Lepromin反応に関する研究

1. Rosalind S. Abernathy, MD* 1. 2. *Associate Professor of Pediatrics, University of Arkansas for Medical Sciences; Pediatric Consultant, Tuberculosis, Arkansas State Department of Health, Little Rock, AR. 1. The majority of tuberculosis cases in children are from high-risk populations, that is, African-Americans, Hispanics, immigrants, and those living in poverty and in the inner cities. 2. The only acceptable tuberculin skin test is the intradermal Mantoux test with purified protein derivative (PPD), and three levels of positivity now are accepted. Children exposed to active disease who have findings suggestive of tuberculosis or who have human immunodeficiency virus (HIV) infection are positive at 5 to 9 mm; other high-risk groups are positive at 10 mm. 3. Diagnosis of childhood tuberculosis depends on a high index of suspicion coupled with suggestive epidemiologic data, tuberculin skin test results, and chest radiographic findings. Cultures are not routinely positive, and results are available only after treatment must be started. 4. Treatment is a uniform 6-month course of isoniazid, rifampin, and pyrazinamide for 2 months followed by 4 months of isoniazid and rifampin daily or twice weekly. Additional drugs are needed in cases of drug resistance. 5. Chemoprophylaxis for all children who have a positive tuberculin reaction will prevent future disease. Despite the availability of effective antituberculosis drugs since 1952, tuberculosis remains an important cause of morbidity, mortality, and health care cost in the United States. Tuberculosis case rates declined at a rate of 6% annually for more than 20 years until 1985 when they leveled off (Fig. 1⇓). Factors responsible for this include human immunodeficiency virus (HIV) infection; immigration of individuals from countries where tuberculosis rates are 10 to 30 times that of the United States; transmission of disease in hospitals, homeless shelters, and prisons; and poverty, overcrowded living, and poor access to medical care. While all this was occurring, funds for tuberculosis control by public health programs declined. Fortunately, the number of cases reported annually has decreased by 8.7% in the past 2 years, probably …

To clarify whether the size of tuberculin reaction could be used as an useful index of the severity of tuberculosis, we analyzed the sizes of tuberculin reaction (TR) of 60 children below 4 years of age with active tuberculosis at the time of diagnosis. Of 60 patients, 53 (88.9%) had positive reactions to tuberculin. The mean size of TR of 60 patients was 24.0 +/- 13.9 mm and maximum size was 60 mm. Seven patients who had no reaction to the tuberculin skin test consisted of three primary complex and four serious tuberculosis (two miliary tuberculosis and two tuberculous meningitis). The patients without BCG vaccination showed significantly smaller TR than the patients with BCG vaccination (p < 0.05). The patients less than 1 year of age showed significantly smaller TR than the patients of 4 years of age (p < 0.05). The patients with serious tuberculosis showed significantly smaller TR than the patients with primary complex (p < 0.05). Of patients with primary complex, there were no difference of the size of TR between the patients with pulmonary tuberculosis (III) and hilar lymphadenopathy (H). Together with, it did not necessarily mean that negative TR showed no infection with tuberculosis and the sizes of TR depended on the severity of tuberculosis in infantis and young children.

Some recent studies have suggested that bacillus Calmette-Guérin (BCG) vaccination or mycobacterial infection early in life is inversely related to asthma. We wondered if an increase in tuberculin reactivity was inversely related to commonly used indices of asthma in a population of young adults who were BCG vaccinated at age 14. Men and women aged 20-44 years, randomly selected from the general population, were tuberculin tested with the epinephrine-Pirquet method with Norwegian-produced synthetic medium tuberculin (n = 588). In addition they were interviewed using eight questions on asthma symptoms and medication. Lung function and bronchial responsiveness were also tested. Altogether 95% of those studied had been BCG vaccinated at age 14 (n = 558). In the 386 subjects with complete examinations, there was no relationship between a positive tuberculin reaction (> or = 4 mm) and asthma symptoms or use of asthma medication. Furthermore we did not observe any relationship between a positive tuberculin reaction and the level of forced expiratory volume (FEV1) or a positive bronchial responsiveness test, assessed as the percent of predicted of FEV1 and PD20 < 2 mg methacholine, respectively. In multiple logistic regression analyses neither respiratory symptoms, level of FEV1, nor bronchial hyperresponsiveness were related to tuberculin reactivity after adjustment for age, gender and smoking habits. In this young adult population who were BCG vaccinated at the age of 14 no significant relationship existed between tuberculin reactivity and asthmatic symptoms, level of FEV1 or bronchial hyperresponsiveness. Our data does not support the hypothesis that BCG immunization is beneficial in reducing asthmatic symptoms and disease in young adults.

Tuberculin reactions in patients with immunocompromised conditions have been reported to be attenuated compared with healthy controls. In the case of rheumatoid arthritis (RA), several studies have reported conflicting results. We performed this study to evaluate the tuberculin reaction in patients with RA in a region with intermediate burden of tuberculosis. Eighty-one RA patients and 104 age- and sex-matched controls who underwent tuberculin skin test (TST) at Severance Hospital in Seoul, South Korea were reviewed. TST was carried out using the Mantoux method. Indurations larger than 10 mm were considered positive. Information about risk factors for latent tuberculosis infection was acquired. The mean age of the patients with RA was 48 ± 14 years, and the median disease duration was 9 (1-203) months. The mean DAS28 was 5.22 ± 0.13. The control group consisted of healthy living donors for liver transplantation and the patients with diseases not related with immunosuppression. BCG vaccination, close contact history with active tuberculosis, and history of pulmonary tuberculosis were not different between the two groups. The positive rate of TST (34.6% vs. 38.5%) and the median skin induration size (5 mm vs. 6 mm) of the two groups were similar. Medications and DAS28 were not associated with the TST result. The tuberculin reaction of patients with RA is not attenuated compared with that of controls in South Korea.

Experimental and epidemiologic basis for the interpretation of tuberculin sensitivity

Inbred strain 2 guinea pigs were vaccinated with Mycobacterium bovis BCG or were left unvaccinated and challenged 6 weeks later by the respiratory route with virulent Mycobacterium tuberculosis. By using a double rosette assay with isotype-specific antibody-coated ox and uncoated rabbit erythrocytes, the proportions of T lymphocytes bearing Fc receptors for immunoglobulin G (IgG) (T gamma cells) or IgM (T mu cells) were quantified in tissues taken from animals that were killed within 4 weeks postchallenge. Tuberculin reactivity in vivo and in vitro and antimycobacterial resistance were also measured. BCG vaccination protected the guinea pigs and resulted in significantly enhanced proportions of T mu cells in the blood during the first 3 weeks and in the spleen during weeks 2 and 3 postchallenge. Levels of T gamma cells declined in all tissues during the first 3 weeks of infection and were unaffected by prior vaccination with BCG. Increased proportions of T mu cells in the blood were accompanied by dramatic tuberculin skin reactions and purified protein derivative-induced lymphoproliferation in BCG-vaccinated guinea pigs during the first 2 weeks following virulent pulmonary challenge. Peak levels of T mu cells in the spleens of vaccinated animals at 2 weeks coincided with the first appearance of virulent mycobacteria in that organ. BCG vaccination appears to influence immunoregulatory events in pulmonary tuberculosis through effects on the distribution of IgM Fc receptor-bearing (T mu cell) T lymphocytes.

Various strategies have been implemented to prevent tuberculosis. Vaccination with Bacille Calmette Guerin (BCG) vaccine is still used around the world. Generally, most people in have gained BCG vaccine as an infant, but the effectiveness of these vaccines do not survive to adulthood. Therefore, the necessary replacement BCG vaccine more effective to eliminate tuberculosis. Mycobacterium tuberculosis is an intracellular pathogen and it was inside the macrophage, which is considered to be the most important component of the immune system. M. tuberculosis has two sets of genes are highly polymorphic referred to as PE and PPE families. These unique families of proteins account for about 10% of the mycobacterial genome and have attracted great interest from a variety of different studies around the world. One member of the as a vaccine candidate is Rv 2430c. It is known that the sera of all patients infected with TB showed strong antibody responses against Rv 2430c compared to healthy individuals. The existence of these antibodies indicates that this protein is found in vivo during infection and is a native immunogenic molecule. The purpose of this study was to clone the Open Reading Frame (ORF) Rv 2430c M. tuberculosis Indonesian isolates to host cells Esherichia coli JM 109. The method used is by isolating -chromosomal DNA from clinical isolates from Indonesia, amplifying the ORF Rv 2430c with , ligating into cloning vectors pGEM-T and transform to E.coli JM 109. Characterization of clones do with migration analysis, restriction analysis and . The results obtained are recombinant clones that carry insertion was Rv 2430cKeywords: Mycobacterium tuberculosis, Rv 2430c, ORF, , JM 109.

BackgroundT cell infiltration around dying motor neurons is a hallmark of amyotrophic lateral sclerosis (ALS). It is not known if this immune response represents a cause or a consequence of the disease. We aimed to establish whether individual variation in regulation of a T cell driven immune response is associated with long-term ALS risk. MethodsTuberculin skin test (TST) following BCG vaccination represents a standardized measure of a secondary T cell driven immune response. During a Norwegian tuberculosis screening program (1963–1975) Norwegian citizens born from 1910 to 1955 underwent TST. In those previously BCG vaccinated (median 7 years prior to TST), we related tuberculin skin tests to later ALS disease identified through validated Norwegian health registers. We fitted Cox proportional hazard models to investigate the association between tuberculin reactivity and ALS risk. ResultsAmong 324,629 participants (52 % women) with median age 22 (IQR 10) years at tuberculosis screening, 496 (50 % women) later developed ALS. Hazard ratio for ALS was 0.74 (95% CI 0.57–0.95) for those who remained TST negative compared to those who mounted a positive TST. The association was strongest when time between BCG immunization and TST was short. The associations observed persisted for more than four decades after TST measurement. ConclusionsNegative TST responses after BCG vaccination is associated with decreased long-term risk for ALS development, supporting a primary role for adaptive immunity in ALS development.

Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000–2002

The lepromin and tuberculin test have been examined in 1, 3, 6 and 12 months after the BCG-vaccination, in leprosy patients vaccinated BCG, who were not positive reactors on both reactions :The results were as follows ;The positive conversion rate were higher in the tuberculin reaction, but lower in the lepromin reaction, on either 111 cases examined by Mitsuda's antigen, or 141 cases examined by Fernandez's antigen. Therefore, the results in leprosy patients were different from that in healthy.

Strain-2 guinea pigs received two separate intradermal immunizations. The first was a mixture of living BCG (Phipps strain of bacille Calmette-Guerin) and syngeneic line-10 hepatoma cells. The second, administered after 6 weeks or more, was keyhole limpet hemocyanin (KLH) in saline. One week after the second injection, the animals were skin tested at separate sites with tumor cells, purified protein derivative of tuberculin (PPD) and KLH. Delayed cutaneous hypersensitivity (DCH) reactions were evident by 24 h. At this time the reaction sites were processed by histological methods that preserved basophil morphology and staining qualities. Three distinctive infiltrates were elicited by the different antigens. In addition to the mononuclear cell infiltrate common to all three reactions, the KLH site had a high concentration of basophils and few neutrophils, characteristic of cutaneous basophilic hypersensitivity (CBH); the PPD site had practically no basophils but many neutrophils; and the tumor cell reaction was predominantly mononuclear, with small numbers of basophils and virtually no neutrophils. Simultaneous generation of different DCH reactions in the same animal and quantitative description of the cellular infiltrate provided a basis for DCH classifications, with KLH CBH and tuberculin reactions as standards for comparison. Since challenge with three antigens at separate sites in the same animal generated DCH reactions with widely differing patterns of cellular infiltration, the reason for the differences must occur at the local sites or, if circulating, must be antigen-specific.

<h3>Objectives.</h3> —To determine the incidence of active tuberculosis in human immunodeficiency virus (HIV)—seropositive and HIV-seronegative drug injectors with cutaneous anergy and to examine the effectiveness of isoniazid chemoprophylaxis in preventing tuberculosis among drug injectors with positive tuberculin test results. <h3>Design and Setting.</h3> —Prospective observational study linked to an ongoing study of HIV infection within a New York City (NY) methadone program; subjects also underwent routine intradermal tuberculin testing and multiple-antigen delayed-type hypersensitivity skin testing. The 31-month study period ended December 31, 1990. <h3>Methods.</h3> —Anergic subjects and tuberculin reactors who were HIV seropositive were compared by HIV disease status and CD4⁺T-lymphocyte levels. Tuberculosis incidence was calculated for anergics (none treated with isoniazid) and for treated and untreated tuberculin reactors, by HIV serological status. <h3>Results.</h3> —Among those seropositive for HIV, anergic subjects had more advanced HIV disease and fewer CD4⁺cells (median 0.33 vs 0.56 ×10⁹/L,<i>P</i>&lt;.01) compared with tuberculin reactors, although neither clinical status nor CD4⁺cell counts consistently predicted anergy. Five (7.6%) of 68 anergic subjects who were HIV seropositive and none of 52 anergic subjects who were HIV seronegative (n=18) or of unknown (n=34) HIV serological status developed active tuberculosis during the study period (<i>P</i>&lt;.05). The tuberculosis incidence rate among anergic subjects who were HIV seropositive was 6.6 cases per 100 person-years (95% confidence interval [CI], 2.1 to 15.3). Of 25 HIV-seropositive tuberculin reactors who did not receive or complete 12 months of isoniazid prophylaxis, tuberculosis incidence was 9.7 cases per 100 person-years (95% CI, 2.6 to 24.7;<i>P</i>=0.56, compared with the rate among anergic HIV seropositives); there were no cases of tuberculosis in 53.4 person-years of follow-up for 27 HIV-seropositive tuberculin reactors who received 12 months of prophylaxis (rate difference between treated and untreated groups, 9.7 cases per 100 person-years, 95% CI, 1.3 to 18.0). <h3>Conclusion.</h3> —Drug injectors with cutaneous anergy who are seropositive for HIV are at high risk of active tuberculosis, similar to that among untreated HIV-seropositive tuberculin reactors. A decreased incidence of active tuberculosis was seen in HIV-seropositive tuberculin reactors receiving 12 months of isoniazid chemoprophylaxis, compared with untreated or partially treated subjects. These results support the routine use of delayed-type hypersensitivity testing to accompany tuberculin testing for drug injectors with known or suspected HIV infection, and consideration of isoniazid prophylaxis for anergic as well as tuberculin-reactive subjects who are HIV seropositive, in populations with a high prevalence of coexisting HIV and<i>Mycobacterium tuberculosis infection</i>. (<i>JAMA</i>. 1992;268:504-509)

Tuberculosis (TB) is still a public health problem worldwide. Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis germ and is one of the 10 leading causes of death worldwide. The methods section should be able to explain the research methods used, including how the procedures were carried out. Tools, materials, media or research instruments must be well described. There is no gold standard for ILTB diagnosis. Tuberculin Skin Test (TST) and Immunoglobulin Release Assay (IGRA) are the WHO recommended ILTB tests. The purpose of TPT is to prevent the occurrence of TB disease so as to reduce the burden of TB. One of the efforts in preventing tuberculosis disease in children is the Bacille Calmette Guerin (BCG) vaccine. BCG vaccine is very effective in preventing tuberculosis in children, where children who do not get BCG vaccine have a 6.87 times higher risk of developing tuberculosis compared to children who get BCG vaccine. The effectiveness of the BCG vaccine in preventing tuberculosis is 85%.

BackgroundBacillus calmette guerin (BCG) immunization has been associated with a reduction in Mycobacterium tuberculosis (MTB) infection. BCG immunization has been shown to enhance innate immunity. This effect of BCG can be explained by an enhancing effect on innate immunity.ObjectiveThis study aimed to test the following hypotheses: (1) BCG immunization can prevent infection with MTB, (2) prevention of infection occurs via stimulation of NOD2 (nucleotide oligomerization domain) and toll-like receptors 2 (TLR2), and (3) the effect of BCG immunization on prevention of infection with MTB can be enhanced by giving stimulators of NOD2 and TLR2.MethodsTo detect the influence of immunization on infection rates, the ultralow dose (ULD) infection model is used. The infection rate of mice vaccinated with BCG and exposed after 6 weeks to ULD of MTB and unvaccinated mice are compared via cultures of lung homogenates and interferon (IFN) gamma release assay. If a reduced infection rate by BCG immunization is confirmed, the experiment is repeated by giving BCG combined simultaneously or in time sequence with the enhancers of innate immunity murabutide or beta-glycan. The influence of murabutide or beta-glycan alone on infection rates is investigated. To quantify the contribution of innate immunity levels of tumor necrosis factor, IFN gamma expression, histone H3 K4me3 trimethylation, and concentrations of monocytes with features of activation of innate immunity as defined by the Ly6Chigh as well as CD11b positive phenotype in immunized versus unimmunized infected and uninfected mice in the various immunization protocols is compared. The experiments will be repeated with prior application of the inhibitors of epigenetic programming of innate immunity histone methyltransferase inhibitor 5’-deoxy-5’-methylthio-adenosine and histone acetyl transferase inhibitor epigallocatechin-3-gallate. The influence of BCG on innate immunity is further corroborated by a prospective observational study in human infants.ResultsInvestigations of derivatives of muramyl dipeptide (MDP) to enhance early immunity in the C57BL/6 mouse strain (mice aged 7 weeks) by another group used 300 micrograms per mouse of oil-associated 6-0-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) 50/50 mixed with Freund’s incomplete adjuvant. Comparison of colony-forming unit (CFU) count in the lungs 3 weeks after aerosol challenge with Mycobacterium bovis of groups (n=5) between groups receiving mycol-MDP in oil emulsion (see above) versus controls (n=5) showed a significantly lower CFU count of 94.5 x106 (SD 22.0) in cases versus controls with 204.0 X 106 (SD 77.6). It is important to note that after elimination of T-cells in this model, a reduction of CFU in lungs of mice treated with mycol-MDP persisted albeit without statistical significance, which was possibly related to the small number of animals used.ConclusionsDemonstration of a reduction of MTB infection by enhancement of innate immunity could show a new approach to improving vaccine efficacy against this pathogen.International Registered Report Identifier (IRRID)PRR1-10.2196/13045

Tuberculosis in Japan has increased recently. Cervical tuberculous lymphadenitis is an extrapulmonary tuberculosis. We report a case of a 29-year-old woman who was 28 weeks pregnant, with cervical tuberculous lymphadenitis, which was diagnosed by tuberculin reaction and polymerase chain reaction test (PCR test) after delivery. The patient was treated with rifampicin (RFP), isoniazid (INH) and levofloxacin (LVFX) as antituberculous chemotherapy for a year, and was treated with INH and LVFX for the next half-year. The baby was treated with bacillus Calmette-Guerin vaccine (BCG vaccine) instead of antituberculous chemotherapy. The patient and the baby were making satisfactory progress. Although antituberculous chemotherapy should be done immediately when a pregnant woman is diagnosed with pulmonary tuberculosis, it should not be done immediately when the pregnant woman has cervical tuberculous lymphadenitis.