Measles immunisation in children with allergy to egg.

OBJECTIVE--To examine the occurrence of adverse reactions to measles vaccine given as a single dose to children with egg allergy, and to determine if the administration of single dose to children with a positive result in an intradermal skin prick test with the vaccine is associated with adverse reactions. DESIGN--Review of results of immunisation and prospective study of 96 consecutively presenting children given intradermal skin testing with the vaccine. SETTING--Children''s allergy centre. SUBJECTS--410 children sensitive to egg referred to the allergy unit for advice about measles immunisation. MAIN OUTCOME MEASURES--Nature and severity of reactions associated with the administration of measles vaccine. RESULTS--All children had a positive result in a skin prick test with egg white, and five had a positive result in a skin prick test with vaccine. Of 96 consecutive children, 46 had a positive result in an intradermal test with vaccine. After immunisation with a full dose (0.5 ml) of vaccine adverse reactions were associated with a mild reaction in four children, none of whom required treatment. Only one of the 46 children with a positive result in an intradermal vaccine skin test had a reaction associated with vaccine administration. None of the children with a positive result in a skin prick test with measles vaccine reacted to the vaccine. The rate of minor reactions to the vaccine not requiring treatment was 0.98% (95% confidence interval 0.27% to 2.48%) and serious reactions requiring treatment was 0% (0% to 0.9%). CONCLUSION--Children with IgE mediated allergic reactions to egg protein should be investigated and managed by practitioners with special knowledge in this subject. Measles immunisation should be performed in a setting where any adverse reactions can be dealt with appropriately. Skin tests and measles vaccine and desensitisation are not necessary.     

Preventive treatment of tuberculin-negative contacts

Five children who had been in close contact with highly infectious tuberculous individuals presented recently to the tuberculosis service of The Montreal Children''s Hospital. Four had developed serious pulmonary tuberculosis and one tuberculous meningitis, all within the three months which followed a post-contact negative tuberculin test.The management of tuberculin-negative children recently exposed to active infectious tuberculosis by repeated skin tests and chest radiography alone is inadequate for their protection. These children are at high risk of developing disease by the time their tuberculin sensitivity has become evident. It is inadvisable to vaccinate them with BCG until three months after their last exposure to the disease. A plea is made for preventive chemotherapy in these cases.     

A New Approach in Dispensing Tuberculin PPD and in Performing a Multi-Puncture Tuberculin Test

A simple and low-cost kit for single-dose tuberculin testing is described. For those who perform occasional tuberculin tests only, this kit is proposed as a substitute for the Heaf apparatus used in carrying out a multi-puncture test. No difference in the tuberculin skin reactions could be observed when the needle multi-puncture test was compared with the Heaf test in BCG-sensitized guinea pigs and in 12 volunteers. A comparative study on 37 student nurses, using the needle multi-puncture method and the intracutaneous method (Mantoux test), showed that with the needle multi-puncture method more positive reactors were detected than with the Mantoux test using 1:2000 dilution of OT. However, more positive reactors were obtained with the Mantoux test using 1:100 dilution of OT. It is felt that the singledose kit can be a valuable asset when only few skin tests are performed.     

Comparison of Mantoux and Tine Tuberculin Skin Tests in BCG-Vaccinated Children Investigated for Tuberculosis

Background

Tuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result.

Methodology/Principal Findings

1512 South African children younger than 5 years of age who were investigated for tuberculosis (TB) during a Bacille Calmette Guerin (BCG) trial were included in this analysis. Children underwent both Mantoux and Tine tests. A positive test was defined as Mantoux ≥15 mm or Tine ≥ Grade 3 for the binary comparison. Agreement was evaluated using kappa (binary) and weighted kappa (hierarchical). Multivariate regression models identified independent risk factors for TST positivity. The Mantoux test was positive in 430 children (28.4%) and the Tine test in 496 children (32.8%, p<0.0001), with observed binary agreement 87.3% (kappa 0.70) and hierarchical agreement 85.0% (weighted kappa 0.66). Among 173 children culture-positive for Mycobacterium tuberculosis, Mantoux was positive in 49.1% and Tine in 54.9%, p<0.0001 (kappa 0.70). Evidence of digit preference was noted for Mantoux readings at 5 mm threshold intervals. After adjustment for confounders, a positive culture, suggestive chest radiograph, and proximity of TB contact were risk factors for a positive test using both TST methods. There were no independent associations between ethnicity, gender, age, or over-crowding, and TST result.

Conclusions/Significance

The Tine test demonstrated a higher positive test rate than the Mantoux, with substantial agreement between TST methods among young BCG-vaccinated children. TB disease and exposure factors, but not demographic variables, were independent risk factors for a positive result using either test method. These findings suggest that the Tine might be a useful screening tool for childhood TB in resource-limited countries.     

Leishmania (V.) braziliensis: detection by PCR in biopsies from patients with cutaneous leishmaniasis

Cutaneous leishmaniases present similar clinical appearances, but differing prognosis in the course of infection. Ulcers caused by parasites of the subgenus Viannia are more aggressive than ulcers caused by parasites of the subgenus Leishmania. Another problem is distinguishing between true Leishmania infection and other skin diseases in endemic areas, where cutaneous lesions and a single positive Montenegro intradermal test are enough to submit patients to specific treatment for cutaneous leishmaniasis. This study evaluated the efficacy of PCR in detecting in Leishmania in patients with cutaneous lesions. Leishmania (V.) braziliensis complex was determined by a primer pair from the multicopy spliced leader RNA. The results were compared to those of traditional methods. We analyzed biopsies of 109 patients with cutaneous lesions in the second most endemic region of Sao Paulo State, Brazil. Definitive diagnosis was established by clinical and “consensus laboratory criteria” (positive culture, stained tissue smears or PCR). Of 52 patients with cutaneous leishmaniasis, 96% had positive PCR, 69%, positive parasitological tests and 100%, positive Montenegro intradermal tests. Histopathological examination (only in 32 samples) were positive in 14 samples, suggestive in 14 and negative in 4 samples. All 57 patients with other etiologies had negative results in parasitological methods, PCR and histopathological examination (in 39 samples), but Montenegro intradermal tests were positive in 35%. PCR was highly sensitive and specific for L. (V.) braziliensis complex detection compared with other laboratory methods. Despite the specificity of the parasitological tests, the sensitivity was less than 70%. Montenegro intradermal reaction was highly sensitive, but with low specificity, only 65%. As suggestive results in histopathological examinations were shown in 14 samples, it was difficult to determine the true result. PCR applied to biopsies proved to be useful for differential diagnosis of cutaneous lesions of other etiologies in patients living in endemic areas. The advantages are most striking in clinical specimens with scarce amastigotes for which conventional methods have low sensitivity and should be considered for clinical and epidemiological patterns. On the other hand, both Montenegro intradermal test and parasitological methods are only modestly effective in cutaneous leishmaniasis diagnosis.     

An attempt to predict anergy in tuberculosis suspect cynomolgus monkeys.

Acid-fast microorganisms were identified from the tuberculous lesions of a male cynomolgus monkey (Macaca fascicularis). Twenty-two other cynomolgus monkeys housed in the same room were presumed exposed to tuberculosis (Mycobacterium spp.). In addition to standard intradermal (ID) tuberculin testing, clinicians attempted to evaluate the immune status of these monkeys in order to identify animals exhibiting false negative (anergy) ID tuberculin tests. Twenty-one of the potentially exposed monkeys were immunized with tetanus toxoid (TT). Tetanus antitoxin (TAT) titers were measured before and after immunization. The delayed cutaneous hypersensitivity (DCH) reaction to TT was evaluated using a commercially available human test panel. Some animals did not exhibit a DCH reaction to TT. At necropsy 1 of the 21 animals exhibited tuberculous lesions, and acid-fast microorganisms were identified on direct smears of lymphatic tissue of a second animal. Although reported to be of value in assessing the cellular immune status of rhesus monkeys (Macaca mulatta), the delayed cutaneous hypersensitivity response to tetanus toxoid was not helpful during this outbreak in identifying cynomolgus monkeys infected with M. tuberculosis, or in interpreting suspect ID tuberculin tests.     

Assessment of tine tuberculin test.

Mantoux (10 tuberculin units) and tine tuberculin tests were performed in 190 subjects and the results recorded at 48, 72, and 96 hours. Altogether 1010 readings were recorded. Of these, 555 (55%) were Mantoux-test positive and 525 (52%) tine-test positive. While the tine test is marginally less sensitive, its advantages are simplicity and ease and speed of application. It thus provides a useful screening test for eliciting tuberculin sensitivity.     

Interpretation of Positive Reactions to Heaf Tuberculin Test in London Schoolchildren

A study of 289 children aged 12-14 years found to be Heaf test positive at routine testing was made to determine the likely cause of the positive tests. Only 12% of children grade 1 Heaf positive were likely to have had a previous infection with Mycobacterium tuberculosis, 49% were likely to have had infections with atypical mycobacteria, and in 39% no cause for the positive Heaf test was found.The positive Heaf test seems to us to be too sensitive. Both a negative and grade 1 positive should be regarded as not significant and these children given B.C.G. vaccine. Heaf grades 2, 3, and 4 should be regarded as significant and the children investigated for M. tuberculosis infection.     

Skin reactivity to mycobacterial antigens in children living in an area of Mycobacterium xenopi endemicity

Intradermal skin tests with a 2TU dose of PPD-RT 23 prepared from M. tuberculosis and 0.1 ug/0.1 ml of PPD-RS 631 from M. xenopi were simultaneously carried out in 378 7-year-old children from two localities in North-Bohemian region's capital Ustí n. Lab., a focus of M. xenopi endemicity repeatedly confirmed since its disclosure in 1980 by positive M. xenopi isolations from humans and public water supply network. A further group 157 children serving as controls was from Prague district 4 where no presence of M. xenopi strains was ever recorded. All of these children had received routine immunization at birth with Czech BCG vaccine. The children from the two endemic localities were found to give a positive 6 mm or greater reaction to M. xenopi mycobacterin in 43.3% and 22.3%, to human tuberculin in 12.8% and 12.6%, respectively. The frequency histogram clearly separated a group of reactors with 8-18 mm indurations from a group of nonreactors showing a skin induration of 4-8 mm. The higher reactivity of this exposed child population was also reflected in a larger proportion of reactions greater to M. xenopi PPD than to human tuberculin antigen: the reactions greater by 1-5 mm accounted, respectively, for 25.1% and 20.6%, reactions greater by 6 mm or more for 23.7% and 15.9%. Among a group of children from Prague district 4, 6.4% had medium-sized and 3.8% large-sized reactions to M. xenopi antigen; the proportion of reactions greater to M. xenopi antigen than to human tuberculin accounted for only 5.1%, reactions greater to tuberculin than to sensitin were here in slight predominance. The evidenced skin sensitization to M. xenopi mycobacterin is suggested to result from the different degrees of exposure to infection by environmental mycobacteria.     

Drawing a Close to the Use of Human Figure Drawings as a Projective Measure of Intelligence

The practice of using children''s human figure drawings (HFDs) to assess their intellectual ability is pervasive among psychologists and therapists in many countries. Since the first systematic scoring system for HFDs was published in 1926, their continued popularity has led to the development of several revised versions of the test. Most recently, the Draw-A-Person Intellectual Ability Test for children, adolescents, and adults (DAP:IQ) was published. It is the most up-to-date form of HFD test designed to assess intellectual functioning across a wide age range. In the present study, we assessed the validity of the DAP:IQ as a screening measure of intelligence in both children and adults. In Experiment 1, 100 4- to 5-year-old children completed the DAP:IQ and the Wechsler Preschool and Primary Scale of Intelligence-Third Edition. In Experiment 2, 100 adults completed the DAP:IQ and the Wechsler Abbreviated Scale of Intelligence. In both experiments, we found only weak to modest correlations between scores on the DAP:IQ and the Wechsler tests. Furthermore, when we compared individual''s scores on the two tests, the DAP:IQ yielded high false positive and false negative rates when screening for borderline and superior intellectual functioning. Based on these findings, and based on the lack of validity of previous HFD tests, we conclude that practitioners should not rely on HFD tests as a projective measure of intelligence.     

New approaches to tuberculosis surveillance in nonhuman primates

Despite significant progress in reducing the incidence of tuberculosis in nonhuman primates (NHPs) maintained in captivity, outbreaks continue to occur in established colonies, with potential serious consequences in human exposures, animal losses, disruption of research, and costs related to disease control efforts. The intradermal tuberculin skin test (TST) using mammalian old tuberculin (MOT) has been the mainstay of NHP tuberculosis surveillance and antemortem diagnosis for more than 60 years. But limitations of the TST, particularly its inability to reliably identify animals with latent TB infections, make it unsuitable for use as a single, standalone test for TB surveillance in nonhuman primates in the 21st century. Advances in technology and the availability of Mycobacterium spp. genomic sequence data have facilitated the development and evaluation of new immune-based screening assays as possible adjuncts and alternatives to the TST, including in vitro whole blood assays that measure the release of interferon gamma in response to stimulation with tuberculin or specific mycobacterial antigens, and assays that detect antibodies to highly immunogenic secreted proteins unique to M. tuberculosis, M. bovis, and other species belonging to the M. tuberculosis complex. It is becoming apparent that no single screening test will meet all the requirements for surveillance and diagnosis of tuberculosis in nonhuman primates. Instead, the use of several tests in combination can increase the overall sensitivity and specificity of screening and surveillance programs and likely represents the future of TB testing in nonhuman primates. In this article we describe the characteristics of these newer screening tests and discuss their potential contributions to NHP tuberculosis surveillance programs.     

Risk factors associated with negative in-vivo diagnostic results in bovine tuberculosis-infected cattle in Spain

Background

Despite great effort and investment incurred over decades to control bovine tuberculosis (bTB), it is still one of the most important zoonotic diseases in many areas of the world. Test-and-slaughter strategies, the basis of most bTB eradication programs carried out worldwide, have demonstrated its usefulness in the control of the disease. However, in certain countries, eradication has not been achieved due in part to limitations of currently available diagnostic tests. In this study, results of in-vivo and post-mortem diagnostic tests performed on 3,614 animals from 152 bTB-infected cattle herds (beef, dairy, and bullfighting) detected in 2007–2010 in the region of Castilla y León, Spain, were analyzed to identify factors associated with positive bacteriological results in cattle that were non-reactors to the single intradermal tuberculin test, to the interferon-gamma (IFN-γ) assay, or to both tests applied in parallel (Test negative/Culture + animals, T-/C+). The association of individual factors (age, productive type, and number of herd-tests performed since the disclosure of the outbreak) with the bacteriology outcome (positive/negative) was analyzed using a mixed multivariate logistic regression model.

Results

The proportion of non-reactors with a positive post-mortem result ranged from 24.3% in the case of the SIT test to 12.9% (IFN-γ with 0.05 threshold) and 11.9% (95% CI 9.9-11.4%) using both tests in parallel. Older (>4.5 years) and bullfighting cattle were associated with increased odds of confirmed bTB infection by bacteriology, whereas dairy cattle showed a significantly lower risk. Ancillary use of IFN-γ assay reduced the proportion of T-/C + animals in high risk groups.

Conclusions

These results demonstrate the likelihood of positive bacteriological results in non-reactor cattle is influenced by individual epidemiological factors of tested animals. Increased surveillance on non-reactors with an increased probability of being false negative could be helpful to avoid bTB persistence, particularly in chronically infected herds. These findings may aid in the development of effective strategies for eradication of bTB in Spain.     

Diagnostic usefulness of the intradermal test with histoplamin in non-endemic areas of histoplasmosis

The histoplasmosis in Spain is an imported disease presenting in most of case diagnostic difficulties. In this paper, the intradermal skin test with Histoplasma capsulatum antigen as diagnostic method in immunocompetent patients with clinical and radiological signs compatible with histoplasmosis after being visited Central and South American endemic counties, in which this mycosis is endemic. Nine Spanish patients coming from different countries of Latin America with fever and acute respiratory symptoms compatible with histoplasmosis were studied. Other nine accompanying subjects and five controls were also evaluated. Patients underwent mycological cultures and and serological tests for H. capsulatum. Intradermal test with 1% histoplasmine were done in all patients. Serology and skin tests tests were also performed in accompanying people. Intradermal were done in healthy controls. Skin test with histoplasmine were positive in seven of the nine patients. Six of these showed precipitating antibodies against the same antigen. H. capsulatum was only isolated from bone marrow biopsy samples in one patient. The seven patients were given itraconazole by oral route and all symptoms improved after 2 and 4 weeks. In five accompanying subjects the skin test were also positive so that a subclinical histoplasmosis was diagnosed. In the remaining patients and healthy accompanying subjects histoplasmosis infection was excluded. In non endemic geographical areas of histoplasmosis intradermal skin test with histoplasmin when used in immunocompetent individuals is an easy and reliable method for the diagnosis of this mycosis as well as for epidemiological studies.     

Tuberculosis in wild olive baboons, Papio cynocephalus anubis (Lesson), in Kenya

Several wild olive baboons from a single troop in the Masai Mara Game Reserve, Kenya were observed to be lethargic and emaciated. Five were trapped and tuberculin tested by intradermal inoculation of 0.1 cc (100 IU) mammalian old tuberculin in the upper eyelid. Two of the five showed positive reaction at 72 hr and were examined at necropsy. Gross lesions in both animals consisted of multiple nodules with caseation in the lung, spleen and tracheobronchial lymph nodes. There were multiple granulomas throughout the lung, spleen and the lymph nodes. Tissues were cultured on Lowenstein-Jensen media with and without pyruvic acid. Isolates were typed as Mycobacterium bovis.     

Detection of Mycobacterium bovis in bovine tissue samples by the Abbott LCx Mycobacterium tuberculosis assay and comparison with culture methods.

A ligase chain reaction (LCR) DNA amplification method for the molecular diagnosis of Mycobacterium tuberculosis complex (Abbott LCx MTB) was evaluated in comparison with solid (Lowenstein Jensen), liquid (7H12, Bactec 460 system) phase culture and microscopic examination (ME) on 86 tissue samples collected from 86 intradermal tuberculin positive cattle and one pool from 4 guinea pigs experimentally infected with M. bovis. Overall, 48 samples (58.81%) were culturally positive for mycobacteria, and on the basis of biochemical characters, all the isolates were identified as M. bovis. Sensitivity was 83.92% for LCx, 53.57% for LJ, 85.71% for Bactec and 41.07% for ME. In 3 out of 25 "no visible lesion" tissue samples, M. bovis was detected only by LCx and Bactec but not by LJ and ME. The concordance in the determination of positives and negatives among the methods observed in pairs was calculated according to Cohen's K concordance coefficient and showed 81.1% of concordance of LCx vs Bactec, 68.8% LCx vs LJ, 72.2% LCx vs ME, 80.0% Bactec vs LJ, 66.7% Bactec vs ME, 85.5% LJ vs ME. Despite a certain variability in concordance rates, both Cohen's K concordance coefficients or standardized (Zk) values were statistically significant. Both LCx and Bactec appear not alternative but subsidiary to the other methods traditionally applied for direct diagnosis of bovine tuberculosis on tissue samples from cattle reacting to intradermal tuberculin test.     

The epidemiologic significance of tuberculosis mycobacteria of the avian type]

Reaction to intradermal injection of tuberculin from Mycobacteria tuberculosis of the avian type proved to be negative in all the 505 students examined who never came in contact with fowl farms. Of 738 local residents it was found to be positive in 23.8% and of 320 workers of fowl farms--in 54.5% of cases. In response to the injection of Koch tuberculin and PPD-L the number of positive reactions in all the mentioned groups constituted 69-80%. A conclusion was drawn on the epidemiological danger of Mycobacteria of the avian type for the workers of fowl farms and, to a certain degree, for the surrounding population.     

A three-way comparison of tuberculin skin testing, QuantiFERON-TB gold and T-SPOT.TB in children

Background

There are limited data comparing the performance of the two commercially available interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at risk for latent TB infection or TB disease.

Methods and Findings

The results of both IGRAs were compared with diagnosis assigned by TST-based criteria and assessed in relation to TB contact history. Results from the TST and at least one assay were available for 96 of 100 children. Agreement between QFT-IT and T-SPOT.TB was high (93% agreement, κ = 0.83). QFT-IT and T-SPOT.TB tests were positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There was moderate agreement between TST and either QFT-IT (75%, κ = 0.50) or T-SPOT.TB (75%, κ = 0.51). Among 38 children with TST-defined latent TB infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39% respectively. Three TST-negative children were positive by at least one IGRA. Children with a TB contact were more likely than children without a TB contact to have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR 1.4). Multivariate linear regression analysis showed that the magnitude of both TST induration and IGRA IFN-γ responses was significantly influenced by TB contact history, but only the TST was influenced by age.

Conclusions

Although a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs.     

High Prevalence of Bovine Tuberculosis in Dairy Cattle in Central Ethiopia: Implications for the Dairy Industry and Public Health

Background

Ethiopia has the largest cattle population in Africa. The vast majority of the national herd is of indigenous zebu cattle maintained in rural areas under extensive husbandry systems. However, in response to the increasing demand for milk products and the Ethiopian government''s efforts to improve productivity in the livestock sector, recent years have seen increased intensive husbandry settings holding exotic and cross breeds. This drive for increased productivity is however threatened by animal diseases that thrive under intensive settings, such as bovine tuberculosis (BTB), a disease that is already endemic in Ethiopia.

Methodology/Principal Findings

An extensive study was conducted to: estimate the prevalence of BTB in intensive dairy farms in central Ethiopia; identify associated risk factors; and characterize circulating strains of the causative agent, Mycobacterium bovis. The comparative intradermal tuberculin test (CIDT), questionnaire survey, post-mortem examination, bacteriology, and molecular typing were used to get a better understanding of the BTB prevalence among dairy farms in the study area. Based on the CIDT, our findings showed that around 30% of 2956 tested dairy cattle from 88 herds were positive for BTB while the herd prevalence was over 50%. Post-mortem examination revealed gross tuberculous lesions in 34/36 CIDT positive cattle and acid-fast bacilli were recovered from 31 animals. Molecular typing identified all isolates as M. bovis and further characterization by spoligotyping and MIRU-VNTR typing indicated low strain diversity within the study area.

Conclusions/Significance

This study showed an overall BTB herd prevalence of 50% in intensive dairy farms in Addis Ababa and surroundings, signalling an urgent need for intervention to control the disease and prevent zoonotic transmission of M. bovis to human populations consuming dairy products coming from these farms. It is suggested that government and policy makers should work together with stakeholders to design methods for the control of BTB in intensive farms in Ethiopia.