MyMedR

Fulltext Vaccines for TB: Lessons from the Past Translating into Future Potentials

Tye GJ, Lew MH, Choong YS, Lim TS, Sarmiento ME, Acosta A, et al.

J Immunol Res, 2015;2015:916780.

PMID: 26146643 DOI: 10.1155/2015/916780

Development of vaccines for infectious diseases has come a long way with recent advancements in adjuvant developments and discovery of new antigens that are capable of eliciting strong immunological responses for sterile eradication of disease. Tuberculosis (TB) that kills nearly 2 million of the population every year is also one of the highlights of the recent developments. The availability or not of diagnostic methods for infection has implications for the control of the disease by the health systems but is not related to the immune surveillance, a phenomenon derived from the interaction between the bacteria and their host. Here, we will review the immunology of TB and current vaccine candidates for TB. Current strategies of developing new vaccines against TB will also be reviewed in order to further discuss new insights into immunotherapeutic approaches involving adjuvant and antigens combinations that might be of potential for the control of TB.

Matched MeSH terms: BCG Vaccine/immunology

Unusual case of cerebral demyelination and bilateral optic neuritis in an infant with suppurative BCG lymphadenitis

Anandakrishnan P, Khoo TB

BMJ Case Rep, 2018 May 30;2018.

PMID: 29848532 DOI: 10.1136/bcr-2018-224496

Cerebral demyelination and optic neuritis are often seen in children with acute disseminated encephalomyelitis following various infections and immunisations. An eight month old girl presented with a left axillary lymph node swelling and an erythematous lace-like rash over her cheeks and trunk. She then developed acute encephalopathy, bilateral nystagmus, right hemiparesis and left facial nerve palsy. Her electroencephalogram showed an encephalopathic process and visual evoked response study were grossly abnormal. Her MRI brain showed hyperintensities in the midbrain, pons and bilateral cerebellar peduncles. She was treated as postinfectious cerebral demyelination with intravenous antibiotics, methylprednisolone and immunoglobulin. Left axillary lymph node excision biopsy and GeneXpert test detected Mycobacterium tuberculosis complex that prompted initiation of antituberculous therapy. Her chest X-ray and cerebrospinal fluid examinations for tuberculosis were normal. She showed significant recovery after 2 weeks. This case illustrates a rare presentation of cerebral demyelination and bilateral optic neuritis following suppurative BCG lymphadenitis.

Matched MeSH terms: BCG Vaccine/adverse effects*

Tuberculosis vaccine candidates based on mycobacterial cell envelope components

Sarmiento ME, Alvarez N, Chin KL, Bigi F, Tirado Y, García MA, et al.

Tuberculosis (Edinb), 2019 03;115:26-41.

PMID: 30948174 DOI: 10.1016/j.tube.2019.01.003

Even after decades searching for a new and more effective vaccine against tuberculosis, the scientific community is still pursuing this goal due to the complexity of its causative agent, Mycobacterium tuberculosis (Mtb). Mtb is a microorganism with a robust variety of survival mechanisms that allow it to remain in the host for years. The structure and nature of the Mtb envelope play a leading role in its resistance and survival. Mtb has a perfect machinery that allows it to modulate the immune response in its favor and to adapt to the host's environmental conditions in order to remain alive until the moment to reactivate its normal growing state. Mtb cell envelope protein, carbohydrate and lipid components have been the subject of interest for developing new vaccines because most of them are responsible for the pathogenicity and virulence of the bacteria. Many indirect evidences, mainly derived from the use of monoclonal antibodies, support the potential protective role of Mtb envelope components. Subunit and DNA vaccines, lipid extracts, liposomes and membrane vesicle formulations are some examples of technologies used, with encouraging results, to evaluate the potential of these antigens in the protective response against Mtb.

Matched MeSH terms: BCG Vaccine/chemistry

Fulltext Tuberculin reactivity and subsequent development of tuberculosis in a cohort of student nurses

Jeyakumar D

Med J Malaysia, 1999 Dec;54(4):492-5.

PMID: 11072468

This retrospective study documents a strong correlation between tuberculin reactivity and the subsequent development of active tuberculosis in student nurses. 12% of the 25 student nurses with tuberculin reactions above 20 mm developed tuberculosis over a period of 2 years, compared to only 0.3% of the 341 student nurses with reactions of 20 mm or less. The implications of these findings for preventive therapy are discussed.

Matched MeSH terms: BCG Vaccine/therapeutic use

Fulltext The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

Abbas MA, Suppian R

J Infect Dev Ctries, 2019 11 30;13(11):1057-1061.

PMID: 32087079 DOI: 10.3855/jidc.11331

INTRODUCTION: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4).

METHODOLOGY: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively.

RESULTS: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242.

CONCLUSIONS: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

Matched MeSH terms: BCG Vaccine/immunology*; BCG Vaccine/pharmacology

The effect of early BCG and smallpox immunization on serum bilirubin levels in the newborn

Sinniah D, Nagalingam I, Chua CP, Khoo KP, Dugdale AE

Clin Pediatr (Phila), 1974 Sep;13(9):765-6.

PMID: 4429633 DOI: 10.1177/000992287401300913

Matched MeSH terms: BCG Vaccine*

The early immunisation of infants in Malaysia

Chen ST, Choong MM

Med J Malaya, 1971 Sep;26(1):15-9.

PMID: 4258569

Matched MeSH terms: BCG Vaccine*

The delivery of a total tuberculosis service in a scattered rural community with poor communications

Webb AH

N Z Med J, 1973 Nov 14;78(502):412-4.

PMID: 4129253

Matched MeSH terms: BCG Vaccine

Fulltext The Kveim test in lepromatous and tuberculoid leprosy

Pearson JMH, Pettit JHS, Siltzbach LE, Ridley DS, Hart PD, Rees RJ

Int. J. Lepr. Other Mycobact. Dis., 1969;37(4):372-81.

PMID: 5394258

Kveim tests using a validated material have been undertaken in Malaysia on 39 patients (32 Chinese; 4 Malay and 3 Aboriginal) with lepromatous or tuberculoid leprosy. All the patients had been treated for leprosy, most for two or more years. The tests were read microscopically. Of the 21 lepromatous patients one gave a weak positive and two an equivocal Kveim test whereas four of the nine tuberculoid patients gave equivocal or weak Kveim positivity. Only the tuberculoid form elicits a higher proportion of granulomas than might be expected in a comparable normal population. Of nine patients (8 lepromatous; 1 tuberculoid ) who failed to sensitize well to tuberculin
following two BCG vaccinations, two gave equivocal Kveim tests similar in appearance to those in the other groups.

Matched MeSH terms: BCG Vaccine

The "built-in failure-rate" of immunisation at infant-health clinics

Dugdale AE

Lancet, 1969 Feb 22;1(7591):409-11.

PMID: 4179241 DOI: 10.1016/S0140-6736(69)91371-3

Matched MeSH terms: BCG Vaccine

TUBERCULOSIS IN MALAYA

SODHY JS

Med J Malaysia, 1964 Jun;18:239-50.

PMID: 14199442

Matched MeSH terms: BCG Vaccine*

Systemic anti-CTLA-4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism?

Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G

Med Hypotheses, 2016 Jul;92:57-8.

PMID: 27241256 DOI: 10.1016/j.mehy.2016.04.037

Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.

Matched MeSH terms: BCG Vaccine/therapeutic use*

Fulltext Successful treatment of anogenital warts with single dose Bacillus Calmette Guerin vaccine without prior sensitization in tuberculosis endemic country: Two case report

Achdiat PA, Suwarsa O, Hidayat YM, Shafiee MN, Dwiyana RF, Gunawan H, et al.

Hum Vaccin Immunother, 2023 Dec 31;19(1):2187591.

PMID: 36942667 DOI: 10.1080/21645515.2023.2187591

Anogenital Warts (AGWs) are benign proliferations caused by Human Papillomavirus (HPV) infection on the genital or anal areas. Various therapeutic options are available for the treatment of AGWs but there is no best or ideal therapy, and the recurrence of AGWs is significantly high. A promising new therapy that is currently being evaluated is immunotherapy with the intralesional Bacillus Calmette-Guérin (BCG) vaccine. Two cases of a 23-year-old woman and a 41-year-old man were presented with manifestations of condyloma acuminata type AGWs. The patients were immunocompetent and received single dose intralesional BCG vaccine on the largest lesion. Clinical improvements of AGWs lesions were noted starting on the 14th day after receiving therapy by the disappearance of some lesions with no recurrence and side effects. Intralesional BCG vaccine activates the immune system, treats other AGWs lesions that do not receive an intralesional injection, and also prevents recurrence. Although the intralesional BCG vaccine is effective for treating AGWs, further evaluation is still needed for its recurrence.

Matched MeSH terms: BCG Vaccine/therapeutic use

Fulltext Social expectations and government incentives in Malaysia's COVID-19 vaccine uptake

Abdul Aziz NI, Flanders S, Nungsari M

PLoS One, 2022;17(9):e0275010.

PMID: 36156604 DOI: 10.1371/journal.pone.0275010

High vaccination rates are integral to reducing infection and severity rates of COVID-19 infections within a community. We examine the role of social expectations in COVID-19 vaccination take-ups and its interaction with potential government actions in Malaysia. We find that individuals' expectations of others in their social groups towards vaccination predicts those individuals' vaccination registrations. Using a vignette experiment, we examine the extent of normative expectations in normalizing pro-vaccination behavior beyond an individual's reference group. We find that unless moderated by a high level of public trust, individuals prefer punitive policies as a way to increase vaccination rates in their communities.

Matched MeSH terms: BCG Vaccine

Fulltext Ruptured Aortic Aneurysm Secondary to Psoas abscess after Intravesical Bacilli Calmette-Guérin

Khandelwal A, Gupta A, Virmani V, Khandelwal K

Med J Malaysia, 2012 Oct;67(5):534-5.

PMID: 23770877

Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used as effective treatment for early-stage transitional carcinoma of the urinary bladder. We present a case of a 68 year old man who had an abdominal aortic aneurysm following BCG therapy for bladder cancer. Contrast enhanced computerized tomogram (CECT) of abdomen and pelvis revealed bilateral hypodense lesions suggestive of psoas abscesses. In addition, a saccular abdominal aortic aneurysm measuring 4x3.6 cm involving infrarenal aorta with surrounding hematoma was seen. At surgery, he was found to have a psoas abscess and hemorrhage. He underwent ligation of the aorta and an axillary-bifemoral bypass. He was given one year of anti-tubercular therapy to which he responded clinically.

Matched MeSH terms: BCG Vaccine

Fulltext Risk of tuberculosis to healthcare workers

Liam CK

Med J Malaysia, 2001 Mar;56(1):107-11; quiz 112.

PMID: 11503290

Matched MeSH terms: BCG Vaccine/immunology

Fulltext Reiter's syndrome postintravesical Bacillus Calmette-Guérin instillations

Ng KL, Chua CB

Asian J Surg, 2017 Apr;40(2):163-165.

PMID: 25183290 DOI: 10.1016/j.asjsur.2014.01.016

Intravesical Bacillus Calmette-Guérin (BCG) has been a proven and effective immunotherapy treatment for superficial transitional cell carcinoma (TCC) of the bladder, especially for high-grade tumors and carcinoma in situ. Nevertheless, significant side effects are associated with BCG instillations, including fever, myalgia, malaise, dysuria, hematuria, and irritable lower urinary tract symptoms. We herein report the case of a patient who developed Reiter's syndrome following intravesical BCG instillations. A 39-year-old Chinese man presented with a 3-week history of dysuria, suprapubic pain, and pain at the tip of the penis postmicturition. Initial investigations revealed that he had microhematuria, and an ultrasound with computed tomography scan of the abdomen showed a bladder mass. Transurethral resection of the bladder tumor was performed and the patient received a single dose of intravesical mitomycin postoperatively. Results of histopathological examination revealed high-grade bladder TCC (G3pT1), and the patient was managed with intravesical BCG for 2 weeks following the surgery. Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain. Reiter's syndrome was diagnosed as a rare but known complication of BCG instillation and the BCG immunotherapy was withheld. The patient was treated with nonsteroidal antiinflammatory drugs (for back pain) and eye ointment (for conjunctivitis) and his condition improved. This case report of Reiter's syndrome should be highlighted as a rare but significant complication of BCG immunotherapy and urologists should have a high index of suspicion to diagnose this rare complication.

Matched MeSH terms: BCG Vaccine/administration & dosage; BCG Vaccine/adverse effects*

Recent advances in experimental leprosy

Rees RJ

Bibl Tuberc, 1970;26:189-232.

PMID: 4244234

Matched MeSH terms: BCG Vaccine

Pulmonary tuberculosis in a rural area of Sarawak, Malaysia

Yano K, Goto S, Sado M, Takeuchi M, Iguchi M

Southeast Asian J. Trop. Med. Public Health, 1974 Sep;5(3):417-23.

PMID: 4215145

Matched MeSH terms: BCG Vaccine

Fulltext Protective effect of a lipid-based preparation from Mycobacterium smegmatis in a murine model of progressive pulmonary tuberculosis

García Mde L, Borrero R, Lanio ME, Tirado Y, Alvarez N, Puig A, et al.

Biomed Res Int, 2014;2014:273129.

PMID: 25548767 DOI: 10.1155/2014/273129

A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.

Matched MeSH terms: BCG Vaccine/administration & dosage; BCG Vaccine/immunology

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