1. Transfusion-Transmitted Infections

2. Introduction Blood transfusion is the process of receiving blood or blood products into circulation intravenously

3. Used in a variety of medical conditions to replace lost components of the blood such as: Inherited blood diseases: Thalassemia, hemophilia, sickle cell anemia Hemolytic anemia of newborn. Bleeding: Post –traumatic, operative Malignancy: leukemia Other conditions: hepatic coma, kidney failure

4. Procedure for Voluntary Blood Donation Pre-Donation: Donor Screening Donor Consent Form Medical examination Blood Donation: o Blood donation procedure Post donation  Rest, advice & refreshment  Donor Certificate, Donor ID card

5. Criteria for Blood Donation (WHO Recommendations) Donors are evaluated for safety according to the following criteria: Age: 18-55 years old Weight: 50 Kg or above Pulse Rate: Normal 60–100 per minute and a regular rhythm Body temperature: Normal 36- 37.6°C

6. Blood pressure: Normal(systolic 120– 129 mmHg, diastolic 80–89 mmHg) Hemoglobin concentration: 12.5 g/dl for females and 13.5 g/dl for males Medical History, epilepsy, psychotic disorders, bleeding tendencies, thalassemia, sickle cell anemia, malignancy Infections: HIV, hepatitis, malaria, syphilis

7. How much blood can be taken during blood donation? The amount of blood drawn varies from 200 milliliters to 550 milliliters depending on the country, but 450-500 milliliters is typical The blood is usually stored in a flexible plastic bag that also contains sodium citrate, phosphate, dextrose, and sometimes adenine

8. Factors that play a role in establishment of blood transfusion infection Viral Window Period: period between the onset of infection and the appearance of detectable antibodies to the virus (3-6 weeks up to 6 months) Donor immune status (Asymptomatic immunocompetent donor) Laboratory and personal error Bacterial contamination

9. The Infectious Microbes Transmitted by Blood Transfusion

10. Transfusion Transmitted Infections (TTI) HIV HTLV Hepatitis B and C Cytomegalovirus Epstein-Barr virus Human Parvovirus (B19) Human Herpesvirus 8 Bacterial contamination of blood products Syphilis Malaria prions

11. Human Immunodeficiency Virus (HIV): Classification Family: retroviridae Genus: lentivirus Specie (types): HIV-1, HIV-2 Lentiviruses are single-stranded, positive-sense, enveloped icosahedral RNA viruses.

12. Integrase

13. HIV Replication Cycle  attachment (interaction b\w gp120 and CD4) then interact with CCR5 and CXCR4  Entry and Uncoating  Formation of Ds DNA by reverse transcriptase enzyme, and integration by integrase.  Stay latent or reproduce (produce RNA and proteins)  Assembly  release by budding destroying the cell

15. Routs of HIV Transmission  Unprotected sexual transmission  Blood transfusion  From mother to child (late in pregnancy, during birth and breast feeding)  Needle-sharing injection drug use  Percutaneous needle stick  Tissue transplantation

16. Human T cell Lymphotropic Viruses (HTLV) type I and type II Virology: Single stranded ss RNA enveloped Icosahedral Family: retroviridae Genus: deltaretrovirus Oncovirus

17. Pathogenesis The virus infect T cells and, activate some host cell genes; and places the infected cell in an uncontrolled mode of growth The majority of infected patients stay as carriers. Some patients develop Adult T-cell leukemia (ATL) after 20-30 years.

18.  Epidemiology It is endemic in Japan (15-30%), Caribbean (3-6%), Guinea and some parts of Africa  Transmission: Sexual route Blood transfusion Vertical transmission and breast-feeding  Laboratory diagnosis: PCR for detection of provirus genome Anti-HTLV antibodies by ELISA

19. Hepatitis B Virus  Family: Hepadnaviridae  Icosahedral enveloped Ds DNA virus  One of the smallest enveloped animal viruses.  Pleomorphic forms exist, including spherical and filamentous bodies lacking a core (none infectious lipids and proteins surface antigen (HBs Ag))

20. incomplete forms

21. Transmission Highly infectious Sexual Route Vertical Route: Transmission of virus from mother to child during childbirth perinatal, transmission of viral genetic material within the cells. Parenteral Route: Blood transfusion and contaminated syringes

22. Diagnosis Hepatitis B virus surface antigen (HBs Ag) detection by ELISA for diagnosis Differentiation between acute and chronic infection

23. Hepatitis C virus Virology: enveloped, Ss RNA virus Classification Family: flaviviridae, Genus: hepacivirus Transmission Blood\blood products transfusion Injection drug use Needle sticks or sharps exposure:1.8% (range 0%-7%) Sexual exposure

24. In developing countries, the primary sources of HCV infection are inadequately screened blood and blood products Hepatitis C transmission in developed countries

25. Epstein - Barr virus: (EBV) Virology Family: Herpesviridae Enveloped, Icosahedral, Ds DNA Derives envelope from nuclear membrane Establishes Latency in B lymphocytes. Transmission Direct person-person contact (Saliva) Blood transfusion. Most adults are seropositive.

26. Pathogenesis EBV infects nasopharyngeal epithelial cells, salivary and lymphoid tissues The virus binds to CD21 of B- Lymphocytes and acts as mitogen (encourages a cell to commence cell division) This will stimulate the production of atypical reactive T cell (Downey cells=70% of the total WBC count)

27. Downey cells

28. EBV Diseases and malignancies Diseases: asymptomatic in infants and young children Heterophile positive mononucleosis (infectious mononucleosis) (kissing disease) Fatigue, fever, sore throat, lymphadenopathy, and splenomegaly Lymphoproliferative disease: Uncontrolled B- Cell growth in immunocompromised patients hairy leukoplakia: nonmalignant, white-gray lesions on the tongue in AIDS patients.

29. Hairy leukoplakia

30. Malignancies Burkitt lymphoma Nasopharyngeal carcinoma Hodgkin lymphoma Diagnosis (serology) Anti-E.B virus IgM antibodies detected by ELISA test

31. Lymphadenopathy

32. Cytomegalovirus (CMV) Virology Belongs to the Herpesviridae family like EBV Transmission: Saliva, sexual, blood transfusion, vertical (during pregnancy, breast milk) Pathogenesis Latency in monocytes and macrophages (mononuclear cells). Approximately 50% to 80% of the adult population are infected with the virus

33. Mononucleosis syndrome (like IM): usually asymptomatic or mild symptoms. cytomegalic inclusion body disease, jaundice, hepatosplenomegaly, pneumonitis, CNS damage (loss of hearing & mental retardation), death. (most sever in vertical transmission) Interstitial pneumonitis to severe systemic infection (immunocompromised patients : AIDS, tissue transplant)

36. Parvovirus B19 Virology Ss DNA virus, non enveloped, icosahedral virus Transmission Respiratory, vertical (from mother to child), blood transfusion This virus has been transmitted to patients with hemophilia through infusion of clotting factors

37. Pathogenesis It infects immature erythroid progenitor cells, resulting in cell lysis The resulting anemia is clinically significant in patients with sickle cell anemia Disease In children and adults Fifth disease; erythema infectiosum (slapped cheek disease) In fetus Severe anemia, hydrops fetalis (anaemia & edema)

40. Human Herpes Virus 8 (HHV-8) Virology: enveloped Ds DNA virus, family: herpesviridae Transmission: Sexual contact, Saliva, vertical, transplantation & transfusion Pathogenesis It has a gene that turns on vascular endothelial growth factor (VEGF), which plays a direct role in the development of Kaposi Sarcoma

41. Disease: Kaposi Sarcoma in immunosuppressed esp. AIDS patients. Diagnosis Serology: ELISA Molecular genetics: PCR

43. Bacterial contamination The most common and severe infectious complication associated with transfusion It has been estimated that 1 in 38,500 units of red cells, 1 in 3,300 units of random donor platelets, are contaminated with bacteria

44. Gram–positive bacteria normally found on the skin, such as S.epidermidis or S.aureus, are the most common bacterial contaminants of blood products. Gram negative bacteria, such as E.coli, may contaminate the donation when blood is collected from donors who have bacterial infection without symptoms.

45. Improved methods of collection, handling, and storing of blood products has decreased bacterial contamination in recent years.

46. Treponema pallidum Transmission: Sexually, transplacentanlly and by blood transfusion (rare; 6 in million; can not survive more than 48 hrs. in refrigerator) Bacteriology Thin spirochete; Basically it has Gram’s negative cell wall Axial filaments present (endoflagella) Can not be cultivated in vitro; serodiagnosis

47. Obligate pathogen (but not intracellular) Pathogenesis Primary: genital chancre of skin Secondary: skin lesions Latent infection Tertiary: CNS and cardiovascular infection

48. Chancre

49. Diagnosis Direct: Examination of microbe by Dark field or immunofluorescent microscopes. Indirect (Serology) Non treponemal antibodies (non-specific antibodies): Anti-cardiolipin by VDRL or RPR test Treponemal antibodies (specific): by TPHA or IFA

51. Malaria About 300-500 million people are infected, over 1 million people die each year Transmission bite of infected female Anopheles mosquito, transplacentanlly, and by blood transfusion Microbiology Etiology: Plasmodium species (P.vivax, P.malariae, P.ovale, P. falciparum) Classification: Sporozoa

53. Man is the intermediate host (asexual stage of microbe= Schizogony cycle) Anopheles is the definitive host (sexual stage = Sporogony cycle)

54. sexual cycle (Sporogony) Asexual cycle (Schizogony)

58. Diagnosis: Thick and thin blood smears Rapid dip stick tests

59. Blood smear with Plasmodium falciparum

61. Map showing the distribution of malaria in the world: ♦ Elevated occurrence of chloroquine- or multi-resistant malaria ♦ Occurrence of chloroquine-resistant malaria ♦ No Plasmodium falciparum or chloroquine-resistance ♦ No malaria