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Purpose: To predict the efficacy of intravesical BCG therapy in patients with nonmuscle-invasive bladder tumors (NIBC) by using components of the cellular immune response such as the tuberculin skin test (PPD) and natural killer (NK) activity measurement., Methods: Ninety-nine patients who were started on intravesical BCG therapy for NIBC were evaluated prospectively. Patients who were included in the intermediate, high, and very high-risk groups according to the EAU NMIBC Scoring System and who had never received intravesical BCG therapy previously were included. The clinical and demographic characteristics of the patients (age, gender, EAU NMBIC risk group, EORTC progression and recurrence scores, CUETO progression and recurrence scores, presence and types of comorbidity) were recorded. NK activity was measured and the PPD test was applied 3 days before the start of intravesical BCG therapy. The results of PPD were measured in millimeters 72 h after the test., Results: PPD values measured before BCG treatment, as an independent variable, were found to be significantly lower in patients with recurrence. A significant correlation was detected between NK activity results obtained before BCG treatment and recurrence after treatment, when the cutoff was 200-500 pg/dl. There was no significant relationship between the time to recurrence and PPD and NKA measurements., Conclusion: We conclude that the results of PPD test and NK activity measurement performed before starting intravesical BCG therapy in NIBC may be a marker that can be used to predict the risk of recurrence under treatment., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Palmoplantar and periungual warts tend to be recalcitrant. Intralesional immunotherapy can provide high efficacy with additional benefit to distant warts. However, evidence on comparative effects between intralesional immunotherapy with measles, mumps, rubella vaccine (MMR) and tuberculin purified protein derivative (PPD) and roles of dermoscopy in predicting treatment outcomes in palmoplantar/periungual warts is limited., Objectives: The study aimed to compare efficacy and safety of intralesional MMR and PPD injections in treatment of palmoplantar/periungual warts and explore associations between dermoscopic findings and treatment outcomes., Methods: We conducted a double-blind randomized controlled trial involving 40 patients with palmoplantar/periungual warts who were equally assigned to receive MMR or PPD. Intralesional injection was done every 2 weeks until clearance or maximum of 5 treatments., Results: Complete resolution was higher in MMR than PPD group (90.0% vs. 80.0% in index lesion and 81.3% vs. 54.6% in distant lesions, respectively), although the differences were statistically nonsignificant. Dermoscopic findings were not significantly associated with complete resolution. Local swelling, i.e., the most common adverse event, occurred more frequently in PPD (40.0%) than MMR group (10.0%)., Conclusion: This study suggests that intralesional immunotherapy with either MMR or PPD is efficacious in palmoplantar/periungual warts, with MMR showing a trend toward higher clearance and lower adverse events., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections., Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective., What Is Known: • The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain. • Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease., What Is New: • A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone. • Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases., (© 2022. The Author(s).)

Approximately 10 million people worldwide were infected with tuberculosis (TB) in 2019, resulting in 1.4 million deaths. In the United States that same year, there were nearly 9,000 reported cases of TB disease and up to 13 million people were living with latent TB infection (LTBI), which is an asymptomatic, noncommunicable infection caused by Mycobacterium tuberculosis. Without treatment, LTBI will progress to active TB disease in approximately 5% to 10% of affected people. Individuals with symptoms of TB disease warrant testing. The U.S. Preventive Services Task Force recommends testing individuals at increased risk of LTBI with an interferon-gamma release assay or tuberculin skin testing. Because the incidence of LTBI in health care professionals is similar to that of the general population, periodic retesting is not recommended. After a positive test result, chest radiography should be performed and, in patients with suspected pulmonary TB disease, sputum collected for diagnosis. Both suspected and confirmed cases of LTBI and TB disease must be reported to local or state health departments. Preferred treatment regimens for LTBI include isoniazid in combination with rifapentine or rifampin, or rifampin alone for a duration of three and four months, respectively. Treatment of drug-susceptible TB disease includes an eight-week intensive phase with four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol), followed by a continuation phase lasting 18 weeks or more, with two drugs based on susceptibility testing results. Consultation with a TB expert is necessary if there is suspicion or confirmation of drug-resistant TB.

Purpose: To report a case of bilateral ocular tuberculosis (OTB) in a child with negative Tuberculin skin test (TST)., Methods: Case report., Observations: A 12-year-old malnourished systemically asymptomatic boy presented with sudden profound loss of vision in both eyes. Dense vitritis precluded fundus visualization in right eye (RE). In left eye, fundus findings of extensive vasculitis associated with multifocal retinochoroiditis were suggestive of OTB. However, negative TST, normal chest X-ray, and gram negative bacteriuria led to confusion between endogenous endophthalmitis and OTB. Based on strong clinical suspicion and high-resolution chest tomography (HRCT) of thorax which was suggestive of TB-pneumonitis, a diagnosis of presumed OTB was made. A good response to anti-tubercular-treatment and corticosteroids, with resolution of retinochoroiditis lesions, vasculitis, and vitritis, further supported our diagnosis., Conclusions: This case highlights the importance of keeping a high index of suspicion for TB-associated uveitis in children, based on clinical findings.

Objectives: Anergy reduces the sensitivity of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis infection in people living with HIV. Antiretroviral treatment (ART) can reverse TST anergy, but data is scarce., Methods: To estimate TST conversion rates and factors associated with TST conversion, TST was placed at ART initiation, and 6 and 12 months thereafter (if TST negative at prior assessment)., Results: Of 328 ART-eligible participants, 70% (231/328) had a valid TST result of whom 78% (180/231) were TST negative. At 6-month follow-up, 22% (24/109, 95% confidence interval [CI] 15%, 31%) of participants on ART, without incident tuberculosis (TB), and with a valid TST result converted to a positive TST. Of these 109 individuals, those with baseline CD4+ cell count >250 cells/μl were more likely to TST convert compared to those with baseline CD4+ cell count ≤250 cells/μl (odds ratio [OR] 3.54, 95% CI 1.29, 11.47). At 12 months post-ART initiation, an additional 12% (9/78, 95% CI 6, 20) of participants on ART, without incident TB and with a valid TST result experienced TST conversion. After 1 year on ART, TST conversion rate was 38 per 100 person-years (95% CI 26, 52), and lower in individuals with baseline CD4+ cell count ≤250 cells/μl (23/100 person-years, 95% CI 11, 41) compared to those with baseline CD4+ cell count >250 cells/μl (50/100 person-years, 95% CI 32, 73)., Conclusions: TST conversion rate in the first year of ART is high, especially among people with CD4+ cell count >250 cells/μl. A TST-based eligibility strategy at ART initiation may underestimate eligibility for preventive therapy for tuberculosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Warts are common viral infection of the skin. Treating warts are still an ongoing challenge and no general agreement is reached, on the best treatment, despite different therapeutic approaches. Intralesional (IL) immunotherapy has recently been shown to be effective in treating various wart forms., Aims: To assess the efficacy and safety of IL tuberculin, IL MMR vaccine, and intradermal (ID) BCG vaccination in treating viral warts., Patients and Methods: Sixty patients with single or multiple warts were divided equally into three groups. Group A received IL MMR vaccine, and group B received IL tuberculin every 3 weeks (maximum 3 times). Group C received ID BCG vaccination in the arm with one month interval (maximum 3 times). Recurrence was followed up for 6 months., Results: In group A, complete response occurred in 30%, partial response in 5%, and no response in 65%. In group B, complete response occurred in 45%, partial response in 20%, minimal response in 10% and no response in 25%. In group C, complete response occurred in 70%, partial response in 5%, minimal response in 5%, and no response in 20%. No recurrence was observed in group A and B but occurred in one patient in group C with the same lesion., Conclusions: Immunotherapy by IL tuberculin and ID BCG vaccination are safe, effective, and inexpensive techniques in treating all types of warts even if recalcitrant or multiple but immunotherapy by IL MMR vaccine has shown less effectiveness and less safety technique., (© 2021 Wiley Periodicals LLC.)

Background: Several destructive and immunotherapeutic methods are used in treatment of plantar warts, but an effective method with no or reduced recurrence has not been found till now., Objectives: To evaluate the efficacy and safety of intralesional (IL) vitamin D 3 (Vit.D 3 ) injection vs IL tuberculin purified protein derivative (PPD) injection in the treatment of plantar warts., Methods: Sixty patients with plantar warts were randomized into 3 equal groups: group I treated using IL tuberculin PPD every 2 weeks, group II treated using IL Vit.D 3 every 4 weeks, and group III treated with IL saline every 2 weeks till complete clearance or for a maximum of 3 sessions. The follow-up period was 6 months., Results: There was a statistically significant improvement in therapeutic groups than control with more significant improvement in group II than I. Regarding number of sessions required for complete response, there was a positive significant correlation in both groups, but more significant in group I. There was a negative correlation between the number of lesions and the response to treatment in both groups. Group II showed significantly better response to treatment in male patients. Both modalities were well tolerated, with no remarkable side effects and no recurrence in cured patients of both groups., Conclusions: Both IL PPD and Vit.D 3 injection are safe and effective for treatment of plantar warts even recalcitrant or multiple, with no postprocedural downtime, better results, and patient satisfaction. IL Vit.D 3 injection has a superior advantage than PPD., (© 2020 Wiley Periodicals LLC.)

Background: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations., Aims: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts., Methods: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence., Results: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann-Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann-Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann-Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study., Limitation: Unicentric trial., Conclusion: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts., Competing Interests: None

Background: Childhood Tuberculosis remains one of the major public health concerns in developing countries like Pakistan and is responsible for high rates of morbidity and mortality in children. Although tuberculin skin test is very commonly used by physicians all over the world, its interpretation always remains difficult and challenging. The objective of this study was to determine the frequency of positive tuberculin skin test in vaccinated and unvaccinated children suffering from tuberculosis., Methods: This Cross-sectional study was conducted in the department of Paediatric Ayub Teaching Hospital, Abbottabad from 1st February 2015 to 30th April 2016. A total of 150 patients were observed in this study. Children of either gender who were aged 1-15 years admitted in ward with tuberculosis were included in the study by using nonprobability convenient sampling technique. We injected 0.1 ml (10 units) of tuberculin purified protein derivative (PPD) into the anterior surface of the forearm and induration was read at 72 hours after administration. Data was entered and analysed using SPSS version 10., Results: Out of 150 children, 84 (56%) were males and 66 (44%) were females. The mean age was 7.8±3.84 years. Of these 75 (50%) were vaccinated and 75 (50%) were unvaccinated. In vaccinated Group 5.3% children had positive tuberculin skin test while in unvaccinated Group 2.7% children had positive tuberculin skin test and this difference was found statistically insignificant (pvalue= 0.40). Pulmonary TB was the diagnosis in 67 (44.7%), TBM in 65 (43.3%), abdominal TB in 7 (4.7%), disseminated TB in 4 (2.7%) and military TB in 7 (4.7%) patients., Conclusions: The positivity of tuberculin skin test in vaccinated and unvaccinated children suffering from tuberculosis was found to be insignificant in our study. We conclude that Tuberculin Skin Test should not be used as a sole diagnostic tool for diagnosing the disease in children of our region..

During the 19th and early 20th century the achievements in the study of ocular tuberculosis were of great significance. The development of pathological anatomy in those years helped physicians to understand the histological image and the pathophysiology of the disease and allowed the scientists to detect the specific anatomical structures of the eye, where the disease could be present. The physicians of those years tried to describe the clinical image of the disease and to give value information, in order to facilitate the diagnosis. Despite major efforts made in the field of clinical approach to ocular tuberculosis, the treatment of the disease in those years was not very effective. Nevertheless, the physicians of the time used every new pharmacological or not pharmacological treatment to fight the disease.

Background: Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of 'in situ' tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC., Methods: Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety., Results: Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year., Conclusions: Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted.

TB is typically caused by Mycobacterium tuberculosis, a symbiotic bacterium present in one-third of the world's population. There any many factors triggering overt clinical disease in a small proportion of humans. In our view the major role in the process is played by the host's immune response, especially self-directed, destructive inflammation. Conventional chemotherapy produces bactericidal or bacteriostatic effects, but immunopathological changes can only be corrected by immunotherapy. Various attempts have been made to identify the optimal immune intervention. Some have shown promising effects, but many have failed. It is commonly believed that the field started in 1890: the year Robert Koch announced his tuberculin therapy. In the Pên Ts'ao Kang Mu, classical Chinese materia medica, published during Ming dynasty, Li Shi Chen (1518-1593) recommended, as a remedy for hemoptysis, to collect from the sputum "…blood lumps, roast them till they are black, and take then them as a powder". In retrospect, this is perhaps the earliest recorded reference relating to immunotherapy of TB with heat-killed mycobacteria. Modern science is obviously geared toward more palatable approach, but without hindsight from often disdained empirical evidence no progress can be made. The clinical experience from various trial and error processes is briefly discussed in this review.

Immunotherapy for treatment of recalcitrant warts was used through different modalities including intralesional injection of purified protein derivative (PPD), which is an extract of Mycobacterium tuberculosis, used for testing exposure to tuberculin protein, either from a previous vaccination or from the environment. This method is used to evaluate the efficacy of a new approach of intradermal injection of PPD in the treatment of anogenital warts in pregnant women. A total of 40 pregnant women, aged 20-35 years, and presented with anogenital warts were enrolled in this study. Human papillomavirus (HPV) typing was done using the GP5+/GP6+ PCR assay. The patients were treated with weekly injections of PPD given intradermally in the forearms, and evaluated for the response regularly. HPV type-6 was the predominant genotype (67.5%). Overall, the improvement in this study was 85% and was related to the extent of tuberculin reactivity. Nineteen (47.5%) patients demonstrated complete clearance, 15 (37.5%) had partial response, and three (7.5%) had minimal response. Three (7.5%) cases did not respond to treatment. Side effects were minimal and insignificant. Treatment of anogenital warts in pregnant women with intradermal injection of PPD was found to be a unique, safe, and effective modality of immunotherapy., (© 2011 Wiley Periodicals, Inc.)

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., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

John Hughlings Jackson articulated a neurologic method of systematically evaluating the anatomy, physiology, and pathology of every patient with neurologic disease. He used this mode of analysis to develop a theory of the physiology of epilepsy. We examined an example of his method in a newly discovered, unpublished manuscript containing his suggestions for the treatment of epilepsy based on his physiologic ideas. He had his private papers destroyed at the time of his death, but the Rockefeller Library of the University College London Institute of Neurology, Queen Square, contains a collection of his papers probably saved from destruction by his collaborator James Taylor. Among these articles is an 1899 memorandum, labeled "For Private Circulation" and entitled "A Suggestion for the Treatment of Epilepsy." In it, Hughlings Jackson claimed that focal discharging lesions cause both focal and generalized epilepsy, and that the cells in the lesion discharge their energy more easily than normal tissue. Citing microscopic evidence that such lesions are congested and inflamed, and that tuberculin destroys such tissue in the lung, he reasoned that destroying these unstable neurons with tuberculin would improve epilepsy. In this private manuscript, Hughlings Jackson uses an unusually detailed analysis of the pathology, anatomy, and physiology of epilepsy to predict a scientific approach to its treatment.

In 1906, at a late evening tea party in Sir Almroth Wright's laboratory when the pathologist was working on his opsonic index as a guide to the therapeutic use of tuberculin, Bernard Shaw instigated a discussion on patient selection in the face of limited resources. In converting the various responses into a play Shaw turned the choice between a rogue artist and an honest doctor into a moral dilemma, and then thickened the plot by involving the artist's beguiling wife innocently in the decision. He added a blackly comedic denouement to answer a public challenge that he could not write a convincing death scene. With his penchant for irrepressible exaggeration, his doctors are amiable but inordinately opinionated, each convinced that he alone holds the secret of healing. The senior physician escapes censure and even measured praise is bestowed on the panel doctor who accepts a full-time public post. This article summarises the play and how it came to be written.

At the centenary of Robert Koch's Nobel Prize award, tuberculosis treatment with tuberculin, which was announced in Berlin in 1890, is still considered a failure. Nevertheless, there is now sufficient information supporting the idea that tuberculin therapy was widely used until the second half of the twentieth century; thus, the impact of this treatment should be studied and related to the decrease in tuberculosis-related mortality recorded in that period. Moreover, tuberculin therapy has inspired at least two new immunotherapies; these, however, were directed toward precisely the opposite effect: suppression of the Koch phenomenon. Thus, inoculation of Mycobacterium vaccae polarizes the immune response towards the Th1 type; and inoculation of RUTI avoids local immunodepression after short-term chemotherapy without inducing toxicity. For this reason, Robert Koch's work on antituberculosis therapy should be reread and proper recognition given to his contribution in this field.

The German medical bacteriologist Robert Koch is commonly considered one of the founding fathers of medical bacteriology. His investigations into the aetiology of tuberculosis uncovered the pathogen of this condition, the tubercle bacillus today known as Mycobacterium tuberculosis, in 1882. This work can be seen as a cornerstone of contemporary medical bacteriology, its technologies and methods. It has often been asked how such successful research connected to the tuberculin episode of 1890/91, when Koch produced a medicine for that disease, which spectacularly failed when applied in practice. The analysis concentrates on the path of mostly experimental investigations which Koch followed between 1882 and 1890. From Koch's laboratory notes it becomes clear that tuberculin therapy did in fact work in Koch's laboratory, even though it failed to do so almost anywhere else. The clue to this contradictory picture lies in the peculiar nature of Koch's understanding of tuberculosis as a disease e.g. his reliance an animal experiments, which essentially differed from what many of his contemporaries held as essentials of that condition.

Setting: A rural community in Chingleput district in Tamil Nadu state in south India., Objective: To determine the value of dual testing with PPD-S and PPD-B for identifying subjects with a tuberculous infection., Design: About 240,000 subjects in rural south India, all of whom were tested initially with PPD-S and PPD-B, were followed up for 15 years, mainly by total population survey once in every 212 years. The incidence of culture-positive tuberculosis was estimated using life-table technique., Results: Among 17,530 subjects with an intermediate reaction (8-11 mm) to PPD-S at intake, 285 with an induration to PPD-S exceeding the induration to PPD-B by at least 2mm, had a significantly higher incidence of culture-positive tuberculosis than the remaining (154 and 93 per 100,000), and similarly 481 who had an induration of <10mm to PPD-B compared to those with >or=10 mm (131 and 93 per 100,000). These subjects may be regarded as having a tuberculous infection. Infection with non-tuberculous mycobacteria conferred protection of about 30% against the development of tuberculosis over a 15-year period., Conclusion: In subjects with an intermediate reaction (8-11 mm) to PPD-S, dual testing with PPD-B enabled identification of those with a tuberculous infection. Most of the reactions were due to non-tuberculous mycobacteria.

The recent rise in the incidence of allergic diseases, including allergic dermatoses, requires a comprehensive approach to solving a number of problems associated with this disease. Analyzing the case reports of 62 children with allergic dermatoses has indicated that this is a particular contingent of children, which needs a more careful approach to different preventive measures, to interpreting tuberculin reactions and hence to substantiating the use chemotherapeutical prevention. A graded skin tuberculin test and an immunological study should be performed in critical cases.

Introduction: The increased prevalence of asthma has become a major public health issue worldwide. It has been proposed that this increase is due to the steady decline of infectious diseases such as tuberculosis., Aim of the Study: Supporting this view was, the suppressive effect of live Bacillus Calmette-Guerin (BCG) infection on allergen (ovalbumin) induced airway eosinophilia was published previously., Methods: Next the authors compared the effects of live, heat killed BCG and purified protein derivative of Mycobacterium tuberculosis (PPD) on a murine model of ovalbumin induced airway eosinophilia., Results: The results showed that both live and heat killed BCG, but not PPD strongly suppressed airway eosinophilia. This inhibition was correlated with the reduced number of Th2 cells in the lung., Conclusion: Their data support the hypothesis that the application of bacterial antigens may be a safe vaccination method against asthma in the future.

Robert Koch's description of the etiologic agent of tuberculosis on 24 March 1882 made him the hero of tuberculosis research overnight. In 1890, at the 10th International Congress of Medicine in Berlin, he claimed that he had discovered a remedy for the disease. This announcement was received with great excitement by both the medical community and the public. Medical trials performed in the subsequent months failed, however, to reveal a protective effect of Koch's remedy. In contrast, the diagnostic potential of tuberculin is still used and valued nowadays. This short article discusses Koch's reasons for fighting for the success of his remedy.

Previous work has shown that American cutaneous leishmaniasis (ACL) patients treated with viable BCG plus heat killed promastigotes of Leishmania amazonensis show the same rate of cure as patients receiving conventional chemotherapy. The treatment is safe and economical, but the immunological correlates of cure have not been examined. In the present study, T cell responses have been analysed in 43 ACL patients, including patient groups sampled before and after therapy, and in 10 endemic controls. Lymphocyte proliferation, interferon (IFN)-gamma and interleukin (IL)-5 responses to crude antigen (L. amazonensis, MEL; Mycobacterium tuberculosis PPD; M. bovis BCG) stimulation, and serum IL-5 levels, were analysed. In endemic volunteers, proliferative responses to BCG were high and IFN-gamma responses low. In contrast, localized cutaneous (LCL) and mucocutaneous (MCL) patients showed low proliferative and high IFN-gamma responses to BCG. Treatment enhanced the IFN-gamma response and further decreased the proliferative response to BCG, especially in MCL patients. LCL and MCL patients showed an increase in proliferative and IFN-gamma responses to MEL with treatment, but the response was not exaggerated in MCL patients, either before or after treatment, compared to LCL patients. IL-5 production was low in T cell assays, and > 62% of untreated patients had very low serum IL-5 levels. There were no significant changes in serum IL-5 with treatment. Overall results show enhanced antigen-specific IFN-gamma responses to the two components of the immunotherapy, live M. bovis BCG and heat killed L. amazonensis, which is consistent with a shift in balance of T cell response towards a T helper 1 response and clinical cure mediated by IFN-gamma.

Starting from an assessment of how far Robert Koch's bacteriology had developed in the late 1880s this paper attempts to analyse different aspects of the process that led to the foundation of the Berlin Institute for Infectious Diseases in 1891. With the development of his supposed cure against tuberculosis, tuberculin, Koch attempted to give his research a new direction, earn a fortune with the profits and become more independent of Prussian government officials who, up to that point, had had a major influence on his career. In the period following the presentation of the cure in autumn 1890, however, it became clear that tuberculin's value in treatment was at most dubious. Thus, the failure of tuberculin meant that Koch had to drop his own plans and accommodate those of the Prussian Ministry of Culture. As a result he assumed directorship of the newly founded Institute for Infectious Diseases in Berlin. Even though this was definitely a prestigious position it reaffirmed Koch's dependency on Prussian government officials and was by no means the kind of institution he had aimed for at the outset.

Background: Since the immune system is considered to be a major determinant in the outcome of malignant melanoma, vaccination with BCG (bacillus Calmette-Guérin) or more recently with interleukins is used in this condition, although the effects of this immunotherapy are unclear., Objective: The present study was to elucidate clinical aspects and the prognostic relevance of the cellular and humoral immune responses of melanoma patients treated with two different BCG vaccines., Methods: A subgroup of patients from a multicenter adjuvant trial with BCG in stage I (pT3-4N0M0) high-risk melanoma was prospectively subjected to detailed analysis regarding tuberculin (PPD, purified protein derivate) skin test reactivity, local, regional and systemic reactions to BCG vaccination, PPD antibody response and disease-free survival. Patients were randomized into three arms and received either no adjuvant treatment (22 patients), BCG RIV (40 patients) or BCG Pasteur (44 patients). All patients were followed for up to 10 years (median follow-up 6 years)., Results: Patients treated with BCG Pasteur mounted a stronger antibody response, experienced stronger regional and systemic reactions to vaccination and converted more frequently to positive PPD skin tests, compared to controls and to patients vaccinated with BCG RIV. All BCG-treated patients who developed an antibody response had a longer disease-free interval (p = 0.05), with slightly higher significance for BCG Pasteur-treated patients (p = 0.02)., Conclusions: Cellular as well as humoral immune responses to PPD and BCG thus identify stage I malignant melanoma patients with an overall better prognosis.

We investigated the responsiveness of peripheral blood lymphocytes (PBLs) from patients with M. avium-intracellulare complex (MAC) infection to the stimulation with PPDs by measuring their IFN-gamma producing ability. PBLs were obtained from MAC patients at active stage (culture-positive after three-month chemotherapy), those at inactive stage (culture-negative for three months after or during chemotherapy), and healthy donors. PPDs used were PPD-S prepared from M. tuberculosis, PPD-B from M. intracellulare, and PPD-Y from M. kansasii. PBLs from active MAC patients did not produce IFN-gamma to a significant extent by stimulation with any of three PPDs, while PBLs from inactive MAC patients showed higher responses to each PPD compared to those from active patients. In inactive MAC patients, the maximal response was observed to PPD-B among three PPDs. On the other hand, PBLs from healthy controls produced different levels of IFN-gamma in response to three different PPDs, and their response was most remarkable to PPD-S. These results indicated that the responsiveness of patients' PBLs to PPDs was impaired during active stage of MAC infection and restored on recovery from the disease.

The immunological survey of 1,688 patients with tuberculosis and 486 with non-specific pulmonary diseases was made. Criteria were identified for immunodiagnosis. The use of current mathematical methods of analysis allowed the development of high performance immunodiagnostic systems for pulmonary abnormalities, which included diagnostic tables and discriminant analysis by employing a computer. The major immunological disorders were determined, which in agreement with the definite direction of a tuberculous process with the subsequent use of data for monitoring the patient's status and correcting the treatment. The most potent immunocorrective drugs were studied, indications for their use were specified, proceeding from the immunological characterization of a specific patient. It was shown that the comprehensive assessment of various links of the immune system is of undoubtful value for the diagnosis and prediction of diseases, and prescription of immunocorrective therapy for pulmonary tuberculosis.

The paper presents the therapeutical results of 82 adolescents suffering from respiratory tuberculosis. During multi-modality therapy by using tuberculin, oliphen plus prednisolone there were clear-cut changes in immunological parameters, an increase in therapeutical efficiency and an average 3-month reduction in hospital stay.

Two procedures for treating experimental tuberculosis were compared. One comprised a rapid administration of tuberculin up to large doses (20,000 TE), the other included weakly stimulating therapy with tuberculin (its maximum dose being 150 TE). Treatment with tuberculin in combination with isoniazid ensures a higher resolution of specific abnormalities than that with isoniazid alone. However, when either procedures were used, the weakly stimulating procedure led to experimental animals' death, which generates the need to take a preliminary account of the body's response to tuberculin in the clinical setting in order to choose tuberculin therapy on an individual basis.

Mantoux test with 2 TU and tuberculin test results gave evidence for the pattern of body responses. A form of tuberculin therapy is suggested. The latter is shown to stimulate a spontaneous and BCG-enhanced NBT test (p < 0.05) and specific desensitization in the absence of humoral immunity changes (IgM, IgG, IgA and titers of circulating antituberculous antibodies).

In August 1890, Robert Koch dramatically announced that he had discovered a cure for tuberculosis, and the world rejoiced. The miracle substance was subsequently revealed to be tuberculin, inoculated as a 'vaccine therapy'. However, within a matter of months his claims were disputed and debunked, and his reputation was grievously damaged. The nationalistic pressures, professional jealousies and pecuniary interests that drove Koch's premature announcement are reviewed here and discussed in a context relevant to the development of therapeutic vaccines for human immunodeficiency virus infections.

Study of a combination of immunologic parameters in 29 adolescents with pulmonary tuberculosis who were subject to a combined treatment with the use of tuberculin demonstrated a decline in heightened specific cellular sensitivity, enhancement of antituberculous antibodies synthesis, normalization of the content and functional activity of T- and B-lymphocytes and rise of the level of class G and M immunoglobulins. It has been concluded that tuberculin has a desensitizing action combined with simultaneous stimulation of humoral response and the normalizing action on the T-lymphocyte system.

We have constructed PPD monoclonal antibody heteroconjugates specific for a tumour-associated antigen of C57BL/6 melanomas or for human complement component C3d fixed de novo to murine fibrosarcoma cells (MC6A). The ability of our heteroconjugates to target CD4+ PPD-reactive T cells against the appropriate tumour targets was then determined in vitro. Heteroconjugate-treated B16-F10 and MC6A tumour targets were both able to present PPD to the specific T cells, resulting in activation and concomitant lymphokine secretion. Secreted lymphokines were then demonstrated to cause significant tumour cytolysis and cytostasis in vitro. Preliminary experiments in vivo suggest that this targeting system may provide the basis for a future immunotherapeutic strategy.

It has been possible to achieve cavity closure earlier than usual in 162 patients aged from 15 to 25 years with newly discovered pulmonary tuberculosis by combining an intensive chemotherapy with early and differential administration of levamisole, tuberculin, intraorganic electrophoresis and ultrasound. Immunologic examination of the patients upon their admission to a hospital and in the course of their treatment made it possible to exercise a differential approach to the administration of pathogenetic drugs. The use of the immunostimulators, like levamisole in the first months of treatment and tuberculin at the second stage of therapy, significantly enhances the efficacy of chemotherapy.

The organism resistance to the appearance of 20-methylcholanthrene-induced tumours may be enhanced by application of different immunologic factors (BCG, PPD, low-molecular allogenic protein) in combination with a single administration of cyclophosphane (CPh). The positive effect was observed both when CPh was applied prior to the immunologic impact (3 or 7 days before) and after it (3 or 8 days later). In the last case the effect was more stable.