Background
In Poland, hepatitis A virus (HAV) RNA screening was performed in plasma for fractionation usually immediately before shipment.
Objective
Our goal was to study epidemiology, rate of ...transfusion transmitted HAV during epidemic (2017–2019), and viral characteristics of infected plasma donors.
Study Design and Methods
HAV RNA was tested in 1,866,590 donations from 1,210,423 donors using RT‐PCR in mini pools of 96 (MP96) or TMA in MP16. Virological characteristics included RNA level (RL), antibody testing, and sequencing.
Results
Twenty‐one HAV infections were identified (1.13/100,000 donations; 95% confidence interval 95% CI: 0.74–1.72) and (1.73/100,000 donors; 95% CI: 1.35–2.65). The Blood Transfusion Centers were also informed about three donors, who were hospitalized for hepatitis A soon after their blood donation. In addition, we identified a donor, who had reactive result for HAV after receiving HAV vaccination. He tested positive twice 10 days after receiving the first and the second dose.
The highest RL was 16 million IU/ml, mean 1,706,905 IU/ml, and median 220 IU/ml. The longest detectable RL lasted for 113 days. HAV‐infected donors were seronegative (36%) or IgM positive (64%).
We followed up on 12 HAV contaminated blood components issued for transfusion. In two out of seven identified patients viral transmission was confirmed (28.6%).
Conclusion
Based on our results, we propose a 6 month deferral after HAV infection and 14 days post HAV vaccination. The infectivity rate was below 30%. The HAV RNA testing could be considered as an additional safeguard against HAV transmission at the time of increased incidence of HAV infections in the general population.
BACKGROUND
Until now, markers of hepatitis E virus (HEV) infection have not been studied in blood donors throughout Poland, and no acute case of HEV infection has been closely documented or confirmed ...by HEV RNA detection. The prevalence of HEV infection markers, including HEV RNA in Polish blood donors and virus genotypes was investigated.
STUDY DESIGN AND METHODS
In total, 12,664 individual donations from 22 Polish blood transfusion centers were tested for HEV RNA by transcription‐mediated amplification. In addition, 3079 first‐time donors sampled throughout Poland also were screened for antibodies to HEV. HEV RNA and immunoglobulin M‐positive donations were confirmed using real‐time reverse transcription‐polymerase chain reaction and Western blotting, respectively.
RESULTS
Ten donors were identified as RNA initial reactive (one of 1266 donors), and six (one of 2109) were identified as repeat reactive and confirmed by real‐time reverse transcription‐polymerase chain reaction or seroconversion. Sequence analysis identified HEV Genotype 3c in one donor and Genotype 3i in two others. On average, 43.5% of donors were immunoglobulin G‐positive. Immunoglobulin G seroprevalence ranged from 22.7% to 60.8% in group ages 18 to 27 years and 48 to 57 years, respectively and differed between administrative regions from 28.9% in Podlasie to 61.3% in Wielkopolska. Thirty‐nine of the donors were immunoglobulin M‐positive, and seven donors were IgM positive only (0.2%). Of 37 immunoglobulin M‐reactive samples tested by Western blot, 24 (64.9%) were confirmed.
CONCLUSIONS
The current results indicate a high level of HEV endemicity throughout Poland compared with other countries. There is an urgent need to consider the protection of recipients of blood components against transfusion‐transmitted HEV infection.
Nucleic acid testing (NAT) was implemented in Poland in 1999 for screening of plasma for fractionation and for all blood donors in 2002. To analyze seronegative NAT‐positive samples representing ...hepatitis C virus (HCV) window‐period (WP) in the years 2000 to 2016 and to determine infection outcome. We analyzed results of 17 502 739 donations screened in minipools (6‐48) or individually. Index samples underwent viral load (VL) quantification, genotyping and Ag, and anti‐HCV re‐testing using chemiluminescence (CMIA), electrochemiluminescence (ECLIA), and fourth‐generation enzyme‐linked immunosorbent assay (IV EIA) assays. HCV‐seronegative infections were identified in 126 donations (7.2/mln donations; 95% confidential intervals, 6.0‐8.6). Frequency of NAT yields was decreasing over time. Of the initial 126 seronegative index cases 106 were retested: 32.1% were reactive in IV EIA, 11.3% in ECLIA, and 1.9% in CMIA. The lowest VL correlated with absent anti‐HCV and HCV Ag, while VL was highest when the antigen was detectable and then it decreased when anti‐HCV appeared at a level detectable by sensitive third generation tests while retesting. The proportion of genotype 1 was 38.9% in samples positive only for HCV RNA and 71.4% in samples that were anti‐HCV reactive in re‐testing. In parallel, genotype 3 frequency was 50% in the former group and 21% in the latter. NAT is an effective measure to limit HCV transmission by transfusion and IV EIA seems to have higher clinical sensitivity than ECLIA. Samples representing likely successive phases of early HCV infection were characterized by different genotype distribution probably due to very early elimination of genotype 3.
Highlight
NAT is highly effective in prevention of transmission of HCV seronegative infections.
In nearly 7% of followed up donors antibodies appeared later than 50 days after index donation.
The highest clinical sensitivity was demonstrated by the IVth generation tests.
Among the third generation assays, ECLIA showed higher sensitivity than CMIA.
Samples representing likely successive phases of early HCV infection demonstrated different genotype distribution.
BACKGROUND
Since the introduction of nucleic acid testing (NAT) for routine blood donor screening, hepatitis C virus (HCV) RNA‐only detection rates reported from Poland have been higher than in most ...other European countries.
STUDY DESIGN AND METHODS
To examine factors that likely contribute to these window‐period donations, we conducted a case‐control study among 47 recently HCV‐infected blood donors (cases), who gave blood between July 2002 and June 2014, and 141 controls matched by age, sex, and donation dates. Firth‐corrected, conditional logistic regression models were fitted to estimate adjusted odds ratios and 95% confidence intervals. Adjusted population‐attributable fractions were calculated based on the distribution of exposure among the cases.
RESULTS
On multivariate analysis, recent exposures in health care environments not routinely ascertained through predonation questionnaires were strongly associated with recently acquired HCV infection. These exposures included minor medical and dental procedures in the preceding 6 months (adjusted odds ratio, 5.77; 95 % confidence interval, 2.01‐18.53). However, based on the population‐attributable fraction, more important were behavioral deferrable risks that went unreported at the time of donation, such as high‐risk sexual behaviors in the preceding 6 months (population‐attributable fraction, 34%) or lifetime histories of drug use (population‐attributable fraction, 28%).
CONCLUSIONS
This study raises questions about the effectiveness of deferral policy in excluding high‐risk individuals. In addition, it provides further evidence supporting short, temporal deferrals for small medical procedures and dental treatments in Poland.
Abstract
Most Hepatitis C virus (HCV)-infected subjects develop chronic infection, whereas a minority clear the virus in the early phase of infection. We analyzed factors associated with outcome ...(chronicity vs clearance) during the preclinical seronegative phase of community-acquired HCV infection. Among 17.5 million blood donations in the years 2000–2016, 124 blood donors were found to be HCV RNA-positive/anti-HCV-negative. All were contacted after 0.5–12.7 years and 40 responded and provided blood sample. Hypervariable region 1 was analyzed by ultradeep pyrosequencing and cytokines in serum were quantified by Luminex (R&D Systems) multiplex immunoassay. Twenty-one (52.5%) donors were found to be HCV-RNA-positive, while 19 (47.5%) were HCV RNA negative (none received antiviral treatment). All but one seroconverted to anti-HCV. Donors with resolving hepatitis did not differ significantly from donors with chronic infection with respect to age, genotypes, IL28B polymorphisms, number of viral variants, nucleotide diversity per site or the overall number of nucleotide substitutions. However, the former group had significantly higher levels of IL-1beta, IL-1RA, IL-6, IFN-gamma and FGF-2 in serum. In our study of community-acquired acute hepatitis C approximately half of all subjects eliminated the virus spontaneously, and this clearance was associated with marked cytokine response in the early seronegative stage of infection.
In Poland, independent evaluations under the auspices of the Institute of Hematology and Transfusion Medicine (IHTM) are mandated for any new device, assay, systems for screening samples from whole ...blood and plasma donors prior to implementation by Blood Transfusion Center (BTC). In last 5 years, two new systems were introduced to the market by Abbott GmbH, namely the Alinity s and the Alinity i. The evaluations performed for these two systems included the assessment of sensitivity, specificity and precision for each of the four mandatory serological screening markers in Poland: Hepatitis B Surface Antigen (HBsAg), Hepatitis C virus antibodies (Anti-HCV), HIV antibodies (anti-HIV) and Syphilis antibodies (anti-Treponema pallidum, anti-TP). Sensitivity was assessed by testing seroconversion panels, HBsAg international reference standard, well characterized local samples, and dilution panels. Specificity was assessed by testing routine donor samples. The results from Alinity i assays were compared to the results from Abbott ARCHITECT i2000SR and Ortho VITROS 3600 assays, while the results from Alinity s assays were compared to the results of ARCHITECT i2000SR assays. The evaluation of the Alinity s and Alinity i assays for sensitivity (100 %), specificity (99,92–100 %) and precision generated results that were as good as or better than generated by routinely used systems, were within acceptance criteria, and met all requirements for screening blood donor samples in accordance with Polish regulations. The specificity of the assays in routine use by BTCs, analyzed after approximately 150,000 donations on both systems, was comparable to the specificity observed during the evaluations at IHTM.
Blood donor screening of viral markers in Poland is based on serologic testing for anti-HCV, HBsAg, anti-HIV1/2 (chemiluminescence tests) and on nucleic acid testing (NAT) for RNA HCV, RNA HIV-1 and ...DNA HBV performed in minipools of 6 with real-time PCR (MPX 2.0 test on cobas s201) or with TMA in individual donations (Ultrio Plus or Ultrio Elite). Donors of plasma for anti-D and anti-HBs production are tested for parvovirus B19 DNA. Before implementation tests and equipment are evaluated at the Institute of Hematology and Transfusion Medicine (IHTM). The last 20 years witnessed a decreasing trend for HBsAg in both first time and repeat donors (1%-0.3% and 0.1%-0.02% respectively). Prevalence of anti-HCV repeat reactive results was stable and oscillated around 0.8% for first time donors and 0.2% for repeat donors. Elevated prevalence of seropositive HIV infected donors was recently observed (7.5-9 cases/100,000 donors). Since respective molecular markers implementation HCV RNA was detected on average in 1/119,235 seronegative donations, HIV RNA in 1/783,821 and HBV DNA in 1/61,047. HBV NAT yields were mostly occult hepatitis B (1/80,248); window period cases were less frequent (1/255,146). The efficiency of HBV DNA detection depends on the sensitivity of the HBV DNA screening system.
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