Tuesday, March 5, 2019

DTP associated with 2-10 times increased mortality in African babies

The following blog post is about something so unbelievable and so terrible it kept me awake most of last night.  Here it is: "All currently available evidence suggests that DTP vaccine may kill more children from other causes than it saves from diphtheria, tetanus or pertussis."  A highly respected group of Danish researchers say this after studying the results of vaccinations for many years.  

This group of Danish physicians and scientists has been studying vaccines in a center in Guinea Bissau, Africa (and sometimes in other places) since 1979.  Their work is widely published and has not been subject to significant criticism of any kind.

What they have found, in a series of different studies going back 15 years, is that vaccinating young infants with DTP increases the likelihood of early death from 2 to 10 times expected.  (Different numbers came up in different studies, but each study found at least a doubling of mortality related to DTP).  The researchers have looked at this in a variety of ways, but kept getting the same answer: that DTP is associated with significantly increased death rates.  They propose that the reason may be that the vaccine makes babies more susceptible to other infections (other than Diptheria, Tetanus and Pertussis) than they would be otherwise.

The researchers are so convinced of this effect they asked WHO to study it further and change the international program to vaccinate with DTP.  The WHO's Strategic Advisory Group of Experts did not dispute their data, and agreed that randomized trials of DPT needed to be done.  But then a decision was made not to do such trials. 

I have previously blogged on Peter Aaby's group's finding of a negative effect on mortality of DTP vaccine.  Here, below, are the group's recent (2017) findings.  (They have additionally found that live polio vaccines, in contrast to killed DPT vaccines, reduce childhood mortality rates, but not nearly so strongly as the DPT seems to increase them.)  Please excuse the confusing jargon and abbreviations, which are explained below. 

"4.3. Comparison with Previous Studies of DTP and OPV 

There is only one other study of the introduction of DTP. In rural Guinea-Bissau, DTP (±OPV) was associated with 2-fold higher mortality (Aaby et al., 2004a). All studies that documented vaccination status and followed children prospectively indicate that DTP has negative effects; a meta-analysis of the eight studies found 2-fold higher mortality for DTP-vaccinated compared with DTP-unvaccinated, mostly BCG-vaccinated controls (Aaby et al., 2016) (Appendix A). 

The negative effect of DTP was much worse in this natural experiment than has been reported in previous studies of DTP. This is presumably due to the “unvaccinated” control children in previous studies having been a frail subgroup too frail to get vaccinated. Previous studies have not been able to compare DTP-vaccinated children with “normal” controls. Hence, most previous studies have probably underestimated the negative effect of DTP. 

The potentially differential effects of DTP and OPV have only been examined in few studies. However, we have recently been able to document marked beneficial NSEs of OPV. In an RCT, OPV at birth (OPV0) reduced infant mortality by 32% (0–57%) before the children received campaign-OPV (Lund et al., 2015). In Bissau campaign-OPV reduced the mortality rate by 19% (5–32%) (submitted). When DTP was missing for several months in Bissau, we showed that the all-cause case-fatality at the pediatric ward was 3-fold lower if the children had OPV-only as their most recent vaccination rather than the recommended combination of DTP and OPV (Aaby et al., 2004b). Thus, OPV may have modified the negative effect of DTP. 

This pattern was also seen when DTP was first introduced in the rural areas of Guinea-Bissau in 1984 (Aaby et al., 2004a). OPV was not used the first year and the HR for DTP versus unvaccinated was 5.00 (0.63–39.7). In the period from 1985 to 1987, when DTP and OPV were nearly always administered together, the MRR was 1.90 (0.91– 3.97). In the present study, the hazard ratio was 10.0 (2.61–38.6) for DTP-only but 3.52 (0.96–12.9) for children who received DTP and OPV simultaneously (Table 3). Based on these two studies of the introduction of DTP, the HR compared with DTP-unvaccinated children was significantly different for children who had received DTP-only (HR = 8.14 (2.63–15.2)) and for children who received both DTP and OPV (HR = 2.21 (1.16–4.19)) (test of interaction, p = 0.049). Hence, simultaneous administration of DTP and OPV may have alleviated the negative nonspecific effect of DTP.

5. Conclusions 

DTP was associated with 5-fold higher mortality than being unvaccinated. No prospective study has shown beneficial survival effects of DTP. Unfortunately, DTP is the most widely used vaccine, and the proportion who receives DTP3 is used globally as an indicator of the performance of national vaccination programs. 

It should be of concern that the effect of routine vaccinations on all cause mortality was not tested in randomized trials. 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. 

The recently published SAGE review called for randomized trials of DTP (Higgins et al., 2014). However, at the same time the IVIR-AC committee to which SAGE delegated the follow-up studies of the NSEs of vaccines has indicated that it will not be possible to examine the effect of DTP in an unbiased way. If that decision by IVIR-AC remains unchallenged, the present study may remain the closest we will ever come to a RCT of the NSEs of DTP."

BCG: tuberculosis vaccine
HR: hazard ratio: how much more likely an event is in one situation than in another being compared
IVIR-AC: Immunization and Vaccines-Related Implementation Research Advisory Committee of the World Health Organization
MRR: mean reciprocal rank: see en.wikipedia.org/wiki/Mean_reciprocal_rank
NSE: non-specific effect: a result of a vaccine which is not specifically related to what the vaccine is supposed to be doing
OPV: Oral polio vaccine
RCT: randomized controlled trials

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