S320

INFECTIOUS DISEASE

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 Cover pictures
Top left: Schistosome parasites. Coloured scanning electron micrograph of adult
female (upper, thinner) and male (lower, fatter) Schistosoma mansonii parasitic
worms, cause of the disease bilharzia (schistosomiasis).
Top right: Scanning electron micrograph of Staphylococcus sp.
Lower left: Coloured electron transmission micrograph of Mycobacterium
tuberculosis.
Lower right: False colour transmission electron micrograph of influenza viruses
(orange) budding from the surface of an infected cell.

This publication forms part of an Open University course S320 Infectious Disease.
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1.1

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 POLIO CASE STUDY

CONTENTS
1 THE HISTORY OF POLIO 5

2 PATHOLOGY AND IMMUNOLOGY 8

3 THE POLIO VIRUS 11

4 DIAGNOSIS 12

5 POLIO VACCINES 12

6 THE GLOBAL VACCINATION CAMPAIGN 15

7 LEARNING OUTCOMES 17

8 QUESTIONS 17

9 ANSWERS TO QUESTIONS 18

ACKNOWLEDGEMENTS 19

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 S320 INFECTIOUS DISEASE

FIGURE 1.1 About 1% of people who contract polio develop muscular weakness or flaccid
paralysis, usually in the legs, due to the destruction of motor neurons in the spinal cord.
Muscular wasting occurs in the paralysed limbs. Children with partial paralysis may be helped to
walk by supporting the affected limb with iron braces. Here a doctor examines a boy who was
paralysed in a polio epidemic in the USA in the 1920s.

4
 POLIO CASE STUDY

POLIO CASE STUDY

We have chosen polio (poliomyelitis) to illustrate the use of mass vaccination to
control an infectious disease that was formerly a major health problem in many
parts of the world. By 2001, polio had almost been eradicated by an aggressive
global programme of vaccination coordinated by the WHO, but there was a
setback in 2002 when it resurged in India and Nigeria. In this case study we
use the example of polio to explain why vaccination is an effective strategy
against some infectious diseases, but not against others, and to illustrate the
biological and social reasons why even a vaccine-preventable disease such as
polio may still be difficult to eradicate completely. We suggest that you spend
no more than 3 hours on this case study, including time to explore some
Internet resources concerning polio, which can be located by following the links
under Course Resources on the S320 website.

1 The history of polio

Poliomyelitis or polio is an acute viral illness, which produces muscular paralysis in
about 1% of infected individuals. The disease was described by Landsteiner and
Popper in 1909, although the earliest case report of a paralytic disease that may
have been polio dates from England in 1789. The polio virus was not identified until
the 1930s. It only infects humans, so there is no separate animal reservoir – a
feature that hugely increases the prospects for successful control of an infectious
disease through vaccination.
In the first half of the 20th century, frequent outbreaks of polio occurred in
temperate countries, particularly during the summer months. For example, in the
summer of 1916 an epidemic in New York left 27 000 people paralysed and 9000
dead. Epidemics in the Western hemisphere increased in frequency and in severity
(Figure 1.1), until they were brought under control by the introduction of polio
vaccination in the USA in the 1950s and 60s and, subsequently, in other parts of the
developed world. The last case of polio in the USA as a result of person-to-person
transmission of the wild-type (i.e. naturally occurring) polio virus occurred in
1979.
However, attempts to tackle polio in developing countries lagged far behind the
progress made in the Western world. Surveys of ‘lameness’ in Africa and Asia in
the 1970s concluded that hundreds of thousands of children were paralysed each
year due to polio virus infection, and a concerted effort to introduce vaccination
programmes worldwide began. By 1988, the rapid decline of polio in North America
and Western Europe encouraged the WHO to adopt the goal of global eradication by
2000 – a target which has subsequently been put back to 2005. Figure 1.2 overleaf
shows the geographical distribution of wild-type polio virus in 1988, when an
estimated 350 000 cases of polio were occurring worldwide, and the position in
December 2002, when most regions of the world had been officially certified as
free of polio infection. The Americas (North and South) were the first region to be
declared polio-free in 1994, the Western Pacific region and China followed in 2000,
and the entire continent of Europe in June 2002 – four years after the last known
European case of paralytic polio caused by wild-type virus was detected in Turkey.

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 S320 INFECTIOUS DISEASE

1988

known or probable wild polio virus transmission

no wild virus

2002

certified as polio free low intensity indigenous transmission

no wild virus high intensity indigenous transmission
importation/under investigation

FIGURE 1.2 (a) Regions with known or probable transmission of wild-type polio virus in 1988. (b) Global polio status in December
2002. The designation ‘no wild virus’ indicates countries reporting no cases of wild-type polio virus transmission in 2002, within a WHO
region that has not yet been certified polio free. Isolated cases in countries with no other evidence of wild-type virus are probably imported
and shown as ‘under investigation’.

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 POLIO CASE STUDY

The speed of decline in case reports since the global eradication initiative began in
1988, and the slower progress in the regions where it remains endemic, can be
traced in Figure 1.3. The presumed endemic countries in 2002 are Afghanistan,
Bangladesh, India and Pakistan in South Asia, and the African states of Angola,
Democratic Republic of Congo, Egypt, Ethiopia, Niger, Nigeria, Somalia and Sudan.
However, Afghanistan, Egypt, Niger and Somalia reported a combined total of only
25 cases of polio in 2002, and several other countries had no reports. The greatest
concern is focused on India and Nigeria, where rates rose sharply in 2002; for
example, reports of polio in India increased from 268 in 2001 to 1562 cases a year
later. We consider the organization of the global eradication campaign in the final
section of this case study.

40000
reported number of cases

30000

20000

10000

0
1988 89 90 91 92 93 94 95 96 97 98 99 00 01 02
(a) year

12000

10000
reported number of cases

8000

6000

4000

2000

0 FIGURE 1.3
Decline in the global incidence of
1990 91 92 93 94 95 96 97 98 99 2000
year polio. (a) Total number of new cases
(incidence) reported to the WHO
South Asia Sub-Saharan Africa CEE/CIS East Asia/Pacific annually, 1988–2002. (b) Reported
incidence in most affected WHO
Middle East /North Africa Latin America/Caribbean
regions, 1990–2000. (CEE/CIS refers
CEE/CIS = Central and Eastern Europe/Commonwealth of Independent States to countries in Central and Eastern
Europe, including independent states
(b) such as Armenia, Belarus, Russian
Federation, Ukraine and Uzbekistan.)

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 S320 INFECTIOUS DISEASE

2 Pathology and immunology

The incubation period for polio virus infection is variable, but is commonly between
1 to 3 weeks. The virus is transmitted primarily from person to person via the
faecal–oral route, because large quantities of virions are shed in the faeces of
infected individuals. In the early stages of an infection, the virus may also be passed
on via the respiratory route, when aerosol droplets of infected saliva are coughed or
sneezed into the local atmosphere, but the virus does not remain long in the throat.
The initial sites of infection are the tonsils (the main lymphoid tissues in the
pharynx) and the gut-associated lymphoid tissues or GALT, including Peyer’s
patches (Figure 2.1). Soon after initial replication in these sites, the virus circulates
in the blood (viraemia) and distributes to other lymphoid organs, where it undergoes
a secondary replication phase. In under 10% of cases, a transitory flu-like illness
occurs lasting less than a week, with symptoms of sore throat and fever, and
occasionally nausea and vomiting. The secondary viral replication may result in the
virus load in the blood reaching a high level, and in 1–2% of individuals it can
spread to the central nervous system (CNS) and cause a mild meningitis, with
stiffness in the neck, back and limbs, which resolves spontaneously. In less than
1% of cases, the motor neurons in the spinal cord and brain stem become infected
and paralysis can result. Motor neurons innervate the skeletal muscles and are
central to the initiation and control of movement.

1 infection 3 lymphoid tissue

(oral, respiratory) (subsequent
replication site)

4 CNS
(target organ
pathology)

2 tonsils and GALT

(initial
replication site)

5 transmission
(faecal–oral route)

FIGURE 2.1 Polio infection is mainly acquired orally (or less often by the respiratory route),
and initially the virus replicates in the tonsils and gut-associated lymphoid tissues (GALT). Later,
the virus spreads via the blood (viraemia) to other lymphoid tissues and a second phase of
replication may occur. The virus may then spread to the central nervous system (CNS) and infect
motor neurons, especially in the brain stem and spinal cord.

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 POLIO CASE STUDY

Within a week of initial infection, polio virus is excreted in the faeces and
continues to be shed for several weeks. What problems does this pose for the
control of polio virus transmission?
Over 95% of infected individuals remain asymptomatic, and even those who
become ill generally develop only mild transitory symptoms, which are easily
confused with other viral flu-like illnesses. Thus the majority of infected people
remain unaware that they are shedding large amounts of polio virus in their
faeces and are infectious to others. Lack of adequate resources for washing and
for maintaining food hygiene increases the risk of transmission.

The typical R0 for polio virus infection is between 4 and 7. Explain what this
means. (If you are unsure, revise Book 6, Section 1.2.)
Polio virus is highly infectious: 4–7 secondary infections can be expected
among the contacts of each case in a totally susceptible population.

The sites of polio virus replication are determined by the tissue distribution of the
receptor to which it binds on the surface of human cells. The polio-virus receptor
is expressed on monocytes and macrophages in the lymphoid tissues, epithelial cells
in the gut and motor neurons in the CNS. The receptor has structural similarities to
the immunoglobulins (and has been designated CD155), but the normal
physiological function of this molecule has not yet been determined. (The CD
system of cell surface markers is described in Book 3, Box 1.1.)

What immune defences are available to prevent viruses from infecting the gut
epithelium or spreading in the blood?
Antibodies: particularly IgA at epithelial surfaces in the gut and IgG in the blood
(Book 3, Section 2.1.1). From 7 days after initial infection, IgG antibodies that
bind specifically to polio-virus antigens appear in the blood (Book 3, Figure 2.6).

The infection is controlled by the immune response in the majority of individuals,

particularly by the rapid increase in IgG antibodies. But if the virus reaches the CNS
it can replicate in motor neurons and has a cytopathic (cell damaging) effect which
may kill the nerve cells directly. It is not yet known exactly how the virus causes
cell death, but within 1–2 hours of it entering the host cell a rapid decline in the
synthesis of the cell’s own macromolecules occurs. It appears that the virus is able
to shut down the translation of host proteins and divert resources to make new
virus particles.
Virus infection in the CNS also provokes a strong local inflammatory response.
Infiltrating neutrophils and monocytes can damage infected neurons by the local
release of toxic molecules and inflammatory cytokines (Figure 2.2 overleaf). Up to
1% of individuals who have a polio virus infection will develop an acute flaccid
paralysis (AFP), usually of the lower limbs, due to the destruction of motor
neurons. This characteristic form of paralysis is so named because it develops so
quickly (acute) and the paralysed muscles are relaxed (flaccid) rather than
contracted. Polio virus mainly infects children aged under 5 years, but it is more
likely to result in paralysis in older children, adolescents and young adults for
reasons that remain unclear. No effective drug treatment for polio virus infection
has ever been developed.

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 S320 INFECTIOUS DISEASE

30 mm
FIGURE 2.2 Polio virus infection in the spinal cord. Compare the distinct outline of an
uninfected neuron (A), with the damaged appearance of an infected neuron (B), surrounded by a
dense infiltrate of inflammatory cells.

Deaths from polio occur in 5–10% of those with AFP if they cannot be artificially
ventilated, because the virus infects motor neurons in the brain stem, leading to
paralysis of the muscles required for breathing. In the 1940s and 50s, some patients
with respiratory paralysis in the USA and Western Europe were kept alive for
several years in an ‘iron lung’, which mimicked normal respiratory movements by
rhythmically increasing and decreasing the atmospheric pressure on the patient’s
thorax.
Neurons cannot be replaced by cell division, so there is generally some permanent
disability in individuals who have developed any degree of paralysis after polio
infection. However, there may be partial recovery of function, because motor
neurons can develop collateral branches to replace the functions of cells that have
been lost. People who have recovered from paralytic polio may develop post-polio
syndrome, with pain and progressive muscular weakness occurring decades later.
They remain free of polio virus and so are not infectious. It is thought that the
reduction in neurons during the original infection leaves these individuals with
insufficient capacity to compensate for the slow loss of neurons that normally
occurs with age.

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 POLIO CASE STUDY

3 The polio virus

The structure, genome and replication cycle of the polio virus were described in
detail in Book 2, Chapter 3, see particularly Figures 3.5, 3.13 and 3.14. The
main points are summarized briefly here.

The polio virus, like all Picornaviridae, is an un-enveloped virion with a small
positive-sense RNA genome (‘pico’ means small). Picornaviruses display varying
degrees of genetic homology, as shown in Figure 3.1 (a dendrogram is a
conventional way of depicting the proportion of nucleotide sequences common to
related strains or species). Polio viruses belong to the Picornavirus subgroup
known as enteroviruses, which infect the gut. They are most closely related to the
coxsackie viruses and to rhinoviruses (the causative agent of the common cold). As
with other Picornaviridae, the viral capsid consists of 60 protomers each formed
from four proteins generated by the cleavage of a single original protomer. Figure
3.2 shows a computer-generated model of the polio virus capsid, in which its
icosahedral symmetry is clearly visible.

rhino

polio
enteroviruses

coxsackie

other
entero

40 50 60 70 80 90 100
% nucleotide identity Ä

FIGURE 3.1 A dendrogram showing the genetic relationship between different Picornaviruses
based on nucleotide homology. There are three serotypes of polio viruses with 60–70% genetic
homology. The polio viruses are related to the coxsackie and other enteric viruses and to the
rhinoviruses that cause colds.

The polio virus is extremely stable. Its genome is highly resistant to mutation under
natural conditions and only three strains of wild-type polio virus are known: the P1,
P2 and P3 serotypes, distinguished on the basis of the antibodies that bind to them.
FIGURE 3.2
Although the three strains show 60–70% genetic homology, there is minimal cross- A computer-generated model of the
reactivity between them in terms of the antibodies they elicit. Thus, recovery from polio virus capsid. The arrow points
infection with one polio strain confers little or no protection against infection with to one of the vertices of the
another. The P2 serotype now appears to be extinct in the wild. icosahedral structure.

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 S320 INFECTIOUS DISEASE

4 Diagnosis
A diagnosis of polio is confirmed by testing for the presence of polio virus in swabs
from the throat or rectum of a suspected case.

What laboratory methods are most commonly used to determine the identity of
a virus in such a sample? (If you are unsure, you may need to revise parts of
Book 4.)
The concentration of the virus is increased to testable levels by growing it in
tissue culture in suitable host cells (Book 4, Section 2.2.1). The identity of the
virus is usually determined by serological methods employing specific antibodies
that bind to unique antigens in the viral structure, linked to some method of
visualizing whether they have bound (Book 4, Section 3). Advanced molecular
biological methods are increasingly being used to amplify sections of the viral
RNA genome by RT-PCR technology (reverse transcriptase-polymerase chain
reaction, Book 4, Section 3.5) to reveal characteristic nucleotide sequences.

Efficient laboratory confirmation of polio virus infection is an essential feature of

the WHO’s global eradication campaign. Countries whose system of surveillance,
case notification and laboratory testing are considered to be inadequate to detect
every case are given assistance to improve their methods and technology. A high
standard of detection efficiency is required before ‘polio-free’ certification can be
awarded after a minimum of three years with no laboratory-confirmed isolates of
wild-type virus.

5 Polio vaccines
The repeated summer epidemics of polio in the USA during the earlier part of the
20th century led to a major research effort to develop a polio vaccine. The first
vaccine to progress to clinical trials in 1954 was a chemically-inactivated
preparation developed from all three wild-type virus strains by Dr Jonas Salk. The
Salk vaccine is given by intramuscular injection and was tested in the USA on a
huge sample of 623 972 children aged 7–8 years, who received either the vaccine or
a placebo. The results of the trial announced the following year showed that the
incidence of polio and its sequelae had been reduced by 80–90% in the vaccinated
children compared with the controls. The American government immediately
introduced a mass vaccination programme for polio using the intramuscular polio
vaccine (IPV is an alternative term for the Salk vaccine).

What factors allowed the USA to introduce mass polio vaccination after just
one clinical trial, and without waiting to see whether the vaccine had long-term
adverse effects?
In the 1950s, there was a considerable real and perceived risk of contracting
polio, particularly among children, and the consequences could be lifelong
paralysis or death. The results of the pilot programme were very promising.
There was a more general acceptance of medical authority, and of a role for the
government in directing health promotion at that time, than there is now.

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 POLIO CASE STUDY

In 1962, a second vaccine was authorized for public use in the USA, named after
its developer Albert Sabin. Like the Salk vaccine it was ‘trivalent’, i.e. it contained
all three serotypes, but the Sabin vaccine consisted of live attenuated strains of
the virus and it was administered orally (and is also known as the oral polio vaccine,
OPV). Attenuated strains have been treated (as described in Book 7, Chapter 3) to
promote the acquisition of mutations, which ideally abolish their pathogenicity
without affecting their immunogenicity. Thus, the aim of such a vaccine is to elicit
a strong immune response without harming the recipient.
The attenuated virus strains in the Sabin vaccine replicate in the vaccinated person
in the gut epithelium and lymphoid cells, just like the wild-type polio virus (see
Figure 2.1), until a sufficiently strong immune response has developed to destroy
them. Infants receiving their first series of OPV shed attenuated viruses in their
faeces for a short period, and parents are advised to take particular care over
hygiene to avoid spreading the attenuated strains to other people. (It will become
clear in Section 6 why accidental spread of OPV strains poses a risk.)

Explain why the Sabin vaccine (OPV) is given by mouth, while the Salk
vaccine (IPV) is administered by injection.
The Sabin vaccine is ‘live’ and is delivered by the same route as the wild-type
virus in order to elicit a protective immune response in the gut. The Salk vaccine
is a non-replicating antigen preparation that would be broken down in the gut if
given by mouth, so the antigens are injected directly into the muscle.

The impact of the introduction of these two vaccines on cases of paralytic polio in
England and Wales can be seen in Figure 5.1, curtailing a post-war polio epidemic
which threatened to reach new and frightening levels. Note that in this period, polio
case notifications were largely based on the clinical diagnosis of acute flaccid
paralysis and relatively few cases of non-paralytic polio were recorded.

8
Salk vaccine (IPV)
7

6
number of reported cases

5
(thousands)

2 Sabin vaccine (OPV)

1

0 FIGURE 5.1
Effect of the introduction of mass
1930 1940 1950 1960 1970 1980 polio vaccination programmes in the
year 1950s and 1960s on the incidence of
paralytic polio in England and Wales.

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 S320 INFECTIOUS DISEASE

Explain why improved levels of personal and household hygiene may

(paradoxically) have been a factor in the large rise in polio cases shown in
Figure 5.1 around the end of World War II.
Improved post-war levels of personal and household hygiene reduced the
transmission of polio virus to infants and young children, resulting in an increase
in the average age of infection with polio. The young are the most susceptible
group because they have no prior immunity, but they are also less likely to
develop paralysis than older individuals (the risk of paralysis rises with age), so
most cases of polio in young children were not notified as such. As the average
age of infection rose in the post-war period, so too did the proportion of cases
who developed paralysis and appeared in official statistics. Thus, although
changes in domestic hygiene may have contributed to a fall in polio incidence in
the population, they may also have contributed to a rise in paralytic polio.

Modern polio vaccines are based on viruses grown in bulk in tissue cultures derived
from monkey kidney cells. Live attenuated vaccines such as OPV generally elicit a
stronger and longer-lasting immune response than is provoked by ‘killed’ viral
antigen preparations like IPV. The strong IgA response elicited by OPV in the gut
also gives a high level of protection against subsequent infection with wild-type
virus becoming established there. The low IgA response in people vaccinated with
IPV means that wild virus may still replicate in the gut, with the result that these
individuals are asymptomatic but infectious. The ease with which an oral vaccine
can be given by drops into the mouth (Figure 5.2) or on a sugar lump, and its low
cost (around US$1 per dose), are further reasons why OPV has replaced IPV in
many countries.
However, the OPV has one drawback. It contains live virus, so there is always a
possibility of pathogenic reversion in the vaccinated individual, i.e. the genetic
changes that occurred in the attenuated strain are reversed, or new mutations are
acquired, to produce a virus with similar properties to the wild-type strain. The
closer the similarity between the wild-type strain and the attenuated strain, the
greater the chance of pathogenic reversion occurring. For example, an attenuated
FIGURE 5.2 P1 strain with 57 mutations has never reverted to wild-type, but reversion has
A child receiving oral polio vaccine occurred in attenuated P2 and P3 strains each with only two relevant mutations.
(OPV).
The risk of pathogenic reversion in the strains used in the OPV is very low, but
cases of vaccine-associated paralytic polio (VAPP) have been reported at an
incidence estimated at 1 case per 1.5 to 3 million OPV doses (it varies between
countries). That risk is now higher in most parts of the world than the risk of
contracting polio from wild-type virus, for the simple reason that (as Figure 1.2b
showed) many regions are now certified as polio-free. Figure 5.3 traces changes in
the incidence of VAPP and paralytic polio due to wild-type virus in the USA after
mass vaccination with OPV was introduced in 1962. More recent data record a
total of 144 cases of VAPP in the USA in the 20 years from 1980 to 2000,
compared with around 20 000 cases of wild-type paralytic polio each year in
the 1950s.
By contrast with OPV, the IPV has been responsible for only one instance of
vaccine-associated paralytic polio in its 50-year history, when a batch of IPV was
not fully inactivated and a proportion of recipients developed the disease. For this
reason, several countries including the USA and the Netherlands have increasingly
switched back to using IPV, or a combination of IPV followed by OPV to maximize
the safety and effectiveness of each vaccine. The oral vaccine has not been

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 POLIO CASE STUDY

3000
vaccine associated
2500
non-vaccine-associated
1000
number of reported cases

300

100

80

60
FIGURE 5.3
40 Annual incidence of vaccine-associated
paralytic polio and paralytic polio due
20 to wild-type virus in the USA, 1960–
1994. (Note the breaks in the vertical
0
axis of this diagram.) The danger of
1960 1965 1970 1975 1980 1985 1990 1995 contracting vaccine-associated polio
year exceeded the risk of the natural
infection by about 1980.

recommended for use in the USA since 2000. This switch in vaccine strategies
illustrates the necessity to evaluate the changing risks of an infectious disease over
time compared with the unchanging risks of intervention.

6 The global vaccination campaign

In those regions of the world where wild-type polio is still endemic, the very low
risk of VAPP is far outweighed by the much greater risk of indigenous disease, so
vaccination programmes use OPV for the reasons stated earlier. The goal of the
global eradication initiative has been to achieve a high level of vaccine coverage in
every country in the world, by whatever means are available. In polio-endemic
countries, the key strategy has been to organize sub-national or National
Immunisation Days (NIDs), followed up where possible by house-to-house visits
to reach any children who were missed. NIDs involve massive advance publicity
encouraging all parents to bring their children to vaccination centres throughout the
country on specific dates.

We noted earlier that children vaccinated with OPV shed live virus in their
faeces for a few weeks. What risk is posed by accidental transmission of OPV
strains by this route, and how could vaccinating a high proportion of children
on the same day reduce this risk?
Unvaccinated individuals who accidentally acquire OPV strains via the faecal–
oral route may fail to develop a protective immune response, perhaps because
the infective dose is too low and is not boosted by repeat vaccinations, or
because their immune system is deficient. The OPV strains could become
established in these individuals, and although they replicate without causing
harm, over time they could spread to other susceptibles in the population. NIDs
attempt to ensure that a high proportion of the population receives an
immunising dose of vaccine at the same time, so there are too few susceptibles
to support the OPV strains becoming established ‘in the wild’.

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 S320 INFECTIOUS DISEASE

OPV strains are not harmful, so why is it a concern if they become established
in the wild?
It is possible that an OPV strain could, at some point in the future, revert to
pathogenicity and paralytic polio could emerge again as a major threat. It would
also be impossible for the world to be declared ‘polio-free’ while vaccine strains
of the virus are in still in circulation.

By scheduling a series of NIDs in a short period, a momentum

infants < 1 year is also created in which parents who did not attend one of the
earlier dates are motivated by peer-pressure within their
community to have their children vaccinated at a later NID.
Africa 54 For example, in November 2002, sixteen countries in West
Africa organized simultaneous NIDs with the aim of
vaccinating 60 million children with OPV. The sharp rise in
The Americas 90 cases of polio in India in 2002 was attributed to a drop in
vaccination coverage that year, and the response was to
Eastern organize a series of six NIDs in February 2003 to vaccinate
Mediterranean 79
WHO regions

160 million children.

Europe 94 The recommended polio vaccination schedule requires three
doses of vaccine (OPV or IPV) to be given to each child in the
first year of life, with a booster before the fifth birthday.
South-East Asia 73
Figure 6.1 shows the proportion of infants in each WHO
region who were protected by three doses of polio vaccine in
Western Pacific 80 2001 – a combined total of 575 million children in 94
countries.
global 75

20 40 60 80 100
FIGURE 6.1 Proportion of children in each WHO region in 2001 who
3rd dose vaccine coverage (%)
received three doses of polio vaccine in their first year of life.

Think back to Book 6 and the discussion of the critical immunization threshold
for polio (Table 4.1). How does the vaccine coverage in the various WHO
regions shown in Figure 6.1 compare with this threshold?
Wild-type polio transmission can be expected to die out in a population that
consistently exceeds a critical immunization threshold of 75–85%. Figure 6.1
shows that except in Africa and South-East Asia, this threshold has already been
met.

The financial cost of the global eradication programme in the last 20 years has been
huge – around US$2 billion – and the WHO has reported a funding gap of US$275
million to meet the target of certifying the remaining endemic countries as polio-free
by 2005. And there are other challenges on the path to the eradication of polio.
Stocks of wild-type polio virus must be maintained in secure laboratories as the
basis for bulk production of vaccines. There must be a watertight system of
detection of all cases of AFP in people aged under 15 years to ensure that the
condition is accurately attributed either to wild-type polio virus, VAPP, or is
unrelated to polio infection. And in the future, there are concerns that if vaccination

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levels fall, then live oral vaccine strains may become established in the wild in
populations with low immunity to polio-virus antigens, with all the risks discussed
earlier.

We suggest that before returning to Book 7 to complete your study of

vaccination in Chapter 3, you spend about one hour exploring the polio websites
maintained by WHO and UNICEF, which give regularly updated information on
the current global status of polio, specific country data on vaccination
coverage and the latest news on the progress towards eradication. The
websites can be located by following the appropriate links in the Resources
section of the S320 website. If you have time, you may also find that the Public
Broadcasting Service (PBS) website ‘A short timeline of polio history’ for the
USA from 1916 to 1961 gives you a deeper insight into the severity and public
perceptions of the disease (however this is optional). Seen together, the social
history and the current epidemiology give an insight into the enormous
progress that has been made against polio in the last 50 years. If you have a
particular interest in the biology of the polio virus and its genome, you will also
find a link to a website on Picornaviridae (run by the University of Leicester’s
Virology Department), which gives greater detail.

7 Learning outcomes
When you have completed this case study and explored the websites indicated in
Section 6, you should be able to:
1 Define and use, or recognize definitions and applications of, each of the terms
printed in bold in the text. (Questions 1–3)
2 Give a short description of the symptoms and progression of polio infection
and its consequences, relating this to the biology of the polio virus and the
cellular pathology it causes. (Question 1)
3 Describe the vaccines that have been developed to combat polio, their relative
advantages and disadvantages, and their impact on the epidemiology of the
disease. (Question 2)
4 Explain why the polio virus has been so susceptible to control by vaccination,
and identify the problems that will need to be overcome in order to eradicate it
completely. (Question 3)

8 Questions

Question 1
What are the principal cells of the body that become infected with polio virus and
why do these cells become infected and not others? How does the distribution of
susceptible cells relate to the symptoms of polio infection?

Question 2
What kinds of antibody response are induced by the oral polio vaccine (OPV) and
the intramuscular polio vaccine (IPV), and how does this relate to the protection
they offer?

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Question 3
Suggest a number of biological and immunological factors that have contributed to
the success of polio vaccination programmes. What are the principal barriers to
eradicating the wild-type virus in those countries in which it is still endemic?

9 Answers to questions
QUESTION 1
The initial sites of polio virus replication are in monocytes and macrophages in the
tonsils and the gut-associated lymphoid tissues (GALT), and subsequently in the gut
epithelium and other lymphoid tissues. Neurons only become infected in 1–2% of
individuals. The virus can infect these cell types because they express the polio
virus receptor on their surface membranes. Most infected individuals develop no
symptoms at all, but those who do generally experience a mild flu-like illness
characteristic of an immune response against a viral infection, sometimes with gut-
associated symptoms such as nausea and vomiting. If the virus spreads to the
central nervous system (CNS), there may be transient stiffness in the muscles.
Infection of motor neurons in the spinal cord or brain stem can lead to cell death
and acute flaccid paralysis (AFP) usually in the lower limbs, and less often to
asphyxiation through paralysis of the respiratory muscles.

QUESTION 2
The oral vaccine initiates a strong IgA response, which is long-lasting and can
protect the epithelial surfaces of the gut against subsequent infection with wild-type
virus. The intramuscular vaccine tends to favour an IgG response, which prevents
viral spread during the viraemic phases, but is less effective at protecting the gut.
Polio virus may still replicate in the gut of individuals who have been vaccinated
with IPV, allowing transmission of viruses shed in the faeces, even though
vaccinated people are protected from developing polio. A good antibody response to
either vaccine is enough to prevent the virus from reaching the spinal cord, thereby
protecting the person from serious pathology.

QUESTION 3
The success of the vaccination programme can be partly attributed to the fact that
polio virus only infects people – there is no animal reservoir. However, it can be
grown in bulk for vaccine production in tissue cultures derived from monkey
kidney cells. Polio virus is stable and does not mutate under normal conditions (as
do viruses such as influenza and HIV). There are only three different serotypes
(strains) of polio virus to be incorporated into a vaccine. Killed or live attenuated
strains have been developed which are highly immunogenic, eliciting a protective
antibody response which is long-lasting if repeated doses are given in childhood.
Barriers to the final eradication of polio are primarily the huge financial cost (with a
funding gap of US$275 million at the end of 2002) and the organizational difficulties
in ensuring that more than 85% of children are vaccinated three times within a year
of birth, and given a booster dose before they are five. Polio-endemic countries
often lack the infrastructure and personnel to reach remote regions. Advertising
campaigns for mass vaccination days may not have sufficient impact to persuade
parents to travel long distances – perhaps on foot – to bring their children to the
nearest vaccination centre.
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Acknowledgements
Grateful acknowledgement is made to the following sources for permission to
reproduce material in this book:

Cover images
Top left: NIBSC/Science Photo Library; top right: David M. Philips/Visual Sun
Limited; lower left: Dr Kari Lounatmaa/Science Photo Library; lower right: CNRI/
Science Photo Library.

Figures
Figure 1.1: Courtesy George Eastman House; Figure 1.2: The World Health
Organisation; Figure 1.3: de Quadros, C. A. (1997) ‘Global eradication of
poliomyelitis’, Annals of Internal Medicine, Vol. 127, Issue 2, pp.156–158,
American College of Physicians; Figure 2.2: Reprinted from Infectious Diseases by
Armstrong & Cohen, Vol 1, p. 22.3 by permission of the publisher Mosby; Figure
3.1: Dr Alan Cann; Figure 3.2: Reproduced by permission of Jean-Yves Sgro from
[Link] Figure 5.2: Photograph provided
courtesy of The World Health Organisation.

Every effort has been made to trace all the copyright holders, but if any has been
inadvertently overlooked the publishers will be pleased to make the necessary
arrangements at the first opportunity.

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The Open University

ISBN 0 7492 5663X

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