Injection Of BCG Research Articles

Comparison of the efficacy of BCG intravesical immunotherapy using the conventional Rotisserie method with the non-Rotisserie method

BackgroundIntravesical BCG injections are administered following transurethral resection of the superficial bladder tumor in order to increase the success rate and decrease the risk of tumor recurrence. BCG therapy has been examined extensively in terms of dosage and injection time intervals to determine its effectiveness. However, no study has yet been conducted to compare the two qualitatively different methods of administering BCG (Rotisserie and non-Rotisserie).MethodsThis study included 30 patients with non-muscle-invasive bladder TCC, whose tumor stage was Ta or T1. Two groups of 15 patients were randomly selected. The first intravesical injection of BCG was administered 2 weeks following transurethral resection of the bladder tumor and then continued as the maintenance treatment. But, in one group, the injection was done by Rotisserie method, and in the other group, non-Rotisserie method was performed. Then, the patients underwent periodic follow-up by cystoscopy to determine if recurrences had occurred.ResultsA total of 23 participants (76.66%) were males, while seven patients (23.34%) were females. There were 20 participants (66.66%) with tumors in the Ta stage and ten participants (33.34%) with tumors in the T1 stage. There were 22 patients (73.3%) with low-grade tumors and eight (26.7%) with high-grade tumors. Five participants (16.66%) experienced tumor recurrence during the study, three of whom were in the Rotisserie group and two in the Non-Rotisserie group. In terms of preventing tumor recurrence, there were no significant differences between Rotisserie and non-Rotisserie methods (P value = 0.6).ConclusionDue to the lack of significant difference in the rate of tumor recurrence between the two methods of intravesical BCG injection (Rotisserie and non-Rotisserie), it is not necessary to rotate the patients after BCG injection. This will also allow patients to be discharged from the hospital earlier and reduce the likelihood of complications.

Safety of BCG vaccination and revaccination in healthcare workers

ABSTRACT BCG vaccination and revaccination are increasingly being considered for the protection of adolescents and adults against tuberculosis and, more broadly, for the off-target protective immunological effects against other infectious and noninfectious diseases. Within an international randomized controlled trial of BCG vaccination in healthcare workers (the BRACE trial), we evaluated the incidence of local and serious adverse events, as well as the impact of previous BCG vaccination on local injection site reactions (BCG revaccination). Prospectively collected data from 99% (5351/5393) of participants in Australia, Brazil, Spain, The Netherlands and the UK was available for analysis. Most BCG recipients experienced the expected self-limiting local injection site reactions (pain, tenderness, erythema, swelling). BCG injection site itch was an additional common initial local symptom reported in 49% of BCG recipients. Compared to BCG vaccination in BCG-naïve individuals, BCG revaccination was associated with increased frequency of mild injection site reactions, as well as earlier onset and shorter duration of erythema and swelling, which were generally self-limiting. Injection site abscess and regional lymphadenopathy were the most common adverse events and had a benign course. Self-resolution occurred within a month in 80% of abscess cases and 100% of lymphadenopathy cases. At a time when BCG is being increasingly considered for its off-target effects, our findings indicate that BCG vaccination and revaccination have an acceptable safety profile in adults.

EFFICACY OF INTRALESIONAL BCG IN RECALCITRANT WARTS – A STUDY AT TERTIARY CARE CENTRE

Background:Warts are benign cutaneous and mucosal epithelial proliferations caused by Human papilloma viruses (HPV).[1]Several therapeutic approaches have been used in treating warts like topical medication such as salicylic acid, trichloroacetic acid, podophyllin, podophyllotoxin, glutaraldehyde, formalin, imiquimod,5-uorouracil and ablative procedures and surgical excision. This study is designed to determine the efcacy of intralesional immunotherapeutic agent BCG vaccine in clearing warts. Materials and Methods: The study group comprised of 20 cases of multiple recalcitrant cutaneous warts. Ethical clearance was sought and informed consent was obtained from all patients.The wart with longer duration and largest size was selected for this procedure. 0.1ml of BCG vaccine was injected intralesionally into the wart and was repeated every 3 weeks till complete clearance of the warts or for a maximum of 9 weeks. Results: After completion of 3 sittings at an interval of 3 weeks we observed the complete response in common warts , palmar warts and plantar warts was 64.5% , 58% and 40% respectively. Conclusion: Our study showed that intralesional BCG injection was safe and efcacious in the treatment of multiple recalcitrant cutaneous warts.

Disseminated Bacillus Calmette\u2013Gu\xe9rin (BCG) infection and acute exacerbation of interstitial pneumonitis: an autopsy case report and literature review

BackgroundIntravesical administration of Bacillus Calmette–Guérin (BCG) has proven useful for treatment and prevention of recurrence of superficial bladder cancer and in situ carcinoma. However, fatal side effects such as disseminated infections may occur. Early diagnosis and accurate therapy for interstitial pneumonitis (IP) are important because exacerbation of IP triggered by infections is the major cause of death. Although some fatality reports have suggested newly appeared IP after intravesical BCG treatment, to our knowledge, there are no reports which have demonstrated acute exacerbation of existing IP. Moreover, autopsy is lacking in previous reports. We report the case of a patient with fatal IP exacerbation after BCG instillation and the pathological findings of the autopsy.Case presentationA 77-year-old man with a medical history of IP was referred to our hospital because of fever and malaise. He had received an intravesical injection of BCG 1 day before the admission. His fever reduced after the use of antituberculosis drugs, so he was discharged home. He was referred to our hospital again because of a high fever 7 days after discharge. On hospitalisation, he showed high fever and systemic exanthema. Hepatosplenomegaly and myelosuppression were also observed. Biopsies revealed multiple epithelioid cell granulomas with Langhans giant cells of the liver and bone marrow. Biopsy DNA analyses of Mycobacterium bovis in the bone marrow, sputum, and blood were negative. His oxygen demand worsened drastically, and the ground-glass shadow expanded on the computed tomography scan. He was diagnosed with acute exacerbation of existing IP. We recommenced the antituberculosis drugs with steroid pulse therapy, but he died on day 35 because of respiratory failure. The autopsy revealed a diffuse appearance of multiple epithelioid cell granulomas with Langhans giant cells in multiple organs, although BCG was not evident.ConclusionsWe report the first case of acute exacerbation of chronic IP by BCG infection. This is also the first case of autopsy of a patient with acute exacerbation of existing IP induced by intravesical BCG treatment. Whether the trigger of acute IP exacerbation is infection or hypersensitivity to BCG is still controversial, because pathological evidence confirming BCG infection is lacking. Physicians who administer BCG against bladder cancer should be vigilant for acute exacerbation of IP.

Intravitreal thalidomide ameliorates inflammation in a model of experimental uveitis induced by BCG

Uveitis encompasses a heterogeneous and complex group of conditions characterized by intraocular inflammation, frequently affecting young individuals and representing an important cause of irreversible blindness worldwide. Animal models have been critical to understand etiology and pathogenesis of uveitis, being also employed to assess new therapeutic strategies, preceding human studies. However, there is still a need of developing and studying different models, due to the difficulties in recapitulating all forms of human uveitis effectively. Although corticosteroids are usually the first-line therapy for non-infectious uveitis, their long-term use is limited by potentially serious side effects in all possible delivery routes. Thus, thalidomide, a drug with anti-inflammatory and antiangiogenic properties, was investigated in a novel experimental model of uveitis, induced by Mycobacterium bovis Calmette-Guérin Bacillus (BCG), in rabbits. The experimental protocol consisted of two subcutaneous injections of BCG, followed by two intravitreal injections of the same antigen, inducing panuveitis. Animals were treated with a single intravitreal injection of thalidomide suspension or PBS. Clinical manifestations of uveitis improved after intravitreal thalidomide, involving both anterior and posterior segments. Protein content, N-acetyl-b-glucosaminidase (NAG) and myeloperoxidase (MPO) activities were elevated in ocular tissues after disease induction, further decreasing post-treatment with intravitreal thalidomide. This therapeutic response was also confirmed on ocular electrophysiology, as well as histopathology. This experimental model induced panuveitis in rabbits using a low-cost mycobacterial antigen, with intraocular inflammation subsequently improving after treatment. Intravitreal thalidomide may be a potential alternative to treat intraocular inflammation in corticosteroid-sparing therapies.

Effect of pirfenidone on cardiac complications in a model of Kawasaki disease in female Balb/C Mice: Histological and Immunohistochemical study

Introduction: Kawasaki disease (KD) is an immune mediating vasculitis affecting many systems especially the cardiovascular system. Pirfenidone is known for its anti-fibrotic and anti-inflammatory effects.Aim of work: to study the possible protective effect of pirfenidone on cardiac complications in a model of KD induced by Bacillus Calmette-Gue´rin (BCG) injection.Materials and Methods: This study included 18 female Balb/C mice that were divided into three groups. Group I (control group), group II (KD group) that received single injection of BCG in tail vein, and group III (pirfenidone group) that received BCG as group II and daily oral pirfenidone till end of experiment. All mice were sacrificed 21 days after the injection, hearts were collected and examined.Results: Group II revealed irregular separated cardiac myocytes and interstitial inflammation. Coronaries were seen with thin wall and irregular lumen. Localized intimal thickening and irregularly arranged smooth muscles were noticed in the media. Perivasular inflammation was also noticed. Mallory stained sections revealed interstitial, vascular and perivascular fibrosis. Orcein stained sections revealed disruption of internal and external elastic laminae. Positive immune reaction for TNF-α was also noticed in group of KD. Pirfenidone treatment minimized the histological changes induced in KD. Little mononuclear cellular infiltration was still noticed in the myocardium. Moderate collagen fibers were seen in the adventitia and intact elastic laminae.Conclusions: Pirfenidone aborted the cardiovascular complications associated with KD.

Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations

Intradermal (ID) BCG injection provides incomplete protection against TB in humans and experimental models. Alternative BCG vaccination strategies may improve protection in model species, including rhesus macaques. This study compares the immunogenicity and efficacy of BCG administered by ID and intravenous (IV) injection, or as an intratracheal mucosal boost (ID + IT), against aerosol challenge with Mycobacterium tuberculosis Erdman strain. Disease pathology was significantly reduced, and survival improved, by each BCG vaccination strategy, relative to unvaccinated animals. However, IV induced protection surpassed that achieved by all other routes, providing an opportunity to explore protective immunological mechanisms using antigen-specific IFN-γ ELISpot and polychromatic flow cytometry assays. IFN-γ spot forming units and multifunctional CD4 T-cell frequencies increased significantly following each vaccination regimen and were greatest following IV immunisation. Vaccine-induced multifunctional CD4 T-cells producing IFN-γ and TNF-α were associated with reduced disease pathology following subsequent M.tb challenge; however, high frequencies of this population following M.tb infection correlated with increased pathology. Cytokine producing T-cells primarily occupied the CD4 transitional effector memory phenotype, implicating this population as central to the mycobacterial response, potentially contributing to the stringent control observed in IV vaccinated animals. This study demonstrates the protective efficacy of IV BCG vaccination in rhesus macaques, offering a valuable tool for the interrogation of immunological mechanisms and potential correlates of protection.

Nodular lymphoid hyperplasia of urinary bladder admixed with non-invasive low-grade urothelial carcinoma

Primary malignant lymphoma of urinary bladder is extremely rare, and benign nodular lymphoid hyperplasia has not been reported in bladder. Nodular lymphoid hyperplasia of bladder associated with bladder carcinoma has also not been reported. Herein the author describe a 64-year-old man who presented with dysuria and his cystscopic examination revealed a papillary tumor in bladder. A transurethral resection of bladder tumor was carried out, and histopathologic examination revealed a non-invasive pTa low-grade papillary urothelial carcinoma and nodular lymphoid hyperplasia that were mixed up. The nodular lymphoid hyperplasia was composed of inner germinal centers and outer marginal and mantle zones. The germinal centers were composed of tangible body macrophages, centrocytes and centroblasts, while the outer zone of mature lymphocytes. Immunohistochemical profile of nodular lymphoid hyperplasia was as follows: cytokeratin AE1/AE3-, cytokeratin CAM5.2-, CD45+++, CD20+++, CD79a++, CD138-, CD3-, CD45RO-, CD15-, CD30-, p53- Ki67 80% (confined to germinal centers), bcl-2-, bcl-6++, CD10++, MUM1-, cyclinD1-, light chains-, CD56-, TdT-, CD68-. The patient is now followed up without any treatments by periodical cystscopy with BCG injection and cytology. No recurrence is noted 13 months after the first presentation. In conclusion, an extremely rare case of nodular lymphoid hyperplasia mixed with non-invasive urothelial carcinoma in bladder is reported.

Higher Performance of QuantiFERON TB Compared to Tuberculin Skin Test in Latent Tuberculosis Infection Prospective Diagnosis

Background: The Tuberculin skin test (TST) has been used for years in the latent tuberculosis infection (LTBI) diagnosis, but it has, well-documented, low sensitivity and specificity. Interferon-γ release assays (IGRA) has been reported to be more sensitive and specific than TST. Therefore, this study aimed to evaluate the performance of a commercial IGRA, QuantiFERON®-TB Gold In-Tube (QFT-GIT), comparatively to TST in LTBI diagnosis. Patients and Methods: This study included 238 patients who were candidate for an anti-TNF therapy. The screening for LTBI was performed by both TST and QFT-GIT test for all patients. In order to evaluate the strength of associations, the odds ratios (OR) together with 95% confidence intervals (CI) were calculated. The correlation between QFT-GIT and TST was evaluated using κ statistics. Results: Sixty-three (26.4%) sera were positive for QFT-GIT with a mean level of IFN-γ of about 1.18 IU/ml, while 81 (34%) patients were positive for TST. Agreement between QFT-GIT and TST was poor (37 QFT-GIT+/TST- and 55 QFT-GIT-/TST+), κ=0.09 (SD=0.065). The positivity of QFT-GIT was not influenced by BCG vaccination or by immunosuppression. Nevertheless, it was significantly associated to both history of an earlier tuberculosis disease (HETD) and its radiological sequel (RS), p=6E-7 and p=1E-8, respectively. Inversely, the TST results were not correlated to either HETD or RS, but the TST positivity was less frequent in immunosuppressed patients (45.5% vs. 73.9%), p=1E-5, OR (95% CI) = 0.29 [0.17-0.52]. Moreover, the extent of both the immunosuppression period and the time elapsed from the last BCG injection was significantly correlated to a lesser TST positivity, p=3E-12 and p=5E-7, respectively. Among the QFT-GIT-/TST+ patients (n=55) whom received an anti-TNF agent without any prophylactic treatment of LTBI, no tuberculosis was detected with a median follow-up of 78 weeks [56-109]. Conclusion: Our study suggests that the QFT-GIT has a higher performance comparatively to TST in the LTBI screening that is unaffected by either BCG vaccination or immunosuppression. Therefore, IGRAs has to replace TST especially in patients who are under consideration for an anti-TNF therapy.

Bacillus calmette-guerin infection in NADPH oxidase deficiency: defective mycobacterial sequestration and granuloma formation.

Patients with chronic granulomatous disease (CGD) lack generation of reactive oxygen species (ROS) through the phagocyte NADPH oxidase NOX2. CGD is an immune deficiency that leads to frequent infections with certain pathogens; this is well documented for S. aureus and A. fumigatus, but less clear for mycobacteria. We therefore performed an extensive literature search which yielded 297 cases of CGD patients with mycobacterial infections; M. bovis BCG was most commonly described (74%). The relationship between NOX2 deficiency and BCG infection however has never been studied in a mouse model. We therefore investigated BCG infection in three different mouse models of CGD: Ncf1 mutants in two different genetic backgrounds and Cybb knock-out mice. In addition, we investigated a macrophage-specific rescue (transgenic expression of Ncf1 under the control of the CD68 promoter). Wild-type mice did not develop severe disease upon BCG injection. In contrast, all three types of CGD mice were highly susceptible to BCG, as witnessed by a severe weight loss, development of hemorrhagic pneumonia, and a high mortality (∼50%). Rescue of NOX2 activity in macrophages restored BCG resistance, similar as seen in wild-type mice. Granulomas from mycobacteria-infected wild-type mice generated ROS, while granulomas from CGD mice did not. Bacterial load in CGD mice was only moderately increased, suggesting that it was not crucial for the observed phenotype. CGD mice responded with massively enhanced cytokine release (TNF-α, IFN-γ, IL-17 and IL-12) early after BCG infection, which might account for severity of the disease. Finally, in wild-type mice, macrophages formed clusters and restricted mycobacteria to granulomas, while macrophages and mycobacteria were diffusely distributed in lung tissue from CGD mice. Our results demonstrate that lack of the NADPH oxidase leads to a markedly increased severity of BCG infection through mechanisms including increased cytokine production and impaired granuloma formation.

FRI-18 THE HISTORY OF BCG AND BLADDER CANCER: ETHICAL CONCERNS FROM UROLOGY’S RECENT PAST

You have accessJournal of UrologyHistory of Urology I (Podium)1 Apr 2014FRI-18 THE HISTORY OF BCG AND BLADDER CANCER: ETHICAL CONCERNS FROM UROLOGY’S RECENT PAST Anees Fazili, Jennifer Gordetsky, and Ronald Rabinowitz Anees FaziliAnees Fazili More articles by this author , Jennifer GordetskyJennifer Gordetsky More articles by this author , and Ronald RabinowitzRonald Rabinowitz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1736AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives In 1976, Morales et al first applied intravesical BCG, ushering in a new chapter in the treatment of bladder cancer. A review of the history of BCG use prior to that study raises some ethical questions about the design of this groundbreaking clinical trial. Methods We performed a review of the literature regarding the historical development of BCG as an anti-neoplastic agent, with a focus on its application to bladder cancer. Results In the 1950s BCG was shown to have anti-neoplastic qualities in mice. Experimentation with BCG for the treatment of human neoplasia began in the 1960s with work on acute lymphoblastic leukemia. By 1970, intra-lesional BCG injections had been reported for the treatment of melanoma. BCG’s anti-neoplastic properties came to the attention of urologists in the early 1970s after a case report was published describing how a transurethral, intra-tumoral BCG injection had eradicated a metastatic melanoma lesion in a patient’s bladder. Two animal studies were subsequently initiated to examine the effect of intravesical BCG administration, with the aim to better understand the safety and tolerability of this route of delivery. The landmark clinical study by Morales et al utilizing intravesical BCG to treat human bladder cancer was begun before the authors had access to the results of these animal studies. Although not referenced in the original study published in 1976 by Morales et al, an historical article published by Morales & Herr in 2008 on the history of BGG use for bladder cancer references an animal experiment utilizing BCG in the guinea pig bladder as a basis for the initial human experimentation. Further review of this article, however, reveals that bovine gamma-globulin, or BGG, was in fact the antigen used in those studies. Hence, despite being scientifically sound and grounded in immunologic principles, there was a lack of appropriate pre-clinical and Phase 1 study data to support Morales’ original study. Thus, study subjects could not have been appropriately counseled and informed regarding the risks and benefits of BCG therapy prior to study involvement. Conclusions The initial clinical study of intravesical BCG for bladder cancer used human subjects at a time when other research groups were still undertaking the necessary preliminary animal experiments. The subsequent creation of Institutional Review Boards in 1978 and more stringent FDA approval processes would make it impossible to perform a similar trial today without prior rigorous animal studies. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e627 Peer Review Report Advertisement Copyright & Permissions© 2014MetricsAuthor Information Anees Fazili More articles by this author Jennifer Gordetsky More articles by this author Ronald Rabinowitz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Mycobacterium bovis BCG killed by extended freeze‐drying induces an immunoregulatory profile and protects against atherosclerosis

Atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. Regulatory T cells (Tregs) and IL-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. We have previously shown that Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) decreases lung and colon inflammation by recruiting IL-10-producing Tregs. Therefore, the aim of this study was to investigate the effect of EFD BCG on the development of atherosclerosis. We used two strains of atherosclerosis-prone mice: Ldlr(-/-) (four or six EFD BCG injections) and Apoe(-/-) (six injections). In both models, EFD BCG significantly reduced the size of atherosclerotic lesions, increased IL-10 production and reduced the serum levels of pro-inflammatory cytokines (IL-6, IL-13, KC and tumour necrosis factor-α). Shortly after treatment with EFD BCG, the number of plasmacytoid dendritic cells (pDCs) and Foxp3(+) Tregs in the draining lymph nodes increased. EFD BCG also led to accumulation of Tregs, but not of pDCs in the spleen, and reduced activity of NF-κB and increased activity of PPAR-γ in both the spleen and vascular tissue of treated mice. EFD BCG has atheroprotective effects through IL-10 production and Treg expansion. These findings support a novel approach to the prevention and treatment of atherosclerosis.

Lepromatous leprosy treated with combined chemotherapy and immunotherapy (injection BCG): three case reports

Lepromatous leprosy is associated with suppressed cell-mediated immunity (CMI). This results in failure of the body to mount an efficient immune response and may render chemotherapy ineffective. The lack of sufficient response may mimic drug resistance. Three case reports in which the immunity was stimulated by administering Injection BCG are presented. All three patients were initially anergic and showed no reaction at the Mantoux testing site, showing an inability to mount type IV hypersensitivity and characterized by live bacilli in smears. Following 1-4 doses of Injection BCG, all three showed dead bacilli in smears. The first case, a 61-year-old man with lepromatous leprosy who continued to show live bacilli in smears after prolonged chemotherapy, was administered a total of four BCG injections, following which he achieved clearance. The second, a 40-year-old man with borderline lepromatous leprosy and severe type 2 reactions, achieved bacterial clearance and control of severe reactions following a single injection. The third, a 67-year-old man with histoid leprosy, achieved effective bacterial killing with a single dose of Injection BCG. All three patients achieved good results when chemotherapy was combined with Injection BCG. Following Injection BCG, all three showed a reaction at the Mantoux testing site. Suppressed CMI may be responsible for the lack of response in recalcitrant cases of lepromatous leprosy. These case reports would lead to the trend in combination therapy (immunotherapy combined with chemotherapy) for such cases, and help lower the tendency for inappropriate diagnosis of drug-resistant leprosy.

The study of novel DNA vaccines against tuberculosis

Results: HSP65 + IL-12 DNA vaccine showed higher protective efficacy compared with BCG in both mouse and monkey models of TB. It induced the TB-specific CTL in the mouse model of TB, while little level of activity was observed after the injection of BCG. It also showed strong therapeutic efficacy against MDR-TB. In the monkey model, the vaccine augmented the production of IFN-γ and IL-2 from PBL and the therapeutic effect was correlated with the level of IL-2. We next evaluated the potential of DNA vaccine encoding a granulysin, which is an important defensive molecule expressed by human T cells. We found that granulysin-encoding vaccine induced the differentiation of the CTL in vitro and in vivo. It also showed therapeutic efficacy against TB in the monkey as well as the mouse model. The DNA vaccine encoding a Ksp37 also induced the TB-specific CTL in vitro and in vivo in the mouse model. It augmented the production of IL-2, IFN-γ and IL-6 from T cells and spleen cells. A synergistic effect on the activation of the TB-specific CTL was observed by the combination of Ksp37 DNA vaccine with granulysin DNA vaccine.Purpose and Methods: Emergence of the multi-drug resistant (MDR) Mycobacterium tuberculosis (TB) is a big problem in the world. We have developed novel TB vaccines [DNA vaccines encoding HSP65 + IL-12, granulysin or killer-specific secretory protein of 37kDa (Ksp37)] using Hemagglutinating virus of Japan -envelope (HVJ-E). It is suggested that the activity of the TB-specific CTL is one of the most important factor for the resistance to TB and immunity for TB in chronic human TB disease. Therefore, we examined the level of activation of the TB-specific CTL after the administration of these vaccines.Conclusion: These data indicate that our novel vaccines (HSP65 + IL-12 DNA, granulysin and Ksp37) have a capability to activate the TB-specific CTL and will be very strong protective and therapeutic vaccines against TB.

A family history of serious complications due to BCG vaccination is a tool for the early diagnosis of severe primary immunodeficiency

Severe Combined Immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency (PID). Complications of BCG vaccination, especially disseminated infection and its most severe forms, are known to occur in immunodeficient patients, particularly in SCID. A carefully taken family history before BCG injection as well as delaying vaccination if PID is suspected could be a simple and effective method to avoid inappropriate vaccination of an immunodeficient child in some cases until the prospect of newborn screening for SCID has been fully developed. We describe a patient with a very early diagnosis of SCID, which was suspected on the basis of the previous death of two siblings younger than one year due to severe complications secondary to the BCG vaccine. We suggest that a family history of severe or fatal reactions to BCG should be included as a warning sign for an early diagnosis of SCID.

Anti-CD20 Therapy Reduces Microglial Activation and Lesion Volume in Focal Models of Pattern I and Pattern II Multiple Sclerosis (P02.085)

Objective: We sought to determine whether anti-CD20 would inhibit lesion development and microglial activation in the focal (pattern I) Th1-type delayed type hypersensitivity (BCG-DTH) model and in an antibody-mediated focal (pattern II) fMOG-EAE of MS. We also compare the effects of anti-CD20 against those of FTY720. Background Pattern II MS lesions are associated with deposition of antibody and complement, but pattern I lesions are thought to be mediated principally by Th1/Th17 T cells and macrophages in a B-cell independent manner. However, there is evidence to suggest that B cells play a role in MS in an antibody independent fashion and B cell directed therapy is proving effective in a broader MS population than expected. Design/Methods: ocal pattern I-like lesions, were induced by the injection of heat-killed BCG into the striatum, followed by intradermal injection of BCG in CFA 28 days later. Focal pattern II lesions were induced by the injection of MOG35-55(25 μg) in IFA, followed by the stereotaxic injection of TNF/IFNg into the corpus callosum 21 days after. Animals (n=6) received anti-CD20 or FTY or vehicle on d1 and d7. The animals were killed on d12. Microglial activation as assessed by the binding of the TSPO ligand [125I]-DPA-713. Results: Anti-CD20-treated rats displayed significantly reduced lesion volume in both the pattern I (65.7%, p≤0.001) and pattern II (56.8%, p≤0.013) models. For the pattern I lesion, [125I]-DPA-713 binding was reduced to the same extent in the FTY720 treated animals compared to the anti-CD20. Thus the anti-CD20 treatment blocked the development of both an aggressive Th1 pattern I-type MS lesion, and the pattern II fMOG-EAE lesion. Conclusions: This suggests that B cells play an important role in lesion development that is independent of local CNS antibody production. Supported by: F. Hoffmann-La Roche Ltd. Disclosure: Dr. Leppert has received personal compensation for activities with Roche Diagnostics Corporation as an employee. Dr. Leppert has received compensation for serving on the University of British Columbia MS/MRI Research Group of Angiotech, Bayer, Berlex-Schering, Bio-MS, Centocor, Daiichi Sankyo, Genentech, Hoffmann-LaRoche, Merck-Serono, Perceptives, Schering-Plough, Teva Neurosciences, Sanofi-Aventis, and Transition Therapeutics. Dr. Leppert holds stock and/or stock options in F. Hoffmann La Roche Ltd., which sponsored research in which Dr. Leppert was involved as an investigator. Dr. Campbell has nothing to disclose. Dr. Seneca has received personal compensation for activities with Roche as an employee. Dr. Warren has nothing to disclose. Dr. Balazs has received personal compensation for activities with Genentech as an employee. Dr. Anthony has nothing to disclose.

Comparison of two methods of neonatal BCG intradermal injection

Objective To compare the success rate of two methods of neonatal BCG intradermal injection.Methods 236 cases of neonatal inoculation conditions were randomly divided into two groups,observed group of 113 cases using the improved technique of intradermal injection of BCG vaccine,in the control group of 123 patients with conventional intradermal injection of BCG vaccine. The inoculation effect was compared between the two groups.Results BCG injection success rate of the observed group was significantly higher than that of the control group (x2=4.3148,P＜0.05). Conclusion The improved method in neonatal injected intradermally. BCG,and no leakage, no exudate,size Picchu meet vaccination requirements,the advantages of vaccination success rate. Key words: Neonatal nursing; BCG vaccine; Injections, intradermal

Neonatal mortality and prevalence of practices for newborn care in a squatter settlement of Karachi, Pakistan: a cross-sectional study.

BackgroundDuring the past two decades there has been a sustained decline in child and infant mortality, however neonatal mortality has remained relatively unchanged. Almost all neonatal deaths (99%) occur in developing countries, where the majority are delivered at homes. Evidence suggests that these deaths could be prevented by simple, inexpensive practices and interventions during the pregnancy, delivery and postnatal period. In Pakistan over the last decade extensive efforts have been made by the international donors and government to implement these practices. However, limited attempts have been made to explore if these efforts have made a difference at the grass root level. This study assessed the burden of neonatal mortality and prevalence of practices for newborn care in a squatter settlement of Karachi, Pakistan.Methodology/Principal FindingsA community based cross-sectional study was performed. A pre-tested structured questionnaire was administered to 565 women who had recently delivered. Information was collected on neonatal morbidity, mortality and practices of women regarding care during pregnancy, child birth and for newborn, till 28th day of birth. Although 70% of women mentioned receiving antenatal care by a skilled provider, only 54.5% had four or more visits. Tetanus toxoid was received by 79% of women while only 56% delivered at a health care facility by a skilled attendant. Newborn care practices like bathing the baby immediately after birth (56%), giving pre-lacteals (79.5%), late initiation of breast feeding (80.3%), application of substances on umbilical cord (58%) and body massage (89%) were common. Most neonates (81.1%) received BCG injection and polio drops after birth. Neonatal mortality rate was 27/1000 live births with the majority of deaths occurring during the first three days of life.ConclusionEven after years of efforts by government and nongovernmental sector to reduce newborn morbidity and mortality, inadequate antenatal care, home deliveries and unhealthy newborn care practices are highly prevalent. This leads us to important questions of why practices and behaviors have not changed. Who is responsible and what strategies are needed to bring this change?

Local BCG injection administered to patients with flat condyloma of the cervix

Local BCG injection administered to patients with flat condyloma of the cervix

Tuberculin sensitivity and morphological immune response in guinea pigs after application of minimal sensitizing dose of BCG vaccine, substrain Sofia SL222

During the investigation of the BCG allergenic potency it is advisable to vaccinate with decreasing doses, estimating the lowest dose that induces tuberculin sensitivity and specific morphological inflammation. Although the biological test does not reveal the mathematical correlation of dose–effect relationships, it is important to look for the determination of the minimal sensitizing dose for every BCG vaccine. In this study, three groups of twenty four guinea pigs were vaccinated with decreasing doses of reconstituted BCG vaccine: 120 ng, 12 ng and 1.2 ng. Tuberculin tests were performed in different groups at the 30th, 60th, 90th and 120th day after BCG injection. The negative tuberculin reactions converted to positive between the 60th and 90th day. The dose of 12 ng elicited the largest tuberculin reactions in the animals. This dose contains 65 viable bacteria and could be regarded as the smallest effective sensitizing dose of the BCG vaccine, substrain Sofia SL222. The morphological examination demonstrated that very low inoculums (1.2 ng or 6 viable cells) were sufficient to induce a specific inflammation after BCG vaccination. The immune response in lungs and bronchus-associated lymphoid tissue (BALT) of all BCG doses applied was strongest on the day 60. In the same term, lymph nodes and spleens were characterized with blast transformed lymphoid follicles with epitheloid and Langhans giant cells even with the smallest injected dose of 1.2 ng.