BY ADEWUYI, SOFIAT ADEDAMOLA G2016/MSC/MCB/FT/004 SUBMITTED TO THE SCHOOL OF GRADUATE STUDIES,UNIVERSITY OF PORT HARCOURT,IN PARTIAL FULFILMENT OF THE REQUIREMENT FOR THE AWARD OFMASTEROF SCIENCE DEGREE IN PATHOGENIC MICROBIOLOGY. MARCH,2018 CONTENT TABLE OF CONTENT.2 CHAPTER 1. INTRODUCTION BACKGROUND OF STUDY5 CHAPTER 2. LITERATURE REVIEW 2.1 Hepatitis B virus8 2.1.1 Hepatitis B virus infection..8 2.1.2 HBV genome..9 2.1.3 Structural proteins10 2.1.4 Non structural proteins11 2.1.5 Genotypes and serotypes12 2.1.6 HBV replication14 2.1.7 Immune response to HBV.14 2.1.8 Infectious dose…16 2.1.9 Signs and symptoms17 2.1.10 Transmission18 2.1.11 Diagnosis of HBV.20 2.1.12 Epidemiology21 2.2 Syphilis23 2.2.1 Syphilis infection23 2.2.2 Signs and symptoms24 2.2.3 Aetiology27 2.2.4 Transmision28 2.2.5 Diagnosis28 2.2.6 Preventive measures30 2.2.7 Epidemiology31 2.3 Blood Transfusion32 2.3.1 Classification of blood donors in Nigeria.32 2.3.2 World Health Organisation (WHO) and National Blood Transfusion Service (NBTS) standard of blood transfusion34 2.3.3 Risk factors of blood transfusion36 2.3.4 Prevalence of HBVand syphilis among blood donors (REVIEW) 37 2.3.5 Syphilis and screening of blood donation41 CHAPTER 3 MATERIALS AND METHOD 3.1 Study design and setting44 3.2 Study population44 3.3 Sample collection44 3.4 Hepatitis B surface antigen44 3.5 Syphilis serology45 REFERENCES.46 CHAPTER 1. INTRODUCTION Background of study The World Health Organization (WHO) recommendation of safe blood transfusion is provision of compatible blood which is cross matched and had been screened at least for five transfusion transmitted infections (TTIs) human immunodeficiency virus (HIV), hepatitis C (HCV),hepatitis B (HBV), syphilis and malaria parasite (WHO, 2011). Blood products, such as blood components for both transfusions and plasma derivatives, are essential therapeutics in modern medicine. Red blood cell transfusions are vital in saving lives during emergencies and in other cases where interventions are necessary (Heiden, 2010) For example, blood coagulation factor concentrates dramatically improve the life expectancy and quality of life of hemophilia patients. Until recently, blood products were considered to be purely physiological materials that were not expected to be harmful (Su et al., 2003). However, HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) were found to be associated with blood transfusions in Chinese adults (Shepard et al., 2005 Shang at al., 2007 Shan et al., 2007). Transfusion therapy has been the mainstay of several medicosurgical therapeutics since 1930 (Zafar, 2000). There are 3 types of blood donors voluntary/unpaid, family/replacement, and paid.2 A voluntary blood donor intentionally donates blood without pursuing any remuneration, whereas are placement donor is requested to do so by the patient or his associates (WHO, 2014). According to World Health Organization (WHO) Global Database on Blood Safety (GDBS) 2008, total around 91.8 million blood donations are collected annually. But, approximately 48 of these emanate from high-income countries, astringent to 15 of earths population. Ten nations vouch for 65 of blood collections worldwide ,and India is the third highest bidder in this respect following United States and China (Agravat et al., 2004). With almost 9.8 million units of yearly collections and 84 voluntary donors, India is expected to bang on the WHO target of 100 voluntary donations by 2020, much before due date ( WHO, 2014). This survey is to compare the current syphilis and Hepatitis B virus screening practices in Nigeria with the recommendations of the WHO and NBSG regarding the use of assays for screening blood donors and their performance. Also the prevalence of syphilis antibodies and Hepatitis B virus in blood donors will be estimated. Additionally, the survey determined whether written SOPs or guidelines were in place for syphilis screening and whether donors with positive syphilis tests were referred for clinical follow-up. CHAPTER 2. LITERATURE REVIEW. 2.1 HEPATITIS B VIRUS 2.1.1 HEPATITIS B VIRUS INFECTION Hepatitis B virus (HBV) is a noncytopathic, hepatotropic virus of the Hepadnaviridae family that causes variable degrees of liver disease in humans. Infection with HBV can be either acute or chronic while adult infections have a relatively low rate of chronicity (around 5), neonatal infections usually have a high persistence rate (McMahon, 2010). Hepatitis B is an HYPERLINK https// o Infectious diseaseinfectious disease caused by the HYPERLINK https// o Hepatitis B virushepatitis B virus (HBV) that affects the HYPERLINK https// o Liverliver (WHO,2014). It can cause both acute and HYPERLINK https// o Chronic infectionchronic infections (WHO,2014). Many people have no symptoms during the initial infection. Some develop a rapid onset of sickness with vomiting, HYPERLINK https// o Jaundiceyellowish skin, HYPERLINK https// o Fatigue (medicine)tiredness, dark urine and HYPERLINK https// o Abdominal painabdominal pain. Often these symptoms last a few weeks and rarely does the initial infection result in death (WHO,2014). It may take 30 to 180 days for symptoms to begin (WHO,2014). In those who get infected around the time of birth 90 develop chronic hepatitis B while less than 10 of those infected after the age of five do (CDC,2011). These complications result in the death of 15 to 25 of those with chronic disease (WHO, 2014). 2.1.2 HBV GENOME HYPERLINK https// The genome organisation of HBV. The genes overlap. 2.1.3 Structural Protein Hepatitis B surface antigen Envelope polypeptides are encoded by the combination of the pre S and S gene regions. The major protein of hepatitis B surface antigen (HBsAg) particles is the smallest gene product (SHBs). The middle protein (MHBs) contains the pre-S2/S component. The large surface protein (LHBs) contains pre-S1, pre-S2 and HBsAg, and is incorporated in intact virus particles (Reifenberg et al., 2006). In viraemic carriers, MHBs and SHBs products predominate in the liver, whereas in non-viraemic carriers, LHBs products predominate. LHBs show direct toxic or immunomodulatory effect and interaction with cytokines (Ayada et al., 2006) which may result in massive hepatocellular necrosis, regeneration and the eventual development of HCC. Core Proteins The hepatitis B core antigen (HBcAg) (25 kD) is assembled into the capsid, which is essential for viral packaging. Its synthesis is restricted to liver tissues, and is an important target for immune recognition in chronic infection. Soluble Hepatitis B e antigen (HBeAg) (21kD) peptide is released into the circulation, and is a reliable marker for actively replicating virus, and hence, for high infectivity (Wu et al., 2007). Seroconversion from HBeAg to anti-HBe is commonly associated with the clearance of wild type (wt) HBV and the resolution of acute liver disease. 2.1.4 Nonstructural Proteins HBV Polymerase Enzyme The HBV polymerase is a 56 to 70kD polypeptide. HBV polymerase has the following domains the amino-terminal region terminal protein (tp) which acts as a prime promoter for synthesis of the minus strand cDNA, spacer domain, the RNA-dependent DNA polymerase (reverse transcriptase), and the RNase H domain at the carboxy-terminus. Mutation of polymerase affecting its activity will affect the amount of virus produced, as well as the number of templates available to encode viral proteins (Bajunaid,2013). X-gene The X gene protein (154 amino acids (aa.)) encoded by the X gene (nt. 1372-1834), exhibits numerous activities affecting intracellular signal transmission, gene transcription, cell proliferation, DNA repair, and apoptosis (Francois et al., 2001). HBx trans-activates and upregulates viral and cellular genes as the transcriptional expression of human telomerase l reverse transcriptase (hTERT) (Qu et al., 2005), through activation of transcription factors, modulation of cell signalling pathways, RNA stabilization, and alteration of nucleocytoplasmic translocation and inhibition of serine protease activity (aa. 67-69 and 135-138 (Blackberg and Kidd-Ljunggren 2003). 2.1.5 GENOTYPES AND SEROTYPES With about 240 million chronic carriers worldwide and more than 686 000 deaths per year (WHO, 2014), Hepatitis B virus (HBV) infection remains a serious public health problem, particularly in endemic areas including Southeast Asia and Sub-Saharan Africa (WHO, 2015). To date, eight genotypes named A H are recognized (Norder et al., 2004) and two additional genotypes, I and J, have been proposed (Tran et al., 2008, Tatematsu et al., 2009). HBV genotypes may have distinct geographical distributions. In Africa, especially genotypes A, D and E are prevalent, with genotype E being dominant throughout West Africa (Hbschen et al., 2008, Cooksley, 2010, Kramvis, 2014, Pourkarim et al., 2014, Kramvis, 2016, Hbschen et al., 2011). Several studies have implicated HBV genotypes in disparate disease progression, clinical outcome, therapeutic response and the degree of protection provided by vaccination (Cooksley, 2010, Kramvis, 2014, Pourkarim et al., 2014). The human HBV is a member of the familyHepadnaviridaeand has been classified into 10 genotypes (A-J), which can be further sub-divided into over 40 sub-genotypes (Kay and Zoulim, 2007 Kurbanov et al., 2010 Locarnini et al., 2013). The geographical distribution of genotypes is shown in HYPERLINK https// l f0005 Fig. 1 (Locarnini et al., 2013). Geographical distribution of the HBV genotypes and sub-genotypes.Genotype I and J are not shown as they have not been ratified by the ICTV genotype I is found in Southern China and Vietnam whilst genotype J was identified from a Japanese World War II person who lived in Borneo (Locarnini et al., 2013). 2.1.6 HBV REPLICATION During infection, HBV penetrates into the cells after surface binding, then the virus is transported into the nucleus without processing, where replication starts by unwinding circular DNA which is converted into a covalently closed circular DNA (cccDNA) that acts as a template for transcription of HBV pregenomic, and messenger RNAs (Beck and Nassal, 2007). Transcription starts from the core promoter to yield the 3.5 kb pregenomic RNA, which is packaged with polymerase into immature core particles, and then serves as a template for reverse transcription and negative strand DNA synthesis. The incomplete positive strand DNA is then synthesized. The mature core particles are packed into HBsAg and pre-S proteins in the endoplasmic reticulum then are exported from the cell. 2.1.7 IMMUNE RESPONSE TO HBV 2.1.8 INFECTIOUS DOSE OF HBV Recent studies in HBV infected chimpanzees using a wide dose range of a single monoclonal HBV inoculum demonstrated that also the size of the viral inoculum contributes to the outcome of HBV infection (Asabe et al., 2009). As shown in, animals inoculated with 1010, 107and 104genome equivalents (GE) of HBV cleared the virus within 830 weeks after its first detection, in a virus dose-related fashion similar to what we have previously observed in several other animals that had been inoculated with 108GE HBV (Thimme et al., 2003). In contrast, both of the animals that were inoculated with 101GE became chronically infected, one of which (like many chronically infected humans) ultimately cleared the virus in the context of an acute disease flare 42 weeks after first detection, while the other remained heavily infected for at least 55 weeks at which point the study was terminated. This suggests that a virus dose window exists between 104and 101GE within which the host-virus dynamics favor persistent infections, while higher doses favor viral clearance. Importantly, viral clearance was heralded by early CD4T cell priming either before or at the onset of detectable viral spread, and it coincided with a sharply synchronized influx of HBV-specific CD8T cells into the liver and a corresponding increase in intrahepatic CD8 mRNA, serum ALT activity and histological evidence of acute viral hepatitis. Interestingly, the first detectable peripheral CD4 T cell response occurred during or before the phase of detectable viral expansion in the animals that cleared the infection in this study (Asabe et al., 2009). In contrast, the CD4 response was delayed until after the onset of viral expansion in the animals that developed persistent infection at which point the virus had infected 100 of the hepatocytes (Asabe et al., 2009) and there was an uncoordinated influx of HBV-specific CD8T cells into the liver and a correspondingly asynchronous increase in intrahepatic CD8 mRNA and serum ALT activity (Asabe et al., 2009). 2.1.9 SIGNS AND SYMPTOMS Extrahepatic manifestations. Symptoms outside of the liver are present in 110 of HBV-infected people and include HYPERLINK https// o Serum-sicknesslike syndromeserum-sicknesslike syndrome, HYPERLINK https// o Acute necrotizing vasculitisacute necrotizing vasculitis ( HYPERLINK https// o Polyarteritis nodosa polyarteritis nodosa), membranous glomerulonephritis, and HYPERLINK https// o Papular acrodermatitis of childhoodpapular acrodermatitis of childhood ( HYPERLINK https// o GianottiCrosti syndrome GianottiCrosti syndrome) (Trepo and Guillevin , 2001). The clinical features are fever, HYPERLINK https// o Skin rashskin rash, and HYPERLINK https// o Polyarteritispolyarteritis. The symptoms often subside shortly after the onset of jaundice but can persist throughout the duration of acute hepatitis B (Liang, 2009). Membranous glomerulonephritis is the most common form (Liang, 2009) Other immune-mediated HYPERLINK https// o Hematologicalhematological disorders, such as essential mixed HYPERLINK https// o Cryoglobulinemiacryoglobulinemia and HYPERLINK https// o Aplastic anemiaaplastic anemia have been described as part of the extrahepatic manifestations of HBV infection, but their association is not as well-defined therefore, they probably should not be considered etiologically linked to HBV (Liang, 2009). Intrahepatic manifestations Hepatitis B virus can cause a variety of liver diseases including acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Acute infections After an incubation period of six weeks to six months, this is inversely proportional to the infective dose of the virus. The spectrum of the acute infection varies from mild to severe attacks. Clinically, acute infections manifest by fever, anorexia, nausea, malaise, vomiting, jaundice, dark urine, clay coloured stools, and abdominal pain. 1 to 2 of acute disease results in fulminant hepatitis, with a case fatality ratio of 63 to 93 (Bracho et al., 2006). Viraemia may reach up to 1010 virions per ml. HBV replicates in extrahepatic tissues, and particularly in peripheral blood mononuclear cells (PBMCs), which may serve as a reservoir for the maintenance of infection (Mazet-Wagner et al., 2006). Acute exacerbations of infection may develop in chronically infected patients (Kao, 2002). Chronic Hepatitis B Chronic infection with hepatitis B virus either may be asymptomatic or may be associated with a chronic inflammation of the liver (chronic hepatitis), leading to HYPERLINK https// o Cirrhosiscirrhosis over a period of several years. This type of infection dramatically increases the incidence of HYPERLINK https// o Hepatocellular carcinomahepatocellular carcinoma (HCC liver cancer). Across Europe, hepatitis B and C cause approximately 50 of hepatocellular carcinomas (El-Serag and Rudolph, 2007, El-Serag, 2011) Chronic carriers are encouraged to avoid consuming HYPERLINK https// o Alcoholalcohol as it increases their risk for HYPERLINK https// o Cirrhosiscirrhosis and liver cancer. Hepatitis B virus has been linked to the development of HYPERLINK https// o Membranous glomerulonephritismembranous glomerulonephritis (MGN) (Gan et al., 2005). Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is one of the 10 most common cancers in man. The annual incidence is 250 000 worldwide. Risk factors are HBV and HCV infections especially those acquired early in life or after prolonged course, cirrhosis, male sex, aflatoxin and smoking, peak incidence in 30-50 year age group. The relative risk of developing HCC is over 200-fold for HBsAg carriers over matched controls. Whilst most HCC arise in cirrhotic liver, this is not always the case (Liu et al., 2006). 2.1.10 TRANSMISSION Possible forms of transmission include HYPERLINK https// o Sexual intercoursesexual contact, (Fairley and Read, 2012) HYPERLINK https// o Blood transfusionblood transfusions and transfusion with other human blood products (Buddeberg et al., 2008), HYPERLINK https// o Needle sharingre-use of contaminated needles and syringes (Hughes, 2000), and HYPERLINK https// o Vertical transmissionvertical transmission from mother to child (MTCT) during childbirth. Breastfeeding after proper immunoprophylaxis does not appear to contribute to mother-to-child-transmission (MTCT) of HBV (Shi et al., 2011). 2.1.11 DIAGNOSIS OF HBV Serological Tests Serological tests are the main stay of diagnosing and differentiating the various viruses causing hepatitis, and for blood bank screening, as they are quick, cheap, and detect HBsAg carriers. Acute HBV is characterized by the presence of HBsAg in serum and the development of IgM core antibodies (anti-HBc IgM), which may be the only marker in active hepatitis, and it correlates with inflammatory activity. In the convalescent stage, HBsAg and HBeAg are cleared with the development of anti-HBs, anti-HBe and antiHBc antibodies. Anti-HBs is also elicited by vaccine. In chronic HBV infections, HBsAg generally persists for life. Total anti-HBc tests for both IgM and IgG antibodies to HBV core protein, they indicate current or past infection by HBV respectively. IgM anti-HBc disappears six months after the acute infection. The IgG anti-HBc appears shortly after HBsAg in acute disease and persists for life. Different methods exist for detection of HBsAg as immunodiffusion, reverse passive haemagglutination assays, and the more sensitive enzyme linked immunoassays ELISA and radioimmunoassays with detection limit of 0.1 ng /ml of HBsAg. Ordinary serological tests may not detect mutant HBsAg and would therefore give rise to false negative results. New immunoassays are designed for the detection of hepatitis B surface escape mutants, and are specifically useful in the monitoring of liver transplant recipients on HBIG prophylaxis (Ijaz et al., 2001). Molecular Biology Techniques Different molecular techniques have been used to detect HBV DNA. HBV DNA is detectable in serum by slot or dot blot hybridization assays (Shao et al., 2007) with detection limit of 1.5 pg per ml (4.0 x105 genomes/ml). PCR detects 103 pg /ml (approximately 100 to 1000 genomes). However, the high sensitivity of PCR is limited by the increased risk of false positive results. Clinical significance of HBV PCR is the same as detection of HBsAg and indicates current HBV infection. HBV DNA monitoring and quantitative PCR are essential in determining the response and follow up of chronic HBV infection to treatment. Nucleic acid sequence analysis is used to identify genetic variants of the virus, and to epidemiologically type nosocomial transmission of HBV (Gunson et al., 2006). 2.1.12 EPIDEMIOLOGY Approximately 5 of the worlds population reaching 350 millions, have chronic HBV infection, which is the leading cause of chronic hepatitis, cirrhosis and HCC worldwide. It is estimated that 500, 000- to 1000, 000 persons die annually from HBV related liver disease (Hou et al., 2005). Most infections occur at birth or during early childhood. Infections usually cluster in households of chronically infected patients. Geographical Distribution Areas of high endemicity where prevalence is 8 are China, Indian subcontinent and Africa. Intermediate endemicity areas show prevalence of 2 to 7 in North Africa, India and Russia. Low endemicity 2 seen in Western Europe and North America. In areas of high endemicity, the lifetime risk of HBV infection is 60 (Bajunaid, 2013). The main risk factors for HBV progression to HCC include HBeAg positivity and HBV DNA levels. Seminal studies from Taiwan established these associations(Chen et al.,2010). The incidence of HCC was 1169/100,000 person-years for HBsAg and HBeAg-positive persons, 324/100,000 person-years for HBsAg positive, HBeAg-negative and 39/100,000 person-years for those who were HBsAg negative. The Risk Evaluation of Viral Load Elevation and Associated Liver Disease (REVEAL-HBV) study established HBV DNA levels as the main determinant of progression to HCC. However, even HBsAg positive carriers with low levels of HBV DNA and normal ALT had an almost 5-fold greater risk for HCC than HBsAg negative controls(Chen et al., 2010 El-Serag,2012). In 2004, an estimated 350million individuals were infected worldwide. National and regional prevalences range from over 10 in Asia to under 0.5 in the United States and Northern Europe. The primary method of transmission reflects the prevalence of chronic HBV infection in a given area. In low prevalence areas such as the continental United States and Western Europe, injection drug abuse and unprotected sex are the primary methods, although other factors may also be important (Redd et al., 2007). In moderate prevalence areas, which include Eastern Europe, Russia, and Japan, where 27 of the population is chronically infected, the disease is predominantly spread among children. In high-prevalence areas such as HYPERLINK https// o Hepatitis B in ChinaChina and South East Asia, transmission during childbirth is most common, although in other areas of high endemicity such as Africa, transmission during childhood is a significant factor (Alter, 2003) The prevalence of chronic HBV infection in areas of high endemicity is at least 8 with 1015 prevalence in Africa/Far East (Komas et al., 2013). As of 2010, China has 120million infected people, followed by India and Indonesia with 40million and 12million, respectively. According to HYPERLINK https// o World Health OrganizationWorld Health Organization (WHO), an estimated 600,000 people die every year related to the infection.In the United States about 19,000 new cases occurred in 2011 down nearly 90 from 1990 (Schillie et al., 2013), 2.2 SYPHILIS 2.2. 1 SYPHILIS INFECTION Transfusion-transmitted syphilis, which is caused byTreponema pallidumsubspeciespallidum, is one of the oldest recognized infectious risks of blood transfusion (Gardella et al.,2002). Syphilisis aHYPERLINK https// o Sexually transmitted infectionsexually transmitted infectioncaused by theHYPERLINK https// o BacteriumbacteriumHYPERLINK https// o Treponema pallidumTreponema pallidumsubspeciespallidum (CDC, 2015 a).The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary) (CDC,2015b). The primary stage classically presents with a singleHYPERLINK https// o Chancrechancre(a firm, painless, non-itchyHYPERLINK https// o Skin ulcerationskin ulceration) but there may be multiple sores (CDC,2015b). In secondary syphilis a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet (CDC,2015b). There may also be sores in the mouth or vagina (CDC,2015b). In latent syphilis, which can last for years, there are few or no symptoms (CDC,2015b).In tertiary syphilis there are HYPERLINK https// o Gumma (pathology) gummas(soft non-cancerous growths), neurological, or heart symptoms (Kent and Romanelli, 2008). Syphilis has been known as HYPERLINK https// o The great imitatorthe great imitator as it may cause symptoms similar to many other diseases (CDC,2015b Kent and Romanelli, 2008). Syphilis is most commonly spread throughHYPERLINK https// o Human sexual activitysexual activity (CDC,2015b). It may also be transmitted from mother to baby during pregnancy or at birth, resulting inHYPERLINK https// o Congenital syphiliscongenital syphilis (CDC,2015b Woods, 2009).Other human diseases caused by relatedTreponema pallidumsubspecies includeHYPERLINK https// o Yawsyaws(subspeciespertenue), HYPERLINK https// o Pinta (disease) pinta(subspeciescarateum), andHYPERLINK https// o Nonvenereal endemic syphilisbejel(subspeciesendemicum) (Kent and Romanelli, 2008).Diagnosis is usually made by usingHYPERLINK https// o Serological testingblood tests the bacteria can also be detected usingHYPERLINK https// o Dark field microscopydark field microscopy (CDC,2015b). TheHYPERLINK https// o Center for Disease ControlCenter for Disease Controlrecommends all pregnant women be tested (CDC,2015b). 2.2.2 SIGNS AND SYPMTOMS Syphilis can present in one of four different stages primary, secondary, latent, and tertiary, (Kent and Romanelli, 2008) and may also occurHYPERLINK https// o Congenitalcongenitally (Stamm,2010).It was referred to as the great imitator byHYPERLINK https// o Sir William OslerSir William Oslerdue to its varied presentations (White, 2000). Primary stage Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person (CDC, 2006).Approximately 3 to 90 days after the initial exposure (average 21days) a skin lesion, called aHYPERLINK https// o Chancrechancre, appears at the point of contact. This is classically(40 of the time) a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders 0.33.0cm in size (Kent and Romanelli, 2008) The lesion may take on almost any form. In the classic form, it evolves from a HYPERLINK https// o Macule maculeto aHYPERLINK https// o Papulepapuleand finally to anHYPERLINK https// l Primary_lesions o Erosion (dermatopathology)erosionorHYPERLINK https// o Ulcer (dermatology)ulcer (Eccleston et al., 2008).Occasionally, multiple lesions may be present (40) (Kent and Romanelli, 2008)with multiple lesions more common when coinfected with HIV. Lesions may be painful or tender (30), and they may occur in places other than the genitals (27). The most common location in women is theHYPERLINK https// o Cervixcervix(44), theHYPERLINK https// o Human penispenisin heterosexual men (99), andHYPERLINK https// o Human anusanallyandHYPERLINK https// o Rectalrectallyrelatively commonly inHYPERLINK https// o Men who have sex with menmen who have sex with men(34) (Eccleston et al., 2008).HYPERLINK https// o Lymph nodeLymph nodeenlargement frequently(80) occurs around the area of infection, (Kent and Romanelli, 2008)occurring seven to 10days after chancre formation (Eccleston et al., 2008). TheHYPERLINK https// o Lesionlesionmay persist for three to six weeks without treatment (Kent and Romanelli, 2008). Secondary stage Secondary syphilis occurs approximately four to ten weeks after the primary infection (Kent and Romanelli, 2008).While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin,HYPERLINK https// o Mucous membranesmucous membranes, andHYPERLINK https// o Lymph nodeslymph nodes (Mullooly and Higgins, 2010). There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles (Dylewski and Duong,2007). The rash may become HYPERLINK https// o Maculopapular maculopapularor HYPERLINK https// o Abscess pustular. It may form flat, broad, whitish, wart-like lesions known as HYPERLINK https// o Condyloma latum condyloma latumonHYPERLINK https// o Mucous membranemucous membranes. All of these lesions harbor bacteria and are infectious. Other symptoms may includeHYPERLINK https// o Feverfever,HYPERLINK https// o Sore throatsore throat,HYPERLINK https// o Malaisemalaise,HYPERLINK https// o Weight lossweight loss,HYPERLINK https// o Hair losshair loss, andHYPERLINK https// o Headacheheadache.HYPERLINK https// l cite_note-Kent08-55Rare manifestations includeHYPERLINK https// o Hepatitisliver inflammation,HYPERLINK https// o Kidneykidney disease,HYPERLINK https// o Arthritisjoint inflammation, HYPERLINK https// o Periostitis periostitis,HYPERLINK https// o Optic neuritisinflammation of the optic nerve, HYPERLINK https// o Uveitis uveitis, andHYPERLINK https// o Interstitial keratitisinterstitial keratitis (Bhatti, 2007).The acute symptoms usually resolve after three to six weeks (Bhatti, 2007). about 25 of people may present with a recurrence of secondary symptoms. Many people who present with secondary syphilis (4085 of women, 2065 of men) do not report previously having had the classic chancre of primary syphilis (Mullooly and Higgins, 2010). Latent stage Latent syphilis is defined as havingHYPERLINK https// o Serologyserologicproof of infection without symptoms of disease (White, 2000).It is further described as either early (less than 1year after secondary syphilis) or late (more than 1year after secondary syphilis) in the United States (Bhatti, 2007).The United Kingdom uses a cut-off of two years for early and late latent syphilis (Eccleston et al., 2008).Early latent syphilis may have a relapse of symptoms. Late latent syphilis isHYPERLINK https// o Asymptomaticasymptomatic, and not as contagious as early latent syphilis (Bhatti, 2007). Tertiary stage Tertiary syphilis may occur approximately 3 to 15 years after the initial infection, and may be divided into three different forms gummatous syphilis (15), late HYPERLINK https// o Neurosyphilis neurosyphilis(6.5), and cardiovascular syphilis (10) (Bhatti, 2007).Without treatment, a third of infected people develop tertiary disease (Bhatti, 2007).People with tertiary syphilis are not infectious (Kent and Romanelli, 2008). Gummatous syphilis or lateHYPERLINK https// o Benignitybenignsyphilis usually occurs 1 to 46years after the initial infection, with an average of 15years. This stage is characterized by the formation of chronic HYPERLINK https// o Gumma (pathology) gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size. They typically affect the skin, bone, and liver, but can occur anywhere (Kent and Romanelli, 2008). HYPERLINK https// o NeurosyphilisNeurosyphilisrefers to an infection involving theHYPERLINK https// o Central nervous systemcentral nervous system. It may occur early, being either asymptomatic or in the form of syphiliticHYPERLINK https// o Meningitismeningitis, or late as meningovascular syphilis,HYPERLINK https// o General paresisgeneral paresis, or HYPERLINK https// o Tabes dorsalis tabes dorsalis, which is associated with poor balance and lightning pains in the lower extremities. Late neurosyphilis typically occurs 4 to 25 years after the initial infection. Meningovascular syphilis typically presents with apathy andHYPERLINK https// o Seizureseizure, and general paresis withHYPERLINK https// o Dementiadementiaand HYPERLINK https// o Tabes dorsalis tabes dorsalis (Kent and Romanelli, 2008). Also, there may beHYPERLINK https// o Argyll Robertson pupilArgyll Robertson pupils, which are bilateral small pupils that constrict when the person focuses on near objects but do not constrict when exposed to bright light. Cardiovascular syphilis usually occurs 1030years after the initial infection. The most common complication isHYPERLINK https// o Syphilitic aortitissyphilitic aortitis, which may result inHYPERLINK https// o Aortic aneurysmaneurysmformation (Kent and Romanelli, 2008). Congenital syphilis HYPERLINK https// o Congenital syphilisCongenital syphilisis that which is transmitted during pregnancy or during birth. Two-thirds of syphilitic infants are born without symptoms. Common symptoms that develop over the first couple of years of life includeHYPERLINK https// o Hepatosplenomegalyenlargement of the liver and spleen(70), rash (70), fever (40), neurosyphilis (20), andHYPERLINK https// o Pneumonitislung inflammation(20). If untreated,HYPERLINK https// o Late congenital syphilislate congenital syphilismay occur in 40, includingHYPERLINK https// o Saddle nosesaddle nosedeformation, HYPERLINK https// o Higoumenakis sign Higoumenakis sign,HYPERLINK https// o Saber shinsaber shin, or HYPERLINK https// o Cluttons joints Cluttons jointsamong others (Woods, 2009).Infection during pregnancy is also associated withHYPERLINK https// o Miscarriagemiscarriage (Cunningham et al.,2013). 2.2.3 AETIOLOGY Treponema pallidumsubspeciespallidumis a spiral-shaped,HYPERLINK https// o Gram-negativeGram-negative, highly mobile bacterium (Eccleston et al., 2008).Three other human diseases are caused by relatedTreponema pallidumsubspecies, includingHYPERLINK https// o Yawsyaws(subspeciespertenue),HYPERLINK https// o Pinta (disease)pinta(subspeciescarateum) and HYPERLINK https// o Nonvenereal endemic syphilis bejel(subspeciesendemicum). (Kent and Romanelli, 2008).Unlike subtypepallidum, they do not cause neurological disease (Woods, 2009).Humans are the only knownHYPERLINK https// o Natural reservoirnatural reservoirfor subspeciespallidum (Stamm, 2010)It is unable to survive more than a few days without a host. This is due to its small genome (1.14 HYPERLINK https// o Base pair Mbp) failing to encode the metabolic pathways necessary to make most of its macronutrients. It has a slow doubling time of greater than 30hours (Eccleston et al., 2008). 2.2.4 TRAMSMISSION Syphilis is transmitted primarily by sexual contact or duringHYPERLINK https// o Pregnancypregnancyfrom a mother to herHYPERLINK https// o Fetusfetus the spirochete is able to pass through intact mucous membranes or compromised skin (Stamm, 2010).It is thus transmissible byHYPERLINK https// o Kissingkissingnear a lesion, as well as oral, vaginal, and anal sex (Kent and Romanelli, 2008).Approximately 30 to 60 of those exposed to primary or secondary syphilis will get the disease (Bhatti, 2007).Its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50 chance of being infected (Eccleston et al., 2008).Most (60) of new cases in the United States occur in men who have sex with men. Syphilis can be transmitted byHYPERLINK https// o Blood productblood products, but the risk is low due to blood testing in many countries. The risk of transmission fromHYPERLINK https// o Sharing needlessharing needlesappears limited (Kent and Romanelli, 2008). It is not generally possible to contract syphilis through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing (CDC, 2010). 2.2.5 DIAGNOSIS Early reports of the transfusion-related transmission of syphilis led to the World Health Organization (WHO) recommendations for syphilis testing of blood donors (Takpo et al., 2007). These recommendations have been questioned, since many syphilis antibodies among blood donors are the result of previous infections or even unspecific reactions. Furthermore, Treponema pallidum does not withstand cold storage (Tagny, 2011). However, as not all blood components can be assumed to be kept cold for a sufficient amount of time, if at all, and as syphilis may also serve as a potential surrogate marker for high risk behaviour in relation to HIV infection, syphilis screening continues to be a requirement in many countries. The WHO recommends several syphilis screening tests the enzyme immunoassay (EIA) and T. pallidum haemagglutination assay (TPHA) as specific tests, or the Venereal Disease Reference Laboratory (VDRL) and rapid plasma reagin (RPR) as non-specific screening tests (WHO,2010).Following a documented case of transfusion-transmitted syphilis in Ghana in 2011, (Owusu et al.,2011). The techniques used for syphilis screening are different from one country to another the VDRL or RPR alone for some, and the VDRL and TPHA for others (Takpo et al.,2007). Tests and algorithms should be selected so that they correspond with the prevalence of the disease and match the technical expertise of the personnel and the availability of reagents and equipment (Tagny, 2009). The selection criteria for a screening strategy must include simple techniques, reliability, sustainability, and cost-effectiveness. Although they are not recommended for blood banks in Africa, rapid test techniques may be preferred because of their affordability, user-friendliness, the availability of test materials, and good sensitivity and specificity furthermore they do not require sophisticated laboratory materials (Tagny, 2009). Direct testing HYPERLINK https// o Dark field microscopyDark ground microscopyofHYPERLINK https// o Serous fluidserous fluidfrom a chancre may be used to make an immediate diagnosis. Hospitals do not always have equipment or experienced staff members, and testing must be done within 10minutes of acquiring the sample.HYPERLINK https// o Sensitivity and specificitySensitivityhas been reported to be nearly 80 therefore the test can only be used to confirm a diagnosis, but not to rule one out. Two other tests can be carried out on a sample from the chancreHYPERLINK https// o Direct fluorescent antibodydirect fluorescent antibodytesting andHYPERLINK https// o Polymerase chain reactionnucleic acid amplificationtests. Direct fluorescent testing usesHYPERLINK https// o Antibodiesantibodiestagged with HYPERLINK https// o Fluorescein fluorescein, which attach to specific syphilis proteins, while nucleic acid amplification uses techniques, such as theHYPERLINK https// o Polymerase chain reactionpolymerase chain reaction, to detect the presence of specific syphilis genes. These tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis (Eccleston et al., 2008). 2.2.6 PREVENTIVE MEASURES Vaccine As of 2018, there is no vaccine effective for prevention (Stamm, 2010).Several vaccines based on treponemal proteins reduce lesion development in an animal model and research continues (Cameron and Lukehart, 2014). Sex HYPERLINK https// o CondomCondomuse reduces the likelihood of transmission during sex, but does not completely eliminate the risk. (Cameron and Lukehart, 2014).TheHYPERLINK https// o Centers for Disease Control and PreventionCenters for Disease Control and Prevention(CDC) states, Correct and consistent use of latex condoms can reduce the risk of syphilis only when the infected area or site of potential exposure is protected. However, a syphilis sore outside of the area covered by a latex condom can still allow transmission, so caution should be exercised even when using a condom. (CDC, 2010). Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis. The CDC states, The surest way to avoid transmission of sexually transmitted diseases, including syphilis, is to abstain from sexual contact or to be in a long-term mutually monogamous relationship with a partner who has been tested and is known to be uninfected. (CDC, 2010). Congenital disease Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected (Schmid, 2004). If they are positive, it is recommend their partners also be treated.(Hawkes et al., 2011). Congenital syphilis is still common in the developing world, as many women do not receiveHYPERLINK https// o Antenatal careantenatal careat all, and the antenatal care others receive does not include screening. It still occasionally occurs in the developed world, as those most likely to acquire syphilis (through drug use, etc.) are least likely to receive care during pregnancy (Schmid, 2004).Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries (Hawkes et al., 2011).Point-of-care testing to detect syphilis appeared to be good although more research is needed to assess its effectiveness and into improving outcomes in mothers and babies (Shahrook et al.,2014). 2.2.7 EPIDEMIOLOGY Syphilis is still a public health problem in the world. The World Health Organization estimated that approximately 12 million new cases are reported each year in the world with more than 90 percent from developing countries (Centers for Disease Control CDC, 2007 World Health Organization WHO, 2001). Moreover, syphilis has acquired a higher potential of morbidity and mortality with the increasing prevalence of HIV infection. If syphilis is rare in developed countries, it is much more common in developing countries where prevalence can reach 25 amongst blood donors (Tagny al., 2009, 2010).The infection is transmitted from person to person through contact with a syphilis ulcer (during vaginal, anal, or oral sex). An infected mother can infect her fetus via the placenta. Furthermore, intravenous drug addicts or other infected person can transmit syphilis through infected blood products i.e. through blood transfusion or use of infected needles for example (Workowski Berman, 2006). 2.3 BLOOD TRANSFUSION Blood transfusion is a life saving intervention that is essential in the management and care of patients. In 2005, all member states of WHO signed a document that commits them to the provision of safe and adequate blood and blood products to patients (WHO, 2010). This concern stems from the fact that there is a wide spectrum of blood borne infections which can be transmitted through the blood of apparently healthy and asymptomatic blood donors. These transfusion transmissible infectious agents include hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency viruses (HIV-1/2), human T-cell lymphotropic viruses (HTLV-I/II), Cytomegalovirus (CMV), Parvovirus B19, West Nile Virus (WNV), Dengue virus, trypanosomiasis, Syphilis and malaria (Allain et al.,2009). This scenario is worsened by the method of replacement of blood either by family members or paid donors as against WHO recommended voluntary donors (WHO, 2010). Regular voluntary, unpaid blood donors are the safest group of donors as the prevalence of blood borne infections is lowest among these donors (WHO, 2010). 2.3.1 CLASSIFICATION OF BLOOD DONORS IN NIGERIA. There are 3 main classifications of blood donors in Nigeria the voluntary (non remunerated) donors, family (replacement) donors (FDs) and commercial (paid) donors (Ahmed et al., 2007). The voluntary donors are the altruistic individuals who donate blood with the sole aim of saving a life, without regard to any form of inducement. They are usually mobilized through the mass media or blood donation drives to schools, churches and mosques. An earlier study had hypothesized that the dearth of voluntary donors in Nigeria and Sub-Saharan Africa is probably associated with the fact that the mentality of altruism (regarding blood donation) is not yet generally accepted in the typical African culture, compared to what is obtainable in the most developed countries (Osaro and Charles, 2011). The family (replacement) donors include those that donate for a hospitalized family member, friend, or associate and is largely nonremunerated, depending entirely on the good will of friends and family members. Osaroet al. had concluded that the continued importance of family donors in Sub-Saharan Africa could be linked to the fact that it may actually cost less to procure and is also well adapted to the extended family support system of many Nigerian and African communities (Osaro and Charles, 2011). However, FDs may be under pressure to donate blood when their relatives are admitted to hospital and in need of a blood transfusion, even when they know that they are potentially at risk of sexually transmitted diseases as a result of high-risk behaviours. They may be more likely to conceal a relevant medical history and the risky sexual behaviours that predispose them to infections and thus pose a threat to the safety of the blood supply. Despite this, family donations remain dominant in the African continent because family and community ties are often considerably stronger than in other types of society making the gift of blood is a natural contribution to relieve sufferers in hospitals (Nebie et al., 2007). Additionally, potential donors may be less willing to donate to someone not known to them. The WHO states that blood from VNRDs who give blood out of altruism is the safest source of blood (Takpo et al.,2007). Persistent blood shortages coupled with increased poverty in Nigeria (and most African countries) created another population of donors who give blood strictly for financial gratification these constitute the commercial (paid) donors. These have continued to increase in number and prominence in Nigeria, fuelled by the very huge deficit in blood supply and utilization. Ahmedet al. succinctly captured this phenomenon in a report among blood donors seen at the University of Maiduguri Teaching Hospital, Northeast Nigeria over a 12 years period (Ahmed et al., 2007). They observed a progressive decrease in the percentage of voluntary blood donation, over the study period, from 31 to 5, against an increase from 20 to 63 in the frequency of commercial blood donation (Ahmed et al., 2007). The above study equally emphasized the wide gap between blood supply and demand in Nigeria by showing that the mean annual increment in the number of blood donations (4) was well below the mean annual increment in in-patient numbers (11) (Ahmed et al., 2007). 2.3.2 WORLD HEALTH ORGANISATION (WHO) AND NATIONAL BLOOD TRANSFUSION SERVICE (NBTS) STANDARD OF BLOOD TRANSFUSION IN NIGERIA. The WHO recommends that each country should decide on the TTIs to be screened for as part of the blood screening programme and develop a screening strategy appropriate to its specific situation, influenced by the incidence and prevalence of infection, the capacity and infrastructure of the blood service, and the costs of screening (WHO, 2009). WHO recommends that universally, blood for transfusion be screened for HIV, HBV, HCV and Syphilis. In selected countries depending on epidemiological evidence, screening should be done for the following also malaria, Chagas disease, Human T-cell lymphotropic viruses 1 2 and Human Cytomegalovirus (WHO, 2010). The World Health Organization (WHO) had projected that Sub-Saharan Africa will attain sustainable blood transfusion safety by the year 2012, through the implementation of sets of policies geared toward provision of safe, affordable, and readily available blood units in hospitals to serve the needs of patients. (Tagny et al.,2008). Up till now, however, this goal is far from achieved in Nigeria and a number of other African countries, with attendant negative impact on health indices. Effective healthcare delivery globally is known to be supported by a robust supply of safe blood units which could indeed be lifesaving in a number of clinical scenarios. Correspondingly, from the road traffic accident victim with acute hemorrhage at the emergency room to the obstetric patient with antepartum/postpartum hemorrhage or the under-five child presenting with anemic heart failure, prompt administration of appropriate units of blood could well make the difference between life and avoidable demise. Earlier, extensive inquests into the causes of the high maternal mortality in Nigeria and Sub-Saharan Africa had highlighted the huge contribution of the very ineffective blood transfusion services (Umeora et al., 2005 Bates et al., 2005). In Nigeria, the national blood transfusion guideline stipulates that donor blood should be screened for specified Transfusion-Transmissible Infections including Human Immunodeficiency Virus (HIV), HBV, HCV and Syphilis (NBTS, 2006). The National Blood Policy Nigeria established a National blood transfusion policy through a published set of guidelines in December 2006. The publication was a fall-out of the baseline survey on blood transfusion practices which was earlier conducted in the country in August 2005. Salient conclusions from the survey included (NBTS, 2006). the national blood transfusion service (NBTS), the zonal blood service centers, state and local government areas blood service centers, the armed forces blood service, and private and other nongovernmental health establishments ( NBTS, Nigeria,2006). The essence of the above stratification was to ensure universal coverage of the country, right to local government councils. 2.3.3 RISK FACTORS OF BLOOD TRANSFUSION Factors contributing to transfusion-related transmissions in sub-Saharan Africa include high rates of transfusion in some groups of patients (particularly women and children) a high prevalence of human immunodeficiency virus (HIV) in the general and blood donor populations inadequate screening facilities and lack of infrastructure and capacity to ensure sustainable operations (Holmberg, 2006 Bournouf and Radesevich,2000). Since a person can transmit an infection during its asymptomatic phase, transfusions can contribute to an ever-widening pool of infection in the population. The economic costs of the failure to control the transmission of infection include increased requirement for medical care, higher levels of dependency and the loss of productive labour force, placing heavy burdens on already overstretched health and social services and on the national economy (WHO, 2002 Kitchen and Barbara, 2001). It should, therefore, be mandatory that blood is screened for transfusion-transmissible infectious disease markers such as antibodies to HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis, and hepatitis B surface antigenaemia (Choudhury and Phadke, 2001Nwabuisi et al., 2002). 2.3.4 PREVALENCE OF HEPATITIS VIRUS AND SYPHILIS AMONG BLOOD DONORS. Hepatitis B and other Hepatitis virus among blood donors In Federal Medical Centre, Umuahia, screening is carried out for HIV, HBV, HCV and syphilis. Human immune deficiency virus, HBV and HCV are of particular concern because of their prolonged infectivity, carrier state and the fact that they also cause various debilitating disorders which may eventually be fatal (Wallace, 2008). Though these viruses can also be transmitted through other means, infectivity estimates for the transfusion of infected blood products are much higher (92) than for other modes of transmission owing to the much larger viral dose per exposure than for other routes (Baggaley et al., 2006). It is also important to discourage and as much as possible eliminate commercial and replacement blood donation by relations of the person as such persons have been shown to be likely to test positive for blood transmitted infections (Eldryd et al., 2004). Although blood transfusion contributes relatively little to the overall HIV and other pathogen transmission, prevention of infection through blood transfusion is a priority for ethical reasons. Apart from this, whatever quantity of the pathogen that is present in blood for transfusion is most likely to be transmitted to the recipient as the blood will act as a direct vehicle. The median overall risks of becoming infected with HIV, HBV, and HCV from a blood transfusion in sub-Saharan Africa were 1, 4.3, and 2.5 infections per 1000 units, respectively (Jayaraman et al., 2010). While in the developed countries the estimate is 1/2 600 000 for HIV, 1/6 500 000 for HCV, 1/1 700 000 for HBV (Traineau et al., 2009). According to the World Health Organization (WHO), each year about 340 million new infections are due to sexually transmitted diseases such as chlamydia, gonorrhea, syphilis and Trichomonas (WHO, 2001). Syphilis remains a major public health problem in sub-Saharan Africa, including Burkina Faso. It is diagnosed routinely in all blood donors using non-treponemal and treponemal tests such as Rapid Plasma Reagin test (RPR) andT. pallidum haemagglutination Test (TPHA) (Wiwanitkit, 2002). Syphilis among blood donors Blood donors with high-risk sexual behaviour and other risk factors may be infected by syphilis and compromise the safety of blood used for transfusion. The medical selection of the blood donors consists of information of the donor, the finding of the risk factors in the behaviours and the medical history using a questionnaire, the physical examination in order to find clinical signs of the infection. Donor deferral follows identification of any risk. Medical selection is crucial because it could permit to defer more than half of infected donors, especially the ones in the early period of infection here laboratory tests are not efficient (de Almeida Neto al, 2007 Tagny, 2009). In some European countries, the prevalence of T. pallidum infection in the general population and thus in blood donors has been increasing since last two decades. An increase in syphilis infections has been associated to the high incidence of HIV. Moreover, an infected blood donor with syphilis is more than 5 times more likely to be HIV-positive. However, the prevalence of syphilis is still very low in developed countries and the very rare cases of recipient contamination raised the question of whether syphilis screening was still necessary for blood donors. In developing countries, the prevalence of positive serologic tests for syphilis can reach 25. The prevalence is however very variable from one area to another and from a country to another. In such settings, the poor quality of laboratory screening due to the lack of equipment, training personnel, reagents and standard procedures highlights the need of the systematic and better screening for syphilis to help ensure a safer blood supply. Very little systematic information is available on the profile of positive blood donors including differences between donors with recent versus past infection. The exclusion of donors with past and treated infection is still a matter of discussion. Abusive exclusion reduces the blood supply and could be problematic in developing countries. However, past history of syphilis may be high-risk sexual behaviour associated to transmitted transfusion infection such as syphilis itself and HIV. The transfusion risk of syphilis is closely related to risk factors in the blood donor, in particular the sexual behaviours, the disease being primarily transmitted by sexual route. The rates of infection are highest amongst homosexual (gay) men – or men who have sex with men (VallMayans al, 2006). Recent syphilis infections have been shown to be associated with younger age, male-male sex, two or more sex partners, past syphilis treatment, past syphilis history, HIV seropositivity. Risk factors usually associated with transfusion transmitted syphillis also include more than one sexual partner, prostitution, bisexuality ( men having sex with both men and women), intravenous drug use, and skin scarification (tattoing,blood rituals). In developing countries, most blood donors infected are first-time donors. The prevalence of syphilis is one of the highest amongst the TTI screened in developing countries. The problem of this disease, first of all, is its high prevalence in blood donors in various areas of Africa. The recent prevalence were 3.7 in Congo (Batina al 2007), 7.9 in Ghana (Adjei al., 2003 Ampofo al., 2002) and 9.1 in Cameroon (Mbanya al., 2003 Tagny al., 2009). It is just as high in females as in males, in the different age groups and in voluntary donor as well as family donors. The family blood donation and remunerated blood donation, mostly found in developing countries is statiscally associated with higher prevalence of the disease (Batina al., 2007 Tagny al., 2010). The donors who have been positive for syphilis during the previous donation are less likely to donate again, whereas donors who were negative for the presence of syphilis in the past would be more likely to donate again. In countries, which use a medical questionnaire for selection of blood donor, there are usually questions related to infection with syphilis. These questions concentrate particularly on sexual behavior (a number of sexual partners, use of condoms, past history of sexually transmitted diseases) and sometimes on specific symptoms observed during clinical examination. However, medical selection remains ineffective for several reasons – Difficulty of understanding the questions due to the level of education (ignorance of the transmissible infections by blood transfusion) (Nbi al., 2007 Agbovi al., 2006), linguistic and cultural (taboos) barriers – Discrete expression of the disease in its primary phase. The syphilitic rosella is not clearly visible on dark skin. – Suppression of clinical signs and symptoms by the various antibiotics following self – medication (ampicilline, penicillin). Thus, the biological screening of this disease remains essential to defer blood donors at risk. Identified safe donors must be retained in the pool of repeated donors and frequently informed and educated to avoid risky behaviours (Claude, 2011). 2.3.5 SYPHILIS AND SCREENINGOF BLOOD DONATION. At the beginning of the 20th century newer tests were developed. Present-day, several labs tests, treponemic or not treponemic exist, among which rapid tests, immunological tests, and genomic (Young al., 2000). Neither there is a specific type of method absolutely indicated, nor is there any confirmatory algorithm for testing based on the different assays available. In fact, the laboratory assessment of syphilis is generally based on the detection of antibodies against T. pallidum antigens in blood by the use of either specific or nonspecific reagents. The detection of genomic particle are more specific but not affordable for most of laboratories (Marfin al., 2001 Orton al. 2002). The detection of specific Treponema antigens is possible using methods as passive agglutination, as T. pallidum hemagglutination (TPHA) assay or the T. pallidum particle agglutination (TPPA) assay, indirect immunofluorescence as the fluorescent treponemal antibody absorbed (FTA-ABS) assay or enzyme immunoassay (EIA) for the detection of specific IgG and IgM or total Ig. Non-treponemal methods are based on non-treponemal lipid antigens (cardiolipin), using frequently the flocculation technique. Of these, the Venereal Disease Research Laboratory (VDRL) and rapid plasma reagin (RPR) tests are the most commonly used. These tests are cheap, fast and more sensitive (Montoya al. 2006 WHO, 2006). They are able to identify the contaminated blood donors few days before the treponemal test and thus useful for acute infection. However, VDRL and RPR cannot be automated and are time-consuming if used for large scale testing. Moreover, they produce more false positive results. These tests are routinely used to screen blood donors. False positives on the rapid tests can be seen in viral infections such as hepatitis, tuberculosis, malaria, or varicella. Thus, non-treponemal tests should be followed up when possible by a treponemal test. The treponemal tests are based on monoclonal antibodies and immunofluorescence they are more specific and more expensive. The tests based on enzyme-linked immunoassays are the more specific and are usually used to confirm the results of simpler screening tests for syphilis. According to the guidelines published by the U.S. Centers for Disease Control and Prevention, the diagnosis of syphilis should be based on the results of at least two tests one treponemal and the other non treponemal (CDC, 2006 CDC, 2004 ). According to WHO, blood banks may choose Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR), or enzyme immunoassay (EIA). VDRL and RPR are sensitive for recent syphilis infection, but not for past infection. Screening should be performed using a highly sensitive and specific test for treponemal antibodies either TPHA or enzyme immunoassay. In populations where there is a high incidence of syphilis, screening should be performed using a non-treponemal assay VDRL or RPR. EIA can detect past or recent infection, but may result in rejecting non-infectious blood with distant past infection (Cole al., 2007). However, one should remember that the reliability of the screening and the diagnosis include the performances as well as the quality assessment notably the use of standard operating procedures, norms, training of the personnel and management of quality. The screening for syphilis is frequently carried out on the African blood donor, and national policies often include the disease in the list of ITT to be screened at the time of blood donation. More than 90 of blood collected in Africa in the year 2004 was screened for syphilis (Tapko al., 2005). The techniques used for screening are different from one country to another VDRL or RPR alone for some, VDRL TPHA for others (Tagny, 2009). Developing countries are characterized by a difficult epidemiologic, sociological and economic environment which limits the implementation of a high quality of blood safety. Thus, this context requires that tests and algorithms should be selected so that they correspond with the high prevalence of the disease, limited technical know-how of the personnel and limited availability of reagents and equipments. The selection criteria of screening strategy must include simple techniques, reliability, sustainability and cost effectiveness. Regular supply of electricity, freezer and ELISA kits is mostly found in big cities and barely available in small towns. Several blood banks use rapid test technique as it does not required sophisticated lab materials (Tagny al., 2009). Screening strategies must also take into account the training of technicians, guarantee their capacity to carry out the test and provide reliable results (Claude, 2011). CHAPTER 3 MATERIALS AND METHODS 3.1. Study design and setting The data of blood donor recorded from January 2017 to April 2018 and Bio-data and positivity of the diseases will be collected at the blood bank of the Meridian Hospitals. Situated at 21 Igbokwe str D/Line. Port Harcourt. Rivers State. Nigeria. This hospital also has as its objective the management of the numerous accidents along the Aba road which is major highway and other surrounding roads due to the reckless driving of taxi drives, management which often requires blood transfusions. 3.2. Study population Donors were either volunteers, or relatives or friends of patients who came to replace blood used or expected to be used by patients. Voluntary donors either belonged to an association of blood donors or came individually on their own account to donate blood. 3.3 Sample collection Blood samples will be aseptically collected from each subject by venipuncture in 5-ml red-top vacutainers (Becton Dickinson, NJ, USA) and allowed to clot naturally at room temperature. Serum specimens will be separated by centrifugation at 3000 g for 5 min and will be used for the analyses. 3.4 Hepatitis B surface antigenemia REFERENCE World Health Organization. (2011). Global Database on Blood safety Summary report 2011. Heiden, RS. (2010). Quality and safety in blood supply in 2010. Transus Med Hemother 37,112-7. Su, B., Liu, L., Wang, F., Zhao, M., Tien, P., etal. (2003). HIV-1 subtype B dictates the AIDS epidemic among paid blood donors in the Henan and Hubei province of China. AIDS, 17,2515. Shepard,C.W., Finelli, L., Alter, M.J. (2005). Global epidemiology of hepatitis C virus infection. Lancet infect Dis, I5,558-67. 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