Fall 2015 exam 2 OMSII CLIs

Clostridia spp.○ Pathogens:

○ Gram +, anaerobic, spore-forming rods○ C. difficile (antibiotic assocaited diarrhea and pseudomembranous colitis)○ C. perfringens (gas gangrene)○ C. botulinum (botulism, “floppy baby” after honey))○ C. tetani (tetanus)

○ Encounter:○ Mostly acquired from the environment○ colonize mammalian colon and are returned to the environment as spores from the feces

○ Entry:○ 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)○ Spread and multiplication:

○ Grow in anaerobic environment of GI or devitalized, anaerobic tissue of necrotic wound○ Damage:

○ Expression of disease depends on production of clostridial cytotoxins of neurotoxins○ Diagnosis:

○ For wounds: gram stains and culture under anaerobic conditions○ C. diff infection usually diagnosed by detecting toxins in feces○ Neurotoxic clostridial infections (tetanus- SPASMOTIC PARALYIS via GABA Inhibition and botulism-

FLACCID PARALYSIS via inhibiting ACH release)○ Treatment :

○ Wound infections – surgical debridement of tissues○ C. diff infection – metronidazole or vancomycin (PO only!)○ Tetanus and botulism – antitoxins

○ Prevention:○ Sterility in canning foods to prevent contamination with C. botulinum spores○ “toxoid” vaccine prevents tetanus○ Proper wound management○ Judicious use of antibiotics

Chlamydia spp.○ Pathogen:

○ Obligate intracellular gram-negative bacteria○ Encounter:

○ Genital, ocular, respiratory infections 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) –enfectious small extracellular infectious particles that attach to and enter into host cells but are metabolically inert (do not grow or divide)

○ Reticulate bodies (RB) – replicate. 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

Candida spp.○ 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.○ Pathogen:

○ 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

○ Encounter:○ Ubiquitous in soil, manure, and decomposing vegetation○ Usual hosts are those who are neutropenic, on corticosteroids, or other immunosuppressive

drugs, or transplant recipients○ Entry:

○ Conidia are inhaled into upper and lower respiratory tracts○ After entry is germination of conidia into hyphae which then invade tissues

○ Spread and multiplication:○ Neutrophils and macrophages are main host defense○ Angioinvasive fungus which can cause tissue infarction, hemorrhage, and necrosis

○ Damage:○ 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:○ Grow on Sabouraud agar○ Tissue biopsy for tissue invasion

○ Treatment:○ 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

TrypanosomesT. cruzi (Chagas disease)

○ Pathogenesis:○ 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

○ 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:

○ Blood culture, positive antibody titer○ Treat with nifurtimox or benznidazole○ No treatments for late complications

T. Brucei (African sleeping sickness)○ Pathogenesis and diagnosis:

○ 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:○ eflornithine

Adenovirus○ Pathogens:

○ Large, nonenveloped, DNA viruses with icosahedral symmetry○ Encounter:

○ Respiratory serotypes: exposure to aerosols or infected fluids (saliva)○ Enteric types: contamination with fecal matter

○ Entry:○ Initial site of replication in most cases is probably oropharynx

○ Spread:○ Most often cause mild infection of respiratory and GI systems○ Severe infections can cause keratoconjunctivitis and acute, severe

pneumonia○ Replication:

○ Temporal regulation of gene expression dependent upon viral regulatory genes

○ Employ both virally encoded and host proteins in the replication process○ Damage:

○ 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:

○ Recognition of clinical features○ Lab Dx not typically done except life-threatening situations (PCR)

○ Treatment/Prevention:○ 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○ 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) [Oct-April 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: ○ 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

Human Papilloma Virus○ Non enveloped, Double stranded, Circular

○ Soo many serotypes○ Encounter/Entry: direct skin to skin contact ie

sex; enters break in skin and sets in the basal layer of skin

○ Since it is non enveloped, it may live on inanimate objects. ○ Respiratory papillomatous: Vertical transmission during

birth;rare○ Oncogenic properties

○ E6- combines with p53- Induces Ubiquitylation proteolysis pathway and inhibits tumor suppression

○ E7- combines with Rb – prevents Rb exerting its normal check on cell proliferation

○ Damage: Warts or Cancer○ Warts-(serotypes 6, 11)

○ Condyloma Accuminata ○ Cancer

○ CIN, cervical cancer (most commonly 16, 18) ○ Diagnosis:

○ Warts- causing Verrucous finger like projections○ Cancer- shows atypia (Koilocytes),

○ Treatment/Prevention:○ Surgical excision ○ Cryotherapy○ Immunomodulators- Imiquimod○ Or it disappears on its on… via cell mediated response ○ Quad Valent Vaccine – 6/11/16/18 serotype protection. Uses

“ capsid like” proteins

Haemophilus influenzae

• Gram-negative, small rod, nutritionally fastidious [Grows on chocolate agar or on blood with another bacteria that can breakdown blood and provide nutrients]

• Multiple types, only type B has a capsule. It is esp associated with meningitis and there is a vaccine for just that type]

• Encounter: Throat, inhalation, hand contact• Pathogenic mechanism: Inflammation facilitated by resistance to

phagocytosis (capsule), endotoxin, IgA1 protease, pili, outer membrane protein

• Typical Dz: Meningitis (infants, 3mo-2y) w/ sequelae, respiratory infx/COPD exacerbation, cellulitis, epiglottitis [thumbprint sign]

From FA:• Culture on chocolate agar (requires factor V(NAD+) and X (hematin) for

growth)• Vaccine: conjugated polysaccharide vaccine [against type B], given

between 2-18 months

Klebsiella Pneumoniae ○ *** very little mention in the book***○ Pathogen:○ Gram Negative Rod, enteric○ Spread: Typically seen in Community Acquired Pneumonia,

Hospital Acquired Pneumonia ;○ Common Case scenario: chronic alcoholic or Diabetic who

aspirates and makes current jelly sputum○ Damage: Polysaccharide capsules- causing mucoid colonies○ Diagnosis: Xray: Shows FOCAL lobar consolidation

○ 4 A’s of KlebsiellA:○ Aspiration pneumonia○ Abscess in lungs and liver○ Alcoholics○ di-A-betics