Epidemiological study of a tuberculosis case in a large manufacturing enterprise in Quebec]

OBJECTIVES: To determine the prevalence of tuberculosis infection related to a case of pulmonary and laryngeal tuberculosis in a workplace and to study PPD predictors. METHODS: The Mantoux skin test (PPD) was offered to all potentially infected contacts. Participants were asked to answer a questionnaire. RESULTS: Among 112 exposed employees, 92 (82.1%) were tested. At the 5 mm level, 65.2% of employees had positive tuberculin skin test (PPD). By controlling prior BCG and the degree of exposure, it showed a positive association between age and PPD (RC: 3.5; 95% CI: 1.25-10.03). When age and BCG were controlled, high exposure was statistically associated with PPD results (RC: 5.6; 95% CI: 1.25-24.68). CONCLUSION: The observed prevalence rate is probably related to the fact that the index case was very infectious and had contact in an enclosed area over a long period of time before withdrawal from work.     

Tuberculin intradermal reaction (IDR) or tuberculin test

Tuberculinic switch is defined as an increase of the intradermal reaction diameter in two tests carried out within three months of each other. The tuberculinic skin reaction proves the presence of a delayed hypersensitivity induced by mycobacterial antigens (Mycobacterium tuberculosis, BCG, some atypical mycobacteria). However, this reaction does not always prove an effective protection against the BK. The intradermal injection of a purified Purified Protein Derivative (PPD) resulting from a culture of M. tuberculosis is the only method validated for the diagnosis of tuberculosis infection (latent infection) and screening for hypersensitivity and post-vaccine BCG (Official French decree No 96-775 of September 5, 1996 and its decree relating to vaccination by BCG and tuberculin tests). The guidelines concerning tuberculin testing are: investigating on a case of tuberculosis; tracking or surveillance of people frequently exposed to tuberculosis (examination on recruitment and follow-up of exposed professionals); prevaccine testing in children over four weeks of age.     

2014年湖北省江陵县中心城区小学生PPD试验 结果分析

摘要:目的　了解江陵县在校小学生人群结核病免疫力和结核感染状况,探讨学校结核病防控措施。方法　应用TB-PPD对在校小学生进行皮内试验,72 h观察并判定反应结果,采用描述流行病学方法对试验结果进行分析。结果　接受PPD试验学生2465名,阳性人数为707名,总阳性率28.68%。其中强阳性20名,强阳性率0.81%。男生与女生阳性率分别为27.58%和30.02%,强阳性率分别为0.52%和1.16%,差异均无统计学意义。农村户藉学生阳性率高于城镇户藉学生,两者差异有统计学意义（χ2＝10.10,P值＜0.01）,年级间阳性率差异亦有统计学意义（χ2＝7.52～30.52,P值均＜0.01）。结论　本次调查在校小学生PPD阳转率较低,与新生儿卡介苗接种质量不高和受检人群抗体保护水平随着时间推移抗体减弱均有关,提示接种单位仍要加强新生儿卡介苗规范接种,同时建议各地定期开展学生PPD试验,及早筛查结核病例,提高学校结核病防控效果。     

Evaluation of the two-step tuberculin skin test in health care workers at an inner-city medical center.

The increased rate of tuberculosis (TB) infection and transmission from patients to health care workers (HCWs) has brought awareness of the need for better surveillance programs. The two-step purified protein derivative (PPD) skin test decreases the misinterpretation of a "boosted reaction" as a recent infection with Mycobacterium tuberculosis in HCWs. We reviewed the medical records of 4082 HCWs at an inner-city medical center who had PPD skin-testing performed as a component of the TB medical surveillance program during the years 1994 and 1995. Of those HCWs tested, 3896 (95.4%) returned for the PPD skin-test evaluation. Of those 3896 HCWs, 3659 (93.9%) had a negative baseline PPD skin test, and 237 (6.1%) had a positive skin test. Of those HCWs with a negative baseline skin test, 252 (6.9%) were eligible for the second PPD skin test. Of the 241 who returned for their second PPD skin-test reading, six (2.5%) had positive results. All six cases were foreign-born physician residents with a previous history of Bacille bilié de Calmette-Guérin (BCG) vaccination. We conclude that the two-step PPD skin test method is not indicted for HCWs at this urban medical facility.     

Is tuberculin skin testing useful to diagnose latent tuberculosis in BCG-vaccinated children?

BACKGROUND: The tuberculin skin test (TST) is the most commonly used tool to detect infection with Mycobacterium tuberculosis. We sought to determine whether tuberculin skin testing is useful to detect latent infection by M. tuberculosis in a population that was vaccinated with the Bacille Calmette Guérin (BCG) vaccine. METHODS: We performed a cross-sectional study during October 2000-February 2001, enrolling first and sixth graders from a random, stratified sample of public elementary schools in Orizaba, Veracruz, Mexico. We assessed the relationship between sociodemographic and epidemiological information, BCG scars, and TST reactivity. RESULTS: There were 858 children enrolled in the study with a completed questionnaire and TST result. The prevalence of a positive TST result (> or =10 mm) was 12.4%. Controlling for BCG scar, age, and other characteristics, close contact with pulmonary tuberculosis patients (odds ratio 6.56, 95% confidence interval 2.05-21.07, P = 0.001) was independently associated with TST reactivity. CONCLUSIONS: TST results helped identify children in a BCG-vaccinated population who had recent exposure to persons with pulmonary tuberculosis, were probably infected with M. tuberculosis, and could benefit from treatment for their latent tuberculosis infection.     

干扰素释放酶联免疫法(TB-IGRA)用于检测结核分枝杆菌的优越性

目的评价TB-IGRA与常用几种结核分枝杆菌检测方法的优越性。方法选择确诊肺内结核70例,肺外结核33例及体检正常人群30例为对照,分别采用TB-IGRA、TST(PPD)、结核抗体、痰涂片及痰菌培养等方法检测结核分枝杆菌感染,进行统计学分析评价。结果结核分枝杆菌感染者TB-IGRA检出阳性率、敏感性、Youden指数(准确性)均比常规方法高,差异有统计学意义(P<0.01);正常对照组阳性检出率比常规方法低,差异亦有统计学意义(P<0.05)。表明TB-IGRA假阳性出现少,准确性高,且对肺内、肺外结核的检测同样准确有效。结论 TB-IGRA检测肺内、肺外结核病简便、快速、敏感、准确有效,值得临床推广应用。     

Utility of dual skin tests to evaluate tuberculin skin test reactions of 10 to 14 mm in healthcare workers.

OBJECTIVE: To define the utility of 10- to 14-mm reactions to a Mycobacterium tuberculosis purified protein derivative (PPD) skin test for healthcare workers (HCWs). DESIGN: Blinded dual skin testing, using PPD and M. avium sensitin, of HCWs at a single medical center who had a 10- to 14-mm reaction to PPD when tested by personnel from the Occupational Health Department as part of routine annual screening. SETTING: A single tertiary-care academic medical center. PARTICIPANTS: Employees of the medical center who underwent routine annual PPD screening and were identified by the Occupational Health Department as having a reaction of 10 to 14 mm to PPD. RESULTS: Nineteen employees were identified as candidates and 11 underwent dual skin testing. Only 4 (36%) had repeat results for PPD in the 10- to 14-mm range, whether read by Occupational Health Department personnel or study investigators. For only 5 (45%) of the subjects did the Occupational Health Department personnel and study investigators concur (+/- 3 mm) on the size of the PPD reaction. Two of the 4 subjects with reactions of 10 to 14 mm as measured by the study investigators were M. avium sensitin dominant, 1 was PPD dominant, and 1 was nondominant. CONCLUSION: A reaction of 10 to 14 mm to PPD should not be used as an indication for the treatment of latent tuberculosis (TB) infection in healthy HCWs born in the United States with no known exposure to TB.     

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 > or =300/mm3 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 in duration 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.     

Risk factors for positive tuberculin skin test in Guinea-Bissau

BACKGROUND: The tuberculin skin test is used for tracing of tuberculosis transmission and identifying individuals in need of prophylactic treatment. METHODS: Using a case-control study design, we recruited 220 smear-positive tuberculosis cases and 223 randomly selected healthy community controls in Bissau, Guinea-Bissau, during 1999-2000. Tuberculin skin tests were performed on family members of cases and controls (n = 1059 and n = 921, respectively). Induration of 10 mm or greater was considered positive. Risk factors were calculated for children (<15 years) and adults separately in multivariate logistic regression analysis. RESULTS: The prevalence of positive tuberculin skin test was 41% in case-contacts compared with 22% in control-contacts, resulting in a prevalence ratio of 1.48 (95% confidence interval = 1.37-1.60). Positive skin tests among case-contacts increased with age for children, as well as with proximity to a case during the night, for both children and adults. A Bacille Calmette Guerin scar increased the likelihood of having a positive tuberculin skin test for adults in case households, but not in other categories of contacts. Among control-contacts the prevalence of positive skin test was associated with older age in children, history of tuberculosis in the family, and a positive tuberculin skin test of the control person. CONCLUSIONS: Risk factors for a positive tuberculin skin test among case- and control-contacts are closely related to tuberculosis exposure. Having a BCG scar did not increase the risk of positive skin test in unexposed individuals. Tuberculin skin testing remains a useful tool for diagnosing tuberculosis infection.     

应用酶联免疫斑点试验检测入伍新兵结核潜伏感染

目的应用酶联免疫斑点试验（ELISPOT）检测入伍新兵结核潜伏感染情况,评价ELISPOT在检测结核潜伏感染中的价值。方法以结核菌素纯蛋白衍生物 (PPD) 皮肤试验为对照,应用ELISPOT试剂盒检测366例2009年驻京部队入伍新兵外周血中分泌结核菌抗原特异性γ干扰素（IFN γ）的T淋巴细胞数。对PPD和ELISPOT均为阴性的入伍新兵接种卡介苗,10个月后再做PPD 皮肤试验和ELISPOT,比较结果。结果366例入伍新兵中,PPD皮肤试验和ELISPOT阳性率分别为44.81%和31.69%。202例PPD皮肤试验阴性和164例PPD皮肤试验阳性者中,分别有53例 （26.24%）和63例（38.41%）ELISPOT阳性,两者的一致率为57.92%（212/366）, 两者的检测结果差异具有统计学意义（χ2=14.34,P＜0.001）。在接种过卡介苗者中,PPD皮肤试验阳性率为58.53%（127/217）,ELISPOT阳性率为29.03%（63/217）,斑点形成细胞数为32.44±26.52 ;在未接种卡介苗者中,PPD皮肤试验阳性率为24.83%（37/149）,ELISPOT阳性率为35.57%（53/149）,斑点形成细胞数为41.81±30.48。110例PPD和ELISPOT均为阴性的入伍新兵接种卡介苗10个月后, PPD 皮肤试验阳转率为78.18%,而ELISPOT检测均为阴性。结论ELISPOT具有较高的特异性和敏感性,能真实反映入伍新兵的结核潜伏感染情况,可推广应用。     

Immune responses to hepatitis B virus and tuberculosis infections in Southeast Asian refugees

Both Mycobacterium tuberculosis and hepatitis B virus infections are common in the Philadelphia Southeast Asian refugee population. Among 224 hepatitis B carriers identified between January 1, 1982 and March 31, 1984, there was a statistically significant association between a negative tuberculin skin test (purified protein derivative (PPD)) and viral replication (hepatitis B e antigen positivity (HBeAg)). This finding suggests that bacille Calmette Guérin (BCG) vaccination might reduce the prevalence of infectious carriers, thereby ultimately reducing the incidence of hepatitis B infection.     

北京市海淀区高校结核病患者及其密切接触者筛查分析

目的 通过分析海淀区高校结核病患者及密切接触者筛查情况,为海淀区高校密切接触者筛查策略的修改提供科学依据。方法 对海淀区2015年3月~2016年3月发现的高校结核患者及其密切接触者进行问卷调查,并对密切接触者均进行结核菌素试验（purified protein derivative test,PPD）及胸片检查。分析患者基本人口学特征,密切接触者人口学特征、结核感染情况及患者检出情况。结果 本次研究共诊断88例结核病患者,筛查得到密切接触者3 604名。密切接触者中共检出肺结核患者16例,且均为菌阴患者,患者检出率为443.95/10万。3 604名密切接触者中,PPD强阳性率8.32%。随着PPD反应直径的增加,密切接触者中患者检出率升高,且趋势有统计学意义（χ_trend²=8.06,P<0.001）。疫情期间密切接触者PPD强阳性率和患者检出率均高于非疫情期（均有P<0.05）。结论 应加强高校学生结核病的筛查,根据不同的结核病检出情况适当扩大筛查范围,从而及早发现感染者及患者,进行预防性治疗,避免高校结核病的暴发流行。     

The production and preliminary investigation of Burulin, a new skin test reagent for Mycobacterium ulcerans infection.

The preparation of a skin test antigen from Mycobacterium ulcerans by ultrasonic disintegration and filtration is described. The reagent, called Burulin, was tested in Africa in normal school children, and in patients with leprosy, tuberculosis or M. ulcerans disease. Those with tuberculosis or M. ulcerans disease were simultaneously tested with Tuberculin PPD. Burulin was found to be highly specific for patients in the reactive stage of M. ulcerans disease, and there was no cross-reaction in patients with other mycobacterioses. On the other hand, the majority of patients with M. ulcerans disease reacting to Burulin also produce positive reactions to Tuberculin PPD.     

First description of concomitant infection with tuberculosis and paratuberculosis in dairy sheep in Argentina

The authors present the results of a comparative intradermal tuberculin test performed on dairy sheep to determine rates of reaction to bovine and avian purified protein derivative (PPD). Test reactions were interpreted by palpation and measurement with a calliper. Results were analysed by plotting the values obtained. Agar gel immunodiffusion tests, growth in culture and histopathological examinations were also performed to allow differential diagnosis between tuberculosis and paratuberculosis. In the first tuberculin test, performed on 288 sheep, 74 animals showed a positive reaction to avian PPD (25.69%), two animals showed a positive reaction to bovine PPD (0.69%), and one animal was positive with respect to both tuberculins (0.34%). In the second test, involving 247 sheep, 55 demonstrated a positive reaction to avian PPD (22.26%), whilst none reacted to bovine PPD. The presence of Mycobacterium avium subsp. paratuberculosis was confirmed by culture and serological testing. In addition, lesions compatible with those caused by M. bovis were found by histopathological examination. These findings highlight the importance of the accurate diagnosis of tuberculosis and paratuberculosis for the effective control of both diseases.     

鹿泉区2011-2015年中小学新生结核菌素试验结果分析

了解石家庄市鹿泉区中小学新生结核病感染情况,探索学校发现和预防肺结核的办法.方法 对鹿泉区2011-2015年51 528名中小学新生进行结核菌素试验(PPD),并分析其肺结核发病情况.结果 BCG-PPD组与TB-PPD组的阳性率及强阳性率差异均有统计学意义(x2值分别为58.424,13.995,P值均<0.05).不同年级学生PPD阳性率及强阳性率间差异有统计学意义(2011-2013年X2值分别为348.501,279.369,2014-2015年x2值分别为203.289,111.693,P值均<0.05).818名强阳性者进一步检查691名(84.47%).发现活动性肺结核高中生4名、初中生2名、无小学生,肺结核检出率为0.73%.420名强阳性者使用“母牛分支杆菌”双向免疫调节剂进行预防.结论 中学生结核分枝杆菌感染不容忽视,应将结核病筛查和结核病健康教育纳入学校的制度化管理.     

母牛分枝杆菌疫苗预防结核病的细胞免疫学和安全性研究

目的评价正常人群接种母牛分枝杆菌疫苗的安全性和细胞免疫学效果,探讨母牛分枝杆菌疫苗用于大龄儿童加强免疫,预防结核病的可行性。方法随机选择5~7岁的健康儿童,先进行结核菌素纯蛋白衍生物(TB-PPD)试验,然后分成TB-PPD试验阳性组和阴性组,每组分别接种母牛分枝杆菌疫苗3针,每针间隔2周。分别采集接种前和接种后1个月的血标本,用流式细胞仪检测各项细胞免疫学指标,观察两组免疫前后细胞免疫学指标的变化情况和接种后不良反应的发生率。结果观察300人次的接种,未发现任何不良反应。TB-PPD试验阴性组免疫前后淋巴细胞、Th细胞(CD4)、Ts细胞(CD8)、T细胞数均比免疫前显著增加,差异有显著的统计学意义。90%的TB-PPD试验阴性者细胞数的增长≥2个标准差,增长率92%~96%。TB-PPD试验阳性者免疫前后淋巴细胞数、Th细胞数均比接种疫苗前增加,差异有显著的统计学意义。TB-PPD试验阳性组免疫前后呈现出良好的双向免疫调节功能,淋巴细胞数、Th细胞数的增长率近70%,且增长幅度在1个标准差左右。结论对TB-PPD试验阴性或阳性者进行母牛分枝杆菌疫苗接种,均显示了较好的安全性和细胞免疫学效果,因此探讨用母牛分枝杆菌疫苗预防结核病,尤其是用于大龄儿童及青少年免疫预防有非常积极的意义。     

Tuberculin skin test conversion among medical students at a teaching hospital in Rio de Janeiro, Brazil.

OBJECTIVE: To describe the cumulative incidence of and risk factors for tuberculosis (TB) infection among medical students. DESIGN: In 1999, a cohort study of medical students with negative results (induration < 10 mm) on tuberculin skin test (TST) was performed. Students who had undergone two-step testing in 1998 were retested. SETTINGS: University and teaching hospital and referral center for TB and acquired immunodeficiency syndrome, and the Health Sciences Building of the Medical School of the Federal University of Rio de Janeiro, Brazil. PARTICIPANTS: A sample of 618 consecutive medical students with negative TST results who had been tested 12 months before were approached. Information about sociodemographic characteristics, bacille Calmette-Guérin vaccination history, and potential exposures to TB was obtained using a standardized questionnaire. Four hundred fourteen (67%) students completed the study. Students were at two different levels of their training programs (juniors = no contact with patients; seniors = intensive contact with patients). RESULTS: Of 414 participants, 16 (3.9%; 95% confidence interval, 1.06% to 12.1%) had converted to a positive reaction after 1 year. In a multivariate logistic regression analysis, higher level of clinical training was confirmed to be an independent factor associated with TST conversion (odds ratio, 4.77; 95% confidence interval, 1.01 to 22.46; P= .048). CONCLUSION: Senior medical students are at increased risk of Mycobacterium tuberculosis infection in this setting. Therefore, a program of routine tuberculin skin testing and specific TB infection control guidelines are needed for this population.     

Investigation of the delayed type hypersensitivity reaction in atopic patients

INTRODUCTION: In the last decades the prevalence of atopic diseases has increased highly in developed countries. Although the reasons for this increase are not clear, it has been hypothesized that a reduction in infections and immunization programs may contribute to the increased prevalence of atopic diseases. AIM: In the present study the relationship between tuberculin response and atopic disease was investigated. METHODS: A total of 1012 children vaccinated with BCG were included in the study. All the children were given five tuberculin units PPD, and PPD indurations were recorded after 72 h. The test result was considered to be positive if the induration size was greater than 9 mm. The atopic anamnesis (atopic dermatitis, rhinitis, conjunctivitis, asthma, urticaria) in the children and their families were investigated using a questionnaire. RESULTS: 608 individual (60.1%) had positive and 404 (39.9%) had negative tuberculin test. Positive atopic personal anamnesis was found in 31.74% in children with positive tuberculin skin test, whereas 39.85% was found in children with negative tuberculin test (p < 0.009, Fischer-test). Similarly more positive family anamnesis for atopic diseases was found among children with negative tuberculin test. In children with negative tuberculin test the prevalence of allergic conjunctivitis and rhinitis was significantly higher as compared to the group with positive tuberculin test. CONCLUSIONS: The authors found an inverse correlation between tuberculin response and atopy status. The observed decreased tuberculin sensitivity in atopic individuals is, however, probably not the cause, but rather the consequence of the disturbed immune regulation in atopic diseases.     

The accuracy of tuberculin skin tests: self-assessment by adult outpatients

Tuberculin skin testing is an accurate, inexpensive screening procedure for detecting tuberculosis infection. The return visit needed to interpret the reaction is inconvenient, costly, and may contribute to under-utilization of the test. Although some clinicians ask patients to read their own purified protein derivative (PPD) test results, patient accuracy and the degree of teaching needed to learn this skill are unclear. This study evaluated the accuracy with which 145 outpatients read their own Mantoux skin test (PPD) reactions and reported by postcard after brief training by nurse practitioners. A total of 89 instructed patients returned postcards and also returned for clinician readings; 46 submitted postcards without returning; 7 returned but did not complete postcards; and 3 neither returned postcards nor returned for readings. Ten of 135 postcards were uninterpretable. For 81 subjects with both interpretable tuberculin self-assessment postcards and clinician readings, overall PPD classification agreement was 88 percent; Kappaw = +0.905 (P less than .001). Compared to clinician readings, 1 of 53 patients falsely reported a positive reaction (greater than or equal to 10 mm) and 2 of 25 patients falsely reported negative PPD readings (0-4 mm). There was 100 percent agreement between postcard readings and clinician classifications in a subgroup of patients (N = 26), prospectively identified by nurse practitioners as capable of accurate tuberculin self-assessment. Inter-clinician reading agreement (N = 37) was 89 percent; Kappaw = +0.943 (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage.

OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1 148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > or = 5 mm, > or = 10 mm, and > or = 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > or = 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > or = 10 mm was 14.2% (95% confidence interval (CI) = 8.0%-20.3%) for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1%) for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0%) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > or = 5 mm and > or = 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > or = 5 mm and > or = 10 mm did not vary with age. There was no evidence for BCG effect on the results > or = 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage.