Fall 2013 exam 2 OMSII CLIs

Herpes Simplex virus• 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.• Pathogens:

• Gram +, anaerobic, spore-forming rods• C. difficile (antibiotic assocaited diarrhea and pseudomembranous colitis)• C. perfringens (gas gangrene)• C. botulinum (botulism)• 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 and botulism) are usually recognized by clinical presentation

• Treatment :• Wound infections – surgical debridement of tissues• C. diff infection – metronidazole or vancomycin• Tetanus and botulism – antitoxins (and

• 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 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.• 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

• Encounter:• May be carried asymptomatically in genital tract (gonococcus) or nasopharynx (meningococcus)

• Entry:• 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:• 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:• 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:• 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:• 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:

• 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.• 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