, Darshini; Kranzer, Katharina; van Schaik, Nienke; Noubary, Farzad; Wood, Robin; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.; Bekker, Linda-Gail

2013-01-01

Background HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care. PMID:24236170

Mapping sites of high TB transmission risk: Integrating the shared air and social behaviour of TB cases and adolescents in a South African township.

PubMed

Patterson, Benjamin; Morrow, Carl D; Kohls, Daniel; Deignan, Caroline; Ginsburg, Samuel; Wood, Robin

2017-04-01

Tuberculosis remains a major public health problem in poverty-stricken areas of the world. Communal gathering places account for the majority of TB transmission in high burden settings. To investigate the social behaviour patterns of individuals who have developed TB disease and adolescents at risk of infection. To develop a cheap and effective method to locate transmission hot spots in high burden communities. Portable, combined CO 2 /GIS monitors and location diaries were given to individuals from a South African township. The three groups: newly diagnosed TB patients, recently treated TB patients and adolescents recorded their activities over a median of two days. Rebreathed air volumes (RAVs) at all GIS locations were calculated from CO 2 levels using the Rudnick-Milton variant of the Wells-Riley TB transmission model. Hot spot analysis was performed to determine the communal buildings which correspond to spatially clustered high RAVs. Analysis of diaries found that the adolescent group spent greater time in congregate settings compared with the other two groups driven by time spent in school/work (new TB: 1%, recent TB: 8%, and adolescents: 23%). Adolescents also changed their location more frequently (9.0, 6.0, 14.3 changes per day; p<0.001). The RAVs reflected this divergence between the groups (44, 40, 127l; p<0.001). Communal buildings associated with high RAVs were found to be a clinic, two schools and a library. Hot spot analysis revealed the most intense clustering of high RAVs at a community school. Our study demonstrates a new methodology to uncover TB transmission hot spots using a technique that avoids the need to pre-select locations. Investigation of a South African township highlighted the high risk potential of schools and high risk social behaviour of adolescents. Consequently the targeting of transmission reduction strategies to schools may prove highly efficacious in high burden settings. Copyright © 2017 The Authors. Published by Elsevier B

Prevalence of latent tuberculosis infection and predictive factors in an urban informal settlement in Johannesburg, South Africa: a cross-sectional study.

PubMed

Ncayiyana, Jabulani R; Bassett, Jean; West, Nora; Westreich, Daniel; Musenge, Eustasius; Emch, Michael; Pettifor, Audrey; Hanrahan, Colleen F; Schwartz, Sheree R; Sanne, Ian; van Rie, Annelies

2016-11-08

South Africa has one of the highest burdens of latent tuberculosis infection (LTBI) in high-risk populations such as young children, adolescents, household contacts of TB cases, people living with HIV, gold miners and health care workers, but little is known about the burden of LTBI in its general population. Using a community-based survey with random sampling, we examined the burden of LTBI in an urban township of Johannesburg and investigated factors associated with LTBI. The outcome of LTBI was based on TST positivity, with a TST considered positive if the induration was ≥5 mm in people living with HIV or ≥10 mm in those with unknown or HIV negative status. We used bivariate and multivariable logistic regression to identify factors associated with LTBI RESULTS: The overall prevalence of LTBI was 34.3 (95 % CI 30.0, 38.8 %), the annual risk of infection among children age 0-14 years was 3.1 % (95 % CI 2.1, 5.2). LTBI was not associated with HIV status. In multivariable logistic regression analysis, LTBI was associated with age (OR = 1.03 for every year increase in age, 95 % CI = 1.01-1.05), male gender (OR = 2.70, 95 % CI = 1.55-4.70), marital status (OR = 2.00, 95 % CI = 1.31-3.54), and higher socio-economic status (OR = 2.11, 95 % CI = 1.04-4.31). The prevalence of LTBI and the annual risk of infection with M. tuberculosis is high in urban populations, especially in men, but independent of HIV infection status. This study suggests that LTBI may be associated with higher SES, in contrast to the well-established association between TB disease and poverty.

Poor outcome is associated with delayed tuberculosis diagnosis in HIV-infected children in Baja California, Mexico.

PubMed

Viani, R M; Lopez, G; Chacón-Cruz, E; Hubbard, P; Spector, S A

2008-04-01

To describe the morbidity and mortality associated with tuberculosis (TB) in human immunodeficiency virus (HIV) infected children in Baja California, Mexico. Retrospective review of the medical records of all children with perinatally acquired HIV infection evaluated at Tijuana General Hospital with a diagnosis of TB between 1998 and 2007. The Stegen-Toledo (ST) clinical criteria for the diagnosis of TB were used. A total of 73 HIV-infected children were followed during the study period. Thirteen (18%) children were diagnosed with TB; one was confirmed by culture to be positive. Among these children, the mean ages at HIV and TB diagnosis were respectively 3.6 and 5.3 years. The mean ST score was 8.1; 10/13 had a score of >or=7, or highly probable TB. There were a cumulative 29 hospital admissions prior to TB diagnosis; 24 of these were due to pneumonia. The mean duration of symptoms at TB diagnosis was 73 days. The most common symptoms were cough (92%) and anorexia (85%). Seven patients (54%) had disseminated TB and five (39%) died as a consequence of TB. We observed high morbidity, hospital utilization and high mortality associated with TB among HIV-infected children in Baja California.

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.

Label-Free Quantitative Proteomics Identifies Novel Plasma Biomarkers for Distinguishing Pulmonary Tuberculosis and Latent Infection.

PubMed

Sun, Huishan; Pan, Liping; Jia, Hongyan; Zhang, Zhiguo; Gao, Mengqiu; Huang, Mailing; Wang, Jinghui; Sun, Qi; Wei, Rongrong; Du, Boping; Xing, Aiying; Zhang, Zongde

2018-01-01

The lack of effective differential diagnostic methods for active tuberculosis (TB) and latent infection (LTBI) is still an obstacle for TB control. Furthermore, the molecular mechanism behind the progression from LTBI to active TB has been not elucidated. Therefore, we performed label-free quantitative proteomics to identify plasma biomarkers for discriminating pulmonary TB (PTB) from LTBI. A total of 31 overlapping proteins with significant difference in expression level were identified in PTB patients ( n = 15), compared with LTBI individuals ( n = 15) and healthy controls (HCs, n = 15). Eight differentially expressed proteins were verified using western blot analysis, which was 100% consistent with the proteomics results. Statistically significant differences of six proteins were further validated in the PTB group compared with the LTBI and HC groups in the training set ( n = 240), using ELISA. Classification and regression tree (CART) analysis was employed to determine the ideal protein combination for discriminating PTB from LTBI and HC. A diagnostic model consisting of alpha-1-antichymotrypsin (ACT), alpha-1-acid glycoprotein 1 (AGP1), and E-cadherin (CDH1) was established and presented a sensitivity of 81.2% (69/85) and a specificity of 95.2% (80/84) in discriminating PTB from LTBI, and a sensitivity of 81.2% (69/85) and a specificity of 90.1% (64/81) in discriminating PTB from HCs. Additional validation was performed by evaluating the diagnostic model in blind testing set ( n = 113), which yielded a sensitivity of 75.0% (21/28) and specificity of 96.1% (25/26) in PTB vs. LTBI, 75.0% (21/28) and 92.3% (24/26) in PTB vs. HCs, and 75.0% (21/28) and 81.8% (27/33) in PTB vs. lung cancer (LC), respectively. This study obtained the plasma proteomic profiles of different M.TB infection statuses, which contribute to a better understanding of the pathogenesis involved in the transition from latent infection to TB activation and provide new potential diagnostic

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.

Incidence of isolation of Mycobacterium tuberculosis from blood samples in tuberculosis patients in Imam Khomeini Hospital, Tehran, Iran.

PubMed

Foroughi, Maryam; Montazeri, Saman Mohaghegh; SeyedAlinaghi, SeyedAhmad; Badie, Banafshe Moradmand; Heiydarpour, Pourya; Roosta, Neda; Rasoolinejad, Mehrnaz; Cochak, Hamid Emadi

2011-01-01

It is estimated that one third of the world's population is latently infected with tuberculosis (TB). The HIV epidemic fuels the TB epidemic by increasing the risk of reactivation of latent TB infection and by facilitating a more rapid progression of TB disease. Although the incidence of TB is constant or decreasing in many regions of the world, rates remain high in developing countries as a consequence of the HIV epidemic. This study was conducted as a collaboration of the Infectious Diseases department of Imam Khomeini Hospital with the Microbiology department of Tehran University of Medical Sciences. The hospital dataset of 94 patients admitted with TB during 2003-2005 was reviewed. We aimed to study factors correlating with positive blood culture including age, sex, immune deficiency status, HIV serology and SIRS (Systemic Inflammatory Response Syndrome) status. In this study, we found that positive blood cultures are more frequent in patients less than 45 years old. Positive blood cultures were also more frequent in HIV infected patients and there was a significant correlation between blood culture and SIRS status. Therefore, we recommend that we obtain blood cultures from these high-risk groups in order to increase early detection of TB.

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

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.

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

Public Health Implications and Risk Factors Assessment of Mycobacterium bovis Infections among Abattoir Personnel in Bauchi State, Nigeria

PubMed Central

Sa'idu, A. S.; Okolocha, E. C.; Dzikwi, A. A.; Gamawa, A. A.; Ibrahim, S.; Kwaga, J. K. P.; Usman, A.; Maigari, S. A.

2015-01-01

Bovine tuberculosis (bTB) is a chronic infectious and contagious zoonotic disease of domestic animals, wild animals, and humans. It poses a public health threat and economic losses due to abattoir condemnation of infected carcasses during meat inspection of slaughtered animals. Bovine tuberculosis is widespread in Africa including Nigeria affecting both cattle and humans, particularly Northern Nigeria. A prospective survey was conducted from June to August 2013 in the three Zonal abattoirs of Bauchi State, Nigeria. A total of 150 structured close-ended questionnaires were administered to abattoir personnel to assess their level of awareness of bTB. This study was aimed at determining the level of public health awareness, attitude, and practices of abattoir workers of bTB in Bauchi State, Nigeria. There was a statistically significant association between respondents' awareness of bTB and their occupational status, age, and duration of exposure to cattle carcasses (P < 0.05); the odds of being aware of bTB were 9.4, 7.3, and 2.1, respectively. In conclusion, these demonstrate the urgent need for public health authorities to intervene in bTB control. The risk of bTB transmission as indicated by the personnel's practices and awareness levels in Bauchi State could be prevented through the use of protective clothing (PPEs). PMID:26464954

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

Integration and task shifting for TB/HIV care and treatment in highly resource-scarce settings: one size may not fit all.

PubMed

Van Rie, Annelies; Patel, Monita R; Nana, Mbonze; Vanden Driessche, Koen; Tabala, Martine; Yotebieng, Marcel; Behets, Frieda

2014-03-01

A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4 count is 100-350 cells per cubic millimeter, and at the end of TB treatment after CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). ART uptake increased (17%-69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%, P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.