Viremia levels in hepatitis C infection among Egyptian blood donors and implications for transmission risk with different screening scenarios

Abstract

BACKGROUND Knowledge about the viral load (VL) distributions in different stages of hepatitis C virus (HCV) infection is essential to compare the efficacy of serologic screening and nucleic acid testing (NAT) in preventing transfusion transmission risk. We studied HCV‐RNA levels in Egyptian blood donors in the preseroconversion window period (WP) and in later anti‐HCV–positive stages of infection. STUDY DESIGN AND METHODS Subsets of individual‐donation (ID)‐NAT and anti‐HCV–yield samples from a screening study among 119,756 donors were tested for VL by quantitative polymerase chain reaction (qPCR). Low viremia levels below the quantification limit of qPCR were determined by probit analysis using the proportion of reactive results on replicate NATs. Poisson distribution statistics were used to estimate transmission risk in different stages of HCV infection based on 50% minimum infectious doses (MID50) of 3.2 (1‐10) and 316 (100‐1000) virions in the absence and presence of anti‐HCV, respectively. RESULTS Rates of total HCV infections and WP‐NAT–yield donations in two Egyptian blood centers varied between 2.6% to 4.5% and 1:3100 to 1:9500, respectively. VLs ranged from 82 to 3 × 107 copies/mL in WP and from fewer than 1600 to 1.6 × 106 copies/mL in anti‐HCV–positive carrier donations. Only two (1.1%) of 175 donors with probable resolved infection had detectable RNA on replicate testing (estimated VLs of 0.5 and 1.8 copies/mL). This translates to an estimated transmission risk of 0.028% if ID‐NAT‐nonreactive, anti‐HCV–positive donations would be used for RBC transfusions. CONCLUSION Almost 99% of anti‐HCV–reactive donations without detectable HCV‐RNA on initial ID‐NAT screening had eradicated the virus from the circulation, while 1% had extremely low VLs and are likely not infectious. The incremental safety offered by serologic testing of ID‐NAT–screened blood seems minimal.

Relative efficacy of nucleic acid amplification testing and serologic screening in preventing hepatitis C virus transmission risk in seven international regions

“…Nevertheless, while there was potential for some PR infections to be misclassified, resulting in regional differences in the proportion of HCV infections categorized as PR, the extent of error would be small and would not substantially influence overall modeling results. Most importantly, infectivity risk from transfusing a PR donation missed by ID‐NAT was assessed to be very low due to the very rare detection of HCV RNA by replicate NAT of PR donation plasma and the low infectivity even when virus is present due to neutralizing activity of anti‐HCV …”

“…Poland was considered a separate region due to significant differences in prevalent HCV infections in FT donations compared to the other countries in Europe. Egypt was analyzed as a separate region in the risk and efficacy analyses, as HCV prevalence was the highest in this country and the submitted data did not separate out the small number of lapsed or repeat donations …”

Diverse Genotypes of Hepatitis C Virus in Voluntary Blood Donors in Shanghai, China

“…The low detection rate could be generally interpreted by different dynamics of antibody and viral nucleic acid, such as spontaneous clearance of HCV or resolved HCV RNA in blood specimens (20)(21)(22)(23). However, no partial sequence was amplified in the specimens negative for anti-HCV while positive by NAT.…”

Interpretation of pathogen load in relationship to infectivity and pathogen reduction efficacy

“…The period of high viremia (estimated as 50 days) has a rapid development of positive NAT and rapid doubling time of virus with copies ranging from 10 5 to 10 7 (Table ) . Carriers with viral loads below detectability have been reported …”