Hugo W.B., Russel A.D.(ed). Pharmaceutical Microbiology

Подождите немного. Документ загружается.

behavioural patterns, age of the population group and population density (i.e. urban

versus rural). Each infective individual will be capable of transmitting the disease to

those susceptible individuals that they encounter during their infective period. The

number of persons to which a single infective individual might transmit the disease,

and hence the rate of occurence of the infection within the population, will depend

upon the population density with respect to susceptible and infective individuals, the

degree and nature of their social interaction, and the duration and timing of the infective

period. Clearly if infectivity precedes the manifestation of disease then spread of the

infection will be greater than if these were concurrent. Since each infected individual

will, in turn, become a source of infection then this leads to a near exponential increase

in the incidence of disease. Fig. 16.3 shows the incidence of disease within a theoretical

population group. This hypothetical group is perfectly mixed, and all individuals are

susceptible to the infection. The model infection has an incubation period of 1 day

and an infective period of 2 days commencing at the onset of symptoms and recovery

1 day later. For the sake of this illustration it has been assumed that each infective

individual will infect two others per day until all of the population group have

contracted the disease. In practice, however, the rate of transmission will decrease as

the epidemic progresses since the recovered individuals will become immune to further

infection and reduce the population density with respect to susceptible individuals.

Epidemics therefore often cease before all members of the community have been

infected (Fig. 16.3, dotted line). If the proportion of immune individuals within a

population group can be maintained above this threshold level then the likelihood of an

epidemic arising from a single isolated infection incident is small (herd immunity).

The threshold level itself is a function of the infectivity of the agent and the population

density. Outbreaks of measles and chickenpox therefore tend to occur annually in the

late summer amongst children attending school for the first time. This has the effect of

concentrating all susceptible individuals in one, often confined, space and thereby

reducing the proportion of immune subjects to below the threshold for propagated

transmission.

An effective vaccination programme is therefore one that can maintain the proportion

of individuals who are immune to a given infectious disease above the critical level.

Such a programme will not prevent isolated cases of infection but will prevent these

from becoming epidemic.

Objectives of a vaccine/immunization programme

There is the potential to develop a protective vaccine/immunization programme for

each and every infectious disease. Whether or not such vaccines are developed and

deployed is related to the severity and economic impact of the disease upon the

community as well as the effects upon the individual. Principles of immunity and of

the production and quality control of immunological products are discussed in Chapters

14 and 15, respectively.

Severity of the disease

The severity of the disease, not only in terms of its morbidity and mortality and the

Vaccination and immunization 325

probability of permanent injury to its survivors, but also in the likelihood of infection,

must be sufficient to warrant the development and routine deployment of a vaccine and

its subsequent use. Thus, whilst influenza vaccines are constantly reviewed and stocks

maintained, the control of influenza epidemics through vaccination is not recommended.

Rather, those groups of individuals, such as the elderly, who are at special risk from the

infection are protected.

Vaccines to be included within a national immunization and vaccination programme

are chosen to reflect the infection risks within that country. Additional immunization,

appropriate for persons travelling abroad, is intended not only to protect the at-risk

individual, but also to prevent importing the disease into an unprotected home

community.

3.2 Effectiveness of the vaccine/immunogen

Vaccination and immunization programmes seldom confer 100% protection against

the target disease. More commonly the degree of protection is ca. 60-95%. In such

instances whilst individuals receiving treatment will have a high probability of becoming

immune, virtually all members of a community must be treated in order to reduce the

proportion of susceptibles to below the threshold for epidemic spread of the disease.

Antidiphtheria and antitetanus prophylaxis, which utilize toxoids, are amongst the most

efficient immunization programmes whereas the performance of BCG is highly variable,

and cholera vaccine (killed) gives little personal protection and is virtually useless in

combating epidemics.

3.3 Safety

No medical or therapeutic procedure comes without some risk to the patient. All possible

steps are taken to ensure safety, quality and efficacy of vaccines and immunological

products (Chapter 15). The risks associated with immunization procedures must be

constantly reviewed and balanced against the risks of, and associated with, contracting

the disease. In this respect, smallpox vaccination in the UK was abandoned in the mid

1970s as the risks associated with vaccination then exceeded the predicted number of

deaths that would follow importation of the disease. Shortly after this, in May 1980,

The World Health Assembly pronounced the world to be free of smallpox. Similarly,

the incidence of paralytic poliomyelitis in the USA and UK in 1996 was low but the

majority of cases related to vaccine use. As the worldwide elimination of poliomyelitis

approaches, there is much debate as to the value of the vaccine outside of an endemic

area.

Public confidence in the safety of vaccines and immunization procedures is essential

if compliance is to match the needs the community. In this respect public concern and

anxiety, in the mid 1970s, over the perceived safety of pertussis vaccine led to a reduction

in coverage of the target group from ca. 80% to ca. 30%. Major epidemics of whooping-

cough, with over 100000 notified cases, followed in 1977/1979 and 1981/83. By 1992,

public confidence had returned, coverage had increased to 92% and there were only

4091 reported cases.

326 Chapter 16

Cost

Cheap effective vaccines are an essential component of the global battle against

infectious disease. It was estimated that the 1996 costs of the USA childhood vaccination

programme, directed against polio, diphtheria, pertussis, tetanus, measles and tuber-

culosis, was $1 for the vaccines and $14 for the programme costs. The newer vaccines,

particularly those that have been genetically engineered, are considerably more expensive,

putting the costs beyond many budgets of developing countries.

Longevity of the immunity

The ideal of any vaccine is to provide life-long protection to the individual against

disease. Immunological memory (Chapter 14) depends upon the survival of cloned

populations of small B and T lymphocytes (memory cells). These small lymphocytes

have a lifespan in the body of ca. 15-20 years. Thus, if the immune system is not

boosted, either by natural exposure to the organism or by re-immunization, then

immunity gained in childhood will be attenuated or lost completely by the age of 30.

Those vaccines which provide only poor protection against disease have proportionately

reduced time-spans of effectiveness. Yellow fever vaccination, which is highly effective,

must therefore be repeated at 10-year intervals, whilst typhoid vaccines are only effective

for 1-3 years. Whether or not immunization in childhood is boosted at adolescence or

in adult life depends on the relative risks associated with the infection as a function of

age.

Classes of immunity

The theoretical background which underlies immunity to infection has been discussed

in detail in Chapter 14. Immunity to infection may be passively acquired through the

receipt of preformed, protective antibodies or it may be actively acquired through an

immune response following deliberate or accidental exposure to microorganisms or

their component parts. Active acquired immunity might involve either or both humoral

and cell-mediated responses.

Passive acquired immunity

Humoral antibodies of the IgG class are able to cross the placenta from mother to

fetus. These antibodies will provide passive protection of the new-born against those

diseases which involve humoral immunity and to which the mother is immune. In this

fashion, new-born infants in the UK have passive protection against tetanus but not

against tuberculosis which requires cell-mediated immunity. Secretory antibodies are

also passed to the new-born together with the first deliveries of breast milk (colostrum).

Such antibodies provide some passive protection against infections of the gastro-

intestinal tract.

Maternally acquired antibodies will react not only with antigen associated with

a threatening infection but also with antigens introduced to the body as part of

an immunization programme. Premature immunization, i.e. before degradation and

Vaccination and immunization 327

elimination of the maternal antibodies, will therefore reduce the potency of an

administered vaccine. This aspect of the timing of a course of vaccinations is discussed

later.

Administration of preformed antibodies, taken from animals, from pooled human

serum, or from human cell-lines is often used to treat an existing infection (e.g. tetanus,

diphtheria) or condition (venomous snake-bite). Pooled human serum may also be

administered prophylactically, within a slow-release vehicle, for those persons entering

parts of the world where diseases such as hepatitis A are endemic. Such administrations

confer no long-term immunity and will interfere with concurrent vaccination procedures.

4.2 Active acquired immunity

Active acquired immunity (Chapter 14) relates to exposure of the immune system to

antigenic materials. Such exposure might be related to a naturally occurring, or vaccine-

associated infection, or it might be associated with direct introduction of non-viable

antigenic material to the body. The latter might occur through insect or animal bites

and stings, inhalation, ingestion or deliberate injection. The route of exposure to antigen

will influence the nature of the subsequent immune response. Thus, injection of antigen

will lead primarily to humoral (IgG, IgM) production, whilst exposure of epithelial

tissues (gut, respiratory tract) will lead not only to the production of secretory antibodies

(IgA, IgE) but also, through the common immune response, to a stimulation of humoral

antibody.

The magnitude and specificity of an immune response depends not only upon the

duration of the exposure to antigen but also upon its time-concentration profile. During

a naturally occurring infection the levels of antigen are very small at onset and localized

to the portal of entry to the host. Since the amounts of antigen are small they will react

only with a small, highly defined group of small lymphocytes. These will undergo

transformation to produce various antibody classes specific to the antigen together

with cloned B and T cells. The immune responses and the infection will progress

simultaneously. The microorganisms will release greater amounts of antigenic materials

as the infection progresses. These will, in turn, react with an increasing number of

cloned lymphocytes, to produce yet more antibody. Eventually the antibody levels will

be sufficient to bring about the elimination, from the host, of the infecting organism.

The net result of this encounter is that the host has developed a highly specific

immunological memory of the encounter.

This situation should be contrasted with the injection of a non-replicating im-

munogen. Often the amount of antigen introduced is large when compared with the

levels present during the initial stages of an infection. In a non-immune animal these

antigens will react not only with those lymphocytes that are capable of producing

antibody of high specificity but also with those of a lower specificity. Antibody (high

and low specificity) produced will react with and remove the residual antigen. The

immune response will cease after this initial (primary) challenge. On a subsequent

(secondary) challenge the antigen will react with residual preformed antibody relating

to the first challenge together with a more specific subgroup of the original cloned

lymphocytes. As the number of challenges is increased the proportion of lymphocytes

specific to the antigen is also increased. After a sufficient number of consecutive

328 Chapter 16

challenges the magnitude and specificity of the immune response matches that which

would occur during a natural infection with an organism bearing the antigen. This

pattern of exposure brings with it certain problems. Firstly, since introduced immunogen

will react preferentially with preformed antibody rather than lymphocytes then sufficient

time must elapse between exposures so as to allow the natural loss of antibody to

occur. Secondly, immunity to infection will only be complete after the final challenge

with immunogen. Thirdly, low specificity antibody produced during the early exposures

to antigen might cross-react with host tissues to produce adverse reactions to the vaccine.

Classes of vaccine

Vaccines may be considered as representing live microorganisms, killed microorganisms

or purified bacterial and viral components (component vaccines). These vaccine classes

have been described in detail in Chapter 15. Some additional points about their use are

discussed below.

Live vaccines

Vaccines may be live, infective microorganisms, attenuated with respect to their

pathogenicity but retaining their ability to infect or they might be genetically engineered

such that one mildly infective organism carries with it antigens from an unrelated

pathogen.

Two major advantages stem from the use of live vaccines. Firstly, the immunization

mimics a natural infection such that only a single exposure is required to render an

individual immune. Secondly, the exposure may be mediated through the natural route

of infection (e.g. oral) thereby stimulating an immune response that is appropriate to a

particular disease (e.g. secretory antibody as primary defence against poliomyelitis

virus in the gut).

Disadvantages associated with the use of live vaccines are also apparent. Live

attenuated vaccines, administered through the natural route of infection, will be

replicated in the patient and could be transmitted to others. If attenuation is lost during

this replicative process then infections might result (see poliomyelitis, below). A second,

major disadvantage of live vaccines is that the course of their action might be affected

by the infection and immunological status of the patient.

Killed and component vaccines

Since these vaccines are unable to evoke a natural infection profile with respect to the

release of antigen they must be administered on a number of occasions. Immunity is

not complete until the course of immunization is complete and, with the exception of

toxin-dominated diseases (diphtheria, tetanus) where the immunogen is a toxoid, will

never match the performance of live vaccine delivery. Specificity of the immune response

generated in the patient is initially low. This is particularly the case when the vaccine is

composed of a relatively crude cocktail of killed cells where the immune response is

directed only partly towards antigenic components of the cells that are associated with

the infection process. This increases the possibility of adverse reactions in the patient.

Vaccination and immunization 329

Release profiles of these immunogens can be improved through their formulation with

adjuvants (Chapters 14, 15), and the immunogenicity of certain purified bacterial

components such as polysaccharides can be improved by their conjugation to a carrier.

6 Routine immunization against infectious disease

6.1 Poliomyelitis vaccination

Poliovirus, a picornavirus, has three immunologically distinct types (I, II & III). The

first phase of poliomyelitis infection is an acute infection of the gastrointestinal tract,

during which time the virus is found in the throat and in faeces. The second phase is

characterized by an invasion of the bloodstream, and in the third phase the virus migrates

from the bloodstream into the meninges. Infections range in severity from clinically

inapparent (>90%) to paralytic. Paralytic poliomyelitis is a major illness, but only occurs

in 0.1-2% of infected individuals. It is characterized by the destruction of large nerve

cells in the anterior horn of the brain resulting in varying degrees of paralysis. The

infection is transmitted by the faecal-oral route and unvaccinated adults are at greatest

risk from paralytic infection than children.

Polio is the only disease, at present, for which both live and killed vaccines compete.

Since the introduction of the killed virus (Salk) in 1956 and the live attenuated virus

(Sabin) in 1962 there has been a remarkable decline in the incidence of poliomyelitis

(Fig. 16.1). The inactivated polio vaccine (IPV) contains formalin-killed poliovirus of

all three serotypes. On injection, the vaccine stimulates the production of antibodies of

the IgM and IgG class which neutralize the virus in the second stage of infection. A

course of three injections at monthly intervals produces long-lasting immunity to all

three poliovirus types.

A live, oral polio vaccine (OPV) is widely used in many countries, including the

UK and USA. Its main advantages over the IPV vaccine are its lower cost and easier

administration. OPV contains attenuated poliovirus of each of the three types and is

administered, as a liquid, onto the tongue. The vaccine strains infect the gastrointestinal

mucosa and oropharynx, promoting the common immune response, and involving both

humoral and secretory antibodies. IgA, secreted within the gut epithelium, provides

local resistance to the first stages of poliomyelitis infection. Infection of epithelial cells

with one strain of enterovirus often, however, inhibits simultaneous infection by related

strains. At least three administrations of OPV are therefore required with each dosing

conferring immunity to one of the vaccine serotypes. These doses must be separated by

a period of at least 1 month in order to allow the previous infection to elapse. Booster

vaccinations are also provided to cover the eventuality that some other enterovirus

infection, present at the time of vaccination, had reduced the response to the vaccine

strains.

Faecal excretion of vaccine virus will occur and may last for up to 6 weeks. Such

released virus will spread to close contacts and infect/(re)immunize them. Since the

introduction of OPV, notifications of paralytic poliomyelitis in the UK have dropped

spectacularly. From 1985-95, 19 of the 28 notified cases of paralytic poliomyelitis

were associated with vaccine strains (14 recipients, 5 contacts). Vaccine-associated

poliomyelitis may occur through reversion of the attenuated strains to the virulent wild-

330 Chapter 16

type, particularly with types II and III and is estimated to occur once per 4 million

doses. Since the wild-type virus can be isolated in faeces, infection may occur in

unimmunized contacts as well as vaccine recipients. Since the risks of natural infections

with poliomyelitis within developed countries has now diminished markedly, the greater

risk resides with the live vaccine strains. Proposals are therefore now being considered

in the USA that OPV should be replaced with IPV.

Measles, mumps and rubella vaccination (MMR)

Measles, mumps and rubella (German measles) are infectious diseases, with respiratory

routes of transmission and infection, caused by members of the paramyxovirus group.

Each virus is immunologically distinct and has only one serotype. Whilst the primary

multiplication sites of these viruses is within the respiratory tract, the diseases are

associated with viral multiplication elsewhere in the host.

Measles

Measles is a severe, highly contagious, acute infection that frequently occurs in epidemic

form. After multiplication within the respiratory tract the virus is transported throughout

the body, particularly to the skin where a characteristic maculopapular rash develops.

Complications of the disease can occur, particularly in malnourished children, the most

serious being measles encephalitis which can cause permanent neurological injury and

death.

A live vaccine strain of measles (Chapter 15) was introduced in the USA in 1962

and to the UK in 1968. A single injection produces high-level immunity in over 95% of

recipients. Moreover, since the vaccine induces immunity more rapidly than the

natural infection, it may be used to control the impact of measles outbreaks. The measles

virus cannot survive outside of an infected host. Widespread use of the vaccine therefore

has the potential, as with smallpox, of eliminating the disease worldwide. Mass immu-

nization has reduced the incidence of measles to almost nil, although a 15-fold increase

in the incidence was noted in the USA between 1989 and 1991 because of poor compliance.

Mumps

Mump virus infects the parotid glands to cause swelling and a general viraemia.

Complications include pancreatitis, meningitis and orchitis, the latter occasionally

leading to male sterility. Infections can also cause permanent unilateral deafness at any

age. In the absence of vaccination, infection occurs in >90% of individuals by age 15

years. A live attenuated mumps vaccine has been available since 1967 and has been

part of the juvenile vaccination programme in the UK since 1988 when it was included

as part of the MMR triple vaccine (see below).

Rubella

Rubella is a mild, often subclinical infection that is common amongst children aged

between 4 and 9 years. Infection during the first trimester of pregnancy brings with it a

Vaccination and immunization 331

major risk of abortion or congenital deformity in the fetus (congenital rubella syndrome

(CRS)).

Rubella immunization was introduced to the UK in 1970 for pre-pubeftal girls and

non-immune women. The vaccine utilizes a live cold-adapted Wistar RA27/3 vaccine

strain of the virus. The major disadvantage of the vaccine is that, as with the wild type,

the fetus is infected. Whilst there have been no reports of CRS associated with use of

the vaccine, the possible risk makes it imperative that women do not become pregnant

within 1 month of vaccination. Until 1988 boys were not routinely protected against

rubella. Their susceptibility to the virus was thought to maintain the natural prevalence

of the disease in the community and thereby reinforce the vaccine-induced immunity

in vaccinated, adult females. This proved not to be the case, rather cases of CRS could

be related to incidence of the disease in children. Rubella vaccine is now given to both

sexes at the age of 15 months.

6.2.4 MMR vaccine

MMR vaccine was introduced to the UK in 1988 for young children of both sexes,

replacing single-antigen measles vaccine. It consists of a single dose of a lyophilized

preparation of live attenuated strains of the measles, mumps and rubella viruses.

Immunization results in sero-conversion to all three viruses in over 95% of recipients.

For maximum effect MMR vaccine is recommended for children of both sexes aged

12-15 months but can also be given to non-immune adults. From October 1996 a

second dose of MMR was recommended for children aged 4 years in order to prevent

the re-accumulation of sufficient susceptible children to sustain future epidemics. Single-

antigen rubella vaccine will continue to be given to girls aged 10-14 years if they have

not previously received MMR vaccine.

6.3 Tuberculosis

Tuberculosis (TB) is a major cause of death and morbidity worldwide, particularly

where poverty, malnutrition and poor housing prevail. Human infection is acquired by

inhalation of Mycobacterium tuberculosis and M. bovis. Tuberculosis is primarily a

disease of the lungs, causing chronic infection of the lower respiratory tract, but may

spread to other sites or proceed to a generalized infection (miliary tuberculosis). Active

disease can result either from a primary infection or from a subsequent reactivation

of a quiescent infection. Following inhalation, the mycobacteria are taken up by

alveolar macrophages where they survive and multiply. Circulating macrophages and

lymphocytes, attracted to the site, carry the organism to local lymph nodes where a

cell-mediated immune response is triggered. The host, unable to eliminate the pathogen,

contains them within small granulomas or tubercles. If high numbers of mycobacteria

are present then the cellular responses can result in tissue necrosis. The tubercles contain

viable pathogens which may persist for the remaining life of the host. Reactivation of

the healed primary lesion is thought to account for over two-thirds of all newly reported

cases of the disease.

The incidence of TB in the UK declined 10-fold between 1948 and 1987, since

when just over 5000 new cases have been notified each year. Those most at risk include

332 Chapter 16

pubescent children, health service staff and individuals intending to stay for more than

1 month in countries where TB is endemic.

A live vaccine is required to elicit protection against TB since both antibody and

cell-mediated immunity are required for protective immunity. Vaccination with BCG

(bacille Calmette-Guerin) derived from an attenuated M. bovis strain is commonly

used in countries where TB is endemic. The vaccine was introduced in the UK in 1953

and was administered intradermally to children aged 13-14 years and unprotected adults.

Efficacy in the UK has been shown to be greater than 70% with protection lasting at

least 15 years. In other countries, where the general state of health and well-being of

the population is less than in the developed world, the efficacy of the vaccine has been

shown to be significantly less than this.

Because of the risks of adverse reaction to the vaccine by persons who had already

been exposed to the disease a sensitivity test must be carried out prior to immunization

with BCG. A Mantoux skin test assesses an individual's sensitivity to a purified protein

derivative (PPD) prepared from heat-treated antigens (tuberculin) extracted from

M. tuberculosis. A positive test implies past infection or past, successful immunization.

Those with strongly positive tests may have active disease and should be referred to a

chest clinic. Many people with active TB, especially disseminated TB, however, sero-

convert from skin test positive to skin test negative. Results of the skin test must therefore

be interpreted with care.

Much debate surrounds the use of BCG vaccine, a matter of some importance,

considering that TB kills ca. 3 million people annually and that drug-resistant strains

have emerged. Whilst the vaccine has demonstrated some efficacy in preventing juvenile

TB, it has little prophylactic effect against post-primary TB in those already infected.

One solution is to bring forward the BCG immunization to include neonates.

Immunization at 2-4 weeks of age will ensure that immunization precedes infection,

and will also negate the requirement for a skin test. Passive-acquired maternal antibody

to TB is unlikely to interfere with the effectiveness of the immunization since immunity

relates to a cell-mediated response. Alternative strategies involve improvement of the

vaccine possibly through the introduction, into the BCG strain, of genes that encode

protective antigens of M. tuberculosis.

6.4 Diphtheria, tetanus and pertussis (DTP) immunization

Immunization against these three, unrelated diseases, is considered together since the

vaccines are all non-living and are often co-administered as a triple vaccine as part of

the juvenile vaccination programme.

6.4.1 Diphtheria

This is an acute, non-invasive infectious disease associated with the upper respiratory

tract (Chapter 4). The incubation period is from 2 to 5 days although the disease remains

communicable for up to 4 weeks. A low molecular weight toxin is produced which

affects myocardium, nervous and adrenal tissues. Death results in 3-5% of infected

children. Diphtheria immunization protects by stimulating the production of an antitoxin.

This antitoxin will protect against the disease but not against infection of the respiratory

Vaccination and immunization 333

tract. The immunogen is a toxoid, prepared by formaldehyde treatment of the purified

toxin (Chapter 15) and administered whilst adsorbed to an adjuvant, usually aluminium

phosphate or aluminium hydroxide. The primary course of diphtheria prophylaxis

consists of three doses starting at 2 months of age and separated by an interval of at

least 1 month. The immune status of adults may be determined by administration of

Schick test toxin, which is essentially a diluted form of the vaccine.

6.4.2 Tetanus

Tetanus is not an infectious disease but relates to the production of a toxin by germinating

spores and vegetative cells of Clostridium tetani that might infect a deep puncture

wound. The organism, which may be introduced into the wound from the soil, grows

anaerobically at such sites. The toxin is adsorbed into nerve cells and acts like strychnine

on nerve synapses (Chapter 4). Tetanus immunization employs a toxoid and protects

by stimulating the production of antitoxin. This antitoxin will neutralize toxin as it is

released by the organisms and before it can be adsorbed into nerves. Since the toxin is

produced only slowly following infection then the vaccine, which acts rapidly, may be

used prophylactically in those unimmunized persons who have recently suffered a

candidate injury. The toxoid, as with diphtheria toxoid, is formed by reaction with

formaldehyde and adsorbed onto an adjuvant. The primary course of tetanus prophylaxis

consists of three doses starting at 2 months of age and separated by an interval of at

least 1 month.

6.4.3 Pertussis (whooping-cough)

Caused by the non-invasive respiratory pathogen Bordetella pertussis, whooping-cough

(Chapter 4) may be complicated by bronchopneumonia, repeated post-tussis vomiting

leading to weight loss and to cerebral hypoxia associated with a risk of brain damage.

Until the mid 1970s the mortality from whooping-cough was about one per 1000 notified

cases with a higher rate for infants under 1 year of age. A full course of vaccine, which

consists of a suspension of killed Bord. pertussis organisms (Chapter 15), gives complete

protection in over 80% of recipients. The primary course of pertussis prophylaxis consists

of three doses starting at 2 months of age and separated by an interval of at least 1

month.

6.4.4 DTP vaccine combinations and administration

The primary course of DTP protection consists of three doses of a combined vaccine,

each dose separated by at least 1 month and commencing not earlier than 2 months of

age. In such combinations the pertussis component of the vaccine acts as an additional

adjuvant for the toxoid components. Monovalent pertussis and tetanus vaccines, and

combined vaccines lacking the pertussis component (DT) are available. If pertussis

vaccination is contraindicated or refused then DT vaccine alone should be offered. The

primary course of pertussis vaccination is considered sufficient to confer life-long

protection, especially since the mortality associated with disease declines markedly

after infancy. The risks associated with tetanus and diphtheria infection persist

334 Chapter 16