|DR B C DASGUPTA MEMORIAL ORATION
|Year : 2016 | Volume
| Issue : 3 | Page : 171-175
Challenges in new vaccine introduction in a national program in India
Consultant to Sabin Vaccine Institute, Washington, USA
|Date of Web Publication||24-Aug-2016|
Dr. Dipika Sur
Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO box #04, Faridabad - 121 001 (Haryana)
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Vaccines have a long history dating back to the days of Edward Jenner (1749-1823) and Louis Pasteur (1822-1895). Vaccines can be viewed from a public health perspective as well as scientific perspective. Public health experts would focus epidemiological relevance, immunological competency, and technological feasibility. Scientists however will look for a good immune response as well as long-lived immunity, stability considerations, and safety issues such as danger of reversion to virulence. In India, the vaccine coverage is far from satisfactory, national average for full immunization being only 65%. Presently, nine vaccines are being used in the Universal Immunization Program. However, some more have started in pilot, and some are still in the pipeline. Although administrative, logistic and operational challenges have to be faced when introducing a new vaccine into the public health system; these are solvable and should not be a hindrance to the introduction. A real-life example of nonintroduction of a lifesaving vaccine is - the oral cholera vaccine. This vaccine which is manufactured and licensed in India has been the World Health Organization (WHO) prequalified, and it is being used worldwide. Although the disease is a major threat, the disease has its stigma and has led to its low reporting even from cholera endemic areas of the country. Thus, in spite of the WHO recommendations, the vaccine is not being introduced into the national program which would take it to people who need it the most only because of apparent lack of sufficient disease burden data and political commitment.
Keywords: Cholera, immunization, introduction, new vaccines
|How to cite this article:|
Sur D. Challenges in new vaccine introduction in a national program in India. Indian J Public Health 2016;60:171-5
| Glimpses of Vaccination History|| |
Edward Jenner: Dawn of the vaccine era
Jenner (1749-1823) was an English physician and scientist who was the pioneer of smallpox vaccine, the world's first vaccine. He is often called "the father of immunology," and his work is said to have "saved more lives than the work of any other human." Noting the common observation that milkmaids were generally immune to smallpox, Jenner postulated that the pus in the blisters that milkmaids received from cowpox (vaccinia) which is a disease similar to smallpox, but much less virulent, protected them from smallpox. On May 14, 1796, Jenner tested his hypothesis by inoculating James Phipps, an 8-year-old boy, who was the son of Jenner's gardener. He scraped pus from cowpox blisters on the hands of Sarah Nelmes, a milkmaid who had caught cowpox from a cow called Blossom. Jenner inoculated Phipps in both arms that day, subsequently producing in Phipps a fever and some uneasiness, but no full-blown infection. Later, he injected Phipps with variolous material, the routine method of immunization at that time. No disease followed. The boy was later challenged with variolous material and again showed no sign of infection. 
Jenner not only received honors but also found himself subjected to attacks and ridicule. Caricatures were made of Jenner vaccinating patients who feared it would make them sprout cow-like appendages.
Inoculation (variolation) with variola (smallpox material) was replaced by vaccination using cowpox (vaccinia) by Jenner and gradually, vaccination replaced variolation, which became prohibited in England in 1840. In 1967, a global campaign was begun under the guardianship of the World Health Organization (WHO) and finally succeeded in the eradication of smallpox in 1977.  The discovery and promotion of vaccination enabled the eradication of smallpox: This is Edward Jenner's ultimate vindication and memorial. 
Louis Pasteur and the World's First Rabies Vaccine
Louis Pasteur (1822-1895) was a French chemist and microbiologist renowned for his discoveries of the principles of vaccination, microbial fermentation, and pasteurization. 
He developed the rabies vaccine by growing the virus in rabbits, then drying the affected nerve tissue to weaken the virus. On July 1885, the vaccine was administered to Joseph Meister, a 9-year-old boy who had been bitten by a rabid dog. The boy survived and did not contract rabies, which would have almost certainly proved fatal. Three months later, Pasteur examined Meister and found that he was in good health. 
Pasteur also invented a process in which liquids such as milk were heated to a temperature between 60 and 100°C. This killed most bacteria and molds already present within them. The method became known as pasteurization, and it was soon applied to beer and milk. 
| Vaccines|| |
From a public health perspective
There are several important aspects for considering a vaccine as ideal. To begin with, it should be epidemiologically relevant and should be applicable only for diseases of public health importance. Obviously, immunological competency of the vaccine has to be initially established. Technological feasibility is a criterion, especially for those vaccines which have to be administered in a route other than the routine immunization (RI) methods and also methods of reconstitution of the vaccine, etc., As an example, if the vaccine has to be delivered intravenous, it will not be feasible for the health workers to handle it. Further, issues such as maintaining very low temperature at the vaccination centers, using buffers, etc., need to be considered when introducing a new vaccine. Social acceptability again depending on the route of administration (like intravaginal route), the disease under consideration which might have a stigma attached to it like HIV have to be kept in mind during the planning stage of a vaccine introduction. For introduction of a vaccine through the public health program, affordability and sustainability are important aspects to be considered.
From a scientific perspective
Again from a scientific point of view, good immune responses (both cell-mediated immunity and antibody response) are important parameters as well as long-lived immunity. A single dose vaccine is always preferable to multiple doses.
Safety issues such as danger of reversion to virulence or severe disease in immunocompromised are totally unacceptable in a vaccine. Important stability considerations of the organisms in the vaccine are that they must remain viable to infect and replicate in the host. At the same time, the preparation should be less sensitive to adverse storage conditions. Of course, the expenses to the exchequer should be another point of consideration.
Major Benefits of Vaccination
Vaccines prevent disease, save lives, improve health, especially in children, improve quality of life, and very effectively reduce antibiotic resistance. 
Vaccines: Global Facts and Figures
Currently, vaccines are available against 26 infectious diseases; however, many more are in the pipeline. In the past before smallpox eradication in 1977, the disease threatened 60% of the world's population. Since introduction of the measles vaccine, measles deaths decreased worldwide by almost 40% by 2003.
- Vaccines save over 2 million children every year. ,
Present status of immunization in India
Approximately, 9 million RI sessions are held in India each year targeting 26 million children and 30 million pregnant women. The sessions are served through a massive 27,000 cold chain stores.
The national average for full immunization is 65%, and for DPT-3 coverage is 72%.
India has the biggest number of children not immunized with DPT-3: 7.4 m. Each National Immunization Day, 172 million children are immunized for polio. India's polio vaccination campaigns cover 800 million children a year. A 3-year campaign to ensure children receive the second measles vaccination is targeting 135 million children, with 70 million children covered in 2012-2013 alone. In a special drive in 2012-2013, 15.35 million doses of vaccines were administered to children who had earlier been missed. ,
Rural children are least likely to have complete vaccination, and this inequity is most pronounced in states such as Madhya Pradesh, Rajasthan, Chhattisgarh, Jharkhand, and Uttar Pradesh. The number of districts with <80% DPT3 coverage: 403 out of 601, i.e., 67% or two-thirds.
Vaccines in Universal Immunization Program
Presently 9 vaccines:
- BCG - mainly against miliary TB and TB meningitis
- OPV - poliomyelitis
- DPT- diphtheria, pertussis, and tetanus
- Measles - measles infection
- Hep B - hepatitis B infection
- JE - Japanese Encephalitis
- Hib - Hemophilus influenzae B in the form of pentavalent vaccine containing DPT, Hib, and Hep B.
To start in pilot mode:
- Adult JE, MR (Measles, Rubella), inactivated polio vaccine, and rota (rotavirus vaccine).
- Pneumococcal conjugate vaccine.
The new vaccine initiatives of the Government of India are to continue polio eradication initiatives to its conclusion, measles elimination and rubella and congenital rubella syndrome control, introduction of new and underused vaccine based on the burden and evidence and strengthen RI through "Mission Indradhanush."
Decision to introduce a new vaccine depends on:
- Evidence and documentation of disease burden
- Availability of vaccine(s) doses
- Cost-effectiveness and cost-benefit analysis: Managing competing health-care priorities better
- Implementation issues: Sustainable financing, cold chain, etc.
- Last mile delivery: Training of personnel
- Physician and user: Knowledge, attitude, and practice, advocacy, and communication
- Assessment of expected impact.
General World Health Organization position on new vaccines 
Vaccines for large-scale public health use should:
- Meet the quality requirements as defined in the Global Programme on Vaccines policy statement on vaccine quality
- Be safe and have a significant impact against the actual disease in all target populations
- If intended for infants or young children, be easily adapted to schedules and timing of the national childhood immunization programs
- Not interfere significantly with the immune response to other vaccines given simultaneously
- Be formulated to meet common technical limitations, for example, in terms of refrigeration and storage capacity
- Be appropriately priced for different markets.
In spite of all recommendations, certain challenges remain to be solved before planning to introduce a new vaccine in the public health system. Most vital of the issues is political commitment and will. Provided this is in the affirmative, other aspects such as administrative involvement, demand and supply of the vaccine, and ultimately the finances, need to be resolved in due course.
Some operational challenges such as logistic supply including cold chain storage and microplanning have to be taken into consideration. Further workforce training including training of trainers as well as frontline health workers is necessary.
However, these challenges are solvable and should not be a hindrance to introduction of a new vaccine.
| A Real-Life Example: Introduction of Cholera Vaccine - Still Awaited|| |
Cholera is a disease of inequity. It is caused by poverty, lack of sanitation, and clean water. High-risk groups include young children and pregnant women. It is also a potential source of diarrheal outbreak in disaster situations and humanitarian crises. Those most vulnerable can be provided with vaccine.
Cholera is described by the WHO as "one of the most rapidly fatal infectious illnesses known." It has an extremely short incubation period and has endemic as well as epidemic potentials. Although there is gross underreporting, the WHO estimates more than 120,000 deaths and 3-5 million cases (mortality of ~4%) per year. A literature survey revealed that India had more than 222,038 cases over 10 years (1997-2006) although because of underreporting, the WHO reported only 37,783 over the same time period. The study revealed that most of the states in India are affected by cholera. 
The main problem of underreporting is that notifying cholera has political as well as economic (affecting travel and trade) implications and thus it is more convenient to describe a cholera outbreak as acute watery diarrhea or gastroenteritis. Years of conveying such a wrong impression has removed the problem of cholera from public memory, and now the notion is that there is very little or no cholera in India. 
The cholera vaccine story
A bivalent killed oral cholera vaccine (OCV) was developed in Sweden initially as killed whole cell vaccine with recombinant B subunit (WC/rBS). Following technology transfer to Vietnam, a WC-only vaccine was produced which showed similar protection as the WC/rBS. This vaccine was reformulated by the International Vaccine Institute and transferred to Shantha Biotech in India for large scale manufacture. 
Based on the results of a Phase II study, a double-blind randomized Phase III trial of the reformulated OCV was conducted in a cholera-endemic urban slum area in Kolkata among 110,000 populations. It is a two-dose vaccine given at an interval of at least 2 weeks and administered to all participants aged 12 months and older (excluding pregnant women).
This study was carried out by the National Institute of Cholera and Enteric Diseases, Kolkata, in collaboration with International Vaccine Institute, Seoul, Korea. Protective efficacy of the vaccine after 2, 3, and 5 years was 67%, 66%, and 65%, respectively. This has resulted in its licensure in India in 2009, as well as WHO prequalification in 2011.  The WHO along with Global Alliance for Vaccines and Immunization has setup a stockpile of the vaccine which is now being used worldwide. Till date, more than 2.9 million doses of the vaccine have safely been given in more than 14 countries.
The WHO recommendation on cholera vaccination is as follows:
Cholera control should be a priority in areas with endemic cholera since cholera outbreaks can disrupt health systems. Cholera vaccines should be used in areas where the disease is endemic and should be considered for use in areas at risk for outbreaks in conjunction with other prevention and control strategies. 
Recommendations of Indian Policymakers
On April 10, 2009, a meeting was organized by the Indian Council of Medical Research, the Department of Biotechnology. This meeting was attended by Indian state and national officials, representatives from the international institutes and organizations such as the WHO and UNICEF. The outcome of the meeting was very encouraging with commitment from the attendees to advocate for the use of the OCV in cholera control.  The recommendations from the meeting are as follows:
- As the modified WC vaccine is safe, effective, and cost-effective, it was suggested that the National Technical Advisory Group on Immunization should consider recommending introduction of the vaccine in public health programs targeted to appropriate populations in India
- Vaccination should be initiated in selected highly endemic and/or slum areas such as known areas in West Bengal or Odisha. The pilot vaccination programs will be monitored and evaluated. Further expansion to other areas and wider policy changes will be made in a step-by-step fashion based on the pilot programs. Logistical and operational issues need to be defined. Follow-up meetings are suggested to ensure that the agenda moves forward
- Underreporting is an issue, and thus a national surveillance system should be established to generate more disease burden data
- While vaccination is an effective short- to medium-term solution for the prevention and control of cholera, it should be considered complementary to other long-term interventions such as improvements in water safety, sanitation, and hygiene. ,
As an effect of underreporting of the disease as mentioned above, OCV is not yet being used in India through the national program which should take it to people who need it the most. In spite of the fact that the vaccine is manufactured and available in India, it is WHO prequalified and recommended for epidemic and endemic situations, available through WHO stockpile and it is cost-effective when used strategically, the vaccine is not being given due importance by the policymakers in India.
Thus, the story for cholera vaccine introduction in India remains an enigma. Although we have recommendations of the WHO for a safe and effective vaccine, and we undoubtedly have cholera in the country, but no decision has yet been taken on its introduction in the national program. 
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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