Wednesday, July 11, 2012

Unscientific, Excessive Use of Newer Vaccines


Unscientific, Excessive Use of Newer Vaccines
Dr. Anant Phadke *
8, Ameya Ashish co-op. Hsg. Society, Kokan Express Hotel lane, Kothrud, Pune 411038,
anant.phadke@gmail.com  020 25460038, 09423531478


Vaccines are among the most cost-effective medicines in reducing morbidity and mortality and have an important supplementary role as a public health measure in the control of many communicable diseases. However, the manner in which some newer vaccines are being pushed into the National Immunization Programme in India is a cause for concern. Since in the National Immunization Programme, as vaccines are given to a very large number of healthy population/children, both their safety and cost-efficacy should be thoroughly assessed before any vaccine is introduced into this Programme. Secondly, comparative cost-efficacy of newer vaccines has to be determined in India and then it has to be assessed where each of them stands in the list priorities. These basic requirements are not being fulfilled when the newer vaccines are being recommended for use in India in the National Immunization Programme. In case of safe and fairly effective vaccines, some parents may be able to follow doctor’s advice for individual protection of their children even if the vaccine is very costly. But the decision about inclusion in the National Immunization Programme has to be based on comparative cost-efficacy.
The phenomenon of irrational/excessive use of vaccines is a new phenomenon. As an illustrative example, this note deals with a few examples.  It questions the use the Oral Polio Vaccine for polio eradication, and critiques the impending introduction into the National Immunization Programme of some newer vaccines despite problems as regards their either efficacy or safety or cost-efficacy.  

Excessive use of the Oral Polio Vaccine
Excessive use of the Oral Polio Vaccine (OPV) is a good example of how a much hyped vaccination programme can be fundamentally flawed. Polio, like many other infectious diseases, is primarily a disease of under/mal-development, of poverty, insanitation, and malnourishment. In developed countries polio and other infectious diseases declined along with improvement in living standards including food and sanitation. Vaccination and other medical technological interventions have played a supplementary role. The famous Nelson’s Text Book of Pediatrics has noted “Undoubtedly, good sanitation explains the virtual eradication of polio as a disease from United States in early 1960s, when only about two third of population was immunized with Salk vaccine, and subsequent absence of circulating wild-type poliovirus in US and Europe. In contrast, poor sanitation and crowding have permitted the continued transmission of polio virus in certain poor countries in Asia and Africa, despite massive global efforts to eradicate polio, in some areas with an average of 12-13 doses of polio vaccine administered to children younger than 5 years of age.”  (17th edition)
When this lesson is ignored and hence when vaccine is used more or less as alternative to social progress and when an illusion is created that we can overcome diseases primarily with the help of modern technology that becomes very problematic. In case of polio this is what has happened in India–
In India OPV was introduced in the National Immunization Programme in 1988 and by 1994, this polio controlled programme reduced the incidence of paralytic polio by 80%; from 24257 in 1988 to 4793 in 1994. The vaccination coverage was only 60%. By increasing this coverage the polio incidence could have been brought down by 95% or so. But obsessed with the idea of vaccine induced polio-eradication, the authorities have been pushing more and more doses of OPV into the population, without coupling it with progress on the front of improvement in nutrition, sanitation.  It is well known that OPV inevitably causes Vaccine Associated Paralytic Polio (VAPP) albeit in a miniscule proportion of OPV receivers – in India the incidence is low - an average 1 case of VAPP per 4 million doses polio. The authorities have neglected the fact that more the OPV doses, the more are the number of VAPP cases. In India due to the Polio Eradication Programme, it is expected that annually there are about 200 to 300 cases of VAPP.(1) These children have to sacrifice their limbs involuntarily or the altar of the supposed ‘Public Good’ this eradication programme is to achieve. None of them have been rehabilated or their parents compensated despite the complaint by the Jan Swasthya Abhiyan to the National Human Rights Commission.
What is worse, there has been unprecedented, unexpected huge rise in the number of cases of Acute Flaccid Paralysis (AFP) in children with the progress of the Pulse Polio programme. This number increased from 9461 to 50,371 during 1997 to 2009! (2)  Officials argue that this apparent rise is due to better and more thorough documentation of AFP cases and due to increase in the sensitivity of the surveillance system for recording AFPs. However if the sensitivity of the surveillance system has  increased in say in the year 2000, we would see a steep rise in AFP cases in only 2001 and may be 2002. There has been continuous, steep rise in AFP cases seen every year from 1998 till today. This clearly shows that the heightened sensitivity of the surveillance system is not the cause of this galloping of the AFP cases.
Data on follow-up of these AFP cases is not released by NPSP. In UP when it was obtained by invoking the Right to Information, it was revealed that about 40% of these cases continued to have residual paralysis even 60 days after the onset of paralysis!! (3)  The mechanism for this huge increase is not clear. But the startling fact is that annually, thousands of children are getting paralysed with the progress of the Polio Eradication Programme. A rational and humane response to this unprecedented, stupendous rise in paralysed children should be to immediately suspend the additional doses of OPV and investigate the matter in detail. Secondly it is necessary that all these children who have lost their limbs be fully rehabilitated and their parents adequately compensated.

Hepatitis B vaccine
Chronic hep b carriers are certainly at much higher risk of cirrhosis, carcinoma of liver. The Hep B vaccine is quite safe, effective. Hence the WHO has recommended hep-B vaccination of all newborns in countries where the hep B chronic carrier rate is more than 2%. (4). The Indian Academy of Pediatrics recommended it for inclusion in the National Programme in India on the grounds that it is an important public health problem, that in India, hep B chronic carrier rate is 4.7%.  This figure is gross overestimation based on a paper, (5) which surprisingly made an elementary arithmetical mistake and also a conceptual confusion. We pointed this out and showed that using the same data correctly, the actual ‘hep.B carrier rate’ works out to be only 1.42%. (6)  But we were ignored. Later an expert Sub-Committee under the leadership of Prof. Mittal was appointed by the Indian Medical Association to take an overview of this issue. It reviewed all available studies and arrived at an estimate of Hep B chronic carrier rate of 1.6%. (7) But this paper too was ignored!! Despite absence of scientific evidence for Universal Hep B vaccination of all newborns in India, this vaccine is being pushed, presumably at the behest of the Pharma industry.

Pneumococcal vaccine for children
The National Technical Advisory Group on Immunization NTAGI has recommended that Pneumococcal vaccine be introduced in the Indian public health system in a phased manner from 2010.  What is the scientific evidence about the utility of this vaccine? (NTAGI made this recommendation before the results of immunogenicity studies of the Pneumococcal vaccine in Indian children were available.)
 Joseph L. Mathew (8) has pointed out –
 “ In most developing countries (i) the burden of disease (total number of Pneumococcal cases in the population) is not clear, (ii) knowledge of serotypes causing invasive disease is limited, (iii) even if IPD is a significant cause of pneumonia morbidity and mortality, it is not likely to supersede other causes including H. influenzae and measles owing to poor immunization coverage, (iv) the contribution of viral pneumonia is not clear, (v) antibiotic (penicillin) resistance is not a significant problem in several countries although limited information from some settings suggests otherwise and (vi) there is ongoing as well as expected, scope for improvements in quality of life and hence morbidity/mortality. Therefore attempts to extrapolate the significance of Pneumococcal disease and practice(s) to control it in developed countries may not be appropriate in the scenario of developing countries. -------- This relatively low case-fatality suggests that either the 44 million pneumonia cases are fairly ‘mild’ and/or amenable to treatment with whatever medication (antibiotics or otherwise) is currently used. The fact that only two-thirds of these children are taken to an appropriate health-care provider again suggests a mild disease.”  He further notes –
“CV-7 was designed to protect children in developed countries; and hence serotype coverage is 90% for USA and Canada, 78% for Australia and 75% for Europe. It is much lower for Africa (67%) and Latin America (63%), though this is still much better than for Asia (43%) and India (53% or lower) “.
Secondly the protective efficacy of this CV-7 Pneumo Vaccine, that is being used  in India is low. (Newer versions have been claimed to be more effective). The oft quoted clinical trial by Keith P. Klugman, Shabir A. Madhi et al, found the protective efficacy of this vaccine to be only 25%. The authors report – “Among children without HIV infection, the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent (95 percent confidence interval, 2 to 35; 212 cases in the control group and 169 in the vaccinated group) in the intention-to-treat analysis and by 25 percent (95 percent confidence interval, 4 to 41; 158 and 119 cases, respectively) in the per-protocol analysis (i.e., among fully vaccinated children).” Further, this study found that “The mortality rate was reduced by 5 percent among all children (229 deaths among vaccine recipients and 242 among controls, P=0.58) and by 6 percent among HIV-infected children (166 and 176 deaths, respectively; P=0.63).” (9) It should be noted that the P value is more than .05; there is no statistically significant reduction in this mortality. A Cochrane meta analysis (10) of 11 published clinical trials of this vaccines has shown that the reduction in the “World Health Organization X-ray defined pneumonia was 27% (95% CI 15% to 36%, P < 0.0001); clinical pneumonia, 6% (95% CI 2% to 9%, P = 0.0006); and all-cause mortality, 11% (95% CI -1% to 21%, P = 0.08). Here also it should be noted that the P value is more than .05; there is no statistically significant reduction in this mortality. This meta analysis indicates that the balance of evidence of all studies shows that this vaccine has very limited protective efficacy and no protection from deaths.
Further, Sona Chowdhary and Jacob Puliyel have drawn attention to the fact that “The Cochrane database states that PCV does not reduce the incidence of clinical pneumonia, although it has been shown to reduce vaccine-serotype bacteraemic pneumonia and radiological pneumonia. The benefit of reducing bacteraemic pneumonia and radiological pneumonia is so minimal that it has no effect on clinical pneumonia. Poor nations will need to assess its cost utility carefully.” (11)
Apart from the very limited protective efficacy of this vaccine, the second problem is safety of this vaccine. This clinical trial by Klugman et al mentioned above found an increased incidence of bronchial asthma in the vaccinated group as compared to the non-vaccinated group,. The authors have commented –
 “The increased incidence of asthma among vaccinated children in our study (2.96 cases per 1000 children, vs. 1.66 per 1000 among controls) should be seen in the context of a reduction in the risk of radiologically confirmed pneumonia among vaccinated children (17.9 cases per 1000, vs. 21.5 per 1000 among controls).”
Most cases of pneumonia can be easily treated with Sulfamethoxazole/Trimethoprim) at less than $1 per child, if the WHO protocol is followed. In India, currently parents from 16000 to 30,000 to vaccinate a child with this vaccine. Secondly, if the child gets asthma after vaccination, it likely to be long term or even permanent and needs repeated inhaled treatment with bronco-dilators and steroids.

Hib vaccine
Hib vaccine is also sought to be included in the national Immunization programme with the claimed objective of protecting children from the serious ailment - meningitis caused by H. Influenzae B. However, incidence of Hib in India is very low. The study done by CMC Vellore (12) has reported that amongst 56,153 children (less than 5 yr of age) under study “Eighteen had proven bacterial meningitis, an annual incidence of 15.9 per 100,000. Eight CSF had Hib by culture or antigen testing, an annual incidence of 7.1 per 100,000 (95%CI 3.1 to 14.0) in children 0-59 months. In infants 0-11 months of age,---------” Compared to this, the incidence is much higher in Western countries and this incidence should not be used for taking decision for India. However the NTAGI’s recommendation is based on this Western data.
It is claimed that Hib vaccine is protective also against Hib pneumonia. But the extent of this protection has no public health importance. A recent review paper has pointed out “The most recent meta-analysis showed pooled per-protocol vaccine efficacy of 80% (95% CI 51–92%) against vaccine-type IPD, 24% (95% CI 6– 39%) against chest radiograph-confirmed pneumonia, 6% (95% CI 2–9%) against clinical pneumonia, and 14% (95% CI 0–26%) against all-cause mortality.” (13)
The cost of the vaccines used in our National Programme ranges from Rs. 3 to Rs. 30.  The cost-efficacy of newer vaccines is quite unfavourable compared to that of these old vaccines. For example assuming that the cost of the hepatitis B vaccine would be Rs. 40 for three paediatric doses and that the chronic carrier rate is 1.6%, the cost per life-year saved for hepatitis B vaccine has been estimated to be 35 times that of the measles vaccine. (14)
Nobody has estimated the cost-efficacy of the Hib vaccine and of pneumococcal vaccine.  Currently, the cost of the Hib vaccine and of pneumococcal vaccine is Rs. 500 and Rs 3000 respectively. It is quite clear that given the very low incidence of Hib meningitis in India (less than 10 per lac child years compared to 1600 per lac child years in case of Hep. B); the lack of efficacy of the pneumo vaccine in preventing pneumonia mortality the cost-efficacy of these two vaccines would be quite unfavourable compared even to the Hep. B vaccine. Even if the cost of these vaccines is brought down to one tenth, even then there is no scientific basis for including them in the National Programme.

Pentavalent vaccine, Injectable Polio Vaccine (IPV)
Global Alliance for Vaccines and Immunization (GAVI) has agreed to provide subsidy for introduction in India of Pentavalent vaccine, which combines the triple vaccine with hep B and Hib vaccine. After GAVI subsidy, its price would drop from Rs. 525/child to Rs. 380/child which is still too high. However it is usual practice of GAVI to withdraw its subsidy after 5 years. Secondly there is a question-mark over the efficacy of this pentavalent vaccine.  Cochrane Database of Systematic Reviews undertook a meta-analysis of the results of 18 studies to compare the effectiveness of combined DTP-HBV-HIB vaccine with DTP-HBV and HIB vaccinations. It was found that in two immunological responses the combined vaccine achieved lower responses than the separate vaccines for HIB and HBV. (15) Apart from the issue of cost-efficacy, there is thus a question mark over the efficacy of the pentavalent vaccine. It will not be prudent to introduce it unless this issue is resolved. Moreover there is a question mark over it’s safety also. We will simply quote a recent Editorial in Indian Journal of Medical Research - “Pentavalent vaccine was introduced in the national immunization programme in Sri Lanka in January 2008 but after several thousand doses were administered, it was withdrawn in April 2008 because of 25 serious adverse reactions that included 5 deaths. A WHO expert panel investigated the adverse effects and deaths and in its report said that the vaccine was ‘unlikely’ to have caused the adverse events. It states that although it was not certain if the vaccine was responsible; the committee could not declare categorically that the pattern of adverse events was unrelated to the vaccine and conclusive evidence regarding an alternate cause of the events and outcome was lacking. This nuanced WHO report was misleadingly summarized to suggest that ‘investigations conducted by WHO did not reveal any causal association between the events and the Hib containing vaccine’. Pentavalent vaccine was then introduced in national immunization programme of Bhutan in July 2009. Within 2 months, after 8 deaths, the vaccine was withdrawn in that country” (16)

In the private sector, doctors are giving the new vaccines to children of ‘affording parents ’. Paediatricians tend to give any vaccine to children of ‘affording parents’ which has some efficacy and is considered safe, even if it is unnecessary or superfluous. For example, in Injectable Polio Vaccine (IPV) is being given at a cost of Rs. 500 per dose to children of ‘affording parents’ in addition to the Oral Polio Vaccine that is being given through the National Programme. This additional IPV is justified on the grounds that it will protect children from Vaccine Associated Paralytic Polio (VAPP). Actually VAPP occurs only in poor children. Like other infectious diseases, it is mainly a disease of malnourishment, insanitation.

The Human Papilloma Virus (HPV) vaccine
The Human Papilloma Virus (HPV) vaccine be given to adolescent girls before they enter into sexual relations is being pushed by a lobby. The declared objective of this vaccination is to prevent Cervical Cancer that can occur about thirty years later due to HPV infection that can occur during sexual relations. It may be given discretely to those who are at high risk of acquiring this infection. However even if cervical cancer is the second most common malignancy in women, there are a number of basic flaws in the suggestion that the HPV vaccine should be given en mass to Indian adolescent girls -
    1. HPV Infection rarely leads to progression to cancer. Only a minority of infections persist for several years, and only about 10% of low-grade lesions progress to higher grade. About 5%of high-grade lesions progress to invasive cancer. (17)
    2. Out of about 100 subtypes of HPV virus, the HPV vaccine protects only from the HPV subtypes 6, 11, 16 and 18. These four subtypes account for only 70% of the HPV infections causing cervical malignancy. (18)
c.    A recent study from India found that out of 31,488 women (30 to 59 years old), who were followed up for over 8 years with no intervention, only 64 died of cervical cancer. (19) Even If we assume that HPV vaccine has 100% efficacy, 4000 women would have to be vaccinated to prevent one death and the cost per life saved would be Rs. 75 million. The average per capita annual income in India in 2010 is Rs. 40,000.
    1. Studies have shown that HPV vaccine protects against these subtypes for 5 years. It is not known whether protection lasts longer than this. Thus if booster doses would be required, the cost of this vaccination would increase substantially. Currently the vaccine costs Rs. 9000 for three doses for primary vaccination. With each booster dose, the cost would increase by Rs. 3000 per dose.
    2. The cost of all vaccines together, currently used in the National Immunization Programme in India is less than Rs. 100. Even if the cost of the HPV vaccine is brought down to Rs. 1000 per girl, the cost of this single vaccine would be still 10 times the cost of all other 6 vaccines! It is impossible to include this vaccine in National Immunization Programme and hence it is unethical to conduct any mass vaccination programme of this vaccine in India to asses it’s suitability for mass vaccination in India. All such programmes are effectively using Indian women as guinea pigs, even if these programmes/trials are conducted with due consent of the recipients. In fact, proper informed consent is generally not taken, as seen from the fact finding done by SAMA, the Delhi based women’s health group, after reported deaths amongst vaccinated tribal adolescent girls in the ‘Demonstration Project’ in Khammam district, in Andhra Pradesh)
    3. It is recommended that vaccinated women too should continue to have regular Pap test screening. Thus the vaccination expenses would be in addition to the expenses for pap screening.
    4. Side-effects-  Just to quote one source, according to the US Centre for Disease Control and Prevention, between June 2006 through December 2008, 772  serious adverse events (6.2 % of the reports) including 32 deaths were reported. The remaining 11652 (93.2%) were classified as non-serious.
             The most common events reported were, syncope), local reactions at the site of immunization (pain and redness), dizziness, nausea and headache. Venous thrombo-embolic events, autoimmune disorders, Guillian Barre Syndrome, motor neuron disease, anaphylaxis, transverse myelitis, pancreatitis and death were amongst the serious adverse events reported. Amongst reports of autoimmune disorders to the VAERS system, 88% were associated with the HPV vaccine alone. (20)

Handsome margin for doctors
Doctors are induced to give unnecessary vaccines by giving them handsome margin. The table below gives the financial incentive to doctors to give the vaccines to children. It is clear from this table that it is no wonder that doctors tend to give these vaccines to any child whose parents can pay for it!
In some places paediatricians charge patients more than the MRP of the vaccine, even after getting the handsome margin from pharma companies. Doctors justify this on the grounds that this is their consultation fee for giving advice to parents about the vaccination. But in fact hardly any ‘consultation’ is done. Most paediatricians have a printed table of which vaccine is to be given at what age. Whichever parent affords any of the vaccine is advised to give it for the child!
Over and above their purchase price of the vaccine, doctors can take 15% margin that pharma companies give to retail chemists and also charge for administering the injection. However, the benefit of the substantial discount they get should be passed on to the patient. When doctors charge more than this by charging MRP to the patients, in my view they are becoming a party to the profiteering in the pharma business. Doctors’ organizations like IMA or IAP or FOGSI should ask the doctors not to indulge into such participation in profiteering. Consumer and various Health Organizations should also make this same demand and put social pressure on these doctors’ organizations on this issue.   


Illustrative List of Margin for Doctors in Newer Vaccines *

Name of Vaccine
Doctor’s purchase price  (Rs)
M.R.P (Rs)
  1.  
Cervical Cancer Vaccine, CERVARIX,
GARDASIL
2299
2132
3300
2800
  1.  
Pentavalent (IPV+HIB+DTaP), PENTAXIM
1308
1735
  1.  
Pain/Feverless DTaP TRIPACEL
717
1220
  1.  
Injectable Polio – IMOVAX
295
345
  1.  
Influenza –VAXIGRIP
449
580
  1.  
Pneumococal Pediat- PREVENAR
3070
3801
  1.  
Chicken Pox – VARILRIX
1055
1430
  1.  
Hepatitis A - HAVRIX PAED
725
906
  1.  
HIB Vaccine : HIBRIX-GSK
                           SHANHIB -SHANTA
                           PEDAHIB - BIOMED
275
320
145
400
425
350
  1.  
HIB+DTP+HEP B =PENTA = EASY 5
404
585
  1.  
HIB +DTP- TETRA ACTHIB   
                                      EASY4
295
360
485
500
  1.  
HEP.B+ D.P.T = TRIANTRIX  MULTI
                            TRIANTRIX-HB MONO
945
193
1130
225
  1.  
Hepatitis-B -- REVAC - B 10ML
150
550
* Prices in Mumbai in December 09,  4 % VAT EXTRA

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References

  1. Yash Paul, Polio Eradication : Experts have misled us, Medical Veritas 3 (2006) pg. 781-785, P. 784
  2. based on data from www.npsindia.org
  3. Jacob M. Puliyel, Manoj Anand Gupta, Joseph L.Mathew.  Polio eradication & the future for other programmes: Situation analysis for strategic planning in India. Editorial, Indian J Med Res 125, Jan. 2007, pp 1-4; Sathyamala, Indian J Med Res 125, May 2007, Correspondence, pp 695-696)
  4.  Ghendon Y. WHO Strategy for the global diminution of new cases of hepatitis B, Vaccine 1990, 8: S 129-133
  5. Thyagarajan S.P, S.Jayaram, B. Mohanvalli. Prevalence of HBV in the General Population of India, in Hepatitis B in India, (Ed.) S.K.Sarin, A.K.Singhal, CBS Publishers & distributors, 1996, P.9.
  6. Anant Phadke, Ashok Kale . HBV Carrier Rate in India. Indian Pediatrics, (Letters to the Editor), Vol. 39, Aug. 17, 2002
  7.  Issues Related to Hepatitis B Vaccination in India: Systematic Review of Literature, Indian Medical Association Sub-committee on Immunization, Chairperson Professor S K Mittal, Indian Medical Association Delhi, May 2006.
  8. Joseph L. Mathew. Pneumococcal vaccination in developing countries: Where does science end and commerce begin? in Vaccine 27 (2009) 4247–4251.
  9. Keith P. Klugman, M.B., B.Ch., Ph.D., Shabir A. Madhi, M.B., B.Ch., Robin E. Huebner, Ph.D., Robert Kohberger, Ph.D., Nontombi Mbelle, M.B., B.Ch., M.Med., Nathaniel Pierce, M.D. A Trial of a 9-Valent Pneumococcal Conjugate Vaccine in Children with and Those without HIV Infection. NEJM, Volume 349, Number 14: pp.1341-1348,
  10. Lucero MG, Dulalia VE, Nillos LT, Williams G, Parreño RA, Nohynek H, Riley ID, Makela H. Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and X-ray defined pneumonia in children less than two years of age. Cochrane Database Syst Rev. 2004;(4):CD004977.
  11. Sona Chowdhary  and Jacob Puliyel. Incidence of pneumonia is not reduced by pneumococcal conjugate vaccine. Letters, Bulletin of the World Health Organization | October 2008, 86 (10)
  12. Minz S, Balraj V, Lalitha MK, Murali N, Cherian T, Manoharan G, Kadirvan S, Joseph A, Steinhoff MC. Incidence of Haemophilus influenzae type b meningitis in India.” by Minz S, Balraj V, Lalitha MK, et al. Indian J Med Res. 2009 Feb;129(2):205;
  13. Global status of Haemophilus influenzae type b and pneumococcal conjugate vaccines: evidence, policies, and introductions. Orin S. Levine, Maria Deloria Knoll, Andrew Jones, Damian G. Walker, Nicholas Risko and Zunera Gilani Current Opinion in Infectious Diseases 2010, 23:236–241
  14. Anant Phadke,  Ashok Kale, Comparative Cost-efficacy of Hepatitis-B-Vaccination in Indian Infants. Paper presented at the National Workshop on Sustainable Vaccine Policy, NISTADS, New Delhi, 4th-5th June 2009.
  15. Edna S Bar-On, Elad Goldberg, Abigail Fraser, Liat Vidal, Sarah Hellmann, Leonard Leibovici. Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB). Cochrane Database of Systematic Reviews, Issue 4, 2009
  16. Zubair Lone & Jacob M. Puliyel. Introducing pentavalent vaccine in the EPI in India: A counsel for caution. Editorial, Indian J Med Res 132, July 2010, pp 1-3
  17.  Human papillomavirus: often harmless but in some cases carcinogenic. Prescrire International, Vol. 16, Issue 89, Pages 115-119
  18. Human papillomavirus vaccines: WHO position paper, in Weekly epidemiological record,10 APRIL 2009, ANNÉE, No. 15, 2009, 84, 117–132, http://www.who.int/wer,  HPV.
  19.  Sankaranarayanan R, Nene BM, Shastri SS, JayantK, Muwonge R, Budukh AM, et al. HPV screeningfor cervical cancer in rural India. N Engl J Med 2009; 360: 1385-1394.
  20. Centre for Disease Control and Prevention, USA, “Summary of HPV adverse events reports published by JAMA” http://www.cdc.gov/vaccinesafety/vaers/HPV_JAMA.htm


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4503 words






* 8, Ameya Ashish co-op. Hsg. Society, Kokan Express Hotel lane, Kothrud, Pune 411038,
anant.phadke@gmail.com  020 25460038, 09423531478

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