Medical microbiology made memorable

113 Pages·1999·3.403 MB·English

by  Steven Myint, et al

Medical
Microbiology
made memorable
Steven H. M y i n t
MD MRCP DipClinMicro
Professor of Clinical Microbiology, University of Leicester Medical School, Leicester, UK
Simon Kilvington
PhD
Clinical Scientist, Public Health Laboratory, Leicester, UK
Anthony Maggs
MBPhDMRCPath
Clinical Lecturer, University of Leicester Medical School, Leicester, UK
R∎ Andrew Swa n n
MA BM BCh FRCPath
Consultant Microbiologist, Leicester Royal Infirmary, Leicester, UK
Contents
Principles of infectious disease
31. Infections of the immunocompromised
host 74
1. Introduction to micro-organisms 2
32. Zoonoses 76
2. Viruses - the basic facts 4
3. Bacteria - the basic facts 6 Case study 4 78
4. Fungi - the basic facts 8 33. Malaria 80
5. Protozoa -the basic facts 10 Case study 5 82
6. Helminths - the basic facts 12 34. Other tropical infections 84
7. Viroids, prions and virinos 14 35. Pyrexia of unknown origin 88
Short answer questions I 36. New and re-emerging infectious diseases 90
Basic microbiology 16
8. Epidemiology of infectious diseases 18 Control of infectious disease
9. Pathogenesis of infectious disease 20 37. Principles of hospital infection control 94
10. Pathology of infectious disease 22
Case study 6 96
11. Innate host defences to infectious disease 24
38. Sterilisation and disinfection 98
12. Adaptive host response to infectious
39. Food, water and public health
disease 26
microbiology 100
Short answer questions 2
40. Antibacterials - the principles 102
Immunity to infection 28
41. Antibacterial therapy - the practice 104
13. Diagnosis of infectious disease 30
Case study 7 106
Diseases caused by micro-organisms
42. Antiviral therapy 108
14. Upper respiratory tract infections 34 43. Antifungal therapy 110
15. Lower respiratory tract infections 36 44. Antiprotozoal and antihelminthic
16. Meningitis 38 therapy 112
Case study 1 40 45. Non-drug control of infection 114
17. Encephalitis and other nervous system 46. Genetically modified micro-organisms
infections 42 (GMOS) in the environment and
biotechnology 115
18. Eye infections 44
47. Immunisation to infectious disease 116
19. Viral skin rashes 46
20. Cutaneous infections - bacterial and
Appendices
fungal 48
21. Gastrointestinal infections 50 Appendix 1 Answers 120
22. Hepatitis and pancreatitis 52 Appendix2 The language of microbiology 122
23. Infections of the heart 54 Appendix3 Commonly used abbreviations 126
24. Urinary tract infections 56 Appendix4 Notifiable diseases (UK) 128
25. Genital tract infections 58 Appendix5 Common helminth infections of
humans 129
Case study 2 60
Appendix 6 Newly emerging pathogens and
26. Obstetric and neonatal infections 62
diseases 130
27. Infections of bone, joints and muscle 64
Appendix7 Examples of common disinfectants
28. Septicaemia 66 and antiseptics 131
Case study 3 68 Appendix 8 Vaccines available in the UK 130
29. Acquired immunodeficiency syndrome
(AIDS) 70 Further reading 133
30. Infectious mononucleosis and other systemic
infections 72 Index 135
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M E D I C A L
MICROBIOLOGY
I ntroduction to micro-organisms
Micro-organisms are mostly harmless, and because some of them are capable
non-pathogenic, and indeed may be beneficial. of causing disease.
It is estimated that a human body has about • Eukarya, with their larger, more diverse
10" cells, but only 10% of these are human in and complicated cells (Fig. 1.2), include
origin; the rest is almost entirely microbial flora. fungi (yeasts and moulds) and parasites
Medical microbiology is the study of microscopic (single-celled protozoa and helminths).
organisms and their effect on man. It encompasses • Viruses, viroids and prions are not truly
their biology, diagnosis, treatment and prevention. 'living' agents, but are transmissible and
able to replicate.
There is a vast array of agents that are capable of
causing human disease (Table 1.1). A 'family tree' If we are to reduce morbidity and mortality
of all living organisms is shown opposite (Fig. 1.1). from infection, a number of issues must be
This tree, with its three main branches, is very considered. The environment must be managed
different from that suggested twenty years ago through public health measures to reduce the
and has come about because of advances in chances of contact with virulent micro-organisms.
molecular biology. The eukaryotic domain is a In hospitals, this process is called 'infection control'
single group containing an almost unbelievable and it includes steps to ensure that patients with
amount of diversity, from single-celled amoebae hazardous agents do not disseminate them to
through worms, fungi and plants right up to others. Innate and specific immunity are clearly
complex animals such as humans. important in determining the outcome of contact
with pathogenic organisms; we must understand
The prokaryotes are divided up into two
how immunity works, what happens when it is
fundamentally separate domains: the Archaea
disturbed through modern medical treatments
and Bacteria. But just because many bacteria look
and how it might be increased by methods such
the same under the microscope, it doesn't follow
as immunisation. Disease must be diagnosed
that they will behave similarly - indeed there
quickly and accurately, either clinically or
is as much difference between the genes of the
through laboratory methods, before it has spread
bacteria Treponema pallidum and Staphylococcus
to others or the individual is too ill to be saved.
aureus as there is between those of human beings
We must develop and apply high-quality,
and sweet corn!
evidence-based treatments which include the
• The Archaea are a group of prokaryotes that prompt and appropriate use of drugs; the ideal
live in extreme conditions such as thermal antibiotic will kill the infecting micro-organism
pools. Whilst they may be very important to but not the commensal bacterial flora or the
the health of natural environments, they are patient, and yet will not lead to antibiotic
not known to cause human infection. resistance amongst virulent bacteria over time.
• The Bacteria, however, are very significant Infections are extremely common, and it is vital
when it comes to human health, both because that all medical doctors thoroughly understand
some of them must live on us or in us if we basic microbiology if they are to prevent,
are to remain healthy (our commensalflora) diagnose and treat infections effectively.
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Basic features of infectious agents
Prokaryotes Eukaryotes
Prions Viruses/viroids Bacteria Protozoa Fungi Helminths
Living? No No Yes Yes Yes Yes
Self-replication Yes/No No Yes Yes Yes Yes
Size Atomic microscope Electron microscope Microscope Microscope Microscope/naked eye Microscope/naked eye
Nucleus No No No Yes Yes Yes
Nucleic acid No (only protein) DNA or RNA DNA & RNA DNA & RNA DNA & RNA DNA & RNA
Cell structure No cell No cell Bacterial Eukaryotic Eukaryotic Eukaryotic
Cell wall Yes (peptidoglycan) No Yes (chitin) No
Multicellular No No Variable Yes
Ribosomes 70S 80S 80S 80S
Internal organelles - No Yes Yes Yes
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M E D I C A L
MICROBIOLOGY
Viruses - the basic facts
Termed after the Latin for 'poison', viruses are Classification of viruses
the smallest and simplest of the agents of
infection in man, with the possible exception of Viruses are currently classified into different
prions (Fig. 2.1). They are both the commonest taxonomic groups on the basis of:
organisms found in the environment and the most
• the nature of the host (animal, plant,
frequent cause of human infection. The following
bacterial, insect or fungal)
properties distinguish them from living
• whether they possess an envelope
(prokaryotic and eukaryotic) cells:
• the type of nucleic acid they possess
• They are acellular and have a simple • the morphology of their capsid
organisation. • the diameter of the virion or nucleocapsid
• They possess eitherDNA or RNA in the • their immunological properties
same structure. • the intracellular location of viral replication
• They cannot replicate independently of • their clinical features, i.e. disease(s) caused
host cells. and method of transmission.
They can exist extracellularly as virions with The first three of these are the most commonly
few, if any, enzymes and intracellularly when used. In addition, there is a commonly used term
they 'hijack' the host biochemical machinery to 'arbovirus' which encompasses a range of virus
produce copies of virion components. families which are all arthropod-borne. The term
'phage' is used to denote viruses which parasitise
Virus structure and morphology bacteria, i.e. bacteriophage.
Virions are 15-400 nm in diameter and exhibit The range of viruses that infect humans is shown
one of five basic morphologies (Fig. 2.2). They in Table 2.1.
basically consist of a shell, called a capsid which
may be icosahedral or helical in shape. Capsids Viral replication
may be surrounded by an outer membrane,
called the envelope. There is a fifth structure All viruses make copies of themselves in the
type, termed complex, with a capsid structure intracellular phase. The major difference between
which is neither helical nor icosahedral; complex viruses is their strategy for genome replication.
viruses may also possess an envelope. The capsid All viruses have to generate messenger RNA to
is an arrangement of protein subunits, termed produce protein and nucleic acid copies. The
protomers or capsomeres. Enclosed within the route by which they do this forms the Baltimore
capsid is the genetic material, which is either system of classification (Fig. 2.3).
RNA or DNA, and may be single stranded or
The end-result of viral infection may be lysis
double stranded. If single-stranded RNA, this
of the cell, lysogeny where the host cell is not
may be capable of acting as messenger RNA,
destroyed but continues to support viral
so-called positive-sense, or will have to be made replication, or latency where there is little,
into a complementary copy to do so, termed
or no, viral replication. In the latter states the
negative-sense. Some genomes are also
viral genome may be integrated into that of
segmented, such as rotaviruses.
the host.
Viral replication is not perfect, and mutant
genomes are also made: this is the means by
Major virus families that infect humans
which viruses evolve. Non-replicative mutants
Family Nucleic acid Envelope Capsid Example are termed defective-interfering (DI) particles,
Adenoviridae dsDNA No Cubic Adenovirus which interfere with the replication of the
Arenaviridae ssRNA Yes Complex Lassa initial virus.
Bunyaviridae ssRNA Yes Helical Hantaan
Caliciviridae ssRNA No Cubic Norwalk virus
Coronaviridae ssRNA Yes Helical 229E The protean manifestations
Filoviridae ssRNA Yes Helical Marburg of virus infection
Flaviviridae ssRNA Yes Cubic Hepatitis C
Hepadnaviridae dsDNA No Cubic Hepatitis B Viruses produce acute, persistent or chronic and
Herpesviridae dsDNA Yes Cubic Epstein-Barr virus
Orthomyxoviridae ssRNA Yes Helical Influenza A virus latent infections. In latent infections the virus is
Papovaviridae dsDNA No Cubic Papillomavirus dormant for long periods and may not produce
Paramyxoviridae ssRNA Yes Helical Respiratory syncytial virus detectable virions. Apart from the classic
Parvoviridae ssDNA No Cubic B19
Picomaviridae ssRNA No Cubic Rhinovirus diseases, viruses are increasingly recognised
Poxviridae dsDNA Yes Complex Molluscum contagiosum as causes of cancer (e.g. hepatoma) and
Reoviridae dsRNA No Cubic Rotavirus autoimmune disorders. It should also be noted
Retroviridae ssRNA Yes Complex Human immunodeficiency
that there are many 'orphan' viruses, such as
virus
Rhabdoviridae ssRNA Yes Helical Rabies adeno-associated viruses and hepatitis G virus,
Togaviridae ssRNA Yes Cubic Rubella for which a disease has yet to be established.
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FIG 2.3 Baltimore system of classification of viruses
FIG 2.2 Basic virus morphologies (In addition there is a complex morphology that
does not follow a regular structure)
• (in addition there is a complex morphology that does not follow a regular structure)
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M E D I C A L
MICR0131OLOGY
Bacteria - the basic facts
Bacteria are divided into two main groups flagellae which, when rotated, lead to the
by chemical staining and light microscopy: movement of the bacterial cell.
Gram-positive and Gram-negative. The Gram • Fimbriae (also called pili) are hair-like
stain, established in the 19th century, involves structures typically 6 nm thick, I tm long.
fixing of the bacterium with heat or alcohol and There may be up to 1000 per cell, and they are
staining with crystal violet, and then iodine. composed of proteins (adhesins) that enable
If the bacterium is Gram-positive, this blue the specific attachment of the bacterium to
stain is then resistant to decolorisation with its target.
alcohol or acetone. Gram-negative bacteria are • Sex pili are straighter, thicker and longer than
decolorised and then counter-stained with a red fimbriae. A pilus can extend from one cell to
dye, safranin or carbol-fuchsin. The differential another 'receptive' bacterium and allows the
staining is based on a major difference in the transfer ofplasmid DNA.
cell wall (Fig. 3.1). Both have a lipid bilayer
Most bacteria that commonly affect human health
cytoplasmic membrane with various inserted
are described inTable 3.1, although there are a
proteins, the most important of which are
few that do not take up the Gram stain:
membrane-spanningpermeases that control
active transport of nutrients and waste products • Mycobacterium species, have a thick waxy
into and out of the cell. A complex web of coat which can be detected by the
cross-linked peptidoglycan outside the Ziehl-Neelsen stain
cytoplasmic membrane provides the cell with • Chlamydia, Rickettsia and Mycoplasma species,
mechanical strength. It is particularly abundant which do not have conventional cell walls;
in Gram-positives, when it also contains strands specialised techniques are used for their
of teichoic and lipoteichoic acid. Gram-negatives visualisation and culture
have an additional outer membrane enclosing a • the spirochaetes (Borrelia, Leptospiraand
thin layer of peptidoglycan and enzymes within Treponema).
the periplasm, an environment controlled by
the movement of substrates through membrane Bacteria may be small, but what they do, they do
porins. Some bacterial species may have a well. Most that cause disease grow at human
loosely-adherent polysaccharide capsule exterior body temperature (37°C). The majority grow in
to the cell wall and possibly additional structures air (aerobes) but can grow without it (facultative
which project from the cell surface: anaerobes); a few can only grow in the absence
of oxygen (true anaerobes). Bacteria multiply
• Flagellae are whip-like cords, typically 0.02 pm by binary fission, each cell dividing into two
thick, 10 ttm in length. A cell may have 1-20 'daughter' cells, and, with division times as short
as 20 minutes, their growth can be explosive
(Table 3.2). Although mutations can occur in
chromosomal DNA, their rapid adaptability is
due to the ability to exchange DNA:
Gram stain reactions of common bacteria
Gram-positive Gram-negative • Some bacteria take up DNA from solution
outside the cell and incorporate it into their
Cocci (=round) chromosomes (transformation).
Staphylococcus (clusters) Neisseria (pairs)
• Many cells contain small circular pieces of
Streptococcus (chains/pairs) Moraxella
Enterococcus(chains) DNA, called plasmids, in addition to their
chromosome. Plasmids may contain genes
Bacilli (=rod-like)
for virulence factors and antibiotic resistance,
Listeria Enterobacteriaceae
Bacillus • Escherichia and they can move from one bacterial cell to
Corynebacterium • Klebsiella another (conjugation).
• Salmonella • Bacterial cells can be infected by specialised
• Shigella
viruses, called bacteriophagesor phages,
• Proteus
which move between cells, sometimes
Pseudomonas
carrying genes for virulence factors
Haemophilus
(transduction).
Bordetella
Legionella
The great majority of bacteria do not cause
Campylobacter disease and live quite happily, and often to our
Helicobacter
benefit, on us or in us as commensals (Fig. 3.2).
Vibrio However, under some conditions, these, or more
virulent micro-organisms, cause infections which
Clostridium (anaerobic) Bacteroides (anerobic)
may be life-threatening.
FIG 3.1 The bacterial cell wall
Time (h) No. of bacteria
0 1
1 8
2 64
3 512
4 4096
5 32768
6 262 144
7 2097 152
8 16777 216
9 134217 728
10 1 073741 824
11 8 589934 592
12 68 719476 736
FIG 3.2 Normal flora of the human body
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M E D I C A L
MICROBIOLOGY
Fungi the basic facts
Fungi are eukaryotic organisms that comprise characteristic red inflammation with central
yeasts, moulds (filamentous fungi) and higher clearing that forms at the site of infection.
fungi (mushrooms and toadstools). They are Dermatophyte infection affects various sites:
widely distributed in the environment and can e.g. scalp (tinea capitis), foot (tinea pedis:
survive in extreme conditions where nutrients are 'athletes foot') and groin (tinea cruris).
limited. Most fungi are saprophytes (living off Although becoming less common, tinea pedis
dead organic matter) in soil and water and are is still the most common fungal infection in the
vital to the carbon cycle. Certain fungi are also United Kingdom.
of great commercial value in the production of
Yeast infections are most commonly caused by
bread, alcohol and antibiotics.
Candida albicans and are confined to the vagina,
Yeasts are the simplest of the fungi. They are mouth and soft skin (candidiasis or 'thrush').
unicellular, spherical in shape and reproduce by Acommensal of the vagina and gastrointestinal
budding (Fig. 4.1). In some yeasts, including the tract, the organism can flourish if ill health,
medically important genus Candida, the buds impaired immunity or antibiotic treatment alter
elongate to form filaments (pseudohyphae). the normal bacterial flora.
Moulds are composed of numerous microscopic Subcutaneous mycoses These are infections
branching, filamentous hyphae, known caused by a number of different fungi that arise
collectively as mycelia, that are involved in gaining from injury to the skin. They usually involve
nutrients and reproduction. The reproductive the dermis, subcutaneous tissues and muscle.
mycelia produce spores, termed conidia, either The fungi commonly live saprophytically on
by asexual or sexual reproduction from opposite thorn bushes, roses and tree bark, from which
mating strains. Spores are disseminated in the wounds can occur. Certain occupational groups
atmosphere, enabling fungi to colonise new (e.g. florists and agricultural workers) are more
environments. at risk from infection. Such mycoses are difficult
to treat and may require surgical intervention.
Certain pathogenic fungi are dimorphic, being a
yeast form when invading tissues but a mould Systemic (deep) mycoses These are
when living in the environment. The exception life-threatening invasive infections caused by
is Candida, which forms pseudohyphae when in a variety of fungi.
the body.
Theprimary pathogenic fungi infect previously
healthy persons and are caused by dimorphic
Diseases caused by fungi fungi normally found in soil. Infection usually
arises from inhaling spores, and the lungs are the
The study of fungi is called mycology, and the
main site of infection. However, dissemination
diseases they cause, mycoses. Mycoses are
to other organs and the central nervous system
classified depending on the degree of tissue
can occur. The incidence is largely confined to
involvement and mode of entry into the host
endemic areas in North and South America.
(Table 4.1):
The opportunistic fungi infect persons who,
• superficial -localised to the epidermis,
usually, have some serious immune or metabolic
hair and nails but can extend deeper into
defect, are on broad-spectrum antibiotics or
keratinised tissue
immunosuppressive drugs, or have undergone
• subcutaneous - confined to the dermis,
major surgery.
subcutaneous tissue or adjacent structures
• systemic - deep infections of the internal
Other fungi-related diseases
organs caused by:
- primary pathogenic fungi that infect Certain fungi may indirectly cause human
previously healthy persons infections. Constant exposure to fungal spores in
- opportunistic fungi of marginal the atmosphere can induce respiratory allergies,
pathogenicity that infect the particularly among certain occupational groups
immunocompromised host. (e.g. Farmer's lung). Some mushrooms and
Superficial mycoses These are the most toadstools cause poisoning if ingested. Certain
common mycoses of humans and are acquired moulds produce toxic secondary metabolites
from the environment, infected humans or (mycotoxins) that can contaminate food.
natural animal hosts.
Diagnosis and treatment
Pityriasis versicolor is an infection of the
superficial skin and hair which is prevalent in the The diagnosis and treatment of common mycoses
tropics. Fungi that invade deeper into keratinised and related diseases is by microscopy and culture
cells are termed dermatophytes. These diseases of lesions or serology. Antifungal agents are
are often called tinea or ringworm because of the discussed elsewhere.
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Common human mycoses
Mycosis Fungi Type Main infection Epidemiology
Superficial: epidermis, hair Candida albicans Dimorphic Oral thrush; vaginitis; cutaneous candidiasis World-wide
and nails but can extend
deeper into keratinised tissue Malassezia furfur Dimorphic Pityriasis versicolor: brown discoloration of World-wide,
the skin especially tropics
Dermatophytes: Trichophyton, Filamentous Tinea (ringworm): skin, hair, nails World-wide
Microsporum, Epidermophyton
Subcutaneous: arise from Sporothrix schenckii Dimorphic Sporotrichosis: ulcerative skin lesion World-wide; common
injury to skin and contamination progressing along the lymphatics in soil and vegetable
with organic matter matter
Systemic - primary Histoplasma capsulatum Dimorphic Histoplasmosis: lung lesions (similar to North and
pathogenic fungi:internal those seen in tuberculosis) spreading into South America
infections in previously reticuloendothelial system and other organs
healthy persons
Blastomyces dermatitrdis Dimorphic Blastomycosis: primarily in lung but can spread Eastern parts of USA,
to skin, bone, viscera and meninges Canada, Africa
Coccidioides immitis Dimorphic Coccidioidomycosis: lung lesions leading to South-western USA
generalised tuberculosis-like illness
Paracoccidioides brasiliensis Dimorphic Paracoccidioidomycosis: nasopharynx and lung, South America
with spread to lymphatics (especially Brazil)
Systemic - opportunistic Aspergillus fumigatus Filamentous Invasive aspergillosis, aspergilloma World-wide
fungi: disseminated infections (fungal mass in lungs)
in the immunocompromised host
Candida albicans Dimorphic Candidiasis World-wide
Cryptococcus neoformans Yeast Cryptococcosis: can also occur in World-wide
immunocompetent
Pneumocystis carinii Yeast-like' Pneumocystis pneumonia World-wide
Fungal related: allergic Allergic reactions
reaction; mycotoxin Aspergillus Allergic rhinitis, asthma World-wide
contamination; poisoning
by ingestion Alternaria
Cladosporium
Penicillium
Aspergillus fumigatus Allergic bronchopulmonary aspergillosis World-wide
Aspergillus clavatus Malt workers' lung (extrinsic allergic alveolitis), World-wide
an occupational disease
Various fungal spores Sick building syndrome: extrinsic allergic World-wide
alveolitis often via air conditioning units
Mycotoxins
e.g. Claviceps purpurea Ergotism ('madness'): from bread made with rye World-wide
infected with fungal mycotoxin but now rare
Poisoning
e.g.Amanita phalloides Nausea, vomiting, bronchospasm, bradycardia, World-wide
('Death cap' mushroom) hallucination, collapse
Pneumocystis cariniiis an intracellular organism, with a life cycle of trophozoite and cyst. Formerly considered to be a protozoan, DNA and RNA sequence
analysis have established that it is related to the yeasts.
FIG 4.1 (a) Mould, with branching hyphae, forming the mycelium, and fluffy colony;
(b) Yeast with budding cells, and smooth-surfaced colony
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