Tuberculin Test in Children with Malnutrition

Tuberculin tests with Heaf''s multiple-puncture method, as well as intradermal tests with varying strengths of old tuberculin, were carried out on 402 children with severe malnutrition. From the radiological and bacteriological findings 51 children (12.5%) were considered to have active tuberculosis. The Heaf test was positive in only 11 of these children, but the intradermal test using 100 tuberculin units was positive in a further 18. This confirms previous findings that tuberculin sensitivity is impaired in malnourished children, and suggests that a higher dose of tuberculin is more likely to elicit a positive response.     

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.     

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.     

The utility of the macrophage migration inhibition test for in vitro titration of tuberculins

The purpose of this study was to explore the fundamental principle of the potency estimation of tuberculins, as applied in vitro by the macrophage migration inhibition test (MIT) under agarose. The MIT was performed using specifically sensitized mouse and guinea-pig peritoneal macrophages and serial dilutions of the analogous PPD (purified protein derivatives of tuberculin) tuberculins as antigen. Statistical studies performed included (a) the standard deviation of the mean migration areas, (b) the analysis of variance, (c) the regression analysis, (d) its corresponding linearity test and (e) the determination of the related correlation coefficient. It was shown for the first time and in both animal species under study that there is correspondence between the log dose-response relationship of the tuberculin PPD in MIT under agarose and the well known in tuberculin cutaneous reaction. The MIT may therefore successfully replace the in vivo titration of tuberculins.     

Antibody response to a sterile filtered PPD tuberculin in <Emphasis Type="Italic">M. bovis</Emphasis> infected and <Emphasis Type="Italic">M. bovis</Emphasis> sensitized cattle

Background  

Bovine tuberculosis, caused by Mycobacterium bovis, afflicts approximately 50 million cattle worldwide and is detected by the tuberculin skin test (TST). While it has long been recognized that purified protein derivative (PPD) tuberculin is composed of a mixture of M. bovis derived protein components, little is known about the quality, relative quantity and identity of the proteins that make up PPD tuberculin. We manufactured a sterile filtered PPD tuberculin (SF-PPD) from a nine-week-old M. bovis culture supernatant in order to characterise the culture filtrate proteins (CFP) which make up M. bovis PPD tuberculin and to compare the antibody response of M. bovis infected versus M. bovis sensitized cattle.     

Tuberculin immunotherapy: its history and lessons to be learned

The use of tuberculin for the therapy of tuberculosis was attempted more than 100 years ago and abandoned because of its adverse reactions. In this historical review we point out that some of the intensive efforts to avoid the reactions were based on the best scientific rationale available at that time. Balancing the dosage and intervals of tuberculin delivery with clinical and laboratory monitoring of patients achieved a limited success, with implications, toward current research in the field. The role of economical and social aspects at that time is also a lesson to be learned toward current approaches to tuberculosis control.     

Cell-mediated response to BCG investigated by leukocyte migration test from an agarose droplet

The modified leukocyte migration test (LMT) from an agarose droplet with the antigen stimulation (by BCG) is proposed in the present work. The BCG concentrations ranging from 1.25 up to 130 mg/l were used to examine 20 tuberculin (PPD) skin test negative and 10 PPD positive patients, which suffered from lung diseases. The optimal concentrations were 6.25 and 25.0 mg/l. The mean index values of a 20 membered control group ranged from 0.7 up to 0.88 when stimulated with the lower BCG concentration, and they were of 0.53 up to 0.69 at higher BCG concentration. In spite of its suitable indicatory properties as to ascertain cell mediated immunity state, the LMT with the BCG were of no use as a tuberculin skin test correlate.     

Leukocyte procoagulant activity in man: an in vitro correlate of delayed-type hypersensitivity

Human mononuclear leukocytes generate cell-bound procoagulant activity (LPCA) after incubation with an antigen (mumps or tuberculin) to which the donor was previously sensitized. An inhibitor of coagulation appears to be liberated into the extracellular culture fluid during incubation of leukocytes with the sensitizing antigen. Removal of this activity before measuring LPCA resulted in a reliable test that correlated directly with delayed skin reactivity. The assay was particularly sensitive in that cells from weakly sensitized donors who reacted only to high doses of tuberculin (100 TU) in the delayed skin tests produced detectable LPCA in vitro. By contrast cells from weakly sensitized donors did not react to PPD in the lymphocyte blast transformation test or the direct macrophage migration inhibition factor test. The LPCA assay correlated closely with the blast transformation and MIF tests in which cells were used from more strongly sensitized donors who reacted in skin tests with lower doses of tuberculin (1 or 10 TU). The assays were antigen-specific in that cells from donors sensitive to mumps antigen but not to tuberculin reacted only to mumps antigen in vitro. The assay was extremely reproducible; cells from individual donors reacted to the same extent over a period of 8 mo). We propose that the assay system reported here represents an improved method for the measurement of cell-mediated immunity in vitro because it requires fewer donor cells, is technically simpler, and is more sensitive than previously described methods.     

Chromatographic analysis and immunobiologic properties of tuberculins]

Immunobiologic activities of tuberculin preparations and their components have been comparatively studied using gel filtration and high-performance liquid chromatography (HPLC) techniques. It is shown that high-molecular weight fraction of protein-purified derivate tuberculin (PPD) had higher activity as compared to nonfractionated preparation in skin tests on guinea pigs sensitized with Mycobacterium bovis BCG as well as in enzyme-linked immunosorbent assay with affinity purified rabbit antibodies against PPD. Using the preparative HPLC-technique we failed to isolate a component of PPD having greater tuberculin test potency than nonfractionated preparation.     

Purified Protoplasmic Peptides of Mycobacteria: Isolation of Species-Specific Peptides from Protoplasm of Mycobacteria

Infections with mycobacteria other than tubercle bacilli are responsible for a variable percentage of cross-reactions to tuberculin. Two major suggestions for circumventing this problem have been made: the first, development of a quantitative tuberculin test, is based on the fact that most cross-reactions are smaller than those caused by true tuberculous infections; the second, preparation of purified skin test antigens from other mycobacteria, is based on the hope that greater specificity will be displayed by homologous sensitin. Effort so far has been focused on the culture filtrates as the source of antigen. This article describes the preparation of low molecular weight purified protoplasmic peptides (PPP) of specificity and sensitivity superior to purified protein derivatives.     

Causes of para-allergy to tuberculin

Experiments on 56 rabbits infected with microorganisms of the genera Mycobacterium, Nocardia and Rhodococcus revealed that in response to the action of different antigens used T and B systems of immunity induced synthesis of antibodies reactive with nonspecific antigens (mycobacterial antigens, tuberculin). In some cases the statistically significant correlation between the dynamics of blast transformation and the specific lysis of lymphocytes in animals with Nocardia and Rhodococcus infections (in comparison with the controls) was determined when P.P.D. tuberculin was used as specific antigen. In the rabbits sera infected by Nocardia and Rhodococcus complement-fixation and hemagglutination antibodies to mycobacterial antigens were detected. These rabbits also exhibited skin reaction to P.P.D. tuberculin. The presence of common group-specific antigens in Nocardia and Rhodococcus, as well as in mycobacteria, determined the capacity of the former to sensitize experimental animals to tuberculin, with should be taken into consideration in making the allergic test to tuberculosis.     

Role of T- and B-lymphocytes in the heterogeneity of human cell-mediated reactions to bacterial antigens]

Leucocytes from 30 patients with allergy to tuberculin and bacterial antigens were treated with antithymus (ATS) and anti-immune globulin (AIGS) sera. The leucocyte migration inhibition test (LMIT) was performed with these antigens. ATS abolished the LMIT induced by tuberculin and sometimes by bacterial antigens (staphylococcal, streptococcal etc.). AIGS frequently abolished the LMIT induced by bacterial antigens, but not by tuberculin. In some cases the treatment with any serum abolished the LMIT induced by the antigens, or, on the contrary, it was abolished only by a successive treatment with both sera. The lymphocyte types (T or B) determining the secondary immune response to the same antigen are different in various patients, as well as they differ in the same patients in relation to diverse antigens. Five types of lymphocyte - antigen interrelation in the LMIT have been distinguished.     

Cattle owners' awareness of bovine tuberculosis in high and low prevalence settings of the wildlife-livestock interface areas in Zambia

Background  

Awareness of bovine tuberculosis (BTB) by cattle owners is of extreme importance to policy makers when considering mitigation. However, to our knowledge, little is known on cattle owners' awareness of BTB in Zambia. Similarly, such knowledge is uncommon within and outside Africa. The current study investigates the epidemiological characteristics of BTB in Zambian cattle in relation to awareness by cattle owners in high and low cattle BTB prevalence settings. A cross sectional study was designed and data was gathered based on 106 cattle owners and cattle herds; subjected to an interviewer-administered questionnaire and comparative intradermal tuberculin test using a cut-off for positivity of 4 mm, respectively.     

Genetic Predisposition to Pass the Standard SICCT Test for Bovine Tuberculosis in British Cattle

Bovine tuberculosis (bTB) imposes an important financial burden on the British cattle industry, yet despite intense efforts to control its spread, incidence is currently rising. Surveillance for bTB is based on a skin test that measures an immunological response to tuberculin. Cattle that fail the test are classified as “reactors” and slaughtered. Recent studies have identified genetic markers associated with the reaction of cattle to the tuberculin test. At marker INRA111 a relatively common ‘22’ genotype occurs significantly more frequently in non-reactor cattle. Here we test the possibility that the putative protective ‘22’ genotype does not confer resistance but instead causes cattle that carry it to react less strongly to the prescribed test, and hence avoid slaughter, potentially even though they are infected. We show that, after controlling for age and breed, ‘22’ cattle react less strongly to the immunological challenge and may therefore be less likely to be classified as a reactor. These results highlight the potential discrepancy between infection and test status and imply that the effectiveness of the test-and-slaughter policy may be being compromised by selection for cattle that are genetically predisposed to react less strongly to tuberculin.     

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.     

Correlation of tuberculin-induced lymphocyte transformation with skin test reactivity and with clinical manifestations of sarcoidosis

In vitro lymphocyte reactivity to tuberculin (PPD) was studied in buffy coat cultures from 87 patients with sarcoidosis and from 64 controls. A strong correlation was found between PPD-induced lymphocyte transformation and skin reactivity. No significant differences were found in the in vitro response of lymphocytes from skin test positive patients with sarcoidosis and from controls with the same degree of skin test reactivity. In patients with sarcoidosis negative to 100 TU, tuberculin sensitivity could be demonstrated in vitro significantly more often than in comparison subjects. Both in vivo and in vitro tuberculin sensitivity and “spontaneous” transformation were significantly more frequent in patients with erythema nodosum.     

Tuberculosis in childhood

Those physicians who deal with children have much to contribute toward case finding in tuberculosis among these patients as well as adults. The tuberculin test is the most accurate weapon at hand. Contacts other than the parents should be looked for. Symptoms, beside fever, to be noted are eye and skin complaints. In the physical examination the chest is relatively unimportant as compared to the eye, the skin, the lymphatic and skeletal systems. In the roentgenographic examination, epituberculosis and atelectasis should be differentiated. When stomach washings are necessary for the diagnosis, the tuberculin test on the guinea-pig should not be forgotten. Careful laboratory studies will clear up roentgenographic confusion. In the treatment, removal of contact is essential, and often all that is necessary, but other factors should be considered. Of the more common complications, atelectasis, bronchiectasis, and cavitation or reinfection, may be treated surgically with all the accepted methods except thoracoplasty. Heliotherapy should not be forgotten in bone and joint tuberculosis. It is to be hoped that BCG will prove efficacious in vaccination, but published reports are not scientifically convincing. It destroys the value of the tuberculin test where used, and it should never be substituted for removal of contact as a prophylactic measure.     

Evaluation of quality of contents of general practice records.

The quality of contents of general practice records was assessed by retrieving clinical information pertaining to hypertension in 171 consecutive records, and the quality of communication storage was assessed by seeking evidence of tuberculin skin tests or BCG vaccination, or both, in 298 consecutive records. There was no mention of urine analysis and blood test results in 43.3% and no record of fundal examination in 61.4% of the records of patients with hypertension. Electrocardiography was performed in 67.8% and chest x ray examination was done in 65.5% of these patients. These observations have importance for patient care, education, and research. The information regarding tuberculin skin test or BCG immunization, or both, was not available in 78% of the records. Reassessment of the individuals, however, showed that 89% of the studied population had had the test or vaccination, or both. There was thus a deficiency in communication and storage.     

Vaccination with Freeze-Dried BCG

Sixty first-year medical students, negative to 1:2000 and 1:100 dilutions of old tuberculin (OT), were vaccinated with freezedried BCG vaccine. At six months, 98.3% were found to be positive reactors as ascertained by the intracutaneous (Mantoux) method, using 1:2000 and 1:100 dilutions of OT, and 73.7% as ascertained by the Heaf test, using a tuberculin PPD solution containing 100,000 T.U. per ml.