“Evidence suggests that DTP vaccine may kill more children from other causes than it saves from diphtheria, tetanus or pertussis.”

04-30-2013guineabissau

A nurse gives a measles vaccination to a child in Guinea-Bissau. Photo: UNICEF/Roger Lemoyne

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Study: DTP Vaccine Associated With 212% Increased Infant Mortality Risk

Posted on: Wednesday, March 15th 2017 at 12:15 pm Written By: Jefferey Jaxen

Study: DTP Vaccine Associated With Increased Infant Mortality.

A study from West Africa’s Guinea-Bissau discovered that all-cause infant mortality more than doubled after the introduction of the DTP vaccination.

(Follow the above link to read more.)

Here is the study referred to in Jeffrey Jaxen’s article.

The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine
Among Young Infants in an Urban African Community: A
Natural Experiment
Available online 1 February 2017Abstract

Background
We examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s.

What I consider to be the important points….

  • In this natural experiment vaccinated children had 5-fold higher mortality than not-yet-DTP-vaccinated children. DTP-only vaccinations were associated with higher mortality than DTP + OPV vaccinations. Hence, DTP may be associated with a negative effect on child survival.
  • Except for the measles vaccines, surprisingly few studies examined the introduction of vaccines and their impact on child survival.
  • DTP was associated with 5-fold higher mortality than being unvacci-
    nated. No prospective study has shown beneficial survival effects of
    DTP. Unfortunately, DTP is the most widely used vaccine, and the pro-
    portion who receives DTP3 is used globally as an indicator of the perfor-
    mance of national vaccination programs.
  • All currently available evidence suggests that DTP vaccine may kill more children from other causes than it saves from diphtheria, tetanus or pertussis. Though a vaccine protects children against the target disease it may simultaneously increase susceptibility to unrelated infections.

Cocooning to protect infants from pertussis

Recent studies on cocooning to protect infants from pertussis

Evaluation of the impact of a pertussis cocooning program on infant pertussis infection.

Healy CM, Rench MA, Wootton SH, Castagnini LA. 2015

Postpartum immunization and cocooning did not reduce pertussis illness in infants ≤6 months of age. Efforts should be directed toward increasing tetanus, diphtheria and acellular pertussis immunization during pregnancy, combined with cocooning, to reduce life-threatening young infant pertussis.


Impact of maternal postpartum tetanus and diphtheria toxoids and acellular pertussis immunization on infant pertussis infection. 

Castagnini LA, Healy CM, Rench MA, Wootton SH, Munoz FM, Baker CJ. 2012

It was disappointing—but not surprising, given the likelihood of contact with other pertussis-infected individuals—that we were unable to demonstrate any
impact of this program on the occurrence of pertussis in infants.


Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model

Jason M. Warfel, Lindsey I. Zimmerman, and Tod J. Merkel 2013

Consistent with these findings, seroepidemiological studies have concluded that B. pertussis circulation is still high in countries with excellent aP uptake (27, 50), and a cross-sectional study showed that postpartum aP vaccination of mothers did not reduce pertussis illness in young infants (51). These data suggest that cocooning is unlikely to be an effective strategy to reduce the burden of pertussis in infants.


The impact of parental postpartum pertussis vaccination on infection in infants: A population-based study of cocooning in Western Australia.

Carcione D, Regan AK Tracey L Mak DB, Gibbs R, Dowse GK, Bulsara M, Effler PV. 2015

There was no difference in the incidence of pertussis among infants whose parents were both vaccinated postpartum compared to those with unvaccinated parents


Cost-benefit of the introduction of new strategies for vaccination against pertussis in Spain: cocooning and pregnant vaccination strategies. 

Fernández-Cano MI, Armadans Gil L, Campins Martí M 2015

The number of parents needed to vaccinate with the cocoon strategy to prevent 1 pertussis hospitalization would be 4752 and to prevent 1 death, more than 900,000. With VPW, 1331 pregnant women would have to be vaccinated to prevent 1 hospitalization and 200,000 to prevent 1 death. The benefit-to-cost ratio was 0.04 for cocooning and 0.15 for VPW.


Finding the ‘who’ in whooping cough: vaccinated siblings are important pertussis sources in infants 6 months of age and under. 2014
Bertilone C, Wallace T, Selvey LA.

At its peak, siblings were the most important sources of pertussis in infants 6 months and younger, particularly fully vaccinated children aged 2 and 3 years. Waning immunity before the booster at 4 years may leave this age group susceptible to infection. Even if cocooning programs could achieve full vaccination coverage of parents and ensure all siblings were fully vaccinated according to national schedules, waning immunity in siblings could provide a means for ongoing transmission to infants.

Pertussis vaccine – under vaccine selection pressure? Resource page

Any cause that reduces reproductive success in a proportion of a population potentially exerts evolutionary pressure or selection pressure.With sufficient pressure, inherited traits that mitigate its effects—even if they would be deleterious in other circumstances—can become widely spread through a population – Wikipedia

A resurgence of pertussis or whooping cough has been observed in highly immunized populations. Studies have shown that there are other causes beyond increased awareness of disease, use of better diagnostic tools and improved surveillance methods. Waning vaccine-induced immunity (secondary failure) has been identified in many countries and antigenic divergence has been found between vaccine strains and clinical isolates in many countries with high vaccination coverage.

Here are the links to some studies that identify vaccine selection pressure / antigenic divergence as a cause for pertussis re emergence.

 http://www.ncbi.nlm.nih.gov/pubmed/11485646

Adaptation of Bordetella pertussis to vaccination: a cause for its reemergence?

In the Netherlands, as in many other western countries, pertussis vaccines have been used extensively for more than 40 years. Therefore, it is conceivable that vaccine-induced immunity has affected the evolution of Bordetella pertussis. Consistent with this notion, pertussis has reemerged in the Netherlands, despite high vaccination coverage. Further, a notable change in the population structure of B. pertussis was observed in the Netherlands subsequent to the introduction of vaccination in the 1950s. Finally, we observed antigenic divergence between clinical isolates and vaccine strains, in particular with respect to the surface-associated proteins pertactin and pertussis toxin. Adaptation may have allowed B. pertussis to remain endemic despite widespread vaccination and may have contributed to the reemergence of pertussis in the Netherlands.


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828859/

Antigenic Divergence between Bordetella pertussis Clinical Isolates from Moscow, Russia, and Vaccine Strains

Together with waning immunity, the antigenic divergence between vaccine strains and clinical isolates observed in the Moscow area may explain the persistence of pertussis, despite the high rates of vaccine coverage.

In the past few years, the pertussis epidemiological situation in Russia has been unfavorable. Regardless of the high rates of vaccination coverage for pertussis, we have registered an increase in the incidence of pertussis among school-aged children,  along  with  persistently  high  incidences  among  infants under 12 months of age. In addition, some cases of pertussis have been registered among vaccinated children (8, 23). Similar trends have been observed in many other countries (1, 2, 5, 6, 10). Researchers point to many reasons for the increased incidence of pertussis, including improved surveillance, waning immunity, and pathogen adaptation. The last possibility is supported by the fact that divergence in the protective antigens pertussis  toxin  (Ptx)  and  pertactin  (Prn)  has  been  observed between  vaccine  strains  and  the  strains  circulating  in  many countries


http://www.ncbi.nlm.nih.gov/pubmed/18816412

Bordetella pertussis isolates in Finland: serotype and fimbrial expression.

  1. pertussis continues  to  cause  epidemics  in  vaccinated populations  in  spite  of  high  vaccination  coverage.  As  a result  of  this  study  we  gained  more  information  of  the possible mechanisms the bacterium uses to infect highly vaccinated populations. This information is important for the future development of vaccines against pertussis.

Conclusion

Despite  extensive  vaccinations  in  Finland,  Fim2  strains were  the  most  common  serotype.  Fim3  strains  emerged since 1999 and the emergence coincided with nationwide epidemics. In a population with long-term vaccinations, Fim2 strains could express Fim3 during infection, showing a difference in fimbrial expression between in vivo and in vitro.


http://www.ncbi.nlm.nih.gov/pubmed/24757216

Global Population Structure and Evolution of Bordetella pertussis and Their Relationship with Vaccination.

Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production.

We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.


http://www.ncbi.nlm.nih.gov/pubmed/19158267

Changes in genetic diversity of the Bordetella pertussis population in the United Kingdom between 1920 and 2006 reflect vaccination coverage and emergence of a single dominant clonal type.

This supports a hypothesis that MLVA-27 is under some form of positive selection conferring increased survival in a highly vaccinated population.


http://jid.oxfordjournals.org/content/early/2014/12/08/infdis.jiu665.abstract

Genomic analysis of isolates from the UK 2012 pertussis outbreak reveals that vaccine antigen genes are unusually fast evolving

Importantly, we demonstrate that acellular vaccine  antigen encoding genes are evolving at higher rates than other surface protein encoding genes. This was true even prior to the introduction of pertussis vaccines, but has become more pronounced since the introduction of the current acellular vaccines.

The fast evolution of vaccine antigen genes has serious consequences for the ability of current vaccines to continue to control pertussis.


http://www.ncbi.nlm.nih.gov/pubmed/9453625

Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in The Netherlands: temporal trends and evidence for vaccine-driven evolution.

These results suggest that vaccination has selected for strains which are antigenically distinct from vaccine strains.

There is evidence that the incidence of pertussis is increasing in populations vaccinated with WCVs (1, 4, 5, 11, 12), and our results suggest that one of the factors which has contributed to this phenomenon may be the decline of vaccine efficacy due to antigenic shifts in the B. pertussis population. Our findings also may have implications for the efficacy of ACVs, many of which contain  both  P.69  and  pertussis  toxin  (35).


http://www.ncbi.nlm.nih.gov/pubmed/22717007

Evolution of French Bordetella pertussis and Bordetella parapertussis isolates: increase of Bordetellae not expressing pertactin.

Hence, the generalized use of wP vaccine revealed polymorphisms within the B. pertussis population because it was not able to control all the circulating isolates [13]. The wP vaccine-induced herd immunity enabled isolates, as virulent as but different from the vaccine strains, to emerge [3].

In conclusion, even though genetic rearrangements took place in the absence of human interference [28], human vaccination strategies introduced a new challenge that bacterial populations had to overcome, promoting evolution and selection among these populations. It is clearly known now that in France, wP vaccination favoured genotypic changes (PFGE IV, ptxP3, prn2, ptxA1) in the B. pertussis population [6,7], changes which could not be observed in regions of low vaccine coverage (Senegal) [21]. Gene loss (RDs) and increase in insertion sequence elements are also part of the adaptation of the B. pertussis population to its host. Whether they are influenced by vaccination should be appreciated in regions with no or very low vaccine coverage. Continuous surveillance for antigenic change in B. pertussis and B. parapertussis strains is therefore required as a tool for monitoring pertussis vaccine effectiveness.


http://www.ncbi.nlm.nih.gov/pubmed/16048777

Pathogen adaptation under imperfect vaccination: implications for pertussis.

Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination.


This is exemplified by figure 1 (bottom panel),which shows the estimated incidence in vaccinated and unvaccinated children aged 5–9 years. This panel shows
that, although the incidence in unvaccinated children (ca 4% of the population) has increased considerably since 1995, the incidence in vaccinated children (ca 96% of the population) has increased much more strongly. As a result, the incidences in the vaccinated and unvaccinated cohorts are at present not significantly different.


Waning immunity – Pertussis vaccination resource page

A resurgence of pertussis or whooping cough has been observed in highly immunized populations. Studies have shown that there are other causes beyond increased awareness of disease, use of better diagnostic tools and improved surveillance methods. Waning vaccine-induced immunity (secondary failure) has been identified in many countries. Secondary failure is when a person produces antibodies after vaccination, but the levels decline or wane over time.(Primary failure is when a person fails to make antibodies or doesn’t reach a level considered to be protective.)

Here are links to some of the studies that refer to waning immunity / secondary failure associated with the Pertussis vaccination.

http://www.ncbi.nlm.nih.gov/pubmed/23188029

Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine dose, California, 2010.

In 2010, California experienced its largest pertussis epidemic in more than 60 years; a substantial burden of disease was noted in the 7- to 10-year-old age group despite high diphtheria, tetanus, and acellular pertussis vaccine (DTaP) coverage, indicating the possibility of waning protection.

http://www.ncbi.nlm.nih.gov/pubmed/25184820

Characteristics of pertussis outbreaks in Catalonia, Spain, 1997 to 2010.

Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10-6 persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10-6 person-year) (RR = 0.78, 95% CI 0.46-1.31; P = 0.35). Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged

http://www.ncbi.nlm.nih.gov/pubmed/25560446

Duration of pertussis immunity after DTaP immunization: a meta-analysis

Pertussis incidence is increasing, possibly due to the introduction of acellular vaccines, which may have decreased the durability of immune response.

Assuming 85% vaccine efficacy, we estimated that 10% of children vaccinated with DTaP would be immune to pertussis 8.5 years after the last dose.

http://www.ncbi.nlm.nih.gov/pubmed/25621762

Effectiveness of routine and booster pertussis vaccination in children and adolescents, federal State of Brandenburg, Germany, 2002-2012.

In Germany whole-cell pertussis vaccines (wP) were rapidly replaced by high-concentration acellular pertussis-containing vaccines (aP, 3+1 doses) starting in 1995. Boosters were recommended for 9-17 year-olds (2000) and for 5-6 year-olds (2006). Pertussis incidence remains high despite rising vaccination coverage

http://www.ncbi.nlm.nih.gov/pubmed/21034823

Imperfect vaccine-induced immunity and whooping cough transmission to infants

However, by the 1970s, most people obtained immunity through vaccination rather than transmissible natural infection. With so little circulating pathogen people’s immunity wasrarely boosted, thereby creating a large pool of people susceptible to pertussis, and allowing epidemic outbreaks in the current era despite high vaccine coverage. Another potential explanation is that vaccine-driven pathogen evolution selected for a strain that can infect more quickly or symptomatically after vaccination [26].

http://www.nejm.org/doi/full/10.1056/NEJMoa1200850

Waning Protection after Fifth Dose of Acellular Pertussis Vaccine in Children

….indicating that after the fifth dose of DTaP, the odds of acquiring pertussis increased by an average of 42% per year.

CONCLUSIONS

Protection against pertussis waned during the 5 years after the fifth dose of DTaP.

http://pediatrics.aappublications.org/content/early/2013/03/06/peds.2012-1928.abstract

Waning Immunity to Pertussis Following 5 Doses of DTaP

CONCLUSIONS: This evaluation reports steady increase in risk of pertussis in the years after completion of the 5-dose DTaP series. This rise is likely attributable in part to waning immunity from DTaP vaccines. Continuing to monitor disease burden and vaccine effectiveness in fully vaccinated children in coming years will be important to assess ongoing risk as additional cohorts vaccinated solely with acellular pertussis vaccines are introduced.

http://www.ncbi.nlm.nih.gov/pubmed/25483496

Licensed pertussis vaccines in the United States.

….to review evidence that waning protection following licensed acellular pertussis vaccines have been significant factors in the widespread reappearance of pertussis.

http://www.ncbi.nlm.nih.gov/pubmed/25316461

Pertussis. A reemerging and an underreported infectious disease.

Pertussis resurgence has been observed in highly vaccinated populations of Western countries since 1990s. Poor vaccine quality, waning vaccine induced immunity, pathogen adaptation, and enhanced surveillance as well as advancements in diagnostic facilities are some of the reasons considered responsible for the increased reporting of pertussis cases.

http://www.ncbi.nlm.nih.gov/pubmed/20822735

Pertussis outbreak in northwest Ireland, January – June 2010

Epidemiological  investigations  suggest  that waning  immunity  and  the  absence  of  a  booster  dose during  the  second  year  of  life  could  have  contributed to the outbreak.

http://www.ncbi.nlm.nih.gov/pubmed/24066885

Pertussis vaccines: state-of-the-art and future trends.

Waning vaccine-induced immunity and antigenic divergence in circulating strains seem to be the major problems accounting for resurgence of pertussis.

http://www.ncbi.nlm.nih.gov/pubmed/23487373

Reduced risk of pertussis among persons ever vaccinated with whole cell pertussis vaccine compared to recipients of acellular pertussis vaccines in a large US cohort

Unexpected waning of immunity after pertussis vaccination is now well described

We found a markedly increased risk of disease associated with an entirely aP series.

http://www.ncbi.nlm.nih.gov/pubmed/23151168

Resurgence of pertussis calls for re-evaluation of pertussis animal models.

Pertussis has recently re-emerged in well-vaccinated populations most likely due to a combination of pathogen adaptation and waning of vaccine-induced pertussis immunity.

http://www.nejm.org/doi/full/10.1056/NEJMp1209051?query=TOC

Epidemic Pertussis in 2012 — The Resurgence of a Vaccine-Preventable Disease

Recent data from California also suggest waning of vaccine-induced immunity after the fifth dose of DTaP vaccine.5 Certainly the major epidemics in 2005, in 2010, and now in 2012 suggest that failure of the DTaP vaccine is a matter of serious concern.

http://www.ncbi.nlm.nih.gov/pubmed/25093268

Waning vaccine immunity in teenagers primed with whole cell and acellular pertussis vaccine: recent epidemiology.

These epidemics demonstrated a new pattern, with particularly high rates of disease among pre-adolescents and early adolescents. These high rates of pertussis coincided with the first cohorts vaccinated with purely acellular pertussis vaccine

http://www.ncbi.nlm.nih.gov/pubmed/16221076.

Are vaccination programs and isolate polymorphism linked to pertussis re-emergence?

More likely explanations for the re-emergence of pertussis include the change in the epidemiology and transmission patterns of pertussis in highly vaccinated populations, and a shift of disease from young children to adolescents and adults due to waning protective immunity.

http://www.ncbi.nlm.nih.gov/pubmed/24530743

Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy.

The recent increase in whooping cough in vaccinated populations has been attributed to waning immunity associated with the acellular vaccine.

We conclude that the cumulative data is yet insufficient to address many fundamental questions related to vaccine failure and this underscores the need for further investigation of B. pertussis immunity at the molecular level.

http://cid.oxfordjournals.org/content/54/12/1730

Unexpectedly Limited Durability of Immunity Following Acellular Pertussis Vaccination in Preadolescents in a North American Outbreak

Our unvaccinated and under-vaccinated population did not appear to contribute significantly to the increased rate of clinical pertussis. Surprisingly, the highest incidence of disease was among previously vaccinated children in the eight to twelve year age group. We sought to examine the factors that resulted in this peak.

Conclusions. Our data suggests that the current schedule of acellular pertussis vaccine doses is insufficient to prevent outbreaks of pertussis. We noted a markedly increased rate of disease from ages 8–12 years, proportionate to the interval since the last scheduled vaccine. Stable rates of testing ruled out selection bias. The possibility of earlier or more numerous booster doses of acellular pertussis vaccine either as part of routine immunization or for outbreak control should be entertained.