Transfusion-Transmitted Infections (TTIs) - Lecture Notes PDF

‫كلية الطب‬ Transfusion Transmitted Infections Dr. Sozan Mohamed Fadl Head of Microbiology & Immunology Unit  Objectives By the end of this lecture, the student should be able to: Outline the measures used in blood banks to decrease the risk of trans...

‫كلية الطب‬ Transfusion Transmitted Infections Dr. Sozan Mohamed Fadl Head of Microbiology & Immunology Unit  Objectives By the end of this lecture, the student should be able to: Outline the measures used in blood banks to decrease the risk of transfusion-transmitted infection (TTI). Recognize the criteria for blood donation and the causes of rejection. Outline the factors that play a role in the establishment of TTI. Name the most common pathogens of TTI and describe their morphology, classifications, modes of transmission, pathogenesis and ways of diagnosis.  Introduction Blood transfusion is the process of receiving blood or blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood or as a therapy. Loading… Transfusion-transmitted infections (TTIs) are infections resulting from the introduction of a pathogen into a person through blood transfusion.  Most Common Infectious Diseases Transmitted by Blood Transfusion: RNA Viruses: Protozoa: – HIV - Plasmodium – HTLV - Toxoplasma – HCV Bacterial DNA Viruses: contamination – HBV Treponema – Epstein-Barr virus Prions – Cytomegalovirus Currently 72 agents can – Human Herpesvirus 8 be acquired by blood – Parvovirus (B19) transfusion  Reducing the risk of TTI: – The use of a standard donor screening questionnaire. – Screening of the donated blood: PCR, Bacterial culture Antigen and antibodies detection. Loading… Tested organisms: HBV, HCV, HIV, HTLV, and Syphilis – Pathogen inactivation technique: The process of treating the blood component by certain chemicals and/or UV light to inactivate the infectious agents. 1- Age: 17-65Criteria years old.for Blood Donation: 2- Weight: 50 Kg or above. 3- Pulse Rate: Normal. Body temperature: Normal. Blood pressure: Normal. Hemoglobin concentration: > 12 grams/dL (women) and 13 grams/dL (men). 4- Medical History: Epilepsy, psychotic disorders, abnormal bleeding tendencies, thalassemia, sickle cell anemia, malignancy are permanently unfit for blood donation. 5- Infection: HIV, Hepatitis, Malaria, syphilis.  Factors of Establishment of Transfusion transmitted Infection: 1- Viral Window Period. o The period between acquiring the viral infection to its detection by laboratory tests o False-negative results. o Range between few days to 6 months, e.g., the window period of HIV is 11-180 days depending on the test type. 2- Bacterial contamination. 3- Asymptomatic immuno-competent donors. 4- Laboratory errors 5- Personal error.  Humanagent The causative Immunodeficiency Virus (HIV) of acquired immunodeficiency syndrome (AIDS) Virology: enveloped SS RNA viruses. Classification: Family: Retroviridae. Species: HIV-1 and HIV-2. Transmission of HIV: Sexual transmission. Parenteral: Blood transfusion, needle stick injury, sharing needles. Tissue transplantation. Vertical: pregnancy, childbirth, and breastfeeding. HIV replication cycle: Adsorption: to T helper cells, macrophages and dendritic cells. Uncoating: release of viral RNA. Converting the viral RNA genome into DNA by a virally encoded reverse transcriptase. The viral DNA is integrated into the cellular DNA by a virally encoded integrase Transcription and protein synthesis. Assembly Release by budding. Some of the viruses will remain in a latent stage for a long period. Loading…  Human T-cell Lymphotropic Virus (HTLV) Virology: Single-stranded, enveloped RNA viruses Classification: Family: Retroviridae. Target cells: T helper cells: HTLV is an oncogenic virus known to cause adult T-cell leukemia and lymphomas. Transmission: Sexual route. Blood transfusion. Vertical transmission. Breast-feeding.  Hepatitis C virus: Virology: Enveloped, SS RNA virus. Oncogenic virus: Hepatocellular carcinoma Transmission: Parenteral: Needle sharing, needlestick, blood transfusion, dialysis Organ transplantation Rare: Sexual and vertical transmission (during birth)  Hepatitis B Virus Classification: Family: Hepadnaviridae. Virology: - Double-stranded, icosahedral DNA virus. - Different forms exist in the patients’ blood: - Complete infectious viruses - Filamentous and spherical bodies without a core: They are none infectious lipids and proteins that form the Hepatitis B surface antigen (HBsAg). HBV is an oncogenic virus: Hepatocellular carcinoma  Transmission: Sexual. Parenteral: Contaminated needles or instruments (piercings, tattoos, and acupuncture), blood transfusion. Organ transplants Vertical transmission during birth. Prevention: Vaccine made of surface antigen (HBsAg)  Virology: Epstein-Barr virus (EBV) - Enveloped Ds DNA virus. - Derives envelope from nuclear membrane - Establishes latency in the B lymphocytes. Classification: Family: Herpesviridae. Transmission: Through body fluids, especially saliva: 90-95% of the adult population are seropositive. Blood transfusion and organ transplantations. Sexual contact. Pathogenesis: EBV infects the epithelial cells of the oropharynx then infect the B lymphocytes: Uncontrolled function → heterophile antibodies production Hyper activation of T cells→ atypical T lymphocytes (Downey cells). Uncontrolled multiplication→ lymphomas Latency and reactivation → shedding of EBV in saliva → infect others.  Disease: Mostly asymptomatic Infectious mononucleosis (Kissing disease; glandular fever): o Fever o Myalgia & fatigue o Pharyngitis o Lymphadenopathy o Hepatosplenomegaly o Maculopapular skin rash → specially after amoxicillin treatment. Oral hairy leukoplakia (in HIV patients)  Complications: Splenic rupture (activity restriction, avoid trauma) Malignancies: Lymphoma Nasopharyngeal carcinoma Diagnosis: Monospot test detect the heterophile antibodies. Peripheral smear: lymphocytosis with > 10% atypical lymphocytes (in some cases, up to 90%) PCR to detect the viral DNA. Serology: Anti-EBV antibodies.  Cytomegalovirus (CMV) Virology: - Family: Herpesviridae. - Enveloped Ds DNA virus. - Establishes latency in mononuclear cells e.g., monocytes & macrophages. - Intra-nuclear inclusion; owl eye - Most common cause of congenital disease. Transmission: Body fluids specially saliva; (up to 80% of the adult are infected) Sexual Vertical: transplacental, during birth, breast feeding Blood transfusion, tissue transplantation. Diseases: In immunocompetent patients: - > 90%: asymptomatic - < 10%: heterophile negative mononucleosis syndrome In immunocompromised patients: – Interstitial pneumonitis, retinitis, encephalitis, colitis. Congenital CMV infection (fetus): Diagnosis: PCR to detect the viral DNA. Serology: Anti-CMV antibodies. Peripheral smear: lymphocytosis with atypical lymphocytes (Downey cells)  Kaposi’s Sarcoma-Associated virus (HHV-8) Virology: Same as Epstein-Barr virus and CMV. Classification: Family: Herpesviridae. Transmission: Sexual, saliva, transplacental. Pathogenesis: HHV-8 has a gene that turns on vascular endothelial growth factor→ development of Kaposi Sarcoma. Disease: Kaposi Sarcoma: tumor of the endothelial cells.  Parvovirus B19 Virology: Non-enveloped, icosahedral, SS DNA virus. Transmission: Inhalation, vertical, and blood transfusion. Pathogenesis: replicates in the upper respiratory tract then spreads to the bone marrow → kills erythroid precursor cells Disease: Fetus: severe anemia, abortion. Children: erythema infectiosum (fifth disease, slapped cheeks disease). Adults: polyarthritis Patients with chronic hemolytic anemia (e.g., sickle cell  Bacterial Contamination Due to improper donor skin disinfection, contaminated donation equipment, or donor bacteremia. Decreased by: o Disinfect the skin by chlorhexidine & alcohol or iodine & alcohol. o Gram staining & culture of blood. Transmitted bacteria: Gram–positive bacteria: - Staphylococcus epidermidis - Staphylococcus aureus - Cutibacterium acnes. Gram-negative bacteria (Enterobacteriaceae): - Escherichia coli (E. coli), Klebsiella, Proteus, …. - Yersinia enterocolitica is the most common due to  Treponema pallidum Bacteriology: - Thin spirochete. Basically, it has Gram’s negative cell wall - Axial filaments present (endoflagella). Transmission: sexually, Vertical: transplacental or during birth blood transfusion. Disease: Syphilis  a Diagnosis: Cannot be cultured in vitro. 1-PCR 2-Microscopy: Darkfield, immunofluorescent, light microscope (silver stain). 3-Serology: Nonspecific antibodies: anti-cardiolipin antibodies. Treponemal antibodies: Detect anti-treponema antibodies by TPHA test.  Plasmodium Etiology: Plasmodium species P. vivax, P. malariae, P.ovale, P. falciparum. Classification: Sporozoa. Obligate intracellular protozoa. Transmission: Loading… Bite of infected female Anopheles mosquito, transplacental, and blood transfusion. Pathogenesis: Infect the hepatocytes and the RBCs  Plasmodium life cycle: a schizonts Ring stage  Clinical Features: https://next.amboss.com/us/article/Kf0UM2?q=malaria Incubation period: …..-…… days General Symptoms: 1. 2. 3. Organ Specific symptoms: Blood: ………………… ………………….. Liver: …………………………….. CNS: …………………………… Diagnosis: Rapid antigen detection test. a Microscopy: Stained blood film to detect the stages of plasmodium: – Ring stage. – Schizonts. – Gametocyte.  Toxoplasma gondii Classification: Sporozoa. Obligate intracellular protozoa. Transmission: Oral ingestion: – Oocysts: directly from cats' feces or from contaminated food and water – Tissue cyst: in raw or undercooked meat. Transplacental transmission. Blood transfusion or organ transplantation Diseases: o Immunocompetent patients: asymptomatic (∼ 90%) or mononucleosis-like symptoms (negative heterophile) o Latent infection. o Fetus & immunosuppressed patients: infect the brain, eyes, lungs, heart, and other organs  4 5 1 2 3 Study Smart not Hard  Types of Organisms Enveloped RNA viruses: Spirochete: Protozoa: Enveloped Ds DNA viruses: Non-enveloped Ss-DNA viruses:  Group the organisms by similarities Oncogenic viruses: Vertical Transmitted 1. Organisms: 2. 1. 3. 2. 3. 4. 4. 5. 5. 6. 7. 8. 9.  Match A. Aplastic crisis in 1. Epstein-Barr virus chronic hemolytic 2. Cytomegalovirus anemic patients 3. Human Herpesvirus B. Heterophile 8 negative 4. Parvovirus (B19) mononucleosis 5. Plasmodium C. Syphilis 6. Treponema D. Malaria. Erythema infectiosum. Lymphoma G. Kaposi sarcoma  1 A boy is brought to the physician because of fever, fatigue, and throat pain. Physical examination shows cervical lymphadenopathy and inflamed tonsils. A peripheral blood smear shows lymphocytosis with atypical lymphocytes. A heterophile antibody test is positive. Which of the following is the most appropriate recommendation by the physician? 1. Start amoxicillin therapy 2. Start anti-HIV therapy 3. Avoid cat contact 4. Avoid violent sports Organism Name Transmission Diseases HIV/ HTLV HCV HBV EBV CMV HHV-8 Parvovirus Treponema Plasmodium Toxoplasma Organisms Mood of Transmission HIV/ HTLV Parenteral, sexual, vertical HCV Parenteral, sexual, vertical HBV Parenteral, sexual, vertical EBV Saliva, blood transfusion, tissue transplantation, sexual HHV-8 Saliva, blood transfusion, tissue transplantation, sexual. CMV Saliva, blood transfusion, tissue transplantation, sexual, vertical. Parvovirus Inhalation, blood transfusion, vertical Treponema Sexual, blood transfusion, tissue transplantation, vertical Toxoplasma Cats' feces, ingestion, blood transfusion, tissue transplantation, vertical Plasmodium Arthropod, blood transfusion, tissue transplantation, vertical  References Lippincott Illustrated Reviews of Microbiology, 4th edition, Cynthia Nau Cornelissen. https://www.moh.gov.sa/en/HealthAwareness/Edu cationalContent/PublicHealth/Pages/017.aspx https://next.amboss.com/us/article/lS0v-2? q=HCV https://next.amboss.com/us/article/OS0I-2? q=HbV https://next.amboss.com/us/article/nf0752#Lb4c4 5480fdeddb516ce3b06ca475ca42 https://next.amboss.com/us/article/Lf0w52?