Mims Medical Microbiology and Immunology

Mims Medical Microbiology and Immunology 6th Edition......Page 1
Prelimins......Page 2
Title......Page 4
Copyright......Page 5
Foreword by Cedric Mims......Page 6
Preface to the sixth edition......Page 7
Acknowledgements......Page 8
A contemporary approachto microbiology......Page 9
Bacteria are prokaryotes; all other organisms are eukaryotes......Page 13
Living outside cells provides opportunities for growth, reproduction and dissemination......Page 14
Correct identification of bacteria below the species level is often vital to differentiate pathogenic and non-pathogenic forms......Page 15
Classification assists diagnosis and the understanding of pathogenicity......Page 16
Bacteria are ‘prokaryotes’ and have a characteristic cellular organization......Page 17
Pili are another form of bacterial surface projection......Page 18
All pathogenic bacteria are heterotrophic......Page 19
Growth and Division......Page 20
Cell division is preceded by genome segregation and septum formation......Page 21
Translation......Page 22
The principles of gene regulation in bacteria can be illustrated by the regulation of genes involved in sugar metabolism......Page 23
Some bacteria form endospores......Page 25
Widespread use of antimicrobials has applied a strong selection pressure in favour of bacteria able to resist them......Page 26
Bacteriophages are bacterial viruses that can survive outside as well as inside the bacterial cell......Page 27
Insertion sequences are the smallest and simplest ‘jumping genes’......Page 28
Other mobile elements also behave as portable cassettes of genetic information......Page 30
Gene transfer and recombination......Page 31
Transduction involves the transfer of genetic material by infection with a bacteriophage......Page 32
Conjugation is a type of bacterial ‘mating’ in which DNA is transferred from one bacterium to another......Page 33
DNA microarrays have been especially useful in the identification of mutations and studies on bacterial gene expression......Page 34
Sequence of the entire bacterial chromosome (whole genome sequencing; WGS) represents the most global approach to genomic analysis......Page 35
Major groups of bacteria......Page 36
The outer surface of the virus particle is the part that first makes contact with the membrane of the host cell......Page 38
Viruses show host specificity and usually infect only one or a restricted range of host species. The initial basis of specificity is the ability of the virus particle to attach to the host cell......Page 39
Viruses must also replicate their nucleic acid......Page 40
Replication of viral DNA occurs in the host nucleus – except for poxviruses, where it takes place in the cytoplasm......Page 41
Some viruses can ‘transform’ the host cell into a tumour or cancer cell......Page 42
Viral oncogenes have probably arisen from incorporation of host oncogenes into the viral genome during viral replication......Page 43
Fungal pathogens can be classified on the basis of their growth forms or the type of infection they cause......Page 46
Control of fungal infection......Page 47
Protozoa can infect all the major tissues and organs of the body......Page 49
Protozoa use a variety of routes to infect humans......Page 50
Transmission of helminths occurs in four distinct ways......Page 52
Adult tapeworms are acquired by eating undercooked or raw meat containing larval stages......Page 53
Certain nematodes are highly specific to humans; others are zoonoses......Page 54
Survival of helminths in their hosts......Page 55
Arthropod infestation carries the additional hazard of disease transmission......Page 56
Prions are host-derived molecules......Page 58
Development, Transmission and Diagnosis of Prion Diseases......Page 59
Prions can cross species boundaries......Page 60
Prion diseases are incurable......Page 61
The skin is an example of a complex microbiome due to multiple microenvironments......Page 63
In the gut the density of microorganisms increases from the stomach to the large intestine......Page 64
Studies of germ-free animals underscore the importance of the microbiota......Page 65
Commensalism, mutualism and parasitism are categories of symbiotic association......Page 66
Many different groups of organisms are parasitic and all animals are parasitized......Page 67
The Evolution of Parasitism......Page 68
The pathway of virus evolution is uncertain......Page 69
Pressure of infection has been a major influence in host evolution......Page 70
Social and behavioural changes can be as important as genetic changes in altering host–parasite relations......Page 71
A variety of biochemical and physical barriers operate at the body surfaces......Page 73
Phagocytosis......Page 74
Macrophages are widespread throughout the tissues......Page 75
How do phagocytes sense infection?......Page 77
Activation of the complement system......Page 78
C9 molecules form the ‘membrane attack complex’, which is involved in cell lysis......Page 81
Acute phase proteins......Page 82
Interferons are a family of broad-spectrum antiviral molecules......Page 83
Innate lymphoid cells (ILCs)......Page 86
Eosinophils act against large parasites......Page 87
The thymus is a highly specialized organ producing mature T cells......Page 89
Why do we need so many types of T cell?......Page 92
Antibody Structure and Function......Page 94
Antibodies come in different classes and subclasses, with different structures and functions......Page 96
Recirculation of T and B Cells......Page 97
Beneficial Inflammatory Reactions Can Also Be Enhanced by Antibodies......Page 99
Activation of T Cells Involves Antigen-Presenting Cells and Additional Co-Stimulatory Signals......Page 100
T cells need additional signals for activation......Page 101
Clonal Expansion......Page 103
Monoclonal antibody technology exploits clonal expansion and transformation to produce large quantities of monoclonal antibodies......Page 104
Cytokines Play an Important Part in These Cell–Cell Interactions......Page 105
Immunological Memory Enables a Second Infection With the Same Microbe to Be Dealt With More Effectively......Page 106
Armies Must Be Kept Under Control......Page 108
The speed with which host adaptive responses can be mobilized is crucial......Page 111
Adaptation by both host and parasite leads to a more stable balanced relationship......Page 114
More than 100 microbes commonly cause infection......Page 115
Conclusions about causation are now reached using enlightened common sense......Page 116
It is uncommon for a pathogen to cause exactly the same disease in all infected individuals......Page 117
Microorganisms gaining entry via the skin may cause a skin infection or infection elsewhere......Page 118
The conjunctiva......Page 119
Some microorganisms can survive the intestine’s defences of acid, mucus and enzymes......Page 120
Successful intestinal pathogens must counteract or resist mucus, acids, enzymes and bile.......Page 122
Urethral and bladder defences......Page 123
Mechanisms of oropharyngeal invasion......Page 124
Stability in the environment......Page 125
Respiratory infections spread rapidly when people are crowded together indoors......Page 126
Sexually transmitted infections (STIs)......Page 128
Shedding to the environment......Page 129
Vertical transmission takes place between parents and their offspring......Page 130
Passive carriage......Page 131
Other invertebrate vectors spread infection either passively or by acting as an intermediate host......Page 132
Many pathogens are transmitted directly to humans from vertebrate animals......Page 133
Domestic pets or pests?......Page 134
C-reactive protein is an antibacterial agent produced by liver cells in response to cytokines......Page 136
Macrophages can recognize bacteria as foreign using Toll-like receptors......Page 137
NKT cells and γ δ T cells......Page 138
Oxidative killing involves the use of ROIs......Page 139
Nitric oxide......Page 140
Interferons......Page 141
Antibody-Mediated Immunity......Page 143
Blocking and neutralizing effects of antibody......Page 144
Opsonization......Page 145
Further evidence for the protective effects of IFNγ......Page 146
Cytotoxic T lymphocytes kill by inducing ‘leaks’ in the target cell......Page 147
Nutrition may have more subtle effects on immunity to infection......Page 150
Introduction......Page 151
In systemic infections, there is a stepwise invasion of different tissues of the body......Page 152
The fate of microorganisms in the blood depends upon whether they are free or associated with circulating cells......Page 153
Rapid spread from one visceral organ to another can take place via the pleural or peritoneal cavity......Page 154
The pathogenicity of a microorganism is determined by the interplay of a variety of factors......Page 155
Virulence is often coded for by more than one microbial gene......Page 156
The brain can influence immune responses......Page 157
Many pathogens target the TLR signalling pathway......Page 159
Strategies to evade adaptive defences are more sophisticated than those for evading innate defences......Page 160
Concealment of Antigens......Page 161
Colonizing privileged sites keeps the pathogen out of reach of circulating lymphocytes......Page 162
Mimicry sounds like a useful strategy, but does not prevent the host from making an antimicrobial response......Page 163
Infection during early embryonic life......Page 164
Regulatory T cells......Page 165
Gene switching was first demonstrated in African trypanosomes......Page 166
Many virus infections cause a general temporary immunosuppression......Page 167
Certain pathogen toxins are immunomodulators......Page 168
Successful pathogens often interfere with signalling between immune cells, with cytotoxic T-cell recognition or with host apoptotic responses......Page 169
Persistent infections represent a failure of host defences......Page 170
It is useful to distinguish two stages in viral reactivation......Page 171
Pathogens are clever and often use a number of these evasion strategies......Page 173
Exotoxins are a common cause of serious tissue damage, especially in bacterial infection......Page 175
Toxins may damage or destroy cells and are then known as haemolysins......Page 178
Diarrhoea is an almost invariable result of intestinal infections......Page 179
Overactivity can damage host tissues......Page 180
The cytokine most closely linked to disease is TNF......Page 181
Complement is involved in several tissue-damaging reactions......Page 182
Allergic reactions are a feature of worm infections......Page 183
Antimyocardial antibody of group A β-haemolytic streptococcal infection is the classic autoantibody triggered by infection......Page 184
Occupational diseases associated with inhalation of fungi are the classic examples of immune complex deposition in the tissues......Page 185
Cell-mediated immune responses invariably cause some tissue destruction, which may be permanent......Page 186
The SARS coronavirus caused lung immunopathology and T-cell loss......Page 187
The hygiene hypothesis – are we too clean?......Page 188
Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukaemia / lymphoma......Page 189
Certain human papillomavirus infections are associated with cervical cancer......Page 190
Hepatitis B and hepatitis C viruses are major causes of hepatocellular carcinoma......Page 191
Bacteria associated with cancer......Page 192
Viral co-infections are being detected using more sensitive tests......Page 194
Cytomegalovirus can be transmitted by saliva, urine, blood, semen and cervical secretions......Page 197
Cytomegalovirus infection is often asymptomatic, but can reactivate and cause disease when cell-mediated immunity (CMI) defences are impaired......Page 198
Prevention of CMV infection......Page 199
The clinical features of EBV infection are immunologically mediated......Page 200
Epstein–Barr virus is closely associated with Burkitt’s lymphoma in African children......Page 201
Complications of Strep. pyogenes throat infection include quinsy, scarlet fever and rarely, rheumatic fever, rheumatic heart disease and glomerulonephritis......Page 202
Treatment and prevention......Page 204
Common causes of acute otitis media are viruses, Strep. pneumoniae and H. influenzae......Page 205
Changes in the oral flora produced by broad-spectrum antibiotics and impaired immunity predispose to thrush......Page 206
Actinomyces viscosus, Actinobacillus and Bacteroides spp. are commonly involved in periodontal disease......Page 207
Diphtheria is caused by toxin-producing strains of Corynebacterium diphtheriae and can cause life-threatening respiratory obstruction......Page 209
Diphtheria is prevented by immunization......Page 210
Whooping cough can be prevented by active immunization......Page 211
Infection is only one component of chronic bronchitis......Page 212
RSV RNA is detectable in throat swab specimens and ribavirin is indicated for severe disease......Page 213
A wide range of microorganisms can cause pneumonia......Page 214
A variety of bacteria causes primary atypical pneumonia......Page 218
The usual laboratory procedures on sputum specimens from patients with pneumonia are Gram stain and culture......Page 219
Pneumonia is treated with appropriate antimicrobial therapy......Page 220
There are four types of parainfluenza viruses with differing clinical effects......Page 221
Influenza viruses undergo genetic change as they spread through the host species......Page 222
Rarely, influenza causes CNS complications......Page 226
Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome Coronavirus Infections......Page 227
Pathogenesis may be viral as well as immune mediated......Page 228
Secondary bacterial pneumonia is a frequent complication of measles in developing countries......Page 229
Tuberculosis is one of the most serious infectious diseases of the resource-poor world......Page 230
TB illustrates the dual role of the immune response in infectious disease......Page 231
Tuberculosis is prevented by improved social conditions, immunization and chemoprophylaxis......Page 233
Treatment of lung abscess should include an antianaerobic drug and last 2–4 months......Page 234
Aspergillus can cause allergic bronchopulmonary aspergillosis, aspergilloma or disseminated aspergillosis......Page 235
A variety of protozoa localizes to the lung or involve the lung at some stage in their development......Page 236
Viral causes of UTI appear to be rare, although there are associations with haemorrhagic cystitis and other renal syndromes......Page 239
Pregnancy, prostatic hypertrophy, renal calculi, tumours and strictures are the main causes of obstruction to complete bladder emptying......Page 240
Acute lower UTIs cause dysuria, urgency and frequency......Page 241
Infection can be distinguished from contamination by quantitative culture methods......Page 242
Interpretation of the significance of bacterial culture results depends upon a variety of factors......Page 243
Initial treatment of complicated UTI (pyelonephritis) usually involves a systemic antibacterial agent......Page 244
Many of the features of the pathogenesis of UTI and host predispositions are not clearly understood......Page 245
Syphilis is caused by the spirochete Treponema pallidum......Page 246
Non-specific tests (non-treponemal tests) for syphilis are the VDRL and RPR tests......Page 248
Commonly used specific tests for syphilis include the treponemal antibody test, FTA-ABS test and the MHA-TP......Page 249
Gonorrhoea is initially asymptomatic in many women, but can later cause infertility......Page 250
A diagnosis of gonorrhoea is made from microscopy and culture of appropriate specimens......Page 251
C. trachomatis serotypes D–K cause sexually transmitted genital infections......Page 252
The clinical effects of C. trachomatis infection appear to result from cell destruction and the host’s inflammatory response......Page 253
Lymphogranuloma venereum is a systemic infection involving lymphoid tissue and is treated with doxycycline or erythromycin......Page 254
Candida albicans causes a range of genital tract diseases, which are treated with oral or topical antifungals......Page 255
Bacterial vaginosis is associated with Gardnerella vaginalis plus anaerobic infection and a fishy-smelling vaginal discharge......Page 256
Genital herpes is characterized by ulcerating vesicles that can take up to 2 weeks to heal......Page 257
Acquired immune deficiency syndrome (AIDS) was first recognized in 1981 in the USA......Page 258
Human immunodeficiency virus infection started in Africa between 1910 and 1930......Page 259
Human immunodeficiency virus mainly infects cells bearing the CD4 glycoprotein on the cell surface and also requires chemokine co-receptors, CCR5 and CXCR4......Page 260
At first the immune system fights back against HIV infection, but then begins to fail......Page 261
Heterosexual transmission has not so far been as important in resource-rich as in resource-poor countries......Page 262
Antiretroviral therapy results in a dramatic improvement in disease prognosis......Page 264
Laboratory tests for HIV infection involve both serological and molecular analysis......Page 265
There are a number of preventative measures to reduce the spread of HIV......Page 266
There are a number of challenges in developing a successful vaccine against HIV infection......Page 268
Genital scabies is also treated with permethrin cream......Page 269
Food-associated infection versus food poisoning......Page 270
In the resource-poor world, diarrhoeal disease is a major cause of mortality in children......Page 271
Enterohaemorrhagic E. coli (EHEC) isolates produce a verotoxin.......Page 273
EPEC and ETEC are the most important contributors to global incidence of diarrhoea, whereas EHEC is more important in resource-rich countries.......Page 275
Salmonellae are almost always acquired orally in food or drink that is contaminated with human faeces.......Page 276
Campylobacter infections are among the most common causes of diarrhoea.......Page 277
Cultures for Campylobacter should be set up routinely in every investigation of a diarrhoeal illness.......Page 278
The symptoms of cholera are caused by an enterotoxin.......Page 279
Prompt rehydration with fluids and electrolytes is central to the treatment of cholera.......Page 280
V. parahaemolyticus and Yersinia enterocolitica are food-borne Gram-negative causes of diarrhoea.......Page 281
Enterotoxigenic strains of Staph. aureus are associated with food-borne illness......Page 282
Polyvalent antitoxin is recommended as an adjunct to intensive supportive therapy for botulism......Page 283
Treatment with broad-spectrum antibiotics can be complicated by antibiotic-associated C. difficile diarrhoea......Page 284
Rotaviruses......Page 286
Replicating rotavirus causes diarrhoea by damaging transport mechanisms in the gut......Page 287
Helicobacter pylori is associated with most duodenal and gastric ulcers......Page 288
Transmission of intestinal parasites is maintained by the release of life cycle stages in faeces......Page 289
E. histolytica infection may cause mild diarrhoea or severe dysentery.......Page 290
Like Entamoeba, Giardia has only two life cycle stages.......Page 291
Routine faecal wet preparation examinations are inadequate for diagnosing cryptosporidial diarrhoea.......Page 292
Female Ascaris and Trichuris lay thick-shelled eggs in the intestine, which are expelled with faeces and hatch after being swallowed by another host.......Page 293
Laboratory diagnosis......Page 294
Many other worm species can infect the intestine, but most are uncommon in resource-rich countries.......Page 295
Before antibiotics, 12–16% of patients with enteric fever died, usually of complications......Page 296
Diagnosis of enteric fever depends upon isolating S. typhi or paratyphi types using selective media......Page 297
An alphabetical litany of viruses directly target the liver, from hepatitis A to E......Page 298
Clinically, hepatitis A is milder in young children than in older children and adults......Page 299
Hepatitis E virus (HEV) spreads by the faecal–oral route......Page 300
Hepatitis B......Page 301
Certain groups of people are more likely to become carriers of hepatitis B......Page 302
Hepatitis B infection can be prevented by immunization......Page 304
Direct-acting antivirals (DAA) have revolutionized HCV treatment in a short time period......Page 305
Inflammatory responses to the eggs of Schistosoma mansoni result in severe liver damage......Page 306
Peritonitis is generally classified as primary (without apparent source of infection) or secondary (e.g. due to perforated appendicitis, ulcer, colon)......Page 308
The fetus has poor immune defences......Page 310
Intrauterine infection may result in death of the fetus or congenital malformations......Page 311
The fetus is particularly susceptible to rubella infection when maternal infection occurs during the first 3 months of pregnancy......Page 312
Mothers with a poor T-cell proliferative response to CMV antigens are more likely to infect their fetus......Page 313
Acute asymptomatic infection by Toxoplasma gondii during pregnancy can cause fetal malformation......Page 314
Maternal exposure to animals or foods infected with Listeria can lead to fetal death or malformations......Page 315
Fetal infection with HSV must be considered in a baby who is acutely ill within a few days or weeks of birth......Page 316
Other neonatal infections......Page 317
Invasion of the CNS via peripheral nerves is a feature of herpes simplex, varicella-zoster and rabies virus infections......Page 319
The pathological consequences of CNS infection depend upon the microorganism......Page 320
Neisseria meningitidis is carried by about 20% of the population, but higher rates are seen in epidemics.......Page 321
Type b H. influenzae causes meningitis in infants and young children.......Page 323
Tuberculous meningitis usually presents with a gradual onset over a few weeks.......Page 324
Encephalitis is usually caused by viruses, but there are many cases where the infectious aetiology is not identified......Page 326
Poliovirus used to be a common cause of encephalitis......Page 328
More than 55 000 people die of rabies worldwide each year......Page 329
Numerous arthropod-borne togaviruses can cause meningitis or encephalitis......Page 330
Viral myelopathy......Page 331
Toxocara infection can result in granuloma formation in the brain and retina......Page 332
Sleeping sickness is a trypanosomal infection that is being better controlled......Page 333
Clinical features of tetanus include muscle rigidity and spasms......Page 334
Botulism is treated with antibodies and respiratory support......Page 335
Chlamydial infections are treated with antibiotic and prevented by face washing......Page 336
Conjunctival infection may be transmitted by the blood or nervous system......Page 337
Toxocara canis larvae cause an intense inflammatory response and can lead to retinal detachment......Page 339
Onchocerca volvulus infection causes ‘river blindness’ and is transmitted by Simulium flies......Page 340
Microbial disease of the skin may result from any of three lines of attack......Page 341
Staphylococcus aureus is the most common cause of skin infections and provokes an intense inflammatory response......Page 343
Toxic shock syndrome is caused by toxic shock syndrome toxin-producing Staph. aureus......Page 344
Clinical features of streptococcal skin infections are typically acute......Page 345
Cellulitis is an acute spreading infection of the skin that involves subcutaneous tissues......Page 346
Amputation may be necessary to prevent further spread of clostridial infection......Page 347
Leprosy is caused by Mycobacterium leprae......Page 348
The clinical features of leprosy depend upon the cell-mediated immune response to M. leprae......Page 349
Leprosy is treated with dapsone given as part of a multidrug regimen to avoid resistance......Page 350
Dermatophyte infections are acquired from many sources and are spread by arthrospores......Page 351
Dermatophyte infections are treated topically if possible......Page 353
Candida requires moisture for growth......Page 354
Mycetoma......Page 355
Onchocerciasis is characterized by hypersensitivity responses to larval antigens......Page 356
Mucocutaneous Manifestations of Viral Infections......Page 357
Papillomavirus infects cells in the basal layers of skin or mucosa and are tissue tropic......Page 358
Clinical features of HSV infection include painful vesicles and a latency state......Page 359
HSV reactivation is provoked by a variety of factors......Page 360
Varicella is characterized by crops of vesicles that develop into pustules and then scab over......Page 361
Zoster results from reactivation of latent VZV......Page 362
Parvovirus B19 causes slapped cheek syndrome......Page 363
Global smallpox eradication was officially certified in December 1979......Page 364
Clinical features of measles include respiratory symptoms, Koplik’s spots and a rash......Page 365
Complications of measles are particularly likely among children in resource-poor countries......Page 366
Other Maculopapular Rashes Associated With Travel-Related Infections......Page 367
It has been difficult to establish postviral fatigue syndrome as a clinical entity......Page 368
The larvae of Trichinella invade striated muscle......Page 369
Circulating bacteria sometimes localize in joints, especially following trauma......Page 370
HTLV-1 infects T cells and up to 5% of those infected develop T-cell leukaemia......Page 371
HTLV-2 infection......Page 372
Only a small number of arboviruses are important causes of human disease......Page 374
Dengue fever may be complicated by dengue haemorrhagic fever / dengue shock syndrome......Page 375
The encephalitic arboviruses only occasionally cause encephalitis......Page 376
Typical clinical symptoms of rickettsial infection are fever, headache and rash......Page 377
Rocky Mountain spotted fever is transmitted by dog ticks and has a mortality of 10% or more......Page 378
Untreated epidemic typhus has a mortality as high as 60%......Page 379
Relapsing fever is characterized by repeated febrile episodes due to antigenic variation in the spirochetes......Page 380
Erythema migrans is a characteristic feature of Lyme disease......Page 381
Clinical features of malaria include a fluctuating fever and drenching sweats......Page 382
Malaria is diagnosed by finding parasitized red cells in thin and thick blood films......Page 385
T. cruzi is transmitted by the reduviid (‘kissing’) bug......Page 386
Leishmania is an intracellular parasite and inhabits macrophages......Page 387
Clinical features of schistosomiasis result from allergic responses to the different life cycle stages......Page 388
Lymphatic filariasis caused by Brugia and Wuchereria is transmitted by mosquitoes......Page 389
Few drugs are really satisfactory for treating filariasis......Page 390
Arenavirus infection is diagnosed by viral genome detection, serology or virus isolation......Page 391
Ebola virus disease (EVD) – gradual evolution of outbreaks to an unprecedented epidemic in West Africa from 2013 to 2016......Page 393
Infection control strategies to manage travellers from EBOV-affected countries......Page 394
Crimean–Congo Haemorrhagic Fever, a Tick-Borne Virus......Page 395
Cutaneous anthrax is diagnosed by culture and treated with ciprofloxacin......Page 396
Plague is diagnosed microscopically and treated with antibiotics......Page 397
Clinical features of tularaemia include painful swollen lymph nodes......Page 398
Leptospirosis is caused by the spirochete Leptospira interrogans, which infects mammals such as rats......Page 399
Clinical features of rat-bite fever can include endocarditis and pneumonia......Page 400
Clinical features of brucellosis are immune mediated and include an undulant fever and chronicity......Page 401
Echinococcus multilocularis (alveolar echinococcosis; alveolar hydatid disease)......Page 402
Strongyloides infections are usually asymptomatic, but can cause disseminated disease in patients with immunodeficiency states or malnutrition......Page 403
Infective causes of classical FUO......Page 405
Stage 1 comprises careful history taking, physical examination and screening tests......Page 406
Stage 2 involves reviewing the history, repeating the physical examination, specific diagnostic tests and non-invasive investigations......Page 407
Stage 3 comprises invasive tests......Page 408
Almost any organism can cause endocarditis, but native valves are usually infected by oral streptococci and staphylococci......Page 409
A patient with infective endocarditis almost always has a fever and a heart murmur......Page 410
The antibiotic treatment regimen for infective endocarditis depends upon the susceptibility of the infecting organism......Page 411
Most people with an FUO have a treatable disease presenting in an unusual manner......Page 412
Secondary defects of innate defences include disruption of the body’s mechanical barriers......Page 413
Causes of secondary adaptive immunodeficiency include malnutrition, infections, neoplasia, splenectomy and certain medical treatments......Page 414
Burns damage the body’s mechanical barriers, neutrophil function and immune responses......Page 415
P. aeruginosa is a devastating Gram-negative pathogen of burned patients......Page 416
Catheter-associated infection of the urinary tract is common......Page 417
A lack of circulating neutrophils following bone marrow failure predisposes to infection......Page 418
Candida is the most common fungal pathogen in compromised patients......Page 419
Disseminated Histoplasma capsulatum infection may occur years after exposure in immunocompromised patients......Page 420
Pneumocystis jirovecii (formerly P. carinii) causes symptomatic disease only in people with deficient cellular immunity......Page 421
Mycobacterium avium-intracellulare disease is often a terminal event in AIDS......Page 422
Certain virus infections are both more common and more severe in compromised patients, and regular surveillance is critical......Page 423
Hepatitis B and C infection in transplant recipients......Page 424
Polyomaviruses can cause haemorrhagic cystitis and progressive multifocal leukoencephalopathy......Page 425
Specimen handling and interpretation of results is based upon a knowledge of normal microbiota and contaminants......Page 426
Bacteria and fungi can be cultured on solid nutrient or liquid media......Page 427
Bacteria are identified by simple characteristics and biochemical properties......Page 428
Mass spectrometry heralds a novel diagnostic era......Page 430
Other staining techniques can be used to demonstrate particular features of cells......Page 431
Although not routinely used in the clinical laboratory, electron microscopy provides the ultimate in microbe visualization and can aid in microbe identification......Page 432
Immunoassay can be used to measure antigen concentration......Page 433
Monoclonal antibodies can distinguish between species and between strains of the same species on the basis of antigenic differences......Page 434
For diagnostic purposes, traditional PCR has been largely replaced by real-time PCR......Page 435
More than one pathogen can be detected in a single reaction – multiplexing......Page 436
Second-generation ‘sequencing by synthesis’......Page 437
Amplification-based techniques and point of care (POC) tests......Page 438
Phagocytic activity is a key element of proper immune function......Page 439
Individual cells secreting antibodies or cytokines can be counted by the ELISPOT technique or by flow cytometry......Page 440
Putting It All Together: Detection, Diagnosis and Epidemiology......Page 441
Cross-sectional studies......Page 443
Cohort studies......Page 444
Intervention studies......Page 445
Time periods of infections......Page 448
Basic and net reproduction number......Page 449
Vaccine Efficacy......Page 450
Discovery and Design of Antimicrobial Agents......Page 451
The genetics of resistance......Page 453
‘Cassettes’ of resistance genes may be organized into genetic elements called integrons......Page 454
Inhibitors of Cell Wall Synthesis......Page 455
Most beta-lactams have to be administered parenterally......Page 456
Resistance by alteration in target site.......Page 457
Toxic effects of beta-lactam drugs include mild rashes and immediate hypersensitivity reactions.......Page 458
Glycopeptides are large molecules and act at an earlier stage than beta-lactams......Page 459
Both vancomycin and teicoplanin are active only against Gram-positive organisms......Page 460
Inhibitors of Protein Synthesis......Page 461
The aminoglycosides are a family of related molecules with bactericidal activity......Page 462
Production of aminoglycoside-modifying enzymes is the principal cause of resistance to aminoglycosides......Page 463
Tetracyclines should be avoided in pregnancy and in children under 8 years of age......Page 464
Erythromycin is a widely used macrolide preventing the release of transfer RNA after peptide bond formation.......Page 465
Newer macrolide-related (macrocycle) drugs show promise for targeted therapy......Page 466
Pseudomembranous colitis caused by C. difficile was first noted following clindamycin treatment.......Page 467
Fusidic acid has few side effects......Page 468
Resistance to quinolones is usually chromosomally mediated......Page 469
Sulphonamides are useful in the treatment of urinary tract infection, but resistance is widespread......Page 470
Trimethoprim is a structural analogue of the aminohydroxypyrimidine moiety of folic acid and prevents the synthesis of THFA......Page 471
Lipopeptides are a newer class of membrane-active antibiotics......Page 472
M. tuberculosis and other mycobacterial infections need prolonged treatment......Page 473
A dilution test provides a quantitative estimate of susceptibility to an antibiotic......Page 474
Killing curves provide a dynamic estimate of bacterial susceptibility......Page 475
Antibiotic Assays......Page 476
Antiviral drugs do not kill viruses but stop viral replication......Page 477
Foscarnet......Page 481
Nelfinavir, saquinavir, indinavir, ritonavir, lopinavir plus ritonavir (Kaletra), atazanavir, amprenavir, darunavir, fosamprenavir and tipranavir.......Page 482
Oseltamivir, zanamavir and peramivir.......Page 483
Hepatitis C treatment......Page 484
Antifungal Agents......Page 485
Echinocandins interfere with cell wall synthesis......Page 486
Drug resistance is an increasing problem......Page 487
Control and eradication are different objectives, although eradication is always an ideal endpoint......Page 490
Use and Misuse of Antimicrobial Agents......Page 491
Antimicrobial use results in the selection of resistant strains......Page 492
Vaccination – a Four Hundred Year History......Page 494
Vaccines Can Be of Different Types......Page 495
Adjuvants......Page 496
Vaccine safety......Page 498
Measles, mumps and rubella vaccines......Page 499
Meningococcal vaccines......Page 500
Haemophilus influenzae type b (Hib)......Page 501
BCG and new vaccines for tuberculosis (TB)......Page 502
Human papillomavirus (HPV)......Page 504
Complexity of vaccine schedules......Page 505
HIV vaccines......Page 506
New delivery systems and technologies for future vaccines......Page 507
New routes of vaccination......Page 508
Adoptive Immunotherapy......Page 509
Antibody in pooled serum can provide protection against infection......Page 510
Single-domain variable region fragments have several advantages......Page 511
Monoclonal antibodies were then made more efficacious and are increasingly used in the clinical setting......Page 512
Probiotics......Page 513
Staphylococci and Escherichia coli have traditionally been the most important Gram-positive and Gram-negative causes of infection, respectively, however the list is expanding......Page 515
Some infections historically associated with hospitals are now increasingly seen outside of the healthcare setting......Page 516
Viral infections probably account for more hospital infections than previously realized......Page 517
Sources of hospital infection are people and contaminated objects......Page 518
Hospital infections affect both the patient and the community......Page 519
Exclusion of inanimate sources of infection is achievable, but it can be difficult to avoid contamination by humans......Page 520
Bacteriologically effective hand washing is one of the most important ways of controlling hospital infection.......Page 521
Care of invasive devices is essential to reduce the risk of endogenous infection.......Page 522
There must be a description of an outbreak in epidemiological terms......Page 523
Bacteriophage (phage) typing has been used to type Staph. aureus, Staph. epidermidis and Salmonella typhi......Page 524
‘Fourth-generation’ molecular epidemiology is based on DNA sequence analysis......Page 525
Sterilization and Disinfection......Page 527
The rate of killing of microorganisms depends upon the concentration of the killing agent and time of exposure......Page 528
Filters are used to produce particle- and pyrogen-free fluid.......Page 529
Many different antimicrobial chemicals are available, but few are sterilant.......Page 530
Disinfectants can be monitored by microbiological ‘in-use’ tests......Page 531
Useful Websites......Page 532
Viruses......Page 534
Gram-positive Cocci......Page 550
Beta-haemolytic Streptococci......Page 551
Alpha-haemolytic Streptococci......Page 552
Gram-positive Rods......Page 553
Gram-negative Rods......Page 560
Gram-negative Cocci......Page 566
Other Bacteria......Page 572
Deep Mycoses......Page 574
Protozoa......Page 576
Tapeworms......Page 580
Flukes......Page 581
Nematodes......Page 582
Vaccine parade......Page 585