PPD RT23 Research Articles

Neonatal BCG vaccine and response to the tuberculin test in BCG vaccinated children in contact with tuberculosis patients in Recife, Brazil.

This case-control study analyses the association between the tuberculin response and the neonatal BCG vaccine in 330 children under 15 who are home contacts of tuberculosis patients, taking into account risk factors for the transmission of infection. Interviews were conducted with 330 children, their parents or legal guardians. Chest X-rays were taken and the tuberculin test (TT) applied using 0.1 ml of PPD RT23, taking an induration reading of > or = 10 mm as the cut-off point for a positive test result. Prior BCG vaccination was ascertained by observing the presence of a scar on the deltoid region of the right arm. Six children were excluded because they had signs/symptoms of pulmonary tuberculosis, thereby reducing the final sample to 324 children. The multivariate analysis showed that being exposed to a patient with pulmonary lesions with cavities (OR = 3.14; CI: 1.59-6.20; p = 0.000), a positive sputum smear (OR = 3.65; CI: 1.52-8.78; p = 0.002) or a positive culture (OR = 4.42; CI: 1.39-14.1; p = 0.005), being under five (OR = 0.47; CI: 0.22-0.99; p = 0.045) are independently associated with a positive TT. The fact that a prior BCG scar is not associated with a positive response to the TT indicates the need to re-open discussion of the guidelines which exist in many poor countries where tuberculosis is still a serious public health problem. Such guidelines include those issued by the Brazilian Ministry of Health, which considers the child under 15 in contact with a tuberculosis case to be infected only if there is a TT of 10 mm or more and the child received no prior BCG vaccination.

Predictive value of tuberculin induration at 24 h in healthy schoolchildren.

Tuberculin (1 TU PPD RT23 Tween 80) was administered to 500 healthy schoolchildren, aged 5-9 years. The induration at 24 h was compared with that at 72 h. The mean (standard deviation) induration of the tuberculin reaction at the end of 24,48 and 72 h was 4.5 (6.75), 4.4 (7.11) and 4.0 (6.91) mm, respectively. When the tuberculin reaction was 0-9 mm, a significant difference was noted between the 24- and 72-h reading (p = 0.0001). There was no difference in the size of the tuberculin reaction between the 24- and 72-h readings when the reaction size was > or = 10 mm (p > 0.05). Considering a tuberculin induration of < 10 mm as negative tuberculin reaction for our reference population in South India, the sensitivity, specificity, positive predictive value and the negative predictive value in our study for the 24-h reading were found to be high. The predictive value of 24-h induration was not affected by age. Reading and interpretation of tuberculin test after 24 h needs due consideration in clinical practice.

Usefulness of Tuberculin Skin Test by Tuberculin PPD RT23 2 TU

Background : Tuberculin skin test is a method to examine M. tuberculosis infection and has been used all over the world. But various factors make it difficult to understand testing results. In 2000, the American Thoracic Society recommended that skin test results should be decided by considering risk factors of the tested. In Korea, high tuberculosis infection rate and BCG vaccination rate make it difficult to differentiate current infection, past infection, and no infection by the skin test. This study was attempted to examine a negative predictive value of the skin test to understand how the skin test acts on deciding administration of anti-tuberculosis drug. Methods : From Mar. 1 to Jul. 31 in 2001, the test was performed for patients hospitalized in Department of Internal Medicine, Hallym University College of Medicine, Chunchon, Korea by administering Tuberculin PPD RT23 2 TU (0.1 ml)to them that has been currently used in Korea based on Mantoux method. They were decided to be infected with tuberculosis bacilli by following diagnostic standard: 1) tuberculosis bacilli was cultured in sputum by microbiological diagnostic standard or Acid-fast bacilli was proven on a microscopic examination or 2) tuberculosis bacilli was not proven in the aforesaid microbiological test by clinical diagnostic standard, while there was opinion or symptom suitable for tuberculosis by radiographic or histological standard so the doctor decided to apply the tuberculosis treatment. Results : In this study, total 210 patients except 20 patients (8.7%) among 230 hospitalized patients were evaluated. Their average age was 60±16.8 years, and male-female rate was 1.28 : 1 (male: 118, female: 92). Number of patient, who was diagnosed and decided as tuberculosis, was 53(25.2%). Pulmonary tuberculosis was found in 45 patients (84.9%); 22 patients were decided to be positive in the Acid-fast bacilli smear test by microbiological examination (culture positive: 13, culture negative: 9), and 23 patients were decided to be tuberculosis patients by clinical diagnosis standard. Tuberculosis pleuritis was found in 8 patients (15.1%); 4 patients were diagnosed and decided by histological standard, and 4 patients were decided and treated by clinical standard. In differentiating patients into 'Negative' and 'Positive' by the skin test standard of the American Thoracic Society, negative predictive value 92.3%, positive predictive value 47.3%, sensitivity and specificity were 83%, 68.8%, respectively. Conclusion : In hospitalized respiratory patients, there was high negative predictive vlaue 92.3% by tuberculin skin test, therefore skin test would be a important factor for deciding administration of anti-tuberculosis drug on negative skin test patient.

Tuberculin test.

Although tuberculin test is widely used for detection of tuberculous infection among children, there is no clear understanding about its performance and interpretation. This article has been written with the purpose of elucidating the performance and interpretation of standard tuberculin test, based on the experiences gained at the National Tuberculosis Institute, Bangalore and other centres. The standard tuberculin test involves intradermal injection of '1TU PPD RT23 with Tween 80' on the mid-volar aspect of forearm and measurement of the maximum transverse diameter of induration after 3 days. Larger the size of induration, higher is the probability of it being due to tuberculous infection. The majority of reactions with induration size of 15 mm and above are attributable to infection with tubercle bacilli, irrespective of BCG-vaccination status. While indurations of less than 5 mm indicate absence of any kind of tuberculin sensitivity, the majority of indurations in 5-9 mm range are usually of non-tuberculous nature. An induration of 10-14 mm requires more careful interpretation. It is more likely to be attributable to infection with tubercle bacilli in case of history of contact with smear positive case or among children with clinical findings of tuberculosis. However, the size of induration in an infected child may be diminished in the presence of immuno-suppressive conditions. One should also consider the purpose of the test while interpreting the test results.

Tuberculin test in the diagnosis of childhood tuberculosis: Analysis of quantitative and qualitative features

OBJECTIVE: To evaluate the role of the tuberculin test in the diagnosis of tuberculosis in children. METHODS: Test diagnosis study; Tuberculin test with PPD Rt 23 (2 UT) was performed in 158 children, distributed in 2 groups: 101 no tuberculous, BCG vaccinated children and 57 tuberculous ones (diagnosis by clinical-radiological and epidemiological features). The interpretation of the tuberculin test was made by quantitative analysis (Mantoux test) and qualitative analysis (Koch and Listeria phenomena). RESULTS: Using cutoff = 10mm in Mantoux test, we found sensitivity of 85.9% and specificity of 86.1%. The qualitative analysis (Koch phenomenon), showed sensitivity of 77.2% and specificity of 98%. CONCLUSION: The qualitative analysis of the tuberculin test was useful in the diagnosis of tuberculosis in children, associated to the Mantoux test interpretation.

Mycobacterial infections in HIV-infected patients in Cali, Colombia

The prevalence of mycobacterial infections was determined in a sample of 155 individuals infected with human immunodeficiency virus (HIV) who were treated in the Social Security Institute (SSI) of Cali, Colombia. A tuberculin test (2 TU PPD RT23) was used, and the presence of mycobacteria was checked through direct microscopy and culturing blood, urine, feces, and gastric aspirate. When clinically indicated, samples of cerebrospinal fluid, bone marrow, and sputum were also examined and cultivated. The absence of reactivity to tuberculin was significantly more frequent in the patients than in the controls (91.3%, compared to 57.4%; chi 2 = 33, P = 0). The prevalence of tuberculosis was 6.5%, in comparison with 0.04% among a group of HIV-negative ISS members (exact binomial 95% confidence interval: 0.0313% to 0.1154%). Nontuberculous mycobacteria (NTM), present in 43 patients, were significantly more frequent than Mycobacterium tuberculosis (27.7%, versus 6.5%; chi 2 = 24.78, P = 0.000,001), but they caused illness only in some cases. The most common species were those of the M. avium-intracellulare complex. M. avium-intracellulare and M. fortuitum had a total prevalence of 7.1% and were the most-prevalent NTM that caused disease in these patients (4.5%); they were also responsible for three cases of disseminated infection. Clinical disease caused by M. tuberculosis or NTM and complete tuberculin anergy were associated with stage-IV HIV infection and with CD4 lymphocyte counts < or = 400/microL. However, the lack of immunocellular response, shown by limited tuberculin reactivity, was found beginning with the asymptomatic HIV carrier stage. The progressive deterioration of the immune system of HIV-positive patients is the determining factor in the high morbidity and mortality with mycobacteria infections and requires prompt chemoprophylaxis or treatment.

Tuberculosis infection and disease among schoolchildren: the influence of the HIV epidemic and of other factors.

BACKGROUND: The HIV/AIDS epidemic has caused an excess of tuberculosis cases in Spain and in other countries, but its impact on tuberculosis infection is less well understood. This study presents...

Use of two methods of analysis to estimate the annual rate of tuberculosis infection in Southern Algeria

Setting: Analysis of tuberculin skin test surveys. Objective: To estimate the annual tuberculous infection rate in Tamanrasset (southern Algeria) by applying on the one hand the classical method of the Tuberculosis Surveillance Research Unit (TSRU) of the International Union Against Tuberculosis, and on the other the study of variations of allergy published by Raj Narain et al. Methods: 3675 pupils aged 5–18 years were tested in October 1982 or November 1983; 1240 of them were tested on both occasions. The technique of the World Health Organization, with 2 TU PPD RT23 tuberculin was used by trained testers. The TSRU method was applied to the 863 children aged 5–15 years without bacille Calmette-Guerin (BCG) scar, according to three estimates of the prevalence of infection (cut-off points of the distribution of reactions of 10 mm, of 14 mm corrected by dividing by 0.82, and mirror technique with a mode of 17 mm), and to three hypotheses of the decrease in infection risk (1%, 3% and 5%). The study of variations of allergy was used in the 1240 pupils tested twice (BCG-vaccinated or not). Results: The average annual risk of tuberculous infection estimated by the TSRU method was lower than 1 % (0.5%–0.6% according to the most stringent criteria). By the method of variations of allergy, the estimated annual infection rate was 0.9%. For the latter, our results are consistent with those obtained by other researchers. Conclusions: These findings suggest that the study of variations of allergy might be a good alternative approach to estimate the annual infection rate in countries where children are BCG-vaccinated at birth, which is the case for most developing countries.

Clinical evaluation of MPT-64 and MPT-59, two proteins secreted from Mycobacterium tuberculosis, for skin test reagents

Setting: Department of Pulmonary Medicine P, Bispebjerg Hospital, Copenhagen, Denmark. Objective: To study the ability of two proteins secreted from Mycobacterium tuberculosis, MPT-64 and MPT-59 to induce delayed type hypersensitivity (DTH) reactions following intradermal administration. Design: In a small scale clinical investigation, skin reactions to these antigens were compared to reactions to tuberculin PPD RT23 in 1) patients with active tuberculosis, 2) BCG vaccinated healthy subjects with close contact with tuberculous patients, and 3) BCG vaccinated healthy subjects without contact with tuberculous patients. Tests for in vitro reactivity to these antigens were carried out in similar groups. Results: All subjects gave positive reaction to tuberculin PPD RT23, whereas approximately half of the subjects in each of the three groups reacted to MPT-59. Two subjects (one patient with tuberculosis and one healthy bacille Calmette-Guérin vaccinated subject without patient contact) reacted to MPT-64. The studies of cell proliferation and induction of interferon-γ (IFN-γ) following stimulation with tuberculin PPD and MPT-64 supported this profile of reactivity. Conclusion: None of the experimental skin test antigens had properties superior to tuberculin PPD RT23 in humans. The failure of MPT-64 to induce delayed type hypersensitivity reactions in the majority of tuberculosis patients is discussed, in view of the potent reactivity to MPT-64 in tuberculous guinea pigs.

Palpable lymph nodes of the neck in Swedish schoolchildren

We studied 3592 Swedish schoolchildren, 8 or 9 years old, examined for palpable submandibular, cervical and supraclavicular lymph nodes. All children were skin tested with 2 TU PPD RT23 and with 0.1 microgram of Mycobacterium avium sensitin or 0.1 microgram of M. scrofulaceum sensitin. A total of 991 children had palpable lymph nodes in any of the three locations. Among them, 811 had lymph nodes in one location, 162 in two locations and 18 in three. In 312 children, the lymph nodes were > or = 5 mm in size in any location. The most common location was submandibular. Boys had a significantly higher prevalence of palpable lymph nodes than girls. There was also seasonal variation. Children infected by atypical mycobacteria (sensitin reaction > or = 6 mm) did not have a higher prevalence of palpable lymph nodes than those not infected.

The evolution of tuberculosis infection among schoolchildren in Barcelona and the HIV epidemic

Setting: First grade students in primary schools in the city of Barcelona, Spain. Objective: To estimate the prevalence of tuberculin reaction and sources of infection; to analyse trends in comparison with previous data. Design: Tuberculin screening of first grade schoolchildren (1985 birth cohort) was undertaken in 1991–1992 using 2 TU of PPD RT23. Results: The prevalence of reactors among the 12 007 children tested from the 1985 cohort was 0.87%, varying among districts between 0.13% and 3.03%. Follow-up of positive tests was completed for 75 children, which led to the identification of 6 cases of previously unknown clinical tuberculosis among these children, while for 14 infected children index cases were found, one of whom was a confirmed HIV-infected IVDU. Conclusion: The comparison of results with data from previous studies suggests that tuberculosis infection among schoolchildren in Barcelona may not be declining as in previous years, especially in areas such as the inner city, where poverty combines with HIV infection and with increasing migration from countries with a higher tuberculosis prevalence.

Sensitivity to sensitins and tuberculin in Swedish children. Part 5: a study of school children in an inland rural area

Setting: Since 1986 we have tested approximately 7000 non-BCG-vaccinated Swedish children with tuberculin and with Mycobacterium avium or M. scrofulaceum sensitin. In Göteborg, an urban coastal area, 25% of 8–9-year-old school children reacted to M. avium sensitin and 32% of M. scrofulaceum sensitin using a 6 mm cut-off. Objective: To evaluate if geographical factors have an influence on the prevalence of children reacting to tuberculin and sensitins. Design: 2000 schoolchildren of the same age as those in Göteborg but living in an inland rural area were Mantoux-tested in a similar way (simultaneously on separate arms with PPD RT23 and either of the two sensitins). Results: 15% reacted to PPD RT23, 9.7% to M. avium and 13.9% to M. scrofulaceum sensitin. None of the children with a PPD RT23 reaction >=6 mm showed signs of tuberculosis or had any known exposure. A reaction to PPD RT23 was usually combined with a still larger sensitin reaction. Conclusion: There was a considerable geographic difference in sensitin reactivity, low in an inland rural area compared to a coastal urban area. Children reacting to PPD RT23 had probably not been infected by M. tuberculosis but more likely by atypical mycobacteria. The reactions should be interpreted as cross-reactions.

Comparative study of skin testing with PPD and new tuberculins by the WHO Mantoux test

PPD RT 23 tuberculin and two batches of new tuberculin (NT) were tested for concordant skin indurations in the WHO standard Mantoux test in 11- to 13-year-old Finnish school children BCG vaccinated at birth. All were double tested with RT 23 and with either batch T1327 (614 children) or with batch T1456 (312 children) of NT. The results were compared with data available from an earlier study employing RT 23 and T1327 in Ethiopian children, 50/134 of whom had a BCG scar. The mean induration to RT 23 after 72 h was slightly smaller than to the NTs. The individual readings for RT 23 had significant linear correlations with T1327 in Finland (r = 0.77) and in Ethiopia (r = 0.89), and for T1456 (r = 0.83; P < 0.001 for all three). Zero reactions were much fewer to NTs (5.5 % to T1327 and 0.3 % to T1456) than to RT 23 in Finland (18.2 % and 9.3 % respectively for the two groups). The results were similar in Ethiopian children. Our results indicate that RT 23 and the two NTs give concordant results, but NTs seem to be more specific, perhaps because they retain more species-specific antigens. Analysis of our results suggests that different peaks in the distribution of reaction sizes were due to responses to different antigens or combinations of antigens, and in the case of the largest reactions, to a different type of immunological response.

Sensitivity to sensitins and tuberculin in Swedish children. IV. The influence of BCG-vaccination

BCG-vaccinated schoolchildren, 8-9 yrs of age, were simultaneously tested on separate arms with tuberculin and a sensitin. Using the 6 mm cut-off they reacted in 49% to two tuberculin units purified protein derivative (PPD RT23), in 67% to 0.1 micrograms Mycobacterium avium sensitin RS10, and in 58% to 0.1 micrograms M. scrofulaceum sensitin RS95. The corresponding figures for non-BCG-vaccinated schoolchildren of the same age tested at the same time were 3, 25 and 32%, respectively. The results indicate a stimulating influence of BCG-vaccination on tuberculin and sensitin reactivity. Since the sensitin reactions were the larger ones, these reactions were not only due to the vaccination. The BCG-vaccinated schoolchildren seem to have acquired infections by atypical mycobacteria despite vaccination.

Sensitivity to PPD tuberculin and M. scrofulaceum sensitin in schoolchildren BCG vaccinated at birth

Objective: To determine the degree of and variation in sensitivity to PPD RT 23 tuberculin and M. scrofulaceum sensitin RS 95 at school age in children BCG vaccinated at birth. Design: Double-testing by applying standard WHO Mantoux tests and inspecting BCG scars. Setting and participants: Urban and rural schools in Southwest Finland, 1091 children aged 11–13 years. Main outcome measures: Size of tuberculin and sensitin indurations and BCG scar (mm). Results: The mean size of tuberculin indurations was 7.2 mm, sensitin indurations 8.1 mm and BCG scars 7.9 mm. The reaction to sensitin was significantly larger than to tuberculin (95% confidence interval 0.58−1.10 mm) and the zero reactions to sensitin were fewer. Correlation between tuberculin and sensitin indurations was significant (r = 0.75, 95% confidence interval 0.72−0.77). There were induration ⩾ 15 mm to tuberculin in 16% and to sensitin in 14%. Sensitin indurations exceeded those of tuberculin by 4 mm or more in 14% of the children with at least 5 mm tuberculin indurations. Conclusions: High tuberculin sensitivity in healthy schoolchildren may be partially maintained by contact with environmental mycobacteria. Our data do not prove but very probably indicate that children have protective immunity. In view of the current incidence of tuberculosis in Finland and the likelihood that lymph node infections and sensitivity to environmental mycobacteria will increase, continued BCG vaccination at birth is recommended.

Sensitivity to sensitins and tuberculin in Swedish children I. A study of schoolchildren in an urban area

Non-BCG-vaccinated schoolchildren (8 or 9 years of age) were simultaneously tested on separate arms with 2 IU PPD RT23 and 0.1 pg Mycobacterium avium sensitin RS10 or 0.1 Fig Mycobacterium scrofulaceum sensitin RS95. None of the 2819 analysed children had any known exposure to tuberculosis. A total of 3.4% reacted with an induration ⩾ 6 mm to PPD RT23. Half the number of children were tested with M. avium sensitin and 25.4% reacted while the remaining were tested with M. scrofulaceum sensitin and 32.4% reacted when the cut-off was 6 mm. For about 90% of the children the sensitin reaction was larger than or equal to the tuberculin (PPD RT23) reaction. Correlation analyses showed that moderate and high PPD RT23 values were combined with still higher sensitin values, indicating that the tuberculin reactions were mainly cross-reactions due to the antigenic similarity between tuberculin and sensitins. The presence of birds, dogs and cats in the homes was combined with an increased frequency of children reacting to the sensitins used. The children with reactions to PPD RT23 ⩾6 mm were examined and chest X-rays were performed. None of them showed any signs or symptoms of mycobacterial disease. In non-BCG-vaccinated Swedish schoolchildren without clinical signs of tuberculosis and without known contact with a contagious tuberculous person, indurations less than 12 to 14 mm on tuberculin testing are probably caused by atypical mycobacteria. In such cases sensitin tests should be performed to verify the suspicion.

Sensitivity to sensitins and tuberculin in Swedish children II. A study of preschool children

Non-BCG-vaccinated preschool children (4 or 5 years of age) were simultaneously tested on separate arms with a 2 IU PPD RT23 and 0.1 μg Mycobacterium avium sensitin RS10 or 0.1 μg Mycobacterium scrofulaceum sensitin RS95. None of the 762 children had any known exposure to tuberculosis. A total of 8.8% reacted with an induration (⩾ 3 mm to PPD RT23 while 2% reacted with ⩾ 6 mm. Half the children were tested with M. avium sensitin: 18.9 and 7.8% reacted when 3 and 6 mm cut-off points, respectively, were taken. The remaining children were tested with M. scrofulaceum sensitin: 18.4 and 6.3%, respectively, reacted. In a previous study of schoolchildren aged 8 or 9 years, reactions to sensitins were considerably more frequent. Thus, sensitisation by atypical mycobacteria seems to increase from the preschool to the early school age. This finding probably reflects a continuous exposure of the children to atypical mycobacteria from various sources. The preschool children with a reaction to PPD RT23 ⩾ 6 mm were examined and chest X-rays were performed. All children were healthy but one child had enlarged lymph nodes in the mediastinum and abdomen. It cannot be excluded that these pathological findings were caused by atypical mycobacteria.

Reacción tuberculinica en lactantes sanos vacunados con BCG al nacer

Tuberculin test with PPD RT-23 with Tween 80 (2 TU strength), was performed to 228 infants under two years of age. None of them had any history of contact with tuberculosis. All were healthy, well-nourished infants, and had been vaccinated with BCG at birth. A positive PPD reaction (greater than 6 mm), was found only in 8.8%, of them and 16.2% had no BCG scar on examination; 14.9% of the studied infants had negative PPD (0-5 mm) reactions together with absent BCG scars. These findings are significantly different from those previously reported by chilean authors, which showed higher proportion of positive (greater than = 6 mm) reaction to 2 TU PPD in infants from similar populations that had been vaccinated with different BCG preparations than our patients. These results suggest the need to evaluate the efficacy of the BCG vaccines that are currently being used in our country to determine the factors that may affect it and the protection that they afford.

Tuberculin response of Sri Lankan children after BCG vaccination at birth

A total of 740 healthy children aged between 3 months and 11 years who had received BCG vaccination in the first month of life were Mantoux tested in Sri Lanka. Despite 97 % having a visible scar following vaccination, 80 % showed Tuberculin anergy (0–1 mm). Those without a scar showed no response. There was no correlation between scar size and the Mantoux response.A low mean Mantoux reaction was seen at all ages: 3.5 mm at 3 months, 3.2 mm at 18 months, 1.8 mm at 5–7 years and 1.9 mm at 9–11 years. A significant waning of the Mantoux reaction occurred at 5–7 years but there was no significant change at 9–11 years. Children who had received routine revaccination at 10 years, having received the first at birth, had a significantly higher mean Mantoux reaction (9.6 mm) when tested 3 months after revaccination. In 90 bacteriologically proven tuberculous patients, there was a significantly increased Mantoux reaction compared to all other groups. 1 T.U. PPD RT 23 (with tween 80) was used in all instances for Mantoux testing.The present study shows that routine BCG vaccination at birth, using a reduced dose of 0.05 ml, is unlikely to interfere subsequently with the diagnostic value of the Mantoux test. However, revaccination at 10 years may do so.

Comparisons in sensitized and unsensitized guinea-pigs of tuberculin PPDs RT 23 and PPD-M by skin tests and lymphocyte stimulation tests. Effect of immunization time

The biological activities of tuberculin PPD RT 23 and the International Standard for Purified Protein Derivative of Mammalian Tuberculin (PPD-M) were compared in sensitized and unsensitized guinea-pigs by skin tests and lymphocyte stimulation (LS) tests. Estimates of relative potency (RP) from skin test results were dependent on the dose level, on the immunogen used, and, in guinea-pigs immunized with killed tubercle bacilli in oil, also on the immunization time. Relative potency estimates from LS results were dependant on the source of the lymphocytes and were different from estimates obtained from skin tests. Lymphocyte stimulation dose-response curves for the tuberculins were qualitatively different. In contrast to RT 23, PPD-M gave rise to non-specific skin reactions in unsensitized guinea-pigs. Both tuberculins were mitogenic to lymph node lymphocytes isolated from unsensitized guinea-pigs, PPD-M being the more mitogenic of the two tuberculins. The present results confirm that qualitatively different tuberculins cannot be unambiguously calibrated in identical terms and thus emphasize that the uncritical use of (international) standards should be avoided in tuberculin calibration.