  VARIETIES OF TUBERCULIN—THEORIES OF TUBERCULIN REACTION—TUBERCULIN TESTS. By THEODORE B. SACHS, M. D. VARIETIES OF TUBERCULIN AND METHODS OF PREPARATIONOld Tuberculin—T. Announced by Koch in 1890. Tubercle Bacilli of human origin. Grown on beef broth containing 5% glycerine, 1% peptone, sodium chloride; growths 6 to 8 weeks. Sterilized by steam one-half hour. Evaporated (at a temp. not higher than 70° C.) to 1?10 its volume. Filtered. 1?2% carbolic acid added. Let stand. Filtered (porcelain filter). Old Tuberculin contains: 1. 40 to 50% glycerine (a small percentage of glycerine is evaporated) 2. 10% of peptones or albumoses 3. Toxic secretions of the tubercle bacilli into the culture fluid, or such of them as are soluble in 50% glycerine 4. Substances extracted from the bacterial bodies by the alkaline broth during the process of boiling and evaporation. Appearance and Characteristics: 1. A clear brown fluid 2. Of syrupy consistency 3. Mixes with water in all proportions without producing any turbidity 4. Keeps indefinitely, but not advisable to use brands older than one year. Boullion Filtrate—B. F. Denys—1907. Method of preparation same as Old Tuberculin, with the exception of subjection to heat; B. F. is a filtered, unconcentrated culture. Contains less peptone and less glycerine than Old Tuberculin. Contains no substances extracted from tubercle bacilli by heat. Some toxic substances may be more active (not having been subjected to heat). Tuberculin Ruckstand (Residue)—T. R. Announced by Koch in 1897. Ground, dried tubercle bacilli. Distilled water added. Centrifugalization. Supernatant fluid removed (not to be used). Sediment dried and ground; distilled water added; centrifugalization. Fluid removed and set aside. Sediment dried and ground again; distilled water added; centrifugalization. Fluid removed and set aside. Sediment dried and ground, etc., as above. The process continued until water takes up the sediment, then all the fluids set aside (except the first one) mixed together. Glycerine 20% added. The mixture is T. R. Koch was prompted by the following consideration in bringing out T. R.: He thought that the Old Tuberculin conferred only a toxic immunity, not bacterial. T. R. was supposed to confer bacterial immunity. Each 1 cc. of T. R. contains 10 milligrams of dried bacilli. Bacillen Emulsion—B. E. Announced by Koch in 1901. b Ehrlich considers the formation of antibodies an essential feature in the mechanism of reaction. Formation of antibodies takes place in the middle of the three layers encircling the tubercle, the layer damaged by toxins, but not yet rendered incapable of reaction. c Wassermann maintains that the antituberculin found in the tuberculous process draws the injected tuberculin out of the circulation to the tuberculous focus. The interaction that takes place between antituberculin and tuberculin results in formation of ferments which digest albumin, resulting in the softening of tissue. Absorption of softened tissue causes fever. d Carl Spengler—Toxins in the blood of the tuberculous are kept in check by antibodies. Injected tuberculin unites with antibodies, thus setting the toxins free. Result—autointoxication. e Wolff-Eisner—Bacteriolysin is present in the organism of the tuberculous, as result of previous infection; bacteriolysin sets free the potent substances of the injected tuberculin; this acts on the body and the tuberculous focus, producing a reaction. TUBERCULIN TESTSI. Subcutaneous (hypodermic); introduced by Robert Koch in 1890. II. Cutaneous; introduced by Von Pirquet in 1907. III. Conjunctival (ophthalmic); introduced about the same time by Wolff-Eisner and Calmette in 1907. IV. Percutaneous (inunction or salve); introduced by Moro in 1908. V. Intracutaneous (needle track reaction); introduced as a test by Mantoux in 1909. Described previously by Escherich. I. SUBCUTANEOUS TUBERCULIN TEST1. Apparatus and Solutions Necessary: Glass cylinder graduated to cc. 1 cc pipette graduated to 1/10 cc. 10 cc pipette graduated to 1/10 cc. Hypodermic needle suited to the syringe. Two or more 1/2 oz. bottles. 1/2% carbolic acid solution. Normal salt solution. 1 cc. Old Tuberculin. 2. Preparation of Apparatus: Glass apparatus, syringe and needles boiled before use. Some keep needles and syringe in 95% alcohol. 3. Making Solutions:
In making dilutions you may use your syringe instead of pipette. Dilutions can be kept one week in a dark, cool place. Discard turbid solutions. 4. Preparation of the Patient for the Test: Patient to keep quiet in bed, or reclining chair, for two or three days before injection. Take temperature every two or three hours for two or three days (daytime). If the test is to be applied, highest temperature should not be above 99.1 F, by mouth, according to Koch; not above 100 F, according to others. Site of injection—back, below the level of the shoulder blades, alternately on the two sides. Rub skin with ether or alcohol. An exact record of physical signs, just before injection, should be made by the physician. 5. Time of Injection: Between 8 and 10 A. M. (Bandelier and Roepke). Late in the evening, 9 or 10 P. M., or later (others). 6. Dose: According to Koch: Begin with 1/2 mg., or 1 mg., according to condition of patient; give larger dose if no reaction. Order of increase: 1 mg.; 5 mg.; 10 mg. (last dose repeated if necessary). Interval between injections: two or three days. Present Usage: First dose in adults, 1/2 mg., or 1/5 mg., or smaller, according to physical condition. First dose in children: 1/10 mg., or 1/20 mg., or even smaller. Thus, in adults: 1/2, or 1, 3, 5, 8, and rarely 10; In children: 1/10, 1/2, 1, 3. Loewenstein and Kaufmann's Scheme: Repetition of small dose, relying on exciting hypersensibility—2/10 mg.; in 3 days, 2/10 mg.; in 3 days, 2/10 mg.; in 3 days, 2/10 mg. Some use 1/10 mg., or 3/4, or 11/4, in same way. This scheme is based on hypersensibility created by repetition of same dose in tuberculous subjects. Scheme not used at present. Some advise single dose: 3 or 5 mg., (on the ground that gradual increase of doses creates tolerance). 7. Rules to Follow in Increasing Dose: a If no reaction with one dose, give a larger one next time, according to b. b If temperature rises less than 1 degree F, repeat same dose; otherwise increase. c Avoid large doses in cases of weakness, nervous temperament, children, etc. In a majority of cases smaller doses suffice. 8. After Injection: a Rest in reclining chair two or more days, unless severe reaction requires absolute rest in bed. b Take temperature every 2 or 3 hours for 2 or 3 days. 9. General Reaction: a Rise of Temperature. Positive reaction, if temperature rises at least .5° C. (.9° F.), higher than previous highest temperature.
Typical reaction temperature curve: Rapid rise, slower fall, normal temperature after 24 hours. Rise begins, in average case, 6 to 8 hours after injection (may begin within 4 hours or be delayed for 30 hours). Acme of rise in 9 to 12 hours. Duration of reaction, 30 hours or longer. Rise, acme and duration of reaction vary. b Symptoms: May begin with rigor or chilliness, followed by feeling of warmth. Following symptoms may be present: Malaise, giddiness, severe headache, pain in limbs, pain in affected organ, palpitation, loss of appetite, nausea, vomiting, thirst, sleeplessness, lassitude, etc.; in short, a general feeling of "illness." With fall of temperature—disappearance of symptoms. 10. Reaction at Point of Injection: Area of redness, swelling, tenderness; important as indicative of sensitiveness, pointing to probable general reaction with repetition or increase of dose. 11. Focal Reaction: Reaction at site of process, due to congestion around it. Focal reaction is demonstrable by: a Change in physical signs; breath sounds, resonance, appearance of rales, etc. b Localizing symptoms, pointing to location of the tuberculous process. Lungs—increase of cough, sputum, appearance of bacilli, pain in chest, etc. Kidney—pain in the region of kidney, changes in urine findings, etc. Joint—swelling, tenderness, etc. Lupus—redness and exudation. Focal reaction is an important feature of the subcutaneous tuberculin test; it permits localization of the disease in a certain percentage of cases. Physical examination, sputum examination, urinalysis, etc., are very important during the course of the reaction. 12. Contraindications: Subcutaneous tuberculin test should not be employed in: 1. Cases with temperature above 100° F, by mouth (99.1° F, by mouth, according to Koch). 2. Cases in which the clinical history and physical signs make the diagnosis certain (presence of tubercle bacilli in the sputum render, of course, any other test unnecessary). 3. Cases of recent haemoptysis. 4. Grave conditions, as severe heart disease, nephritis, marked arteriosclerosis, etc. 5. Convalescence from acute infectious diseases, typhoid fever, pneumonia, etc. 13. Interpretation of the Positive Subcutaneous Tuberculin Reaction: Occurrence of reaction, following the subcutaneous tuberculin test, signifies the existence of infection; it does not signify that the individual is clinically tuberculous. To quote E. R. Baldwin, of Saranac Lake: "The tuberculin test is of very limited value in determining tuberculous disease; it is of extreme value in detecting tuberculous infection." The test results in positive reaction in cases with latent as well as active processes. The decision as to the patient being clinically tuberculous (ill with tuberculosis) must rest on the consideration of the clinical history and the results of the physical examination. It is maintained by some that the subcutaneous tuberculin reaction is more rapid in onset and more marked in degree in cases of recent infection. On the other hand, the test is negative in a certain proportion of far advanced cases. Occurrence, then, of a subcutaneous tuberculin reaction does not indicate necessarily sanatorium or institutional treatment; neither does it absolutely indicate the necessity of tuberculin treatment. The decision rests on the consideration of all the clinical features of the case. In the absence of any symptoms or physical signs of disease, a reaction should call for regulation of every day life, tending to increase the state of general resistance (improvement of nutrition, etc.) frequently without discontinuance of work. The occurrence of reaction, in the presence of slight symptoms or physical signs, calls, according to individual condition, either for home treatment with or without discontinuance of work, or sanatorium treatment. 14. Indications for the Subcutaneous Tuberculin Test: The following considerations should guide its employment: 1. A thorough study of the history, thorough physical examination, examination of sputum (if any) give sufficient data for a reliable diagnosis in the vast majority of cases. 2. Cases, with uncertain symptoms or inconclusive physical signs, pointing to possible existence of tuberculous infection, may be treated as "suspicious" cases (without resorting to subcutaneous tuberculin test), the treatment consisting of rearrangement of mode of life, diet, work, etc., that would tend to increase of general resistance of the patient. This can and should be done in the vast majority of suspicious cases. 3. The subcutaneous tuberculin test is indicated in cases in which, in the absence of conclusive symptoms or signs, an absolutely positive diagnosis is desired; then the test should be applied, with the consent of the patient, after all other methods of diagnosis are exhausted (thorough study of the case, thorough physical examination, repeated examinations of sputum, etc). 4. The focal reaction (the reaction pointing to the seat of the disease) occurs in about 1/3, or less, of the general reactions following the subcutaneous tuberculin test; this enhances the value of the test in some cases where a focal reaction would clear the diagnosis. Above all, the subcutaneous tuberculin test should be used rarely, and then only after all other methods of diagnosis were thoroughly applied. II. CUTANEOUS TUBERCULIN TEST1. Synonyms: Von Pirquet Test or Skin Test 2. Apparatus and Dilutions Necessary: Inoculation needle of Von Pirquet Koch's Old Tuberculin (undiluted or dilutions according to method). A centimeter tape measure (divided to 1/10 cm.) to measure reactions Ether Alcohol lamp Medicine dropper 3. Application of Test: Inner surface of the forearm; clean the site with ether; place two drops of tuberculin 4 inches apart; stretch the skin and scrape off the epidermis (at a point midway between the two drops of tuberculin) by rotating the Von Pirquet needle between thumb and index finger, with slight pressure on the skin; repeat same through the two drops of tuberculin; let the tuberculin soak in for a few minutes. No dressing is necessary. The middle scarification is the control test. One tuberculin and one control test may suffice. A separate needle should be used for the control test. After each inoculation, clean the needle of tuberculin and heat the point red hot in the alcohol flame before applying it again. 4. Reaction: Gradual elevation and reddening of skin around the point of tuberculin inoculation, beginning in 3 hours or later; the reaction (papule) well developed, generally, in 24 hours and most distinct in 48 hours after inoculation. Size of papule varies from a diameter of 10 millimeters in the average case to 20 mm. occasionally, and 30, rarely (Bandelier and Roepke). At the end of 48 hours the swelling and redness subside gradually, with the subsequent bluish discoloration of the skin, remaining for various periods of time, and slight peeling of the epidermis. Individual reactions vary in degree of redness, elevation, size, contour of the border, etc. All these points should be observed and recorded. Time of inspection—24 and 48 hours after inoculation. Single inspection—best time in 48 hours. 5. Cause of Reaction: Interaction between inoculated tuberculin and the antibodies (bacteriolysins, according to Wolff-Eisner) present in the skin of a tuberculous individual; interaction results in hyperaemia and exudation (papule). 6. Interpretation of Reaction: Occurrence of positive reaction signifies presence of a tuberculous focus somewhere in the body. No indication as to activity or location of the focus. A negative reaction in adults (especially if repeated) signifies non-existence of tuberculosis (unless great deterioration of health, far advanced process, or tolerance to tuberculin established by tuberculin treatment). A positive reaction in children under two years of age signifies, generally, active tuberculous process; with the advance of age the determination of active tuberculous processes by means of cutaneous tuberculin test becomes impossible. III. CONJUNCTIVAL TUBERCULIN TEST1. Synonyms: Eye Test; Ophthalmic Test; Wolff-Eisner's Test; Calmette's Test. 2. Apparatus and Dilutions Necessary: 1 cc. pipette graduated to 1/10 cc. 10 cc. pipette graduated to 1/10 cc. 10 cc. glass cylinder Medicine dropper Koch's Old Tuberculin 1/2% and 1% dilution of Old Tuberculin in .85% sterile normal salt solution. To make 1% dilution, add .1 cc. Old Tuberculin to 9.9 cc. of diluent. 3. Application of Test: Patient sitting, with head thrown back Lower eyelid drawn slightly down and toward the nose—to form a small pouch of the lid; One drop of 1% or 1/2% instilled in that pouch and the lower lid moved up gently over the eye until the lids meet; Eye kept closed for one minute or so. 4. Reaction: Onset in 12 to 24 hours (may begin earlier); acme in 24 to 36 hours; duration of reaction—3 to 4 days or even longer (in severe cases). Some reactions are of short duration. 3 grades of reaction, according to Citron: 1. Reddening of caruncle and palpebral (lid) conjunctiva. 2. More intense reddening, with involvement of ocular (eyeball) conjunctiva, and increased secretion. 3. Very intense reddening of the whole conjunctiva, with much fibrinous and purulent secretion, etc. 5. Time of Inspection: 12 and 24 hours after instillation; then once a day. 6. Cause of Reaction: Hyperaemia and exudation resulting from interaction between instilled tuberculin and antibodies in conjunctiva (bacteriolysin, according to Wolff-Eisner). 7. Interpretation of Reaction: Wolff-Eisner maintains that positive conjunctival tuberculin reaction means active tuberculosis, a conclusion accepted by but a few. 8. Field of Application of Conjunctival Tuberculin Test: Should not be used; connected with danger to the eye. Conjunctival test used very rarely at present. IV. PERCUTANEOUS TUBERCULIN TEST1. Synonyms: Salve Test; Moro Test. 2. Salve: Equal parts of Old Tuberculin and anhydrous lanolin. 3. Application of Test: Site: abdominal wall below ensiform process, or breast below nipple, or inner surface of forearm. Application: rub in with the finger (using moderate pressure) a small particle of salve about the size of a pea. Rub it in into an area about 5 cm.; rub 1 minute. 4. Reaction: In 24 to 48 hours—either numerous small reddened spots which disappear in a few days, or numerous small nodules, or coalescing nodules on a red base, etc. 5. Interpretation of Reaction: Positive reaction is assumed to indicate existing tuberculous infection somewhere in the body; does not indicate that the process is active. 6. Field of Application of Percutaneous Tuberculin Test: The percutaneous tuberculin test fails in a large proportion of tuberculosis cases. The test is used rarely at present. Lignieres TestA modification of the Moro Test Instead of salve, a few drops of Old Tuberculin rubbed in. Used rarely at present. V. INTRACUTANEOUS TUBERCULIN TEST1. Synonyms—Mantoux Test 2. Application of Test: Injection into skin (needle parallel to skin) of 1/100 mg. of Old Tuberculin (according to Mantoux). 3. Reaction: Onset in a few hours, well developed in 24 hours, acme in 48 hours. Reaction consists of a central nodule surrounded by a halo of redness. This is the intracutaneous test as originally suggested by Mantoux. CONCLUSIONSComparing the various tuberculin tests we find that: 1 The Subcutaneous Tuberculin Test has the advantage of focal reaction, disclosing in a certain percentage of cases the seat of the disease. The subcutaneous test should, however, never be employed unless as a last resort, and then only after all other methods of diagnosis are exhausted and an absolute diagnosis is very essential. In the vast majority of suspected cases of tuberculosis, thorough study of the history of the case, combined with thorough physical examination, furnishes all the necessary data for diagnosis and an efficient plan of treatment. 2 The Cutaneous Tuberculin Test is a very efficient diagnostic measure in children under two years of age in whom a positive cutaneous tuberculin reaction indicates active disease. Positive cutaneous tuberculin reaction in adults indicates existence of a tuberculous process, somewhere in the body; it does not indicate that the process is active. Negative cutaneous tuberculin reaction is one of the corroborative evidences of absence of tuberculosis, unless reaction is prevented by very advanced disease or tolerance to tuberculin established by tuberculin treatment. 3 Thorough study of the history and thorough physical examination of each individual case are more important and should precede the application of any test. FOOTNOTES:(END) Transcriber's Note: Blank pages have been deleted. Paragraph formatting has been made consistent. The publisher's inadvertent omissions of important punctuation have been corrected. Other changes are listed below. The listed source publication page number also applies in this reproduction except possibly for footnotes since they have been moved. Page Change 7 the acute inflamatory[inflammatory] at the beginning, 9 systematic treatment was underaken[undertaken]. 9 Bodingon of Sutton, Coldfield[Sutton Coldfield], England, 10 The fundimental[fundamental] principle 19 fit to make to a printed questionaire[questionnaire]. 23 who visits the physican[physician] 28 Tuberculosis Sanitarium is extending sanatorum[sanatorium] care 35 [Split first footnote into two.] 36 in the shelter of a strong windbrake[windbreak]. 43 makes a family, ordinnarily[ordinarily] 58 [Split first footnote into two.] 58 Hyperdermic[hypodermic] needle suited to the syringe 62 absence of conclusive symptons[symptoms] or signs, 62 (thourough[thorough][et seq.] study of the case, 63 all other methods of diagnosis were thouroughly[thoroughly] 63 from a diameter of 10 millimeters in [the] average case 66 [Added (END).] On page 50 of the original publication, the following portion of a paragraph has two extraneous lines here marked in brackets: All of the cooking was done by the teacher. Careful attention to [is given. Children are weighed once in two weeks. Instruction] [is chiefly practical. Instruction in gardening is given twice a week] general cleanliness and hygiene of the teeth was insisted upon. Individual drinking cups and tooth brushes were provided. The children took turns in washing dishes, setting the table and helping.... The extraneous lines are duplicates of lines further up the page and have been deleted. |
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