Transcript Lecture #16 Bio3124 - University of Ottawa

Medical Microbiology
Part I: Infections of Skin,
Respiratory &
Gastrointenstinal tracts
Lecture #15
Bio3124
Characterizing Microbial Diseases
• Identification of pathogen is important
– Determines method of treatment
• Clues to rapid identification
– Signs and Symptoms
– Testing of specimens
– Knowing patient histories
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Environment
Occupation and social activities
Nutrition
Previous medical history
Human infectious diseases
Source and origin of pathogens
• Airborne infections
• Arthropod-borne diseases
• Direct contact diseases
• Food-borne and water-borne infections
• Zoonotic infections
Human infectious diseases
By the site of infection,
• Skin and soft tissue infections
• Respiratory system infections
• Gastrointenstinal tract infections
• Genitourinary tract infections
• Central nervous system infections
• Cardiovascular system infections
• Systemic infections
Human skin infections
• Staphylococcal infections
– Boils and scalded skin syndrome
• Streptococcal infections
– Necrotizing faciitis
• Clostridial infections
– Gas Gangrene
• Viral skin infections
– Measles, Chickenpox , Smallpox
Staphylococcal infections
• members of genus of Staphylococcus
– gram-positive cocci, grape-like clusters
– facultative anaerobes and usually catalase positive
– normal inhabitants of upper respiratory tract, skin,
intestines, and vagina
– S. aureus – coagulase positive, pathogenic
– S. epidermidis – coagulase negative, less pathogenic
– many pathogenic strains are slime producers
Slime
• viscous extracellular
glycoconjugate that
allows bacteria to
adhere to smooth
surfaces and form
biofilms
• inhibits neutrophil
chemotaxis,
phagocytosis, and
antimicrobial agents
slime
Staphylococcal Skin infections
• localized abscess and boils
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S. aureus established in a hair follicle, tissue necrosis
coagulase forms fibrin wall limiting spread
Liquefaction, abscess spreads
may be a furuncle (boil) or carbuncle
Furuncle
Carbuncle
Toxic shock syndrome (TSS)
• caused by S. aureus strains that release toxic shock
syndrome toxin (TSST-1)
• disease results from body’s response to staphylococcal
superantigens
• Resulting in massive cytokine production leading to
circulatory collapse , shock and multi-organ failure
• clinical manifestations
– low blood pressure, fever, diarrhea, extensive skin rash,
and shedding of the skin
Staphylococcal scalded skin syndrome (SSSS)
• S. aureus that carry a plasmid-borne gene for exfoliative
toxin (exfoliatin)
• A protease, weakens skin
• epidermis peels off
• Diagnosis
– isolation/identification of staphylococcus
involved /use of commercial kits
– isolation and identification based on catalase test,
coagulase test, serology, DNA fingerprinting, and phage
typing
• Treatment, prevention, and control
– antibiotic therapy: Vancomycin, cephalosporins, rifampin
• many drug-resistant strains
– personal hygiene and aseptic management of lesions
Invasive Streptococcus A Infections
• Streptococcus pyogenes: important pathogen in the group
• causes invasive infections
• virulence is due to:
– Pyrogenic exotoxin A (SpeA), a superantigen
• nonspecific T cell activation and large amount of cytokine
production, damaging endothelial cells -> multiorgan failure
– rapid fluid loss from tissues
– A cystein protease (exotoxin B) breaks down host
proteins, cause further tissue damage
Necrotizing Fasciitis
• clinical manifestations
– necrotizing fasciitis
• destruction of sheath covering skeletal
muscle
– myositis
• inflammation and destruction of skeletal
muscle and fat tissue
– toxic shock-like syndrome (TSLS)
• precipitous drop of blood pressure,
failure of multiple organs, and high
fever
• Treatment:
• Surgical removal of affected tissues,
amputation
• Penicillin G therapy
Gas Gangrene or Clostridial Myonecrosis
• Agent: Clostridium perfringens
– gram-positive, spore-forming rod
– Cause gas gangrene, a necrotizing infection of skeletal
muscle or clostridial myonecrosis, produces H2
– secretes α-toxin, a lecithinase cause membrane damage
and cellular death
– tissue damaging enzymes eg. Collagenase → invasion
• transmitted by spores from soil, bowel microbiota or infected
tissues
Gas gangrene…
• clinical manifestations
– severe pain, edema, drainage, and
muscle necrosis
• diagnosis
– recovery of appropriate clostridial
species and characteristic disease
symptoms
• treatment, prevention, and control
– surgical debridement, administration
of antitoxin, antibiotic therapy, and
hyperbaric oxygen therapy
– prompt treatment of all wound
infections and amputation of limbs
Chickenpox (Varicella) and Shingles (Herpes Zoster)
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Highly contagious skin disease
varicella-zoster virus (VZV), Herpesviridae, dsDNA
enveloped virus, icosahedral symmetry
infects children 2-7 years old
humans serve as reservoir
• droplets carrying virus enter respiratory system
• Incubation (10-23 days)
• Day 0: infection of mucosa of URS, viral replication in
lymph nodes
• Day 6: enters blood stream (primary viremia) replication
in liver and spleen
• followed by secondary viremia
• Day 10: moves to skin (vesicular rash)
• vesicles erupt on face and upper trunk
• filled with pus, rupture, covered by scabs
• Diagnosis: by symptoms
• Lab tests: not required, if so ELISA for IgM or PCR
• Prevention: attenuated varicella vaccine
• Treatment: acyclovir (Zovirax) inhibits viral DNA
polymerase
Chickenpox (Varicella) and Shingles (Herpes Zoster)
Shingles (Herpes zoster)
 recovery→natural immunity
 virus enters a latent stage, nucleus of cranial
nerves & dorsal ganglia
 ~ 500,000 cases per year in US
 virus reactivated, weaker immune system,
(Herpes zoster virus)
 migrates down nerve axon, replicates and
damages sensory nerves
 painful vesicles called shingles along dorsal
trunk
 syndrome is called post-herpetic neuralgia
 Therapy: not required; if necessary acyclovir or
other antivirals such as Famvir can be prescribed
Smallpox (Variola)
• caused by variola virus
– large, brick-shaped virus
– linear dsDNA virus of Poxviridae
• transmitted by aerosol or contact
– humans are only natural host
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Enters to regional lymph node
Incubation period 12-14 days
Multiplies in macrophage and monocytes
Enters blood (viremia)
Prodromal stage: is the symptomatic
imminent attack of disease characterized by
– Virus moves to epithelial cells in mouth and
throat
– Severe head and body aches, high fever
(40C), malaise and vomiting
– Infects the capillary epithelia of skin
– Vesicles filled with pus form and later rupture
to leave a skin lesion
Eradication of Smallpox
• Protection achieved by vaccination
– Vaccina virus in a live virus vaccine
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use of vaccine is controversial because of its unknown efficacy
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Food and Drug Administration has not approved any treatment for smallpox
• 1977 – last case from a natural infection occurred in Somalia
• Why eradication was possible
– disease has obvious clinical features
– humans are only hosts and reservoirs
– there are no asymptomatic carriers
– short infectivity period (3-4 weeks)
Human respiratory tract infections
• Infection of upper/lower respiratory tract, mostly viral
• Seldom spread to other tissues
• Streptococcal infections of lungs
– Bacterial pneumonia
• Mycobacterial infections
– Tuberculosis
• Viral infections of respiratory tract
– Influenza
– Respiratory syncytial virus infection (RSV)
Streptococcal pneumonia
• Opportunistic pathogen Streptococcus pneumoniae
– normal microbiota in upper R.tract
– polysaccharide capsule and a toxin
– rapidly multiplies in alveolar spaces
• Capsule prevents phagocytosis
• rapid growth in alveoli
• Bloody sputum
• 13000-66000 death in US/year
• occasionally results in otitis
media
• major opportunistic infection
among AIDS patients
Streptococcal pneumonia…
• diagnosis
– chest X-ray, gram stain, culture, and
tests for metabolic products
• clinical manifestations
– abrupt onset of chills, hard labored
breathing, chest pain, and rust colored
sputum
• treatment, prevention, and control
– antibiotic therapy with penicillin G
• resistant strains have appeared
– Vaccine: Pneumovax vaccine
pooled collection of 23 different
S.pneumonia capsular
polysaccharides
Tuberculosis (TB)
• Mycobacterium tuberculosis
• At the time of identification by Robert Koch
responsible for 1/7 of deaths in Europe, and 1/3
of young adults
• ~ 1/3 of world’s population infected
• resistance to phagocytic killing
– Mycolic acids in cell wall form hydrophobic barrier
– toxic to cells
– Inhibit phagosome-lysosome fusion
• Transmission
– person to person
– also transmitted from infected animals and
their products
TB - Course of Disease
• M. tuberculosis not killed in lung phagocytes
• tubercles form in alveolar lymphatic node
– composed of bacteria, macrophages, T cells and human proteins
– subsequent changes in tubercle may occur
• caseous lesion
– cheese-like consistency
• Ghon complexes
– calcified caseous lesion
• show up prominently in chest X-rays
• miliary tuberculosis: Tubercles liquefy and
bacteria spread
• also called reactivation tuberculosis because
bacteria reactivated at initial infection site
TB tubercle
Persons Infected With TB
• develop cell-mediated immunity (sensitized T cells)
– basis for tuberculin skin test
• incubation period
– 4-12 weeks
• symptoms
– fever, fatigue, weight loss
– cough
• characteristic of pulmonary involvement
• may result in expectoration of bloody sputum
Tuberculosis…
• diagnosis
– observation of acid-fast bacteria, chest X-ray, DNAbased tests, Mantoux or tuberculin skin test
• antimicrobial therapy
– Isoniazid, rifampin, pyrazinamide and ethambutol
• multi-drug-resistant strains of tuberculosis (MDR-TB) have
developed
• prevention and control
– rapid, specific therapy to interrupt spread, retreatment of
patients with MDR-TB, immunization, improved sanitation
and housing, and reduction in homelessness and drug
abuse
Influenza (Flu)
• caused by influenza virus
• classified into subtypes based on
hemagglutinin (HA) and neuraminidase (NA)
– HA and NA function in viral attachment
and virulence
– 16 HA and 9 NA antigenic forms are
known; they recombine to produce HA/NA
influenza subtypes
Influenza (Flu)
• clinical manifestations
– chills, fever, headache, malaise, and general muscle
aches and painful joints
– recovery usually within 3 to 7 days
– often leads to secondary infections by bacteria
• treatment, prevention, and control
– rapid immunologic tests for diagnosis of subtype
– symptomatic/supportive therapy
– Tamiflu, neuraminidase inhibitor shortens the course of
illness
• Prevention: inactivated virus vaccine
Gastrointestinal tract infections
• Bacterial diarrhea
– Enterohemorrhagic E.coli
• Peptic ulcer and gasteritis
– Helicobacter pylori
• Viral gastroenteritis
Enterohemorrhagic E.coli infection
 Reservoir: cattle, fecal contamination of water or food
 since 1982; “Jack-in-the Box” 1993 hamburger outbreak in US
 Walkerton, Canada (2000)
 Agent: EHEC strain O157:H7
 Shiga toxin -> cleaves host 28S rRNA
 Signs and symptoms: diarrhea, fever, abdominal cramps
 endothelial damage in different tissues
 Platelet-fibrin micro-clots form leading to
o Kidney failure (Hemolytic Uremic Syndrome)
o Skin hemorrhage (Purpura)
o Brain hemorrhage, neurological disorder, coma, &
death
Diagnosis: positive test for EHEC in food stock or in patient,
or testing positive for toxin
Treatment: cidal antibiotics not recommended due to toxin, statics in sever
cases, supportive treatment for electrolytes
Gastritis and Peptic Ulcer
• caused by Helicobacter pylori, a spiral
microaerophilic G- bacterium
• Discovered in 1982 and initially named
Campylobacter pylori
– colonizes gastric mucus-secreting
cells
– produces urease, elevates pH
– releases toxins that damage
epithelial mucosal cells
H. pylori attached to gastric cells
H. pylori …
• transmission probably from person to person
– common source has not been ruled out
• diagnosis
– culture of gastric biopsy specimens,
examination of stained biopsies, serological
testing, urea breath test, tests for ammonia in
urine, and detection of urease activity in
biopsies
• treatment, prevention, and control
– a combination of drugs to decrease stomach
acid and antibiotics to kill the bacteria
Viral Gastroenteritis
• acute viral gastroenteritis
– inflammation of stomach or intestines
– important disease of infants and children
– leading cause of childhood death in developing countries (5-10
million a year)
– usually spread by fecal-oral route
• caused by six major groups of viruses
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Rotaviruses
Adenoviruses
Caliciviruses
Asteroviruses
Norwalk virus
Noroviruses
Viral Gastroenteritis
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Asymptomatic to mild diarrhea
Headache and fever
Or sever diarrhea with abdominal cramps
Vomiting
Death is due to loss of electrolytes
• Treatment:
– usually self-limiting disease
– Electrolytic replacement with isotonic solutions
– symptomatic/supportive therapy