Eurosurveillance

ECDC

Immunization Strategy in the Era of Communicable Diseases Elimination

 Rediger
  Published: 29.04.04 Updated: 11.05.2004 15:41:32

Kuulo Kutsar

The Estonian Expanded Programme on Immunization

The strategy for the prevention, control and elimination of vaccine-preventable communicable diseases includes:

  • routine immunization of children following a national schedule,
  • immunization campaigns in high-risk areas or high-risk groups of a population,
  • sustainable supply of vaccines,
  • cost-effectiveness of immunization,
  • strengthened communicable disease surveillance,
  • early warning of outbreaks,
  • strengthened outbreak response through epidemic preparedness and inter-country planning and support,
  • laboratory capacity to confirm suspected clinical cases.

National Expanded Programme on Immunization

An expanded national programme (EPI) plans the routine immunization of children following a national schedule and immunization campaign in high-risk areas and groups of a population on immunization. The sustainable vaccine supply is a cornerstone of EPI. Sustainable supply of vaccines may be disrupted during outbreaks or epidemics when large amounts of a vaccine are needed at very short notice. Due to a temporary shortage of a particular vaccine that may be the result of a reduction in the demand and the low profitability of the vaccine, resurgence of a vaccine-preventable communicable disease may happen.

Over the past decade some events such as resurgence of diphtheria in the eastern part of the Baltic Sea region were a warning of the fragility of the achievements in immunization and indicate what can happen when immunization is neglected.

National Communicable Disease Surveillance Programme

A strengthened surveillance for communicable diseases that includes early warning of outbreaks as well as relevant laboratory capacity to confirm suspected clinical cases is planned by a national communicable disease surveillance programme. Strengthened outbreak and epidemic response is planned according to the communicable disease surveillance programme and the epidemic preparedness plan. Emergency outbreak or epidemic response is very expensive. It may disrupt a fragile health care system and place strain on national, human and financial resources. It is far less cost-effective than routine delivery of vaccines through the EPI.

Cost-Effectiveness of Immunization

Immunization of children is one of the most cost-effective of all health interventions -  it saves more lives for the money invested than almost any other health intervention. It costs an average of 25 US dollars (including delivery costs) to fully immunize a child in a developing country with the six traditional EPI vaccines. The cost of the vaccines and administration of all scheduled vaccines to a child during the first five years of life would be approximately 400 US dollars in developed countries, but the cost may be highly variable between countries. Immunization in developed countries includes more antigens, vaccine doses, more visits to a physician and vaccines at a higher cost than in developing countries. Even this is far less than the cost of treating children whom succumb to vaccine-preventable diseases.

The cost-effectiveness has been further underlined by the rapid increase in anti-microbial  resistance, which has made some communicable diseases very difficult and many times more expensive to treat.

Poliomyelitis

The elimination of poliomyelitis has been certified in most parts of the world, but poliovirus is still circulating in ten countries. Until WHO has developed a polio post-certification policy, it is recommended to continue polio immunization and to use OPV where this vaccine has been used in the poliomyelitis elimination programmes. WHO's future policy will be based on an evaluation of the risks of the reintroduction or re-emergence of poliomyelitis following the global certification. The risks include those arising from the OPV itself; the capacity to induce vaccine-associated acute poliomyelitis paralysis, outbreaks due to circulating vaccine-derived polioviruses and persons with immunodeficiency who are long-term excretors of vaccine-derived polioviruses. Episodes of circulating vaccine-derived poliovirus cases occurred in the Dominican Republic and Haiti in 2000-2001 and in the Philippines in 2001. There were 12 notified episodes of vaccine-associated paralytic polio cases in 2000 and 11 episodes in 2001 in Russian Federation.

Measles

Many countries in the Baltic Sea region have made good progress in controlling measles due to the routine high immunization coverage of children. To stop measles virus circulation in a population, the immunization coverage for measles needs to be above 90% mainly because up to 15% of children vaccinated at nine months fail to develop immunity.

WHO recommends that all countries implement plans for universal measles immunization coverage, regardless of the current measles morbidity status. The measles immunization implementation strategy includes:

  • increasing routine immunization coverage with one dose of measles vaccine to at least 90% of infants aged nine months;
  • providing a routine second dose of measles vaccine to increase the chances that every child gets at least one dose (who have failed to get first dose) and also to provide a second dose for the 15% of children who may not have developed a protective immune response following the fist vaccination.

Viral hepatitis B

Hepatitis B infection accounts for 60-80% of primary liver cancer worldwide. At least one in four of those infected before the age of seven will acquire chronic hepatitis B infection and become long-term carriers recovering disease much later in life. The problem is very serious in the eastern part of the Baltic Sea region, where hepatitis B virus is predominantly transmitted through the use of nonsterile needles and unprotected sex.

The «invisibility» of the chronic form of hepatitis B infection is one of the reasons why the disease has been neglected for a long time in some countries. As a result, there has been a failure to attract national government funding for the hepatitis B vaccine and the introduction of the vaccine in routine immunization schedules. In 2002 the lowest price for countries eligible to buy vaccines through the UNICEF  procurement system was 0.25-0.43 US dollars for a ten-dose vial. By the end of 2001, 142 countries were using hepatitis B vaccine in infant immunization schedules and global hepB3 coverage by age six months was approximately 40%.

Rubella and congenital rubella syndrome (CRS)

The primary target for the rubella immunization is the prevention of congenital rubella syndrome. Two immunization strategies are used to achieve this target:

  • administration of combined measles-mumps-rubella (MMR) vaccine in the second year of life and, if needed, a second dose of MMR may be given at school age,
  • selective targeting of adolescent females (15-40 years) with a mono-valent rubella vaccine or screening pregnant women and offering the rubella vaccine following delivery to those found to have no immunity to rubella.

Childhood rubella immunization is only recommended where coverage of at least 80% can be achieved. Where coverage is lower or not sustained, reduced circulation of rubella virus in the population can lead to a shift in the incidence of the disease towards older age groups, increasing the risks for women of childbearing age.

In countries with a continual high transmission of rubella virus among children, few women of childbearing age are susceptible to rubella, and thus the incidence of CRS may be too low to start large-scale rubella immunization.

There are few surveillance data on CRS incidence in the Baltic Sea region; CRS is notifiable only in Germany.

Haemophilus influenzae type b infection

Haemophilus influenzae b (Hib) infection is a leading cause of pneumonia in developing countries and also accounts for one-third to one-half of all cases of bacterial meningitis in children under two years. In developing countries about 40% of Hib meningitis cases are fatal, and 15-35% of children who survive are left with permanent disabilities.

During 2002, 93% of all countries in the Americas have introduced the Hib conjugate vaccine into national immunization programmes. In other parts of the world, the initiation of Hib vaccination has been slower. Three doses of the vaccine are needed during the first year of life starting from the age of six weeks.

The main reason for the slow initiation of Hib vaccination in developing countries as well as in the eastern part of the Baltic Sea region has been the lack of data on the Hib disease burden and the difficulty in assessing the impact and cost-effectiveness of introducing the vaccine. Other microbes frequently cause pneumonia and meningitis and accurate diagnosis can be difficult. The precise cause of pneumonia is more difficult to determine, even with a good laboratory support. As a result, physicians are giving empiric treatment and the burden of Hib infection is not well documented.

Tuberculosis

The BCG vaccine is delivered in many countries of the Baltic Sea region.

This vaccine protects against miliary TB and TB meningitis in the first years of life. However, BCG  is an imperfect vaccine. It creates immunity that lasts at least up to the teenage years. Protection against adult forms of TB is variable and depends on nutritional and environmental factors, geographic location, genetic make-up and type of disease. A new vaccine is needed to protect against adult TB. Candidate TB vaccines include: subunit vaccines carrying protective elements from several antigens in a single molecule, DNA vaccines expressing protective M. tuberculosis genes and improved recombinant BCG. Among key participants in the field of development of a new TB vaccine is the Statens Serum Institute (Copenhagen, Denmark).

Pneumococcal infection

The burden of pneumococcal disease is not well documented in eastern part of the Baltic Sea region. The problem is that the etiology of the disease, as with Hib pneumonia and meningitis, is difficult to establish. Conventional microbiological techniques usually fail to determine the causal agent of pneumonia, especially in children.

Polysaccharide vaccines, which protect against the 23 serotypes of Streptococcus pneumoniae, have been available for many years, but they do not reliably protect children under two years of age. A seven-valent second-generation conjugate vaccine has been licensed by Wyeth Lederle and in clinical trials has demonstrated a good level of protection against invasive pneumococcal infection (bacteraemia and meningitis) and middle ear infection. Wyeth Lederle has also developed a nine-valent vaccine and Aventis Pasteur an 11-valent vaccine. Several vaccine producers are concentrating their efforts on the development of a protein vaccine. Protein vaccines are not serotype specific and may overcome the potential limitations of conjugate vaccines that only protect against a limited number of serotypes.

Meningococcal infection

Meningococcal infection is endemic throughout the world and can occur in explosive outbreaks and epidemics. Meningococcal serotypes A, B and C are responsible for most cases worldwide.

Polysaccharide vaccines are available to protect against serotypes A and C or against serotypes A, C, W135 and Y. Although these vaccines provide only short-term immunity and have variable effectiveness among children under two years, they are essential during outbreaks and epidemics to protect people at risk.

A second-generation conjugate meningococcal serotype C vaccine has been successfully used in the UK and a prototype serotype A and C conjugate vaccine has been tested in children and found to be safe and effective. Efforts to develop a vaccine against serotype B, which is the main causal agent of the disease in Europe and the Baltic Sea region, have been variable. Protein vaccines have demonstrated 50-80% efficacy but fail to protect young children and induced immunity wanes over time. There is some evidence that these vaccines may be effective against single rather than multiple strains of meningococcus.

Shigella infection

Shigellosis is endemic in the eastern part of the Baltic Sea region. The disease is highly contagious and can occur in explosive outbreaks and epidemics in conditions of poor hygiene.

A vaccine covering all six major Shigella flexneri serotypes, Shigella sonnei and Shigella dysenteriae 1 (epidemic serotype) are expected to protect against 79% of shigella infection in developing countries and 83% in developed countries. Of the candidate vaccines under development, the injectable conjugate Shigella flexneri 2a, Shigella sonnei and live attenuated Shigella flexneri 2a oral vaccines are the most advanced.

Enterotoxigenic Escherichia coli (ETEC) infection

ETEC-infection is a serious problem among children under five years in developing countries, but is also observed among older age groups and adults.

Due to the antigenic similarity of the B subunits of cholera vibrio toxin and ETEC heat-labile toxin, a recombinant toxin-killed whole cell cholera vaccine was created that prevented 23% of all diarrhoea cases and 52% of ETEC cases in tested tourists visiting a developing country. A vaccine developed at the University of Goteborg in Sweden includes cholera vibrio toxin that is combined with five strains of formalin-killed ETEC cells. The vaccine provided about 80% protection against ETEC-infection in tested tourists visiting a developing country. Live attenuated shigella microbes are being used as vectors for the expression of ETEC heat-labile toxin and fimbrial antigens to develop a vaccine that may protect against both shigella and ETEC infections.


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