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Immunization Dialogue

Indian Pediatrics 2000;37: 1141-1145

The views expressed by Prof. T. Jacob John in this section are personal in nature and should not be construed as the official stand of the Indian Academy of Pediatrics. -Editor-in-Chief

Misguiding Guidelines from IAP?


Hallowed Be Vaccine HBV, but Many More Reasons needed for MMR! This seems to be new motto of IAP. At least, that is the impression one gets after reading the "Update on Recommendation of the Academy to other Agencies on Immunization" which appeared in the Indian Pediatrics of August 1999(1), and the previous ones including the first recommendation for HB Vaccine in 1995(2).

The decision of the Committee is not to recommend MMR for Universal infant Immunization but to suggest HB Vaccine for such. A distinction is being made between this recommendation for universal immunization from government funds and IAP recommenda-tion to pediatricians in their practice. Still, the overall impact of this changed emphasis will be to diminish the importance of MMR and raise that of the HB Vaccine and it will definitely affect the prescribing practice of many physicians. Two infants seen by me at six months of age, who got 2 doses of HB Vaccine but not a single dose of DPT or OPV from their previous physicians, are obviously victims of such distorted emphasis. Those robust data, which walked into my office, was sufficient live proof for me!

To continue giving MMR at 15 months after the Measles vaccine at 9 months is important for several reasons. The neutralizing effect of maternal antibodies to suppress the effect of Measles vaccine upto 12 months or even beyond is widely accepted. This is especially important in the Indian context where most of the mothers will have higher levels of antibodies from Measles disease than the lower levels from Measles vaccine. Such children should have a booster after 15 months which minimally should be another Measles vaccine and ideally should be MMR. The changing recommendations regarding age of Measles vaccination by the American Academy of Pediatrics (AAP) during the last several years, was mainly based on the influence of maternal antibodies on the vaccine effect. Actually, the AAP now recommends that if the child receives a dose of measles vaccine before 12 months of age, two additional doses are required beginning at 12 to 15 months(3). But paradoxically IAP is indifferent to such data and recommends a single measles vaccine at 9 months, and where there is no similar data about HB Vaccine, it recommends 2 extra boosters just to be sure(2).

The importance of Rubella vaccine in reducing the incidence of Congenital Rubella has also been widely accepted. Before the development of the Rubella vaccine, 0.1% to 0.4% of children were born with congenital rubella, but since the introduction of the vaccine, congenital rubella has become rare in such countries(4). Hearing loss is the most common permanent manifestation and affects 68% to 93% of children with congenital rubella(4). There is no reason to believe that the incidence of Congenital Rubella and its manifestations are any different in India from the figures given above. If this is true, out of the 2.5 crore children born in India every year. 25,000 to 1,00,000 children will be affected by Congenital Rubella if the mothers are not protected. Even assuming the lower figure, the numbers are huge by any reckoning.

Recent data from Vellore, shows that 9.8% of children with suspected congenital infections had congenital rubella as the cause(5). And it is the experience of most pediatricians here to see at least few children with congenital rubella in their practice. Considering the inadequacy of facilities for early diagnosis and manage-ment of such children in India, it is especially important to prevent this. The reason given for not recommending MMR is that "sufficiently robust data, qualitative and quantitative, have not emerged in our country". How many more deaf children will have to be born before such robust data become sufficient? Should we start from scratch, stop giving Rubella vaccine altogether, and count the increased number of congenital rubella for the next decade to get such data?

In the current recommendation from IAP, it is stated that if universal vaccination of HB Vaccine is started, the cost will come down considerably as in other countries and hence it will become cost-effective.The fact that this will be true for MMR Vaccine also is conveniently ignored. The total cost for universal immunization of HB Vaccine is given as Rs. 190 crores. Comparing the present cost of 3 doses of HB Vaccine (Rs. 240) and the cost of one dose of MMR (Rs. 40), it can be projected that if the total cost of HB Vaccine is Rs. 190 crores, the total cost for universal MMR immunization will be only Rs. 32 crores. The Vellore study quoted above shows that the number of infants with congenital rubella seen there in two years is nine(5). It can be fairly assumed that the total incidence in India will be at least several hundred times this number, making the total number to several thousands per year. If India will not invest Rs. 32 crores for preventing this many cases of permanent deafness and congenital rubella, "it also cannot be because of poverty but because of ignorance and callousness", and a little bit of help from IAP too! Considering that a mere Rs. 32 crores will eradicate measles and mumps also, it is worse than ignorance and callousness; it is scandalous.

Other less robust data are also there to recommend MMR as a routine to all children. Many cases of isolated congenital hearing loss without any other features of congenital rubella are also thought to be caused by it. There are suggestions that at least some cases of childhood diabetes (IDDM) may be caused by early rubella infection and recently it has been shown that rubella disease may trigger antibodies against the Islet cells(6). The role of mumps in the causation of sterility is known, and the possible reduction of sterility may be an added bonus with giving MMR. Consider-ing the emotional and financial cost of fertility treatment, even minor reduction in sterility will be a great benefit.

In this context it could be asked: what kind of robust data is there for the Committee's previous recommendation in 1995 for HB Vaccine boosters at 5 and 15 years?(2) The reason given for the need for HB Vaccine Boosters is the possible interference from passively transferred maternal antibodies(7). This apparently is not a widely discussed problem with HB Vaccine. The fact that HBIG is given along with the HB Vaccine to new-borns of HbsAg positive mothers, supports the assumption that such interference may not be significant. In 1995, IAP's immunization timetable recommends boosters at 5 and 15 years for HB Vaccine without having any data to support(2). Even the 1997 Red Book of the AAP states "For children and adults with normal immune status, routine booster doses of vaccine are not recommended currently, but their need will continue to be assessed as additional information becomes available"(8). Even the AAP schedule for immunization for 1999 does not make any recommendation for boosters for HB Vaccine(9). In 1995, when the IAP made the initial recommendation for HB Vaccine, it could very well have waited till 2000 for making any recommendations for the need for boosters after 5 years. Instead of such reticence, IAP went even beyond the millenium and recommended a booster at 15 years also!

There are new data, which may change the recommendations for HB Vaccine due to concerns about increased Thimersal content in vaccine causing risk of high exposure to mercury during infancy. Already, the AAP has recommended to change the timing of the first dose of HB Vaccine from birth to six months, for infants whose mothers are HbsAg negative(10). And new data is there to suggest that three yearly HB Vaccines may be as effective as the current schedule(11). In such a dynamic field, IAP may be the only agency to have suggested a booster after 5 and 15 years already. It indeed will be interesting to know whether there is any other Pediatric Academy in the world, making such recommendation for boosters for HB Vaccine and not recommending universal MMR vaccine. It is indeed a paradox that India, which may be at the bottom regarding many basic health needs, is at the top for such costly recommendations with no relevant data.

This inordinate fondness for HB Vaccine at the cost of other important ones by the IAP is indeed inexplicable.

Alexander Mathew,
Department of Pediatrics,
St. Joshep's Hospital,
Manjummel, Kochi,
Kerala 683 501, India.
E-mail: amathew@satyam.net.in

  References
  1. Update on the Recommendations of the Academy to other agencies on immunization. Indian Pediatr 1999; 32: 785-787.

  2. IAP's Immunization Time Table in Pediatrics. Indian Pediatr 1995; 32: 1329-1330.

  3. American Academy of Pediatrics, Measles. In: Red Book: Report of the Committee on Infectious Diseases, 24th edn. American Academy of Pediatrics, Elk Grove Village, Illinois, 1997; pp 349-350.

  4. Roizen NJ. Etiology of hearing loss in chidlren. Pediar Clin N Am 1999; 46: 55-56.

  5. Sridharan G, John TJ, Mathai E, Moses PD, Cherian T, Kuruvilla KA, et al. Serology in congenital infections: Experience in selected symptomatic infants. Indian Pediatr 1999; 36: 667-669.

  6. Lindberg B, Ahlforks, Carlson A, Ericsson UB, Landin-Olssan M, Lenmark A, et al. Previous exposure to measles, mumps and rubella but not vaccination during adolescence. Correlates to the prevalence of pancreatic and thyroid autoantibodies. Pediatr 1999; 104: e12.

  7. John TJ, IAP's Immunization Time Table in Pediatrics: Reply. Indian Pediatr 1996; 33: 610-611.

  8. American Academy of Pediatrics. Hepatitis B In: Red Book: Report of the Committee on Infectious Diseases, 24th edn. American Academy of Pediatrics, Elk Grove Village, Illinois, 1997; pp 250-251.

  9. Recommended childhood Immunization Schedule, United States, January-December 1999. Pediatrics 1999; 103: 182-184.

  10. Committee on Infectious Diseases and Committee on Environmental Health. Thiomersal in vaccines: An interim report to clinicians. Pediatrics 1999; 103: 570-573.

  11. Halsey NA, Moulton LH, O'Donovan C, Walcher R, Thorns ML, Margolis HS, et al. Hepatitis B vaccine administration to children and adolescents at yearly intervals. Pediatrics 1999; 103: 1243-1246.

 
 Reply

The licencing of newer vaccines by the Drugs Controller without providing guidelines for their use, has had a disturbing effect on several pediatricians, as seen from the number and variety of dialogue questions in recent years. Dr. Alexander Mathew's poser is one such example. The IAP Committee on Immunization has grappled with this issue and has developed policies for the members of the Academy, guidelines for them to use informa-tion with discretion in designing immunization packages for their client families, and recommendations to the Government and other relevant agencies.

The Committee's recommendation to the Government, duly ratified by the Executive Board and the General Body meetings, was to include the Hepatitis B (HB) vaccine in the National Immunization Program(1). In 1999, the Committee refrained from so recommend-ing MMR vaccine(1). Thus, what appears to be the complaint of Dr. Mathew is regarding IAP's Recommendations rather than its guidelines regarding the use of newer vaccines. So, let me state categorically that no evidence to substantiate the title"misguiding guidelines" has been submitted. Personal disagreement has to be resolved by dialogue and it does not merit the adjective of misguidance.

The IAP guidelines covered the use of HB vaccine beyond infancy, immunization camps and campaigns, immunization records and vaccines against typhoid fever, Hib, Hepatitis A and Varicella(2). In the absence of data to support a recommendation to include MMR in the National Immunization program, the Committee expressed the hope "that sooner than later, the Government will also include the MMR and HB vaccine in the UIP schedule"(2).

We all share with Dr. Mathew, the frustration of seeing children who have not been managed correctly regarding their immunization. If I were to see two infants at 6 months of age who had received 2 doses of HB vaccine but no DPT or OPV, I would use the opportunity to teach the family the correct immunization requirements and also gently inform the 'previous physicians' what they had missed, rather than to blame the IAP for their errors. I would strongly recommend proper documentation of immunization of every child, and a family-retained card, in order to avoid such mistakes. It is unfair and unkind to blame the Immunization Committee for such problems.

It is also frustrating to note that even Dr. Mathew misunderstands the IAP policies on MMR vaccine. Let me quote the official policy statement: "MMR vaccine is to be given in the second year of life, with a minimum interval of 3 months after the measles vaccine dose given at or after 9 months of age"(3). It is thus a gross error to say that: "But paradoxically IAP is indifferent to such data and recommends a single measles vaccine at 9 months...." His entire argument in favour of the rubella component in the MMR is on the mistaken premise that IAP does not require MMR vaccine by policy. The Committee strongly recommends that IAP members learn and practice what IAP teaches. Loyalty to other Academies is a matter of personal choice.

The direct extrapolation of the incidence of congenital rubella from North America to India is unscientific. There is no evidence to presume that 25,000 to 100,000 infants are born annually with congenital rubella. Our data in Vellore showing nearly 10% of a highly selected group of infants with evidence of congenital rubella is an indication of its prevalence, not its magnitude in the community. I would strongly recommend to Dr. Mathew to document the actual frequency of congenital rubella he sees annually and try to put in perspective in terms of available denominator or at least a comparison with other illnesses of known frequency. That is how to contribute to robust data, not by rhetoric or false logic. The statement that: "a mere Rs. 32 crores will eradicate measles and mumps also" is mere wishful thinking. It is not realistic to assume that measles and mumps could so easily be eradicated.

It appears that Dr. Mathew disagrees with the recommendation of IAP to the Government to include HB vaccine in the National Immunization Program. This issue has recently been discussed and there is no further need to reiterate the rationale for this decision(4,5). New data have recently appeared in Indian Pediatrics(6) confirming the several earlier studies.

The thiomerosal issue has been reviewed and there seems to be no real need to change any IAP policy or recommendations at the present time. The mercurial salt in the vaccines is not toxic in the doses given in vaccines. The Committee has to take a formal stand on it in one of the future meetings. Regarding the need for a booster at 10 years, there are several reasons why the Committee had so resolved. While it is true that the American Academy of Pediatrics has deferred this question, it must be realized that the carrier rate and the magnitude of exposure to the virus in the USA are only a fraction of what they are in India. The actual protective antibody level is unresolved and some experts believe that 10 IU are not enough but 100 IU may be necessary. There are ample data on the waning of antibody level after 3- dose primary immunization. After waning, reinfection has been documented. There is some evidence that reinfection also results in integration of viral genome with host cell genome. It is very likely that in future there will be recommendation for a booster by several experts. There are already some countries offering booster. Yet, the Committee has also shelved this recommendation as may be seen in the 1999 statements because of the differences of opinion that are valid(3). If the Committee appears to be inordinately fond of HB vaccine, one may also ask why a few persons are inordinately allergic to the idea.

T. Jacob John,
Emeritus Medical Scientist (ICMR),
439, Civil Supplies Godown Lane,
Kamalakshipuram, Vellore 632 002,
Tamil Nadu, India.
E-mail: tjjohn @md4.vsnl.net.in

 References
  1. Committee on Immunization. Update on the recommendations of the Academy to other agencies on immunization. Indian Pediatr 1999; 36: 785-787.

  2. Committee on Immunization. IAP guidelines on optional vaccines and related matters. Indian Pediatr 1999; 36: 677-679.

  3. Committee on Immunization. Update on immunization policies, guidelines and recommendations. Indian Pediatr 1999; 36: 567-568.

  4. John TJ. Should Hib vaccine be given priority over Hepatitis B vaccine: Reply. Indian Pediatr 2000; 37: 105-107.

  5. John TJ. Universal immunization with Hepatitis B vaccine: What it will cost? Reply. Indian Pediatr 2000; 37: 107-110.

  6. Singh J. Bhatia R, Khare S et al. Community studies on prevalence of HBsAg in two urban populations of southern India. Indian Pediatr 2000; 37: 149-152.

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