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Bacille Calmette-Guerin-BCG

Interacting, Nonspecific, Immunological Effects of Bacille Calmette-Guérin and Tetanus-diphtheria-pertussis Inactivated Polio Vaccinations: An Explorative, Randomized Trial
Published: 2020
SYNOPSIS

The data indicated non-live vaccines like Tdap are immunosuppressive. It could mean each non-live vaccine administered could defeat the benefits of all previously administered vaccines. And of course, the general immunosuppressive effect means the person is more susceptible to all pathogens except the ones the vaccine is intended to protect.

CITATION
Blok BA, de Bree LCJ, Diavatopoulos DA, Langereis JD, Joosten LAB, Aaby P, van Crevel R, Benn CS, Netea MG. Interacting, Nonspecific, Immunological Effects of Bacille Calmette-Guérin and Tetanus-diphtheria-pertussis Inactivated Polio Vaccinations: An Explorative, Randomized Trial. Clin Infect Dis. 2020 Jan 16;70(3):455-463. doi: 10.1093/cid/ciz246. PMID: 30919883.
SUMMARY

Certain vaccines, such as Bacille Calmette-Guérin (BCG), have nonspecific effects, which modulate innate immune responses and lead to protection against mortality from unrelated infections (trained immunity). In contrast, in spite of the disease-specific effects, an enhanced overall mortality has been described after diphtheria-tetanus-pertussis (DTP) vaccination in females. This randomized trial aimed to investigate the nonspecific immunological effects of BCG and DTP-containing vaccines on the immune response to unrelated pathogens. The trial results showed Tdap vaccination led to short-term potentiation and long-term repression of monocyte-derived cytokine responses, and short-term as well as long-term repression of T-cell reactivity to unrelated pathogens. BCG led to short-term and long-term potentiation of monocyte-derived cytokine responses. When given together with Tdap or after Tdap, BCG abrogated the immunosuppressive effects of Tdap vaccination.

The data indicated non-live vaccines like Tdap are immunosuppressive. It could mean each non-live vaccine administered could defeat the benefits of all previously administered vaccines. And of course, the general immunosuppressive effect means the person is more susceptible to all pathogens except the ones the vaccine is intended to protect.

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Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality? A meta-analysis testing the hypotheses of sex-differential non-specific effects of DTP vaccine.
Published: 2016
SYNOPSIS

In seven studies of BCG-vaccinated children, DTP vaccination was associated with a 2.54 (95% Cl 1.68- 3.86) increase in mortality in girls (with no increase in boys [ratio 0.96, 0.55-1.68]). The ways in which the female and the male immune systems may respond differently to vaccinations in infants are only beginning to be studied.

CITATION

Peter Aaby, Henrik Ravn, Ane B. Fisker, Amabelia Rodrigues, and Christine S. Benn; Transactions of the Royal Society of Tropical Medicine and Hygiene. 2016 Dec; 110(10): 570–581.doi: 10.1093/trstmh/trw073.

SUMMARY

Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG (bacille Calmette-Guerin, is a vaccine for tuberculosis), DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review by WHO found no convincing evidence that DTP increases mortality in females. Now, ten years later, we have tested the two hypotheses using studies from before, but also those published since formulation of the hypotheses. All studies published after the formulation of the hypotheses of the association of DTP with increased mortality.

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Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial.
Published: 2012
SYNOPSIS

Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality.

CITATION

Aaby P, Ravn H, Roth A, Rodrigues A, Lisse IM, Diness BR, Lausch KR, Lund N, Rasmussen J, Biering-Sorensen S, Whittle H, Benn CS. Archives of Disease in Childhood. 2012 Aug;97(8):685-91. doi: 10.1136/archdischild-2011-300646. Epub 2012 Feb 13.

SUMMARY

Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants and found, surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.

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Evaluation of non-specific effects of infant immunization on early infant mortality in southern Indian population.
Published: 2005
SYNOPSIS

Among girls, those who received both BCG and DTP experienced higher mortality than those who received only one of the two vaccines (hazards ratio 2.4; 95% confidence interval 1.2-5.0).

CITATION

Moulton LH, Rahmathullah L, Halsey NA, Thulasiraj RD, Katz J, Tielsch JM. Tropical Medicine and International Health, 2005 Oct;10(10):947-55.

SUMMARY

In a study of children under 2 years of age in Guinea-Bissau, Kristensen et al. (2000) found immunization with Bacille Calmette Guerin (BCG) vaccine to be associated with lower mortality, but stated that oral polio vaccine (OPV) and diphtheria, tetanus, polio (DTP) vaccines were associated with higher mortality. More recently, it has been suggested that this effect may be gender-specific, existing primarily among girls. This evaluation, focused on relating timing of BCG and DTP vaccine receipt to mortality from 1 week to 6 months of age, with emphasis on gender differentials found that girls that received both BCG and DTP experienced higher mortality than those who received only one of the two vaccines.

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The introduction of diphtheria-tetanus-pertussis vaccine and child mortality in rural Guinea­Bissau: an observational study.
Published: 2004
SYNOPSIS

The MR (mortality rate) was 1.81 (95% Cl: 0.95, 3.45) for the first dose of DTP and 4.36 (95% Cl: 1.28, 14.9) for the second and third dose

CITATION

Aaby P, Jensen H, Gomes J, Fernandes M, Lisse IM. International Journal of Epidemiology. 2004 Apr;33(2):374-80.

SUMMARY

Prior to the introduction of vaccines, children who were absent at a village examination had the same mortality as children who were present. During 1984-1987, children receiving DTP at 2-8 months of age had higher mortality over the next 6 months, the mortality rate ratio (MR) being 1.92 (95% CI: 1.04, 3.52) compared with DTP-unvaccinated children, adjusting for age, sex, season, period, BCG, and region. The MR was 1.81 (95% CI: 0.95, 3.45) for the first dose of DTP and 4.36 (95% CI: 1.28, 14.9) for the second and third dose. BCG was associated with slightly lower mortality (MR = 0.63, 95% CI: 0.30, 1.33), the MR for DTP and BCG being significantly inversed. Researchers found in low-income countries with high mortality, DTP as the last vaccine received may be associated with slightly increased mortality. Since the pattern was inversed for BCG, the effect is unlikely to be due to higher-risk children having received vaccination. The role of DTP in high mortality areas needs to be clarified.

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Routine vaccinations and child survival: follow up study in Guinea Bissau, West Africa.
Published: 2000
SYNOPSIS

One dose of diphtheria, tetanus, and pertussis vaccine was associated with a mortality ratio of 1.84 (1.10 to 3.10) and two to three doses with a ratio of 1.38 (0.73 to 2.61) compared with children who had received no dose of these vaccines.”

CITATION

Kristensen I, Aaby P, Jensen H. British Medical Journal. 2000 Dec 9;321(7274):1435-8.

SUMMARY

Research on vaccines in developing countries recommended by the World Health Organization has emphasised serological responses and protection against specific diseases. The aim of the research has been to optimise vaccine schedules for control, elimination, or eradication of disease. In modelling exercises, vaccination against diphtheria, pertussis, tetanus, and polio has been assumed to save 1.5­2.0% of the children in areas with high infant mortality. However, these assumptions are not supported by data. Mortality was lower in the group vaccinated with any vaccine compared with those not vaccinated, however, recipients of one dose of diphtheria, tetanus, and pertussis or polio vaccines had higher mortality than children who had received none of these vaccines.

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