Definition.
A skin test used to diagnose type IV hypersensitivity reactions due to tuberculosis infection. It is informative in the diagnosis of active tuberculosis and in the determination of the cellular immune function of the body.
Applied disciplines.
Immunology (primary discipline); Applied immunology (secondary discipline); Immunological testing and diagnosis (tertiary discipline)
The above content is reviewed and published by the National Committee for the Review of Scientific and Technical Terminology
Encyclopedia card
The tuberculin test (also known as the Muntu test and the PPD test) is a tool for diagnosing tuberculosis. It is one of the two major tuberculin skin tests in the world and has largely replaced many puncture tests, such as the Tine test. Until 2005, the Heaf test was used in the United Kingdom, but it has now been replaced by the tuberculin test as well. The tuberculin test is also used in Australia, Canada, Hungary, the Netherlands, Portugal, South Africa, and the United States, and is recommended by the American Thoracic Society and the Centers for Disease Control and Prevention. It is also used by the former Soviet Union and countries that were once part of the Soviet Union.
Currently, the types of tuberculin commonly used in China
1.Old Tuberculin OT (Old Tuberculin OT).
2.Pure protein derivative of tuberculin (PPD).
1.Negative reaction
2.Positive reaction
3.Pure protein derivatives (PPD).
A skin test based on the principle of type IV metaplasia (see metaplasia), used to detect whether the body has been infected with Mycobacterium tuberculosis. Where the infection has been tuberculosis
Tuberculin test
The body that has been infected with Mycobacterium tuberculosis produces sensitized lymphocytes that have the ability to recognize Mycobacterium tuberculosis. When a small amount of Mycobacterium tuberculosis or tuberculin is encountered again, the sensitized T lymphocytes are stimulated again by the same antigen to release a variety of soluble lymphokines, leading to increased vascular permeability and local accumulation of macrophages, resulting in infiltration. Within approximately 48 to 72 hours, a positive local reaction of red, swollen and hard nodules appears. If the subject has not been infected with Mycobacterium tuberculosis, no local metaplasia occurs with the injection.
Tuberculin is the mycobacterial component of Mycobacterium tuberculosis, and there are two kinds. old tuberculin (OT) was first invented by Koch (R, Koch). The old tuberculin (OT) was first invented by Koch (R, Koch), while the purified protein derivative (PPD) was first prepared by Seibert (R, Koch). There are many methods of tuberculin test, commonly used is Mantoux’s method, that is, OT or PPD diluted into different concentrations with sterile saline, take 0, 1 ml injected into the forearm palm side skin, 48 to 72 hours later to check the reaction, should pay attention to the local presence of hard nodules, not alone to the redness as the standard. If the injection site has a pinhole-sized red spot or slightly red and swollen, and the diameter of hard nodes is less than 0, 5 cm, it is a negative reaction. If the diameter of the hard nodes at the injection site is more than 0, 5 cm but less than 1, 5 cm, it is a positive reaction. If the injection site has a strong reaction or the diameter of the hard nodule is more than 1,5 cm, it is a strong positive reaction. A positive reaction indicates that the organism has a metabolic reaction to Mycobacterium tuberculosis and has been infected with tuberculosis in the past, but does not indicate disease, as people who have been vaccinated with BCG also show a positive reaction. A strong positive reaction indicates a possible active infection and should be further examined for tuberculosis. A negative reaction indicates the absence of tuberculosis infection, but the following should be considered: a negative reaction may occur temporarily in such cases if the subject is in the early stages of primary infection and has not yet developed a metabolic reaction, or if the subject is suffering from severe tuberculosis and the organism has lost the ability to respond, or if the subject is suffering from another infectious disease. The tuberculin test can provide a basis for BCG vaccination and determination of the immunization effect. If the tuberculin test is negative, the BCG vaccine should be administered, and if the reaction turns positive after the vaccination, it means that the vaccination has produced an immune effect. The tuberculin test can also be used as a reference for the diagnosis of tuberculosis in infants and children, to determine nonspecific cellular immunity in patients with tumors, and to investigate the prevalence of tuberculosis in people who have not been exposed to BCG.
Tuberculin is extracted from Mycobacterium tuberculosis by glycerol. pPD bacteriocin is a precipitated, non-species-specific molecule obtained from the filtrate by sterilization. It was first described by Robert? Koch in 1890, when it was first described.
In 1939, M.A. Linnikova of the former Soviet Union created a modified version of PPD, PPD-L. In 1954, mass production of PPD-L began in the former Soviet Union.
The standard dose was 5 tuberculin units (0, 1 ml), which were injected intradermally and the results observed after 48 to 72 hours. A person who had been exposed to the germ would show an immune response.
The results of this test are reflected by the diameter (perpendicular to the arm) of the sclerotic nodule (a distinct raised area of sclerosis). If no sclerosis is present, the result should be recorded as 0 mm. erythema of the skin should not be measured.
If a person has a history of positive tests, other tests are not required.
Classification of results
Test results should be interpreted with caution. A positive result reflects a history of exposure to TB.
Tuberculin test
① 5 mm or greater.
Positive reaction for HIV.
Prednisone ≥ 15 mg/d.
Chest radiograph showing old union.
Recent exposure to a person with TB infection.
Patients with organ transplants and other immunosuppressed patients.
② 10 mm or greater.
Previous exposure from a high incidence country in the last 5 years.
Intravenous drug use.
Low-income populations.
Patients with chronic diseases.
Patients with silicosis.
Residents and employees of high-risk areas (e.g., prisons, nursing homes, hospitals, shelters, etc.).
Bifidobacterium laboratory personnel.
Children less than 4 years of age, or children and adolescents at high risk of exposure to adults.
③ 15 mm or greater.
Persons without risk exposure to Mycobacterium tuberculosis
Tuberculin test conversion: defined as an increase of 10 mm or more over a 2-year period (regardless of age)
Positive PPD test after BCG immunization, general hard node size: >5 mm, <15 mm
Purpose of the test
(1) To provide a basis for BCG vaccination. If the tuberculin test is positive, it indicates that the body has been infected with tuberculosis bacteria and no further BCG vaccination is required. If the test is negative, BCG vaccination is indicated.
(2) To provide a basis for determining the immunity effect: Generally, after 3 months of BCG vaccination, tuberculin test should be done to find out whether the body is immune to BCG vaccine. If the tuberculin test is positive, it means that the BCG vaccination is successful; otherwise, the BCG vaccination should be repeated.
(3) For diagnosis and differential diagnosis: Tuberculin test is an important tool for the diagnosis and differential diagnosis of tuberculosis in adolescents, children and the elderly, and is a commonly used auxiliary test.
Principle
Tuberculin skin reaction is a delayed cellular hypersensitivity reaction. The antigen (Mycobacterium tuberculosis or BCG) enters the body and sensitizes the body’s immune T-lymphocytes, which then proliferate. When the sensitized organism is again invaded by the antigen, the sensitized lymphocytes bind to it and cause a metaplastic inflammation. This results in the formation of hard nodules or even blisters and necrosis at the site of tuberculin injection. A positive tuberculin test indicates that the body has been infected with tuberculosis or has received BCG vaccination, and also indicates that the body has some immunity to tuberculosis. However, there are a few immunocompromised individuals (about 5%) who are negative or have a false negative due to technical reasons. Usually, a negative PPD skin test after BCG vaccination indicates a failure of vaccination.
Tuberculin
Old tuberculin (OT) is a metabolite of the tubercle bacillus extracted from the liquid medium in which the tubercle bacillus has grown, and contains mainly tuberculin. When screening in the population, 1:2000 OT dilution of 0,1ml (5IU) can be used for intradermal injection in the flexor side of the left forearm, and the diameter of skin nodules can be measured after 48-72h. -19 mm is a positive reaction, and 20 mm or more or localized blistering and necrosis is a strong positive reaction.
The pure protein derivative (PPD) of tuberculin is pure tuberculin, which does not produce non-specific reaction, and PPD-PT23 is made in Denmark and used in many countries around the world and has replaced OT. 5IU, used for clinical diagnosis, the average diameter of hard nodules ≥5mm is a positive reaction.
In addition to causing local skin reaction, the nodule test can also cause the original TB lesions and systemic reaction. 5IU is generally used for clinical diagnosis, and if there is no reaction, 5IU skin test can be used again after a week (to produce enhanced effect of nodulin), and if it is still negative, tuberculosis infection can be mostly excluded.
Judgment method
China stipulates 72 hours as the observation time of reaction, and the reaction can be measured within 48-96 hours. The recording method is to express the measured number of mm of transverse diameter of hard nodes × mm of longitudinal diameter, if there are blisters, hard nodes, necrosis and lymphadenitis, it should be recorded.
Negative reaction
No hard nodes or those with a mean diameter of hard nodes <5mm.
Positive reaction
A hard node with an average diameter of 5 mm or more is considered positive, 5-9 mm is generally positive, 10-19 mm is moderately positive, and 20 mm or more with local blistering, hemorrhage, necrosis and lymphadenitis are strongly positive.
Positive nodule test
A positive nodule test only indicates tuberculosis infection, not necessarily disease. The rate of tuberculosis infection among urban adult residents in China is more than 60%, so the general positive result of the test with 5IU nodulin is not significant. However, if the skin test is strongly positive with high dilution (1IU), it often indicates the presence of active TB foci in the body. The diagnostic value of the nodule test is greater in infants and children than in adults because the younger the age, the lower the natural infection rate; a strong positive reaction under 3 years of age should be considered as having recently infected active TB and should be treated.
Negative nodule test
In addition to suggesting the absence of tuberculosis infection, a negative tuberculin test reaction is seen in the following cases It takes 4-8 weeks for the metabolic response to become fully established after tuberculosis infection; in this pre-metabolic period, the nodulin test may be negative. In patients with immunosuppressive agents such as glucocorticoids, or in patients with malnutrition and measles or whooping cough, the tuberculin reaction may also disappear temporarily. Severe tuberculosis and various critically ill patients do not respond to nodulin or are only weakly positive, which is due to the temporary suppression of human immunity along with the metabolic reaction; when the condition improves, it will turn positive again. Other patients with lymphocyte immune system defects (e.g., lymphoma, leukemia, nodular disease, AIDS, etc.) and the elderly also often have negative nodulin reactions.
Two-step test
There are two main types of tuberculin commonly used in clinical practice: one is called “old tuberculin” (0, T), which is a culture filtrate of tuberculosis bacteria, except for the test containing
tuberculin test
In addition to tuberculin, there are also mycobacterial autolysis components, tuberculosis metabolites and culture medium components. The other type is called “pure tuberculin” (P, P, D), which mainly contains tuberculin, and its specificity and purity are better than those of the old tuberculin. When tuberculin is injected locally, the activated immune cells in the body will collect and stay in the injection site from the blood, resulting in local skin redness, hard nodules and blisters, i.e. positive reaction to tuberculin, while those without such reaction are negative. Observation of this reaction is based on 72 hours. In an immunocompetent person, a positive tuberculin reaction can be observed if a tuberculosis bacillus enters the alveoli and causes an infection. Conversely, a person who is not infected with TB bacteria has little to no resistance to TB bacteria and will have a negative nodulin reaction.
The nodulin test is a highly sensitive and specific test, and a positive test reaction is valuable for diagnosing tuberculosis infection, but it cannot diagnose the presence or absence of tuberculosis in the lungs or determine the nature of the lesion. In addition, a positive tuberculin reaction is also a manifestation of the metamorphosis produced by BCG vaccination, and is often used epidemiologically to assess the effectiveness of BCG vaccination. A positive tuberculin test is not necessarily a bad thing, it indicates that the tuberculosis bacteria are present in the body, but it also indicates that the body has developed a certain degree of immunity to tuberculosis, and when the bacteria are re-infected, or when the bacteria multiply in the body to form foci, the specific immune cells in the body “surround” the bacteria locally, so that it is not easy to spread to other parts and organs. If the tuberculosis test is negative, BCG vaccination should be given to promote the body’s resistance to tuberculosis and make the tuberculosis test positive. Of course, there may be false negatives or false positives in the tuberculosis test, and these should be considered by the doctor.
There are some people who cannot or temporarily cannot perform tuberculin skin test, such as: recovery period of various infectious diseases, fever, acute period of organic heart, liver and kidney diseases; people with neurological and mental abnormalities, people with their own and family history of allergy; people with less than two weeks of other vaccinations; people with systemic or localized skin diseases. To know if you have been infected with TB or if you are resistant to TB you only need to go to a specialist hospital and have a tuberculin test done for 72 hours.
Some people previously infected with TB may test negative when the test is performed several years after infection, as the immune system’s response may gradually wane. This initial skin test, although negative, may stimulate the body’s immune system, resulting in a positive test result later.
Use a two-step process for the initial test. This will ensure that in the future, if the test is positive, it can be interpreted as a new infection rather than a simple reaction to an old infection.
Check the results 48 to 72 hours after the first injection
Positive, consider the infected person
Negative, second test given 1 to 3 weeks later
Results 48 to 72 hours after the second injection
Positive, consider previous infection
Negative, consider uninfected
A person who is diagnosed as “infected” by a two-step test is called a “tuberculin convert.
A brief history of tuberculin
The discovery of tuberculin was first announced in 1890. On April 4 of that year, Robert Koch gave a lecture at the 10th World Medical Conference. Koch gave a lecture at the 10th World Medical Conference in that year and announced the discovery of a substance that could prevent tuberculosis in guinea pigs and had a therapeutic effect.
In 1891, Koch identified this liquid as the culture filtrate of tuberculosis bacteria and named it tuberculin.
In 1908 the method of tuberculin test was discovered (C, Mantoux).
In 1928 the United States P, B, Seibert made a pure protein derivative tuberculin (PPD) from the culture fluid of tuberculosis bacteria.
In 1941, a standard pure protein derivative of tuberculin (PPD-S) was developed in the United States.
In 1958, a purer and more concentrated pure protein derivative of tuberculin (PPD-RT23) was developed in Denmark and is a WHO recommended preparation;
Note: The PPD produced in Japan is called PPDS
The types of tuberculin commonly used in China at present
1.Old Tuberculin OT (Old Tuberculin OT).
It is the metabolite of Mycobacterium tuberculosis extracted from the glycerol broth medium in which Mycobacterium tuberculosis has grown, sterilized and concentrated to form the original solution, and then diluted to a certain number of times (usually 2000 times) when used, so that each 0.1ml contains 1U. components.
2.Pure protein derivatives of tuberculin (PPD).
Tuberculin pure protein derivative (purified protein derivative, PPD) is more pure, pure nodulin, does not produce non-specific reactions. Its production process: strain → culture → sterilization, filtration → concentration → salting, desalting → drying, preservation → distribution. PPD-RT23 is made in Denmark and supplied to many countries around the world, has replaced OT. It is used for clinical diagnosis.