Block 1

Summary of Unit 1
Summary of Sections 1 and 2
• The domestication of large mammals and poultry in the Eurasian continent from about 8000
BC initiated the gradual adaptation of infectious agents from these species to survival in
human hosts, resulting in major epidemic and pandemic disease outbreaks with huge loss
of human life in susceptible populations.
• Of the infectious diseases currently identified in humans, over 60% are zoonoses (i.e.
caused by infectious agents transmissible to humans from reservoirs in other vertebrate
animals, either by direct or indirect contact, or by arthropod vectors).
• Large settled communities created conditions favouring the transmission of infection
between individuals and across continents while trading with each other, disputing territory
in warfare, and clearing land for grazing and farming.
• Over many generations, European populations exposed to infections originating in
domestic species evolved some resistance to them. This resistance was not shared by the
indigenous peoples whose lands they colonised.

Summary of Section 3
• At the start of the twentieth century, infectious diseases accounted for around 40% of all
deaths in high-income countries (HICs), disproportionately affecting children aged under 5
years – a situation mirrored in low- and middle-income countries (LMICs) today.
• By the end of the twentieth century, deaths from infection in HICs had fallen to around 15%
of all deaths, and life expectancy at birth had risen by around 30 years. Advances also
occurred in LMICs, but at a much slower pace.
• Most of the decline in infectious disease before 1950 was due to rising living standards,
increased personal hygiene and public health strategies to improve water quality, sanitation
and food safety. This decline accelerated after 1950 due to mass vaccination programmes
and new drug treatments.
• In 1958, the WHO put tackling infectious disease in LMICs at the top of the health agenda
with some success, culminating in the global eradication of smallpox in 1980. The trend
continues downwards for most infectious diseases, but the start of the HIV/AIDS pandemic
in about 1982 quenched earlier optimism that all infectious disease could be eradicated.
• Vaccination programmes are currently preventing the deaths of an estimated 2.5 million
children aged under 5 years worldwide; a further 2 million if available child vaccines could
reach every child.

Summary of Section 4
• Disease-causing infectious agents are commonly distinguished as either pathogens
(pathogenic bacteria, viruses, fungi and prions), or as parasites, which include certain
single-celled protists and invertebrate animals (mainly worms).
• The underlying causes of an infectious disease encompass not only the infectious agent
involved, but also factors in the host and in the environment.
• Infectious diseases can be categorised in terms of the causative infectious agent, the
symptoms, duration or site of infection, and the route of transmission. Zoonoses are caused
by infectious agents that can be transmitted to humans by other vertebrates under naturally
occurring conditions.

Summary of Section 5
• Since the 1980s, health organisations have identified 175 emerging infectious diseases
(EIDs; new, re-emerging or drug-resistant infections), which have increased greatly in
human populations since the 1990s, or which threaten to increase in future.
• International surveillance of EIDs has intensified; some have been made legally notifiable,
and the WHO has set up global rapid response teams to attend new outbreaks.
• The interaction of cultural and biological factors underlies many EIDs, for example
increased air travel and intercontinental tourism, global transport of livestock and foodstuffs,
 logging and agricultural encroachment into formerly pristine habitats, intensive farming
practices, ‘fast-food’ catering, indiscriminate use of antibiotics as a factor in the evolution of
antibiotic-resistant bacteria, and (possibly) climate change.

Summary of Section 6
• Infectious diseases remain the most important cause of death, sickness and disability in
LMICs, accounting for around 40% of mortality. However, until the HIV/AIDS pandemic
began in the 1980s, the health burden due to infection had been slowly declining to levels
below those experienced in pre-industrial Europe.
• Acute respiratory infections (ARIs) cause the highest levels of mortality of any category of
infection worldwide, and among young children they are followed in importance by
diarrhoeal diseases, malaria and measles; almost all deaths from malaria occur in LMICs.
Many other infections that cause major mortality in such countries are less often fatal in
richer countries (e.g. hepatitis B, bacterial meningitis) or are not present (e.g. cholera,
sleeping sickness, yellow fever, plague).
• For infectious and all other disorders, the incidence (number of new cases per year) and
prevalence (total number of individuals affected at a given time point) are calculated on the
basis of the rate in the population at risk (i.e. those individuals capable of being affected by
that disorder).
• The UK illustrates the pattern in HICs, where infectious diseases now account for around
15% of deaths, mainly in older people. In the UK population of 62 million (2010), an
estimated 26 million episodes of infection annually result in a GP consultation. The
incidence of vaccinepreventable diseases has declined to very low levels.
• Caution must be exercised when interpreting epidemiological data, which may be distorted
by incomplete surveillance, changes in detection methods and diagnostic inaccuracy. Data
based on crude numbers of disease episodes or deaths can be misleading where
population size and/ or age structure has changed over time or differs between locations;
age standardisation and the expression of data as a rate in the population at risk improves
the reliability of comparisons.

Summary of Unit 2
• Biological agents of disease include representatives of helminths and protoctists (generally
called parasites), fungi, bacteria and viruses (generally called pathogens) and prions
(infectious proteins).
• Koch’s postulates are widely used to determine the identity of the causative agent of a
disease, though they have limitations.
• Parasites, including pathogenic microbes, are specially adapted to penetrate a host, spread
within it, and produce and release progeny, without succumbing to the host’s defence
systems.
• The symptoms of disease are often caused by the body’s response to the disease agent,
as well as by the agent itself.
• Infectious diseases can have endogenous or exogenous causes.
• Routes of horizontal transmission of exogenous agents are via the air, via direct contact, or
via food and water; vertical transmission occurs from mother to fetus or newborn.

Summary of Unit 3
Summary of Sections 1 and 2
• Viruses are extremely diverse in the range of hosts they infect and the degree of disease
they induce (if any) but they all are incapable of independent life.
• Viruseswere first discovered as filterable disease-causing substances that can replicate in
host cells.
• The first virus studied was tobacco mosaic virus.
• The activity of bacterial viruses was first demonstrated in 1915, and they have been
extensively studied since.
• Viral culture techniques involve finding a suitable host that can be manipulated easily in the
laboratory. This may be a whole organism or cells in tissue culture.
 • Some viruses still cannot be cultured in vitro.

Summary of Section 3
• Whether viruses are ‘alive’ remains a controversial point.
• Viruses are completely dependent on their host cells for proliferation.
• Viruses consist of a nucleic acid genome contained within a capsid. Some viruses have an
additional envelope, derived from host cell membranes.
• Capsids are generally helical or icosahedral, though others may have a more complex
structure.
• Viral nucleic acid may be DNA or RNA, single- or double-stranded, and may be present as
one or more distinct molecules; RNA genomes may be in sense (+), antisense (−) or
ambisense strands.
• The evolutionary origin of viruses is obscure.

Summary of Section 4
• Viruses can be classified in several ways, such as by shape or size, host, type of capsid,
family and genus, replication strategy, or nucleotide sequence.
• Reverse-transcribing viruses make DNA from an RNA template and hence challenge the
central dogma of gene expression.

Summary of Unit 3
Summary of Section 5
• Generally, replicating viruses undergo attachment, uncoating, genome replication,
expression of early and late genes, maturation and release.
• There are seven distinct replication strategies and the details of these processes are highly
variable.

Summary of Section 6
• Pathogenic viruses may be cytocidal, and kill the host cell quickly, or non-cytocidal, in
which case persistent infections may ensue. A latent infection is a persistent infection in
which viral replication is suppressed.
• Viruses often have cytopathic effects such as the formation of syncytia and inclusion
bodies, membrane damage, or the triggering of apoptosis.
• Some viruses transform host cells and may give rise to cancers.

Summary of Sections 7 and 8

• The routes of transmission used by viruses to infect susceptible hosts are diverse.
• Viruses can cause acute or persistent infections.
• Persistent infections can be latent, when the virus is essentially dormant until it is
reactivated, or slow, when the virus replicates only very slowly.
• HIV is transmitted via sexual activity, vertically, or by direct contact with infected blood.
After an acute phase, infected individuals remain asymptomatic for many years until they
develop AIDS.
• Smallpox virus is transmitted by the respiratory route. It causes a mild primary viraemia,
then a secondary viraemia with characteristic skin symptoms. It has a high mortality.
• Measles virus is also spread by the respiratory route and also gives rise to two viraemias.
The symptoms include a skin rash and Koplik’s spots. Measles can have severe
complications, which can themselves lead to death.
• Very similar viruses can produce very different diseases.
Summary of Section 9
• New viral diseases often emerge following a disturbance in the ecological balance.
• Some new viral diseases can only be identified when new molecular technology allows their
detection.
Summary of Section 10
Viruses have been useful to humans in the following ways:
 • as a tool for basic research
• as therapeutic agents for bacterial diseases
• as vectors for gene therapy.

Summary of Unit 4
Summary of Sections 1 and 2
• Prions are abnormally folded molecules of a membrane glycoprotein.
• Prions spread by corrupting normal protein molecules to the abnormal conformation.
• Abnormal folding is facilitated by glycolipid and RNA cofactors.
• Prions cause transmissible spongiform encephalopathies (TSEs).
• Animal TSEs have been known for centuries, but human TSEs have been identified only
relatively recently.

Summary of Section 3
• Most CJD cases are sporadic, though 10% may be inherited and 1% patrogenic in origin.
• TSE-infected tissue is a source of infection, although not all TSEs are infectious in normal
circumstances.
• The best understood example of a human TSE is kuru, where infection was transmitted
through cannibalism.
• There is still some controversy about the role of PrPsc in TSEs.

Summary of Section 4.4

• The outbreak of BSE in the UK was caused by animal feeding practices that were driven by
economic considerations.
• The UK government’s response was criticised as ‘too little, too late’.
• Variant CJD is thought to be a result of eating BSE-infected cattle.
• The full scale of the BSE epidemic may not be known for many years.

Summary of Unit 5
Summary of Sections 2–5
• Only a few bacteria are pathogenic, and not all cause disease in all host individuals.
• Important surface structures include flagella, fimbriae, pili, capsules and the glycocalyx.
• The structures of different bacterial cell walls can be used as a basis for selective
antibacterial therapy.
• The pathogenicity of a bacterium depends on the virulence factors, often encoded in
pathogenicity islands, which it can deploy.
• Genes for virulence factors can be transmitted vertically, but of major clinical importance is
horizontal transmission, which is mediated by plasmids, transposons, or bacteriophages.
• A major virulence factor is the production of one or more toxins.
• Exotoxins are secreted proteins that often have an A–B structure.
• Endotoxins are bacterial surface components that can stimulate the immune system and
cause symptoms of endotoxic shock.

Summary of Section 6
• Diseases may be caused by vegetative bacteria (most commonly), endospores (in a few
cases) or occasionally toxins.
• Once a bacterium has gained entry to a host, it must adhere to it. This is facilitated by
external structures such as adhesins or fimbriae.
• Adherent bacteria have a range of strategies for amassing materials for growth and
division. When sufficiently large numbers are established, the pathogen can spread within
the host.
• Bacteria are adapted to evade host immune responses.
• Some individuals carry and disseminate pathogens without showing signs of the disease
themselves.
Summary of Section 7
• Pathogens can be transmitted by air, arthropods, direct contact, or food and water.
• Major airborne pathogens include diphtheria and pertussis.
• Diphtheria symptoms are caused by a toxin that has a classic A–B structure and affects
protein synthesis. Corynebacterium grows inside macrophages.
• Pertussis symptoms are also caused by toxins, one of which inhibits the mucociliary
escalator.
• Both diphtheria and pertussis can be controlled by vaccination.
• Major arthropod-borne disease include: bubonic plague, caused by Yersinia pestis, which
has many virulence factors encoded in the Yop virulon; Lyme disease, caused by tick-borne
Borrelia burgdorferi; and typhus, caused by Rickettsia prowazekii and transmitted by body
lice.
• Major diseases spread by direct contact include staphylococcal infections and chlamydial
infections.
• Staphylococcus spp. produce many toxins and other virulence factors that enable them to
resist phagocytosis and proliferate. Antibiotic resistance is an increasing problem, as shown
with the appearance of MRSA and C. difficile in hospitals and other institutions.
• Chlamydia spp. are intracellular pathogens and cause urinogenital infections and eye
disease.
• Pathogens contracted through contaminated food include Salmonella, E. coli and
Staphylococcus. All cause diarrhoea, and there may be further complications.
• Salmonella strains grow within intestinal epithelial cells, and so do some types of E. coli.
Other types of E. coli and Staphylococcus cause disease by toxin production.

Summary of Section 8
• In the post-antibiotic era we will once again be at risk of many bacterial infections that can
be fatal.
• Consumption of probiotics can confer some resistance to gut pathogens.
• Bacteriphage therapy holds promise for the future.

Summary of Unit 6
Summary of Section 1
• Protists are eukaryotic organisms, and are taxonomically and structurally highly diverse.
• Almost all protists have flagella, and those in which flagella are present in the dominant
stage are known as flagellates.
• Single-celled protists that cannot photosynthesise are known as protozoa.
• Few protists are pathogens, but those that are cause serious diseases.
• It is difficult to treat diseases caused by protists, as it is hard to achieve selective toxicity

Summary of Section 2
• Giardiasis is a chronic diarrhoea caused by Giardia lamblia.
• Giardiasis is passed on by cysts in infected water or food.
• Giardia cysts are resistant to water chlorination, but can be removed by filtration.
• Trypanosomes cause African sleeping sickness and, in Central and South America,
Chagas’ disease.
• Trypanosomes have a complex life cycle involving other hosts and an insect vector.
• Trypanosomes can vary the antigens in their protein coats.

Summary of Section 3
• Amoebiasis is caused by several species of amoeba.
• Entamoeba histolytica causes amoebic dysentery and ulcerative colitis.
• Acanthamoeba species can cause keratitis and, sometimes, primary amoebic
meningoencephalitis.

Summary of Section 4
 • The apicomplexans are all single-celled parasites of animals.
• Among the diseases they cause are malaria, toxoplasmosis and cryptosporidiosis.
• Apicomplexans have complex life cycles involving sexual and asexual reproduction.
• Diseases caused by apicomplexans are particularly serious in immunocompromised
individuals.

Summary of Unit 7
• Fungi generally grow as filamentous hyphae or single-celled yeasts, although some
(dimorphic fungi) switch between filamentous and singlecelled growth forms.
• The fungal cell wall is composed largely of chitin, a polymer of Nacetylglucosamine (NAG).
• The fungal plasma membrane contains ergosterol.
• Fungi reproduce by forming sexual and asexual spores.
• Filamentous fungi grow by hyphal extension; yeasts can replicate by fission or budding.
• Mycoses are caused by biotrophic fungi.
• Enzymes released by the fungus cause tissue damage to the host.
• Mycoses can be superficial, subcutaneous or systemic. Only superficial mycoses are truly
infectious.
• Ringworm infections, caused by dermatophytes, commonly affect the scalp or the feet, and
have a global distribution.
• Thrush is caused by Candida yeasts, and is very common throughout the world.
• Subcutaneous mycoses occur most often in people who work barefoot in tropical and sub-
tropical agricultural settings.
• Systemic mycoses can result in disseminated infections, which are serious diseases,
especially in immunocompromised people.

Summary of Unit 8
• Parasitic ‘worms’ belonging to the phyla Platyhelminthes (flukes and tapeworms) and
Nematoda (roundworms) are worldwide in distribution, but are particularly prevalent in low-
and middle-income countries (LMICs).
• Parasite life cycles include a number of larval stages, which enhance transmission from
host to host, either directly or indirectly by means of intermediate hosts or vectors.
• Schistosomiasis (blood fluke disease) is a major disease, adult flukes infecting blood
vessels around the intestine or bladder, depending on the species.
• Other flukes may occur in the liver or lungs.
• Tapeworms in the gut are less debilitating, but sometimes larval stages in the tissues may
cause severe disease symptoms.
• Roundworms are worldwide in distribution, both adults and larvae being responsible for
disease symptoms.
• Parasites and hosts appear to show coevolution.

Summary of Unit 9
• Early, accurate diagnosis is important for successful treatment, but is not easily achieved in
some parts of the world.
• For accurate diagnosis it is important to obtain sufficient quantities of relevant samples, and
they must be handled correctly to allow identification of any pathogen, and compliance with
safety measures.
• Tests for infectious agents, or the effects they cause to the host can be grouped into:
metabolic, morphological, immunological, and genetic tests.
• For each test a suitable positive and negative control should be used.
• Correct diagnosis requires a logical approach that takes into account the patient’s
symptoms and history, a knowledge of endemic infections, and test results.

Block 2
Summary of Unit 1
• The immune system has evolved different ways of protecting the host against different
pathogens. The immune system appears complex, because it has to respond against a
wide variety of pathogens and defence systems have evolved which are appropriate for
each pathogen. The innate immune defences act in concert with adaptive immune
responses mediated by lymphocytes.
• The immune system can recognise both intracellular and extracellular pathogens.
• The route of infection is important in determining the type of response that develops.
• Leukocytes are distributed in lymphoid organs and tissues, which are strategically placed to
protect different areas of the body.
• Recognition of pathogens and their antigens is carried out by lymphocytes, which fall into
two main subsets: B cells use surface antibody to recognise intact antigens in solution and
on the surface of infected cells. Eventually they differentiate into plasma cells that produce
a secreted form of the antibody. T cells use their T cell receptor to recognise processed
antigen fragments presented by MHC molecules on the surface of other cells of the body.
• T cells fall into three principal groups:
◦ Th1 cells release cytokines that activate phagocytes.
◦ Th2 cells help B cells to make antibody.
◦ Tc cells can kill infected cells of the body.
Large granular lymphocytes are also involved in recognising infected cells.
• Phagocytes including neutrophils and macrophages internalise and destroy material that
they have phagocytosed.
• Antigen-presenting cells (APCs) are a functionally defined group that includes B cells,
macrophages and dendritic cells. They present antigens to T helper cells. Leukocytes
migrate through the body in the blood and lymphatics, moving between lymphoid tissues
and other tissues of the body. The route of migration depends on the type of cell.

Summary of Unit 2
• Pathogen-associated molecular patterns can be recognised by receptors which are
expressed on mononuclear phagocytes and other cells of the body.
• Antibodies, produced by B cells, specifically bind to antigens. Different classes of antibody
have different functions. IgA is secreted across mucosal membranes, and is important in
protecting these sites against pathogen entry. IgG and IgM antibodies promote
phagocytosis, either directly, or by activating the complement system. IgE is important in
the development of inflammation.
• Antibodies bind to epitopes using multiple non-covalent bonds. The binding strength
determines the affinity of the antibody.
• The complement system is a group of molecules, present in blood and issue fluids, which
can be activated either by immune complexes or by the surface of many pathogens, and
which leads to pathogen destruction and/or the induction of inflammation.
• MHC molecules present antigen fragments to T cells.
• Antigen from within cells, processed by the internal pathway, is presented by MHC class I
molecules. Cytotoxic T cells (Tc cells) recognise antigen presented by MHC class I
molecules on the surface of virally infected cells. Any nucleated cell can present antigen to
a Tc cell.
• Antigens that have been endocytosed (external pathway) are presented to T helper cells
(Th cells) by class II molecules expressed on antigenpresenting cells.
• In order to be activated, T cells require a signal of antigen presented on an MHC molecule
and costimulation. Infectious agents may promote antigen presentation by enhancing
costimulation.
Summary of Unit 3
• T-independent antigens are often carbohydrates or polyclonal activators, which induce
production of IgM. They tend to be low affinity antibodies.
• T-dependent antigens require B cells to present antigen to T cells. They induce class
switching and affinity maturation.
• Class switching is the switch from production of IgM to other antibody classes, which
 occurs by rearrangement of the Ig heavy chain genes.
• Affinity maturation is the increase that is seen in the binding affinity of antibodies during a
secondary immune response, as a result of mutations in the antibody genes and selection
of high affinity clones.
• Inflammation involves an increase in blood supply, enhanced vascular permability and
leukocyte migration into the affected area.
• Leukocyte migration is controlled by chemotactic molecules, including chemokines which
activate specific populations of leukocytes. Adhesion molecules on the vascular
endothelium induced by inflammatory cytokines interact with integrins on the leukocytes,
allowing the leukocytes to migrate across the endothelium.
• Mast cell derived mediators and products of the kinin and complement systems control
blood supply and vascular permeability at sites of inflammation.

Summary of Unit 4
• Antibodies and complement protect against bacteria by neutralising bacterial toxins and
enzymes, by preventing bacterial adhesion, by directly damaging the bacterial cell
membrane and by promoting phagocytosis.
• IgA is important in protecting mucosal surfaces and preventing bacteria from attaching to
mucosal epithelium.
• Phagocytes are important in defence against many bacterial infections. They phagocytose
pathogens and subject them to a barrage of toxic reactive oxygen and nitrogen compounds.
• Macrophages are particularly important in defence against intracellular bacteria, including
those causing typhoid, tuberculosis and leprosy. Macrophage activation by IFNγ is required
for the cells to develop their full bactericidal potential.
• Activated macrophages act as antigen-presenting cells and they release cytokines and
chemokines which promote inflammation.
• Cells can recognise some intracellular bacterial infections using NOD molecules and some
of the toll-like receptors that are present on intracellular membranes.

Summary of Unit 5
• Eosinophils can bind to schistosomes opsonised by antibody and release their toxic granule
contents onto the surface of the parasite to kill it.
• Strong antibody responses are induced by T. brucei, which can effectively clear the
parasites. However, the parasites undergo antigenic variation to evade the immune
response.
• In Chagas’ disease, a chronic cell-mediated immune reaction fails to completely clear the
parasites and may itself cause considerable damage to the host tissue.

Summary of Unit 6
• Interferons induce the synthesis of antiviral proteins. If activated by viral products, the
antiviral proteins inhibit general protein synthesis in the cell, thus limiting the ability of the
virus to replicate.
• Cytotoxic T cells can recognise virus-infected cells that present viral peptides on MHC class
I molecules.
• NK cells can recognise cells that have reduced expression of MHC molecules, using their
killer inhibitory receptors (KIR) and the CD94 family of receptors, which recognise MHC-
encoded peptides presented on HLA-E
• Cytotoxic cells kill their targets by ligation of CD95 (Fas) and by release of TNFs which
activate caspases to induce apoptosis in the target. Perforin produces pores in the target
cell membrane and granzymes enter the target cell’s cytoplasm to cause further damage.
• Antibodies and complement help control extracellular virus; they prevent attachment of the
virus to uninfected cells and promote phagocytosis and clearance of the virus.
• Antibodies also protect against reinfection with the same virus.

Summary of Unit 7
• Antigen is the primary control on immune responses.
 • How an immune response develops in an individual depends on how they first encounter
the antigen (antigen presentation) and genetic factors as well as on the nature of the
antigen/pathogen.
• Th1 cells tend to inhibit Th2-type immune responses and vice versa.
• IL-4, IL-10 and IL-13 (Th2-cytokines), and IL-12 and IFNγ are important in establishing the
mode of an immune response, by controlling cell proliferation and differentiation.

Summary of Unit 8
• Infection often causes tissue damage, with inflammation and cell death followed by repair
and regeneration. These processes leave a characteristic histological signature in the
infected tissue.
• Some chronic infections can induce tumours either by direct mutation of the host DNA, or
by altering host cell metabolism and the controls on cell proliferation.
• Disease symptoms are often caused by cytokines, or host signalling systems released as a
consequence of infection, rather than the infectious agent itself.
• Immunodeficiency and immunosuppression both result in increased susceptibility to
infection. Which pathogens are involved depends on which part of the immune system is
deficient.
• The immune deficiency caused by HIV is due to a loss of CD4+ T helper cells, which make
the person more susceptible to a range of infections and tumours normally controlled by
cell-mediated immunity.
• Excessive immune reactions (hypersensitivity) are induced by a number of pathogens. In
these cases the immune response itself contributes to the pathology.
• Infection may lead to the breakdown of self-tolerance, by introducing cross-reactive
antigens into the host, by altering the ways in which antigens are presented to T cells, or by
interfering with immunoregulation.

Summary of Unit 9
• Serotyping uses antibodies to identify variants of a microorganism.
• Diagnosis of infection can be carried out by identifying rising titres of antibodies against the
pathogen in the serum of a patient.
• The ELISA test can be used to measure antibodies in tissues and body fluids.
• Variants of the ELISA are used to detect the presence and levels of many different proteins,
peptides and hormones both in diagnosis and research.
• Genetic serotyping is used to identify genetic variants of different pathogens. It can be used
for diagnosis and for epidemiological tracing of the spread and evolution of particular
strains of a pathogen.

Summary of Unit 10
• Active immunisation is aimed at inducing an appropriate immune response in the host that
can protect against a true infection. Passive immunisation uses directly administered
antibodies.
• A critical antigen is one that can induce a protective immune response. For B cell-mediated
responses, the critical antigens are often on the outside of the pathogen and may be used
by the pathogen to attach to host cells or evade phagocytosis.
• Vaccine preparations in current use may be toxoids, killed organisms, live attenuated
organisms, subunits or conjugates.
• The appropriate vaccine design depends on the immune mechanisms that normally protect
against the particular pathogen.
• The immunogenicity of a vaccine is related to how it is first presented, including the site of
vaccination, the use of adjuvants, and factors that induce costimulation of T cells.

Summary of Unit 11
• Human cultures have a long history of using biocidal chemicals outside the body to combat
infection. From the 1800s onwards, the formulation of biocides and of chemotherapeutic or
prophylactic medicines has increasingly been based on theoretical as well as empirical
 knowledge of chemistry and the biology of hosts and their pathogens.
• Anti-infective chemical agents vary in their efficacy at killing or preventing the replication of
pathogenic organisms; those within the range of a particular chemical constitute its
spectrum of activity, which may be broad or narrow. Efficacy varies even against organisms
within a chemical’s spectrum of activity.
• Selectivity is an important factor when considering the usage of antiinfective chemicals. The
concept incorporates the spectrum of activity and efficacy of a chemical against a range of
target organisms, and the level of selective toxicity for non-target organisms, both within the
human body and in the external environment.
• The therapeutic index defined as TD50/ED50 is a useful measure of the efficacy and
selectivity of a pharmaceutical agent.
• Chemicals can be used in diverse ways to combat infection either outside the body
(biocides) or within the body (medicines), based on their physico-chemical properties.
• Surfactants are used to remove microbial contamination by disrupting the surface tension of
adherent material (mainly fats). They also make an important contribution to strategies to
control insect vectors that breed in still water.
• The ability of chemicals to denature proteins is exploited in non-specific biocides that
destroy a broad range of microbes, for example alcohols.
• For some chemical agents, there may be a relatively narrow optimum range (e.g. of
temperature, water content, pH) at which their action against pathogenic microbes reaches
maximum efficacy – many biocides have to be in a partially ionised state to be effective
disinfectants.

Summary of Unit 12
• Antibacterial drugs exploit specific characteristics of bacterial metabolism, including their
distinctive systems of protein synthesis and the requirement to build cell walls.
• The sulfonamide drugs illustrate how antimetabolites, as analogues of naturally occurring
bacterial substrates, act as competitive compounds in antibacterial chemotherapy; they
also illustrate the concept of prodrugs.
• The penicillins illustrate how bacteria can develop drug resistance, and how treatment with
combinations of drugs can partly circumvent this problem.
• Antiviral drugs exploit the ways in which viruses enter and leave the host cell and the ways
in which they replicate their genome. Examples are the neuraminidase inhibitors for
influenza and anti-retrovirals, used to treat HIV.
• Antimycotic drugs are primarily targeted at the requirements that fungi have for ergosterol,
to control their membrane fluidity, in distinction from mammalian cells which use cholesterol
for this purpose.
• Multiple therapy can overcome some problems of drug resistance (as in the addition of
beta-lactamase inhibitors to beta-lactam antibiotics), compensate for the unacceptable
toxicity of single anti-infective agents, or act as the first resort when an unidentified
pathogen is producing a life-threatening infection.
• Problems associated with multiple therapy can include the additional cost of treatments,
adverse drug interactions or side effects and the complexity of dosing regimens which may
impact on patient compliance. These difficulties are exemplified by HAART regimens for
HIV infection.

Summary of Unit 13
• Drug treatment of infection involves not just targeting the pathogen, but alleviating
symptoms.
• The selection of the appropriate anti-infective agent for an individual involves
considerations of patient tolerance, the dosing regime, and the potential for drug resistance
in the pathogen.
• Prophylactic chemotherapy is advised for individuals whose ability to resist infection is
compromised by an underlying medical condition (e.g. cancer treatment, organ
transplantation, cystic fibrosis), or when there is a known exposure to a high infection risk
(e.g. during ‘dirty’ surgery, or contact with a potentially life-threatening pathogen as in
 mother-to-child HIV transmission).
• The prophylactic use of antimalarial drugs prior to travel in an endemic area illustrates the
issues of giving drugs to healthy individuals to prevent infection.
• Pharmaceuticals can be used to prevent or treat the adverse consequences of infection.
Over-the-counter remedies for respiratory tract infections include antipyretic drugs to
reduce fever, analgesics to reduce pain and decongestants to reduce nasal secretions.
Prescription drugs may include bronchodilators to reduce constriction of the airways. The
dehydration and electrolyte loss associated with acute diarrhoea can be reversed by
drinking equivalent amounts of a solution of oral rehydration salts (ORS).

Block 3
Summary of Unit 1
• Public health strategies aim to prevent disease or reduce its impact by taking actions to
protect or promote the health and wellbeing of the population as a whole, in contrast to
medical strategies for treating disease in its individual members.
• The global burden of infectious disease remains a significant threat to health, economic
development and equity of opportunity, particularly (but not exclusively) in low- and middle-
income countries and disproportionately among young children.
• A systematic and evidence-based approach to addressing threats to public health began
with the sanitarian movement in England in the nineteenth century and remains the basis
for public health strategies today.
• Public health approaches to infectious diseases focus on one or a combination of:
◦ screening, surveillance, monitoring and reporting of disease outbreaks
◦ community education to promote health-related behaviour change
◦ increasing the resistance of the human host to infection, e.g. through vaccination and
nutritional support
◦ community mobilisation to tackle sources of infection in the environment
◦ case finding, case containment and (where necessary) isolation of infectious
individuals.
• Vaccination, the provision of clean drinking water and improved sanitation, the promotion of
personal and institutional hygiene, and the organisation of surveillance and response
strategies to detect and control disease outbreaks are integral to the public health
approach. Raising sustainable living standards, improving the quality of housing, nutrition
and education, and promoting gender equality and personal security are also important
public health goals.
• International health regulations (IHRs), including trade and travel agreements, and the work
of international organisations (e.g. the WHO) contribute at a global level to public health
approaches to infectious disease.
• Three levels of prevention of infectious diseases can be identified in a public health context.
Primary prevention aims to prevent new cases from occurring; secondary prevention aims
to treat the disease at the earliest stage to prevent it from spreading; and tertiary prevention
aims to alleviate the worst effects of an established disease in an individual, which may
indirectly benefit the rest of the community.
• Community participation and community health workers with minimal training and
equipment are central to the success of infection-control campaigns in many parts of the
world, and particularly in low- and middle-income countries.

Summary of Unit 2
• The subject of epidemiology is the study of health in populations. An important aspect of
the epidemiology of infectious diseases is the study of how infections are transmitted within
populations.
• The basic measures of epidemiology include risks and rates. A risk is the probability that an
event, such as infection or disease, occurs within a defined group. A rate is the number of
occurrences per unit time in a given population.
• An important measure in infectious disease epidemiology is the basic reproduction number,
 R0. This is the average number of individuals directly infected by a single infective
introduced into a population that is completely susceptible to the infection.
• f R0 is less than or equal to 1, the infection will die out in the population. If R0 is greater
than 1, the infection may become endemic. The larger the value of R0, the more difficult the
infection is to control.
• Commonly used epidemiological data for infectious diseases includes case reports,
laboratory reports, and serological survey data. Awareness of the possible shortcomings of
these data, for example because of lack of completeness, or diagnostic inaccuracy, is
required when interpreting them.
• Compartmental models such as the SIR model provide a simple framework that can help
focus on the key stages of infectious disease transmission.
• For directly transmitted infections, the types of contacts that are relevant in transmission
are determined by the route of transmission. Contact rates are difficult to estimate directly
in most settings.
• The force of infection is the rate at which susceptibles become infected. The force of
infection is important because it can be estimated more easily than contact rates,
particularly under the assumption of homogeneous mixing, which assumes that contacts
occur at random within the population.

Summary of Unit 3
Summary of Section 1
• Changes in population abundance in time and space are referred to as population
dynamics. Geographical ranges, comprising the full range of a species, are also dynamic.
• The geographical range of the malaria pathogens has declined in the last century and is
now largely confined to tropical regions.
• Prevalence of disease may be a misleading description of pathogen abundance. Similarly,
mean pathogen abundance may be unhelpful in describing the distribution of pathogens
among hosts. Aggregated distributions of pathogens (especially larger species) are well
known.
• Hosts may also be aggregated in space with the resulting high population densities
favouring the transmission of certain pathogens.

Summary of Section 2
• A compartmental model is constructed to investigate the possible spread of malaria through
a village. Four compartments of host and vector are recognised: susceptible, infected but
latent, infectious and recovered.
• The assumptions of the model include equal susceptibility of the hosts, a constant high
vector population and the introduction of the pathogen by a single infected host.
• Changes in the numbers of hosts and vectors in the different compartments are calculated
over a total of 34 days. In this example, comparison of the number of infected persons on
Day 34 with the number on Day 1 (one person) show whether the pathogen will increase or
decrease in the village.
• Based on the assumptions of this model, a daily bite rate of 0.4 is required for persistence
of the pathogen. This value is identified as a threshold for persistence.

Summary of Section 3
• Fluctuations or cycles of abundance of pathogens could be due to extrinsic causes, e.g.
seasonal weather patterns.
• Evidence from historical and current data points to diseases with a variety of time periods of
outbreaks or epidemics.
• Intrinsic processes underlying cycles of abundance in ecological systems have been linked
to host specialisation and delays in response of one population to changes in the other.
These processes are illustrated by the interaction between grouse and its major parasitic
nematode.
• Delays in host–pathogen systems appear to be widespread, with pathogens benefiting by,
for example, avoiding the host defence and timing completion of the life cycle in the host
 with vector activity.
• Cycles of abundance of human pathogens may be rare due to the variety of human
pathogens, the long generation time of humans and the lack of numerical responses in
fecundity. If they do occur, such cycles might be undetectable over the normal timescales
of scientific study.

Summary of Unit 4
• An infection is in an endemic steady state when it is established in a population and
undergoes regular fluctuations around a constant longterm average. In such a population,
the proportion of the population that is immune is called the herd immunity level. For
homogeneously mixing populations, the basic reproduction number, R0, can be estimated
directly from the herd immunity level.
• The basic reproduction number can also be estimated from the average age at infection in
the population (A).
• Serological survey data and case reports can be used to estimate the herd immunity level
and the average age at infection, and hence the basic reproduction number of an infection.
• Endemic infections with short latency and infectious periods (D′ and D, respectively) often
exhibit regular epidemic cycles. These cycles are related to the build-up of susceptibles
through births, and their depletion by infections that result in immunity.
• For infections exhibiting epidemicity, the inter-epidemic period (T) is related to the average
age at infection and the serial interval of the infection (D′ + D).
• Epidemic models offer insights about population effects on the spread of infectious agents
that are essential in designing effective control strategies.

Summary of Unit 5
Summary of Section 1
• Three models of host–pathogen coevolution were presented: mutual aggression (host and
pathogen engaged in arms race); prudent pathogen (pathogen evolves towards doing less
harm to host) and incipient mutualism (where pathogen and host come to benefit each
other).
• Genetic variation among hosts is one reason for variation in susceptibility to infection. This
is illustrated by alleles associated with malaria defence and infection with HIV. The most
variable region of the mammalian genome is the major histocompatibility complex (MHC).
• Genetic variation in hosts may be decreased by inbreeding, which may reduce resistance
to disease. Conversely, genetic variation in hosts may be increased by pathogens due to
selective infection of commoner genotypes, preferential mating with partners with different
MHC loci, temporal variation in the pathogen environment and selection against
homozygotes.
• Genetic variation in pathogens is generated, as in the hosts, by sexual reproduction
(among protists and invertebrate pathogens) and, unlike the hosts, by horizontal transfer of
genes (bacteria and viruses). A single host may possess several pathogen strains at one
time, exemplified by HIV. Pathogens vary greatly in their genetic variation (e.g. high in
Staphylococcus aureus and low in Mycobacterium tuberculosis).
• HIV provides a good example of a pathogen that has high genetic variation both within and
between hosts. The variation is generated by copying errors by reverse transcriptase and
recombination between the RNA strands. This variation is realised within hosts due to the
rapid replication of the virus and may be patchy due to the movement of the viruses to
different parts of the host, creating a metapopulation structure.
• The relatively short generation times of pathogens and their high capacity for genetic
variation pose a major problem for hosts with long generation times.

Summary of Section 2
• Virulence has been defined as both the ease with which an infection is established and the
degree of damage. The best definition from an evolutionary point of view is effect on host
fitness, but this is difficult to measure.
• Virulence can be thought of as collateral damage of pathogen reproduction. As such,
 evolution of virulence may be misleading and we should be considering evolution of
reproduction rates.
• Quantitative definitions of virulence include lethal dose and case fatality rate.
• Conventional wisdom is that pathogens evolve from more to less virulent. However, there
are counter-examples, especially in the initial stages of pathogen evolution (e.g. Yersinia
species). What is certain is that virulence factors may change rapidly, e.g. as in cholera.

Summary of Section 3
• There are three interpretations of changes in host behaviour and/or physiology due to
pathogens. First, as incidental consequences of pathogens, second as adaptive defensive
reactions by the host and third as changes which favour the pathogen, e.g. in transmission.
• Wolbachia bacteria manipulate their invertebrate host species by killing or harming males
or removing the need for males by causing females to reproduce parthenogenetically.
• Studies of the role of fever as either host manipulation or an adaptive response of hosts
show that fever increases host survival, probably by enhancing the immune response.
• The evolutionary aspects of two types of transmission were discussed – transmission by
host-to-host contact through sexual activity and transmission by vectors.

Summary of Section 4
• Sexually transmitted infections (STIs) are caused by viruses, bacteria and fungi and affect
large numbers of people worldwide and generally cause chronic infections.
• STIs are host-specific with the pathogen adopting a strategy of stealth and/or evasion in the
host.
• There is no evidence that sexually transmitted pathogens manipulate their hosts to increase
promiscuity.
• Studies across a wide range of animal species support the idea of STIs as diseases of low
mortality (with the exception of HIV), caused by longlived pathogens with a narrow host
range and eliciting weak immune responses.
• Insect vectors are effectively ‘flying syringes’, providing a reliable means of transmission.
• The immune systems of insect vectors provide defence against the pathogens they carry.
In response, the pathogens protect themselves against the vector’s immune system.
• Genetic modification of the insect vector and the discovery of pathogeninduced apoptosis
offer hopes of novel methods for controlling malaria.
• There are various reasons for emerging or resurging vector-borne diseases, including
urbanisation, deforestation, evolution of drug-resistant pathogens and pesticide-resistant
vectors, and possibly climate change.
Summary of Unit 6
Summary of Sections 1 and 2
• Progress towards reducing the burden of infectious diseases is constrained by the
interaction of many factors, including poverty, shortage of food, clean water and sanitation,
inadequate housing, and lack of education.
• The biological adaptability of many pathogens and vectors enables the rapid evolution of
evasion mechanisms that render vaccines ineffective and promote resistance to chemical
treatments and controls.
• Rapid mutation rates among some viruses (e.g. HIV) and the ability of influenza viruses to
recombine to produce novel strains contributes to the pandemic spread of these viral
diseases.
• Antigenic drift and shift in some pathogens, multiple-strain infections, gene switching and
difficulties in isolating suitable target antigens present significant problems for the design of
new vaccines and chemical agents.
• The increasing prevalence of multidrug-resistant tuberculosis (MDR-TB) and the
emergence of extensively or totally drug-resistant strains is a serious cause for concern in
many parts of the world.
• Healthcare-associated infections (HCAIs) – particularly those due to drug-resistant bacteria
– pose an increasing threat in health facilities in all parts of the world, causing large
numbers of deaths and increased health service costs.
 • Insecticide resistance can emerge very rapidly in vector species due to overexposure to the
small number of chemicals approved for public health use.

Summary of Section 3
• Difficult circumstances of geology and climate, the risks posed by major natural disasters,
and the impact of climate change and agricultural practices are expanding the distribution
of pathogens and vectors, and increasing the size of the population at risk of infection.
• Attempts to provide microbiologically safer groundwater from tube-wells in Bangladesh and
some other locations had the unintended consequence of exposing the population to
arsenic poisoning from natural underground deposits.
• Naturally occurring reservoirs of pathogens and vectors in diverse environments such as
forests, agricultural land, surface water and other animals, mean that infectious diseases
will never be completely eradicated.
• HCAIs are most prevalent in intensive care units and other locations where medical devices
and tubing enter the patient and can quickly become colonised by bacterial biofilms.

Summary of Sections 4 and 5

• The lack of finance in low- and middle-income countries is a major barrier to reducing
infection because installing infrastructure projects delivering clean water and sanitation is
hugely expensive.
• Hand washing with soap can significantly reduce the transmission of diarrhoeal and
respiratory infections, but progress is constrained by lack of attention to hygiene
behaviours, inadequate access to soap and clean water, and the persistence of cultural
norms that place a low value on hand washing.
• Vaccination programmes require billions of dollars of investment to reduce the 1.7 million
child deaths every year from vaccine-preventable diseases. Lack of transparency about the
costs of vaccines may hamper the expansion of vaccination programmes.
• The shortage of essential skills, knowledge, trained personnel and equipment, not only in
the health service but also in engineering, management and many other sectors, is a
barrier to progress. Globally, there is an estimated shortfall of 4.25 million health workers
who are needed to provide basic health services.
• Ignorance of cultural contexts, the power of social norms, the impact of negative rumours
and moral or religious opposition can limit the effectiveness of health education initiatives
and make individuals and communities highly resistant to behavioural change.