PubMed Health⌕ Search

Biomedical subjects

Susan L Stramer

Publications and source records attributed to Susan L Stramer.

At least 19 recordsLinked to original sources
PubMed2007

Emerging infectious diseases that threaten the blood supply.

Following the devastating effects of blood-transmitted human immunodeficiency virus (HIV), blood establishments have become increasingly vigilant for the emergence or re-emergence of new threats to the safety of the blood supply. Many agents have fulfilled the broad definition of emerging blood-transmitted infections, including West Nile virus (WNV), Trypanosoma cruzi, Plasmodium spp., Babesia spp., parvovirus B19, dengue virus, and the prions that cause variant Creutzfeld-Jacob disease (vCJD). Other agents such as human herpes virus-8 (HHV-8-Kaposi's sarcoma virus) and Borellia (Lyme disease) and, perhaps, avian flu virus, are known to have a viremic phase, but have not yet been proved to be transfusion-transmitted. In the wake of these threats, transfusion services use a variety of donor screening interventions, including serologic assays, nucleic acid assays, and geographic exclusions based on potential exposure. The ultimate safeguard may be a pre-emptive pathogen inactivation strategy that will disrupt all nucleic acid-containing agents (though not prions). Considerable effort and resources have been invested in this arena, but currently no single technique is effective for inactivation of both liquid and cellular blood products and toxicity issues have not been completely resolved. The blood supply is remarkably safe with the risk of major pathogens such as hepatitis C virus (HCV) and HIV now reduced to less than one transmission per 2 to 3 million exposures. However, to approach near-zero infectious disease risk for emerging and re-emerging pathogens, new strategies such as pathogen inactivation or multi-pathogen microarray technology will need to be developed or refined.

Blood Donors↗
PubMed2006

Correlates of hepatitis C virus (HCV) RNA negativity among HCV-seropositive blood donors.

BACKGROUND: Approximately 20 percent of persons infected with hepatitis C virus (HCV) clear viremia. Factors associated with resolution of viremia are not well defined. Implementation of routine nucleic acid testing (NAT) of blood donors has yielded a large data set for analysis of demographic correlates of resolved viremia. STUDY DESIGN AND METHODS: HCV antibody and NAT data, liver enzyme (alanine aminotransferase [ALT]) results, and donor demographic characteristics were compiled for 2,579,290 allogeneic donations given at five large blood centers after NAT implementation in 1999 through December 2001. Donation HCV RNA status was compared between first-time donors categorized by ALT levels, sex, age, race and/or ethnicity, country of birth, level of education, blood center location, and blood group, with chi-square tests and multivariable logistic regression methods. RESULTS: Of 35 confirmed-seropositive repeat donors, 19 (54.3%) tested negative for the presence of HCV RNA; there was no association between RNA status and preseroconversion intervals (p = 0.74). Of 2105 RIBA-positive, first-time donors, 402 (19.1%) tested negative for the presence of HCV RNA by NAT (presumptive resolved infections). There were significant differences in the frequency of RNA negativity among first-time donors categorized by ALT levels and by race and/or ethnicity. ALT levels were more likely to be elevated in RNA-positive, first-time donors (p < 0.0001). Viremia was less likely to resolve in Asian (8.2%) and black non-Hispanic (14.4%) donors than in white non-Hispanic (20.7%), Hispanic (22.1%), and other race and/or ethnicity (22.1%) donors (p = 0.02). No significant associations were found for age, sex, country of origin, level of education, blood type, and donor center location. CONCLUSION: These results confirm that the frequency of HCV RNA negativity among seropositive persons differs by race and/or ethnicity. Follow-up studies of donors with resolved viremia are warranted to further elucidate viral, immunologic, and genetic factors underlying spontaneous viral clearance.

Adult↗
PubMed2006

Integration of nucleic acid amplification test results into hepatitis C virus supplemental serologic testing algorithms: implications for donor counseling and revision of existing algorithms.

BACKGROUND: The routine use of hepatitis C virus (HCV) nucleic acid amplification testing (NAT) donor screening assays has provided an opportunity for revision of the current HCV supplemental testing algorithm, which requires that recombinant immunoblot assay (RIBA) be performed on every HCV enzyme immunoassay (EIA)-repeat-reactive donation. The FDA has approved variance requests to use a new algorithm that eliminates the need to perform RIBA when HCV NAT results are reactive. Data are provided in support of this new algorithm. STUDY DESIGN AND METHODS: HCV EIA (including signal-to-cutoff optical density ratio), RIBA, and NAT data were compiled from 33.2 million donations screened over an approximately 4-year period by the American Red Cross and Blood Systems Laboratories. Further, donations having specific combinations of HCV EIA, RIBA, and minipool (MP) NAT results were evaluated, with more sensitive individual-donation (ID) NAT, to construct improved counseling messages for donors. RESULTS: Of 47,041 EIA-repeat-reactive donations, 49.3 percent were RIBA-positive, 17.1 percent RIBA-indeterminate, and 33.5 percent RIBA-negative. NAT-reactive rates were 79.2, 2.5, and 0.18 percent for RIBA-positive, -indeterminate, and -negative donations, respectively. The new algorithm classified an additional 1 percent of donations as HCV-infected while at the same time detecting all infections classified as HCV-infected under the current algorithm. An additional 2.4 percent of RIBA-positive, MP NAT-nonreactive donations were reactive when a frozen-thawed aliquot was retested by ID NAT. CONCLUSION: Integrating HCV NAT results with RIBA results for purposes of donor notification allows more appropriate counseling messages to be given to EIA-repeat-reactive donors. The new HCV supplemental algorithm is an acceptable alternative to the current algorithm because it provides equivalent or superior accuracy in formulating donor counseling messages and may also result in reduced costs and more timely notification of infected donors.

Algorithms↗
PubMed2006

West Nile virus infections projected from blood donor screening data, United States, 2003.

National blood donor screening for West Nile virus (WNV) RNA using minipool nucleic acid amplification testing (MP-NAT) was implemented in the United States in July 2003. We compiled national NAT yield data and performed WNV immunoglobulin M (IgM) testing in 1 WNV-epidemic region (North Dakota). State-specific MP-NAT yield, antibody seroprevalence, and the average time RNA is detectable by MP-NAT were used to estimate incident infections in 2003. WNV donor screening yielded 944 confirmed viremic donors. MP-NAT yield peaked in August with >0.5% of donations positive for WNV RNA in 4 states. Peak IgM seroprevalence for North Dakota was 5.2% in late September. The average time viremia is detectable by MP-NAT was 6.9 days (95% confidence interval [CI] 3.0-10.7). An estimated 735,000 (95% CI 322,000-1,147,000) infections occurred in 2003, with 256 (95% CI 112-401) infections per neuroinvasive case. In addition to preventing transfusion-transmitted WNV infection, donor screening can serve as a tool to monitor seasonal incidence in the general population.

Blood Donors↗
PubMed2005

West Nile virus among blood donors in the United States, 2003 and 2004.

BACKGROUND: West Nile virus first appeared in the United States in 1999 and has since spread throughout the contiguous states, resulting in thousands of cases of disease. By 2002, it was clear that the virus could be transmitted by blood transfusion, and by the middle of 2003, essentially all blood donations were being tested for West Nile virus RNA with the use of investigational nucleic acid amplification tests; testing was performed on individual samples or on "minipools" of up to 16 donations. METHODS: We analyzed data from the West Nile virus testing program of the American Red Cross for 2003 and 2004 to identify geographic and temporal trends. In areas with a high incidence of infection, individual donations were tested to increase the sensitivity of testing. Donors with reactive results participated in follow-up studies to confirm the original reactivity and to assess the natural history of infection. RESULTS: Routine testing in 2003 and 2004 identified 540 donations that were positive for West Nile virus RNA, of which 362 (67 percent) were IgM-antibody-negative and most likely infectious. Of the 540 positive donations, 148 (27 percent) were detectable only by testing of individual donations, but only 15 of the 148 (10 percent) were negative for IgM antibody. The overall frequencies of RNA-positive donations during the epidemic periods were 1.49 per 10,000 donations in 2003 and 0.44 per 10,000 in 2004. In 2004, 52 percent of the positive donations were from donors in four counties in southern California. CONCLUSIONS: Rapid implementation of a nucleic acid amplification test led to the prospective identification of 519 donors who were positive for West Nile virus RNA and the removal of more than 1000 potentially infectious related components from the blood supply of the Red Cross. No cases of transfusion-transmitted infection were confirmed among recipients of the tested blood.

Adolescent↗
PubMed2005

Preventing disease transmission by deceased tissue donors by testing blood for viral nucleic acid.

Nucleic acid testing (NAT) has reduced the risk of transmitting infectious disease through blood transfusion. Currently NAT for HIV-1 and HCV are FDA licensed and performed by nearly all blood collection facilities, but HBV NAT is performed under an investigational study protocol. Residual risk estimates indicate that NAT could potentially reduce disease transmission through transplanted tissue. However, tissue donor samples obtained post-mortem have the potential to produce an invalid NAT result due to inhibition of amplification reactions by hemolysis and other factors. The studies reported here summarize the development of protocols to allow NAT of deceased donor samples with reduced rates of invalid results. Using these protocols, inventories from two tissue centers were tested with greater than 99% of samples producing a valid test result.

Blood Specimen Collection↗
PubMed2005

A new strategy for estimating risks of transfusion-transmitted viral infections based on rates of detection of recently infected donors.

BACKGROUND: Estimates for human immunodeficiency virus (HIV)-1 and hepatitis C virus (HCV) transfusion-transmitted risks have relied on incidence derived from repeat donor histories and imprecise estimates for infectious, preseroconversion window periods (WPs). STUDY DESIGN AND METHODS: By use of novel approaches, WPs were estimated by back-extrapolation of acute viral replication dynamics. Incidence was derived from the yield of viremic, antibody-negative donations detected by routine minipool nucleic acid testing (MP-NAT) of 37 million US donations (1999-2002) or from sensitive/less-sensitive HIV-1 enzyme immunoassay (S/LS-EIA) results for seropositive samples from 6.5 million donations (1999). Incidences and WPs were combined to calculate risks and project yield of individual donation (ID)-NAT. RESULTS: The HIV-1 WP from presumed infectivity (1 copy/20 mL) to ID-NAT detection was estimated at 5.6 days, and the periods from ID to MP-NAT detection and from MP-NAT to p24 detection at 3.4 and 6.0 days, respectively; corresponding estimates for HCV were 4.9, 2.5, and 50.9 days (the latter represents period from MP-NAT to HCV antibody detection). The HIV-1 incidence projected from MP-NAT yield or from S/LS-EIA data was 1.8 per 100,000 person-years, resulting in a corresponding HIV-1 transfusion-transmitted risk of 1 in 2.3 million. The HCV incidence from MP-NAT yield was 2.70 per 100,000 person-years with a corresponding risk of 1 in 1.8 million donations. Conversion from MP-NAT to ID-NAT was projected to detect two to three additional HIV-1 and HCV infectious units annually. CONCLUSIONS: MP-NAT yield and S/LS-EIA rates can accurately project transfusion risks. HCV and HIV-1 risks, currently estimated at 1 per 2 million units, could be reduced to 1 in 3 to 4 million units by ID-NAT screening.

Acute Disease↗
PubMed2005

Utilization of follow-up specimens from viremic blood donors to assess the value of west nile virus immunoglobulin G avidity as an indicator of recent infection.

The value of West Nile virus immunoglobulin G avidity for distinguishing recent from past infection was investigated using 348 follow-up specimens from 170 viremic blood donors. Low avidity accurately indicated infection within the previous 4 months. However, due to rapid avidity maturation in some individuals, high avidity did not accurately indicate past infection.

Antibodies, Viral↗
PubMed2005

Development and persistence of West Nile virus-specific immunoglobulin M (IgM), IgA, and IgG in viremic blood donors.

West Nile Virus (WNV) antibody development and persistence were investigated in blood donors who made WNV RNA-positive (viremic) donations in 2003. Plasma samples from the index donations and follow-up serum or plasma samples were tested for WNV immunoglobulin M (IgM), IgA, and IgG by using enzyme-linked immunosorbent assays. Antibody development was investigated with 154 samples collected from 84 donors 1 to 21 days after their RNA-positive, antibody-negative, index donation. WNV IgM and IgA were first detected on day 3, and all samples collected after day 9 were WNV IgM and IgA positive; WNV IgG was first detected on day 4, and all samples collected after day 16 were positive. Antibody persistence in this donor group (index donations antibody negative) was evaluated by using 128 samples collected from 89 donors on days 22 to 440 of follow-up; 88% of samples were WNV IgM positive, 86% were WNV IgA positive, and 100% were WNV IgG positive. In linear regression analysis, trendlines for WNV IgM and IgA reached the value discriminating positive from negative results at 218 days and 232 days of follow-up, respectively. Similar WNV IgM and IgA persistence trends characterized 27 donors whose index samples were positive for WNV IgM and IgA, as well as 14 donors whose index samples were positive for WNV IgG but negative for WNV IgM. These findings show that WNV IgG emerges after WNV IgM and IgA and that both WNV IgM and IgA typically persist for at least 6 months after infection. Thus, unlike some other flavivirus infections, WNV infection is not characterized by a relatively rapid disappearance of virus-specific IgA.

Antibodies, Viral↗
PubMed2004

Probability of viremia with HBV, HCV, HIV, and HTLV among tissue donors in the United States.

BACKGROUND: Tissue-banking organizations in the United States have introduced various review and testing procedures to reduce the risk of the transmission of viral infections from tissue grafts. We estimated the current probability of undetected viremia with hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and human T-lymphotropic virus (HTLV) among tissue donors. METHODS: Rates of prevalence of hepatitis B surface antigen (HBsAg) and antibodies against HIV (anti-HIV), HCV (anti-HCV), and HTLV (anti-HTLV) were determined among 11,391 donors to five tissue banks in the United States. The data were compared with those of first-time blood donors in order to generate estimated incidence rates among tissue donors. The probability of viremia undetected by screening at the time of tissue donation was estimated on the basis of the incidence estimates and the window periods for these infections. RESULTS: The prevalence of confirmed positive tests among tissue donors was 0.093 percent for anti-HIV, 0.229 percent for HBsAg, 1.091 percent for anti-HCV, and 0.068 percent for anti-HTLV. The incidence rates were estimated to be 30.118, 18.325, 12.380, and 5.586 per 100,000 person-years, respectively. The estimated probability of viremia at the time of donation was 1 in 55,000, 1 in 34,000, 1 in 42,000, and 1 in 128,000, respectively. CONCLUSIONS: The prevalence rates of HBV, HCV, HIV, and HTLV infections are lower among tissue donors than in the general population. However, the estimated probability of undetected viremia at the time of tissue donation is higher among tissue donors than among first-time blood donors. The addition of nucleic acid-amplification testing to the screening of tissue donors should reduce the risk of these infections among recipients of donated tissues.

Adult↗
PubMed2004

Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing.

BACKGROUND: Testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA by means of nucleic acid amplification was introduced in the United States as an investigational screening test in mid-1999 to identify donations made during the window period before seroconversion. METHODS: We analyzed all antibody-nonreactive donations that were confirmed to be positive for HIV-1 and HCV RNA on nucleic acid-amplification testing of "minipools" (pools of 16 to 24 donations) by the main blood-collection programs in the United States during the first three years of nucleic acid screening. RESULTS: Among 37,164,054 units screened, 12 were confirmed to be positive for HIV-1 RNA--or 1 in 3.1 million donations--only 2 of which were detected by HIV-1 p24 antigen testing. For HCV, of 39,721,404 units screened, 170 were confirmed to be positive for HCV RNA, or 1 in 230,000 donations (or 1 in 270,000 on the basis of 139 donations confirmed to be positive for HCV RNA with the use of a more sensitive HCV-antibody test). The respective rates of positive HCV and HIV-1 nucleic acid-amplification tests were 3.3 and 4.1 times as high among first-time donors as among donors who gave blood repeatedly. Follow-up studies of 67 HCV RNA-positive donors demonstrated that seroconversion occurred a median of 35 days after the index donation, followed by a low rate of resolution of viremia; three cases of long-term immunologically silent HCV infection were documented. CONCLUSIONS: Minipool nucleic acid-amplification testing has helped prevent the transmission of approximately 5 HIV-1 infections and 56 HCV infections annually and has reduced the residual risk of transfusion-transmitted HIV-1 and HCV to approximately 1 in 2 million blood units.

Alanine Transaminase↗
PubMed2004

West Nile virus blood transfusion-related infection despite nucleic acid testing.

BACKGROUND: A case of West Nile virus (WNV) encephalitis associated with transfusion of blood that did not react when tested for WNV by minipool (MP) nucleic acid testing (NAT) is described. A Nebraska man developed clinical encephalitis 13 days after surgery and transfusion of 26 blood components. Antibody testing confirmed WNV infection. An investigation was initiated to determine the source of this infection. STUDY DESIGN AND METHODS: The patient's family members were interviewed to identify risk factors for WNV infection. Residual samples were retested for WNV RNA using transcription-mediated amplification (TMA) assay and two polymerase chain reaction (PCR) assays. Blood donors' follow-up serum samples were collected. All samples were tested for WNV-specific immunoglobulin M antibodies. RESULTS: The patient's family denied recent mosquito exposure. The 20 blood components collected after July 2003 did not react when tested for WNV in a six-member MP-NAT at the time of donation. Retrospective individual testing identified one sample as WNV-reactive by the TMA assay and one of the PCR assays. Seroconversion was demonstrated in the donor associated with this sample. CONCLUSION: WNV RNA detection by individual donation NAT demonstrates viremic blood escaping MP-NAT and supports transfusion-related WNV transmission. MP-NAT may not detect all WNV-infected blood donors, allowing WNV transmission to continue at low levels. WNV NAT assays might vary in sensitivity and pooling donations could further impact test performance. Understanding MP NAT limitations can improve strategies to maintain safety of the blood supply in the United States.

Aged↗
PubMed2004

Patterns of age- and sex-specific prevalence of major blood-borne infections in United States blood donors, 1995 to 2002: American Red Cross blood donor study.

BACKGROUND: The American Red Cross has been maintaining a research database of all blood donations, including all testing results for infectious disease markers, since 1995. This study analyzes the temporal trends of major blood-borne infections among blood donors. STUDY DESIGN AND METHODS: Temporal trends for age- and sex-specific prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis infections in US blood donors were analyzed based on linear trend or time series model or other models as appropriate. RESULTS: From 1995 to 2002, significant declines have been observed for infections that used to be at relatively higher levels. Declines in prevalence were slower among first-time donations than repeat donations. There was an increase in prevalence of anti-HCV among first-time male donors of 50 to 59 years of age. Anti-HIV prevalence appeared to have increased among first-time male donors of 30 to 39 years of age since 2000. CONCLUSION: Different sex and age groups showed various patterns of decline and even signs of increase. The increasing prevalence among some age and sex groups may merit further investigation.

Adult↗
PubMed2003

Transmission of West Nile virus through blood transfusion in the United States in 2002.

BACKGROUND: During the 2002 West Nile virus epidemic in the United States, patients were identified whose West Nile virus illness was temporally associated with the receipt of transfused blood and blood components. METHODS: Patients with laboratory evidence of recent West Nile virus infection within four weeks after receipt of a blood component from a donor with viremia were considered to have a confirmed transfusion-related infection. We interviewed the donors of these components, asking them whether they had had symptoms compatible with the presence of a viral illness before or after their donation; blood specimens retained from the time of donation and collected at follow-up were tested for West Nile virus. RESULTS: Twenty-three patients were confirmed to have acquired West Nile virus through transfused leukoreduced and nonleukoreduced red cells, platelets, or fresh-frozen plasma. Of the 23 recipients, 10 (43 percent) were immunocompromised owing to transplantation or cancer and 8 (35 percent) were at least 70 years of age. Immunocompromised recipients tended to have longer incubation periods than nonimmunocompromised recipients and infected persons in mosquito-borne community outbreaks. Sixteen donors with evidence of viremia at donation were linked to the 23 infected recipients; of these donors, 9 reported viral symptoms before or after donation, 5 were asymptomatic, and 2 were lost to follow-up. Fever, new rash, and painful eyes were independently associated with being an implicated donor with viremia rather than a donor without viremia. All 16 donors were negative for West Nile virus-specific IgM antibody at donation. CONCLUSIONS: Transfused red cells, platelets, and fresh-frozen plasma can transmit West Nile virus. Screening of potential donors with the use of nucleic acid-based assays for West Nile virus may reduce this risk.

Adolescent↗
PubMed2003

Impact of changes in viral marker screening assays.

BACKGROUND: Monitoring the performance of routinely used infectious disease serologic tests is necessary to evaluate their effectiveness in identifying true-positive units and erroneously disqualifying safe blood donors. METHODS: With two large screening test data sets collected between 1991 and 1998 and between 1997 and 2000, the impact of changes in screening assays for HIV, HCV, and HBsAg was analyzed with regard to the prevalence of confirmed-positive, indeterminate, and confirmed-negative results and the deferral of donors with an indeterminate or negative results (donor loss). RESULTS: The prevalence of indeterminate results and donors loss increased significantly in the 6 months after introduction of an HIV-1/2 EIA. A second-generation HCV EIA increased the detection of confirmed-positive donations in repeat donors (p < 0.001) and increased the prevalence of indeterminate donations. Implementation of a third-generation HCV EIA resulted in a significant decrease in indeterminate results in first-time donors. Nonspecific test results increased when HBsAg test kits from a different manufacturer were introduced or different lots of HIV antibody screening test kits from the same manufacturer were used. CONCLUSION: Introduction of newly licensed versions of assays, switching kit manufacturers, and lot-to-lot variations have an impact on rates of deferrals of safe donors as well as sensitivity of routine screening. Before considering changes in screening tests, blood centers should be aware of, and evaluate, the potential impact on donor loss.

Antigens, Viral↗
PubMed2003

Impact of HCV 3.0 EIA relative to HCV 2.0 EIA on blood-donor screening.

BACKGROUND: In 1996, the Ortho HCV Version 3.0 ELISA Test System (HCV 3.0 EIA) was licensed in the United States for donor screening but was neither mandated nor universally implemented. Data from two studies comparing the differential performance of HCV 3.0 EIA and HCV 2.0 EIA are presented. The first study evaluated the differential performance in a cross-section of screened whole-blood donors after implementation of HCV 3.0 EIA; the second study evaluated the differential performance of HCV 3.0 EIA in plasma donors acutely infected with HCV, identified during routine Abbott HCV 2.0 EIA and HCV NAT (using Roche Ampliscreen plate assay) donor screening. STUDY DESIGN AND METHODS: The first study evaluated HCV 3.0 EIA repeat-reactive donations from four US blood centers, identified during the first 5 months of HCV 3.0 EIA implementation. HCV EIA repeat-reactive donations confirmed by RIBA HCV 3.0 SIA were retested using both Ortho HCV Version 2.0 ELISA Test System and Abbott HCV 2.0 EIA. All EIA-discordant donations were tested by polymerase chain reaction (PCR). In the second study, Abbott HCV 2.0 EIA-nonreactive, HCV PCR-positive donors were enrolled in a follow-up study in which the index and follow-up samples were re-evaluated by HCV 3.0 EIA. RESULTS: In the first study, of 292,459 donations, 501 (0.17%) confirmed HCV 3.0 EIA-reactive donations were identified; 15 (0.005%) were nonreactive by Ortho HCV 2.0 EIA and were all HCV RNA negative. In the second study, Ortho HCV 3.0 EIA retesting of Abbott HCV 2.0 EIA-nonreactive, RNA-positive index donations identified 16 (23%) as 3.0 EIA reactive. In 42 panels with a discordant time of seroconversion, HCV 3.0 EIA sero-conversion preceded HCV 2.0 EIA in all cases (p < 0.001). Two donors with HCV 3.0 EIA-reactive index donations never seroconverted by HCV 2.0 EIA during 160 to 180 days of follow-up. CONCLUSION: These studies demonstrate that HCV 3.0 EIA compared to HCV 2.0 EIA can better detect 1) remote nonviremic HCV infections, 2) acute infection, and 3) HCV antibodies in cases of atypical seroconversion.

Blood Donors↗