A world without vaccines
N.K. GANGULY and SANJUKTA SENGUPTA
VACCINES have been used to protect millions from disease since the time of Edward Jenner. The results of his pioneering experiments, successfully demonstrating that protection from smallpox was possible by inoculating cowpox virus into an incision in a boy’s arm, was published way back in 1798. This experiment was based on a simple observation that only milkmaids had faces free from pockmarks in England circa 1700. His work, followed by that of Louis Pasteur, led to the elimination of smallpox in 1979. At that time the disease threatened nearly 60% of the world’s population.
Since then mass vaccination programmes have prevented illness or death from a number of diseases for millions of people every year. For example, after the measles vaccine was introduced, measles deaths decreased worldwide by almost 40% between 1999 and 2003. In many countries of the world where vaccines are in use, infectious maladies like diptheria, tetanus, measles, diarrhoea and meningitis have been controlled significantly. In recent years, vaccines have also been central in the reduction of polio cases in India alone by 95% between 2009 and 2010.
While it is true that smallpox is the only disease to have been eradicated, there are many more which have been markedly reduced. Before Hib vaccine became available, Hib used to be the most common cause of bacterial meningitis in infants and children in the United States. There were around 20,000 invasive cases each year of which two thirds were meningitis. Hib-meningitis killed 600 children each year and left many survivors with deafness, seizures, or mental retardation. Since introduction of conjugate Hib vaccine in December 1987, the incidence of Hib has declined by 98%. Such reductions were also seen in other countries that have introduced the Hib conjugate vaccine. Whether in terms of lives and health resources saved, vaccines are one of the best investments that can be made by a country.1
Unlike other public health interventions, vaccines are unique in the fact that they also confer indirect benefits to the unimmunized – by reducing the number of potentially infective people. These include infants and elderly too. When vaccines are used to prevent illness and death, the push to expand their usage and implementation also delivers major economic and societal benefits to families and the government.
Communicable diseases, many of which are vaccine preventable, account for 77% of the mortality gap between the world’s poorest and richest 20%. They also disproportionately affect the poorest fifth of the population, the quintile that suffers from lack of clean drinking water and proper sanitation facilities as well. As in India, the urban-rural divide in other developing countries is also quite significant, both in access to vaccines as well as clean water and sanitation.
The UN Millennium Development Goals (MDGs), which aim to be achieved by 2015, provide numerical benchmarks for tackling extreme poverty in its many dimensions. They also unite the international community within a framework to work toward several common goals. The percentage of the world’s population with access to improved drinking water sources increased from 77% to 87% between 1990 and 2008. Given the current rate, it is likely this target of the MDG 7 will be met in time. This is, however, not true for sanitation goals; current rate of improvement is insufficient to meet targets by 2015.2 It is a mammoth task to achieve, especially for a vast and diverse country like ours, both in terms of populace and geography.
Although vaccines are a critical component of disease prevention strategies, vaccines alone cannot tackle the high burden of diseases, especially in developing and highly populated countries. There is a growing need to deploy a combination of available strategies. A weak health system coupled with enormous population, spread over diverse geographical regions, makes achieving these goals difficult. Comprehensive disease prevention interventions that include strategies to protect, prevent and treat high burden diseases are needed, along with improvements in the health system that make it more robust and supportive.
Many interventions have a broad application and can be integrated into existing health programmes. For example, exclusive breastfeeding for the first six months of a child’s life could considerably reduce cases of pneumonia and diarrhoea – two of the leading causes of child morbidity and mortality in India. Other preventive interventions include hand washing, improved living environment, and access to appropriate disease management therapy.
Despite improvements in supply of clean water and improvement in sanitation facilities, there are several gaps: financial, infrastructural and social. These need to be bridged in order to create and sustain amenities for longer periods. Unplanned urbanization, migration of rural population towards the cities, and occurrence of natural calamities at regular intervals, keep challenging any progress in this area. Cleaning the environment also requires sustainable innovation, multisectoral cooperation and uprooting a number of ‘cultural’ barriers. Moreover, vaccines have the potential to save lives and help limit epidemics. It is estimated that rapid mass vaccination campaigns with a single-dose oral cholera vaccine could have saved more than 41,000 lives during the Zimbabwe cholera outbreak in 2008.3
Although there has been a reduction in child deaths in absolute numbers so far, with an average annual rate of reduction in under-five mortality at 3.1% India remains off-track to achieve MDG4 by 2015 – a reduction in child mortality by two thirds from the 1990 level. The country contributes to nearly 22% of children aged less than five years dying in this world every year, despite being among the fastest growing economies.4 Pneumonia and diarrhoeal diseases are the two biggest killers of children in this age group, the two together responsible for 33% of childhood mortality in India. Both pneumonia and diarrhoea are vaccine preventable and countries have been able to bring about reduction in mortality and morbidity significantly where vaccines that protect against them have been implemented
Pneumonia is caused by bacteria such as Haemophilus influenzae type B (Hib) and pneumococcus, several viruses, parasites and also fungi. There is no test that can identify the biological cause of pneumonia at the bedside and hence antibiotics are prescribed often under the assumption that the infection is bacterial. In developing country settings like ours, about 50% of cases do happen to have bacterial origin The very fact that antibiotic therapy is effective in reducing mortality from pneumonia suggests that the bacterial assumption is accurate.5
Hib meningitis kills 10% of Indian children infected and leaves 30% of survivors with permanent disabilities. .Studies from surrounding countries in which a vaccine has been used as a ‘probe’ provide confidence that Hib is much more prevalent than seen by surveillance,6 and local data corroborates this assumption. Recently, in a hospital-based study done in four hospitals throughout India, Hib was indeed the leading pathogen for bacterial meningitis in India, with proportions of meningitis due to Hib similar to those observed in the United States in the pre-vaccine era.7
Disease surveillance does not always provide a correct picture of incidence of meningitis for several reasons: (i) Lumbar punctures are invasive and so inconsistently performed in developing country settings; (ii) the organism is fastidious and hard to culture, particularly from children who have had antibiotics, especially in countries like India where antibiotics are widely used prior to seeking treatment at hospitals; and (iii) culturing Hib requires proper sample storage, handling, and processing, all of which are difficult in resource poor settings. Hib pneumonia is even harder to gauge because the majority of pneumonias are not bacteremia (bacteria detected in blood) and therefore not detectable by routine, blood culture based surveillance.
The vaccine against Hib can be given alone or in combination with diphtheria, pertussis, tetanus and Hep B vaccines in pentavalent form, which protects children from five causes of potentially deadly diseases in one shot. This vaccine is now being introduced in Kerala and Tamil Nadu. The presentations of Hib vaccine that have been used in different parts of the world are different. The combination vaccines used in the US and other developed countries mostly contain pertussis component in an ‘acellular form’ while the vaccines used in the developing countries have inactivated whole pertussis bacilli.
The reduction in immunogenicity of the acellular vaccines has not been shown to have any effect on clinical effectiveness, which is truly reflected in impact studies. Results from these studies are unanimously supportive of pentavalent vaccines. Acellular pertussis containing Hib vaccines are used all over the western world with excellent documented effectiveness. Furthermore, the added convenience of a combination vaccine is important for its potential impact on the health system as it replaces one vial for another without having to manage separate products and reduces the risk of refusals due to a desire to have fewer shots. Although the acellular pertussis vaccines cause fewer side effects, they are difficult to manufacture and are substantially expensive. India plans to use the pentavalent vaccines that contain the whole cell pertussis. A field trial carried out in India found the formulation to be used in the country safe and immunogenic (DTwP-HepB-Hib).8 The vaccine has been offered at $1.75 a dose by the company.9
The pneumococcal conjugate vaccine is recommended to be given to infants as a series of three doses, at 6, 10 and 14 weeks and is therefore compatible with the existing Universal Immunization Programme (UIP) schedule. Two of the Indian manufacturers have pledged the vaccine for Advance Market Commitment (AMC) to GAVI at US$7.00 for initial 20% doses and the rest at US$ 3.75 and the vaccine should be available by 2014. Should the Indian government decide to introduce the vaccine, it can negotiate a better price of the vaccine directly from the manufacturer, as the size of the birth cohort in the country is large enough to offer a sizable market. Several pneumococcal protein vaccines, others using a fusion between protein and conjugate vaccine as well as a whole cell vaccine for pneumococcal infections are also being developed to offer pan-serotype coverage but will take several years before they are available.10
The Lives Saved Tool (LisT) is a computer tool used to develop scenarios – using a combination of best scientific information about effectiveness of intervention with information about cause of death and current coverage of interventions – to inform planning and decision making. An estimation using this tool revealed scale-up of non ‘WASH’ interventions such as rotavirus vaccines would be as much as seven times cheaper than ‘WASH’ interventions that include hand washing, improved sanitation, access to safe water and home purification of water and would bring down the mortality due to diarrhoea by 78% in 68 countries that contributed to 95% of diarrheal deaths. There are as many as four different rotavirus vaccines that will be available from Indian manufacturers in a few years, including an indigenous vaccine currently undergoing trials to demonstrate the immunogenicity and safety of co-administration with other Universal Immunization Programme (UIP) vaccines.11
There are several other diseases that are important in public health and are vaccine preventable and cannot be taken care of by other measures, such as rabies and cancer. Until very recently, nearly half of estimated global rabies deaths occurred in India, three quarters of which took place in rural areas. Rabies is transmitted to humans through saliva of a range of animals and is absolutely fatal beyond a certain point. In the endemic countries where 30-60% victims are below the age of 15 years, vaccines can be effectively used to prevent rabies. Rabies control requires that immunity is maintained in dogs by immunizing at least 70% of them and prevent a spill-over from neighbouring areas. This is practically impossible to achieve in India, which has a total dog population of approximately 25 million and shares boundaries with six rabies endemic countries.
Post-exposure treatment with a rabies vaccine with cell-based vaccines is the recommended alternative. This has undergone significant improvements from painful nerve-issue based vaccines, which were administered in the abdomen, to intradermally administered cell-based vaccines that are less painful and cost 60-80% less than the intramuscular injections.
Supportive systems and infrastructure form the backbone of any comprehensive approach for preventive health. India’s National Rural Health Mission has brought about significant changes in the public health scenario in India since its inception in 2005, with respect to delivery and management at the grassroot level. The percentage of institutional births crossed 70% whereas vaccination coverage has reached >70-80% in 11 states. However, significant improvements are needed in record keeping and documentation at all levels irrespective of the intervention chosen. Tracking migrant populations, improving disease surveillance and reporting adverse effects will enable the public health system to respond promptly to emergencies. Health workers should also be used for advocacy and awareness campaigns among the public for optimal utilization of available resources, in addition to their role in delivery of health care.
Although all vaccination programmes strive to supply vaccines that are inherently safe and administered correctly, no vaccine is 100% safe. Eradication of diseases like smallpox with vaccination has also wiped-off memories of pain and the scars of the disease itself and has given way to concerns about adverse events caused by the vaccines. There is a need for appropriate authorities to systematically and promptly clarify rumours associated with serious adverse events seen after mass scale vaccination. A new set of guidelines to resolve the AEFI (adverse effects following immunization) have been framed by the MoHFW, Government of India.12 It remains to be seen how closely compliance to these guidelines is monitored.
It is essential that the results of any investigation are conveyed to the community, as misinformation can lead to derailment of such programmes. During the 1970s, widespread concerns about the safety of the whole cell pertussis vaccine led to a rapid fall in immunization levels in the United Kingdom. More than 100,000 cases and 36 deaths due to pertussis were reported in an epidemic in the mid-1970s. In eight countries where immunization coverage was reduced, incidence rates of pertussis surged to 10 to 100 times the rates in countries where vaccination rates were sustained.13
Clean water and sanitation initiatives should be continued unabated irrespective of the hurdles, both foreseen and unforeseen. The effort to clean the environment will also aid preventive health in the long run. On the other hand, it will be criminal to deprive a population of the benefits of interventions available as a result of advances in the field of medicine and technology, particularly those that have been used effectively elsewhere in the world and have reduced deaths due to infectious diseases considerably.
All the ‘new vaccines’ are available in private sector, but decisions to include them in the public programme on a pan-India scale are pending. Thus, they remain out of reach for a majority of those who are in need and rely on the programme. For India, which has made enormous progress on the economic front, it is ignominious to be contributing to one in five child deaths occurring in the world every year despite effective vaccines against these diseases.14
1. F.E. Andre, R. Booy, H.L. Bock, J. Clement, S.K. Datta, T.J. John et al., ‘Vaccination Greatly Reduces Disease, Disability, Death and Inequity Worldwide’, Bulletin WHO 9200, 86(2), pp. 81-160.
2. The Millenium Development Goal Report ( 2011) http://mdgs.un.org/unsd/mdg/Resources/Static/Data/2011%20Stat% 20Annex.pdf
3. R. Reyburn, J.L. Deen, R.F. Grais, S.K. Bhattacharya, D. Sur, et al., ‘The Case for Reactive Mass Oral Cholera Vaccinations’, PLoS Neglected Tropical Diseases 5(1), 2011, e952.doi:10.1371/journal.pntd.0000952
4. http://www.childinfo.org/files/Child_ Mortality_Report_2011.pdf
5. A.T. Bang, R.A. Bang, et al., ‘Reduction in Pneumonia Mortality and Total Childhood Mortality by Means of Community Based Intervention Trial in Gadchiroli, India’, The Lancet 336(8709), 1990, pp. 201-206.
6. B.D. Gessner, A. Sutanto, et al., ‘Incidences of Vaccine-Preventable Haemophilus Influenzae Type B Pneumonia and Meningitis in Indonesian Children: Hamlet-Randomised Vaccine-Probe Trial’, Lancet 365(9453), 2005, pp. 43-52;
7. P. Ramachandran, S.F. Fitzwater, et al., ‘Prospective Multicenter Sentinel Surveillance for Haemophilus Influenzae Type B and Other Bacterial Meningitis in Indian Children’, Indian Journal of Medical Research, submitted May 2011.
8. H. Sharma, S. Yadav, et al., ‘A Phase III Randomized, Controlled Study to Assess the Immunogenicity and Tolerability of DTPw-HBV-Hib, a Liquid Pentavalent Vaccine in Indian Infants’, Vaccine 29(13), 2011, pp. 2359-2364.
9. http://www.seruminstitute.com/content/news_4.htm (last accessed 30 August 2011)
10. Y.J. Lu, L. Leite, V.M. Gonçalves, et al., ‘GMP-Grade Pneumococcal Whole-Cell Vaccine Injected Subcutaneously Protects Mice From Nasopharyngeal Colonization and Fatal Aspiration-Sepsis’, Vaccine 28(47), 2010, pp. 7468-75.
11. C.L. Fischer Walker, I.K. Friberg, N. Binkin, et al., ‘Scaling up Diarrhoea Prevention and Treatment Interventions: A Lives Saved Tool Analysis’, PLoS Medicine (3), e1000428, 2011.
12. http://126.96.36.199/nihfw/nchrc/index.php?q=content/adverse-events-following-immunization-aefi-operational-guidelines-surveillance-and-response-(last accessed 5 September 2011)
13. E.J. Gangarosa, et al., ‘Impact of Anti- Vaccine Movements on Pertussis Control: The Untold Story’, Lancet 351, 1998, pp. 356-61.
14. http://www.who.int/whosis/whostat/EN_WHS2011_Part1.pdf) (last accessed 30 August 2011)
* Additional Reading: Drinking Water and Sanitation Status in India. Water Aid India 2005.