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This study sought to evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. A prospective longitudinal follow-up was carried out on 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) were homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration or= 5 mm.). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. Active TB developed in 23 of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +or- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test, but a positive Multitest, developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and 9 who converted during follow-up). Active TB developed in 7 of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in 4 of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years), and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +or- 103 x 106/L (range, 1-400 x 106/L). Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 106/L, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.
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PMID:A prospective study of the risk of tuberculosis among HIV-infected patients. 826 7

Between April and December 1989, the chest clinic of the University Teaching Hospital in Lusaka, Zambia, confirmed pulmonary tuberculosis (TB) in 141 adults, 95 (67%) of whom were HIV-1 seropositive. Health workers made home visits to 71 of the index cases (43 HIV-1 positive and 28 HIV-1 negative) to learn whether the 348 household members would also develop TB, thus allowing researchers to determine the effect of HIV on infectiousness of TB. Contacts of HIV-1 positive patients developed TB at a lower rate than did those of HIV-1 negative patients (52% vs. 71%; odds ratio [OR] = 0.43; p .001). This difference continued even after controlling for between-household variations, indicating that confounding variables did not account for the difference. Age of contact, intimacy with the index case, and crowding in the household were associated with the tuberculin response in the contact, but they did not confound the effect of HIV status. Tuberculin response in the contact was associated with the number of bacilli in the sputum smear (crude OR = 3.13; p = .013, and adjusted OR =1.84; p = .28), suggesting that the number of bacilli somewhat explained the difference in infectiousness between HIV-1 positive and HIV-1 negative patients. 12 contacts (8 of HIV-positive cases and 4 of HIV-negative cases) developed active TB after the TB diagnosis in the index case. These findings clearly demonstrated that infection with Mycobacterium tuberculosis was less likely in household members of HIV-1 positive cases than in those of HIV-1 negative cases. The lower bacillary load in the sputum in HIV- 1 cases may have accounted somewhat for the lower infectiousness of pulmonary TB.
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PMID:The impact of HIV on infectiousness of pulmonary tuberculosis: a community study in Zambia. 835 57

Tuberculin and Candida skin tests were done on 98 HIV(+) and 42 control HIV(-) patients of AIDS Diagnosis and Therapy Center in Warsaw. Prevalence of the positive Tuberculin tests in the control group was 29% and it was not significantly different from those groups of patients HIV(+) whose CD4 cell count was higher than 350. For those with CD4 cell count 350 or below, tests were positive only in two cases both of the patients with active tuberculosis. The prevalence of positive Candida tests was in the control group only 12% and such result did not differ significantly from any other group of HIV positive patients with different CD4 cell counts. It is concluded that routine Tuberculin skin tests might be of value due to low initial prevalence among patients of the AIDS Center and that those persons who undergo conversion into positive tests will be under high suspicion of TB asymptomatic infection. Low prevalence and rather random distribution of positive Candida skin tests shows their insufficiency as single reference tests in anergy panel.
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PMID:[Initial evaluation of the diagnostic usefulness of tuberculin tests among the patients of the Center of Diagnosis and Treatment of AIDS]. 913 96

The tuberculin reaction following the intradermal injection of PPD appears 48-72 hours after injection. The positivity is shown by an > 5 mm area of induration of the skin. Tuberculin reaction is an invaluable instrument of epidemiologic investigation. Clinically, the value of tuberculin test, though remarkable, is limited by the fact that its positivity is not necessarily a sign of active tuberculosis. The three control strategies of tuberculosis are: prompt identification and correct management of cases, vaccination, prophylaxis. The latter, that in most cases is performed with isoniazid (300 mg/daily for 12 months) is indicated in the following situations: subjects with > 5 mm tuberculin test; recent contacts with patients with infective tuberculosis; chest X-ray indicative for old fibrotic lesions, HIV infection; subjects with > 10 mm tuberculin test: HIV-negative drug-addicts; clinical conditions at high risk for tuberculosis (e.g. silicosis, hematologic malignancy, iatrogenic immunosuppression).
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PMID:Tuberculin skin test and chemoprophylaxis of tuberculosis. 967 47

In summary, despite the major benefits conferred by aerosol therapy, the risk of transmission of M tuberculosis remains a concern. The most effective approach to preventing nosocomial transmission of respiratory infections such as tuberculosis is to prevent disease in patients at risk, particularly those receiving aerosol therapy. Tuberculin skin tests should be applied to all HIV-infected persons and chemoprophylaxis administered to those with greater than or equal to 5mm reaction. Early detection and treatment of tuberculosis are essential to prevent transmission both inside and outside of health-care settings. Cough-reduction measures should be taken when giving pentamidine aerosol, and patients who do cough should cover their mouths. Proper ventilation of treatment areas with negative air pressure and at least 10 air changes per hour, and more if feasible, is essential. HEPA filters should be installed to cleanse exhaust air from treatment rooms, and air should not be recirculated. The use of UV light to disinfect air is recommended only for special situations. Finally, personal protective devices should be worn by health-care workers who are exposed to patients receiving aerosol therapy when other measures do not offer adequate protection.
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PMID:Control of tuberculosis during aerosol therapy administration. 1014 36

All adult immigrant applicants to Canada undergo chest radiographic screening for tuberculosis (TB). Tuberculin skin testing could reduce the number of chest X-rays, and identify more candidates for prophylaxis. We modeled the cost-effectiveness of chest radiography and tuberculin skin testing for TB prevention over a 20-yr time frame, among three simulated cohorts of 20-yr-old immigrants. Compared with no screening, radiographic screening prevented 4.3% of expected active TB cases in the highest risk cohort (50% TB-infected, 10% human immunodeficiency virus [HIV] seroprevalence), and 8.0% in the lowest risk cohort (5% TB-infected, 1% HIV seroprevalence). Tuberculin skin testing further reduced the expected incidence 8.0% and 4.0%, respectively. Compared with no screening, radiographic screening cost $3,943 Canadian per active TB case prevented in the highest risk cohort, and $236,496 per case prevented in the lowest risk group. Compared with radiographic screening, mass tuberculin skin testing cost $32,601 per additional case prevented in the highest risk group, and $68,799 per additional case prevented in the lowest risk group. Chest radiographic screening of young immigrants from countries with a high prevalence of TB is a relatively inexpensive means of TB prevention. Tuberculin skin testing is considerably less cost-effective. For immigrants from low-prevalence countries, both interventions are extremely costly with negligible impact. The cost-effectiveness of either strategy would be greatly enhanced by increased adherence to chemoprophylaxis recommendations. Radiographic screening of groups with a high prevalence of tuberculous infection will then likely save money.
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PMID:Tuberculosis screening of immigrants to low-prevalence countries. A cost-effectiveness analysis. 1071 22

Although anergy testing is commonly used to help interpret negative tuberculin skin test results, the validity of this approach has not been demonstrated. Specific issues include lack of a standardized protocol for antigen selection, number needed to reliably evaluate inability to respond, and uniform criteria for defining cutaneous reactivity, as well as regional variation in skin test reactivity. Tuberculin skin testing is used to screen for latent infection and to evaluate the need for isoniazid prophylaxis. The presence or absence of reactivity to control antigens does not affect this decision. The results of anergy testing also do not predict the risk for progression to active disease in either HIV-negative or HIV-positive patients. In HIV-negative patients with active tuberculosis, 10% to 20% have negative tuberculin test results, and 5% to 10% have a negative tuberculin result but have a positive reaction to another antigen. A negative tuberculin skin test result does not exclude either latent infection or active disease, even in the presence of a reaction to other antigens. Neither anergy testing nor tuberculin testing obviates the need for microbiologic evaluation when there is suspicion for active tuberculosis infection. Therefore, anergy testing is not useful in screening for asymptomatic tuberculous infection or for diagnosing active tuberculosis.
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PMID:The case against anergy testing as a routine adjunct to tuberculin skin testing. 1078 69

This prospective cohort study was conducted to determine the complication of Bacillus Calmette-Guerin (BCG) vaccination given to newborn infants born to HIV-1 seropositive mothers and to compare the tuberculin reaction 9 months after BCG vaccination between HIV-1 infected and non infected children. Two hundred and twenty-three infants with BCG immunization at birth were examined. No BCG complication was noted. Tuberculin skin tests were performed on 126 children (56.5%). Eleven of them were excluded because of failure to have skin tests read at 48 hours. Of the 115 infants enrolled to this study, 15 (13%) had no BCG scar and 50 (43.5%) had no tuberculin reaction. Twenty-six children were classified as group 1 or HIV-1 infected children and 89 children were group 2 or HIV-1 non infected. Group 1 children had a smaller tuberculin skin response (X+SD) than group 2 (1.15 +/- 2.82 vs 4.64 +/- 4.29 mm; p < 0.0001). Mean weight + SD of group 1 children was also significantly less than those in group 2 (8,013 +/- 741 vs 8,540 +/- 984 g; p < 0.05). The proportion of children with non reactivity to the tuberculin test, a negative tuberculin test and no BCG scar in group 1 was significantly higher than that in group 2 (76.9% vs 33.7%, 92.3% vs 52.8% and 36.4% vs 6.7% respectively; p < 0.0001 for all). But, the proportion of non reactivity to the tuberculin test in children with or without BCG scar of each group was not different (p > 0.05). Positive tuberculin tests were 7.7% and 47.2% in group 1 and 2 respectively. None of the children with positive tuberculin tests had clinical evidence of tuberculosis. The findings of this study indicate that BCG vaccine given to newborn infants of HIV-1 seropositive mothers is safe. Although tuberculin skin responses of HIV-1 infected children are less than those of HIV-1 non-infected children, it is possible that BCG vaccine might protect these children from developing severe tuberculosis.
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PMID:Safety and immunogenicity of Bacillus Calmette-Guerin vaccine in children born to HIV-1 infected women. 1128 6

In the Malaysian setting of multi-ethnicity and high BCG coverage, interpretation of Tuberculin Skin Testing (TST) may be difficult. Between January 2001 and December 2003, a retrospective study on all adult patients with documented TST results treated for tuberculosis (TB) in chest clinics of two government hospitals was conducted to determine the reliability of TST and factors affecting its interpretation. One hundred and three patients [mean age (SD): 43 (17); male: 67%] were eligible for data collection: 72% and 57% of patients had positive TST results based on cut-off points of 10mm and 15mm respectively. The only significant univariate association with TST results was the severity of co-morbidity. A patient with co-morbidity score of 3 defined as those with any cancer, end-stage renal or liver disease, or HIV disease, was more likely to have a negative TST results [10mm cut-off point: Odd Ratio (95% CI) 6.6 (1.82 to 24.35), p = 0.003; 15mm cut-off point: 4.8 (1.21 to 18.95), p = 0.012]. A TST reading of 10mm had a higher sensitivity than 15mm as the cut-off point in diagnosing TB infection. Considering all possible confounding factors like ethnicity, prior BCG vaccination and TB burden in the population, severity of co-morbidity remains strongly predictive of a negative TST. Caution should be exercised in interpreting TST in these patients.
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PMID:Influence of co-morbidity in the interpretation of tuberculin skin reactivity in multi-ethnic adult patients with tuberculosis. 1657 Jul 3

Tuberculin skin testing is used for the identification of individuals with infection by Mycobacterium tuberculosis and other non-tuberculous mycobacteria. However, its value in immunosuppressed individuals due to human immunodeficiency virus (HIV) infection is controversial. This study was aimed at determining the relationship between Mantoux reaction and CD4+ cell counts; and whether the test can be used to predict CD4+ counts in patients dually infected with Human Immunodeficiency Virus and M. tuberculosis. Eighty patients, comprising 42 males (52.5%) and 38 females (47.5%) confirmed to be having antibodies to HIV who also had sputum smear positive pulmonary tuberculosis were recruited over a period of 16 months. They were Mantoux-tested with 0.1 ml of 5TU of PPD which was interpreted thus: <5 mm = negative, =5 mm = positive. CD4+ counts were determined using Dynabeads technique. The ages of all the patients ranged between 18 and 55 years (mean +/- SD: 33.9+/-8.42 years). The males had a mean age of 35.4 +/- 7.7 years while that of the females was 29.6+/-53 years (P<0.05). The CD4+ counts ranged between 73 and 512 cells/microl with a mean of 235.05 +/- 112.8 cells/microl. Fifty seven (71%) patients had negative PPD tests while 23 (29%) tested positive. Of the 37 with CD4+ counts <200 cells/microl, 32 (86.48%) had negative reaction (<5 mm) and 5 (13.51%) were positive (=5 mm) as compared to those with CD4 counts =200 cells/microl, among whom 25 (58.13%) were negative and 18 (41.86%) were positive (P<0.05). The positive predictive value was low at 56.14%. The difference in mean indurations between those with CD4+ count <200 cells/microl versus those with CD4+ count =200 cells/microl was statistically significant (P<0.05). On the whole, Mantoux indurations were noted to weakly correlate positively with CD4+ counts (Pearson's correlation, r=+0.36, P=0.001. It was concluded that there is a weak positive correlation between Mantoux reaction and CD4+ cell counts and that the Mantoux test is a poor predictor of CD4+ cell count.
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PMID:Mantoux reaction in patients with HIV-related pulmonary tuberculosis in Maiduguri, Nigeria. 1674 35


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