Purified Protein Derivative Reaction Research Articles

Anergy to purified protein derivative and chronic energy deficiency in sputum-positive pulmonary tuberculosis: Dynamic assessment at baseline and treatment completion.

Tuberculosis (TB) remains a high burden disease in India. Nutrition plays a pivotal role in holistic recovery of the same. Patients with sputum positive pulmonary TB were consecutively recruited into the study aimed to observe the incidence of under nutrition and anergy purified protein derivative (PPD). Anthropometry and PPD testing were done at baseline. Patients were followed-up at 6 months, with PPD intradermal test repeated to study tuberculin conversion. Nutritional recovery, tuberculin conversion, and determination of persistent anergy were the outcomes of interest. Of the 134 patients enrolled in the study, 43.2% were anergic to PPD at baseline. While 50.8% patients had normal body mass index (BMI), 14.2%, 9.7%, and 25.4% had chronic energy deficiency (CED) Grades I, II, and III, respectively. BMI at baseline showed a positive linear correlation with PPD response (r = 0.44, P < 0.001), and anergy was associated with CED (odds ratio - 3.25, P = 0.001). Forty-six patients completed follow-up and 19.6% showed anergy to PPD. At follow-up, 69.6% had normal BMI. Overall, there was an improvement in anthropometry and PPD reactivity in patients at 6 months, compared to baseline assessment. Anergy was significantly associated with CED at baseline in patients with TB. While most patients had an improvement in nutritional status and PPD reactivity, a small subset of patients had persistent anergy. Recovery from TB is multifactorial and its determinants include microbiological cure, nutritional status, and immunological recovery.

The relationship between lymphocyte subsets, nutritional status and tuberculin reactivity in continuous ambulatory peritoneal dialysis and hemodialysis patients

AimSkin test anergy is common in patients with uremia and during maintenance hemodialysis treatment. However, up to date only one study concerning skin test in peritoneal dialysis patients has focused on the issue. Our cross-sectional controlled study was conducted to analyze the correlation of purified protein derivative (PPD) test response with demographical features, nutritional parameters and the distribution of peripheral blood lymphocyte subsets in peritoneal dialysis and hemodialysis patientsPatients and methodsStable 30 hemodialysis (HD) patients (16 men, 14 women) and 30 continuous ambulatory peritoneal dialysis (PD) patients (17 men, 13 women) were included. Thirty healthy cases (15 men, 15 women) with a mean age of 32.4 ± 9.4 constituted the control group.ResultsIn the HD group, 14 patients (46.6%) were PPD positive, and ın the PD group 16 patients (53.3%) were PPD positive. In the PPD-positive HD patients 64.2% (9/14), and in the PPD-positive PD patients 62.4% (10/16) had an induration of 10 mm or greater. In the control group, 21 of 30 patients (70%) were PPD positive. Comparison of both HD and PD groups with the control group showed significant differences in PPD reactivity (p < 0.01). Albumin levels were significantly high in the control groups (p < 0.01), and cholesterol levels were significantly high in the PD and the control groups (p < 0.05). Transferrin levels were significantly high in the PD (p < 0.01). The lymphocyte counts were significantly high in the control group compared to the HD patients (p < 0.05). The lymphocyte subset percentages CD19 were high in the control groups (p < 0.05), and CD16/56 was significantly high in the PD groups (p < 0.05). All the parameters were also similar between PPD-positive and -negative same groups.ConclusionThe prevalence of PPD positivity was lower in the PD and HD groups. The PPD test responses were not related to the peripheral lymphocyte counts, subsets and malnutrition parameters.

Early Vaccination With Bacille Calmette-Guérin-Denmark or BCG-Japan Versus BCG-Russia to Healthy Newborns in Guinea-Bissau: A Randomized Controlled Trial.

Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) have demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects. This was a parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2851 randomized, 2840 analyzed) vs BCG-Russia (2845 randomized, 2837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and purified protein derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3191 neonates randomized, 3184 analyzed) with BCG-Russia (3170 randomized, 3160 analyzed). Mortality and morbidity data were collected by telephone, at home visits, and at the National Hospital and assessed in Cox models providing 6-week mortality rate ratios (MRRs) and hospitalization incidence rate ratios (IRRs). By age 6 weeks, there were 140 and 130 admissions among neonates vaccinated with BCG-Denmark and BCG-Russia, respectively (IRR, 1.08 [95% confidence interval {CI}, .84-1.37]). For BCG-Japan, there were 185 admissions vs 161 admissions for BCG-Russia (IRR, 1.15 [95% CI, .93-1.43]). The 6-week mortality did not differ: BCG-Denmark/BCG-Russia (MRR, 1.15 [95% CI, .74-1.80]); BCG-Japan/BCG-Russia (MRR, 0.71 [95% CI, .43-1.19]). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia. BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study. NCT02447536.

Estimating Tuberculin Skin Test Reactions among Children and Teenagers Who Received the Bacillus Calmette-Guerin Vaccination at Birth: A Meta-analysis.

ObjectivesTuberculin skin reaction size is one indicator of bacillus Calmette-Guérin (BCG) vaccine efficacy and a way to diagnose latent infection. Several primary studies have examined this issue. Combining the results of these studies using a meta-analysis will provide reliable evidence regarding this indicator for policymakers. This study aimed to estimate the total frequency of different tuberculin skin test reactions among Iranian children and teenagers who received the BCG vaccination at birth.MethodsNational and international databanks were searched using relevant keywords. After the search strategy was restricted and duplicates were excluded, the titles and abstracts of the remaining papers were screened. All included studies included healthy children who received the BCG vaccine without confirmed tuberculosis exposure. Heterogeneity of the results was assessed using the Cochrane test and I2 index showed the random effects model as the best model for estimating the pooled results.ResultsWe combined the results of 14 primary studies including purified protein derivative reaction test measures of 26,281 Iranian children. The frequencies (95% confidence intervals) of the reactions were 8.5% (6.2–10.8) for patients with a reaction size ≥ 10 mm, 29.9% (22.3–37.4) for a reaction size of 5–9 mm, and 60% (48.9–71.1) for a reaction size < 5 mm.ConclusionOur study showed that large numbers of Iranian children and teens have no positive BCG vaccine reaction and a considerable number of children have been exposed to Mycobacterium tuberculosis.

Cytokine gene polymorphisms are associated with susceptibility to tuberculosis in an Amerindian population.

Cytokines play an important role in anti-tuberculosis immune response, combined with antigen-presenting cells and lymphocytes. Immune response gene polymorphisms have been reported to be associated with tuberculosis (TB) susceptibility in some but not all studies. To evaluate the association of immune response genes with susceptibility to tuberculin skin test (TST) reactivity and/or TB. Fourteen single nucleotide polymorphisms were genotyped in 96 individuals of the Aché, a native Paraguayan population, by allelic discrimination using real-time polymerase chain reaction. Univariate and multivariate Poisson regression were employed to assess risk genotypes. A higher prevalence of purified protein derivative reactivity was associated with the TNF-α CCA/TCG haplotype (PR 1.298, 95%CI 1.059-1.589) and with the IL-10 AT/CC diplotype (PR 1.181, 95% CI 1.024-1.362), and the presence of the IL-8 rs4073 T allele was associated with protection against TB (PR 0.482, 95%CI 0.273-0.851). These results suggest that polymorphisms in genes associated with immune response are involved in TST reactivity and susceptibility to TB in the Aché population.

Dual skin tests with Mycobacterium avium sensitin and PPD to detect misdiagnosis of latent tuberculosis infection

A positive tuberculin skin test (TST) may indicate cross-reacting immunity to non-tuberculous mycobacteria (NTM) and not latent tuberculosis infection (LTBI). To assess misclassification of LTBI, as assessed by skin testing with Mycobacterium avium sensitin (MaS), and to determine how this misclassification affects the analysis of risk factors for LTBI. In a population-based survey, participants underwent skin testing with M. tuberculosis purified protein derivative (PPD) and MaS. A PPD-dominant skin test was a reaction that was ≥ 3 mm larger than the MaS reaction; a MaS-dominant skin test was a reaction that was ≥ 3 mm larger than the PPD reaction. Of 447 randomly selected persons, 135 (30%) had a positive PPD test. Of these, 21 (16%) were MaS- dominant, and were therefore attributable to NTM and misclassified as LTBI. PPD reactions of 5-14 mm were more likely to be misclassified than those ≥ 15 mm (OR = 5.0, 95%CI 1.9-13.2). Adjusting for misclassification had only a small impact on the analysis of risk factors for LTBI. A substantial number of individuals who are diagnosed with LTBI are actually sensitized to NTM. Using dual skin testing would reduce misdiagnosis and prevent unnecessary treatment.

Resposta de testes de hipersensibilidade tardia utilizando PPD e outros antígenos em crianças e adolescentes saudáveis e infectados pelo HIV-1 e vacinados com BCG

Among HIV-1-infected patients, CD4+ T cell counts are well-established markers of cell-mediated immunity. Delayed-type hypersensitivity (DTH) skin tests can be used to evaluate in vivo cell-mediated immunity to common antigens. DTH responses to tuberculin purified protein derivative (PPD), sporotrichin, trichophytin, candidin and streptokinase/streptodornase antigens were assessed. Thirty-six HIV-1-infected children/adolescents and 56 age- and sex-matched HIV-1/HIV-2-seronegative participants were tested. All participants had a BCG scar. Fisher's exact test was used to evaluate significant differences between groups (p<0.05). The main characteristics of the HIV-1 patients were as follows: median age 8.1 years; 20/36 were males; 35 were vertical transmission cases; 34 were AIDS cases under antiretroviral therapy; median viral load = 3.04 log10 copies/ml; median CD4+ T cell count = 701 cells/μl. A total of 25% (9/36) and 87.5% (49/56) of HIV-1-infected and healthy participants, respectively, displayed DTH reactivity to at least one antigen (p<0.001). Among HIV-1-infected participants, reactivity to candidin predominated (8/36, 22.2%), while PPD positivity prevailed among healthy participants (40/56, 71.4%). PPD reactivity in the HIV-1-positive group was 8.3% (p<0.01). The median PPD induration was 2.5mm (range: 2-5mm) in the HIV-1 group and 6.0 mm among healthy participants (range: 3-15 mm). There was no correlation between PPD positivity and age. No correlation between CD4+ T cell counts and DTH reactivity was observed among HIV-1-infected patients. DTH skin test responses, including PPD reactivity, were significantly lower among HIV-1-infected participants compared to healthy controls, which likely reflects advanced disease and T cell depletion.

Prognostic factors predicting a fatal outcome in HIV-negative children with neurotuberculosis

To identify prognostic factors predicting a fatal outcome in HIV-negative children with neurotuberculosis based on clinical, epidemiological, and laboratory findings. The clinical records of all in-patients diagnosed with neurotuberculosis from 1982 to 2005 were evaluated retrospectively. The following prognostic parameters were examined: gender, age, close contact with a tuberculosis-infected individual, vaccination for bacillus Calmette-Guérin, purified protein derivative (PPD) of tuberculin results, concomitant miliary tuberculosis, seizures, CSF results, and hydrocephalus. One hundred forty-one patients diagnosed with neurotuberculosis were included. Seventeen percent of the cases resulted in death. The factors that were correlated with a negative outcome included lack of contact with a tuberculosis-infected individual, negative PPD reaction, coma, and longer hospitalisation time. A multiple logistic regression analysis was performed to identify which of these factors most often resulted in death. Coma at diagnosis, lack of tuberculosis contact, and a non-reactive PPD were the most important predictors of fatality in patients with neurotuberculosis.

Factors affecting red deer skin test responsiveness to bovine and avian tuberculin and to phytohaemagglutinin

We studied the effect of management on the responsiveness of red deer ( Cervus elaphus) to skin testing with mycobacterial and non-mycobacterial antigens. We hypothesized that individuals from populations of the same species under different management conditions would have a different immune responsiveness. Deer sampled in this study included 1041 adult animals from 6 Spanish farms and 111 adult wild deer. We injected four sites of the neck with 0.1 ml bovine purified protein derivative (PPD), 0.1 ml avian PPD, 0.1 ml negative control PBS and 0.1 ml of Phytohaemagglutinin (PHA, containing 250 μg) as positive control, and measured the skin fold increase at time 72 h. Bovine PPD reactors were identified in 5 of 6 farms and among wild deer. Apparent prevalence among wild deer (18.9%) was not significantly higher than among farmed deer (14.5%). Avian PPD reactors were found among all 7 study populations, but apparent prevalence was lower among wild deer (<1%) than among farmed deer (12.6%; p < 0.001). Deer management (farmed versus wild) was identified as a key factor affecting deer skin fold thickness increase in response both to mycobacterial (bPPD and aPPD) and non-mycobacterial antigens (PHA). The differences occurred in the same sense, regardless of some interactions; farmed deer showing higher values. The PHA skin fold increase was not affected by the PPD skin test results. We propose that using PHA as a positive control may help in the interpretation of between-population differences in tuberculin responses.

The Impact of Hormone Replacement Therapy on Humoral and Cell-mediated Immune Responses In Vivo in Post-menopausal Women with Rheumatoid Arthritis

It is well known that oestrogen has immunomodulatory properties. We have previously shown disease ameliorating effects of hormone replacement therapy (HRT) in post-menopausal women with rheumatoid arthritis (RA). The aim of this study was to investigate the effects of HRT and the patients inflammatory state on humoral and cell-mediated immune responses. Eighty-eight post-menopausal RA women were allocated to receive HRT (oestradiol and noretisterone acetate), vitamin D3 and calcium or vitamin D3 and calcium alone in a 2-year randomized controlled trial. Immunoglobulins (IgM, IgG and IgA) in serum were measured by nephelometry and rheumatoid factor (RF) concentration by enzyme-linked immunosorbent assay. Immunization with influenza vaccine was performed to quantitate humoral response to recall antigen and tuberculin skin test with purified protein derivative (PPD) to test T-cell-mediated immune response. These immune related measures were correlated with demographic and disease-related variables. HRT during 2 years did not alter concentrations of Ig, RF, IgM response to influenza vaccine or the PPD reaction. The increase in IgM against influenza vaccine was significantly positively correlated with signs of disease activity; C-reactive protein, disease activity score 28 and inversely with haemoglobin. In contrast, PPD reactivity was inversely associated with disease activity. In conclusion, long-term HRT in RA does not influence Ig or autoantibody concentrations in serum and has no significant impact on humoral and cell-mediated immune responses to recall antigens. Interestingly, high disease activity was associated to increased humoral but decreased cell-mediated immune responses irrespectively of hormone treatment.

Retrospective analysis of children with uveitis treated with infliximab

Tumor necrosis factor-alpha (TNF-alpha) antagonists have been successfully used in refractory cases of pediatric uveitis.(1-7) We report our experience with the monoclonal anti-TNF-alpha antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy.

A novel assay for screening patients for latent tuberculosis infection prior to anti-TNF therapy

Screening for latent tuberculosis (TB) infection (LTBI) prior to anti-tumor necrosis factor (TNF) therapy is complicated by the decreased sensitivity of the purified protein derivative tuberculin skin test in immunosuppressed patients, as well as the poor specificity of the tuberculin skin test in bacillus Calmette-Guérin (BCG)-vaccinated patients. Interferon-gamma-release assays that utilize specific TB antigens (e.g. ESAT-6/CFP-10) have greater specificity for LTBI, but their relative sensitivity is unknown in the setting of immune suppression. Dinser et al. evaluated a novel flow-cytometric interferon-gamma detection assay in 97 patients with inflammatory arthritis during LTBI screening for anti-TNF therapy. Overall, 39% of patients had purified protein derivative reactivity in vitro versus 14% cutaneously, and 16% exhibited reactivity in vitro to ESAT-6/CFP-10. The results suggest that flow cytometry using TB-specific antigens might eventually provide another tool for diagnosing LTBI in patients undergoing screening prior to anti-TNF or other immunosuppressive therapies. Further evaluation of the sensitivity and specificity of this novel whole-blood assay is warranted.

The significance of histopathologic patterns in positive tuberculin skin test site

The histologic features of tuberculin skin test site is not uniform. It may be related to status of tuberculosis. Forty-eight purified protein derivative (PPD) positive-cases were chosen for the study. Thirty of the subjects had active tuberculosis. As previously reported, the histologic pattern of inflammatory reaction seen in the test site classified into three type: (a) Perivascular (PV)-type, (b) Basal spongiotic dermatitis (BSD)-type and (c) Erythema multiforme (EM)-type. The frequencies of histological patterns in active tuberculosis and latent tuberculosis were statistically analyzed. In active tuberculosis group including 30 patient, 17 (56.7%) EM-type, 9 (30%) BSD-type and 4(13.3%) PV-type inflammation were seen. Among 18 latent tuberculosis, there were 2 (11.1%) EM-type, 7 (38 8%) BSD-type and 9 (50%) PV-type inflammatory reactions. The EM-type inflammation was more common in active tuberculosis group. Bulla formation was seen in seven subjects with active tuberculosis. The histological pattern of PPD reaction site may be an important sign reflecting the nature of the tuberculosis, which may be either latent or active. The bulla formation is an important sign for active pulmonary tuberculosis. Further, detailed immunohistopathologic studies of PPD reaction with large number of cases may give important clues about tuberculosis immunology.

Purified protein derivative reaction is not augmented in Behcet's syndrome patients

Purified protein derivative reaction is not augmented in Behcet's syndrome patients

Nosocomial Mycobacterium tuberculosis transmission among healthcare students in a high incidence region, in Vitória, State of Espírito Santo

This open comparative study for evaluating hypersensitivity to tuberculin among medical students (n=441), nursing students (n=178) and economics students (n=230) in Vitória, State of Espírito Santo, had the aim of assessing whether the prevalence of positive tuberculin tests among healthcare students could be used as a sentinel event for nosocomial transmission in localities with high endemicity. There was a significant change in the frequency of purified protein derivative reactivity in the nursing students (20.3%) and medical students (18.4%), in comparison with the economics students (6%) (p <0.001). As expected, the medical and nursing students had more knowledge about tuberculosis than did the economics students (p <0.001). Our data suggest that the incidence of Mycobacterium tuberculosis infection among nursing and medical students in our region, which has high endemicity of tuberculosis, does not differ from what is found in low-incidence countries. These data reinforce the need for implementing biosafety programs for this target population.

The burden of tuberculosis in indigenous peoples in Amazonia, Brazil

Tuberculosis (TB) stands out as one of the principal infectious diseases affecting Amazonian Indians. Recent research indicates that incidence rates among indigenous peoples may be as much as ten times higher than those of the general Brazilian population. Purified protein derivative reactivity in Amazonia is low compared with populations of European descent; anergy rates usually surpass 50%, even under high BCG coverage. An annual risk of infection of 1.2-2.2% points to high rates of transmission. Whether or not particular susceptibility to TB is linked to genetics, Amazonian Indians face a disproportionately high risk of contracting and dying from TB.

Risk of tuberculosis in a Chinese registry of rheumatoid arthritis and ankylosing spondylitis for tumour necrosis factor‐α antagonists

AbstractAim: To understand the risk of tuberculosis (TB) infection in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) who required tumour necrosis factor‐α (TNF‐α) antagonist treatment.Methods: Patients with RA and AS who were screened for infliximab and etanercept treatment for up to 6 months were entered in a registry between 2003 and 2005. The purified protein derivative (PPD) test and chest anteroposterior and lateral view X‐ray were performed at screening. The risk of TB infection in theses patients was observed during follow up.Results: Among 67 RA patients screened, a positive PPD reaction was found in one patient. Of the 169 AS patients screened, 23 were positive for the PPD reaction, two had pulmonary TB calcinosis and two were diagnosed as having pulmonary TB. The incidence of PPD positive reaction and pulmonary TB calcinosis or active TB in our screened RA and AS patients was significantly lower than that reported in the recent fourth national TB infection rates and prevalence (P &lt; 0.01). Only one patient with RA developed neck lymph node TB 6 months after completion of infliximab infusion.Conclusion: Patients with AS and RA are not at an increased risk of TB infection if screened properly before short course treatment with anti‐TNF‐α agents.

COINCIDENT FILARIAL, INTESTINAL HELMINTH, AND MYCOBACTERIAL INFECTION: HELMINTHS FAIL TO INFLUENCE TUBERCULIN REACTIVITY, BUT BCG INFLUENCES HOOKWORM PREVALENCE

The prevalence of helminth and tuberculosis infections is high in South India, whereas Bacille-Calmette-Guerin (BCG) vaccine efficacy is low. Our aim was to determine whether concurrent helminth infection alters the ability to mount a delayed-type hypersensitivity response to tuberculin. In a cross-sectional study in southern India, individuals 6-65 years of age were screened for intestinal helminths, circulating filarial antigenemia, tuberculin reactivity, active tuberculosis, and history of BCG vaccination; 54% were purified protein derivative (PPD) positive, 32% had intestinal helminth infection, 9% were circulating filarial antigen positive, and 0.5% had culture-confirmed active tuberculosis. Only age and BCG vaccination were significantly associated with PPD reactivity; however, BCG vaccination was associated with a lower prevalence of hookworm infection relative to those without prior BCG vaccination. Neither intestinal helminth infection nor filarial infection was associated with diminished frequencies of PPD positivity. Our findings suggest that preceding helminth infection does not influence significantly the delayed-type hypersensitivity response to tuberculin.

Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000–2002

The rates of positive tuberculin skin test (TST) reactions and BCG scarring after BCG vaccination vary between studies and populations. Tuberculin reactivity and BCG scarring may be related to better child survival in low-income countries. We therefore studied determinants for TST reaction and scarring in Guinea-Bissau. In a cohort of children born in suburban Bissau from March 2000 to July 2002, we assessed a Mantoux test with Purified protein derivative (PPD) (SSI, 2 T.U.) at 2 (2689 children), 6 ( N = 2148) and 12 months ( N = 1638) of age, and BCG scar was assessed at 2 ( N = 2698) and 6 months ( N = 2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD reactors (>1 mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR = 0.54 (0.31–0.91)) and BCG scars (OR = 0.13 (0.05–0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02–1.43)) and BCG scars (OR 1.66 (1.24–2.21)). In the multivariable analyses of BCG-vaccinated children assessed at 6 months of age, monitoring of vaccination technique and type of BCG vaccine were important. This was not changed by control for other determinants, including sex, season, vaccination place, birthplace, ethnic group, low birth weight, place of residence, education and civil status of mother. We reason that vaccination technique and BCG strain are important for PPD reaction and scarring in response to BCG vaccination. Considering that these responses are associated with better infant survival, the importance of monitoring vaccination technique and of different BCG strains should be evaluated with respect to infant mortality.

Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients

Identification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)-specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection. One hundred and twenty-seven hemodialysis patients and 218 control patients (blood donors, health care workers, and control patients) were analyzed. Specific T cells toward PPD and early secretory antigenic target-6 (ESAT-6), a protein expressed in Mycobacterium tuberculosis but absent from M. bovis bacillus Calmette-Guerin (BCG) vaccine strains, were flow cytometrically quantified from whole blood, and results were compared with skin testing. Compared to blood donors, a high proportion of both health care workers (48.6%) and hemodialysis patients (53.5%) had PPD-specific Th1-type CD4 T-cell reactivity with similar median frequencies of PPD-specific T cells (0.17%; 0.06-3.75% vs. 0.26%; 0.06-4.12%, respectively). In contrast, skin test reactivity was significantly reduced in hemodialysis patients. Whereas 85.7% of control patients with PPD reactivity in vitro were skin test-positive, the respective percentage among hemodialysis patients was 51.4% (P= 0.007). Among individuals with PPD reactivity in vitro, approximately 50% had T cells specific for ESAT-6. Unlike the skin test, measurement of PPD reactivity by in vitro quantitation of PPD-specific T cells was unaffected by uremia-associated immunosuppression. This whole-blood assay may thus be a valuable alternative to skin testing, and detection of ESAT-6-specific T cells could moreover allow distinction of latent M. tuberculosis infection from BCG-induced reactivity to PPD. The assay is well suited for clinical use and may facilitate targeting of preventative therapy in high-risk individuals.