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    Home > Active Ingredient News > Infection > G test and GM test: a "powerful weapon" for early diagnosis of pulmonary mycosis!

    G test and GM test: a "powerful weapon" for early diagnosis of pulmonary mycosis!

    • Last Update: 2021-03-27
    • Source: Internet
    • Author: User
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    AuthorWang Chengcheng, Department of Respiratory Medicine, Danzhou People’s Hospital, Hainan Province.
    Invasive mycosis (IFD) refers to conditional pathogenic fungi that invade the human body when the host’s immune function is low or defective, and grow and reproduce in tissues, organs or blood.
    And cause inflammation and tissue damage diseases.

    With the obvious improvement of detection and diagnosis technology, it is also affected by various factors such as organ transplantation, hematological diseases, malignant tumors, chronic obstructive pulmonary disease, bronchiectasis, and long-term use of broad-spectrum antibiotics, glucocorticoids, immunosuppressants, etc.
    , The prevalence, morbidity and mortality of invasive fungal disease (IFD) have increased significantly compared with the previous period.

    Because the clinical manifestations of invasive mycoses lack specificity, the diagnosis requires histopathological evidence, and histopathology is complicated and risky.
    For example, many patients are accompanied by severe agranulocytosis and thrombocytopenia, and it is difficult to tolerate tissue biopsy; traditional Fungal detection methods (such as fungal smears and cultures of sputum and bronchial lavage fluid) have a low positive rate and a relatively lagging detection time; lung fungal infection imaging (high-resolution CT of the chest) has a relatively valuable "moon halo sign" The occurrence rate only accounts for 33% to 60% of invasive fungal diseases, and this characteristic change only appears within the first 5 days of infection, and most of them disappear within 1 week.

    Therefore, clinically, it is very urgent to have a simpler, faster, less traumatic, better tolerable, high sensitivity and specific detection method to help early clinical diagnosis and timely treatment.

    Therefore, in recent years, the G test and the GM test have received everyone’s attention and popular praise.
    They are of great value and significance in clinical diagnosis of invasive fungal diseases, but there are still a lot of people who still have these two problems.
    I don’t know much about this examination, and I lack awareness and knowledge of fungal diseases.
    The author often encounters such problems and is invited to consult.

    What is fungus? Before introducing the G test and the GM test, let us briefly review what a fungus is? Fungus is a kind of eukaryote, and it is in its own family, which is different from animals, plants, and bacteria.

    Compared with the other three organisms, the biggest difference is that the main components of fungal cell walls are chitin (also known as chitin), cellulose, glucan, mannan, etc.
    These components are the polymerization of monosaccharides.
    Things.

    What is the G test? The G test is used to detect (1-3)-β-D glucan, one of the main components of fungal cell walls, because other microorganisms, animal and human cell components and extracellular fluids do not contain this component, and the human body is invaded In the process of deep fungal infection, (1-3)-β-D glucan can be continuously released into the blood and other body fluids to increase its content (there is no similar phenomenon in superficial fungal infection).

    Before clinical manifestations, microbiological evidence, and chest high-resolution CT signs, serum (1-3)-β-D glucan levels are already higher than normal (4 to 5 days earlier than fever or other clinical symptoms on average) , 9.
    3 days earlier than high-resolution CT of the chest on average), and is not affected by the immune status of the body.

    Therefore, the detection of (1-3)-β-D glucan in the blood is an effective basis for the diagnosis of deep fungal infections, and is of great significance for the early diagnosis of all invasive deep fungal infections except Cryptococcus and Zygobacterium.
    It can be used for the diagnosis of invasive infections caused by fungi such as Candida, Fusarium, Aspergillus, Penicillium/Paecilomyces, Trichosporium, etc.
    It can guide the clinical early use of antifungal drugs, especially for Candida For bacteremia, the G test is the first choice.

    This test is called the G test because (1-3)-β-D glucan can specifically activate factor G in the lysate of horseshoe crab amebocytes, causing the lysate to solidify, hence the name.

    The disadvantage of the G test is that it can only determine whether there is a fungal infection, but the specific species of the fungus cannot be determined, and the G test is negative when it is infected by Zygomycetes (mucor, Rhizopus, etc.
    ) or cryptococcus.

    Although the G test cannot determine the specific bacterial species, the elevated value of (1-3)-β-D glucan may have a certain identification significance.
    Studies have shown that the serum (1-3)-β- of people infected with Candida The mean value of D-glucan was 755 pg/mL; the mean value of Aspergillus infection was 1103 pg/mL; the mean value of Fusarium infection was 1652 pg/mL.

    For patients with oral cavity and other organs colonization of fungi, it generally does not exceed 20 pg/mL.

    Many tests have false positives and false negatives, and the G test and GM test are no exception.

    Common situations of false positives in serum G test ①Intravenous preparations contain glucans, such as blood products (such as human albumin, human hemoglobulin, clotting factors, etc.
    ), certain antibiotics (such as polymyxin, erta) Penon, cefotaxime, cefepime, sulfonamides, etc.
    ), medicines made from mushrooms and plants (such as astragalus polysaccharide, lentinan, shuanghuanglian, Shengmai injection, etc.
    ) and injected fat emulsion.

    ②Medical materials contain glucan, such as gauze, cellulose membrane used in hemodialysis, etc.

    ③ Samples that cause abnormal test results (high hemolysis, high fat, high bilirubin, lipopolysaccharide, etc.
    ).

    ④Patients with streptococcal sepsis.

    ⑤ High immunoglobulin (patients with multiple myeloma).

    ⑥ Samples that cause abnormal test results (high hemolysis, high bilirubin, high fat, lipopolysaccharide, etc.
    ).

    ⑦The specimen is contaminated.

    ⑧The effect of β-glucan-like active substances unknown to patients with postoperative and liver cirrhosis.

    ⑨Polysaccharide anticancer drugs.

    ⑩ Mucosal damage caused by radiotherapy and chemotherapy may cause dextran in food or colonized Candida to enter the blood through the gastrointestinal tract, etc.
    , which may also cause false positives.

    False negative in the serum G test ①Insensitive bacteria: Some fungi, such as Zygomycetes (Mucor, Rhizopus, etc.
    ), do not produce (1-3)-β-D glucan on the cell wall; Cryptococcus cell walls have pods The membrane encapsulation prevents the release of D-glucan, so the G test for these fungi is false negative.

    Therefore, if the patient has the corresponding clinical symptoms and other evidences for the possibility of fungal infection, but the G test is negative, care should be taken to consider the possibility of these two fungal infections.

    ② Focal fungal infection: such as focal aspergillosis, (1-3)-β-D glucan is rarely released into the blood.

    ③The use of antifungal drugs.

    What is a GM test? The substance tested by the GM test is the galactomannan antigen (GM).

    Galactomannan is a type of polysaccharide component widely found in the cell walls of Aspergillus and Penicillium.
    When the hyphae grows, galactomannan is released from the top of the weak hyphae.
    It is the earliest released antigen.
    It can be used by enzyme-linked immunoassay.
    Adsorption test method (ELISA) for detection.

    The amount of GM released is directly proportional to the amount of bacteria.
    Therefore, the GM test can not only reflect the degree of infection, but also continuously detect the dynamic changes of its value as an evaluation and monitoring of the efficacy.

    Aspergillus infection is mainly concentrated in the lungs.
    The key to distinguishing whether Aspergillus is colonizing or invasive growth in the lungs is whether it synthesizes GM.
    If the sputum or alveolar lavage fluid specimen is cultured to Aspergillus and the GM test result is positive , It can be diagnosed as Aspergillus invasive infection, especially for neutrophil-deficient host invasive Aspergillus infection with high sensitivity and specificity, which has important auxiliary diagnostic value.

    Therefore, the GM test is clinically mainly used for the early diagnosis of invasive Aspergillus infection.
    For patients with deep Aspergillus infection, the increase in serum GM test can be about 7 days earlier than the imaging diagnosis and 5-8 days before the appearance of clinical symptoms.
    Serum, cerebrospinal fluid, alveolar or bronchial lavage fluid are tested, which can often advance the diagnosis.

    At present, domestic and foreign standards for the positive threshold of serum GM test are still not unified.

    The commonly used judgment standard in Europe is 0.
    7~1.
    0 ug/L, the American FAD recommends a sensitivity threshold of 0.
    5 ug/L, and the domestic standard is 0.
    5 ug/L.

    The sensitivity and specificity of the GM test can be affected by many factors.

    False positives in the GM test ① Use semi-synthetic penicillin (especially piperacillin/tazobactam), immunoglobulin, blood products, and high-dose adrenal cortex hormones.

    ②Patients with severe mucositis caused by chemotherapy.

    ③ Newborns and children (Bifidobacterium colonization, edible products).

    ④ Hemodialysis.

    ⑤ Autoimmune hepatitis, etc.

    ⑥ Eat high-protein foods such as milk and contaminated rice that may contain GM.

    False negative in GM test ①Aspergillus GM (including mannan) released into the blood circulation does not persist but will be removed quickly; ②Previous use of antifungal drugs; ③The condition is not serious; ④Non-granulocytosis Of patients.

    Although the G test and the GM test are very good test items for the diagnosis of invasive fungal diseases, whether it is the G test or the GM test, only one negative result cannot completely rule out invasive fungal disease, and a simple positive is not the basis for the diagnosis.

    At present, it is recommended that at least two consecutive positive test results within a week are considered as meaningful test results (among which, the guidelines for invasive mycosis treat two consecutive GM test positives as the standard for microbial infection), and attention should be paid to combining clinical symptoms, medical history and characteristics.
    Comprehensive analysis of other inspections.

    The G test is an index for the clinical diagnosis of invasive fungal infections, especially when diagnosing candidaemia, but the G test and PCR test results cannot be used as an index for evaluating the efficacy of Candida infection.

    The GM test can be used as an indicator for diagnosis and judgment of efficacy, especially for invasive Aspergillus infections in neutrophil-deficient hosts.

    The G test and the GM test cannot replace each other, but the combined application of the two can improve the ability to diagnose invasive fungal diseases.

    It can also be seen from the above table: G test is positive, GM test may be negative, such as Candida, Fusarium infection; G test is negative, GM test may be positive, such as Cryptococcus infection.

    References: [1] China Medical Education Association, Professional Committee of Infectious Diseases.
    Expert consensus on interpretation of clinical significance of infection-related biomarkers.
    Chinese Journal of Tuberculosis and Respiratory.
    2017,40(4):243-257.
    [2] Invasiveness in China Fungal Infection Working Group.
    Diagnostic criteria and principles of treatment for invasive fungal diseases in patients with hematological diseases/malignant tumors (fifth revised edition).
    Chinese Journal of Internal Medicine.
    2017,56(6):453-458.
    [3] Chinese Medical Association Branch of Organ Transplantation, Branch of Organ Transplantation Physician of Chinese Medical Doctor Association.
    Guidelines for the clinical diagnosis and treatment of invasive mycosis in solid organ transplant recipients in China (2016 edition).
    Chinese Journal of Organ Transplantation.
    2016, 37(5): 300-305.
    [4] Infectious Science Group of Respiratory Branch of Chinese Medical Association.
    Expert consensus on diagnosis and treatment of pulmonary mycosis.
    Chinese Journal of Tuberculosis and Respiration.
    2007, 30 (11):821-834.
    [5] China Working Group on Invasive Pulmonary Fungal Infection.
    Diagnostic criteria and treatment principles of invasive pulmonary fungal infection (draft)[J].
    Chinese Journal of Practical Internal Medicine, 2006, 26(21): 1748-1751.
    [6] China Working Group on Invasive Pulmonary Fungal Infection.
    Diagnostic criteria and treatment principles for invasive fungal infections in patients with hematological diseases/malignant tumors (third revision) [J].
    Chinese Journal of Internal Medicine, 2010, 49(5): 451-456.
    [7] Yu Shuxian, Cui Xuefan, etc.
    Meta-analysis of the diagnostic value of G test and GM test for invasive mycosis.
    Chinese Journal of Lung Diseases, 2016, 9 (2): 164-170.
    [8] Ren Lina, Zhou Yuechang, etc.
    Serum galactomannan antigen detection in the diagnosis and treatment monitoring of invasive pulmonary aspergillosis.
    Electronic Journal of Clinical Medicine Literature.
    2015 (22) :4534-4535.
    [9] Sun Qixin et al.
    Application value of serum galactomannan in the diagnosis of hematological malignancies complicated with invasive fungal infection.
    Chinese Journal of Infection and Chemotherapy.
    2009.
    9(2):140-142.
    [10] Leng Yun Li Lihong.
    The clinical significance of serum galactomannan detection in the diagnosis of invasive fungal infections in patients with hematological malignancies, Leukemia and Lymphoma.
    2010, 19 (7): 427-431.
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