Underestimation of Mycobacterium tuberculosis infection in HIV-infected subjects using reactivity to tuberculin and anergy panel

BACKGROUND: This study aimed to evaluate purified protein derivative (PPD) reactivity and its interrelationship with anergy panel and CD4+ lymphocytes in HIV-infected subjects as compared to PPD reactivity in HIV-uninfected individuals in a tuberculosis endemic and high Bacillus Calmette-Guérin (BCG) coverage environment. METHODS: Clients of four Mexico City HIV detection centres were screened for HIV-1 antibodies (ELISA or haemagglutination, Western Blot); reactivity to PPD (Mantoux PPD, 5TU RT-23), Candida (1:1000, 0.1 ml), and tetanus toxoid (10Lf, 0.1 ml); and CD4+ T cells. Active tuberculosis was excluded. Informed consent was obtained. RESULTS: From 5130 clients 1168 subjects were enrolled; of these 801 (68.6%) were HIV positive. Reactivity to PPD among HIV-positive subjects was found in 174 (22%), 261 (32.6%), and 296 (37%), at PPD cutoff levels of > or =10 mm, > or =5 mm, and > or =2 mm as compared to 224 (61%) of 367 HIV-negative individuals' reactors to PPD (> or =10 mm) (P < 0.001). After exclusion of anergic individuals using two cutoff levels for cutaneous allergens (< or =2 mm and < or =5 mm), PPD reactivity between HIV-infected and uninfected individuals continued to be significantly different. Only HIV-infected individuals with CD4+ T cells > or =500 cells/mm3 had similar reactivity to PPD as HIV-uninfected individuals. Variables associated with PPD reactivity were CD4+ T cell counts, BCG scar, HIV infection and age. CONCLUSIONS: PPD reactivity was useful to diagnose tuberculosis infection only among HIV-infected individuals with CD4+ counts > or =500 cells/mm3. Among individuals with lower counts, lowering cutoff levels or using anergy panel did not permit comparable reactivity as that observed among HIV-uninfected individuals.     

Delayed hypersensitivity response and vitamin D deficiency

The relationship between delayed hypersensitivity and serum levels of 25-hydroxyvitamin D were examined in sixty-three elderly people. After intracutaneous injection of five recall antigens (Candida, mumps, PPD, tricophyton and varidase) nineteen subjects showed no response (anergy), seven showed only a weak reaction (relative anergy), and thirty-seven a normal reaction. In the anergic group mean serum level of 25-hydroxyvitamin D was significantly lower than in the group with normal immunoreactivity. Five subjects with anergy and serum 25-hydroxyvitamin D below 20 nmol/l were treated with oral vitamin D or UV irradiation for two to three months, after which both the serum 25-hydroxyvitamin D levels and the delayed hypersensitivity were normalized. In a non-treated group anergy persisted in seven out of nine patients in a second skin test. We conclude that anergy in the delayed hypersensitivity skin test in humans may in some cases be due to vitamin D deficiency.     

A study of the association between delayed type hypersensitivity reaction to mycobacterium tuberculosis and atopy in asthmatic children

The purpose of this study was to investigate if there is an inverse association between Mycobacterium tuberculosis infection and atopy among children living in rural and semi urban areas in El Behira governorate, Egypt. METHODS: All the studied children were BCG vaccinated in their newborn period. In Tuberculin testing, indurations greater than or equal to 5 mm were accepted as positive. For atopy, the most common aeroallergens were used in skin intradermal testing, and reactions > or = 3 mm were accepted as positive. RESULTS: Among 150 studied children whose ages ranged from 4-8 years, 89 patients were purified protein derivative (PPD) negative whereas in 61 patients PPD was positive. Among the PPD negative patients skin intradermal test was positive for atopy in 51.6% (n = 46), while among the PPD positive patients skin intradermal test was positive in 52.4% (n = 32). As the two groups were compared for having positive intradermal skin test reaction, no statistically significant difference was detected between them (p >0.05). CONCLUSIONS: In this study no statistically significant difference was detected between Mycobacterium tuberculosis infection as indicated by positive PPD positivity and atopy tested by skin intradermal injection of common aeroallergens.     

Cutaneous inflammation caused by inadvertent intradermal administration of DTP instead of PPD.

In 1979, 101 adults were skin-tested by a health department to evaluate tuberculin reactivity; of the 96 persons followed, 87 (91 per cent) experienced inflammation marked by swelling, erythema, arm pain, and fever. Five months later, a 5 mm to 10 mm purple macule persisted in 76 persons. The vials of PPD reportedly used for testing had been discarded, but PPD had been stored in the refrigerator with DT and DTP. The mean tetanus antitoxin titer in skin-tested persons was 0.14 units per ml (u/ml) vs 0.08 u/ml in untested control persons (p lesser than 0.03). The mean diphtheria antitoxin titer in skin-tested people was 0.90 u/ml vs 0.16 for controls (p = 10(-5)). The mean pertussis antibody in skin-tested persons was 1:169 vs 1:12 for controls (p = 10(-5)). Intradermal DTP in immune rabbits produced histologically typical Arthus reactions similar to those experienced by the humans. Seven months later, 90 persons received PPD injections. Ten had induration; none experienced persistent reactions. We concluded that the humans initially received DTP instead of PPD.     

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

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

Factors associated with tuberculin reactivity in two general hospitals in Mexico.

OBJECTIVE: To identify risk factors associated with tuberculin reactivity in healthcare workers (HCWs). DESIGN: Cross-sectional survey of tuberculin reactivity (2 TU of purified protein derivative (PPD) RT23, using the Mantoux two-step test). SETTING: Two general hospitals located in a region with a high prevalence of tuberculosis and high bacille Calmette-Guerin (BCG) coverage. PARTICIPANTS: Volunteer sample of HCWs. RESULTS: 605 HCWs were recruited: 71.2% female; mean age, 36.4 (standard deviation [SD], 8.2) years; 48.9% nurses, 10.4% physicians, 26.8% administrative personnel; mean time of employment, 10.9 (SD, 6.7) years. PPD reactivity (> or =10 mm) was found in 390 (64.5%). Multivariate analysis revealed an association of tuberculin reactivity with occupational exposure in the hospital: participation in autopsies (odds ratio [OR], 9.3; 95% confidence interval [CI95], 2.1-40.5; P=.003.), more than 1 year of employment (OR, 2.4; CI95, 1.1-5.0; P=.02), work in the emergency or radiology departments (OR, 2.0; CI95, 1.03-3.81; P=.04), being physicians or nurses (OR, 1.5; CI95, 1.04-2.11; P=.03), age (OR, 1.04; CI95, 1.02-1.07 per year of age; P<.001), and BCG scar (OR, 2.1; CI95, 1.2-3.4; P=.005). CONCLUSIONS: Although the studied population has a high baseline prevalence of tuberculosis infection and high coverage of BCG vaccination, nosocomial risk factors associated with PPD reactivity were identified as professional risks; strict early preventive measures must be implemented accordingly.     

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.     

Immunologic significance of the mumps virus skin test in infants, children and adults.

The biologic validity of cell-mediated immunity to mumps virus was evaluated in 395 children, adolescents and adults. The study protocol included the determination of cutaneous delayed hypersensitivity to viral and avian control antigens and in 79% of the subjects an essential double bleeding was performed before and after mumps virus skin test for assay of neutralizing antibody. Seven per cent of subjects expressed sufficient delayed hypersentitivity to the control antigen to erase an apparently positive mumps virus skin test. Anamnestic conversions from seronegativity to seropositivity, elicited by the mumps virus skin test, increased from 4% in children to 25% in adults, which suggests waning B-cell recognition of prior mumps virus infection in adults. Although pregnancy diminished the difference (p smaller than .001), adults showed greater cutaneous delayed hypersensitivity to mumps virus antigen than did children (p smaller than .001), suggesting that mumps virus reinfection or persistence induced the escalation of more sensitive T-cell recognition with increasing age. Humoral immunity, assessed by the double bleeding technique in the vast majority of individuals, rose form 16% (1-4 years), 45% (5-9 years) and 80% (10-14 years) to 94% in adolescents and adults. Ordinarily 75-95% in other age groups, the decline of correlation between mumps virus cellular and humoral immunity to 60% in school children may result from prior parainfluenza virus infection, inconsistent potency of the skin test antigen, concurrent immunosuppressive infection, and lagging induction of mumps virus cellular immunity in recently infected individuals. Immunologic study of a large colony of subhuman primates failed to establish an hierarchial antigenic interrelationship among mumps virus and two additional paramyxoviruses.     

The benefits of evaluating close associates of child tuberculin reactors from a high prevalence group.

To determine the efficacy of evaluating persons (associates) in close contact to children with significant tuberculin reactions, we prospectively evaluated 831 associates of 297 children younger than eight years who had significant (greater than or equal to 10 mm) tuberculin reactions. Eighty-seven per cent of the index reactors were foreign-born, as were 84 per cent of the associates. All associates were evaluated by tuberculin skin testing; chest roentgenograms and sputum cultures were obtained if indicated. Four hundred sixty-one (55 per cent) of the associates had significant tuberculin reactions, and 15 had current tuberculosis. However, only three of these cases were newly discovered (total case rate: 1.81/100, new case rate: 0.36/100). Two of the three new cases were detected in the associates of children younger than three years of age. In addition, 338 candidates for isoniazid (INH) preventive therapy were found. We conclude that although the yield of new cases was low, the evaluation of associates did provide a convenient, high yield method of identifying candidates for INH preventive therapy. Moreover, it served as a useful mechanism for monitoring the adequacy of other case-finding activities.     

Prolonged impairment of cell-mediated immunity after major abdominal surgery in malnourished patients

The effect of the nutritional status on postoperative impairment of the immune response was studied in adults undergoing major abdominal surgery. The immune function was evaluated by measuring in vitro the lymphocytic response to phytohaemagglutinin (PHA), concanavalin A (Con A) and the purified protein derivative of tuberculin (PPD) in whole blood cultures, and in vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD. Nutritional assessment was carried out by evaluating recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and the serum concentration of albumin and prealbumin. The patient was considered malnourished, if at least three of these criteria were abnormal. The immune parameters were measured preoperatively, at the end of the surgery and five days after operation. Before the operation both malnourished and well-nourished patients had normal lymphocytic responses, but the malnourished patients had a slower recovery of immune responses after the operation and they had an increased number of postoperative complications. No significant differences in the incidence of anergy were observed between the well and malnourished patients pre or postoperatively.     

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)     

Mumps in Poland since 1990 to 2003; epidemiology and antibody prevalence

The annual incidence of mumps in Poland over the period 1990-2003 was 45-570 per 100,000 population with the epidemic peak every 4-5 years. Till 2003, mumps vaccination has not been included in the part of National Immunisation Program in Poland that comprises the obligatory vaccinations. However, mumps vaccination was recommended by National Health Authority for children at the second year of life and it could be obtained privately. The proportion of vaccinated children has increased by 50% in last years. It has influenced on decreasing of number of notified mumps cases in Poland, on lengthening of inter-epidemic period as well as on drift of infections towards older groups of children. The results of serological survey carried out on 1390 serum samples have indicated, that the proportion of positive serum samples (>11 VE/ml) was only 24.1% for children aged 1-4 years, 45.4% for children aged 5-9 years, 72.5% for age group 10-14 years, and over 85% for persons aged 15-30 years. Epidemiological data and the high proportion of individuals with negative titres of specific mumps IgG antibodies justify the need of introduction of obligatory mass immunisation against mumps in Poland.     

Tuberculin reactivity in United States and foreign-born Latinos: results of a community-based screening program.

Because of the concern that we were underestimating the prevalence of tuberculosis within the Latino community in San Francisco, we undertook a community-based screening program directed largely towards recent immigrants. Of 1,871 intermediate-strength (5 TU) tuberculin tests applied and read, 37 per cent of the reactions were greater than or equal to 10 mm. Significant reactions were found in 53 per cent of foreign-born persons compared to 7 per cent of those born in the United States. Persons older than 20 years of age were more likely to have significant reactions compared to younger Latinos. Among the foreign-born, the frequency of significant reactions was not influenced by the length of stay in the US or a history of BCG (bacille Calmette-Guérain) vaccination. Two foreign-born children were found to have current tuberculosis. The prevalence of tuberculin reactors among US-born Latino children was 3 per cent, which suggests that undetected transmission of tuberculosis may be occurring. We conclude that Latino immigrants should be systematically screened for tuberculosis.     

Delayed hypersensitivity on a surgical service

Two hundred patients assessed for nutritional deficiencies were analyzed for reaction to skin testing with common antigens and the incidence of sepsis and death. Only 39% of all skin tests were positive, though 50% of the patients had at least one positive test. Associated diagnoses revealed a high incidence of malnutrition, cancer, radiation therapy, and chemotherapy. Analysis using Chi-square and Gamma shows good statistical correlation between skin tests and sepsis and death. Those with negative tests (anergic) using PPD, Candida, and mumps had a threefold higher mortality. Major sepsis also increased in the skin negative group (+80%), but here the incidence varied directly with the number of positive skin tests. Mortality, unlike sepsis, was influenced only by the presence of delayed hypersensitivity and was not related to the number of positive reactions. The basic rate of infection or mortality was not influenced by major surgery.     

Delayed hypersensitivity on a surgical service.

Two hundred patients assessed for nutritional deficiencies were analyzed for reaction to skin testing with common antigens and the incidence of sepsis and death. Only 39% of all skin tests were positive, though 50% of the patients had at least one positive test. Associated diagnoses revealed a high incidence of malnutrition, cancer, radiation therapy, and chemotherapy. Analysis using Chi-square and Gamma shows good statistical correlation between skin tests and sepsis and death. Those with negative tests (anergic) using PPD, Candida, and mumps had a threefold higher mortality. Major sepsis also increased in the skin negative group (+80%), but here the incidence varied directly with the number of positive skin tests. Mortality, unlike sepsis, was influenced only by the presence of delayed hypersensitivity and was not related to the number of positive reactions. The basic rate of infection or mortality was not influenced by major surgery.     

Age-specific prevalence of hepatitis A virus antibody in Thailand

Serum specimens drawn at random from three geographically defined populations of healthy Thais were tested for antibody to the hepatitis A virus (anti-HAV) by radioimmunoassay. A total of 746 specimens were tested. The age by which 50 per cent were antibody positive was 4-5 years for residents of an urban Bangkok housing project, 8-9 years for rural villagers, and 10-11 years for urban Bangkok government school pupils. Overall, specimens from 97 per cent of Thai adults 16 years of age or older were anti-HAV positive. These data suggest widespread distribution of HAV in Thailand.     

桂林市2015年流行性腮腺炎患病人群抗体水平及病毒基因分析

目的 了解桂林市2015年流行性腮腺炎患病人群的抗体水平和腮腺炎病毒的基因分型，为流行性腮腺炎的控制提供科学依据。方法 采用酶联免疫吸附试验测定流行性腮腺炎患者静脉血免疫球蛋白G抗体；采用逆转录聚合酶链反应检测流行性腮腺炎患者咽拭子标本中分离的病毒MuV小疏水蛋白基因的序列和基因型，构建SH基因亲缘关系树。结果 本次调查的桂林市263例流行性腮腺炎患者的抗体阳性率为81.75%，各年龄组间抗体阳性率差异无统计学意义（χ2=1.71，P=0.668），但抗体水平比较差异有统计学意义（H=14.16，P=0.003）。不同性别间抗体阳性率差异无统计学意义（χ2=2.83，P=0.092），而不同性别的抗体水平差异有统计学意义（Z=-2.55，P=0.011）。有、无和流行性腮腺炎免疫史不详者三组人群抗体阳性率和抗体水平差异均无统计学意义（χ2=4.61，P=0.100；H=1.85，P=0.413）。从263份患者咽拭子标本中，分离出6株腮腺炎活病毒和19例咽拭子核酸阳性标本，均为F基。结论 桂林市婴幼儿流行性腮腺炎免疫水平偏低；男性发病率较女性高；桂林市腮腺炎流行主要是由F基因型流行性腮腺炎病毒引起的。     

2005—2019年广州市流行性腮腺炎突破病例流行病学分析

目的 了解广州市流行性腮腺炎突破病例的流行病学特征,分析含流腮成分疫苗接种对流行性腮腺炎的影响。方法 对2005—2019年广州市流行性腮腺炎突破病例进行流行病学特征分析。结果 2005—2019年广州市流行性腮腺炎突破病例为13180例,占同期总病例数的19.5%且该占比呈现逐年波折向上趋势,从2005年的3.26%到2019年的53.52%。突破病例发病年龄高峰在3~5岁,男女性别比为1.95[DK]∶1, 其中一剂突破病例占83.8%。含流腮成分疫苗初免在0岁完成的,突破间隔和发病年龄均较大,平均发病年龄在7~8岁。5岁完成第二剂含流腮成分疫苗可以较大程度地推迟发病年龄,发病年龄可推迟到9岁。结论 采用一剂次含流腮成分疫苗接种策略的,初始免疫在0岁完成的防病效果最佳,采用两剂次含流腮成分疫苗接种策略的,第二剂疫苗在5岁完成可以较大程度地推迟发病年龄。     

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.     

Predictors of tuberculin reactivity among prospective Vietnamese migrants: the effect of smoking

We investigated the prevalence and predictors of positive tuberculin skin test (TST) results among prospective Vietnamese migrants. We interviewed and medically screened 1395 Vietnamese people aged over 15 years who had applied to migrate to Australia. Approximately 44% of applicants had an induration of 10 mm or more, and 18.6% had an induration of 15 mm or more. A positive tuberculin skin test at 5 mm, 10 mm and 15 mm of induration cut-points was significantly associated with age (OR 1.01-1.02 per year) and duration of smoking (OR 1.03-1.12 per year). Smoking appears to be an important factor associated with increased susceptibility to mycobacterial infection. It is not yet clear whether the increased tuberculin reactivity associated with smoking reflects an increased risk of tuberculosis among these migrants.