--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 3 OF 3 --- ADENOVIRUSES Ess
--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 3 OF 3 --- ADENOVIRUSES Essay question in 2018/2019 and CAT 2020/2021 — high priority. Modes of transmission - Respiratory droplets — most common - Fecal-oral route - Direct contact with infected secretions - Contaminated water — swimming pools - Eye-to-eye contact - Associated diseases - Respiratory: pneumonia, bronchitis, common cold - Eye: conjunctivitis, keratoconjunctivitis - GIT: gastroenteritis, diarrhea - Urinary: hemorrhagic cystitis - CNS: encephalitis - Pharyngoconjunctival fever - Prevention strategies - Live oral vaccine available for military personnel - Good hygiene and handwashing - Avoid sharing towels and personal items - Adequate chlorination of swimming pools - Isolation of infected individuals - --- HEMORRHAGIC FEVER VIRUSES Essay question in CAT 2020/2021. Transmission to humans - Contact with infected animals or their excretions - Bite of infected arthropod vectors — mosquitoes, ticks - Direct contact with blood or body fluids of infected person - Nosocomial transmission in healthcare settings - Bushmeat handling - Viruses that cause hemorrhagic fever - Ebola virus - Marburg virus - Lassa fever virus - Yellow fever virus - Dengue virus - Rift Valley fever virus - Crimean-Congo hemorrhagic fever virus - --- VIRAL RECEPTORS AND SPIKES Essay question in 2017/2018 — high priority. Clinical importance of viral receptors - Attachment: viral spikes/receptors mediate attachment to host cell surface — most important step in viral life cycle - Specificity: virus only affects cells expressing specific receptor — determines tissue tropism - Entry: receptor binding triggers viral entry into host cell - Cell signalling: some viral receptors trigger intracellular signalling - Maintenance of cellular structure - Complement mediated lysis - Vaccine development: receptors and spikes are targets for vaccine design - Development of antiviral drugs: blocking receptor-ligand interaction - Viral structure proteins and functions - Capsid: protection of viral genome - Reverse transcriptase: replication - Glycoprotein receptors: attachment - HA: binding and attachment - NA: transmission, cleaves sialic acid, aids release of virus - Examples of viral receptors - HIV: uses CD4 receptor and CCR5/CXCR4 co-receptors on T-helper cells - Influenza: HA binds sialic acid receptors - EBV: binds CD21 on B lymphocytes - Rabies: binds acetylcholine receptors on neurons - Poliovirus: binds CD155 on intestinal cells - --- ENTEROVIRUSES Classification - Member of Picornaviridae family - Naked capsid — survives gastric environment - Transmitted via alimentary/fecal-oral route - Genera - Poliovirus - Coxsackievirus — groups A and B - Echovirus - Enterovirus - Diseases caused - Poliomyelitis - Hand, foot and mouth disease - Herpangina - Myocarditis - Meningitis - Hemorrhagic conjunctivitis — caused by enterovirus - Hepatitis — Hepatitis A virus - Acute hemorrhagic conjunctivitis caused by: enterovirus All following belong to Picornaviridae EXCEPT: Rabies virus — trick MCQ All following viruses disseminated throughout body EXCEPT: Human papilloma virus Viruses transmitted by respiratory routes EXCEPT: Human papilloma virus --- MUMPS AND MEASLES Mumps - Caused by paramyxovirus - Target site: parotid gland - Testes, ovaries and pancreas can also be involved - Vaccine exists — MMR vaccine - Active immunization prevents disease - Second episodes cannot occur — only one serotype - Diagnosis NOT made only on clinical grounds — serology available - Transmitted by respiratory droplets - Measles - Caused by paramyxovirus - Encephalitis after measles: post-infectious encephalomyelitis — NOT direct - Paramyxovirus causing serious croup: RSV - Rubella causes teratogenic effects — NOT measles - --- RUBELLA- Caused by Rubivirus - Only virus that causes teratogenic effects - Baby born at 39 weeks with petechial rash, low birth weight, hepatosplenomegaly, bilateral cataracts — acquired in utero: Rubella virus - Congenital rubella syndrome — classic presentation - --- VIRAL LABORATORY DIAGNOSIS Cell cultures - Neutralization test: mainstay of identification of poliovirus isolate - Haemagglutination inhibition test: mainstay of identification of respiratory viruses - Presence of cytopathic effect is NOT the only way to detect a virus - Viruses cannot only be cultured using cell lines — other methods exist - Whole blood is NOT specimen of choice for many common viruses - Methods to identify virus infected host cell - Immunofluorescence test - Haemagglutination test - Immunoblotting test - All of the above - Antiviral drugs acting by inhibition of viral DNA polymerase - Effective against: Cytomegalovirus - NOT influenza, measles, mumps, rabies — these are RNA viruses - --- RISK FACTORS FOR FUNGAL INFECTIONS Essay question — appears in multiple papers. - Immunosuppression: HIV/AIDS, CD4 below 200 - Post-transplantation and use of immunosuppressive drugs - Prolonged use of broad-spectrum antibiotics — disrupts normal flora - Prolonged use of corticosteroids - Diabetes mellitus - Malignancies: leukemia, lymphoma - Extreme ages: very young and very old - Indwelling catheters and IV lines - Prolonged hospitalization - Neutropenia — low neutrophil count - Pregnancy — increases risk of candidal vaginitis - --- VIRULENCE FACTORS OF FUNGI Essay question — appears in multiple papers. Capsule - Cryptococcus neoformans: polysaccharide capsule — major virulence factor - Mediates attachment, inhibits phagocytosis, evades immune response - Phospholipases - Enzymes that degrade cell membranes to allow pathogens to escape phagosomes - Promote pathogen spread - Melanin production - Produced by Cryptococcus and Paracoccidioides brasiliensis - Protects against oxidative killing by macrophages - Dimorphism - Ability to switch between mold and yeast forms - Yeast form resists phagocytosis at body temperature - Antigenic variation - Plasmodium undergoes antigenic variation to avoid immune defenses - Note: Plasmodium is a parasite but this MCQ appears in mycology section - Adhesins - Ligands on cell walls of certain fungi mediate attachment to host cells - Enzyme production - Proteinases, lipases degrade host tissue - Urease: produced by Cryptococcus — aids tissue invasion - --- LABORATORY DIAGNOSIS OF SYSTEMIC MYCOSES Essay question in 2017/2018. Specimen collection - Sputum, BAL, blood, CSF, tissue biopsy depending on site - Microscopy - KOH wet mount: dissolves keratin, reveals fungal elements - India ink: capsule of Cryptococcus - Calcofluor white: fluorescent stain for fungal cell walls - PAS stain: fungal cell wall appears red - Gram stain: not reliable for fungi - Culture - Sabouraud dextrose agar: standard fungal culture medium - pH 4-6, incubated at 25-30°C - Histoplasma: takes weeks, slow growing - Candida: creamy mucoid colonies - Cryptococcus: creamy mucoid colonies, urease positive - Serology - Latex agglutination: Cryptococcus capsular polysaccharide antigen - Complement fixation: Histoplasma and Coccidioides - IgM detection: early infection - Identification of dimorphic fungi - Many saprobic molds resemble dimorphic mycotic agents at 30°C - Identification must be confirmed by conversion to tissue form in vitro OR detection of species-specific antigens or DNA sequence analysis - Germ tube test: rapid presumptive identification of Candida albicans - NOT Candida glabrata — trick MCQ - --- DIMORPHISM IN SYSTEMIC FUNGI Essay question — describe dimorphism in relation to systemic fungi. - Dimorphic fungi exist in two forms depending on temperature - Mold/filamentous form: at environmental temperature 25-30°C — asexual and sexual spores produced - Yeast form: at body temperature 37°C — this is the parasitic form in tissue - The switch is temperature dependent and is key to pathogenesis - Dimorphic systemic fungi: Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides