Tutorial Topics in Infection For The Combined Infection Training Programme 1St Edition Cheuk Yan William Tong Full Chapter PDF
Tutorial Topics in Infection For The Combined Infection Training Programme 1St Edition Cheuk Yan William Tong Full Chapter PDF
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Tutorial Topics in Infection for the Combined Infection
Training Programme
Tutorial Topics in Infection
for the Combined Infection
Training Programme
EDITED BY
Caryn Rosmarin
Consultant in Medical Microbiology
Department of Infection
Barts Health NHS Trust
London, UK
Armine Sefton
Emerita Professor of Clinical Microbiology
Barts and the London School of Medicine and Dentistry
Queen Mary University of London
London, UK
1
3
Great Clarendon Street, Oxford, OX2 6DP,
United Kingdom
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The moral rights of the authors have been asserted
First Edition Published in 2019
Impression: 1
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Published in the United States of America by Oxford University Press
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ISBN 978–0–19–880174–0
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Oxford University Press makes no representation, express or implied, that the
drug dosages in this book are correct. Readers must therefore always check
the product information and clinical procedures with the most up-to-date
published product information and data sheets provided by the manufacturers
and the most recent codes of conduct and safety regulations. The authors and
the publishers do not accept responsibility or legal liability for any errors in the
text or for the misuse or misapplication of material in this work. Except where
otherwise stated, drug dosages and recommendations are for the non-pregnant
adult who is not breast-feeding
Links to third party websites are provided by Oxford in good faith and
for information only. Oxford disclaims any responsibility for the materials
contained in any third party website referenced in this work.
This book is dedicated to our colleague and friend Dr Cheuk Yan William Tong,
whose knowledge, humility and love for his work continues to inspire us all.
Acknowledgment
Thank you to Dr Maximillian Habibi and Dr Mark Hopkins, who reviewed Dr William Tong’s
chapters. We are grateful for your help.
Contents
Abbreviations xiii
Contributors xxi
PART 8 VACCINATION 3 8 3
48 Different Types of Vaccines 385
49 Vaccination Schedules 391
50 Vaccination of Specific Groups 397
51 Post-Exposure Prophylaxis 404
Index 467
Abbreviations
+ve positive
-ve negative
A&E Accident and emergency
ACDP Advisory Committee on Dangerous Pathogens
ACT Artemisinin combination therapy
ADEM Acute disseminated encephalomyelitis
AFB Acid fast bacilli
AHA American Heart Association
AMR Antimicrobial resistance
AMS Antimicrobial stewardship
ANTT Aseptic non-touch technique
APC Antigen-presenting cells
API Analytical profile index
ART Antiretroviral therapy
ASOT Antistreptolysin O Titer
AST Antimicrobial susceptibility test
ATLL Adult T cell leukaemia/lymphoma
ATP Adenosine triphosphate
ATS American Thoracic Society
BAL Broncho-alveolar lavage
BBV Blood-borne virus
BCG Bacillus Calmette-Guérin
BDG Beta-D-glucan
BNF British National Formulary
BP Blood pressure
BSAC British Association of Antimicrobial Chemotherapy
BSC Biological safety cabinet
BSE Bovine spongiform encephalopathy
BSI British Standards Institution
CA-MRSA Community-acquired MRSA
CAP Community-acquired pneumonia
cART Combination anti-retroviral therapy
cccDNA Covalent-closed-circular DNA
CCG Clinical Commissioning Groups
CCHF Crimean/Congo haemorrhagic fever
CDC Centers for Disease Control
CDI Clostridium difficile
xiv Abbreviations
Fatima Ahmad, Biomedical Scientist, Department of Infection, Barts Health NHS Trust,
London, UK
Sarfaraz Ameen, Anti-Microbial Pharmacist, Barts Health NHS Trust, London, UK
Gurtan Atamturk, Biomedical Scientist, Department of Infection, Barts Health NHS Trust,
London, UK
Zahir O. E. Babiker, Assistant Professor and Consultant in Infectious Diseases, College of
Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
Marina Basarab, Consultant, Department of Infection, Barts Health NHS Trust, London, UK
Ruaridh Buchanan, Specialist Registrar in Microbiology and Infectious Diseases, Barts Health
NHS Trust, London, UK
Duncan Clark, School of Life Sciences, University of Glasgow, Glasgow, UK
Martina N. Cummins, Clinical Director Infection Prevention and Control, Barts Health NHS
Trust, London, UK
Subathira Dakshina, Specialist Registrar in Genitourinary Medicine, Barts Health NHS Trust,
London, UK
Satya Das, Consultant, Barts Health NHS Trust, London, UK
Jayshree Dave, Consultant Microbiologist, HPA Specialist Microbiology Network (SMN), Public
Health England
Heather Dolphin, Chief Biomedical Scientist, Barts Health NHS Trust, London, UK
Rohma Ghani, Specialty Trainee, Infectious Diseases, Barts Health NHS Trust, London, UK
Jennifer Henderson, Biomedical Scientist, Department of Infection, Barts Health NHS Trust,
London, UK
Desmond Hsu, Specialist Registrar in Microbiology, Barts Health NHS Trust, London, UK
Mark Hopkins, Consultant Clinical Scientist, Department of Infection, Barts Health NHS Trust,
London, UK
George Jacob, Consultant in Medical Microbiology, Royal Berkshire NHS Foundation Trust,
Berkshire, UK
Angelina Jayakumar, Specialist Registrar in Infectious Diseases, Barts Health NHS Trust,
London, UK
Anna Jeffery-Smith, Infectious Diseases and Virology Registrar, Barts Health NHS Trust,
London, UK
Steve Kempley, Clinical Senior Lecturer in Paediatrics, Blizard Institute, Barts and The London,
School of Medicine and Dentistry, London, UK
Palwasha Khan, Clinical Epidemiologist, Department of Infectious Disease Epidemiology,
London School of Hygiene & Tropical Medicine, London, UK; Interactive Research and
Development, Karachi, Pakistan
xxii Contributors
B ASI C BIOLO GY
OF BACT ERIA,
V IRUS ES , FUN G I ,
A ND PARA S ITE S ;
HO ST-PATH OG EN
R E L AT IONS H I P S
CH A PTE R 1
CO NT ENTS
1.1 Organisms that cause infection 1.5 How bacteria multiply 6
in man 3 1.6 DNA exchange between bacteria 6
1.2 What determines pathogen, 1.7 What we need to know about each
pathogenicity, and virulence? 3 pathogen we study 6
1.3 The basic structure of bacteria 3 1.8 Assessment questions 7
1.4 Other basic ways of categorizing 1.9 Answers and discussion 7
bacteria 6
Bacterial infections and infestations of man can be caused by both microbes and non-microbes.
Microbes include bacteria, viruses, fungi, and protozoa. Non-microbes include worms, insects, and
arachnids. This chapter concentrates on the basic biology of bacteria.
A pathogen is an organism that is able to cause disease in its host and the pathogenicity of any
organism is its ability to produce disease. Microbes express their pathogenicity by means of their
virulence. The virulence of any pathogen is determined by any of its structural, biochemical, or
genetic features that enable it to cause disease in the host.
The relationship between a host and a potential pathogen is non-static; the likelihood of any
pathogen causing disease in its host depends both on the virulence of the pathogen and the degree
of resistance or susceptibility of the host, due mainly to the effectiveness of the host’s defence
mechanisms. Two of the main factors influencing a bacteria’s pathogenicity are its ability to invade
and it ability to produce toxins—either exotoxins or endotoxins.
Bacteria are unicellular prokaryotic micro-organisms, unlike human cells, which are eukaryotic.
Fungi, protozoa, helminths, and arthropods are also eukaryotic. Prokaryotic organisms contain
both DNA and RNA, but their genetic material exists unbound in the cytoplasm of the cell as,
unlike eukaryotic cells, they have no nuclear membrane. Sometimes bacteria contain additional
smaller circular DNA molecules, called plasmids.
The main features of a bacterium are the cell wall, cytoplasm, and cell membrane. However,
some bacteria have additional features such as spores, capsules, fimbriae (pili), and flagellae. The
4 Chapter 1 The Biology of Bacteria
construction of the cell wall is different in different bacteria, but all cell walls contain peptidoglycan.
The structure of the cell wall determines the staining characteristics when stained using the Gram
stain. Although its first use was over a hundred and fifty years ago, is still the standard method for
primary classification of bacteria. Occasionally, bacteria do not have a cell wall.
Gram staining of a fixed smear of bacteria is used to separate bacteria into Gram positive or
Gram negative, and also to demonstrate their shape. Bacteria with a thick peptidoglycan layer
but with no outer membrane stain purple and are called Gram positive. Bacteria with a thinner
peptidoglycan layer but with an outer membrane stain pink and are called Gram negative. The cell
wall is rigid, and imposes shape on the bacterium.
Svedberg units, which is how a particle behaves under ultracentrifugation) and are composed
of two sub-units—a 30s sub-unit, which contains 16S sRNA, and a 50 S sub-unit. Eukaryotic
organisms are 80 S: they contain a 40 S sub-unit, which contains 18S RNA, and a 60 S
sub-unit;
● Granules: some bacteria have granules containing stored nutrients;
● Mesosome: an invagination of the cell membrane, involved in cell division;
● Other constituents: proteins, carbohydrates, messenger and transfer RNA, amino acids,
etc; and
● plasmids: these structures, which occasionally appear, are independently replicating fragments
of circular double-stranded DNA.
● Endospores: tough, spherical forms that resist extremes of temperature. Spore formation is
triggered by adverse environmental conditions. In this form they remain dormant, with the
ability to survive for many years.
● A capsule: it is outside the cell wall in gram-positive bacteria or outside the outer membrane
in gram-negative bacteria. The capsule is composed of carbohydrates and/or proteins
and helps hide the antigenic proteins, making the bacteria more resistant to host cell
phagocytosis.
● Flagella: whip-like structures that move, making the bacterium motile.
● Pili (fimbriae): long, thin, stiff structures that enable bacteria to adhere to the cells of the host
through specialized molecules called adhesins.
● Chlamydia spp.: small, difficult-to-see, gram-negative bacteria, which can only divide within host
cells. They have a ‘lifecycle’ with two forms: the elementary body and the reticulate body. Both
forms have a cell wall and an outer membrane. They are similar to viruses in that they have
to replicate in a host cell, but they encode all of their own materials, except ATP which they
cannot produce and obtain from the host.
● Rickettsia: only replicate within a host cell, but they lack the special structures and lifecycle of
chlamydia. They are just small, fastidious bacteria with a gram-negative structure.
● Mycoplasma spp.: have no cell wall, are very small, and of no definite shape. As they have no
cell wall, they are resistant to antibiotics such as the penicillins, cephalsosporins, carbapenems,
and glycopeptides that act at this site.
6 Chapter 1 The Biology of Bacteria
● Microscopy (see 1.3.1): shape and staining characteristics. Most bacteria are gram-positive
cocci or bacilli, or gram-negative cocci or bacilli, but some do not fit into either category.
● Growth characteristics, e.g., haemolysis, lactose fermentation, aerobic/anaerobic growth.
● Motility.
● Other tests include biochemical tests, antigen detection, toxin demonstration, or molecular
techniques. Tests commonly used in the laboratory include:
■ Catalase test: used for gram-positive organisms only. Gram-positive cocci are divided
into streptococci and staphylococci by catalase test. Staphylococci are catalase positive
whereas streptococci are catalase negative.
■ Coagulase test for gram-positive organism only. Staphylococci are divided into coagulase
The rate at which bacteria grow and divide depends mainly on their nutritional environment.
Bacteria divide by binary fission. The circular chromosome replicates by using a DNA-dependent
DNA polymerase, with the help of DNA gyrase and DNA topoisomerase to facilitate uncoiling.
When placed in a new environment, they undergo four sequential main phases.
1. Lag phase.
2. Exponential phase—with rapid growth and constant doubling rate.
3. Stationary phase—induced as nutrients are depleted and toxic products accumulate.
4. Death phase—cell growth declines and the cells die.
Information you should know on each pathogen you study includes its:
● Ecology;
● Epidemiology;
● Structure and function;
● Virulence mechanisms;
● Effects on man; and
● Diagnosis, therapy, and prevention.
1.9 Answers and discussion 7
1.8.1 Question 1
Bacterial cells are significantly different from human cells.
Which of the following is the most correct description of the differences between human and
bacterial cells?
A. Bacteria are multicellular eukaryotes with a nuclear membrane and differently sized ribosomes
to humans.
B. Bacteria are multicellular prokaryotic micro-organisms with no nuclear membrane and
similarly sized ribosomes to humans.
C. Bacteria are unicellular eukaryotic organisms with a nuclear membrane and similarly sized
ribosomes to humans.
D. Bacteria are unicellular prokaryotic micro-organisms with a nuclear membrane and differently
sized ribosomes to humans.
E. Bacteria are unicellular prokaryotic micro-organisms with no nuclear membrane and
differently sized ribosomes to humans.
1.8.2 Question 2
Staphylococcus aureus is a common cause of wound infection. The Gram film, catalase, and coagulase
tests are commonly used to help identify infections caused by this organism in the laboratory.
Which of the following is the most accurate description of the properties of Staphylococcus
aureus?
A. Gram-negative coccus, which is catalase negative, coagulase negative.
B. Gram-negative coccus, which is catalase negative, coagulase positive.
C. Gram-positive coccus, which is catalase negative, coagulase negative.
D. Gram-positive coccus, which is catalase positive, coagulase negative.
E. Gram-positive coccus, which is catalase positive, coagulase positive.
1.8.3 Question 3
Some, but not all, bacteria possess a capsule, which is generally regarded as a virulence factor.
Which of the following best describes the main pathogenic function(s) of a bacterium’s capsule?
A. Induction of antibodies.
B. Mediation of detachment from host cell surface.
C. Prevention of bacteriophage-induced cell lysis.
D. Prevention of desiccation of bacterium.
E. Prevention of phagocytosis and complement-mediated cell lysis.
1.9.1 Answer 1
E. Bacteria are unicellular prokaryotic micro-organisms with no nuclear membrane and
differently sized ribosomes to humans.
Bacteria are unicellular prokaryotic organisms with no nuclear membrane, unlike fungi, helminths,
arthropods, protozoa, and human cells, all of which are eukaryotic. Bacteria also have smaller sized
ribosomes (70 S) compared to eukaryotic organisms, which have 80 S ribosomes. In the diagnostic
laboratory for important specimens, when an infective aetiology is thought likely but standard
culture has been negative, the samples can be sent for sequencing of the 16 S gene (for bacteria) or
18 S for fungi to try and determine the infective cause. Additionally, the prokaryotic organisms have
8 Chapter 1 The Biology of Bacteria
a cell wall, which the eukaryotic cells do not. These differences are important when trying to find
an antimicrobial agent with good selective toxicity (selective toxicity means that the antimicrobial
should be highly effective against the microbe, but have minimal or no toxicity to humans). The
selective toxicity of antimicrobials is brought about by finding vulnerable targets for the drug in the
microbe that either do not exist in humans or are dissimilar, e.g., differently sized ribosomes. As a
general rule it is easier to do this for agents effective against the prokaryotic bacteria than against
the eukaryotic fungi, helminths, arthropods, and protozoa.
1.9.2 Answer 2
E. Gram-positive coccus, which is catalase positive, coagulase positive.
The two most common types of aerobic/ facultatively anaerobic gram- positive cocci are
streptococci and staphylococci, and both can cause cellulitis and wound infections. Staphylococci
can be differentiated from streptococci by a simple catalase test. In this test staphylococci are
catalase positive whereas streptococci are catalase negative. Streptococci will then be further
identified by whether or not they cause beta, alpha, or no haemolysis on blood agar plates. The
beta-haemolytic streptococci, Groups A–G, especially Group A beta-haemolytic streptococci, are
the most likely streptococci to cause cellulitis and wound infections. Streptococcus pneumoniae is
the most well-known alpha-haemolytic streptococci and is a common cause of both community-
acquired pneumonia and bacterial meningitis.
Staphylococci are identified further by a rapid test called the coagulase test; S. aureus are coagulase
positive, whereas other staphylococci are coagulase negative. Both S. aureus and coagulase-negative
staphylococci may be present on a person’s skin. However, whereas S. aureus is a common cause
of skin and soft tissue infections and can also cause severe bacterial endocarditis, osteomyelitis,
sepsis, and pneumonia, coagulase-negative staphylococci generally only cause infection if people
have prosthetic material in situ.
1.9.3 Answer 3
E. Prevention of phagocytosis and complement-mediated cell lysis.
For bacteria to cause disease in a host they need to escape phagocytosis by macrophages or
polymorphonuclear phagocytes, and having a capsule is a common way they do this. If a capsule is
removed from a normally capsulated bacterium it becomes much less pathogenic. The capsule has
many pathogenic functions. It helps the bacteria to adhere to the host surface prior to invasion,
The capsule prevents opsonization and prevents phagocytes adhering to and then engulfing the
bacteria. It also deters neutrophil killing of engulfed bacteria. Additionally, the capsule helps shield
the bacterium from desiccation and helps protect anaerobes from oxygen toxicity.
Induction of antibodies by the capsule is not one of it pathogenic functions. However, it is
important in medicine because it is the basic of the serological diagnosis of infections caused by
some capsulated bacterium. It is also the basis for vaccine production against some infections, e.g.,
the polyvalent (twenty-three serotypes) polysaccharide vaccine of the Streptococcus pneumoniae
capsule.
CH A PTE R 2
CO NT ENTS
2.1 What is a virus? 9 2.7 The importance of the cellular
2.2 Why mycoplasma and chlamydia are receptor 14
not viruses 9 2.8 The effects of selection pressure on a
2.3 The structure of a typical virus 11 virus 14
2.4 Virus classification 11 2.9 Outcomes for a cell infected with a
virus 15
2.5 The Baltimore classification system and
its use 12 2.10 Assessment questions 16
2.6 The life cycle of a virus 13 2.11 Answers and discussion 17
Viruses are considered as a bundle of genetic programmes encoded in nucleic acids and packaged
with a capsid +/-envelope protein, which can be activated on entry into a host cell (compare
this with computer viruses packaged in an enticing way in order to infect and take over control of
your PC).
Although they share some similarities in their properties, mycoplasma and chlamydia are true
bacteria (Table 2.1).
Table 2.1 Differences between mycoplasma/chlamydia and viruses
Genomic material–either
DNA or RNA
Non-structural proteins,
such as viral polymerase
The virion (assembled infectious particle) consists of viral nucleic acid and capsid (Figure 2.1).
The nucleic acid of a virus can either be ribonucleic acid (RNA) or deoxyribonucleic acid
(DNA), and the amount of genetic material varies widely, with some viruses able to encode a
few proteins and others having genetic material that encodes hundreds of proteins. In association
with the nucleic acid there may be non-structural viral proteins, such as a viral polymerase. The
nucleic acid and non-structural proteins are protected by a surrounding layer of capsid proteins.
The capsid includes proteins which can attach to host cell receptors. The proteins and the cell
receptors to which they bind determine a virus’ tropism, i.e., the ability to bind to and enter
different cell types. The term nucleocapsid refers to the nucleic acid core surrounded by capsid
protein.
Some viruses also have an envelope made up of phospholipids and proteins surrounding the
nucleocapsid. This envelope can be formed by the host cell membrane during the process of a
virus budding from a cell during replication. Protein spikes from the envelope can also attach to
cell receptors.
Viruses are grouped into families with similar properties based on morphology, chemical
composition, and mode of replication.
2.4.1 Morphology
The Baltimore classification system uses the nucleic acid composition and mechanism of replication
to separate viruses into seven groups (Figure 2.2).
Coding +mRNA is the central point as this is the template from which viral proteins are translated
by the host cell apparatus. The route to obtaining +mRNA is determined by the original nucleic acid
composition of the genome. Viruses within a group all behave in a similar way during the process
VII II
I
Partially + DNA
+/– DNA
+/– DNA
+ mRNA
III
+/– RNA
+/– DNA
VI – DNA
– RNA – RNA
+ RNA IV
V + RNA
of replication, and so understanding of the virus and research into targets for antiviral medications
can be based on this information. Grouping of viruses by disease phenotype or morphology does
not guarantee this due to the diversity of viruses and similarities of infectious presentations. Table
2.2 gives examples of the viruses in each Baltimore group.
The main stages in the life cycle of a virus can be separated into attachment, penetration, uncoating,
replication, assembly, and release (Figure 2.3).
1. Attachment: The virus attaches to the target cells occurs through specific binding between
proteins on the viral surface and receptors on the host cell surface. The specificity of the viral
surface protein determines the cell types to which the virus can bind, and therefore, which
hosts and tissues it can infect.
1
3
Endoplasmic
reticulum
Cytoplasm 4 Nucleus
The cellular receptor determines which cells a virus can enter—the tissue tropism of the virus
(Table 2.3). The proteins within the capsid or envelope of a virus determine to which host cell
receptors the virus can bind, and therefore, which cells it can enter and replicate. Some viruses
have widespread host tissue tropism, i.e., their receptors result in an ability to bind and enter
multiple cell types. Other viruses are very limited in which cells they can bind to and enter.
Cellular receptors are also important as a potential therapeutic target. If the binding between
viral surface proteins and cellular receptors can be blocked the virus will not be able to enter and
replicate within the cell.
Natural selection determines that individuals most suited phenotypically to the environment
are more likely to survive and reproduce. Phenotypic variation in viruses determined by genetic
variation means that some viruses will be better adapted to the changing host environment during
the course of infection, and more likely to survive to perpetuate infection and be transmitted to
others.
During the course of viral infection the environment of the host can change in multiple ways, e.g.,
through host immune system formation of antibodies in response to infection and development
of specific cytotoxic T cells targeting viral epitopes on infected cells. External factors like antiviral
medications will also apply selection pressure. Features favouring survival in the face of these
pressures arise from genetic mutations during viral replication that cause phenotypic differences
in viral progeny. Mutations occur naturally during virion production in the host cell, and are more
likely to occur in some viruses, e.g. HIV and hepatitis B, than others due to the nature of the
enzymes involved in replication. The majority of mutations arising through this route will be lost
due to reduced viral fitness, but some will become fixed in the population due to advantages such
as resistance to anti-viral medications. In the face of anti-viral selection pressure virus with the anti-
viral resistance mutation will become the dominant viral population.
The outcome of a cell infected with a virus depends on both the cell type and the virus. Infected cells
that support viral replication are called permissive. Cells that do not support the virus infection—
and so cannot be used to produce viral progeny—result in abortive infection.
Alterations to a cell following infection with a virus can be morphological, physiological, and
biochemical, and can include toxic effects on the genetic composition of the cell. Combined,
these effects can result in one of three outcomes for the cell—cell death, persistent infection,
or transformation of the cell. Within an infected individual the virus can demonstrate all of these
effects on host cells, e.g., Epstein-Barr Virus (EBV) can cause an acute infection with cytocidal
effects in some infected cells, resulting in the symptoms of glandular fever syndrome. In other
infected cells the virus can become latent, with the ability to reactivate in the future, and in some
cells, transformation can occur resulting in an EBV-related malignancy (Table 2.4).
2.9.3 Transformation
The cell develops the potential to become cancerous after viral infection. In such cases the virus
causes alterations to the cellular DNA such that the cell becomes immortal, usually by incorporation
of the viral genetic material into that of the cell. Following immortalization viral proteins acting
as transcription factors can inactivate tumour suppressor genes resulting in impaired cell cycle
regulation. During unregulated cellular replication, mutations in other cellular genes are likely to
develop, resulting in cumulative genetic changes and highly abnormal malignant cells with the ability
to invade tissues (Table 2.4).
2.10.1 Question 1
A patient known to have long-standing, well-controlled HIV on combination anti-retroviral therapy
(cART) with undetectable plasma viral load presents with new onset confusion. A contrast CT
scan of the head shows volume loss, but no focal lesions. Lumbar puncture is performed and the
following results are obtained:
What mechanism is the most likely to explain these discordant results between plasma and CSF?
A. Elite controller.
B. Failure of drug penetration to central nervous system (CNS).
C. Poor adherence to cART.
D. Progressive multifocal leucoencephalopathy (PML).
E. Switching co-receptor usage to CXCR4.
18 Chapter 2 The Biology of Viruses
that target reverse transcriptase encoded by the virus. Neither HIV nor HBV uses host
polymerase enzymes. RNA- dependent RNA polymerase enzymes are commonly carried
by RNA viruses; DNA-dependent DNA polymerase can be viral (in DNA virus) or host. DNA-
dependent RNA polymerases (transcriptase) are used by viruses and host to transcribe DNA
into RNA.
2.11 Answers and discussion 17
2.10.2 Question 2
A patient is immunosuppressed following chemotherapy for lung cancer. She subsequently presents
to hospital with a unilateral vesicular rash on her trunk, associated with burning pain. She is
diagnosed and commenced on anti-viral medication.
In which cell type does the causative virus lie dormant?
A. Astrocytes.
B. B lymphocytes.
C. Dorsal root ganglion cells.
D. Hepatocytes.
E. Purkinje cells.
2.10.3 Question 3
A patient who is co-infected with HIV and hepatitis B virus is started on a regimen that contains
tenofovir and emtricitabine (Truvada).
What is the target of this drug combination?
A. Cellular RNA polymerase II.
B. DNA-dependent DNA polymerase.
C. DNA-dependent RNA polymerase.
D. RNA-dependent DNA polymerase.
E. RNA-dependent RNA polymerase.
2.11.1 Answer 1
B. Failure of drug penetration to CNS.
Certain anatomical sites in the body, such as the CNS and the genital tract, are identified as
sanctuary sites whereby the selection pressure on the virus could be different from other parts of
the body. This could result in compartmentalization with a different rate of virus replication and
development of drug resistance. One of the mechanisms that leads to compartmentalization is
the restriction of penetration of certain antiretroviral agents into CNS. This patient probably has
good adherence to cART as the plasma viral load is undetectable. Nevertheless, the antiviral agents
for this patient need to be reviewed. CNS HIV are often R5 in tropism but a tropism test will be
required if CCR5 entry inhibitors are to be used for intensification.
2.11.2 Answer 2
C. Dorsal root ganglion cells.
Varicella-zoster virus as the causative agent of shingles lies dormant in the dorsal root ganglia.
Immunosuppression, as in the case of this patient, can result in the virus reactivating and the
patient developing shingles. The vesicular rash typically arises in a dermatomal distribution,
reflecting the sensory nerve root from which the virus has reactivated. In those who are heavily
immunosuppressed, reactivation of varicella can become widely disseminated. In addition, viral
shedding from lesions will persist for far longer periods than from immune-competent individuals
with the concomitant infection control concerns.
2.11.3 Answer 3
D. RNA-dependent DNA polymerase.
RNA- dependent DNA polymerase is reverse transcriptase, which is used in the replication
cycle of both HIV and hepatitis B virus. Tenofovir and emtricitabine are nucleos(t)ide analogues
CH A PTE R 3
CO NT ENTS
3.1 Fungi and how they are classified 19 3.4 The structures of a spore and why
3.2 The fungal structure and its notable they are important for the survival of
organelles 19 fungi 22
3.3 The key elements of the fungal 3.5 Assessment questions 23
reproductive cycle 21 3.6 Answers and discussion 24
Fungi are found ubiquitously in the environment such as soil, water, and food. There are an estimated
1.5 million fungal species worldwide, although this number is felt to be grossly underestimated and
is regularly updated. Of these vast numbers, around 500 fungi to date have been implicated in
human disease.
As opposed to bacteria, which are prokaryotes, fungi are eukaryotes, meaning they have a well-
defined nucleus and have membrane-bound organelles in the cytoplasm, including an endoplasmic
reticulum and a golgi apparatus.
In 1969, the scientist R. H. Whittaker first proposed that organisms be classified into five
kingdoms: Monera (Bacteria), Protista (Algae and Protozoans), Plantae (Plants), Mycetae (Fungi),
and Animalia (Animals). Since then, there have been dramatic changes to the classifications of fungi,
largely due to the appliance of phylogenetic molecular techniques. This has resulted in variances to
the number of phylums, and the species assigned to them.
Table 3.1 shows the seven phyla of the Fungi Kingdom.
The majority of fungi pathogenic to humans inhabit the Ascomycota and Basidiomycota phyla.
Fungi used to be dually named if they had a pleomorphic life cycle with sexual/asexual stages
(teleomorph/anamorph, respectively), which meant that fungi often had two names and were classed
differently. This practice was discontinued in January 2013 after the International Commission on
the Taxonomy of Fungi decided that a ‘one fungus, one name’ approach should be followed.
Fungi can be unicellular (yeast) or multicellular (fungi). Yeasts may look globose in nature when
grown, whereas multicellular fungi grow as tubular, filamentous material called hyphae that can
create a branching, hyphal network called a mycelium. Hyphae may have septa that cross their
walls or be nonseptate, which is a method of differentiating fungi. An early hyphal outgrowth from
a spore is called a germ tube. The germ tube test can be used to differentiate the yeasts Candida
albicans and Candida dubliniensis from other Candida species.
20 Chapter 3 The Biology of Fungi
The fungal cell wall is composed of chitin and glucans, which are different components to the
human cell wall. This means that they can be an effective target for antifungal therapy.
Some fungi grow solely as yeasts, which undergo asexual reproduction by budding (budding
yeasts) or binary fission (fission yeasts). An example is Saccharomyces cerevisiae, a budding yeast.
Some types of fungi are able to exist in both yeast and mould forms (depending on environmental
temperature and conditions), and these are called dimorphic fungi. Examples include Histoplasma
and Coccidioides species.
Candida albicans is a polymorphic fungus that can grow either as an ovoid-shaped budding yeast,
as elongated ellipsoid cells with constrictions at the septa (pseudohyphae), or as parallel-walled
true hyphae.
Spores can be produced by fungi, and vary in size and structure.
Some fungal structures are characteristic of a particular species. For example, Aspergillus and
Penicillium species have multiple-branched hyphae with flask-shaped phialides and conidial spores at
the end, which are released to disseminate in the environment (Figure 3.1)
Fungi can be described as being heterotrophic, meaning that they use organic carbon for growth.
They can be further divided into photoheterotrophs and chemoheterotrophs.
Fungi generate energy from a variety of methods (Table 3.2).
Conidium
Phialides
Vesicle Conidiophore
s Stem
Smaller compounds, like amino acids, can be absorbed via the cell wall. Larger proteins must be
broken down first by extracellular enzymes to allow for absorption.
Reproduction in fungi can either be asexual or sexual, the latter being a more complicated process
(Figure 3.2 and 3.3).
Spores
Germination Mitosis
Asexual
Reproduction
Mycelium (1n)
Plasmogamy:
Haploid cells from Germination:
two different mycelia A multi-cellular
fuse to form a mycelium is formed.
heterokaryotic cell
with two or more
nuclei. Sexual
Reproduction Spores
Heterokaryotic
stage
Karyogamy: Meiosis:
The nuclei fuse to Haploid (1n) spores
form a diploid (2n) Zygote are formed.
zygote,
Spores are specialized structures of a fungus that function as an effective dispersal method to allow
for spread of a species, further reproduction, and provide dormancy in unfavourable environmental
conditions for a prolonged period of time. After they are produced they can be easily dispersed
in the environment, permitting transportation to areas that may potentially be more nutritionally
beneficial to the spore.
Fungal spores can be produced via asexual or sexual reproduction—(see Section 3.3).
Spores may be unicellular or multicellular. They are composed of an outer exosporium
surrounding an inner core. The cell wall is very resistant to any adverse conditions, including
extreme cold, heat, desiccation, and pH changes. The inner core contains a nutrient source of
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