Transcript Infectious Diseases - LSH Student Resources

Infectious Diseases
General Principles
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Categories
Special techniques for diagnosing Table 8-2
New and emerging diseases Table 8-3
Agents of bioterrorism
Transmission and dissemination of
microbes
How microorganisms cause disease
Immune evasion by microbes
Infections in immunosuppressed hosts
Spectrum of inflammatory responses to
infection
Categories
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Prions
Viruses
Bacteria
Fungi
Protozoa
Helminths
Ectoparasites
Table 8-1 Classes of Human Pathogens and their
Lifestyles
Agents of Bioterrorism
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Highest risk
Readily disseminated or transmitted
High mortality
Major public health impact
• Category B
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Moderately easy to disseminate
Moderate morbidity, low mortality
Require specific diagnosis
Require disease surveillance
• Category C
– Emerging pathogens
Transmission and Dissemination of
Microbes
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Routes of entry
Spread and dissemination
Release of microbes from the body
Sexually transmitted infections
Healthcare-associated infections –
”nosocomial”
• Host defenses against infection- innate and
adaptive immune defenses
Routes of Entry of Microbes
• Microbes can enter by:
– Inhalation
– Ingestion
– Sexual transmission
– Insect or animal bites
– Injection
Skin
• Dense, keratinized outer layer is natural
barrier to infection
• Low pH and presence of fatty acids inhibit
growth of microorganisms
• Most organisms enter through breaks in the
skin
GI tract
• Most GI pathogens are transmitted by food or drink
contaminated with fecal material
• Normal defenses
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Acidic gastric secretions
Layer of viscous mucous covering the intestinal epithelium
Lytic pancreatic enzymes and bile detergents
Defensins =mucosal antimicrobial peptides
Normal flora
Secreted IgA antibodies from MALT
Infections via the GI tract our when local defenses are
weakened or the organisms develop strategies to
overcome these defenses
Respiratory Tract
• Large number of organisms are inhaled daily
often in dust or aerosol particles
• Distance they travel in inversely proportional
to their size
• Microorganisms that invade the normal
healthy respiratory tract have developed
specific mechanisms to:
– Overcome mucociliary defenses
– Avoid destruction by alveolar macrophages
Urogenital Tract
• Almost always invaded from the exterior via
the urethra
• Regular flushing of urine serves as a defense
• Short urethra in females, obstruction, reflux
• Lactobacilli in vagina
Spread and Dissemination of Microbes
• Proliferate locally at the site of infection
• Penetrate the epithelial barrier
• Spread to distant sites via
– Lymphatics
– Blood
– Nerves
• Major manifestations may appear at sites
different from the point of entry
• Placental-fetal route
Release of Microbes from the Body
• Person-to-person transmission
– Respiratory
– Fecal-oral
– Sexual
– Blood and blood products
• Animal to human
– Direct contact
– Consumption of animal products
– Indirectly through an invertebrate vector
Sexually Transmitted Infections
• Infections with one STI-associated organism
increases the risk for additional STIs
• The microbes that cause STIs can be spread
from a pregnant woman to the fetus and
cause severe damage to the fetus or child
How Microorganisms cause Disease
• Mechanisms of viral injury
• Mechanisms of bacterial injury
• Injurious effects of host immunity
Mechanisms of Viral Injury
• Directly damage cells by entering them and
replicating at the host’s expense
• Tropism= predilection for viruses to infect certain
cells
• A major determinant of tissue tropism is the
presence of viral receptors on host cells
• Direct cytopathic effects
• Antiviral immune responses
• Transformation of infected cells
• Figure 8-5
Mechanisms of Bacterial Injury
• Bacterial virulence
– Damage to host tissues depends on the ability of the
bacteria to:
• Adhere to host cells – adhesins, pili
• Invade cells and tissues
• Deliver toxins
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Virulence genes
Pathogenicity islands
Plasmids and bacteriophages
Quorum sensing
Biofilms
Bacterial Toxins
• Endotoxin – LPS of Gram negatives
• Exotoxins
– Enzymes
– Toxins that alter intracellular signaling or
regulatory pathways
– Neurotoxins
– Superantigens
Immune Evasion by Microbes
• Replication in sites that are inaccessible to the
host immune response
• Varying the antigens they express:
– High mutation rate
– Genetic reassortment
– Genetic rearrangement
– Large diversity of serotypes
Immune Evasion by Microbes
• Methods for evading the innate immune
defenses
• Produce molecules that inhibit innate
immunity
• Produce factors that decrease recognition of
infected cells by CD4+ helper T cells and CD8+
cytotoxic T cells
Spectrum of Inflammatory Responses
to Infection
• Suppurative (purulent) inflammation
• Mononuclear and granulomatous
inflammation
• Cytopathic-Cytoproliferative reaction
• Tissue necrosis
• Chronic inflammation and scarring
Viral Infections
• Acute (transient) infections
• Chronic (latent) infections
• Chronic productive infections – Hepatitis B
Virus
• Transforming infections
Acute Transient Infections
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Measles
Mumps
Poliovirus
West Nile virus
Viral hemorrhagic fevers
Measles
• Rubeola
• Important cause of death in malnourished
children
• ssRNA virus – paramyxovirus family
• Croup, pneumonia, diarrhea with protein-losing
enteropathy, keratitis with scarring and blindness,
encephalitis, hemorrhagic measles
• Subacute sclerosing panencephalitis (SSPE)
• Rash, Koplik spots, Warthin-Finkeldy cells
Mumps
• Paramyxovirus family
• Parotitis, orchitis, pancreatitis, encephalitis
Poliovirus
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Enterovirus
Fecal-oral route of spread
Most infections are asymptomatic
Spinal poliomyelitis
Bulbar poliomyelitis
West Nile Virus
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Arbovirus
Mosquitos – birds
Most infections are asymptomatic
Meningitis and/or encephalitis -1/150
clinically apparent cases
Viral Hemorrhagic Fevers
• Four different RNA viruses
• Systemic infections
• Animal or insect vector
Chronic Latent Infections
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ds-DNA viruses
Herpes simplex Virus
Varicella-Zoster Virus
Cytomegalovirus
Herpes Simplex Virus
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Fever Blisters or cold sores
Gingivostomatitis
Genital herpes
Corneal lesions- keratitis
Encephalitis
Kaposi varicelliform eruption
Eczema herpeticum
Esophagitis
Bronchopneumonia
Hepatitis
Varicella-Zoster
• Chickenpox – acute
– Crops of lesions from dew drop on a rose petal to
vesicle to crusted lesion
• Shingles – reactivation of latent
– Ramsey hunt syndrome –geniculate nucleus
– Dermatomal
– Pain as well as rash
CMV
• Asymptomatic
• Mononucleosis-like syndrome
• Devastating systemic infection in neonates and
immunocompromised
hosts
• Transmission
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Transplacental
Neonatal
Saliva
Venereal
Iatrogenic
Transforming Infections
• Epstein-Barr Virus
– Figure 8-16 – outcome of EBV infection
– X-linked lymphoproliferation syndrome (Duncan
disease)
– Diagnosis
• Lymphocytosis with atypical lymphocytes
• Postive heterophile antibody reaction (monospot)
• Specific antibodies to EBV antigens
Bacterial Infections
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Gram-positive bacteria
Gram-negative bacteria
Mycobacteria
Spirochetes
Anaerobic bacteria
Obligate intracellular bacteria
Gram-Positive
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Staphococcal infections
Streptococal and Enterococcal
Diphtheria
Listeriosis
Anthrax
Nocardia
infections
Staphylococcal Infections
• Staph. Aureus
– Pyogenic infections
• Skin lesions – impetigo, furuncle, carbuncle, hidradenitis, paronchyia,
felons, staph scalded skin syndrome (Ritter disease)
• Abscesses
• Sepsis
• Osteomyelitis
• Pneumonia
• Endocarditis
– Multitude of virulence factors
– MRSA
– Superantigens
• Food poisoning
• Toxic shock syndrome
Streptococcal Infections
• S. pyogenes (Group A)
– Pharyngitis, scarlet fever, erysipelas, impetigo, rheumatic
heart disease, TSS, glomerulonephritis
• S. agalactiae (Group B)
– Neonatal sepsis, chorioamnionitis
• S. pneumoniae
– Lobar pneumonia
• S. mutans
– Dental decay
• Enterococci
– Endocarditis and UTIs
Diphtheria
• Skin lesions in infected wounds
• Formation of a tough pharyngeal
membrane
• Toxin-mediated damage to heart, nerves and
other organs
Listeria
• Food-borne illnesses
• Pregnant woman, neonates, elderly, and
immunosuppressed
• Meningitis
Anthrax
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Cutaneous
Inhalational
Gastrointestinal
Exposure to animals or animal products such
as hides and wool
• Spores can be ground into a fine powder
making a potent biologic weapon
Nocardia
• Similar to molds – branching filaments
• Opportunistic infections in
immunocompromised hosts
Gram-Negative
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Neisserial Infections
Whooping Cough
Pseudomonas Infections
Plague
Chancroid
Granuloma Inguinale
Neisserial Infections
• Gram-negative diplococci, coffee bean, chocolate agar
• N.meningitidis – meningitis, common colonizer of the
oropharynx, complement important in immune
response
• N. gonorrhoeae – STD, 2nd after chlamydia, urethritis in
men, often asymptomatic in women  PID 
infertility and ectopic pregnancy
• Antigenic variation allows escape from the immune
response
– Multiple serotypes
– Pili proteins and OPA proteins
Whooping Cough
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Gram-negative coccobacillius
Bordetella pertussis
Highly contagious
Violent paroxysms of coughing
Inspiratory “whoop”
Laryngotracheobronchitis
Severe cases – bronchial mucosal erosion, hyperemia,
copious mucopurulent exudate
• Striking peripheral lymphocytosis
• Hypercellularity and enlargement of the mucosal lymph
follicles and peribronchial lymph nodes
• No pneumonia unless superinfected
Pseudomonas Infection
• Opportunistic gram-negative bacillus
• Cystic fibrosis, severe burns, neutropenia
• Pili, adherence proteins, endotoxin, exotoxin,
, enzymes, iron-containing
compounds
• Necrotizing pneumonia, vasculitis
• Ecthyma gangrenosum
• DIC
Plague
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Yersinia pestis
Gram-negative intracellular bacterium
Fleas  rodents  humans
Yop virulon - kills host phagocytes
Plague
– Bubonic plague
– Pneumonic plague
– Septicemic plague
Chancroid
• Soft chancre
• Hemophilus ducreyi
• Tropics – one of the most common causes of
genital ulcers in Africa and
Southeast Asia
Granuloma Inguinale
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Klebsiella granulomatis
Chronic inflammatory disease
Tropics
Extensive scarring and lymph obstruction
Psuedoepitheliomatous hyperplasia
Mycobacteria
• Tuberculosis
• Mycobacterium avium-intracellulare Complex
• Leprosy
Tuberculosis
• Mycobacterium tuberculosis
• TB flourishes where there is poverty, crowding,
and chronic debilitating
illness. HIV
• Differentiate infection from disease
• Most primary TB is asymptomatic
• Pathogenesis – Figure 8-27
• Clinical Features – Figure 8-28
• Fever, night sweats, hemoptysis
• Ghon complex, Pott disease, intestinal TB –
unpasteruerized milk
Mycobacterium avium-intracellulare
Complex
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MAC
AIDS, CD4+ counts < 60/mm3
Fever, night sweats, weight loss
Abundant acid-fast organisms within
macrophages
• Lungs, lymph nodes, liver, spleen
Leprosy
• Hansen disease
• M. leprae
• Skin, peripheral nerves –replicates in
cool
tissues
• Disabling deformities
• T-helper cell response determines tuberculoid
vs lepromatous leprosy
Spirochetes
• Syphilis
• Relapsing fever
• Lyme Disease
Syphilis
• Treponema pallidum
• Silver stain, dark-field,
immunofluorescence
to identify, not Gram stain
• Cannot grow in culture
• Three stages + congenital – Figure 8-37
• Jarisch-Herxheimer reaction
• Pathogenesis – proliferative endarteritis
• Serologic testing
– Nontreponemal – VDRL and RPR, False
– Antitreponemal – fluorescent antibody
positives
Relapsing Fever
• Lice and tick transmitted
• Borrelia recurrentis
Lyme Disease
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Borrelia burgdorferi
Ixodes deer tick
Three stages – Figure 8-40
Pathogenesis – immune response and
accompanying inflammation
Anaerobic Bacteria
• Abscesses
• Clostridial Infections
Abscesses caused by Anaerobes
• Usually mixed anaerobic and facultative aerobic
bacteria
• Commensal bacteria from adjacent sites are the
usual causes, part of normal flora
• Head and neck – Prevotella and Porphyromonas, with
S.aureus and
S.pyogenes
• Fusobacterium necrophorum –Lemierre
syndrome
• Abdominal – Peptostreptococcus and
Clostridium, Bacteriodes fragilis and E. coli
• Genital- Prevotella with E. coli and S. Agalactiae
Clostridial Infections
• Spores, found in soil, do not grow in the
oxygen, virulence=toxins
• C. tetani – Tetanus, neurotoxin
• C. botulinum – neurotoxin, canned foods
• C. difficile –overgrowth in intestine after
use, pseudomembranous colitis
• C. perfringens, C. septicum et al
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Uterine myonecrosis
Mild food poisoning
Small bowel infection with ischemia or
presence of
antibiotic
neutropenia
Obligate Intracellular Bacteria
• Chlamydial Infections
– C. trachomatis
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Serotypes define type of infection
Most common sexually transmitted bacterial disease in the world.
Urethritis
Lymphogranuloma venereum
• Rickettsial Infections
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Vector-borne typhus and spotted fevers
Lice, chiggers, ticks
Ehrlichiosis inclusions
Severe manifestations are primarily due to vascular
leakage secondary to endothelial cell damage
Fungal Infections
• Yeasts and molds
• Mycoses
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Superficial and cutaneous
Subcutaneous
Endemic
Opportunistic
Candidiasis
Cryptococcosis
Aspergillosis
Zygomycosis (Mucormycosis)
Candidiasis
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Candida – usually a benign commensal
Pseudohyphae and budding yeast
Vaginitis, diaper rash, thrush
Esophagitis –AIDS
Invasive – immunosuppressed
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Renal abscesses
Endocarditis – IV drug users
Myocardial abscesses
Brain microabscesses. meningitis
Crytococcosis
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C. neoformans
Meningoencephalitis
Opportunistic – high-dose steroids
Soil, bird droppings, inhaled
Yeast, no hyphae, intense red-staining
with Periodic acid-Schiff or mucicarmine,
thick gelatinous
capsule
Aspergillosis
• Mold, air-borne, fruiting bodies with septate
filaments branching at acute angles
• Allergies in other wise healthy people
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allergic bronchopulmonary
aspergillosis)
• Severe sinusitis, pneumonia, invasive disease in
immunosuppressed
• Colonizing aspergilliosis
• Invasive aspergilliosis
• Aflatoxin
Zygomycosis (Mucormycosis)
• Bread mold
• Opportunistic
• Neutropenia, steroid use, DM, iron overload,
burns, trauma
• Rhinocerebral mucormycosis
Parasitic Infections
• Protozoa
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Babesiosis – deer ticks, fever and hemolytic anemia
Leishmaniasis
African Trypanosomiasis – “Sleeping sickness”, tsetse
flies
Chagas Disease – “kissing bugs” , acute myocarditis or chronic
cardiomyopathy
• Metazoa
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Tapeworms – undercooked meats or fish
Trichinosis – pork, skeletal muscle
Schistosomiasis – freshwater snails,hepatic cirrhosis, colon fibrosis, cystitis,
squamous cell carcinoma of bladder
– Lymphatic filariasis- mosquitos, elephantiasis
– Onchocerciasis- black flies, river blindness
Malaria
• Plasmodium
• Anopheles mosquito
• Life cycle – sporozoites  merozoites trophozoites  schizonts 
gametocytes or more merozoites
• Hypnozoites – relapses
• Host resistance
– Inherited alterations in red cells
– Repeated or prolonged exposure
• Severe malaria = P. falciparum
– Leading cause of death in children under five years of age inn subSaharan
Africa
– High levels of parasitemia, severe anemia, cerebral symptoms, renal failure,
pulmonary edema, death
– Ischemia due to poor perfusion causes the main mamifestations of cerebral
malaria
– High levels of cytokines
Leishmaniasis
• Sandflies, macrophages
• Different species in Old World and New World
• Visceral
– Hepatosplenomegaly
– Pancytopenia, fever, weight loss
• Cutaneous
– Ulcers
• Mucocutaneous
– Nasopharyngeal areas, disfiguring
• Diffuse cutaneous
– Rare form
– Single nodule spreads to entire body