MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 5 OF 5 — FINAL — CYTOMEG
--- 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 IMMUNIZATI