Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

OBJECTIVES:  To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. DESIGN:  Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. STUDY ELIGIBILITY CRITERIA:  Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. DATA SOURCES:  Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. RESULTS:  Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. CONCLUSIONS:  Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.

Immune response modulation to DPT vaccine by aqueous extract of Withania somnifera in experimental system.

Immunopotentiation on oral feeding of standardized aqueous extract of Withania somnifera (Linn. Dunal, Family Solanaceae) was evaluated in laboratory animals immunized with DPT (Diphtheria, Pertussis, Tetanus) vaccine. The immunostimulation was evaluated using serological and hematological parameters. Treatment of immunized animals with test material (100 mg/kg/day) for 15 days resulted in significant increase of antibody titers to B. pertussis (P=0.000007). Immunized animals (treated and untreated) were challenged with B. pertussis 18,323 strain and the animals were observed for 14 days. Results indicate that the treated animals did show significant increase in antibody titers as compared to untreated animals after challenge (P=0.000003). Immunoprotection against intracerebral challenge of live B. pertussis cells was evaluated based on degree of sickness, paralysis and subsequent death. Reduced mortality accompanied with overall improved health status was observed in treated animals after intracerebral challenge of B. pertussis indicating development of protective immune response. Present study indicates application of the test material as potential immunopotentiating agent possible applications in immunochemical industry. The test material also offers direct therapeutic benefits resulting in reduced morbidity and mortality of experimental animals.