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To evaluate the utility of the tuberculin skin test (TST) in detecting latent and active tuberculosis (TB) among human immunodeficiency virus (HIV) infected patients in South India.
TSTs and CD4 counts were collected from 631 HIV-infected individuals without active TB and 209 antiretroviral and anti-tuberculosis treatment-naïve HIV-infected patient...
Contexts in source publication
Context 1
... mean age was 30 7 years (range 18-60), and the mean CD4 count was 378 253 cells/l. In this cohort, 269 (42.6%) individuals were TST-positive based on 5 mm and 227 (36%) based on 10 mm cut-offs (Table 1). Using a 5 mm cut-off, 39% of females (n 155) and 48.7% of males (n 114) were TST-positive, while 34.3% of females and 38.9% of males were TST- positive using a 10 mm cut-off (Table 1). ...
Context 2
... this cohort, 269 (42.6%) individuals were TST-positive based on 5 mm and 227 (36%) based on 10 mm cut-offs (Table 1). Using a 5 mm cut-off, 39% of females (n 155) and 48.7% of males (n 114) were TST-positive, while 34.3% of females and 38.9% of males were TST- positive using a 10 mm cut-off (Table 1). ...
Context 3
... was no significant dif- ference in the rate of TST positivity, mean induration size or mean CD4 cell count between patients with and those without a history of BCG vaccination (Table 2). Using a 5 mm cut-off, patients with CD4 counts 100 cells/l had a lower TST-positive rate of 27.6% (mean induration size 4.1 mm), as compared to 42-48% for those with CD4 counts 100 cells/l (mean induration size 7.9-8.5 mm) (Table 1). ...
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SETTING: Two prisons in Medellín and Itagüí, Colombia.OBJECTIVE: To determine the prevalence of tuberculin skin test (TST) positivity in prisoners and the annual risk of tuberculous infection (ARTI), to identify risk factors associated with a positive result,
and to describe progression to active disease.DESIGN: Cross-sectional study. Inmates were...
Interferon-gamma release assays including the QuantiFERON-TB Gold In-Tube test (QFT-GIT [Cellestis Ltd, Australia]) may be used in place of the tuberculin skin test (TST) in surveillance programs for Mycobacterium tuberculosis infection control. However, data on performance and practicality of the QFT-GIT in such programs for health care workers (H...
The high background rates of positive results on the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) sometimes confuse the investigation of tuberculosis (TB) contact in TB-prevalent countries, particularly in elderly contacts. The aim was to investigate the predictive value of TST and IGRA for diagnosing latent TB infection (LT...
Background
The risk of tuberculosis (TB) is greater for individuals with human immunodeficiency virus (HIV) who are on combined antiretroviral therapy (c-ART) than for the normal population. Therefore, the detection and treatment of latent tuberculosis infections is recommended for all HIV-positive persons with positive tuberculin skin tests (TSTs)...
Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection.
IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected in...
Citations
... However, the same might have some utility in detecting M.tb infection in anergic HIV-TB co-infected patients [6]. TST underestimates the prevalence of LTBI in endemic countries, requires trained health care staff to correctly perform and accurately read the results, and also demands a second patient visit [7][8][9][10][11][12][13]. The test is neither useful to rule in disease nor in high TB prevalence settings to identify eligible individuals for prophylaxis. ...
... Indeed, the presence of slightly high levels of IgM among pockets of our purported NTB controls as pre-qualified Quantiferon® Gold assays, might suggest that these persons had intercurrently or recently been exposed to M.tb. The latter might actually be a representation of the limitation of QuantiFERON TB Gold ® for differentiating TB exposure from NTB [6][7][8][9][10][11][12][13][14][15][16][17][18][19]. For details, see Additional file 1. ...
... (95% CI: 0.2690 to 0.6396) [33]. Indeed, a subsequent attempt to re-categorize the 40 TB exposed household contacts as NTB and LTBI by the QuantiFERON TB Gold® assay alongside the TMKmt-IgG assay revealed high IgG levels among both clusters (see Fig. 5); suggesting that QuantiFERON TB Gold® might be inaccurate towards differentiating LTBI from NTB [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. For details, see ...
Background:
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.
Methods:
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.
Results:
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).
Conclusions:
TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI.
... Patients with a negative TST could still go on to develop active TB due to a false-negative TST or new TB infection. 31 In the base case scenario, patients were given IPT regardless of TST status, but we explored alternative TSTdriven treatment strategies in secondary analysis. ...
Background:
India has a high burden of active tuberculosis (TB) and human immunodeficiency virus (HIV) infection. Pregnancy increases the risks of developing TB in HIV-infected women. Isoniazid preventive therapy (IPT) reduces progression to TB, but may increase costs and hepatotoxicity. The cost-effectiveness of IPT for HIV-infected pregnant women in India is unknown.
Design:
We evaluated the cost-effectiveness of antepartum IPT among HIV-infected women in India using a decision-analytic model. We compared current practice (no IPT) with: Intervention 1 (IPT regardless of CD4 count) and Intervention 2 (IPT for those with CD4 count ⩿ 200 cells/μl). We modeled IPT irrespective of tuberculin skin test (TST) status and TST-driven strategies. Primary outcomes were anticipated costs, disability-adjusted life-years (DALYs) and TB cases.
Results:
Both IPT interventions are highly cost-effective compared to no IPT at current willingness-to-pay thresholds (respectively US$178.00 and US$201.00 per DALY averted for Interventions 1 and 2). However, providing IPT irrespective of CD4 count results in the greatest health benefits (21 TB cases averted/1000 patients) compared to current practice. IPT irrespective of TST status was also highly cost-effective compared to TST-driven IPT (respectively US$1027.00 and US$1154.00/DALY averted for Interventions 1 and 2).
Conclusion:
Antepartum IPT for HIV-infected women is highly cost-effective for TB prevention compared to current practices in India.
... However, while TST was successfully implemented as a screening tool in developed countries [56,57] , it has not been so well received in resource-poor nations where TB burden is greatest. Apart from limitations of low sensitivity and specificity (51.0% in HIV-infected persons vs 94.0% in HIV negative persons with active pulmonary TB) [56,58] , it requires a lot of resources including adequately trained manpower to administer and read the test, need for repeat visits by patients, difficult logistics of cold chain maintenance and cost of tuberculin procurement which may be prohibitive for a large scale prevention program [4,54] . TST status of an individual is influenced largely by the degree of immunodeficiency [59] . ...
... An RCT conducted in India assessed two cohorts of HIV-infected patients; one with active pulmonary TB and the other without evidence of active TB. The cohort without active TB was found to have a lower TST-positive rate of 27.6% at CD4 < 100 cells/µL against 42.0%-48.0% of those with CD4 > 100 cells/µL in the same group [58] . The authors concluded that TST is a poor predictor of both latent and active TB in HIV-infected individuals in TB endemic countries and that programmes offering treatment for LTBI should consider including all HIV-infected individuals regardless of TST status, or use other indicators, such as CD4 count [58] . ...
... The cohort without active TB was found to have a lower TST-positive rate of 27.6% at CD4 < 100 cells/µL against 42.0%-48.0% of those with CD4 > 100 cells/µL in the same group [58] . The authors concluded that TST is a poor predictor of both latent and active TB in HIV-infected individuals in TB endemic countries and that programmes offering treatment for LTBI should consider including all HIV-infected individuals regardless of TST status, or use other indicators, such as CD4 count [58] . Thus a negative TST in an HIV-infected person may be due to anergy leading to missed opportunity for those who should have been offered chemoprophylaxis [4] . ...
Isoniazid preventive therapy (IPT) is the administration of isoniazid (INH) to people with latent tuberculosis (TB) infection (LTBI) to prevent progression to active TB disease. Despite being life-saving for human immunodeficiency virus (HIV)-infected persons who do not have active TB, IPT is poorly implemented globally due to misconceptions shared by healthcare providers and policy makers. However, amongst HIV-infected patients especially those living in resource-limited settings with a high burden of TB, available evidence speaks for IPT: Among HIV-infected persons, active TB-the major contraindication to IPT, can be excluded with symptom screening; chest X-ray and tuberculin skin testing are unreliable and often lead to logistic delays resulting in increased numbers of people with LTBI progressing to active TB; the use of IPT has not been found to increase the risk of the development of INH mono-resistance; IPT is cost-effective and cheaper than the cost of treating cases of active TB that would develop without IPT; ART and IPT have an additive effect on the prevention of TB, and both are safe and beneficial even in children. In order to sustain the recorded gains from ART scale-up and to further reduce TB-related morbidity and mortality, more efforts are needed to scale-up IPT implementation globally. Core tip: To better inform healthcare providers, policy makers and human immunodeficiency virus-infected persons about isoniazid preventive therapy (IPT), this article summarizes the existing evidence in support Debunking the myths perpetuating low implementation of isoniazid preventive therapy amongst human immunodeficiency virus-infected persons. World J Virol 2015; 4(2): 105-112 Available from:
... However TB rates in the 36H arm were lower compared to 6EH both among TST positive and negative subjects, suggesting that the longer regimen may protect both against exogenous infection as well as reactivation of latent disease [29]. Our previous findings that TST (using 1TU PPD) has poor sensitivity in detecting latent TB in patients with HIV suggest that the role of TST in screening patients for TB preventive therapy needs to be examined further perhaps using higher strengths of PPD [30]. The duration of protective effect of TB preventive therapy for HIV-infected patients ranges from 12 months to three years and appears to be higher with multi-drug therapy [12,28,31,32]. ...
The optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown.
An open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared.
Tuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100py (95%CI- 1.4-3.5) and 1.6/100py (95% CI-0.8-3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8-3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6-4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant.
Both regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients. The trial is registered at ClinicalTrials.gov, NCT00351702.
... Among the estimated 2.4 million people living with HIV/AIDS in India, the incidence of active TB has been reported as high as 6.90 cases/100 person-years (PY) [3,4]. This is driven in part by reactivation disease in the estimated 40% of HIV-infected persons latently infected with TB [5]. Given the challenge of controlling these epidemics, major stakeholders convened at the World Health Organization and identified intensified TB case-finding, infection control, and isoniazid-based preventive therapy (IPT) as crucial measures in reducing the impact of TB on people living with HIV [6]. ...
Regimens for isoniazid-based preventive therapy (IPT) for tuberculosis (TB) in HIV-infected individuals have not been widely adopted given concerns regarding efficacy, adherence and drug resistance. Further, the cost-effectiveness of IPT has not been studied in India.
We used an HIV/TB model to project TB incidence, life expectancy, cost and incremental cost-effectiveness of six months of isoniazid plus ethambutol (6EH), thirty-six months of isoniazid (36H) and no IPT for HIV-infected patients in India. Model input parameters included a median CD4 count of 324 cells/mm(3), and a rate ratio of developing TB of 0.35 for 6EH and 0.22 for 36H at three years as compared to no IPT. Results of 6EH and 36H were also compared to six months of isoniazid (6H), three months of isoniazid plus rifampin (3RH) and three months of isoniazid plus rifapentine (3RPTH).
Projected TB incidence decreased in the 6EH and 36H regimens by 51% and 62% respectively at three-year follow-up compared to no IPT. Without IPT, projected life expectancy was 136.1 months at a lifetime per person cost of $5,630. 6EH increased life expectancy by 0.8 months at an additional per person cost of $100 (incremental cost-effectiveness ratio (ICER) of $1,490/year of life saved (YLS)). 36H further increased life expectancy by 0.2 months with an additional per person cost of $55 (ICER of $3,120/YLS). The projected clinical impact of 6EH was comparable to 6H and 3RH; however when compared to these other options, 6EH was no longer cost-effective given the high cost of ethambutol. Results were sensitive to baseline CD4 count and adherence.
Three, six and thirty-six-month regimens of isoniazid-based therapy are effective in preventing TB. Three months of isoniazid plus rifampin and six-months of isoniazid are similarly cost-effective in India, and should be considered part of HIV care.
... “Two stage or booster test” is not a substitute to anergy testing; however, it may have some utility in detecting M.tuberculosis infection in anergic HIV-TB co-infected patients51. Tuberculin skin test underestimates the prevalence of latent tuberculosis in endemic countries; it requires trained health care staff to correctly perform the tests and accurately read the results, and also requires a second patient visit58. The test is neither useful to rule in disease nor in high TB prevalence settings to identify eligible individuals for prophylaxis. ...
Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection.
... However, further Isoniazid preventive trails are needed to confirm which test really gives relevant information. An earlier study that assessed the performance of TST using 1 TU PPD (Statens Serum Institut, Denmark) in our settings among HIV infected individuals, also reported the depressed positivity even in subjects with >500 cell/µl and it went worse, when CD4 cell count decreased further (Swaminathan et al., 2008). In this study, we report, similar to findings in other endemic countries, the positivity of TST even at 2 TU strength is low among HIV infected individuals in our setting. ...
We aimed to compare the positivity of the QuantiFERON TB gold in-tube (QFT-IT antigens) specific interferon gamma (IFN-γ/QFT-IT) and IFN-γ-inducible protein-10 (IP-10/QFT-IT) assays with tuberculin skin test (TST) among human immunodeficiency virus (HIV)-infected individuals in a TB endemic setting. A total of 180 HIV-infected subjects, with no evidence of active TB, were recruited. IFN-γ and IP-10 levels specific to QFT-IT antigens were measured in plasma from QFT-IT tubes. The overall positivity of TST at the 5-mm cut-off point (19%) was significantly lower when compared to IFN-γ/QFT-IT (38%) and IP-10/QFT-IT (45%) assays. The positivity of IP-10/QFT-IT was significantly higher than that of IFN-γ/QFT-IT (P = 0.038). Indeterminate results for IFN-γ/QFT-IT and IP-10/QFT-IT were more frequent in subjects with CD4 count <100 cells/μL than in those with >100 cells/μL. IFN-γ/QFT-IT (9%) yielded significantly higher number of indeterminate results than IP-10/QFT-IT (5%). The frequency of these responses is higher than the proportion of individuals with positive TST results. However, 6 IFN-γ/QFT-IT- or IP-10/QFT-IT-negative subjects were positive for TST at the 5-mm cut-off point. Prospective and prognostic studies are required to clarify the significance of these data.
... At this point, there is no evidence that IFN-g assays offer significant advantages over tuberculin skin testing in HIV-infected patients to be cost-effective in developing countries. The tuberculin skin test itself performs poorly (due to anergy) and underestimates the prevalence of latent tuberculosis in countries of endemicity; it requires trained health care staff to correctly perform the tests and accurately read the results, and it requires a second patient visit [32]. For these reasons, the WHO recommends treatment of latent tuberculosis or isoniazid chemoprophylaxis for all HIV-infected patients in tuberculosis-endemic countries after active tuberculosis has been excluded. ...
The human immunodeficiency virus (HIV) epidemic has led to an increase in the incidence of tuberculosis globally, particularly
in sub-Saharan Africa. Coinfection with HIV leads to difficulties in both the diagnosis and treatment of tuberculosis. Because
of the poor performance of sputum smear microscopy in HIV-infected patients, more sensitive tests—such as liquid culture systems,
nucleic acid amplification assays, and detection of mycobacterial products in various body fluids—are being investigated.
The treatment of coinfected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly;
challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution
syndrome. Both multidrug-resistant and extensively drug-resistant tuberculosis can spread rapidly among an immunocompromised
population, with resulting high mortality rates. Current guidelines recommend starting antiretroviral treatment within a few
weeks of antituberculosis therapy for patients with CD4 cell counts <350 cells/µL; however, important questions about the
drug regimens and timing of antiretroviral therapy remain. Ongoing trials may answer many of these unresolved questions.
... However TB rates in the 36H arm were lower compared to 6EH both among TST positive and negative subjects, suggesting that the longer regimen may protect both against exogenous infection as well as reactivation of latent disease [29]. Our previous findings that TST (using 1TU PPD) has poor sensitivity in detecting latent TB in patients with HIV suggest that the role of TST in screening patients for TB preventive therapy needs to be examined further perhaps using higher strengths of PPD [30]. ...
At a Glance Commentary: There is limited information on the outcome of HIV-infected TB patients treated with short-course intermittent (thrice-weekly) regimens, and the efficacy of extending treatment to 9 months has not been studied. Further, acquired rifamycin resistance has been described with once and twice-weekly TB treatment in the presence of HIV-associated immunodeficiency but limited data is available on thrice-weekly regimens. Our study showed that extending TB treatment to 9 months instead of 6 months did not improve favourable outcome at the end of treatment or mortality, but reduced bacteriologic recurrences significantly over 30 months. A high rate of development of acquired rifamycin resistance at the time of failure was noted irrespective of the length of treatment, with this thrice-weekly fully intermittent regimen in patients with advanced HIV disease, suggesting the need for daily treatment at least in the intensive phase.
... The rate of this prevalence ranged between 16.8% in developed countries and 43% in undeveloped area with the mean of 30%. [13][14][15][16][17] Mohraz et al reported 29% prevalence rate of LTBI in Iranian HIV positive patients. 18 The reason for these differences is unclear. ...
Objective: To determine Latent Tuberculosis Infection (LTBI) prevalence and compare TST results to the anti TB-IgM anti bodies (ATIA) for the diagnosis of LTBI in HIV infected individuals. Methodology: Sixty two randomized sampled HIV infected subjects from an addict treatment center in Ahvaz southwest Iran underwent TST, using 5 TU of purified protein derivative, and measuring ATIA. Data were analyzed in SPSS (version 16, USA). Results: Of 62 participants, 34 (54.8%) had positive result for TST, whereas 6(9.7%) had positive ATIA. Overall concordance between TST and ATIA was 45.2% (Kappa= 0.37, P = 0.32). In subjects with positive test results by either TST or ATIA, only 4.8% had positive test results by both tests. Discordant results were found in 54.8% of subjects. Positive results for both tests in subjects categorized in two groups (above and below 200 CD4-cell/mm 3) had no significant difference (P>0.05). Conclusion: LTBI prevalence among HIV infected individuals in studied area is higher than other parts of the world. TST is a useful test for LTBI diagnosis and prefer to ATIA. Concordance between TST and ATIA is low.
