Incidence and clinical presentation of posttransfusion TT virus infection in prospectively followed transfusion recipients: emphasis on its relevance to hepatitis

BACKGROUND: A novel transfusion-transmissible human DNA virus, TT virus (TTV), has been discovered recently. An attempt was made to determine the incidence and clinical outcome of TTV infection in recipients of blood transfusion. STUDY DESIGN AND METHODS: Serial serum samples collected as part of a prospective study of posttransfusion hepatitis were examined for TTV DNA by a nested PCR assay. RESULTS: Among 150 adults undergoing cardiac surgery, posttransfusion specimens from 59 individuals were positive for TTV DNA. Pretransfusion sera were found to be positive in 13 of these individuals. Therefore, 46 (33.6%) of the 137 previously uninfected patients developed new TTV viremia after transfusion. Among the 46 patients, 3 were coinfected with HCV, 5 were coinfected with HGV, and 38 were infected with TTV alone. No apparent symptoms or signs were noted in the 38 patients infected by TTV alone or the 5 infected with HGV plus TTV. The average peak serum ALT activity was 31 IU per L, with persistently normal levels in 34 of the 38 patients with TTV infection alone. In 8 other patients who subsequently developed well-documented non-A-G hepatitis, 3 were positive for TTV (3/8 vs. 46/137, p = 0.8). In 12 patients followed for more than 1 year, TTV viremia persisted in every case. CONCLUSION: In this population, TTV is transmitted by transfusion to approximately 30 percent of patients who undergo cardiac surgery. Most of the infections appear to become persistent. Despite the high prevalence rate, TTV does not appear to cause hepatitis on its own.     

High prevalence of TT virus infection in French blood donors revealed by the use of three PCR systems

BACKGROUND: The purpose of this study was to determine the prevalence of TT virus (TTV) infection in voluntary blood donors in Southeastern France. STUDY DESIGN AND METHODS: The sera of 289 blood donors were tested for the presence of TTV DNA by two PCR systems detecting genes located in the 5' UTR (primer set A [Set A]) and the open reading frame (ORF2) (primer set B [Set B]) of the viral genome. A randomized sample of 40 blood donors was also tested by a nested-PCR system in the ORF1 by use of primer set C (Set C). Donors were questioned for possible risk factors for virus transmission. RESULTS: In the entire population studied, 30.8 percent of blood donors tested positive with both Sets A and B, and 70.6 percent with at least one set. In the sample tested with three sets of primers, 27.5 percent of blood donors were positive in testing with all PCR systems and 80 percent with at least one system. The specificity of TTV DNA amplification was confirmed by sequencing 10 PCR products obtained with each set of primers. Statistical analysis revealed that the prevalence of TTV reactivity increased with age. CONCLUSION: The high prevalence of TTV reactivity and the absence of a pathologic condition or risk factors obviously associated with the infection in blood donors suggest that there is no need for systematic detection of TTV infection before blood donation. Further studies are required to determine if TTV isolates can be responsible for a pathologic condition in humans after blood transfusion.     

Quantitative and genotypic analysis of TT virus infection in Chinese blood donors

BACKGROUND: The TT virus (TTV) is a member of a newly described family of human viruses related to the C ircoviridae viruses. Its association with specific diseases has not been established, and screening of blood donors has not been implemented. To date, 16 genotypes have been identified. STUDY DESIGN AND METHODS: Sera from 471 healthy blood donors (aged 11-58 years) were randomly selected and tested for TTV by the use of two sets of primers: NG59d/NG61d/NG63d primers and T801/T935 primers. Quantitative competitive PCR (QC-PCR) was developed to measure the TTV DNA concentration among the blood donors. Sequencing of a part of the genome was performed to identify the various genotypes. Several samples showed a mixed genotype infection. RESULTS: TTV was detected in 251 (53.3%) of 471 healthy Hong Kong blood donors by the use of NG59d/NG61d/NG63d primers. The prevalence of the virus increased steadily with age (p = 0.03). TTV DNA was detected in 90 percent (90 of a randomly selected 100) of samples by the use of T801/T935 primers. TTV DNA concentration was also measured by QC-PCR in the blood donors who were positive for TTV DNA in the first round of the heminested PCR. TTV titers ranged from 4.8 x 10(2) copies per mL to 6 x 10(4) copies per mL, with a median value of 1.2 x 10(4) copies per mL. Sequencing and phylogenetic analysis of a 223-bp fragment from open reading frame 1 showed three main genotypes (G1 [60.7%], G2 [24.3%], and G3 [14%]) and a new genotype 17 (G17), with the latter bearing 60-percent nucleotide homology with other genotypes deposited at GenBank. In addition, a new TTV subtype, G2f, was found. CONCLUSION: The prevalence of TTV is high in healthy Chinese blood donors. Three main genotypes (G1, G2, and G3) were detected. In addition, a new TTV genotype, tentatively designated as G17, and a new subtype, G2f, were identified.     

Prevalence of TT virus in serum and peripheral mononuclear cells from a CAPD population.

BACKGROUND: A novel virus named TT virus (TTV) has been isolated recently from patients with posttransfusional hepatitis of unknown etiology. The prevalence of TTV in several groups at risk has been reported, however, there is no information about the prevalence of TTV in patients on continuous ambulatory peritoneal dialysis (CAPD) without blood transfusions or hemodialysis antecedents. OBJECTIVE: To study the incidence of TTV in serum and peripheral blood mononuclear cells (PBMC) of CAPD patients. DESIGN: TTV DNA was detected by polymerase chain reaction, using primers from the open reading frames (ORF) 1 and 2, in serum and PBMC from 22 CAPD patients who had not received blood transfusions or hemodialysis therapy prior to CAPD. As controls, sera from 20 patients with chronic viral hepatitis (10 with HBV and 10 with HCV) and 20 healthy donors were included in the study. RESULTS: TTV DNA was detected in the serum of 5 of 22 (22.7%) CAPD patients with both sets of primers. Four of the 5 (80%) patients with TTV DNA in their serum were TTV positive in their PBMC with primers from ORF1 and ORF2. Five of 20 (25%) patients with chronic viral hepatitis (2 patients with HBV and 3 with HCV) and 4 of 20 (20%) healthy donors were TTV DNA positive in serum. No relation was found between TTV infection and the underlying kidney disease, previous surgery, and abnormal alanine aminotransferase levels. CONCLUSION: We have found a relatively high prevalence of TTV that is similar to that found in healthy donors and in patients with chronic viral hepatitis.     

Prevalence of the newly described human circovirus, TTV, in United States blood donors

BACKGROUND: A novel nonenveloped single-stranded circular DNA virus (TTV) was recently identified. The prevalence of TTV in blood donors in the United States is, however, still unclear. STUDY DESIGN AND METHODS: Viral DNA was detected in US blood donors from five cities by using two sets of TTV primers: NG059/NG061/NG063 primers, which amplified the conserved region of strains 1 and 2, and T801/T935 primers, which amplified the 5' end region of the TTV sequence. A TTV antibody assay system was based on the detection of the truncated open reading frame (ORF)-1 (amino acids 1-411) from type 1b. The truncated ORF-1 was expressed as a fusion protein in Escherichia coli, and the fusion protein was used as the antigen in the antibody assay system. RESULTS: Viremia was detected in 21 (8. 4%) of 250 donors by use of NG059/NG061/NG063 primers and 104 (41. 6%) of 250 by use of T801/T935 primers. There was little correlation among the assays, which suggests the preferential detection of different strains with the different primers. TTV antibody was detected in 38 of 100 donors: 32 (84%) of 38 with concurrent TTV viremia and 6 (16%) of 38 without TTV viremia. TTV viremia and/or TTV antibody-positive samples were detected in 52 (52%) of 100 of US blood donors. CONCLUSION: Evidence of infection or exposure to TTV appears to be common among blood donors in United States.     

Bactericidal properties of Campylobacter jejuni-specific immunoglobulin M antibodies in commercial immunoglobulin preparations.

Campylobacter jejuni is one of the most common enterocolitis-causing microorganisms worldwide. It is of particular importance in immunodeficient patients, who frequently are prone to develop extraintestinal manifestations. Since these cases respond poorly to antibiotic treatment, a supportive immunomodulating therapy including the administration of C. jejuni-specific immunoglobulins would be desirable. In the present study, nine commercial immunoglobulin preparations for intravenous use were tested for the presence of C. jejuni lipopolysaccharide (LPS)- and outer membrane protein (OMP)-specific antibodies by using immunoblot and enzyme-linked immunosorbent assay techniques. The immunoglobulin G (IgG) antibody reactivities against these antigens were comparable in eight of nine tested immunoglobulin preparations. Only in one preparation were C. jejuni OMP- and LPS-specific IgM antibodies found. In this preparation the immunoblot test revealed a strong reactivity against both flagellin and a major OMP. Moreover, all immunoglobulin preparations recognized OMPs of C. jejuni serotypes Lior 4, 9, 11, and 29 equally strongly, while the reactivity to an anti-Lior 36 isolate was less marked. Furthermore, the bactericidal properties of three immunoglobulin preparations were tested by means of chemiluminescence signaling in and bacterial killing by human polymorphonuclear leukocytes (PMNL). The results show that the IgM preparation enhanced Campylobacter-triggered chemiluminescence signaling in PMNL as well as killing of C. jejuni by PMNL, while the other immunoglobulin preparations did not do so. These results suggest that the administration of immunoglobulin preparations containing C. jejuni-specific IgM antibodies would be beneficial for patients with severe C. jejuni infections.     

TT virus infections among blood donors in Iceland: prevalence, genotypes, and lack of relationship to serum ALT levels

BACKGROUND: The TT virus (TTV) is a newly identified blood-borne virus. Its association with disease is still unknown, and screening of blood donors has not been implemented. Several genotypes of the TTV have been identified. STUDY DESIGN AND METHODS: Three hundred seventy healthy blood donors were randomly selected and tested for TTV by the PCR method. Sequencing of a part of the genome was performed to identify various genotypes of the virus. ALT levels were determined in both infected and uninfected individuals. RESULTS: The TT virus (TTV), was detected in the sera of 23 (6.2%) of 370 healthy Icelandic blood donors; this prevalence is lower than that reported in Japan but higher than that in Scotland. The virus was found in all groups over the age of 19. Sequencing and phylogenetic analysis of 202 bp from open reading frame 1 demonstrated genotypes 1b and 2b 2c and genotype 4 isolates, with the latter bearing 89-percent nucleotide homology with other genotype 4 sequences deposited at GenBank. One sample showed a mixed genotype 1b/2c infection. Serum ALT levels were within normal limits in all infected individuals. CONCLUSION: The TTV carrier state does not cause significant liver injury.     

深圳市一般人群HGV和TTV感染的研究

为探讨深圳市一般人群中HGV和TTV感染状况及其影响因素。方法采用随机抽样法选取研究对象 ,对HGV感染的检测先用ELISA法检测样本中的抗 -HGV ,对其中阳性样本再用反转录PCR(RT -PCR)进行检测 ;TTVDNA则采用巢式PCR方法检测。结果表明 ,深圳市一般人群中HGVRNA和TTVDNA阳性率分别为 2 33%和 14 77% ,男女阳性率HGVRNA为 2.45%和2.20% ,TTVDNA阳性率为 17.86%和 12.0%。年龄组间HGVRNA及TTVDNA阳性率差异均无显著性 ;单因素和Logistic回归分析未显示肝炎病史、近期手术史、注射史、拔牙史及乙型肝炎疫苗接种史等因素与HGV及TTV感染有关 ;HBsAg、抗 -HBS和抗 -HBc与HGV及TTV感染无统计学意义。不同职业人群中HGVRNA阳性率以中学生和教师较高 ;TTVDNA阳性率则以税务干部和教师高于其他人群 ,因此证明 ,深圳市一般人群中HGV和TTV感染率较高 ,但其流行因素有待进一步研究。     

献血者TT病毒DNA及其IgG抗体的检测

目的　观察献血者输血传播病毒 (TTV)的感染情况。方法　应用 Nested- PCR对 388例献血者、16 8例非肝炎住院患者进行 TTV DNA检测 ,同时用 EL ISA法检测抗 TTV Ig G。结果　 TTV基因检出率分别为献血组 15 .46 % ,对照组 2 4.40 % ;5 5 6例受检血清中 TTV DNA总的阳性检出率为 18.17% ,抗 TTV Ig G检出率分别为献血组 13.14% ,对照组 2 7.98% ;献血组与对照组相比 TTV DNA及抗 TTV Ig G均存在显著性差异 (P<0 .0 5 )。结论　献血者存在TTV感染 ,TTV存在健康携带状态。     

83例静脉药瘾者的TT病毒感染状况

目的：调查静脉药瘾者中ＴＴ病毒（ＴＴＶ）的感染状况。方法：在ＴＴ病毒开放读码框（ＯＲＦ）１保守区设计引物,建立巢式ＰＣＲ,检测８３例静脉药瘾者和１０５名献血员血清中ＴＴＶ ＤＮＡ。结果：８３例静脉药瘾者中３３例ＴＴＶ ＤＮＡ阳性,阳性率为４０％,而献血员的阳性率为１１％（Ｐ〈０．０５）。结论：静脉药瘾者是ＴＴ病毒感染的高危人群,不洁注射是感染ＴＴ病毒的重要途径。     

肝炎患者中TT病毒DNA及其IgG抗体的检测

目的：了解肝炎患中TTV的感染情况，方法：应用Nested-PCR对137份甲－庚型肝炎、31份非甲－庚型肝炎及104份献血员进行TTV DNA检测，同时用ELISA法检测抗TTVIgG。结果：TTV基因检出率分别为甲－庚型肝炎20．44％，非甲－庚型肝炎29．03％，献血员13．46％，抗TTVIgG检出率分别为甲－庚型肝炎27．74％，非甲－庚型肝炎35．48％，献血员14．42％；甲－庚型肝炎、非甲－庚型肝炎与献血组相比TTV DNA及抗TTV IgG均存在显性差异（P＜0．01）。结论：肝病中存在TTV感染，TTV存在健康携带状态。     

Epitope-specific glutamic acid decarboxylase-65 autoantibodies in intravenous immunoglobulin preparations

Intravenous immunoglobulin (IVIG) has been used to treat many autoimmune disorders including Stiff-Man Syndrome (SMS). SMS is a neurological disorder associated with an immune-mediated deficiency of gamma-aminobutyric acid (GABA) due to autoantibodies against the GABA synthesizing enzyme glutamic acid decarboxylase-65 (GAD65). GAD65 autoantibodies are present among 1-2% of healthy individuals. It can therefore not be excluded that GAD65 autoantibodies may be present in IVIG, which is prepared from multiple blood donors. We report here that GAD65 but not IA-2 autoantibodies were present in commercial IVIG preparations. The presence of autoantibodies may affect the outcome of IVIG treatment and screening commercial preparations of IVIG for GAD65 autoantibodies is therefore recommended before treating patients.     

Serum IgG subclass concentrations before and after administration of intravenous immunoglobulin in common variable immunodeficiency.

IgG subclass levels were measured before and after administration of intravenous immunoglobulins (IVIGs) in patients with common variable immunodeficiency (CVI). Six patients were treated with IVIG at the dose of 100-150mg/kg to maintain a trough level of 200mg/dl every 4 or 5 weeks, except for patient 5 who was given IVIG only 3 or 4 times per year. Three kinds of IVIGs, polyethylene-glycol (PEG)-treated IVIG, alkylated IVIG and sulfonated IVIG were used for replacement therapy. Although serum IgGl levels were low before administration of IVIGs, they increased to the normal levels after each administration of IVIGs in four patients. IgG2 preserved normal levels before and after administration of IVIGs in all patients. IgG3 was present at low normal concentration in patient 1, low concentration in patients 2, 3 and 6, and undetectable in patients 4 and 5 before infusion. Although increases in IgG3 levels were shown after infusion of PEG-treated IVIG, there were no increases after infusion of sulfonated or alkylated IVIG. However, there have been several reports that IgG3 is detected in sulfonated or alkylated IVIG preparations by another method. IgG4 levels were somewhat low before administration, but four patients achieved normal serum levels with treatment. In light of the above results of replacement therapy with IVIGs, we should consider the IgG subclass levels for patients such as CVI or selective IgG subclass deficiency.     

Immunoglobulin G dimers and immune complexes are dispensable for the therapeutic efficacy of intravenous immune globulin in murine immune thrombocytopenia

BACKGROUND: Several mechanisms have been proposed to explain the therapeutic effects of intravenous immunoglobulin (IVIG) in immune thrombocytopenia (ITP). Noteworthy, a major role has been attributed to immunoglobulin (Ig)G dimers present in IVIG. It has also been suggested that immune complexes formed between IVIG and the patient's proteins after infusion could contribute to the therapeutic effect of IVIG in several autoimmune disorders. We recently observed that in‐house preparations of polyclonal human IgG derived from small pools of plasma and devoid of IgG dimers were as efficient as IVIG in a mouse model of thrombocytopenia. In this work, we revisited the role of IgG dimers in the therapeutic effects of IVIG in ITP. STUDY DESIGN AND METHODS: We used the passive mouse model of ITP to determine the therapeutic efficacy of human IgG preparations devoid of IgG dimers and of dimer‐enriched and ‐depleted commercial IVIG. Immune complex formation between IVIG and mouse plasma proteins was evaluated using a combination of chromatography and immunoprecipitation procedures. RESULTS: All preparations tested showed the same efficacy to alleviate ITP, regardless of their dimer contents. Significant amounts of immune complexes formed between IVIG and mouse plasma proteins were detected. However, the amount of immune complexes detected using the in‐house preparation of human polyclonal IgG and mouse plasma was significantly lower, although the in‐house preparation exhibited the same therapeutic efficacy as commercial IVIG. CONCLUSION: IgG dimers and immune complexes are dispensable to prevent thrombocytopenia in a mouse model of the disease.     

Hepatitis C virus infection in hypogammaglobulinemic patients receiving long-term replacement therapy with intravenous immunoglobulin

BACKGROUND: Hepatitis C virus (HCV) seroconversion and viremia have been reported in patients treated with intravenous immunoglobulin (IVIG). STUDY DESIGN AND METHODS: A prevalence study was conducted to evaluate the rate of HCV infection in patients undergoing long-term treatment with IVIG. Fifty-four patients with congenital or acquired hypogammaglobulinemia treated with IVIG at 300 to 400 mg per kg every 14 to 21 days for a mean of 6.6 years were enrolled for clinical and biochemical examination. The type of IVIG preparation (type 1 only, type 2 only, or other products) administered to each patient was recorded. Antibodies to HCV were measured by enzyme-linked immunosorbent assay and immunoblotting; HCV RNA was detected by nested polymerase chain reaction. RESULTS: Anti-HCV was detected in 31 patients (57.4%) and HCV RNA was found in 5 patients (9.2%), all of whom were anti-HCV-positive. Abnormal alanine aminotransferase (ALT) levels were found in 10 patients (18.5%). Circulating HCV RNA (p = 0.01) and elevated ALT (p = 0.01) correlated significantly with anti- HCV positivity. Moreover, the rates of anti-HCV positivity and of ALT elevation were significantly higher among patients treated with type 1 IVIG and other products than among those receiving type 2 IVIG (p < 0.001 and p = 0.05, respectively). CONCLUSION: Anti-HCV positivity and viremia were frequently observed. The significant correlation between the detection of HCV RNA, the elevation of ALT, and positivity for anti- HCV suggests HCV infection. Exclusion of anti-HCV-positive donors and of anti-HCV-positive IVIG lots should improve the safety of IVIG.     

Czech Hizentra Noninterventional Study With Rapid Push: Efficacy,Safety, Tolerability,and Convenience of Therapy With 20% Subcutaneous Immunoglobulin

PurposeImmunoglobulin substitution therapy is an essential therapeutic approach for patients with primary antibody deficiencies. Different methods of administration, including intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) preparations, provide effective and tolerable treatment and enable the adjustment of therapy to patients’ needs. A new 20% SCIG represents a new therapeutic option and a new route of administration using rapid-push application. The aim of the Czech Hizentra Noninterventional Study With Rapid Push (CHHINSTRAP) is to evaluate patient satisfaction with as well as the tolerability and efficacy of nonmedical switch to 20% SCIG from previous treatment with IVIG or SCIG and rapid push as a new way to administer SCIG. CHHINSTRAP is the first Phase IV, noninterventional, open-label, prospective, multicentric study of this type conducted in Central and Eastern Europe.MethodsPrimary end points, including efficacy, adverse effects, convenience of use, and overall satisfaction, were evaluated by Treatment Satisfaction Questionnaire for Medication version II. Secondary end points, such as serum IgG trough levels, infusion duration, number of application sites, frequency of infections, related hospital admissions, and antibiotic consumption, were obtained from patients at each follow-up visit.FindingsTogether, 50 eligible patients with primary antibody deficiency were switched from SCIG or IVIG to an equivalent dose of 20% SCIG and were followed up for 12 months during 5 consecutive visits. The results indicate that patients switched from previous IVIG or SCIG preparations had significantly higher serum trough IgG levels and a lower incidence of infections and related events, such as hospital admissions or consumption of antibiotics. These findings were also reflected in gradually increasing convenience of use and overall satisfaction reported by patients. Apart from duration of application, no differences were found between patients previously receiving SCIG or IVIG. Moreover, our study found a high level of safety of 20% SCIG rapid push, which was comparable to other preparations and application methods.ImplicationsOn the basis of the results of CHHINSTRAP study, we conclude that 20% SCIG is a tolerable and effective immunoglobulin preparation, representing a new therapeutic approach in patients with primary antibody deficiencies. Its efficacy and tolerability have been found in patients on nonmedical switch from previous treatment with IVIG or SCIG.     

Lack of transmission of neutrophil and platelet antibodies by intravenous immunoglobulin in bone marrow transplant patients

BACKGROUND: Several studies have demonstrated that the administration of intravenous immunoglobulin (IVIG) may be followed by the transient appearance of positive red cell antibody screens, positive direct antiglobulin tests, and, occasionally, frank hemolysis. However, little information is available regarding the possibility that IVIG could transmit neutrophil and/or platelet antibodies. STUDY DESIGN AND METHODS: Serum samples were obtained both immediately before and immediately after the administration of 12 separate lots of commercially available IVIG to bone marrow transplant patients. RESULTS: None of the patients were shown by standard granulocyte immunofluorescence testing to have acquired neutrophil antibodies. Four of the 12 postinfusion sera were positive for platelet antibodies in standard platelet suspension immunofluorescence testing, but in all four instances the corresponding preinfusion serum was positive as well. CONCLUSION: The risk of acquiring neutrophil and/or platelet antibodies after the administration of commercially available IVIG appears to be low.     

TT virus genotype changes frequently in multiply transfused patients with hemophilia but rarely in patients with chronic hepatitis C and in healthy subjects

BACKGROUND: TT virus (TTV), a novel DNA virus, was originally thought to be transmitted by transfusion. However, nonparenteral transmission is recently suspected to be a major mode of transmission. To investigate the possibility of reinfection with TTV in multiply transfused patients and to evaluate the significance of transfusion transmission of TTV in patients with hemophilia, serial changes in TTV genotype were investigated in three groups. STUDY DESIGN AND METHODS: Serial changes in TTV genotype were investigated in 16 multiply transfused patients with hemophilia, 16 age-matched patients with chronic hepatitis C, and 16 age-matched healthy subjects. RESULTS: Mixed infection with multiple TTV genotypes was common in all groups. However, changes in TTV genotype were frequent in patients with hemophilia (15/16; 93.8%) but rare in patients with chronic hepatitis C and in healthy subjects (each group: 1/16; 6.3%). CONCLUSION: Changes in TTV genotype were frequently observed in multiply transfused patients with hemophilia but not in patients with chronic hepatitis or in healthy subjects without risk of transfusion transmission. This difference may suggest that exposure to TTV or even reinfection occurs frequently in patients with hemophilia, which could be evidence of transfusion transmission of TTV in this population.     

Value of anti-HBc screening of blood donors for prevention of HBV infection: results of a 3-year prospective study in Northwestern Greece

BACKGROUND: The risk of infection with transfusion-transmitted viruses has been reduced remarkably. However, a zero-risk blood supply remains a popular goal. Some authorities have introduced the screening for antibody to HBc (anti-HBc) as a surrogate test for the presence of several infectious agents. A 3-year prospective study was conducted in the Epirus region of Greece to determine the prevalence of several blood-borne viruses. One component of the study was the prevalence of HBV infection markers and the potential value of anti-HBc testing of donors in this area. STUDY DESIGN AND METHODS: Between January 1, 1995, and December 31, 1997, some 6696 donors were investigated for the presence of HBV infection markers by standard EIAS: Every sample that tested HBsAg-negative but anti-HBc-reactive alone or in combination with either or both antibodies to HBV e antigen (anti-HBe) and low-titered antibodies to HBsAg (anti-HBs <20 mIU/mL) was further investigated for the presence of HBV DNA by a combination of PCR and DNA EIA. RESULTS: Of these 6696 donors, 15.8 percent tested positive for at least one serologic marker of HBV infection (HBsAg prevalence, 0.85%). Anti-HBc reactivity alone or in combination with either or both anti-HBe and low-titered anti-HBs was found in 282 donors (4.2%). None tested HBV-DNA positive. No transfusion-associated HBV infections were recorded in the recipients of the above 282 blood units. CONCLUSION: A moderate prevalence of HBV infection markers was found. However, taking into account previous studies from this region, it appears that the HBsAg prevalence has declined. In addition, the present study cannot recommend the introduction of anti-HBc screening as a surrogate marker of occult HBV infection. The adoption of this exclusion criterion in this region would result in unacceptably high rejection rates among otherwise healthy donors. The absence of any case of transfusion-associated HBV infection after the transfusion of all HBsAg-negative, anti-HBc-positive units appears to provide further support for the negative HBV DNA results. Before a consideration of screening donors, efforts must be focused on reducing the number of false-positive anti-HBc results.