‘IAP Policies, Guidelines and Recommendations on
Immunization 2003’

Citing the Evidence
The IAP has published its updated Policies, Guidelines and Recommendations on Immunization 2003 (1). However unlike the recommendations of the Centre for Disease Control Advisory Committee on Immunization Practice (2), the document published by the IAP cites no references. In the sphere of Evidence-Based-Medicine, the evidence from ‘expert committee reports or opinions and / or clinical experience of respected authorities’, represents Category IV evidence. The strength of the recommendations based on category IV evidence, is the lowest Grade D, according to the categories of evidence described by Eccles and Manson (3).
We believe the recommendations of the IAP expert committee must surely be evidence-based, but the references may have been omitted due to persuasions of brevity. The committee should therefore be able to provide the references on request and this would improve the strength of its recommendation.

We seek to enquire about the evidence-base for 3 of the policy guidelines

1. There is controversy about the mortality from Hepatitis B in India. The WHO has suggested that 250,000 die due to the disease each year (4, 5). The projection made by the Indian Council of Medical Research (ICMR) suggests that about 5000 die from Hepatitis B each year (6). We have recently published in the Lancet, how the WHO figure can be arrived at, by wrongly extrapolating data from Taiwan (7).
The cost-benefit equation is different, depending which figure is accepted. It is crucial to know what figure for mortality the IAP expert committee used, for its cost-benefit evaluation, before recommending hepatitis B vaccine to the government for inclusion in the UIP.

2. With regard to the timing of hepatitis B vaccination, we notice a subtle shift in policy, from the IAP policy in 2001 (8). The old policy suggested, ‘the first dose at birth with subsequent two doses at 6 week and 14 weeks of age’. It stated, “It is important to note that the first dose at birth is essential to prevent perinatal transmission. If the first dose at birth is missed, it should be given at 6 weeks, 10 weeks and 14 weeks of age.” The 2003 recommendation starts instead by stating “We wish to emphasize the fact that in our country, horizontal transmission of the disease appears to be an important mode of transmission of the disease along with vertical ie. mother to child (transmission).”
We have looked for evidence that has appeared since the Policy Statement of 2001, for the assertion that, “horizontal transmission is an important mode of transmission”. There are few good studies looking at this issue after the 2001 recommendation. An old study by Nayak et al (9) suggested that one third of chronic hepatitis B carriers acquired infection by perinatal spread and the remaining acquired infection in early childhood “very likely from contact with perinatally infected children”. Prevention of vertical spread is thus crucial both to prevent mother-to-child transmission and also child-to-child transmission.
Aggarwal et al (10) have done calculations, using primary data that is available in the abstract of the paper by Nayak et al (9) and suggested that 86% of chronic hepatitis B infection in India occur in offspring of mothers who lack HBsAg and so delayed vaccine would be effective. We discuss the issue of this distortion of the findings of Nayak et al, in the Indian Journal of Gastroenterology (11). It will be interesting to know if the IAP has come across other strong evidence of horizontal transmission prompting this change in policy.

3. The 2003 policy suggests that Hib vaccine should be offered to all children. It states that Hib is a vaccine that merits active consideration to be included in the UIP. We find this surprising. International literature is awash with evidence that the incidence of Hib disease is extremely low in India.
In Gambia, Hib vaccination brought down the incidence of Hib meningitis from 200 per 100 000 to just 20 per 100 000(12). In India even without immunization, the incidence of Hib disease is 9 per 100 000, according to a large, prospective, population based study, conducted by the WHO recently (13).
The 4 year IBIS study in 6 referral hospitals in India, after employing sophisticated culture techniques to isolate the organism, also found a remarkably low incidence of Hib disease (14, 15). In the journal Vaccine, we have described how cross-reactive-antigens may be responsible for the low incidence of invasive Hib disease in India (16).
After the two studies quoted above (13, 14.) there can be little argument that the incidence of the disease is truly low in India. It would be useful to know if the IAP has taken cognizance of these 2 studies, in which members of the expert committee may have participated.
Like Yellow-fever-vaccine is not routinely recommended in India because the risk of disease is low, must we not abandon Hib vaccine use, with its low risk of disease?
Members of the IAP are extremely proud of the editorial independence of its journal and for its high standards (17). It is fitting that the evidence-base of what is published here, is discussed in the journal itself. We hope this can be done with reference to literature, and without taking issues of science at a personal level.
-Noopur Baijal, Jacob M Puliyel, Department of Pediatrics, St Stephens Hospital
Tis Hazari, Delhi 110054
puliyel@vsnl.com

References:

1. Indian Academy of Pediatrics Committee on Immunization. Update on Immunization Policies, Guidelines and Recommendations Indian Pediatrics 2004; 41:239-244

2. Advisory committee on Immunization practices and the American Academy of Family Physicians. General recommendations on immunization.
   MMWR Morb Mortal Wkly Rep. 2002 ;51(RR02):1-36.

3. Eccles M, Manson J. How to develop cost-conscious guidelines.
   Health Technol Assess. 2001;5(16):1-69

4. Miller MA, Kane M Routine hepatitis B immunization in India: cost-effectiveness. Indian J Pediatr 2003;70:188-9

5. Miller MA, McCann L. Policy analysis of the use of Hepatitis B, Hemophilus influenzae type B, Streptococcus pneumoniae- conjugate and Rotavirus vaccines in the National Immunization Schedules. Health Economics. 2000; 9: 19-35

6. Dhir V, Mohandas KM. Epidemology of digestive tract cancers in India 111 – Liver. Indian J Gstroenterol 1998;17:100-3

7. Puliyel JM Plea to restore public funding for vaccine development.
   Lancet. 2004;363:659.

8. Committee on Immunization Indian Academy of Pediatrics. Update Policies, Guidelines and Recommendations on immunization - 2001 http://www.iapindia.org/policies.cfm Accessed 27/3/04

9. Nayak NC, Panda SK, Zuckerman AJ, Bhan MK, Guha DK. Dynamics and impact of perinatal transmission of hepatitis B in India J Med Virol 1987;21:137-45

10. Aggarwal R, Naik SR. Prevention of hepatitis B infection: the appropriate strategy for India.
    Natl Med J India. 1994;7:216-20.

11. Sahani M, Jindal K, Abraham N, Aruldas , Puliyel JM. Hepatitis B immunization:cost calculation in a community –based study in India Indian J Gastroenterol 2004;23

12. Adegbola RA, Usen SO, Weber M,Lloyd-Evans N, Jobe K, Mullholland KPWJ et al.Hemophilus influenza type b meningitis in The Gambia after introduction of a conjugate vaccine. Lancet 1999;354:1091-2

13. Watt JP, Levine O, Santosham M. Global reduction of Hib disease: what are the next steps? Proceedings of the meeting Scottsdale, Arizona, September 22-25, 2002.
    J Pediatr. 2003;143(6 Suppl):S163-87.

14. Invasive Bacterial Infections Surveillance (IBIS) Group of the International Clinical Epidemiology Network. Are Haemophilus influenzae infections a significant problem in India? A prospective study and review. Clin Infect Dis. 2002 1;34:949-57.

15. Steinhoff MC. Invasive Haemophilus influenzae disease in India: a preliminary report of prospective multihospital surveillance. IBIS (Invasive Bacterial Infections Surveillance) Group.
    Pediatr Infect Dis J. 1998 Sep;17(9 Suppl):S172-5.

16. Puliyel JM, Agarwal KS, Abed Abas F. Natural immunity to Haemophilus influenza b in infancy in Indian children. Vaccine. 2001 14;19:4592-4.

17. Gupta P, Choudhury P Declaring competing interest. Indian Pediatrics 2003;40: 3-6
    
     

A Rejoinder!
With reference to ‘Recommenations’ of IAP Committee on Immunization (1), I would like to offer few comments.
1-Hepatitis-B vaccination:
The committee has stated that to get “an optimum immune response the recommended interval between second and third dose of HB vaccine should be at least 8 weeks”. However, to devise an ideal schedule of HB vaccine and to take the maximum immunoprotective benefits, it is also imperative that the last dose of any HB schedule, be it 3-dose or 4-dose, should not be administered before 6 months of chronologic age (2). This recommendation is based to achieve the high boosting effects on consequently maximum possible GMT levels of antibodies (2). Hence, any HB schedule concluding before 6 months of age would only offer less than maximum possible immune benefits to the vaccinee. Further, the stated option of 0, 1 and 2 months for adolescent vaccination also does not confirm to the criteria of minimum interval between 2nd and 3rd dose of HB vaccine.
The recommendation of starting HB vaccination of preterm and small-for-dates babies at birth is still debatable and might not confer adequate protection if given to infants weighing <2000 grams at birth. These infants would need an extra dose of HB vaccine if vaccination started at birth (2).

2-Typhoid vaccination:
The committee has recommended Government of India (GOI) to include Vi- polysaccharide vaccine in its national immunization schedule. However, this is to be noted that all the available typhoid vaccines in the market today including Vi-polysaccharide vaccine, are only moderately efficient (50-70%) in traditional target groups of children under 5 years of age (3). Thus, before coaxing GOI to manufacture and include this vaccine in national immunization schedule, it would be more appropriate to wait till a more efficient, conjugate version of current Vi-vaccine is available in the market. Alternatively, the government should be urged to explore possibilities of developing the same in the country.

3-Hib Vaccination:
The recommendation that Hib vaccine “needs serious consideration for inclusion in the national immunization schedule, while awaiting disease burden studies” is a lucid example of contradictory statement and almost amounts to oxymoronic proposition. How could a vaccine be recommended against any disease for universal adoption without first ascertaining and quantifying the disease burden caused by the disease itself?

4- Hepatitis A vaccination:
The committee has recommended Hepatitis A vaccine to children at 2 years of age. Most of the recent Indian studies have shown that there is gradual decline of maternally acquired anti-HAV antibodies after birth and reach their nadir around 12-24 months (4, 5). This is the most vulnerable period for a child to contract the disease. Thus, to cover the most susceptible population, it would be prudent to use the vaccine during this period i.e. between 12-24 months of age.
The dose of Hepatitis A vaccine mentioned in the article reflects the dose recommended by only one vaccine manufacturer, however, the dose of the vaccine marketed by other manufacturer is different.

5-Pneumococcal vaccination:
Contrary to committee’s conclusion that pneumococcal vaccine is not indicated for universal immunization in our country at present, the limited epidemiological data show that this vaccine is indeed urgently needed in the country (6). In fact, the disease burden posed by Pneumococcal disease both in terms of morbidity and mortality far outweighs the one inflicted by Hib disease in the country. However, non-availability of a good conjugate vaccine consisting of all the prevailing serotypes responsible for serious disease in the country and exorbitant cost of the vaccine available elsewhere in the world are altogether different issues.

Recommendations to Ministry of Health, GOI:
The first and foremost recommendation to GOI should be to initiate efforts to generate authentic data on epidemiology of those vaccine preventable diseases (VPDs) on which adequate data are lacking, such as, Hib and Pneumococcal diseases. The government needs to be recommended to sponsor multicentric trials to generate indigenous data, both hospital and community based on these diseases.
The committee should also stress the government the need of starting efforts in the direction of making certain vaccines, not available in India but needed most here such as conjugate Pneumococcal vaccines (available elsewhere in the world) and the vaccines against Rotavirus and other diarrheal diseases and RSV vaccines (currently under process of development) available in India at affordable prices.
-Vipin M. Vashishtha,
Bijnor (U.P.)
(For references, kindly visit our website www.pediascene.com or write to editor).

References:
1-Committee on Immunization, Indian Academy f Pediatrics. Update on immunization policies, guidelines and recommendations. Indian Pediatr 2004; 41: 239-244.
2-American Academy of Pediatrics. In Pickering LK, ed. 2003 Red Book; Report of the Committeeon Infectioud Diseases. 26th edn Elk Grove Village, IL: American Academy of Pediatrics; 2003.
3-World Health Organization. Typhoid vaccines. WHO position paper. Weekly Epidemiological Record, 2000, 75:257–264.
4- Dutta AK, Aggarwal A, Kapoor AK, Ray GN, Batra S. Sero-epidemiology of Hepatitis A in children in Delhi. Indian J Pediatr 2000; 67:77-79.
5-Mittal SK, Rastogi A, Kumar N, Talukdar B, Kar P. Seroprevalence of Hepatitis A in children-Implication for Hepatitis A vaccine. Trop Gastroenterol 1998; 19: 120-121.
6- Prospective multicentre hospital surveillance of streptococcus pneumoniae disease in India. Invasive bacterial infection surveillance (IBIS) group, Internatinal clinical epidemiology network (INCLEN). Lancent 1999; 353: 1216-1221.


 

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