Infectious Disease 1 to 10
What causes Hepatitis C infection?
- Flaviviridae family RNA Virus
Describe the clinical course of Hepatitis C infection.
- Incubation period 2-26 wks (mean 6-12 wks)
- Acute infection usually mild or asymptomatic (1-3 weeks)
- Persistent and Chronic hepatitis with exacerbations in 80%
- Cirrhosis in 20-30%
- Fulminant hepatic failure rare
- 3 out of 5
What are the risk factors for acquiring Hepatitis C?
- IVDU (54%)
- Multiple sex partners (36%)
- Needle stick (10%) ( risk of HCV is 1.8% v 0.3% for HIV)
- HCW (1.5%)
- Blood Transfusion (in the 1980’s),
- Unknown (32%)
- 3 out of 7
What features of the Hepatitis C virus make vaccine development difficult?
- Highly stable core, extremely variable envelope ( E protein)
- RNA polymerase inherently unstable; frequent mutations, multiple quasispeciesfound in any one pt
- Genomic and Antigenic variability
- Actively inhibits interferon mediated cellular response at many levels
Describe the pathogenesis of tuberculosis in a previously unexposed immunocompetent person.
- Infection by M. tuberculosis airborne
- M. tuberculosis usually person to person airborne droplet spread
- M tuberculosis enters alveolar macrophages and replicates
- Enters alveolar macrophages and replicates by blocking phagosome/lysosome fusion leading to bacteraemia (person generally asymptomatic or mild flu like illness
- Immunity through T cell mediated delayed type hypersensitivity reaction that also causes hypersensitivity and tissue destruction- in particular granuloma formation and caseation
- About 3 weeks later T cell activation via MHC antigens on macrophages and IL-2 leading to macrophage becoming bactericidal (thru IFN-gamma)
- This macrophage response also causes tuberculin positivity and formation of granuloma and caseation by recruiting monocytes (“epithelioid histiocytes”)
- Re- exposure or reactivation causes heightened immune reaction as well as tissue destruction
- Infection may be contained or may progress and may reactivate with immunosuppression from any cause
- Bold to pass
What micro-organisms cause malaria?
- Parasitic protozoa
- Plasmodium falciparum, vivax, ovale, malarie
- Falciparum PLUS 1
How does Plasmodium falciparum infection differ from other forms of malaria?
Prompt: How does it compare clinically? By what mechanism?
- All do: sporozoite -> liver -> merozoites formed -> release & bind to RBC -> Hb hydrolysed -> trophozoite -> schizont -> merozoite/gametocyte
- P. falciparum: infects RBCs of any age, causing clumping/rosetting so ischemia, high cytokine production, high level parasitemia, severe anemia, cerebral symps, renal failure, pul oedema, death
- Others: infect only new or old RBCs, P vivax & ovale form latent hynpnozoites (relapses), low parasitemia, mild anemia, rarely splenic rupture, nephrotic synd
- 2/3 Highlighted and 1 clinical feature
What factors can make people less susceptible to malaria?
- Inherited alterations in RBCs: HbS trait, HbC, Duffy Ag neg
- Repeated exposure stimulates immune response: Ab and T lymphocytes (P falc avoids this), HLAB53
- Bold to pass
What is the clinical spectrum of candida infection?
- Benign commensal
- Superficial mucosal infn – mouth, vagina, oesophagus
- Superficial cutaneous infn – intertrigo, nappy rash, balanitis, folliculitis, paronychia, onychomycosis
- Chronic mucocutaneous (T-cell defects, endocrinopathy)
- Invasive (disseminated) – myocardial/ abscess/endocarditis, cerebral abscess/meningitis, renal/hepatic abscess, endophthalmitis, pneumonia
- Bold to pass
What mechanisms enable candida to cause disease?
Prompt: What are the virulence factors?
- Phenotypic switching to adapt rapidly to changes in host environment
- Adhesion to host cells – imp. determ. of virulence –via adhesins (several types)
- Production of enzymes (aspartyl proteases and catalases) degrade extracellular matrix proteins and may aid intracellular survival
- secretion of adenosine – blocks neutrophil degranulation
- Pass – 1 out of 3 bold
Describe the clinical course of Hepatitis A infection.
- Oral faecal transmission.
- Incubation period: 2-6 weeks.
- No carrier state or chronic hep or cause hepatocellular Ca.
- Rarely causes fulminant hepatitis, and so the fatality rate is about 0.1%.
- 3 out of 4
How do the serological markers change with time in Hep A infection?
Describe the potential outcomes of acute hepatitis C infections in adults.
- Acute fulminant rare
- 15% resolve
- 85% chronic – >80% stable/20% cirrhosis (50% mortality) hepatocellular Ca
- 3 major points with most > chronic fulminant) and potential for cirrhosis/Ca
How does the serology for Hepatitis C infection change in case of resolution?
- Incubation period (2-26 weeks)
- HCV-RNA (detectable for 1-3 weeks co-incident with transaminitis)
- Anti HCV antibodies emerge. Only about 50% detectable during symptomatic acute infection. Remainder after 3-6 weeks. IgG/IgM. IgG persists
- All major points & ‘window’ when both virus & Ab may be –ve
- Diagram encouraged.
Name some clostridial diseases and causative organisms?
- Tetanus (lockjaw) – Clostridium tetani
- Botulism (paralytic food poisoning) – Clostridium botulinum
- Gas gangrene, necrotizing cellulitis – Clostridium perfringens, C. septicum
- Pseudomembranous colitis – Clostridium difficile
- 2 out of 4
What is the pathogenesis of gas gangrene (C. perfringens, C. septicum)?
- Release enzymes – hyaluronidase; collagenase
- Virulence factors – TOXINS
- multiple actions
- phospholipase C: degrades membranes; muscle; RBC
- release phospholipid derivatives: ITP; prostaglandins
- these cause derangement in cell metabolism and cell death
- Bold PLUS 2 others
Please give some examples of clinical Herpes Simplex Infection?
- Cold sores, Gingivostomatitis, Encephalitis, Genital herpes, Keratitis (epithelial & stromal)
- Disseminated visceral herpes (esophagitis, bronchopneumonia, hepatitis, Kaposi varicelliform eruption, eczema herpeticum)
- At least 3
After primary herpes simplex infection, how does reactivation occur?
- Viral nucleocapsids travel from the skin/ oropharynx/genitalia to the nucleus in the sensory neurone.
- During latent period, only viral mRNA is produced, no viral proteins are made to escape immune recognition.
- Reactivation from latency occurs by avoiding immune recognition, inhibiting the MHC class I recognition pathway, and elude humoral immune defences by producing receptors for the Fc domain of immunoglobulin and inhibitors of complement. Antidromically along sensory nerve
- 2 out of 3 to pass
What is the mode of transmission of the measles virus?
- Respiratory droplets
- Upper respiratory epithelial cells
Describe some of the systemic features of measles virus infection.
Prompt: One feature is croup or pneumonia. Tell me others?
- Rash–blotchy, red/brown. Skin hypersensitivity reaction
- Oral mucosal ulceration – Koplik’s spots
- Croup, or interstitial pneumonia
- Keratitis, with scarring and visual loss
- Encephalitis; – plus SSPE, measles inclusion-body encephalitis (immunocompromised)
- Diarrhoea with protein-losing enteropathy
- Secondary bacterial infection
- Rash and 3 others
What are the cell-surface receptors for the measles virus?
Prompt: One example is CD46. Tell me about this
- CD 46 ( complement regulatory protein): inactivates C3 convertases; present on all nucleated cells; binds viral haemagglutinin protein
- SLAM (Signalling Lymphocytic Activation Molecule): involved in T cell activation; only present on cells of the immune system; binds viral haemagglutinin protein
What are the different types of meningitis?
- Bacterial, aseptic/viral, chronic (TB, spiro, crypto)
- Chemical: nonbacterial irritant
- Ca, lymphoma
- Bold PLUS 1 other point
What organisms commonly cause bacterial meningitis?
- Neonates: E coli, grp B strep
- Children: Strep pneu, H flu reducing with vaccines
- Young adults: Neisseria meningitidis,
- Elderly: Strep pneum, Listeria
- Immunosuppressed: Klebsiella, anaerobes
- Bold PLUS 1 other
How do the cerebrospinal fluid findings typically differ between acute bacterial and viral meningitis?
- Cloudy, higher pressure, *more neutrophils, raised protein, *reduced glucose
- *lymphocytes, moderately raised protein, *normal glucose
- 3 to pass