The current EPI (Expanded Programme on Immunization) vaccines do not specifically target the organisms that lead to the two main causes of death in children - pneumonia and diarrhoea. This implies that the EPI vaccines will have only a modest effect on total child mortality. However, recent evidence suggests that measles and BCG vaccines dramatically reduce child mortality through nonspecific effects - that is, they reduce mortality from many causes, not just measles and tuberculosis. The combination of BCG at birth and measles vaccine at 6 months probably reduces total mortality to about one-third of its previous level. This means that immunization must now have the very highest priority. If we could improve immunization in Papua New Guinea so that all children received BCG, measles, diphtheria-pertussis-tetanus and polio vaccines, we would reduce child mortality from 120 to approximately 52 per 1000 livebirths - a truly spectacular reduction. The old polysaccharide pneumococcal vaccine is safe and effective and bulk purchases are likely to cost US$1 a dose or less. Further studies are needed of the effects of pneumococcal vaccine. Immunization of mothers and babies might reduce child mortality by 20%, at a cost of only US$83 per life saved. The available evidence suggests that one dose of pneumococcal vaccine given to every Papua New Guinean over 5 years of age every 5 years would save approximately 6600 lives a year and the vaccine would cost only US$121 per life saved. It will not be easy to achieve high immunization rates throughout Papua New Guinea. Vaccines will have to be given the highest possible priority, with curative medical services secondary to immunization. Health workers, government, the general population and overseas donors will have to be convinced of the very great benefits that will come from effective immunization. A sustained education campaign will be needed in addition to the establishment of an effective delivery system. The time has come for a radical shift in emphasis in Papua New Guinea: from hospitalization to immunization.
BCG Vaccine - therapeutic use ; Bacterial Vaccines - therapeutic use ; Immunization - economics ; Infant Mortality ; Papua New Guinea ; Pneumococcal Vaccines - therapeutic use

Animals ; BCG Vaccine ; Immunosuppressive Agents ; therapeutic use ; Lipopolysaccharides ; Liver Failure ; chemically induced ; prevention & control ; Male ; Mice ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use

BACKGROUNDBladder cancer is widely known as the most common malignant tumor in the urinary tract, with 75%-85% of patients suffering from nonmuscle invasive bladder cancer (NMIBC). However, the optimal dose of Bacillus Calmette-Guérin (BCG) remains controversial. The aim of this study was to compare the therapeutic efficacy of full dose (FD) with the reduced dose (RD) of BCG.

METHODSRandomized controlled trials (RCTs) were selected through the Cochrane Library, PubMed and Embase and were supplemented by hand searching of bibliographies. The end points include overall survival rate, recurrence rate, progression rate and side effects.

RESULTSFive RCTs that included a total of 1 473 patients (727 in the reduced dose group vs 746 in the full dose group), with a median follow-up period from 33.5 month to 7.1 year. Disease in 80 of 687 (11.6%) patients assigned to the RD group progress to the muscular layer or distant metastasis, compared with 81 of 698 (11.6%) patients assigned to the FD group (RR = 1.02; 95% CI, 0.77-1.36; P = 0.89). The incidence of recurrence at three year was reported in all five studies to be 41.1% (299 of 727) and 36.1% (269 of 746) in the RD and FD groups, respectively (RR = 1.13; 95% CI, 1.00-1.29; P = 0.05). The 5-year survival rate was 75.9% (502 of 662) in the RD group, and 75.8% (510 of 673) in the FD group. In the RD group 41 of 655 (6.3%) patients and 56 of 663 (8.7%) patients in the FD group did not complete the treatment due to systemic or local side effects (RR = 0.75; 95% CI, 0.51-1.10; P = 0.14) CONCLUSIONS: In general, the results of our study demonstrate a trend towards a reduction of the toxicity in reduced dose group without affecting the efficacy of treatment when compared with full dose. More trials with large sample size are still necessary to explore the prognosis of the patients with high risk of tumor in different dose group.

BCG Vaccine ; therapeutic use ; Female ; Humans ; Male ; Neoplasm Recurrence, Local ; prevention & control ; Randomized Controlled Trials as Topic ; Urinary Bladder Neoplasms ; prevention & control

This study was purposed to explore the anti-leukemia effect of bacillus calmette-guerin vaccine (BCG) on the human myeloid leukemia cell xenograft models. An animal model was established by inoculating the human myeloid leukemia HL-60 cells into the BALB/c (8 - 10 weeks of age) nude mice. The mice were randomly divided into two groups: control group and experimental group. Nude mice in control group were injected with physiological saline, while those of experimental group were given BCG and inactivated BCG respectively. The tumor growth was assayed by using caliper. The survival time of nude mice was determined. Necrotic extent and morphological changes of tumor were observed and examined by HE staining and immunohistochemical method. The results indicated that on 5th-7th days after tumor inoculated, 2 - 3 mm tumor mass could be observed. The tumor volume increased over the time. HE staining of tumor tissues showed that there were different degrees of tumor necrosis in BCG group and inactivated BCG group. Immunohistochemistry results demonstrated that CD20 positive cells were obviously observed in the necrotic area of BCG group, compared with the control group and inactivated BCG group. It is concluded that human myeloid leukemia HL-60 cells have been successfully transplanted in nude mice, and the systemic metastasis occurs along with the prolongation of time. BCG inoculation can delay the tumor growth and prolong the survival time of nude mice with leukemia, suggesting that BCG has an antitumor effect.
Animals ; BCG Vaccine ; therapeutic use ; HL-60 Cells ; Humans ; Leukemia, Myeloid ; therapy ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays

OBJECTIVETo study the prevalence of skin positivity to purified protein derivative (PPD) in human immunodeficiency virus (HIV)-infected patients in Hong Kong.

METHODSConsecutive clients of an HIV clinic were administered the PPD test and 2 units of PPD-RT23 were used. The area of induration was then measured in 48 to 72 h. Results were related to patient characteristics and HIV-related parameters.

RESULTSEight (17.0%) out of 47 clients tested positive to the administration of 2 units of PPD-RT23. If the cutoff were raised to 10 mm according to current practice, only two (4.3%) would test positive.

CONCLUSIONThe prevalence of PPD positivity in HIV-infected patients in Hong Kong is 17%, when a cutoff of 5 mm is used. This figure may form the basis for further studies on the utility of isoniazid preventive therapy in this group of patients.

Adult ; Aged ; BCG Vaccine ; immunology ; Female ; HIV Infections ; complications ; immunology ; Humans ; Isoniazid ; therapeutic use ; Male ; Middle Aged ; Prevalence ; Tuberculin Test ; Tuberculosis ; prevention & control

OBJECTIVEPrevious studies have shown that bacillus calmette-guerin (BCG) can deviate TH2 response toward TH1 response, resulting in a suppressive effect on the development of asthma/atopy. This study examined the effect of BCG treatment on regulatory T cells in asthmatic mice to investigate the possible mechanism.

METHODSKunming mice were sensitized and challenged with ovalbumin (OVA) to establish asthmatic models. Asthmatic mice were injected intradermally with BCG five days before and after sensitization. After 24 hrs of last challenge, bronchoaveolar lavage fluid (BALF) and peripheral blood were collected . The total cells and eosinophils were counted in the BALF. The percentage of CD4(+) CD25(+) in peripheral blood was detected with flow cytometry. Single spleen cell suspension was prepared and cultured in 1640 medium for 48 hrs and then the cytokine IL-10 level in the supernatant was determined using ELISA. The mice which were challenged with normal saline were used as the Normal control group.

RESULTSThe number of total cells and eosinophils in BALF in asthmatic mice [(27.27 +/- 5.36) x 10(7)/L and (6.59 +/- 1.32) x 10(7)/L respectively] were more than in the Normal control group [(1.52 +/- 0.36) x 10(7)/L and zero respectively] (P < 0.01). The number of total cells and eosinophils in BALF in asthmatic mice were reduced after BCG treatment [(13.71 +/- 3.17) x 10(7)/L and (1.43 +/- 0.37) x 10(7)/L respectively] (P < 0.01). The percentage of CD4(+) CD25(+) in peripheral blood of asthmatic mice [(11.59 +/- 1.33)%] was noticeably lower than that of the Control group [(13.66 +/- 1.68)%] (P < 0.01), but increased significantly in asthmatic mice after BCG treatment [(14.40 +/- 2.70)%] (P < 0.05). The IL-10 level in spleen cell supernatant in the BCG-treated group (7.79 +/- 1.34 pg/mL) also increased compared with that in the untreated asthmatic mice (5.54 +/- 0.66 pg/mL) (P < 0.01).

CONCLUSIONSBCG can markedly inhibit the airway inflammation in asthmatic mice possibly by promoting the production of regulatory T cells.

Animals ; Asthma ; immunology ; therapy ; BCG Vaccine ; therapeutic use ; Bronchoalveolar Lavage Fluid ; cytology ; Interleukin-10 ; analysis ; physiology ; Male ; Mice ; T-Lymphocytes, Regulatory ; immunology ; Toll-Like Receptor 2 ; physiology

OBJECTIVE: To investigate the efficacy and safety of polysaccharide nucleic acid-fraction (BCG-PSN) in the treatment of vasomotor rhinitis. METHOD: Sixty patients were randomly divided into BCG-PSN group (n = 30) and control group (n = 30). The patients in BCG-PSN group were administered with BCG-PSN 1.0 mg twice a week for two months, and intranasal azelastine was used if needed. The patients in control group were administered with intranasal azelastine solely twice a day, which could be decreased with the symptom relief. Follow-up was 6 months. Symptom and medication scores were recorded. Side effects were registered. RESULT: The symptom and medication scores of BCG-PSN group were significantly lower than that of control group (P < 0.01) after BCG-PSN treatment. There was no significant difference in symptom score between the two groups at 6 months after BCG-PSN treatment (P > 0.05), while the medication score of BCG-PSN group was still much lower than that of control group (P < 0.01). No serious adverse events were reported in BCG-PSN group except for local pain on the injection place in one patient. CONCLUSION BCG-PSN is effective and safe in the treatment of vasomotor rhinitis.
Adolescent ; Adult ; BCG Vaccine ; adverse effects ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Rhinitis, Vasomotor ; drug therapy ; Single-Blind Method ; Young Adult

OBJECTIVETo evaluate the effect and safety of BCG vaccine on initially treated pulmonary tuberculosis and its controlling effect on multidrug-resistant tuberculosis.

METHODSAll 360 volunteers with initially treated pulmonary tuberculosis of positive smear and culture were divided into immunotherapy group (180 cases, also BCG group) and control group (180 cases) at random pair. The patients in BCG group were treated with chemotherapy of a regimen of 2HRZ/2HR and immunotherapy with BCG for 4 months,and the first BCG vaccine was given a month after chemotherapy. Meanwhile, the patients in the control group were treated with chemotherapy of 2HRZ/4HR only.

RESULTS(1) The negative conversion rate of sputum smear in BCG group was 98.3% (177/180), and it was 97.2% (175/180) in control group. There was no significant difference between the two groups both at the ends of 4 and 6 months after treatment (chi2 = 0.1278, P > 0.05). (2) The positive conversion rate of sputum smear in BCG group was 2.3% (4/177), and it was 6.9% (12/175) in control group followed up for 5 years. The successful rate was 96.1% (173/180) in BCG group, and it was significantly higher than that of 90.6% (163/180) in control group (chi2 = 4.4643, P < 0.05). (3) In the 5-year follow up, bacteriologic result was similar to that of X-ray. (4) The occurrence rate of multidrug-resistant tuberculosis was 2.3% (4/177) in BCG group,significantly lower than that of 7.3% (13/178) in the control group (chi2 = 4.9513, P < 0.05).

CONCLUSIONAs an adjunct chemotherapy,immunotherapy with BCG vaccine should be helpful for patients with initially treated pulmonary tuberculosis. It would further strengthen the effects of chemotherapy and reduce the occurrence rate of multidrug-resistant tuberculosis.

Adjuvants, Immunologic ; therapeutic use ; Adolescent ; Adult ; Aged ; Antitubercular Agents ; therapeutic use ; BCG Vaccine ; therapeutic use ; Child ; Female ; Follow-Up Studies ; Humans ; Immunotherapy, Active ; Male ; Middle Aged ; Tuberculosis, Multidrug-Resistant ; prevention & control ; Tuberculosis, Pulmonary ; therapy

INTRODUCTION: Usage of metformin is associated with improved survival in lung, breast and prostate cancer, and metformin has been shown to inhibit cancer cell growth and proliferation in in vitro studies. Given the lack of clinical data on metformin use in patients with bladder cancer, we aimed to evaluate the role of metformin in their oncological outcomes. METHODS: Medication use data from a prospectively maintained database of 122 patients with non-muscle-invasive bladder cancer treated with intravesical Bacille Calmette-Guerin (BCG), who were recruited under a randomised, double-blinded, controlled clinical trial, was collected and analysed. Kaplan-Meier curves were used to assess overall survival (OS) and disease-specific survival (DSS). RESULTS: At a median follow-up duration of 102 (range 3-357) months, 53 (43.4%) patients experienced disease recurrence and 21 (17.2%) experienced disease progression. There was no significant difference in mortality between patients with and without diabetes mellitus. There was significant difference in OS between patients without diabetes mellitus, patients with diabetes mellitus on metformin and patients with diabetes mellitus but not on metformin (p = 0.033); patients with diabetes mellitus on metformin had the best prognosis. Metformin use was associated with significantly lower DSS (p = 0.042). Other oral hypoglycaemic agents, insulin or statins were not associated with disease recurrence or progression. CONCLUSION Metformin use was associated with improved oncological outcomes in patients with non-muscle-invasive bladder cancer treated with intravesical BCG. Prospective studies with larger patient populations are needed to validate the role of metformin as potential therapy for bladder cancer.
Adjuvants, Immunologic/therapeutic use* ; Administration, Intravesical ; BCG Vaccine/therapeutic use* ; Diabetes Mellitus ; Disease Progression ; Humans ; Male ; Metformin/therapeutic use* ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Prospective Studies ; Retrospective Studies ; Urinary Bladder Neoplasms/drug therapy*

Bacillus Calmette-Guérin (BCG) is a live vaccine and has the potential to cause local disease and systemic dissemination in immunocompromised hosts, including infants who are infected with human immunodeficiency virus (HIV) through vertical transmission, and patients with primary immunodeficiencies (PID) such as severe combined immunodeficiency (SCID), chronic granulomatous disease (CGD), hyper-IgM syndrome, and defects of the IL12- IFNγ axis (Mendelian susceptibility to mycobacterial diseases, MSMD). Disseminated BCG is extremely difficult to treat. The chance of complete eradication is low unless functional immune response is restored by haematopoietic stem cell transplant. Prolonged use of anti-mycobacterial drugs often causes organ toxicities and drug resistance. Inflammatory complications which develop upon immunoreconstitution post-transplant may necessitate immunosuppressive treatment, which adversely affect immune recovery and increases risks of opportunistic infections. Multiple BCG reactivations can occur in patients with CGD and MSMD, and BCG can remain latent until reactivations take place in adulthood and manifest as disease. It is important for neonatologists, general practitioners, primary care clinicians and nurses working in maternal and child care centres to be aware of BCG-related complications, which may be the first sign of an underlying immunodeficiency. As neonatal BCG is included in standard vaccination schedule in many countries, it is a challenge to identify and avoid administration of BCG to infants who potentially have PIDs. Deferring BCG vaccination is recently advocated to protect highly vulnerable populations, but the appropriate strategy is yet to be determined. Newborn screening for SCID offers a potential to avoid this complication, if an integrated system of screening and vaccination can be organised.
Adjuvants, Immunologic ; adverse effects ; therapeutic use ; BCG Vaccine ; adverse effects ; immunology ; therapeutic use ; Humans ; Immunologic Deficiency Syndromes ; diagnosis ; immunology ; Infant, Newborn ; Mycobacterium Infections ; prevention & control ; Mycobacterium bovis ; drug effects ; Neonatal Screening ; methods ; Risk Assessment ; Vaccination ; adverse effects ; methods