Vaccination greatly reduces disease, disability, death and inequity worldwide

FE Andre a, R Booy b, HL Bock c, J Clemens d, SK Datta c, TJ John e, BW Lee f, S Lolekha g, H Peltola h, TA Ruff i, M Santosham j, HJ Schmitt k

Introduction

Vaccination has greatly reduced the burden of infectious diseases. Only clean water, also considered to be a basic human right, performs better.1 Paradoxically, a vociferous antivaccine lobby thrives today in spite of the undeniable success of vaccination programmes against formerly fearsome diseases that are now rare in developed countries.2

Understandably, vaccine safety gets more public attention than vaccination effectiveness, but independent experts and WHO have shown that vaccines are far safer than therapeutic medicines.2,3 Modern research has spurred the development of less reactogenic products, such as acellular pertussis vaccines and rabies vaccines produced in cell culture. Today, vaccines have an excellent safety record and most “vaccine scares” have been shown to be false alarms.4,5 Misguided safety concerns in some countries have led to a fall in vaccination coverage, causing the re-emergence of pertussis and measles.6

Putative vaccine safety issues are commonly reported while reviews of vaccine benefits are few. A Medline search over the past five years using the keywords “vaccine risks” scored approximately five times as many hits (2655 versus 557) as a Medline search using “vaccine benefits” as keywords.7 This reflects the fact that negative aspects of vaccination get much more publicity than positive aspects.

How one addresses the antivaccine movement has been a problem since the time of Jenner. The best way in the long term is to refute wrong allegations at the earliest opportunity by providing scientifically valid data. This is easier said than done, because the adversary in this game plays according to rules that are not generally those of science. This issue will not be further addressed in this paper, which aims to show how vaccines are valuable to both individuals and societies, to present validated facts, and to help redress adverse perceptions. Without doubt, vaccines are among the most efficient tools for promoting individual and public health and deserve better press.8

Disease control benefits

Eradication

Unless an environmental reservoir exists, an eradicated pathogen cannot re-emerge, unless accidentally or malevolently reintroduced by humans, allowing vaccination or other preventive measures to be discontinued.

While eradication may be an ideal goal for an immunization programme, to date only smallpox has been eradicated, allowing discontinuation of routine smallpox immunization globally. Potentially, other infectious diseases with no extrahuman reservoir can be eradicated provided an effective vaccine and specific diagnostic tests are available. Eradication requires high levels of population immunity in all regions of the world over a prolonged period with adequate surveillance in place.9 The next disease targeted for eradication is polio, which is still a global challenge.10 Although high coverage with oral polio vaccine (OPV) has eliminated type 2 poliovirus globally, transmission of types 1 and 3 continues in limited areas in a few countries. OPV-caused paralytic disease, directly or by reversion to virulence, and persistent vaccine-virus excretion in immunodeficient individuals are problems yet to be solved. Global use of monovalent type 1 and type 3 OPV and inactivated polio vaccine (IPV) may eventually be required.10

Elimination

Diseases can be eliminated locally without global eradication of the causative microorganism. In four of six WHO regions, substantial progress has been made in measles elimination; transmission no longer occurs indigenously and importation does not result in sustained spread of the virus.11 Key to this achievement is more than 95% population immunity through a two-dose vaccination regimen. Combined measles, mumps and rubella (MMR) vaccine could also eliminate and eventually eradicate rubella and mumps.11 Increasing measles immunization levels in Africa, where coverage averaged only 67% in 2004, is essential for eradication of this disease. Already, elimination of measles from the Americas, and of measles, mumps and rubella in Finland has been achieved, providing proof in principle of the feasibility of their ultimate global eradication.12 It may also be possible to eliminate Haemophilus influenzae type b (Hib) disease through well implemented national programmes, as experience in the West has shown.13

Local elimination does not remove the danger of reintroduction, such as in Botswana, polio-free since 1991, with importation of type 1 poliovirus from Nigeria in 2004,14 and in the United States of America (USA) with measles reintroduced to Indiana in 2005 by a traveller from Romania.15

For diseases with an environmental reservoir such as tetanus, or animal reservoirs such as Japanese encephalitis and rabies, eradication may not be possible, but global disease elimination is a feasible objective if vaccination of humans (and animals for rabies) is maintained at high levels.

Control of mortality, morbidity and complications

For the individual

Efficacious vaccines protect individuals if administered before exposure. Pre-exposure vaccination of infants with several antigens is the cornerstone of successful immunization programmes against a cluster of childhood diseases. Vaccine efficacy against invasive Hib disease of more than 90% was demonstrated in European, Native American, Chilean and African children in large clinical studies in the 1990s.13 In the United Kingdom, no infant given three doses developed Hib disease in the short-term (boosters may be required for long-term protection), and recent postmarketing studies have confirmed the high effectiveness of vaccination of infants against Hib in Germany and pertussis in Sweden.13,16,17

Many vaccines can also protect when administered after exposure – examples are rabies, hepatitis B, hepatitis A, measles and varicella.18

For society

Ehreth estimates that vaccines annually prevent almost 6 million deaths worldwide.19 In the USA, there has been a 99% decrease in incidence for the nine diseases for which vaccines have been recommended for decades,20 accompanied by a similar decline in mortality and disease sequelae.

Complications such as congenital rubella syndrome, liver cirrhosis and cancer caused by chronic hepatitis B infection or neurological lesions secondary to measles or mumps can have a greater long-term impact than the acute disease. Up to 40% of children who survive meningitis due to Hib may have life-long neurological defects.13

In field trials, mortality and morbidity reductions were seen for pneumococcal disease in sub-Saharan Africa and rotavirus in Latin America.21,22

Specific vaccines have also been used to protect those in greatest need of protection against infectious diseases, such as pregnant women, cancer patients and the immunocompromised.18

Mitigation of disease severity

Disease may occur in previously vaccinated individuals. Such breakthroughs are either primary – due to vaccine failure – or secondary. In such cases, the disease is usually milder than in the non-vaccinated. In a German efficacy study of an acellular pertussis vaccine, vaccinated individuals who developed whooping cough had a significantly shorter duration of chronic cough than controls.23 Such findings were confirmed in Senegal.24 Varicella breakthroughs exhibit little fever, fewer skin lesions and fewer complications25 than unvaccinated cases. Milder disease in vaccinees was also reported for rotavirus vaccine.22

Prevention of infection

Many vaccines are primarily intended to prevent disease and do not necessarily protect against infection. Some vaccines protect against infection as well. Hepatitis A vaccine has been shown to be equally efficacious (over 90% protection) against symptomatic disease and asymptomatic infections.26 Complete prevention of persistent vaccine-type infection has been demonstrated for human papillomavirus (HPV) vaccine.27 Such protection is referred to as “sterilizing immunity”. Sterilizing immunity may wane in the long term, but protection against disease usually persists because immune memory minimizes the consequences of infection.28

Protection of the unvaccinated population

Herd protection

Efficacious vaccines not only protect the immunized, but can also reduce disease among unimmunized individuals in the community through “indirect effects” or “herd protection”. Hib vaccine coverage of less than 70% in the Gambia was sufficient to eliminate Hib disease, with similar findings seen in Navajo populations.29,30 Another example of herd protection is a measles outbreak among preschool-age children in the USA in which the attack rate decreased faster than coverage increased.31 Herd protection may also be conferred by vaccines against diarrhoeal diseases, as has been demonstrated for oral cholera vaccines.32

“Herd protection” of the unvaccinated occurs when a sufficient proportion of the group is immune.33 The decline of disease incidence is greater than the proportion of individuals immunized because vaccination reduces the spread of an infectious agent by reducing the amount and/or duration of pathogen shedding by vaccinees,34 retarding transmission. Herd protection as observed with OPV involves the additional mechanism of “contact immunization” – vaccine viruses infect more individuals than those administered vaccine.10

The coverage rate necessary to stop transmission depends on the basic reproduction number (R0), defined as the average number of transmissions expected from a single primary case introduced into a totally susceptible population.34 Diseases with high R0 (e.g. measles) require higher coverage to attain herd protection than a disease with a lower R0 (e.g. rubella, polio and Hib).

Because of herd protection, some diseases can be eliminated without 100% immunization coverage.

Source drying

Source drying is a related concept to herd protection. If a particular subgroup is identified as the reservoir of infection, targeted vaccination will decrease disease in the whole population.

In North Queensland, Australia, there was a high incidence of hepatitis A in the indigenous population. Vaccination of indigenous toddlers, with catch-up up to the sixth birthday, had a rapid and dramatic impact in eliminating the disease in the indigenous population and in the much larger non-indigenous population (who were not vaccinated) across the whole of Queensland.35 Similar approaches have been very successfully applied in several other larger settings, including Israel and the USA.36

The success of source drying justifies vaccination of special occupational groups, such as food handlers, to control typhoid and hepatitis A.37

Pertussis vaccine boosters for close contacts (such as parents, grandparents, nannies, siblings and baby unit nurses), who are the most common sources of transmission to infants, protect those too young to be given primary vaccination with a surrounding “pertussis-free cocoon”.38

Prevention of related diseases and cancer

Protection against related diseases

Vaccines will also protect against diseases related to the targeted disease. For example, in Finland, the USA and elsewhere, influenza vaccination has been found protective for acute otitis media in children, with a vaccine efficacy of more than 30%.39 Measles vaccination protects against multiple complications such as dysentery, bacterial pneumonia, keratomalacia and malnutrition.40 An enterotoxic Escherichia coli vaccine demonstrated protection against diarrhoea due to Salmonella enterica.41

Cancer prevention

Infective agents cause several cancers. Chronic hepatitis B infection leads to liver cancer. Vaccination against such pathogens should prevent the associated cancer as already observed for hepatocellular carcinoma in Taiwan, China.42 These results could be replicated in Africa.43

Reduction of the incidence of cervical cancer is expected with the use of HPV vaccines against serotypes 16 and 18, responsible for over 70% of the global cervical cancer burden, as reduction in precancerous lesions has been demonstrated in vaccinees.27

Societal and other benefits

Health-care and other savings for society

Immunization programmes require funding for infrastructure (e.g. cold-chain maintenance), purchase of vaccines and adequate staffing. However, the mortality and morbidity prevented translates into long-term cost savings and potential economic growth. Globally, the savings from vaccines were estimated by Ehreth in 2003 to be of the order of tens of billions of US dollars of direct savings.19 Malaria (for which there are currently several promising vaccines in development) costs sub-Saharan Africa US$ 100 billion worth of lost annual gross domestic product (GDP).

Savings are enhanced if several antigens are delivered in a single vaccine. Combination vaccines bring the added benefit of better compliance, coverage, and injection safety. Introduction of a new antigen is facilitated with combination vaccines, ensuring early high coverage by maintaining previous immunization schedules, without compromising (and sometimes improving) immunogenicity and reactogenicity.44,45

When taking into account indirect costs, savings are higher for common diseases with lower mortality and morbidity (such as varicella) than for more severe diseases (such as polio).46 Indirect costs, such as lost productivity (as well as direct medical costs) have been emphasized by eminent health economists in assessing the full value of vaccination.47

Immunization programmes, compared to other common public health interventions such as wearing seat-belts and chlorination of drinking water, are a good investment and more cost effective than, for example, advice on smoking cessation.48

Cost savings will be achieved with the new live-attenuated rotavirus and conjugated pneumococcal vaccines, as well as wider use of hepatitis B and Hib vaccines.49

Preventing development of antibiotic resistance

By reducing the need for antibiotics, vaccines may reduce the prevalence and hinder the development of resistant strains. Introduction of a conjugate pneumococcal vaccine for infants in the USA in 2000 saw a 57% decline in invasive disease caused by penicillin-resistant strains and a 59% decline in strains resistant to multiple antibiotics by 2004 across a broad age spectrum: 81% among children under 2 years of age and 49% among persons aged 65 years and older.50

Vaccines against typhoid can prevent primary infection and the spread of antibiotic-sensitive as well as multidrug-resistant strains.51 The development of new vaccines against infectious pathogens where antibiotic resistance is a global threat (e.g. Staphylococcus aureus) is viewed as a better long-term option to control the problem of increasing resistance.52

Extending life expectancy

Vaccines can increase life expectancy by protecting against diseases against which one would not expect benefit. Elderly individuals given influenza vaccine in the USA had approximately 20% less chance of suffering cardiovascular and cerebrovascular disease and 50% lower risk of mortality from all causes compared to their unvaccinated counterparts.53

In Sweden, administration of polysaccharide pneumococcal vaccine and inactivated influenza vaccine significantly reduced the risk of in-hospital mortality for pneumonia and cardiac failure among elderly persons, with an additive effect when both vaccines had been administered.54

Safe travel and mobility

With global air travel rising, there is an increased risk of exposure to infectious diseases abroad. Travellers transmit and disseminate disease, as has been observed in the case of polio and in the dispersal of meningococcal strains by returning pilgrims from Saudi Arabia.55 In the case of the Muslim Hajj (the largest annual human gathering in the world), local authorities require meningococcal ACWY vaccination and recommend various other vaccinations, such as influenza and hepatitis B, for pilgrims.56

The most common vaccine-preventable diseases among travellers are influenza and hepatitis A.57 Other vaccines to consider for travel include rabies, hepatitis B, typhoid, cholera, yellow fever, Japanese encephalitis and measles.57 Many vaccines can be given by flexible accelerated schedules to ensure early protection.58 Thus the traveller seeking health advice, even within a few weeks of departure, can travel overseas without vaccine-preventable health risks to themselves and others.

Other public health benefits

In developing countries, vaccination programmes are cornerstones of primary health-care services. The infrastructure and personnel required for an effective and sustainable immunization programme give opportunities for better primary health-care services, particularly in the critical perinatal and early infancy period.59–61

Empowerment of women

With improvements in infant and child mortality, women tend to opt for fewer children as the need to have many children to ensure that some will reach adulthood is reduced. This has significant health, educational, social and economic benefits.59

Protection against bioterrorism

The current concern about the potential use of smallpox virus in bioterror is due to the cessation of vaccination (and of vaccine manufacture) following the monumental achievement of smallpox eradication. The potential of vaccines to protect populations from bioterrorism threats such as smallpox and anthrax has led many governments to ensure an adequate supply of the necessary vaccines in preparation against such an attack.62 Surveillance and response systems for vaccine-preventable and other diseases play a critical role in identification, characterization and response to biological weapons.

Promoting economic growth

Poor health has been shown to stunt economic growth while good health can promote social development and economic growth. Health is fundamental to economic growth for developing countries and vaccinations form the bedrock of their public health programmes.47,59,60 The annual return on investment in vaccination has been calculated to be in the range of 12% to 18%, but the economic benefits of improved health continue to be largely underestimated.47,63,64

Enhancing equity

The burden of infectious, including vaccine-preventable, diseases falls disproportionately on the disadvantaged. Vaccines have clear benefits for the disadvantaged. Pneumococcal immunization programmes in the USA have at least temporarily removed racial and socioeconomic disparities in invasive pneumococcal disease incidence, while in Bangladesh, measles vaccination has enhanced equity between high- and low-socioeconomic groups.65,66

Promoting peace

There were at least seven United Nations Children’s Fund (UNICEF) vaccine-mediated ceasefires during civil conflicts.67 These conflicts were in diverse parts of the world, from Liberia to Afghanistan, where even warring factions see the benefit of immunization programmes.

During protracted conflict it is possible to ensure that vaccination coverage remains high. This is seen in Sri Lanka, where despite unrest for the last two decades coverage in 2005 for both three doses of diphtheria–tetanus–pertussis vaccine and one dose of measles vaccine was 99%.68

The high cost-effectiveness and multiple benefits of relatively modest resource investments in immunization contrast starkly with profligate global military expenditures, currently over US$ 1 trillion annually.69

Conclusions

The benefits of vaccination extend beyond prevention of specific diseases in individuals. They enable a rich, multifaceted harvest for societies and nations. Vaccination makes good economic sense, and meets the need to care for the weakest members of societies. Reducing global child mortality by facilitating universal access to safe vaccines of proven efficacy is a moral obligation for the international community as it is a human right for every individual to have the opportunity to live a healthier and fuller life. Achievement of the Millennium Development Goal 4 (two-thirds reduction in 1990 under-5 child mortality by 2015) will be greatly advanced by, and unlikely to be achieved without, expanded and timely global access to key life-saving immunizations such as measles, Hib, rotavirus and pneumococcal vaccines.

We conclude that a comprehensive vaccination programme is a cornerstone of good public health and will reduce inequities and poverty. ■

References

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