Q. It is felt by some workers that measles vaccine should be administered at 9-15 months with revaccination at 12 years of age. In India, is it necessary or not to go in for measles revaccination at 12 years of age?

C.R. Dass,
Consultant Pediatrician,
Children's Clinic,
3-6-216/5, Boosareddyguda,
West Marredpalli,
Secunderabad 26, India.

A. Under the Government's universal immunization program (UIP), one dose of measles vaccine is to be given free of charge to all infants at, or as soon as possible after, 9 months of age. The Immunization Committee of the Indian Academy of Pediatrics (lAP) has endorsed this dose of vaccine and its timing, but we also recommend a further dose of measles, mumps, rubella vaccine (MMR) to be given at 15-18 months for those who can afford to pay for it. Although such children will get 2 doses of measles vaccine in this manner, in effect the net result will be no better than that of giving one dose at 15-18 months, but with the added advantage of protection against measles during the interval of 9 months of age to 15-18 months.

Is there a need to give yet another dose of measles vaccine at an older age (measles revaccination as put in the question), as is practiced in. several western nations? For example, in the United States of America one dose of MMR is given at 12-15 months and a second dose of MMR at 4-6 years of age or at 11-12 years. Why do they give a second dose of measles vaccine? Measles vaccine is highly efficacious and induces seroconversion in some 98% or more children if the vaccine is given at about 15 months of age or later. After introducing measles immunization (as one dose) in the US, the incidence of disease declined rapidly, but later on outbreaks of measles began occurring in different regions at periodic intervals. The average age at which measles occurred in such outbreaks was higher than before. In the pre-immunization era measles outbreaks did not occur in high school and university age groups, but now in the post-immunization outbreaks these were the age groups which were affected predominantly. Those who developed measles belonged to 3 categories in terms of immunization and immunity. Some children had not received any measles Vaccine. Since high immunization coverage had drastically reduced the circulation of measles virus (evidenced by very low incidence of measles), these unimmunized children had not encountered measles virus, and had remained susceptible. Some children had received measles vaccine but presumbaly had not responded; such non-response is called primary vaccine failure. If vaccine is given at 9 months the primary failure rate would be about 5-10%, at 12 months it would be below 5% and at 15 months it would be below 2%. The third category of children were those who had received and responded to the measles vaccine but had subsequently lost their protective immunity over the next several years and had once again become susceptible; this represents secondary vaccine failure. The younger the age at vaccination, the higher the frequency of secondary failure. Once susceptible children had accumulated through these three routes to large enough numbers to sustain the rapid transmission of measles virus among them, and once measles virus was introduced among them, an outbreak would ensure. After this sequence of events became clear, the logical step to prevent such outbreaks was to give a second dose of measles vaccine to as many children as possible; thus the second dose was recommended at school entry (4-6 years) or at 11-12 years.

We have not yet had such post-immunization measles outbreaks in older children in India. On the other hand, there are several pediatricians among us who anecdotally claim to have seen measles in immunized but still young children (indicating that measles virus is still circulating and also that the vaccine failure is predominantly primary, not secondary). As we give 'immunization at 9 months, this is not surprising. Primary vaccine failure would be much less frequent among those who receive the additional MMR at 15-18 months.

So, what problem are we addressing by examining the need for a second dose at school entry or later? Will outbreaks of measles occur in India in spite of routine immunization with measles vaccine under the universal immunization program, supplemented with another dose (of MMR) in a small proportion of young children? If we go by the experience of other countries we must anticipate such outbreaks as well as an upward shift in the age of illness. That such outbreaks will occur is certain, but when the first one will occur and how large it will be are unpredictable without sufficient data to estimate the magnitude of the susceptible population. Such data must be collected in two ways. First, we urgently need a clinical measles case surveillance in all geographic communities in India. The epidemiological features of clinical measles will give us information on the presence or absence of measles virus circulation in all communities, rural and urban. Such data must be supplemented with well designed studies on the seroimmunity profile of selected samples of children and adolescents in order to estimate the size of the pool of susceptibles. In the absence of such data the health policy planners will remain oblivious of the high probability of such resurgence of measles, but will wake up to the unpleasant reality only after the occurrence of the first such outbreak. Our nation does not have a clear vision or policy on these matters and international agencies who should be concerned with them are currently preoccupied with other matters.

It would be easy enough to make an arm chair recommendation to give. a second dose of measles vaccine or MMR to school age children to protect them from measles when such outbreaks will occur. However, such a recommendation will have social consequences, such as a general demand for a second dose by families who may not be able to afford it easily. Without data on the extent of measles virus circulation reinforcing immunity, if any, and on the magnitude of the susceptible population by their age, it is not possible to make a responsible recommendation in this regard. In other words, the additional cost of measles revaccination cannot be justified at the present time, in spite of the fact that such a dose will not do harm. If a small proportion of children in the community do get revaccination, it will not prevent future outbreaks either. The Immunization Committee of lAP has yet to discuss these issues, but pending the committee's decision, my personal view is to watch the scene carefully and to revaccinate older children as soon as we recognize the end of the measles immunization "honey moon" period of low incidence and as we enter the phase of resurgence.

T. Jacob John,
Chairman Immunization Committee and President Elect,
Indian Academy of Pediatrics,
Thekkekara, 2/91 E2,
Kamalakshipuram,
Vellore 632002, India.

Vaccination against Polio, Diphtheria, Tetanus, Whooping cough, Measles and Tuberculosis are compulsory as part of the' National Expanded Immunization Programme. These vaccine are provided free of cost to the patient by the Government. Besides these, there are other newer vaccines against a host of other illnesses. These are costly and of less defined benefits. They are being promoted vigorously by the pharmaceutical companies that manufacture them and profit from their sales. The publicity given to these newer vaccines/has resulted in patients demanding these injections. Doctors have by and large obliged. To accommodate all these vaccines home brewed immunization protocols are resorted to and some of these are attended by unacceptable risks. The Indian Academy of Pediatrics is the professional body to guide the Government on issues related to child health. It is thus in a good position to recommend a well studied immunization schedule for implementation by the Government. However, by publishing its own schedule which is at variance with the Government's policy it has added to the confusion and encouraged and individual improvisions of the immunization schedule.

It is seen that some children are immunized with measles vaccine prior to 9 months-a few as early as 6 months of age. Such vaccination is usually useless as it is neutralised by the babies passive immunity at that age. The more compelling fear is that vaccination with measles prior to the development of immunocompetence may lead to the perpetuation of the virus in the child and result in subacute sclerosing panencephalitis (SSPE) a degenerative disease of the brain.

Hepatitis B vaccination is another case in point. It is known that infection acquired from a carrier mother can result in the baby developing chronic liver disease and liver cancer in adulthood. It is, therefore, re- commended that the vaccine be given to children of mothers who are Hepatitis B carriers. This risk is much lower if the child acquires the infection after the age of 2 years. Vaccination of children whose mothers are not carriers is thus difficult to justify. Selective vaccination after mandatory testing of Hepatitis B carrier state in pregnancy is more cost effective than universal immunization with Hepatitis B.

However, doctors now recommend Hepatitis B immunization to all those who can afford it, who are also those whose mothers who are Hepatitis B screened and so need it least. There is a small risk of reaction to the yeast of the vaccine. In the absence of risk of vertically transmitted Hepatitis B this risk of anaphylaxis is un-acceptable. As this vaccine is not part of the standard national immunization if a child develops fatal anaphylaxis the doctor who advises it will find little support in a court of law.

Vaccination against H. influenzae b is now available. In the West it is routine practice to give this vaccine but in India its need has not been defined and so it is not recommended by the state. In all this it would be better to err on the side of caution and use only vaccines mandated by the state.

Jacob M. Puliyel,
Head, Department of
Pediatrics and Neonatology,
St Stephen's Hospital,
Tis Hazari, Delhi 110 054,
India.

Comments

The Immunization, Committee of the Indian Academy of Pediatrics had led the Academy and its members systematically and steadily in learning to evaluate new developments in vaccines and to define our policies after careful deliberations. Even though we exercise caution and judgment and go by specific information on the epidemiological need, efficacy and safety of each and every vaccine, we must also welcome voices of dissention which force us to reexamine them. In the light of this philosophy, the letter from Dr. Puliyel must be taken seriously and responded to, with responsibility.

The national (government) immunization program is to give BCG, OPV, OPT and measles vaccines to all children, at government expense. Should the Academy merely endorse and adopt the same program or should it go beyond it and recommend the use of some of the newer vaccines as well? Dr. Puliyel puts forth four reasons why we should stick to the government program only. One, the newer vaccines are relatively more expensive and their use adds profit to the companies that manufacture and market them. Second, some of these newer vaccines "are attended by unacceptable risks". Third, the immunization schedule accommodating newer vaccines causes "confusion" as it is at variance with the government's schedule. Finally, the doctor "will find little support in a court of law" in case of adverse reactions to the newer vaccines, especially if there is "fatal anaphylaxis", for example to the recombinant hepatitis B (HB) vaccine produced in yeast cells. We must examine each reason carefully. But, before that, let us get the other issues raised by Dr. Puliyel sorted out. Three specific vaccines were chosen by him to highlight some problems of going beyond the government's program, namely measles vaccine, HB vaccine and Haemophilus influenzae b (Hib) vaccine.

The Academy has endorsed the recommendation of the World Health Organization (WHO) to give measles vaccine at 9 months of age or as soon as possible thereafter. Indeed this age was suggested by us before the Expanded Program on Immunization was established(1). The WHO has considered the problem of measles in infants below 9 months when case fatality is high and allowed immunization of infants at and after 6 months of age when they are at risk, such as during an outbreak. Such infants are to be given their regular dose also, due after 9 months. This is also the official policy of 'the government as well as that of the Academy. Dr. Puliyel thinks that measles vaccine' given at 6 months is "usually useless", but scientific data is contrary to his view(2). While it is true that there will be a vaccine failure rate higher than when given at 9 months, the infant who is susceptible to measles disease at this age will be immunized and protected. It is because of the higher failure rate that repeat immunization is needed at or after 9 months. The "more compelling fear" for him is that measles vaccine given at 6 months -may result in chronic infection and subacute sclerosing panencephalitis (SSPE). Dr. Puliyel is completely misguided on this count also; there is no evidence whatsoever to suggest that measles vaccine may cause SSPE, whether given at 6 months or later (or for that matter, even earlier). On the contrary, measles vaccine protects against measles as well as SSPE.

Regarding HB, he suggests a policy of mandatory testing during pregnancy and selective immunization of infants born to HB virus carrier mothers only. He says it will be more cost effective than universal immunisation. In the early days of HB immunization, selective approach was considered, but it was soon found that it was not effective for the purpose of reducing the HB virus carrier pool in the communty. Universal immunization of all infants with HB vaccine is now routine in about 80 countries in the world, including some with lower carrier rates than in India. The Academy's official policy to immunize all infants whose parents can afford the vaccine is ethically and scientifically the only possible course open to us. Unfortunately, the price of the vaccine is very high, but it remains so high only because our government has not included it in the schedule; other developing countries with a national policy of HB immunization get the vaccine at about 40 rupees per dose. I understand that for the price to fall, the purchase must be on contractual basis so that the manufacturer can produce and hand over the quantity, rather than invest in stocking the vaccine and in marketing it by "vigorous" promotional efforts. Just because polio and measles vaccines are given free by the government one should not conclude that the manufacturers of these vaccines do not make any profits. The manufacturers of measles and polio vaccines are also making profits, but they need not spend money to promote them. The quantities of measles and polio vaccines procured by the government run into over 25 million and 400 million (approximately) per year, respectively. If sufficient doses of HB vaccine for our annual birth cohort of 25 million babies are procured, the cost per dose will fall to less than 30 rupees. According to the WHO recommendation India should have adopted the policy of universal infant immunization with HB vaccine before the end of 1997. The government's policy clearly needs revision, and the Academy recommends to it the adoption of the WHO's recommendation as soon as possible. Universal HB immunization of all infants is in the best interests of the nation.

The Academy has not recommended Hib vaccine for all infants, but has suggested that it be optional to be decided by the pediatricians and the parents. Although invasive Hib disease is a serious clinical problem it is under diagnosed due to less than optimal quality microbiology laboratory support. Therefore the burden of disease remains underestimated. Although expensive, it is highly effective and safe. This stand taken by the Academy is not because it is not recommended by the government, but it is independent of the government policy of not using it. The Immunization Committee will be reviewing this matter periodically.

Now we will come back to the 4 reasons why Dr. Puliyel feels that we must stick to the government's immunization policy and schedule. Here we must make a clear distinction between the government's immunization policy and its schedule. The schedule belongs to the government's program of immunization usually referred to as the Expanded or Universal Immunization Program. I am not aware of any policy decision by the government that vaccines outside . this program are not to be given to children in India; thus, the government's policy allows the use of HB and Rib vaccines. The Delhi government has an official program to immunize several thousands. of infants with HB vaccine for evaluating feasibility and scheduling. So, if the Academy simply accepted the government's immunization program, we will not be serving the children of India with responsibility and academic competence and integrity.

All newer vaccines are and will be more expensive than the older ones and the government must face this problem to make them more affordable. As long as vaccines that should be used universally remain only in the private market, their prices will remain high.

The newer vaccines are very safe products and none of them have unacceptable safety risks. Indeed there is one vaccine manufactured under public sector and . forced on the unsuspecting public, which has unacceptable risk, namely the sheep brain rabies vaccine. It causes allergic encephalomyelitis which can be fatal or disbling in survivors. The safety records . of the newer vaccines approved by the Academy, namely the measles, mumps, rubella vaccine, both recombinant and plasma derived HB vaccine, modem typhoid fever vaccines and Hib vaccine are extremely good.

If the Academy recommendations are followed there need to be no confusion at all. When we serve the cause of children and are, responsible to teach evidence-based, ethical and competent practice to our members, we must learn to assimilate new information and update our practice accordingly. If someone feels confused by it, systematic enquiry and patient answers will dispel such confusion. That indeed is the purpose of the 'Immunization Dialogue' series.

What is the likelihood of liability for negligent I service if a child develops adverse reaction following the giving of a new vaccine? Any vaccine injected sub-cutaneously or intramuscularly can induce unusual responses like syncope or anaphylaxis, albiet very rarely. All medically qualified persons have been taught to recognize them and treat them. There is no reason to worry about them but all injection rooms must have the essential remedies for anaphylaxis, namely adrenaline and resuscitation equipment.

If a child under a pediatrician's care develops Hib meningitis and the parents come to know later that it could have been prevented by immunization, could they take the pediatrician to court for not informing them of the availability of such a vaccine? As far as we know courts of law including consumer courts do not make arbitrary judgements on negligent practice, but take current knowledge, teaching and I practice as well as expert opinion seriously. We must expect fair trial and just decisions. Doctors in non-governmental institutions and clinics are however advised to discuss immunization issues with parents and to record that such conversation took place and that the decision to give or not to give a newer vaccine was taken jointly or unilaterally by the parent. Good record is the best protection in law suits.
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In summary, the Academy must continue to periodically review newer vaccines and immunization policies and practices and their considered recommendations must be formulated and passed on to the members. This is its duty. The government does not seem to have a mechanism to re- view such matters and the Academy must respond positively if assistance is sought. Many countries have Advisory Committees on Immunization Practice and India also deserves one.

T. Jacob John,
Chairman, lAP Immunization
Committee and President Elect,
Indian Academy of Pediatrics,
Thekkekara,
2/91 E2, Kamalakshipuram,
Vellore 632 002, India.

References

1. John IJ, Jesudoss ES. A survey of measles antibody in children. Indian Pediatr 1973; 10: 65-66.

2. Job JS, John IJ, Joseph A. Antibody response to measles immunization in India. Bull WHO 1984; 62: 737-741.