Author reply to response from Drs Phadke and Pramila

6 February 2013

We thank the doctors Phadke and Pramila for their response to our article.

They raise 4 points which I will address individually

a) Disease burden in the population.
We have stated that the Minz study has found that the under five incidence of Hib meningitis is 7.1/100,000 children under 5.
We said that if we immunize the birth cohort in one year (of 25 million babies) we can expect to prevent about 1750 cases of Hib meningitis each year. (Total 8750 in 5 years.) In this we assume deaths are prevented uniformly over the 5 years. However this is not strictly true because more cases are prevented in the first year. We have not bothered to differentiate the deaths in each year because we were looking at the final number of lives saved over 5 years and total lives saved each year by vaccinating the birth cohort in one year.

The correspondents acknowledge that we have quoted the Minz study accurately but they then go on to confuse the issue saying that the incidence of Hib meningitis is 32/100,000 in the first year and less in subsequent years. To prevent an additional 32/100,000 in the next year they need to vaccinate a second birth cohort. In 5 years they have to vaccinate 100 million babies.

When 25 million are vaccinated 7/100,000 cases of Hib meningitis are prevented each year. If 100 million are vaccinated we can expect to prevent 7 X 5 = 35/100,000 cases of Hib meningitis. This is akin to what they report 32/100,000 cases prevented. We hope the correspondents will appreciate that to get to the figure they quote, they have a five fold increase in numbers of babies vaccinated and resultant costs.

Later in the paragraph they state "If we consider all cases of possible meningitis, the annual incidence for below 1 year is reported to be 357 per 100,000"; as if Hib vaccine can prevent all forms of meningitis. There is little evidence for this in literature.

The correspondents point out correctly that we did not consider deaths from Hib pneumonia prevented. The incidence of pneumonia is some 10 times higher than the incidence of meningitis but the mortality from pneumonia is very much lower. According to this study ( pneumonia deaths in Vellore was only 0.77%. The total deaths (pneumonia and meningitis) may be double the figure for meningitis alone but not much higher. This is why most people rely on more easily confirmed figures of Hib meningitis.

Finally the authors point out again that Hib is difficult to culture and so data we have from cultures is unreliable. This was the very argument used to do the 'Probe studies'(which did not need culture proof) in Indonesia and Bangladesh. It will be remembered that the vaccine did not significantly reduce incidence of meningitis or pneumonia there.

b) Safety and efficacy of the vaccine.
We used information obtained from the Government under the Right to Information act 2005, that 5 children had died in the first 6 months when about 40,000 children were vaccinated. The correspondent reports the number of doses of vaccine used, without reporting how many children were vaccinated in the whole year. This is statistically less useful as a denominator. Also they suggest that 12 children have died. However this report says the Government thinks there were at least 15 deaths not 12. (

c) Cost effectiveness and sustainability.
The correspondent states that the NTAGI did not mean to look at the deaths from the vaccine before rolling out to other states. The correspondents are wrong in this. The intention of the NTAGI is clearly stated in the minutes of the meeting and so it needs no further elaboration.

d) Logistic and administrative issues
The authors have suggested that the cost effectiveness model used by Gupta et al must be accepted. As we have not made any reference to this cost calculation nor have we read this paper, we are not in a position to comment.

In summary
Vaccines are given to a large number of health children to prevent disease and deaths. A vaccine that itself causes deaths is not acceptable (especially given that Hib infection responds to antibiotic treatment). Pentavalent vaccine, as a combined vaccine (DPT + Hepatitis B + Hib) was introduced to as a means to increase the uptake of Hib and Hepatitis B vaccine by piggy backing it on the routinely used DPT vaccine. (
As such, it is being pushed in developing countries.

It seems to cause an unacceptably high incidence of hypersensitivity reactions and deaths. The deaths in Vietnam are said to be at least 6 in 2 months. (

The correspondents state that it is important to note that causality could not be established in many of these deaths.

Often when such hypersensitivity deaths occur, the vials are sent for laboratory testing and if no contaminant is found, it is reported that the vaccine was not at fault. This is a negation of the Brighton Classification of adverse events following immunization (AEFI). If a death follows immunization and there is no other adequate reason for the death, it must be presumed that the death was probably due to the vaccine.

I am sure that the correspondents will want these deaths in India and neighboring countries investigated using the Brighton Classification and we must continue the immunization programme only if it is safe.

Competing interests: None declared

Jacob Puliyel, Pediatrician

St Stephens Hospital, Delhi

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