--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 5 OF 5 — FINAL --- CYTOMEGA
--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 5 OF 5 — FINAL --- CYTOMEGALOVIRUS — FULL DETAIL Essay question in 2018/2019 and CAT 2020/2021 — 20 marks — very high priority. Causative agent - Cytomegalovirus — member of Herpesviridae family - Double stranded DNA virus - Enveloped virus - Largest of the human herpesviruses - Establishes latency like all herpesviruses Pathogenesis - Primary infection: virus enters via respiratory tract, genital tract, or oral route - Replicates in epithelial cells of respiratory and genital tract - Spreads to blood — viremia - Infects mononuclear cells — monocytes and lymphocytes - Establishes latency in mononuclear cells - In immunocompetent: infection usually asymptomatic or mild mononucleosis-like illness - In immunocompromised: reactivation occurs — virus replicates actively - Causes cytomegaly — infected cells become very large with characteristic owl-eye inclusion bodies - Owl-eye inclusion bodies in infected cells: pathognomonic of CMV Transmission - Contact with infected body fluids: saliva, urine, blood, semen, breast milk - Transplacental — congenital infection - Blood transfusion and organ transplantation - Sexual contact - Breastfeeding Who is most at risk - Newborns — congenital infection most serious - Immunocompromised: HIV/AIDS patients, transplant recipients - Newborns develop most virulent form of CMV infection Congenital CMV manifestations - Essay question — 10 marks in 2018/2019 - Petechial rash - Low birth weight - Hepatosplenomegaly — enlarged liver and spleen - Bilateral cataracts - Mental retardation - Microcephaly — small head - Sensorineural hearing loss - Jaundice - Thrombocytopenia - Chorioretinitis — eye involvement - Seizures - Answer in MCQ is always any/all of the above CMV in HIV/AIDS patients - CMV retinitis — leading cause of blindness in AIDS - CMV pneumonitis - CMV colitis - CMV encephalitis CMV in transplant patients - Most common viral infection post transplant - Reactivation of latent virus due to immunosuppression - Can cause rejection of transplanted organ Diagnosis - Essay question — 4 marks in 2018/2019 - PCR: detection of CMV DNA — most sensitive - Shell vial culture: rapid culture method - Serology: IgM for primary infection, IgG for past infection - Antigenemia assay: detection of pp65 antigen in leukocytes - Histopathology: owl-eye inclusion bodies in tissue - CMV in blood, urine, saliva, CSF depending on clinical presentation Prevention and treatment - Essay question — 4 marks - Antiviral prophylaxis: ganciclovir in transplant patients - Valganciclovir: oral form of ganciclovir - Foscarnet: alternative for ganciclovir-resistant CMV - Screening of blood products before transfusion - Avoid exposure during pregnancy - No vaccine currently available - Breastfeeding avoidance in seropositive HIV-positive mothers --- BASIC PRINCIPLE OF VACCINATION Essay question in 2017/2018 — 20 marks — very high priority. Basic principle - Vaccination works by introducing an antigen into the body - Antigen stimulates the immune system without causing disease - Immune system mounts a primary immune response - B cells produce specific antibodies - T cells are activated — both helper and cytotoxic - Memory B cells and memory T cells are formed - Memory cells persist long term - On exposure to real pathogen, memory cells mount rapid secondary immune response - Secondary response is faster, stronger, and more specific than primary - Pathogen is eliminated before disease can develop - This is immunological memory — the foundation of vaccination How vaccines prevent microbial infections - Antibodies: neutralize pathogen, prevent attachment to host cells - Opsonization: antibodies coat pathogen, enhance phagocytosis - Complement activation: antibodies activate complement, lyse pathogen - Cell-mediated immunity: cytotoxic T cells kill infected cells - Herd immunity: when enough population is vaccinated, pathogen cannot spread Types of vaccines Attenuated live vaccines - Contains live weakened pathogen - Strongest immune response - Stimulates both humoral and cell-mediated immunity - Long lasting protection, often single dose - Risk of reversion to virulence - Examples: OPV, MMR, yellow fever vaccine Inactivated vaccines - Pathogen killed by heat or chemical - Safer — cannot revert - Weaker immune response — may need boosters - Examples: IPV, hepatitis A vaccine, influenza vaccine Toxoid vaccines - Inactivated toxin - Stimulates antibodies against toxin - Examples: tetanus, diphtheria Subunit vaccines - Only specific antigens of pathogen used - Very safe - Examples: Hepatitis B vaccine, HPV vaccine OPV vs IPV - OPV: oral, attenuated, replicates in gut, stimulates mucosal immunity, risk of vaccine-derived poliovirus - IPV: injected, inactivated, no replication, no reversion risk, preferred in polio-free countries - IPV preferred because: cannot recombine, no neurologic complications, minimal side effects - OPV preferred in endemic areas because: cheaper, oral, stimulates gut immunity, herd immunity through fecal-oral spread --- ACTIVE VS PASSIVE IMMUNIZATION Section B comparison question. Active immunization - Vaccine or antigen administered - Body produces its own antibodies and memory cells - Takes days to weeks to develop full protection - Long lasting — permanent protection - Examples: all routine vaccines Passive immunization - Preformed antibodies given directly - No immune activation, no memory cells formed - Immediate protection - Temporary — lasts weeks to months only - Examples: HRIG for rabies, immunoglobulin for hepatitis A exposure, antivenom - Used when: immediate protection needed, patient cannot mount immune response --- ENTEROVIRUSES — FULL DETAIL Classification - Family: Picornaviridae - Naked capsid — no envelope - Single stranded positive sense RNA - Survive gastric acid and harsh conditions because of naked capsid Genera - Poliovirus - Coxsackievirus group A and group B - Echovirus - Enterovirus 70 and 71 Portal of entry - Alimentary tract — fecal-oral route - Some via respiratory route Diseases caused - Poliomyelitis — poliovirus - Hand, foot and mouth disease — Coxsackievirus A - Herpangina — Coxsackievirus A - Myocarditis and pericarditis — Coxsackievirus B - Aseptic meningitis — enteroviruses most common cause in children - Encephalitis - Acute hemorrhagic conjunctivitis — Enterovirus 70 - Hepatitis — Hepatitis A virus - Common cold — some enteroviruses All following belong to Picornaviridae EXCEPT Rabies virus Enteroviruses are one of the commonest causes of CNS infections in childhood --- PNEUMOCYSTIS JIROVECII — FULL DETAIL Classification - Previously called Pneumocystis carinii - Now classified as a fungus — not a protozoan - Present in lungs of humans and animals - Cannot be cultured on standard fungal media Pathogenesis - Inhaled from environment - Colonizes lungs of healthy individuals asymptomatically - In immunocompromised: uncontrolled proliferation causes pneumonia - Fills alveoli with foamy exudate - Impairs gas exchange Clinical features - Pneumocystis pneumonia — PCP - Dry cough, fever, progressive shortness of breath - Bilateral interstitial infiltrates on chest X-ray - Most common opportunistic infection in HIV/AIDS when CD4 below 200 Diagnosis - Bronchoalveolar lavage — BAL - Silver stain or immunofluorescence to detect cysts - PCR Treatment - Trimethoprim-sulfamethoxazole — TMP-SMX - Prophylaxis: TMP-SMX when CD4 below 200 Key MCQ fact - Budding yeast cells and abundant pseudohyphae are typical of Candida albicans NOT Pneumocystis — trick statement - Pneumocystis jirovecii causes pneumonia in immunocompromised patients --- HEMORRHAGIC FEVERS — ADDITIONAL DETAIL General features - Caused by RNA viruses - Affect multiple organ systems - Damage vascular system — bleeding and shock - High mortality Specific viruses - Ebola: fruit bats reservoir, contact with blood/body fluids,