PPD Skin Test Research Articles

Gamma interferon assay as an alternative to PPD skin testing in selected patients with granulomatous intraocular inflammatory disease

Gamma interferon assay as an alternative to PPD skin testing in selected patients with granulomatous intraocular inflammatory disease

Survey for tuberculosis in an indigenous population of Amazonia: the Suruí of Rondônia, Brazil

A cross-sectional survey was carried out in 2003 to investigate the epidemiology of tuberculosis (TB) among the Suruí Indians, Brazilian Amazon. A total of 736 subjects (50.7% females) were examined (80% of the total population). TB suspects underwent standardised evaluation for the presence of signs and/or symptoms of active TB, including chest radiography, PPD skin test, sputum microscopy examination for acid-fast bacilli and mycobacterial culture. A Bacillus Calmette-Guerin vaccine scar was detected in 699 individuals (95.0%). Of all the individuals examined, 120 (16.3%) had undergone previous TB treatment (46.7% females). One hundred and nine individuals were assessed as TB suspects (52.3% females). The survey identified six new cases of TB in the Suruí (three men and three women). Five of the six cases came from only two of the ten villages. Mycobacterium tuberculosis colonies grew from 5 (4.6%) samples (only two of which were also smear-positive) and mycobacteria other than M. tuberculosis were isolated from 14 (12.8%) samples. Diagnosis of TB based exclusively on clinical grounds was established only in the case of a 4-year-old girl. Based on this survey, the prevalence of active TB in the sampled group (N=736) was 815.2 per 100000. This study highlights the urgent need to review and strengthen control strategies directed at indigenous peoples in the country, taking into consideration their social, cultural and environmental differences.

Effect of Tuberculin Skin Test on Ex-vivo Interferon-gamma Assay for Latent Tuberculosis Infection

Background : Recently, two commercialized whole-blood assays, Gold (QFT) and T (SPOT), which measure the released in the whole blood after being incubation with mycobacterial antigens, were approved for the diagnosis of a latent tuberculosis infection (LTBI). However, there is data on whether or not the previously used PPD skin tests (TST) have any influence on the diagnostic ability of these ex-vivo assays. Methods : Forty-six 15 year-old students who did not appear to be infected with Mycobacterium tuberculosis were enrolled in this study. The peripheral blood was collected and used for two assays. The assays and TST were performed at the baseline (). The TST was repeated two months later (), and the assays were repeated two () and four months () later only in those subjects who had negative results at the baseline in both the assays and TST. An induration size > 10 mm was considered to be positive in the TST. Results : The mean TST value was (range: 0-20). Of the 46 subjects examined, 13 subjects (28.3%) showed positive results in the two-step TST. Nine (19.6%) were SPOT-positive and only one (2.2%) was QFT-positive. The and QFT were carried out in 23 and 25 all-negative subjects, respectively, and all showed negative results. The SPOT was performed in 23 subjects and only one (4.3%) showed a weak-positive result. Conclusion : Even though there were some discrepancies in the results of the two ex-vivo assays, it appears that their results were not influenced by a previous TST carried out in two or four months earlier.

Delayed response to anti-tuberculosis treatment in a patient on infliximab

The introduction of infliximab, an anti-TNF-alpha agent, in the treatment of rheumatic diseases has offered important therapeutic advances in recent years. The main adverse effect from the usage of this drug is susceptibility to infections, mainly reactivation of latent tuberculosis. We present a 23 year-old male with ankylosing spondylitis, who developed endobronchial and widespread pulmonary tuberculosis, 2 years after initiation of treatment with infliximab. The patient had already been treated for a positive PPD skin test with a 9-month prophylactic course of isoniazid. He was treated with a five drug anti-tuberculosis scheme but he showed an extremely slow therapeutic response with daily high fever, even 4 months after initiation of treatment. Seven months after beginning anti-tuberculosis therapy, bronchoscopy still revealed necrotic and inflammatory tissue at the site of the original lesions. This unusual clinical course of tuberculosis infection was attributed to immunosuppression due to the long-lasting anti-TNF-alpha action of infliximab.

Epidemiologic aspects of tuberculosis in the Suruí Indians, Brazilian Amazon

Tuberculosis persists as a serious public health problem in Brazil. Prevalence rates are alarming in certain social groups, including indigenous peoples. This article presents an epidemiological analysis of records for the Suruí Indians available at the Tuberculosis Control Program in the Municipality of Cacoal, Rondônia. The study includes a descriptive statistical analysis of cases reported from 1975 to 2002. There is evidence that the Suruí have an increased risk of acquiring and dying from tuberculosis as compared to other indigenous groups in Rondônia as well as non-Indians. The average incidence coefficient for tuberculosis in the Suruí was 2518.9 per 100,000 inhabitants in the period 1991-2002. It was observed that 45% of the cases were diagnosed in children < 15 years old. Over half of the cases (63.3%) were reported in men. Only 43.2% of the cases were confirmed by sputum microscopy. The use of PPD skin tests, histopathological exams or bacteriological culture were not reported throughout the period. Attention is called to the need for prevention and control measures specifically tailored to the reality of indigenous peoples.

Isolated hepatic tuberculosis in a transplanted liver

The incidence of tuberculosis (TB) has been increasing, especially in immunocompromised patients. It was reported that the overall incidence of TB in solid-organ transplant recipients is 0.8%. Hepatic graft TB was reported once before in a child, who underwent living-related hepatic graft transplantation. A 43-year-old man underwent orthotropic liver transplantation (OLT) in October 1999. His pre-transplant work-up was negative for TB (history and PPD skin test). He developed an episode of acute rejection which responded to steroids. He was discharged home on December 1999 with normal liver function tests (LFT). His LFT remained normal during January 2000, but his serum transaminases were found elevated on February 2000 (aspartate aminotransferase [AST] 206, alanine aminotransferase [ALT] 266). A liver biopsy then showed no evidence of TB or cytomegalovirus disease. The patient continued to have stable elevation of his serum AST and ALT until late March 2000 when a repeat liver biopsy showed caseating granuloma. The patient was started on anti-TB medications, with which he was compliant. By mid-May 2000 he was doing well, with significant reduction in his transaminase levels (AST 72, ALT 79). A retrospective inquiry about the donor revealed that he was a healthy young man from India, who died in a road traffic accident. To our knowledge our patient appears to be the first case reported of isolated hepatic TB in the OLT patient population. It is likely that the allograft was infected prior to transplantation and the disease was reactivated nearly 3 months after the procedure.

Risk factors predict positive PPD skin test in inflammatory bowel disease patients starting infliximab

Risk factors predict positive PPD skin test in inflammatory bowel disease patients starting infliximab

Chest radiography and thoracic computed tomography findings in children who have family members with active pulmonary tuberculosis

Objective: The chest radiography and TCT findings in children who had contacted with adult family members with active pulmonary tuberculosis were compared. The contributions of thoracic computed tomography to the diagnosis of tuberculosis were investigated. Methods and material: The children who were 0–16 years old ( n=173) and children of families with an adult member which was diagnosed as pulmonary tuberculosis were evaluated. The children were considered in two groups based on the absence ( n=125) or presence ( n=48) of complaints and/or ambiguous symptoms such as lack of appetite, mild cough, sweating, history of lung infection, low body weight and those with suspicious chest radiography findings (12 cases) were included in this study. Asymptomatic patients ( n=125) did not undergo TCT. Patients who had positive PPD skin tests only received isoniazid. If the TCT demonstrated enlarged lymph nodes or parenchymal lesions, minimally active pulmonary tuberculosis was diagnosed and antituberculous treatment was given. Results and discussions: TCT revealed lymph node enlargement or parenchymal lesions in 39 children (81.2%). Of the 12 children whose CXRs revealed suspicious lymph node enlargement and/or infiltration, five had normal findings in TCT whereas the initial findings were confirmed in the remaining seven. These data suggest that there is a correlation between the presence of ambiguous symptoms in exposed children and TCT findings; chest radiography and TCT findings do not yield parallel findings. All the patients who received anti-TB treatment were resolved in the control examinations. Conclusion: In this study there is a correlation between presence of ambiguous symptoms and TCT findings, but the chest radiography and TCT findings do not yield harmony in exposed children with ambiguous symptoms (suspicious tuberculosis cases). These observations should be considered in children with symptoms similar to those of exposed children, but with no definite history of exposure. If similar TCT findings observed in such patients, treatment for tuberculosis should be considered.

Do prognostic parameters of remission versus relapse after Bacillus Calmette-Guérin (BCG) immunotherapy exist?. analysis of a quarter century of literature.

To review prognostic factors identified in clinical trials for remission versus relapse after intravesical adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy for superficial bladder cancer (Ta, T1, and carcinoma in situ). Information was retrieved by a MEDLINE search of the English literature. Indexing terms comprised bladder cancer, bladder neoplasm, BCG vaccine, superficial bladder cancer, immunotherapy, intravesical therapy, prognostic marker, and Bacillus Calmette-Guérin. Fifty clinical studies were assessed for the strength of their results on the therapeutic response to BCG instillation. Emphasis was placed on clinical trials that assessed tumor and/or host characteristics, immunological reactions, recurrence rates, progression rates and disease-specific survival after BCG. The predictive value of host factors is extremely controversial, but marked adverse reactions to BCG instillation appear to be associated with a better tumor response. Traditional pathological tumor characteristics, molecular markers (p53) and immunological status (PPD skin test) do not appear to have prognostic value in this setting. There is increasing evidence that immunologic markers are predictive of the BCG response, but most of them have not yet been assessed in large prospective studies. Histologic/cytologic response criteria are the critical determinant of post-BCG outcome. After a quarter century of clinical research, no independent prognostic factor for the bladder tumor response to BCG has yet been identified. Sophisticated individual therapeutic approaches (SITA) appear to be the most promising. Nomograms based on host, tumor and immunological characteristics may help with clinical decision-making and with rationalized BCG schedule design.

Tuberculosis Infection, a Challenge to Diagnose and Treatment in Hemodialysis Patients

PURPOSE OF STUDY: The immunologic rearrangements in chronic renal failure have increased the susceptibility to tuberculosis (TB) infection. We present our experience in the diagnosis and treatment of TB among hemodialysis patients in our centre. METHODS: Since 1997–2001 tuberculosis was diagnosed in 26 patients (17 male, 9 female, mean age: 44.5 ± 14.3 years, HD duration 52.6 ± 34.1 months) that make an incidence of %2 per year. RESULTS: TB infection was characterized with an insidious while the main symptoms were fever in 80.7%, weight loss in 46.1% and night sweats in 30.7% of the patients. PPD skin test was ≥ 10 mm in 46.1%, 5–10 mm in 30.8%, and anergic in 23.1% of the patients. The major site of presentation was extrapulmonary TB in 76.9% of the patients predominating as lymphadenitis in 11 patients where as there were bone involvements in 2, peritoneum 4, and liver granuloma formation in liver in 1 patient. In addition to 4 patients with pulmonary involvement, 2 patients were diagnosed to have miliary TB. Our therapy protocol included administration of morfazinamid and ethambutol for 2 months and isoniazid, rifampicin for 9 months. In patients with miliary TB streptomycin was added to therapy. Mortality rate was 15.3%, while the rest of the patients were completely cured of TB. Old age, presences of malnutrition and infection with other bacterial agents have been found to be the major factors influencing the morbidity and mortality in these patients. CONCLUSION: There is a high incidence of TB infection in HD patients in Turkey. Insidious onset and extrapulmonary involvement are challenging problems in the diagnosis. Mortality rate is still high despite appropriate treatment.

A meta-analysis of the effect of Bacille Calmette Guérin vaccination on tuberculin skin test measurements

Background: The accurate diagnosis of latent tuberculosis infection (LTBI) is an important component of any tuberculosis control programme and depends largely on tuberculin skin testing. The appropriate interpretation of skin...

Tuberculosis exposure of patients and staff in an outpatient hemodialysis unit

Background: Patients receiving hemodialysis are generally considered to be at increased risk of developing tuberculosis (TB). We evaluated a 13-station chronic outpatient hemodialysis unit associated with a community hospital in northern California. Within 6 months, there were 2 incident source cases in the unit of active smear positive pulmonary tuberculosis; the first in a health care worker (HCW), diagnosed April 3, 1998, and the second in a patient undergoing dialysis treatment in October 1998. We describe the cases; the evaluation of exposures; and the institution of an intentional prospective TB control plan, designed specifically for the unique hemodialysis setting. Methods: We evaluated 23 HCWs twice and 89 patients undergoing hemodialysis treatment who were exposed to case 1 and 38 patients who were exposed to case 2. All 23 HCWs had documented prior negative Sierbert purified protein derivative of tuberculin (PPD) status and were retested at 12 weeks after exposure. None of the patients had documentation of PPD status. All of the patients were skin-tested initially with use of the 2-step method, and those with positive test results were offered isoniazid (INH). Results: One of the 23 HCWs' negative baseline PPD skin test status converted after exposure to case 1, and none of the remaining 22 converted after exposure to case 2. Twelve of 89 exposed patients with no prior skin test record had positive results for PPD after initial testing with the 2-step method. Three of the 12 (25%) patients were treated with INH at the discretion of their attending nephrologist. The 77 patients with negative results for PPD still had negative test results when retested at 3 months. None of 38 patients who underwent dialysis on the same schedule as source case 2 had a converted PPD test. Restriction fragment length polymorphism on TB isolates from both source cases ultimately showed them to be unrelated strains. Conclusion: Our experience with these exposures suggests that TB screening of patient populations undergoing renal dialysis—though they have intrinsic high anergy rates—is advisable with a designed prospective plan before any inadvertent and/or repetitive exposure of that population to active TB. A planned intentional TB control program increases HCW awareness of TB, establishes baselines for evaluation, decreases “panic” in the event of subsequent exposures, and emphasizes the rationale for preventive therapy. (Am J Infect Control 2002;30:307-10.)

Disseminated Peritoneal Tuberculosis Mimicking Metastatic Ovarian Cancer

A 41-year-old woman had a 2-week history of low-grade fever, associated with gradually increasing abdominal pain and girth. Ultrasonography showed a complex cystic right adnexal mass. Diffuse nodules (0.1 to 0.5 cm) were found at exploratory laparotomy involving the serosal surfaces of the uterus, fallopian tubes, and ovaries. She had a total abdominal hysterectomy, with bilateral salpingo-oophorectomy and omentectomy for presumed stage IIIC ovarian carcinoma. Histopathologic examination showed chronic granulomatous inflammation with no evidence of neoplasm. Special stains on tissue sections and ascitic fluid were negative for fungi and mycobacteria. Additional history indicated a recently positive PPD skin test (within 6 months), followed by isoniazid therapy for 4 months. Polymerase chain reaction (PCR) done on paraffin-embedded tissues produced evidence of Mycobacterium tuberculosis. Ascitic fluid cultures became positive for M. tuberculosis at 6 weeks. The patient was placed on four-drug antituberculous therapy and had a complete recovery.

Disseminated Peritoneal Tuberculosis Mimicking Metastatic Ovarian Cancer

A 41-year-old woman had a 2-week history of low-grade fever, associated with gradually increasing abdominal pain and girth. Ultrasonography showed a complex cystic right adnexal mass. Diffuse nodules (0.1 to 0.5 cm) were found at exploratory laparotomy involving the serosal surfaces of the uterus, fallopian tubes, and ovaries. She had a total abdominal hysterectomy, with bilateral salpingo-oophorectomy and omentectomy for presumed stage IIIC ovarian carcinoma. Histopathologic examination showed chronic granulomatous inflammation with no evidence of neoplasm. Special stains on tissue sections and ascitic fluid were negative for fungi and mycobacteria. Additional history indicated a recently positive PPD skin test (within 6 months), followed by isoniazid therapy for 4 months. Polymerase chain reaction (PCR) done on paraffin-embedded tissues produced evidence of Mycobacterium tuberculosis. Ascitic fluid cultures became positive for M. tuberculosis at 6 weeks. The patient was placed on four-drug antituberculous therapy and had a complete recovery.

Repeatedly negative tuberculin skin tests followed by active tuberculosis in an immunocompetent individual

We describe a woman who was repeatedly tuberculin (PPD) skin test negative after exposure to smear-positive tuberculosis (TB), but developed active TB with a positive skin test 7 years later. Molecular epidemiologic evidence is presented that the infection was contracted 7 years previously from the original source case. PPD skin testing is subject to many technical and biological variables and this report underscores that this tool can fail to detect latent TB infection in some cases. The causes of false-negative and false-positive PPD skin test results are reviewed.

Enhancement of the human T cell response to culture filtrate fractions of Mycobacterium tuberculosis by microspheres

An improved method of assessment of the human immune response against Mycobacterium tuberculosis antigens will assist the development of new vaccines or diagnostic reagents. In this study, we have analyzed human T cell responses to culture filtrate fractions (CFF) of actively replicating M. tuberculosis strain H37Rv using peripheral blood mononuclear cells from healthy PPD skin test positive and negative individuals. Adsorption of CFF onto polystyrene microspheres, that were approximately the size of the M. tuberculosis (bead-adsorbed antigens, BAA) significantly enhanced IFN-γ production compared to soluble antigens (SA) in PPD skin test positive individuals in an antigen-specific manner. Further, BAA induced activation of both CD4 + and CD8 + T cell subsets. However, CD4 + responses in general were higher and their antigenic repertoire was wider than the CD8 + responses. By contrast, CD8 + responses were strongest to the lower molecular weight BAA. When CFF were chemically coupled to carboxyl modified microspheres (bead-coupled antigens, BCA), induction of IFN-γ was similar to BAA. Enhancement of T cell responses to particulate M. tuberculosis antigens may prove useful in vaccine design strategies.

Evaluation of a Western Blot Test as a Potential Screening Tool for Occupational Exposure to Mycobacterium tuberculosis in Health Care Workers

Health care workers (HCWs) have a higher than average risk for contracting Mycobacterium tuberculosis (MTB) infection and tuberculosis (TB). No markers of MTB-exposure are available, and TB risk assessment is performed by tuberculin screening, identifying individuals with acquired MTB infection. This study evaluated a western blot (WB) anti-M. bovis A60 complex antibody as a MTB-exposure marker. WB reactivity was evaluated on 127 exposed and 28 non-exposed HCWs from four divisions of the Policlinico Hospital of Modena, and 140 non-exposed bacille Calmette-Guérin-vaccinated controls. Excess of occupational TB risk according to the Occupational Safety and Health Administration (OSHA) was calculated in each division. WB-positivity (%) was: (1) significantly higher in exposed HCWs compared with non-exposed (72% vs 25%, P < 0.00001), (2) highly related (r = 0.99) to OSHA risk excess in all divisions, (3) higher than non-exposed in HCWs with short (< 5 years) MTB-exposure (purified protein derivative [PPD], P > 0.18; WB, P < 0.04). PPD-positivity (%) was higher than controls only in HCWs with longer (> 5 years) MTB-exposure. The study suggests that the WB antibody might represent a more sensitive biological marker of MTB contact among exposed HCWs, related to the level of TB risk and detectable earlier than the PPD skin test, thus providing new tools for TB risk assessment in health care facilities.

Broad clonal heterogeneity of antigen-specific CD4 + T-cells localizing at the site of disease during tuberculosis

The repertoire of CD4 + T-lymphocytes was investigated in six patients affected by tuberculosis, who had a negative PPD skin test at diagnosis. Polyclonal CD4 + T-cell lines from the peripheral blood failed to proliferate to PPD and to the 16- or 38-kDa proteins of Mycobacterium tuberculosis, while CD4 + T-cell lines from the site of disease responded to PPD, and to the 16- and 38-kDa proteins, and derived epitopes in vitro. The repertoire of CD4 + T-cells accumulating at the site of disease was found to be widely heterogeneous as demonstrated by the finding that at least seven different peptides from the 16- and 38-kDa proteins were recognized by every patient. These results indicate that CD4 + T-cells localized at the site of disease in tuberculosis recognize a vast array of M. tuberculosis epitopes.

Randomised trial of intradermal Mycobacterium vaccae or intradermal hepatitis B immunisation in children with HIV infection

This study assessed the safety of inactivated Mycobacterium vaccae as a candidate vaccine to prevent disseminated mycobacterial disease in children with HIV infection. 35 children ages 1–8 with CD4 counts ≥300/mm 3 in New Hampshire, Boston and Chicago were randomised in a 2:1 schedule to receive a 3-dose series of intradermal M. vaccae vaccine (MV) or hepatitis B vaccine (HBV) at 2-month intervals. Immunisation was safe and well tolerated; 2-day median vaccine site induration was 5 mm in MV recipients and 0 mm in HBV recipients ( p<0.001). There were no significantly different changes in viral load or CD4 count between the two vaccine groups. No PPD skin test conversions occurred after immunisation. MV is safe and well tolerated and deserves further evaluation as a vaccine to prevent mycobacterial disease in HIV-infected children.

Tuberculin Test Conversion among Employees of a Tertiary Care Hospital in Riyadh, Saudi Arabia

The objective of this study was to determine the tuberculin skin test conversion rate, as well as the course and outcome of the converters, among employees of a tertiary care hospital. The study is a retrospective, cohort descriptive study undertaken at the King Faisal Specialist Hospital and Research Centre, in Riyadh, Saudi Arabia. The study was undertaken over a four-year period from 1993 to 1996, and the subjects were employees who had annual screening PPD skin tests. The outcome measures skin test conversion, prophylactic treatment with isoniazid (INH), side effects, and development of clinical tuberculosis. A total of 6883 tuberculin skin tests were performed during the study period. The mean annual conversion rate was 1.55%. About 78% of the converters received INH prophylaxis, but only 75% of those who started chemoprophylaxis completed the course. The side effects of INH treatment were found in 23% of those on treatment, and one of the converters developed clinically active tuberculosis during the study period. At the King Faisal Specialist Hospital and Research Centre, the mean annual tuberculin skin test conversion rate among employees is similar to that found in other studies, but compliance to oral isoniazide prophylaxis is low. There is a need to develop strategies to improve compliance.