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Fall 2013 exam 2
OMSII CLIs
Herpes Simplex virus
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Pathogen:
• Alphaherpesvirus
• DsDNA virus
• HSV Type I and II and Varicella- Zoster crius (VZV)
Encounter:
• Almost all individuals become infected with HSV type I
• Most infections are asymptomatic
Entry:
• HSV Acquired by direct contact. VSV is usually acquired from infectious aerosols
Replication & spread:
• Establish latent infections following primary infection allowing virus to persist for life of the infected
host; can reactivate
Damage:
• Cause oral and genital herpes and occasionally encephalitis
• HSV I – primarily oral
• HSV II – primarily genital
• VZV – causes chicken pox and shingles
Diagnosis:
• Clinical presentation and virus deteciton in lesion samples, virus isolation in cell culture, or PCR
Treatment:
• Antivirals such as acyclovir. However, doesn’t prevent future recurrence
• Vaccine to prevent VZV
Clostridia spp.
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Pathogens:
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Gram +, anaerobic, spore-forming rods
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C. difficile (antibiotic assocaited diarrhea and pseudomembranous colitis)
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C. perfringens (gas gangrene)
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C. botulinum (botulism)
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C. tetani (tetanus)
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Encounter:
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Mostly acquired from the environment
colonize mammalian colon and are returned to the environment as spores from the feces
Entry:
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Ingestion of clostridial spores in context of antibiotic therapy
Contamination of wounds with soil
Botulism can occur after ingestion of preformed clostridial neurotoxin in contaminated food (does not necessarily change appear or taste of
food)
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Spread and multiplication:
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Damage:
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Diagnosis:
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Expression of disease depends on production of clostridial cytotoxins of neurotoxins
For wounds: gram stains and culture under anaerobic conditions
C. diff infection usually diagnosed by detecting toxins in feces
Neurotoxic clostridial infections (tetanus and botulism) are usually recognized by clinical presentation
Treatment :
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Grow in anaerobic environment of GI or devitalized, anaerobic tissue of necrotic wound
Wound infections – surgical debridement of tissues
C. diff infection – metronidazole or vancomycin
Tetanus and botulism – antitoxins (and
Prevention:
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Sterility in canning foods to prevent contamination with C. botulinum spores
“toxoid” vaccine prevents tetanus
Proper wound management
Judicious use of antibiotics
Chlamydia spp.
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Pathogen:
• Obligate intracellular gram-negative bacteria
Encounter:
• Genital, ocular, respiratory infecitons in humans
• Certain animal and avian isolates cause disease
Entry:
• Sexually transmitted
• Human-to-human droplet spread
• Contact with infected animals
Spread:
• Undergo unique developmental cycle within eukaryotic host cells
Multiplication:
• 2 distinct morphological forms:
• Elementary bodies (EB) – small extracellular infectious particles that attach to and enter into host cells but are
metabolically inert (do no grow or divide)
• Reticulate bodies (RB) – derived from EBs after uptake by cells; larger, intracellular, noninfectious but
metabolically active forms; divide by binary fission within membrane-bound inclusion in eukaryotic host cells
Damage:
• Most damage related to host hypersensitivity reaction
Diagnosis:
• PCR (genital infection) or serologic diagnosis
Treatment and prevention:
• Chlamydiae are sensitive to macrolides, tetracyclines, and fluoroquinolones
Neisseria spp.
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Pathogens:
• N. gonorrhoeae (gonococcus)
• N. meningitidis (meningococcus)
• Gram – diplococci [LPS in Neisseria is also called lipoligosaccharide (LOS) because Neisseria do not produce O antigen]
• Do not have niche outside human host
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Encounter:
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Entry:
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Local gonococcal infection damages GU epithelium causing urethral discharge of pus and leads to urinary pain
Meningococcal septicemia is life-threatening (DIC and meningitis)
Diagnosis:
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Colonize mucosa with pilus and replicate there
Gonococci produce IgA protease (protects against antibodies)
Surface structures undergo phase variation and antigenic variation, enabling them to avoid immune detection
Both can enter bloodstream; only meningococci produces capsule
Damage:
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N. gonorrhoeae is sexually transmitted in men & women; can lead to PID in women and epididymitis in men
N. meningitidis is spread from person to person by respiratory droplets and may cause septicemia and meningitis
Spread and multiplication:
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May be carried asymptomatically in genital tract (gonococcus) or nasopharynx (meningococcus)
Gram stain from genital tract (gonococcus) or CSF (meningococcus)
Chocolate agar for culture Thayer-Martin medium and Martin- Lewis medium (contain unique antibiotics)
PCR widely used for screening
Treatment of prevention:
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Both require antibiotics; resistance is a concern with gonococci
Meningococcal vaccine consists of mixture of all capsule types except serogroup B
Serogroup B vaccine (not available in USA) target protein antigens. Serogroup B capsule is homopolyer of sialic acid that
is identical to human sialic acid polymers. It is poorly immunogenic and dosed not normally elicit protective antibodies.
Group B Streptococci (GBS)
• Pathogen:
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Gram +, cocci, catalase negative, β-hemolysis, bacitracin resistant
Strict human pathogen
Leading cause of neonatal sepsis and meningitis
Polysaccharide capsule (evades opsonization and phagocytosis)
• Encounter:
• Common inhabitant of the lower GI and female genital tracts
• Women screened at 35-37 weeks of gestation with vaginal and rectal swabs; if
positive, given intrapartum antibiotics
• Not a cause of significant disease in healthy people
• Spread:
• Congenital and human-to-human contact
• Multiplication:
• Extracellular growth of organisms occurs on mucous membranes, in skin, or in
deeper tissue
• Damage:
• Infants who survive neonatal sepsis from GBS can have long-term problems
(seizures, deafness, developmental delay, and motor deficits)
• Pregnant women can get UTI, endometriosis, amnionitis
Candida spp.
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Pathogen:
• Round or oval yeasts that reproduce by forming buds or blastoconidia
• Potential to form hyphae in vivo
• C. albicans (most infections), C. glabrata (resistant to some antifungal agents), C. parapsilosis (central venous catheter associated
infections)
Encounter:
• Normally colonize GI tract (mouth to rectum), vagina, and skin
• Most infections endogenous
• Immunosuppressed (especially neutropenic and ICU patients.)
• Risk factors: broad-spectrum antibiotics, renal failure requiring dialysis, central venous catheters, parenteral nutrition
Entry:
• Disruption of normal flora will cause opportunistic infection
• Decreased T- cell immunity allows proliferation
• Neutropenia and central venous catheters
Spread and multiplication:
• Main host defense in T-cell mediated immunity (protects against mucosal surfaces)
• Neutrophils protect from spread through mucosa and subsequent dissemination
Damage:
• Mucosal candidiasis – adherent white plaques on oropharyngeal and vaginal mucosa (thrush); non-painful
• Proliferation in warm moist areas (intertriginous candidiasis and diaper rash)
• Underlying tissues are not damaged
• Candidemia is dissemination which can cause microabscesses in many organs, meningitis, chorioretinitis and vitritis, hepatosplenic
abscesses, and vertebral osteomyelitis. Endocarditis on prosthetic valves.
Diagnosis:
• Scrapings of lesion show budding yeast and pseudohyphae
• Blood culture for disseminated candidiasis with blood agar or Sabouraud agar (selective for fungi).
• C. albicans can be differentiated by development of germ tubes when exposed to calf serum
Treatment and prevention:
• Local antifungal topical creams/powders
• Invasive/disseminated infection can be treated with systemic fungal agent fluconazole or amphotericin B
Aspergillus spp.
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Pathogen:
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Encounter:
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Presents initially as pulmonary or sinus infection
Histopathologically seen are hemorrhagic infarction and necrosis; acutely branching septate hyphae seen invading
through tissues
Invasive pulmonary aspergillosis will show fever, pleuritic chest pain, cough, hemoptysis, and dyspnea
Disseminated aspergillosis include: necrotic skin lesions and brain abscess
Diagnosis:
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Neutrophils and macrophages are main host defense
Angioinvasive fungus which can cause tissue infarction, hemorrhage, and necrosis
Damage:
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Conidia are inhaled into upper and lower respiratory tracts
After entry is germination of conidia into hyphae which then invade tissues
Spread and multiplication:
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Ubiquitous in soil, manure, and decomposing vegetation
Usual hosts are those who are neutropenic, on corticosteroids, or other immunosuppressive drugs, or transplant
recipients
Entry:
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Filamentous fungi that form mycelium of septate hyphae
Reproduce by forming conidia on aerial conidiophores
Major pathogenic species are A. fumigatus and A. flavus
Not part of normal flora of humans
Grow on Sabouraud agar
Tissue biopsy for tissue invasion
Treatment:
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Invasive aspergillosis – voriconazole, amphotericin B, or echinocandin is used
Empiric treatment often initiated based on clinical manifestations and CT scan results
Plasmodium
• Organism:
• Protozoa
• Malaria caused by P. falciparum, P. vivax, P. ovale, and P. malariae
• Encounter and entry:
• Transmission through bite of infected female anopheline mosquitoes (saliva)
• Spread and multiplication:
• Sporozoite is the infectious form present in mosquitoes that is transmitted to humans
• Sporozoites enter liver cells which mature, multiply, and are released as merozoites (form
that invades RBCs)
• Merozoites divide and mature inside RBCs and release new infective merozoites; a minority
form gametocytes
• Damage:
• Fever, chills, anemia
• Can cause splenomegaly
• Diagnosis:
• Giemsa-stain
• P. vivax have Schüffner dots
• Treatment:
• Chloroquine
• Chloroquine resistant P. falciparum can be treated with Malarone, Coartem, quinine +
doxycycline, or quinidine
Trypanosomes
T. cruzi (Chagas disease)
• Pathogenesis:
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Bite of infected reduviid bug (“kissing bug”) (fecal matter)
Chancre or tissue and lymph node swelling at bite site
Most develop mild disease w/ fever, recover spontaneously, and remain asymptomatic
Small proportion develop complications 10-20 years later
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damage to nerves in GI tract (megaesophagus, megacolon)
Conducting tissue in heart (right bundle branch block)
Heart muscle (cardiomyopathy)
Fibrosis is the hallmark of pathology
Diagnosis and treatment:
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Blood culture, positive antibody titer
Treat with nifurtimox or benznidazole
No treatments for late complications
T. Brucei (African sleeping sickness)
• Pathogenesis and diagnosis:
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Bite of infected tsetse flies (saliva)
Undergo antigenic variation of its immunodominant surface antigen (variable surface glycoprotein)
Reservoirs are wild game animals in East Africa (takes only months to reach CNS); humans and domestic animals in
West Africa (takes years to reach CNS)
Bouts of systemic illness with fever and swollen lymph nodes; can eventually reach brain and CNS and infect brain and
spinal fluid. During each bout, undergo surface antigen rearrangement (genetic rearrangement).
Treatment:
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eflornithine
Adenovirus
• Pathogens:
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Large, nonenveloped, DNA viruses with icosahedral symmetry
• Encounter:
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Respiratory serotypes: exposure to aerosols or infected fluids (saliva)
Enteric types: contamination with fecal matter
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Initial site of replication in most cases is probably oropharynx
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Most often cause mild infection of respiratory and GI systems
Severe infections can cause keratoconjunctivitis and acute, severe pneumonia
• Replication:
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Temporal regulation of gene expression dependent upon viral regulatory genes
Employ both virally encoded and host proteins in the replication process
• Damage:
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Evade antiviral host defenses (prevent host cells from expressing MHC proteins, mediate resistance
to TNF, abrogate interferon response, and antigenic diversity)
Infection can be fatal in immunocompormised
• Diagnosis:
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Recognition of clinical features
Lab Dx not typically done except life-threatening situations (PCR)
• Treatment/Prevention:
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No vaccine available
No antiviral drug
Influenza virus
• Pathogen:
• Segmented negative-sense RNAs
• 3 types: A, B, and C (type A can infect animals)
• Possess hemagglutinin (HA) and neuraminidase (NA) as major surface antigens
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antigenic drift is caused by yearly accumulation of mutations in HA and NA
Antigenic shift results from acquisition of a novel HA and NA by the virus
• Encounter: influenza occurs in epidemics and pandemics in the winter (seasonality) [OctApril Peak incidence in December. ]
• Entry: person-to-person and respiratory droplets that infect URT and LRT
• Spread: cell infection initiated by attachment of the viral HA to sialic acid-containing
glycoproteins or glycolipids and subsequent uptake into an endocytic vesicle
• Replication: gene transcription and RNA replication occur in the nucleus
• Damage: causes clinical symptoms, including common cold, pharyngitis, tracheobronchitis,
and bronchiolitis or croup in children
• Diagnosis: virus isolation from sputum and nose/throat swabs; rapid diagnostic tests available
• Treatment/Prevention:
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rimantadine and amantadine (inhibit viral uncoating after uptake) These are NA inhibitors (inhibit viral release from infected cell and cause aggregation of viral
particles). So it won’t help symptomatic patients.
Vaccines: inactivated vaccine or the live, attenuated, cold-adapted vaccine