1-1-10 Transfusion Transmitted Diseases 1. List the pathogens or diseases that blood donations are tested for.

Here are the tests that correspond to the TTDs that they test for: HbsAg: hepatitis B surface antigen test; a screening test which must be followed by a more sensitive and specific confirmatory test Hep B is associated with liver disease and liver cancer Anti-Hbc: antibody to hepatitis B core antigen; a surrogate mar!er for hep B infection Anti-HCV: antibody to hep " virus; a screening test which must be followed up with a confirmatory test Anti-HTLV I/II: combo test for human T cell leu!emia virus #HT$%&; a screening test that must be followed up with a confirmatory test HT$% is associated with adult T cell leu!emia and tropical spastic paraparesis STS: screening test for syphilis' must be followed up with confirmatory test; there(s debate about its usefulness in donor populations Anti-HIV 1/2: combo test for H)% types 1 and * HIV-1 p24 antigen: detects p*+ antigen on H)% virus ALT: detects an en,yme found in liver inflammation; a surrogate mar!er for non--' non-B hepatitis infection .ince the )Ding and implementation of Hep " testing' -$T is no longer used for donor testing in the /. )t is still used in 0urope Anti-C V: test for "1% used for high ris! recipients li!e newborns and immunocompromised HCV and HIV !"A tests: performed using 2"3 viral amplification' allowing small numbers of virus to be amplified and detected These tests allwo for earlier detection of infection' !nown as #closing the $indo$ period of infection 4The window period of infection is the time between getting the virus to when they become infectious to others %est "ile Vir&s !"A: tests for west nile using the 5ucleic -cid--mplification Test #5-T& 2. List the h&'an TS(s and disting&ish their ca&ses.

Sporadic C)*+ ,a'ilial C)*+ -&r&' and .C)*: caused by prions Chagas/ *isease: caused by Trypanosoma cruzi' a parasitic trypansoma that(s harbored in reduviid bugs C0to'egalic incl&sion disease+ heterophile-negati.e 'onon&cleosis+ retinitis+ interstitial pne&'onia+ encephalitis+ colitis+ esophagitis+ and pne&'onia/pne&'onitis: "1% %"V ,e.er+ ne&roin.asi.e disease: 65%

1. (2plain the str&ct&ral differences bet$een 3r3C and 3r3Sc. 3r3 is a protein encoded by the Pmp gene )t is most abundant in the "5.' but can also be found in the spleen and lymph nodes )t can be un-glycosylated' mono-glycosylated' or diglycosylated 3r3C is the 5731-$ protein )ts conformation is an alpha heli8

3r3Sc is the 1).97$D0D protein )t(s defined by an increase in beta pleated sheets and a decrease in alpha helices .uch misfolding results in resistance to proteinase : and nonionic detergents The conse;uence is a vast amount of aggregate of fibrils' rods' etc formed The misfolded protein can act as a <seed4 that converts the ma=ority of otherwise correctly-folded proteins into misfolded ones The misfolded proteins accumulate in endosomes and lysosomes The prions are resistant to heat, irradiation, and chemicals that normally inactivate viral infectivity

4. *isc&ss the epide'iolog0 of .C)*. There are three ways to develop prion diseases: they can arise spontaneously' be acquired' or be inherited Thus' there are three types of "reut,feldt->a!ob Diseases #">D&: Sporadic C)*: .pontaneous #most common& ,a'ilial C)*: inherited #due to Pmp gene mutations& .C)* and -&r&: ac;uired 1ore on .C)*' since that(s what the ob=ective as!s for: v">D occurs in ?7/5@ patients #in contrast to most ">D' which occurs at AB0yoC& and is characteri,ed by a short duration' distinct pathologies in the brain' presence of infectious prion in the spleen, lymph nodes, and tonsils 4C5 prion found in /: beef has identical molecular characteristics to v">D v">D can be ac;uired by 1& in=ection' *& transplantation of contaminated tissues #esp corneas&' D& contact with contaminated medical devices #i e brain electrodes&' +& cuts in s!in' and B& food Diagnosis of ">D is based on 1& clinical grounds with confirmation made by detection of a *& proteinase --resistant for' of 3r3 in a Western Blot using -bs to 2r2 in a tonsil biopsy -utopsy diagnosis involves amyloid plaques' spongiform vacules' and immunohistologically detected PrP Ce8 of a v">D patient: *B yo seen by psychiatrist for anxiety and depression; * months later' he develops problems with balance and muscle control with difficulty remembering He develops myoclonus and dies within 1* months of onset #young' short duration' lots of brain pathologies& 08 of a ">D paitent: ED yo with poor memory and difficulty with vision and muscle coordination 7ver the course of the ne8t year' developed senile dementia' irregular =er!ing movements' progressive loss of muscle function' and eventual death #same brain pathologies' but much older age and of longer duration and slower onset& 6. *escribe ho$ to control the trans'ission of 3r3Sc thro&gh blood transf&sion. The 4ritish have banned anyone who has received a blood transfusion since 19 ! from donating blood )t has also banned the use of "# blood for manufacture of fractional products li$e albumin The ,*A bans anyone who has spent %& years in Western 'urope' (& months for military personnel' and ) months if in the "# -lso' anyone who(s been diagnosed or considered at ris! for any form of ">D is banned from donation 7. *isc&ss the pathogenesis of T. cruzi and ho$ host i''&nit0 reacts to its infection.

T. cruzi is the cause of Chagas/ *isease "hagas( can be asymptomatic, acute, or chronic These three phases are related to the life cycle of T* cruzi

Ac&te infection is defined by two features: 1& the development of a chago'a at the site of a reduviid bug bite #erythematous and indurated& that(s coupled with fever' chills' malaise' myalgia and fatigue' then *& rash and ede'a around the eyes and face There are three possible conse;uences to acute infection: Death Become asymptomatic 2rogress to chornic infectionF 2athogenesis: The red&.iid b&g bites and defecates on the wound' resulting in the chagoma )t contaminates the site with tr0to'astigoes' which enter the host(s circulation During the acute phase' B7TH tyrpomastigotes and amastigotes are present in the blood Chronic infection is characteri,ed by 1& '0ocarditis #cardiac muscle is the most affected tissue' manifesting as megacardia and electrocardiographic changes&' *& hepatospleno'egal0' and D& enlarge'ent of the esophag&s and colon #due to destruction of nerve cells' can also manifest as granulomas in the brain and encephalitis& Death from chronic infection is due to tissue destruction; sudden death can occur from cardiac arrhythmias and brain damage 2athogenesis: The trypomastigotes migrate via circulation to various tissuesGincluding cardiac muscle' liver' brainGand differentiate into a'astigotes "ardiac muscle is the most fre;uently and severely affected tissue )n the chronic phase' 75$? the amastigote form persists

-lso' various T* cruzi antigens cross-react with host antigens' suggesting a role of autoimmunity as the origin of the pathology 8. *escribe the C V infection in neonates. "1% is ac;uired from blood' tissue' and most body secretions Thus' it can be ac;uired early in life across the placenta, +ithin the birth canal, and from breast mil$ -ppro8imately half of neonates born thro&gh an infected cer.i2 ac9&ire C V infection and become e8creters of the virus at D-+ w!s of age -lso' babies of mothers who experience seroconversion during term are at high ris! for congenital defects The disease that "1% causes in neonates is called c0to'egalic incl&sion disease )t is characteri,ed by multinucleated giant cells with a priminant intranuclear inclusion ,-. is the most common cause of congenital abnormalities in the "/* )nfection occurs because of the pri'ar0 infection in the mother when she has no antibodies against the "1%' most commonly during the first trimester Diagnosis of congenital "1% is best documented by isolation of the virus form the infants urine during the first +ee$ of life*

:. (2plain $h0 C V positi.e bone 'arro$ transplant recipients 'a0 de.elop reacti.ated disease after the0 ha.e recei.ed a C V negati.e graft. The ma=ority of "1% positive patients are asymptomatic 7ver H0I of adults have antibodies against it )mmunocompetent individuals utili,e cell0mediated immunity to combat "1%

symptoms; thus' suppression of cell-mediate immunity allows recurrence and severe presentation .omeone who(s received a bone marrow graft is li!ely to be immunosuppressed' resulting in reactivation of the "1% ;. *escribe the clinical diseases ca&sed b0 %"V infection. 1ost 65% infections are asymptomatic 9or those who do develop symptoms' there(s a *-1B day incubation period with two possible outcomes: *0I develop %"V fe.er #659&' flu-li!e symptoms of headache' fever' tiredness' body aches' s!in rash' and swollen lymph nodes There are 57 permanent health effects J1I develop se.ere ne&roin.asi.e disease that includes encephalitis, high fever, nec$ stiffness, disorientation, stupor, coma, tremors, convulsions, muscle +ea$ness and paralysis 5eurological effects may be 2031-505T

1<. List the host 'echanis's in li'iting %"V infection. 65% infects hosts after mosquito inoculation The infection begins in Langerhans cells #epidermal D"(s&' which migrate to lymph nodes There' interferons are made to limit spread: T0pe I I,": bloc!s flavivirus infection by preventing translation and replication of infectious viral 123 T0pe II I,": induces >-:-.T-T signal transduction pathway that generates proinflammatory and antiviral molecules %irus e8its the lymphatics into the peripheral circulation' where they are controlled by Ig ' interferons' and co'ple'ent Humoral immunity produces antibodies that protect against 65% infection by 1& direct neutrali,ation of receptor binding' *& complement-mediated lysis of virus or infected cells' and D& A*CC #antibody-dependent cytoto8icity& .pecific )g1 may limit 65% dissemination by triggering an adaptive )g@ or T cell response "ellular immunity' in the form of C*: c0toto2ic T cells' is important for selectively targeting 65%-infected neurons in the "5. 6hile "- cells normally !ill virally infected cells and produce cyto!ines to limit the infection' they are 57T a very efficient defense against 65% acrophages induce nitric o8ide synthesis within themselves to clear virus form circulation' stimulate cyto!ine production' and facilitate increased antigen presentation to B and T cells in secondary lymphoid organs