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http://www.who.int/vaccines-diseases/history/history.shtml

The History of Vaccination

         Introduction

> The two public health interventions that have had the greatest impact on

> the world's health  clean water and vaccines. Thanks to such pioneers as

Jenner

> and Pasteur, a handful of vaccines prevent illness or death for millions of

> individuals every year.  But there is still a long way to go. Immunization,

> the most cost-effective public health intervention,  continues to be

> uncer-used.. It is profoundly tragic that almost two million children still

die each

> year from diseases for which are available at low cost . And over 90 000 fall

> victim to paralytic polio, which could also have been prevented by

> immunization. Indeed, many years elapsed between the invention of current

vaccines and

> their widespread use in immunization programmes. The reasons for these delays

> are many and complex. If history is to serve any useful purpose, it should 

> help us to find ways to avoid such delays in future.

>

>

        The invention era

>

> The closing years of the 19th century and the early years of the 20th

> century were marked by the achievements of great vaccine scientists such as

> Pasteur. Since the introduction of vaccinia by Jenner 200 years ago

( " vaccination "

> in its true sense), nine major diseases of man have been controlled to a

> greater or lesser extent through the use of vaccines (Table 1.). Several other

> vaccines have been used in individuals at risk from disease of such as rabies

> and plague, but have not been systematically applied on a global scale. While

> BCG has been widely administered to newborns, thus successfully preventing

> complications such as meningitis and miliary tuberculosis,  administration of

> the vaccine has not resulted in control of the disease.

> Table 1.  The date of introduction of first generation of vaccines for use

> in humans*

> 1798   Smallpox

> 1885   Rabies

> 1897   Plague

> 1923   Diphtheria

> 1926   Pertussis

> 1927   Tuberculosis (BCG)

> 1927   Tetanus

> 1935    Yellow Fever

>

> After World War II

> 1955   Injectable Polio Vaccine (IPV)

> 1962   Oral Polio Vaccine (OPV)

> 1964   Measles

> 1967   Mumps

> 1970   Rubella

> 1981   Hepatitis B

>

> *This list is not exhaustive. After Plotkin SA and Mortimer EA , 1994 (ref 1)

Although the first vaccines were, in some respects, crude, they have proved

to be robust and efficient, and continue to be the workhorses of global

immunization programmes. They have dramatically reduced the burden of death and

disease from these nine infections, and have given credibility to the entire

preventive health movement. During the 1920s, diphtheria and tetanus toxoids,

whole

cell pertussis vaccine and BCG were introduced. Thanks to the development of

the chorioallantoic membrane for culturing viruses, a yellow fever vaccine was

available by 1935. After the Second World War, there followed an explosion of

technology, resulting in the emergence of other vaccines still in use today.

These included the killed and oral polio vaccines, and the measles, mumps and

rubella vaccines.

       Early national immunization programmes 1900-1973

>

> During this period, the use of available vaccines was largely confined to

> industrialized countries. For instance, smallpox vaccine was offered to all

age

> groups, but only those at risk - health care workers and travellers - were

> specially targeted. As a result, coverage was patchy and outbreaks continued

> to occur throughout the world. When this happened, massive vaccination efforts

> were mounted by health authorities, often very successfully, to contain the

> infection through vaccination and isolation or quarantine of infected

> individuals or suspected cases.

> Other vaccines such as BCG were gradually introduced in the West, (Table 2)

> as they became available. Better-off families who could afford vaccination

> benefited most - the poor benefited the least. Because of low, irregular

> coverage, communities continued to be devastated intermittently by outbreaks

of

> these vaccine-preventable diseases throughout the 1930s and 1940s.

> An injectable form of killed polio vaccine (IPV) became available in 1955,

> resulting in widespread administration in schools and clinics in

> industrialized countries across a broad age range resulting in a marked drop

in cases in

> these countries. In 1962, the oral polio vaccine (OPV) replaced IPV and

> continues to be the vaccine of choice for eradication of the virus. Despite

initial

> low coverage, the vaccine showed itself capable of dramatically reducing the

> number of polio cases when administered to a wide age range over a short

> period of time.

> Table 2. Vaccines used in national immunization programmes up to 1974

>   Smallpox

>   BCG

>   Diphtheria toxoid

>   Tetanus toxoid

>   Pertussis

>   IPV then OPV

>   Measles

> In terms of strategy, the early programmes offered routine immunization

> through regular maternal and child health services. While efforts were made to

> encourage acceptance, no major effort was made to achieve total coverage. The

> implied target was to raise coverage, but there was no disease reduction

> target specified.

       The eradication era

>

> The early years of the 19th century saw widespread but haphazard use of

> Jenner's vaccine. However, application of smallpox vaccine was systematic in

> Mexico and  Guatemala around 1805 (ref 2). The first attempt to use it on a

> global scale began in 1956 when the World Health Organization and others

selected

> smallpox for eradication from the globe.

> It was not the first time disease eradication had been mooted. Already the

> scientific community had considered the possibility of eradicating   bovine

> contagious pleuropneumonia (a highly fatal disease of cattle), hookworm,

yellow

> fever, malaria and yaws. Now with a clear strategy and a highly effective,

> affordable vaccine, it was possible to unite all countries in a mighty effort

> to rid themselves of this disease and the tremendous annual cost it incurred.

> To meet this special circumstance, very high population coverage with the

> smallpox vaccine was used. Finally in the late 1960s, an additional strategy

> was developed whereby cases were identified through intensive surveillance and

> confined ( " containment " ), and possible contacts within a given radius were

> vaccinated. Details of this effort are chronicled elsewhere (ref 3).

> The next notable attempt at large-scale control was undertaken in   Gambia

> in 1967-1970 when Foege and his team administered measles vaccine in a mass

> country-wide campaign.  As a result, indigenous measles was entirely absent

> from the Gambia until 1972. However, due to the inability to sustain

> immunization coverage, the situation soon reverted to pre-campaign levels (ref

4).

      The Expanded Programme on Immunization (EPI)

>

> Following the impressive success of the smallpox eradication programme, the

> World Health Organization looked for other activities that could build on

> what had already been achieved. In 1974 the Expanded Programme on

Immunization 

> was created. " Expanded " because most programmes until then had only used

> smallpox, BCG and diphtheria, tetanus and pertussis (DTP) vaccines. EPI would

> include two new diseases. The six diseases chosen were tuberculosis,

diphtheria,

> neonatal tetanus, whooping cough, poliomyelitis and measles. Selection was

> made on the basis of a high burden of disease and the availability of a

> well-tried vaccines at an affordable price. " Expanded " also meant increased

> coverage - incredibly, less than 5% of children in developing countries were

being

> reached at that time by immunization services.

> Gradually, global coverage for the six vaccines rose (Fig.1), although

> success was not uniform. Regions and countries with the greatest resources,

> infrastructure and political will were able to raise coverage faster and

higher

> (Fig. 2). Many organizations such as UNICEF and Rotary International became

> partners in the programme. Between 1974 and 1980, the programme developed

> training materials and disseminated them widely. In those busy years, almost

every

> country in the world adopted the principle of a national immunization

> programme. (Many used and continue to use the name " EPI " which has become a

trade

> mark). Hundreds of training courses in dozens of languages were conducted

resul

> ting in a huge mobilizations of human resources. Personnel were trained in the

> management of the programme so that every community was reached (at least in

> theory) by some form of immunization service. The number of doses

> administered and the number of target diseases occurring were recorded and

reported.

> Table 3. Vaccines used by the Expanded Programme on Immunization from 1974

> onwards

>   BCG

>   Polio

>   DTP

>   Measles*

> Added later

>   Yellow Fever (in endemic countries)

>   Hepatitis B

>   Many industrialized countries now use measles, mumps and rubella   

> combined vaccine (MMR)

         Disease control era

>

> Although coverage for all EPI target diseases climbined steadily in all

> regions throughout the 1980s disease incidence was not always proportionate

> decreasing. It became clear that pockets of low coverage in most if not all

> countries could perpetuate disease transmission. In the mid-1980s, more effort

was

> placed on developing surveillance systems. As the programme moved into the

> 1990s with a mandate for eradication of polio, it became imperative that all

> countries should be able to mount effective surveillance of all target

> diseases. Now countries were able to focus attention on areas of low coverage

and

> high disease incidence. Special strategies such as house-to-house visits were

> developed in the Americas and elsewhere, enabling pockets of low coverage and

> high disease incidence to be reached. i) Polio eradication by the year 2000

> In 1988, the World Health Assembly responded to the remarkable successes of

> the Americas in controlling poliomyelitis by selecting this disease as the

> next disease to be targeted for global eradication. Strong commitment at

> global, regional and national levels has led to wide implementation of  WHO's

> recommended strategies with consequent reduction in virus transmission.

Globally,

> as of September 1995, 78% of children had received at least three doses of

> polio vaccine by 12 months of age by routine immunization, and supplementary

> immunization has now been conducted as national or sub-national immunization

> days in 63 countries.

> The key to polio eradication lies in effective surveillance for all cases of

> acute flaccid paralysis in children. One hundred and seven countries are now

> conducting surveillance specifically for cases of acute flaccid paralysis.

> Six specialized reference laboratories, 16 regional and 60 national

> laboratories are now providing virological confirmation of diagnosis in

suspected

> cases. In addition, they are able to identify the source of the virus by

molecular

> studies.

> All countries embarking on polio eradication have undertaken mass campaigns

> using OPV, followed by " mopping-up " (house-to-house visits) in locations

> where cases persist. The incidence of polio has continued downward and, more

> importantly, increasing areas of the world are becoming free of the disease.

In

> 1994, the Americas were declared polio-free. Polio-free zones also exist in

> Western Europe and in the Pacific basin, with emerging low incidence zones in

> the countries of the Mahgreb Union, the Gulf countries and in Southern Africa.

> Dramatic reductions in incidence have been recorded in countries such as

> China and Egypt. As of September 1995, 146 countries reported zero polio

cases.

> While success is in sight, zones and countries where there is currently armed

> conflict remain difficult locations in which to implement effective and

> comprehensive immunization programmes. Here the problems have been partly

> overcome by " Days of tranquillity " when conflicts cease and immunization of

women

> and children is carried out. ii) Neonatal Tetanus elimination

> Since the early 1980s, major progress has been made towards neonatal tetanus

> eliminating. In 1989, the World Health Assembly declared its commitment to

> the global elimination of neonatal tetanus by the year 1995. In 1994, an

> estimated

> 733 000 deaths due to neonatal tetanus were prevented, and immunization

> coverage of pregnant women with at least two doses of tetanus toxoid was 48%.

EPI

> has promoted the administration of tetanus toxoid (TT) to either pregnant

> women, or to all women of child-bearing age. Five doses of TT given to a

mother

> provide full, life-long protection, but even two doses given in pregnancy

> provide impressive protection for the newborn against neonatal tetanus.

> Unfortunately, mothers have not been vaccinated as successfully as their

> babies, and coverage has remained unacceptably low in many countries. As a

> complementary strategy, clean delivery practices have improved in recent

years,

> but most babies in developing countries are still delivered at home without

the

> assistance of a trained attendant. The reduction in neonatal tetanus deaths

> is the result of impressive progress in certain high-risk countries. However,

> as of September 1995, the estimated global number of neonatal tetanus deaths

> still occurring annually was 489 000. Eighty percent of these deaths occur

> in only 12 countries, but 13 other countries have an estimated neonatal

> tetanus mortality rate of more than 5 per thousand. iii) Measles Control

> In 1990, the World Health Assembly set another global goal, this time for a

> " Reduction by 95% in measles deaths and reduction by 90 per cent of measles

> cases compared to pre-immunization levels by 1995, as a major step towards the

> global eradication of measles in the longer run " . As of September 1995,

> estimated global coverage for measles vaccine had reached 78%, and is expected

to

> rise still further. Many countries, especially those mounting mass

> campaigns, have already achieved the reduction goals.

> For many countries, however, the disease reduction goal will be hard to

> reach. Many of them did not introduce the use of measles vaccine until 1985,

> thirty years  it had became available. Since then however the global number of

> reported cases of measles has fallen, but thousands of measles cases continue

> to occur every year in many of the larger developing countries, especially in

> Africa. High transmission rates for measles virus in densely populated areas

> means that very high, uniform measles vaccine coverage is needed to control

> the disease in this environment if a one-dose schedule is followed.

> Mass campaigns in the Americas have resulted in the virtual disappearance of

> measles from that hemisphere. One after another, countries have undertaken

> mass campaigns targeting 9 months to 14 year olds, regardless of previous

> immunization history. There is clearly a role for this strategy to be expanded

to

> other areas of the globe. iv) Hepatitis B

> The vaccine became available in the early 1980s, although the unit price was

> so high, only a few countries could afford it. The price of the vaccine that

> fallen dramatically since then and the vaccine had been introduced into 28

> countries by September 1995 as part of the routine immunization programme,

> with three doses provided in the first year of life. Many countries in Africa

> need protection that most have, until now, been unable to afford this vaccine.

> Prospects are now improving though with the commitment of UNICEF to purchase

> the vaccine in bulk. v) Yellow fever

> Although a vaccine has been available since 1935, this diseases has not yet

> been adequately controlled . While the global burden of disease is not as

> high as some other vaccine-preventable diseases, outbreaks still occur in

> endemic countries with great loss of life. Indeed, statistics indicate the

disease

> is currently on the upswing. References

> Plotkin SA & Mortimer EA (Eds). Vaccines. Philadelphia WB Saunders,  1994.

>

> Reglamento para la propagacion y estabilidad de la vacuna en el reyno de

> Guatemala. Nueva Guatemala, 1805.

>

> Fenner F et al. Smallpox and its eradication. World Health Organization,

> Geneva, 1988.

> Foege WH. Measles vaccination in Africa.  Washington, D.C. Pan American

> Health Organization, 1971 PAHO Scientific Publication 226:207-212

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