di
Anna Giulia Cattaneo, M.D.

Active immunization refers the ability of immune system to produce specific antibodies and memory cells in response to stimulation with antigens. It can follow natural infections or vaccines administration, this last being one of the most powerful and cost-benefit means to contrast infectious diseases and their epidemic outspread. Active immunization could be long-lasting, and even life-long : this is the main reason that in many cases vaccine administration seems to be a preventive practice confined to childhood or early adulthood.

It is important to make a distinction between active immunization and generic stimulation of immune system. This last is a general induction of immune reactions that follows, as an exemple, the intravesical administration of BCG (Calmette-Guerin bacillus) to enhance defences against local tumors, without a true production of specific antibodies and immune memory. The strategy to use adjuvants and polyvalent vaccines has its rational in the ability of immune system to enhance its response via generic stimulations. Toxoids, as tetanus vaccine, are powerful stimulators of immune responses to other antigens, therefore they are usually co-administered (tetanus-dyphteria-pertussis vaccination) or can be used as carrier protein for other vaccines.

In geriatric care, active immunization by vaccine administration is a safe practice, even in the presence of illnessess associated to depressed immune reactivity and compromised general conditions, however the efficiency of immunization could be reduced. It is recommended for a few disease, mainly for influenza and pneumococcal pneumonia, discussed later. However, changes in habits of aging population poses emerging question concerning the opportunities to submit elderly people to a larger set of vaccination. In industrialized countries people had in last century the opportunity to age in better healthy and economic conditions : so it is not uncommon that old and even very old individuals can work, be involved in sports and travel around the world. The potential exposure to exotic infections or to traumatic lesions predisposing to tetanus must be kept in mind. The active immunization with tetanus toxoid involves a large number of adults, but its effectiveness is limited in time (up to 10 years), and it is relatively uncommon for the very old to maintain an effective profilaxis with periodical boots administration. Difficulties to obtain correct anamnestic informations, especially in the case of minor or even minimal traumatic lesions, could imply delayed diagnosis, and confusion with other conditions, as dysphagia, if symptoms at the onset are unclear. Tetanus is fatal in at least 32% of people over 80 years. On the other hand, the practitioner must became more confident in evaluating safety and efficacy of a profilaxis against exotic diseases for retired people that want to travel a long way.

SENESCENCE OF THE IMMUNE SYSTEM AND STRATEGIES FOR VACCINATIONS.

Immunodepressed individuals can show deranged active immunization; as a consequence they can develop unusual complications to otherwise safe vaccinations containing live, attenuated agents. In addition, routine tests as the measure of serological antibody titres could be difficult to interpret, because data concerning the dynamics of humoral responses in this type of patients are often lacking. A comprehensive review of risk and benefits, and precautions in vaccinating immunodepressed subjects could be found in specialized papers.

In the elderly, conditions affecting the immune system (i.e. immunoproliferative disorders, cancer and cancer chemioterapy, autoimmune diseases and their therapy, or renal insufficiency) are frequent, but a true immunodepression cannot be considered a special feature of human and mammals ageing. Instead, senescence of the immune system is usually present, with reduction of germinative centers, production of apoptosis-prone mature lymphocytes and abnormalities possibly due to thymus involution. This fact could in part follows the long-lasting stimulation of both B- and T- cells by the large number of different antigens encountered during the year of a long life, poor nutrition and other similar factors. A number of test have been proposed to characterize responses in senescent immune system, some difficult to standardize (like skin hypereactivity tests or "in vitro" responsiveness of T-cells), other more affordable. Among these last, the characterization of T-cell surface antigen patterns by fluss cytometry appears give the most interesting results. Depletion of CD45RO_null cells and their substitution with CD45RO_ imprinted cells, as well as of CD8_CD28null T cell has been claimed to be associated to elderly accompanying phenomena, and the last to the impaired immunization following vaccination against influenza in older individuals. In its whole, the poor ability of old individuals to perform antibodies in response to vaccinations remains not clearly understood and appears to be heterogeneous.

Some precautions have been claimed to be able to enhance vaccine immunization in ageing, among them booster regimen and use of adjuvants (better rise in serum titre has been obtained by experimentally using the adrenal hormone deihydroepiandrosterone sulfate (DHEAS) as an adjuvant for vaccines against influenza or pneumococcal pneumonia).
In the seriously ill or compromised aged individual, like in younger ones, it is mandatory to be careful when administrating live-attenuated vaccines, that can possibly induce quite serious diseases and induce a negative nitrogen balance, especially in malnourished patients. More frequent is a lack of efficacy.

ANTI-INFLUENZA VACCINATION

1 .. Influenza : causes and consequences.

While influenza is a very common, moderate and self-limited viral infection, it could be seriously complicated, even by death, in elderly and chronically ill subjects. It has been evaluated that the annual incidence of death due to influenza reaches 40 per thousand: 90% of these in individuals are aged 65 or more, in which a well conducted vaccination strategy effectively reduces by 70%-85% the risk.

Two types of Ortomyxoviruses, A and B, are the causative agents of influenza in humans. Their antigenic properties are different, being changes of surface antigens very frequent in influenza A viruses, but not in virus B. Both diseases diffuse epidemically, but virus B seems to cause milder illnesses and self-limited outspreads, while virus A is more often responsible of pandemics, that in the past century have been recorded in 1918, 1957, 1968 and 1977. This event is usually more serious than usual epidemics, with higher mortality observed in elderly people for the majority of the cases. The more stable antigenic pattern of virus B renders sporadic the causality of this agent in pandemias.

Epidemics occur annually in the winter in temperate climate, while in tropics they are biannual, without a seasonal pattern. Vaccines could be no more protective when the antigenic assessment changes : for this reason the WHO maintains a Global Influenza Surveillance Network in 82 country for the early detection of potentially harmful variants and prompt design of a new vaccine.

2 . Anti-influenza vaccines.

Influenza vaccine composition can change every year and is typically polyvalent, to cover the major variants of virus A and B. Vaccination usually require a single administration in the deltoid (a booster regimen could help in non-responders, but it is unusual), and is given without adjuvants. Three types of vaccines are used (inactivated, whith the whole causative agent; split, with disrupted viral fragments, or subunit, with isolated viral haemagglutinins and neuramidases), they induce a similar protective immunization, only the inactivated one shows more striking hyperreactivity in younger individuals. In humans, serum antibodies involved in protection agaist influenza are predominantly IgG1 and IgG3. The contraindications are limited to allergic reactions against egg components. A variant aimed to better miming the immunization to natural infection, is a vaccine which can be administered by nasal route, an earl-induced secrete antibodies production: it remains experimental. A vaccine adsorbed in a licensed adjuvant (MF 59) has been tentatively introduced to enhance the response in aged or immunodepressed people, in which the effective immunization can be more unstable and difficult to obtain, but it has not been approved until now. In fact, while in adult normal subjects an affective HIA (Haemagglutinin-Inibiting-Antibodies) titre (1:40) could persist for months, in high risk subjects the effective titre is higher (1:80 and more), but it disappear in a few weeks. Vaccines against influenza are safe and effective, if the diagnosis has been carefully done and if there is good antigenic match between vaccine and viral antigens. Complications are usually mild, and symptoms are attenuated, in comparison with the wild syndrome, with exception affecting children. and younger, hyperreactive subject.

3. Anti-influenza vaccines and the elderly.

For its relative safety, and for the benefits associated to vaccine administration especially in the elderly and in chronically ill people, the WHO recommend as a first priority the vaccination of residents in long-term care facilities for the elderly and disabled, followed by non-istitutionalized elderly subjects suffering from chronic pulmonary, metabolic and cardiovascular diseases, and from immunodepressed patients. The full recommendations are reported in this link .

The vaccination can actively prevent hospital admission for acute respiratory complications or infections, like pneumococcal pneumonia, progression of existing chronic respiratory distress and even death. The need for vaccination appears to be well understood by both patients and their care-taking, as carried out by survey studies. However, despite of official recommendations, and efforts done by the political healthy organisms, disparities mainly due to socioeconomics, racials and healthy conditions significantly reduces the percentage of immunized individuals in certain groups of individuals, not only socially disadvantaged, in developed countries (6).

Prevention of influenza with neuroaminidase inhibitors is a proven and safe practice, however it could be only supportive to the vaccine at the present day, because of its lower cost-to-benefit ratio. Its use is especially useful in seriously immunocompromised patients, or in those that are exposed to the risk of infection before vaccination.

PNEUMONIA AND OLD AGE.

Old and very old patients can be victims of pneumonia, that frequently follows influenza. It is could be both sporadic as well as community-acquired and and nursing-home acquired : co-morbidity, unusual presentation, pre-existing lung diseases, dementia and general impaired conditions are main determinants for susceptibility to pneumonia and its consequences. Death occurs in 30 to 150 per 105.

Streptococcus pneumoniae or other pathogens (H. influenzae or Staphylococcus aureus among them) the involved agents. These are encapsulated organisms whose antiphagocytic capsular antigens are the main virulence factors, and acts as type 2 antigens that stimulate the production of specific IgG2 form the B-cells without involvement of T-helper cells. Serum opsonizing activity must be present. Antibiotic resistance is frequent, especially in pneumococcal pneumonia.

Vaccines against capsular antigens are available, and the 23-valent anti-pneumococcal vaccine has been recommended in selected people at high risk, among them older subjects with chronic respiratory distress or decreased immunocompetence, and those at high risk of community-acquired infections. Vaccination has been claimed to be efficacious 50% : this means that 1 infection is prevented by 20000 vaccine administrations, and 1 death by 50000.
Controversial on pneumococcal vaccination is sustained also by theoretical facts : memory cells production does not follows immunization against type 2 antigens, while acquired immunity is long-lasting (up to 3 years), and revaccination produces only a partial response. In the elderly the opsonizing activity of serum decreases.

CONCLUSIONS

Vaccination appears to be safe and effective in the elderly as in adulthood, when needed. Vaccination or revaccination against tetanus or tropical diseases, in the case of exposure to the agent, is recommended. A special place is is devoted to the influenza vaccine administration : its benefits are well recognized, and it is recommended especially in old individuals by the WHO, who maintains a special surveillance programme for influence prevention. The efficacy of vaccination against pneumococcal infection is instead controversial, while recommended by certain organisms for public health.
Prevention of influenza with neuroaminidase inhibitors is a proven and safe practice, however it could be only supportive to the vaccine at the present day, because of its lower cost-to-benefit ratio.

REFERENCES

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