M P Busch

Publications (191)1244.75 Total impact

• Article: Estimated cumulative incidence of West Nile virus infection in US adults, 1999-2010.

  L R Petersen, P J Carson, B J Biggerstaff, B Custer, S M Borchardt, M P Busch
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  ABSTRACT: West Nile virus (WNV) was first recognized in the USA in 1999. We estimated the cumulative incidence of WNV infection in the USA from 1999 to 2010 using recently derived age- and sex-stratified ratios of infections to WNV neuroinvasive disease (WNND) and the number of WNND cases reported to national surveillance. We estimate that over 3 million persons have been infected with WNV in the USA, with the highest incidence rates in the central plains states. These 3 million infections would have resulted in about 780 000 illnesses. A substantial number of WNV infections and illnesses have occurred during the virus' first decade in the USA.
  Epidemiology and Infection 05/2012; · 2.84 Impact Factor
• Source

  Available from: Valentina Tefanova

  Article: International survey on NAT testing of blood donations: expanding implementation and yield from 1999 to 2009.

  W K Roth, M P Busch, A Schuller, S Ismay, A Cheng, C R Seed, C Jungbauer, P M Minsk, D Sondag-Thull, S Wendel, [......], C Jennings, E Notari, S Stramer, D Kessler, C Hillyer, H Kamel, L Katz, C Taylor, S Panzer, H W Reesink
  Vox Sanguinis 09/2011; 102(1):82-90. · 2.86 Impact Factor
• Source

  Available from: Roger Y Dodd

  Article: Research and development.

  D V Devine, H W Reesink, S Panzer, D O Irving, G F Körmöczi, W R Mayr, Y Blais, Y Zhu, K Qian, Z Zhu, [......], M Scott, L Williamson, C Prowse, J P AuBuchon, J A López, P Hoffman, M P Busch, P J Norris, P Tomasulo, R Y Dodd
  Vox Sanguinis 11/2010; 99(4):382-401. · 2.86 Impact Factor
• Article: Transfusion-transmitted arboviruses.

  L R Petersen, M P Busch
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  ABSTRACT: There exists considerable risk for transfusion transmission of arboviruses due to short periods of asymptomatic viraemia in populations with variable and sometimes extremely high incidence of arboviral infections. Aside from West Nile virus, few arbovirus transfusion transmissions have been proven, mostly due to difficulties in ruling out vector-borne transmission in recipients with arbovirus disease. Nevertheless, arbovirus transfusion risk models and assessments of viraemia prevalence in blood donations indicate substantial transfusion transmission of dengue and Chikungunya viruses in epidemic areas. Many other arboviruses, several of which are importation risks in the Americas, Europe and Asia, also cause large outbreaks and threaten transfusion safety. Prevention largely depends on excluding donors from outbreak areas or implementation of highly sensitive nucleic acid amplification tests. Because of the increasing emergence of arboviral disease globally, it is prudent to prepare for both endemic and exotic arboviruses capable of producing large epidemics and subsequent transfusion transmission risk.
  Vox Sanguinis 11/2009; 98(4):495-503. · 2.86 Impact Factor
• Article: Genetic variation in CLDN1 and susceptibility to hepatitis C virus infection.

  V Bekker, S J Chanock, M Yeager, A A Hutchinson, T von Hahn, S Chen, N Xiao, M Dotrang, M Brown, M P Busch, B R Edlin, C M Rice, T R O'Brien
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  ABSTRACT: Claudin-1 is a recently discovered co-receptor for hepatitis C virus (HCV) that is required for late-stage binding of the virus. Because variants in the gene that encodes claudin-1 (CLDN1) could play a role in HCV infection, we conducted a 'whole gene association study' among injection drug users (IDUs) to examine whether CLDN1 genetic variants were associated with the risk of HCV infection or with viral clearance. In a cross sectional study, we examined genotype results for 50 single nucleotide polymorphisms (SNPs) across the CLDN1 gene region, comparing genotypes among participants with chronic HCV (n = 658) to those in IDUs who had cleared HCV (n = 199) or remained HCV-uninfected (n = 68). Analyses were controlled for racial ancestry (African-American or European-American) by stratification and logistic regression modeling. We found that participants who remained uninfected more often carried CLDN1 promoter region SNPs -15312C [odds ratio (OR), 1.72; 95% confidence interval (CI) 1.00-2.94; P = 0.048], -7153A (OR, 2.13; 95% CI, 1.25-3.62; P = 0.006) and -5414C (OR, 1.78; 95% CI, 1.06-3.00; P = 0.03). HCV-uninfected participants less often carried CLDN1 IVS1-2983C (OR, 0.55; 95% CI, 0.31-0.97; P = 0.04), which lies in intron 1. CLDN1 -15312C, -7153A and -5414C formed a haplotype in both the African-American and European-American participants and a haplotype analysis supported the association of CLDN1 -7153A in the HCV-uninfected participants. The analyses of HCV clearance revealed no associations with any SNP. These results indicate that genetic variants in regulatory regions of CLDN1 may alter susceptibility to HCV infection.
  Journal of Viral Hepatitis 09/2009; 17(3):192-200. · 4.09 Impact Factor
• Article: Hepatitis C infection: recent insights relevant to transfusion safety

  M. P. Busch, S. H. Kleinman
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  ABSTRACT: Hepatitis C virus (HCV) infects over 100 million persons worldwide, and is hence one of the most prevalent and clinically significant blood-borne pathogens. The introduction of HCV antibody screening in the early 1990s led to detection of large numbers of infected donors and dramatic increases in blood safety. The seroprevalence of HCV in blood donors varies, ranging from rates as low as 0·01% in South Africa to ~0·5% in most developed countries, to > 5% in focal endemic areas such as Egypt. Studies of HCV in infected donors and recipients were instrumental in the discovery of HCV, and have yielded ongoing insights into HCV epidemiology, natural history and pathogenesis. Recent examples include detailed characterization of the dynamics of acute HCV infection based on studies of plasma donor panels, and important contributions to understanding viral and host factors influencing HCV transmission and disease outcome based on linked donor-recipient cohort studies. The addition of nucleic acid testing (NAT) for HCV RNA to routine HCV antibody screening of donors in 1999 further reduced the risk of transfusion-transmitted HCV. Mini-pool (MP)-NAT screening has led to detection of well over 500 donors in the viraemic, preseroconversion phase of primary HCV infection, as well as to discrimination of seropositive donors into those with resolved and chronic infections. Studies of donors with acute, chronic/persistent and resolved HCV infections have further contributed to our understanding of viral and host genetic and immunological determinants of spontaneous clearance of HCV and short- and long-term disease outcomes. This review will highlight these past scientific contributions, and present the results of a recent survey of the yield of HCV MP-NAT screening and estimated residual risks of MP-NAT screened transfusions in different regions of the world. Finally, the review will discuss available evidence for the infectivity of very low-level viraemia that may be missed by MP-NAT, information that is pivotal to modelling the residual risk of MP-NAT screened blood transfusions, and which will guide further strategies to reduce risk by further enhancing screening or implementation of pathogen-inactivation technologies.
  ISBT Science Series 02/2009; 4(1):72 - 79.
• Article: Hepatitis C virus-specific T-cell immune responses in seronegative injection drug users.

  M Zeremski, M A Shu, Q Brown, Y Wu, D C Des Jarlais, M P Busch, A H Talal, B R Edlin
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  ABSTRACT: T-cell responses to hepatitis C virus (HCV) antigens have been reported in high-risk HCV seronegative persons, suggesting that an effective cellular immune response might be able to clear infection without the development of antibodies. Such findings, however, could be explained by waning antibody or cross-reactivity to other antigens. To address these issues, we evaluated HCV-specific T-cell responses in 26 young (age 18-33 years) aviremic, seronegative injection drug users (IDUs) (median duration of injection, 6 years) by interferon-gamma enzyme-linked immunospot (ELISpot) assay using 429 overlapping HCV peptides pooled in 21 mixes. Seventeen aviremic, seropositive IDUs (spontaneous resolvers) and 15 healthy people were used as positive and negative controls, respectively. The percentage of patients with HCV-specific cellular immune responses was similar in seronegative and seropositive aviremic IDUs (46%vs 59%, P = 0.4), while these responses were not detected in any of the negative controls. Among the seronegative IDUs, six (23%) had intermediate to very strong responses to 10-20 peptide mixes and another six (23%) had moderately strong responses for two to six mixes. The 12 seronegative IDUs with HCV-specific T-cell responses had higher demographical and behavioural risk profiles than the 14 IDUs without T-cell responses (estimated risk of HCV infection, 0.47 vs 0.26, P < 0.01). In conclusion, HCV-specific T-cell responses are common among high-risk, seronegative IDUs. The responses are broad and are associated with risk factors for HCV exposure, suggesting that they reflect true exposure to HCV in seronegative persons.
  Journal of Viral Hepatitis 01/2009; 16(1):10-20. · 4.09 Impact Factor
• Article: The inverse relationship between chronic HBV and HCV infections among injection drug users is associated with decades of age and drug use.

  F-C Tseng, B R Edlin, M Zhang, A Kral, M P Busch, B A Ortiz-Conde, T M Welzel, T R O'Brien
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  ABSTRACT: Infection with hepatitis C virus (HCV) may suppress co-infection with hepatitis B virus (HBV) during acute or chronic HBV infection. We examined relationships between HBV infection, HCV infection and other factors among injection drug users (IDUs) with antibodies to both viruses. Participants enrolled in a cross-sectional study during 1998-2000 were considered to have been infected with HBV if they had core antibody, to be chronically infected if they had hepatitis B surface antigen (HBsAg), to have been infected with HCV if they had HCV antibody and to be chronically infected if they had HCV RNA. Among 1694 participants with antibody to both viruses, HBsAg prevalence decreased with increasing age among those positive for HCV RNA [from 4.55% in those 18-29 years to 1.03% in those >or=50 years old (P(trend) = 0.02)], but not among those who were negative for HCV RNA. Chronic HBV infection was less common overall among those with chronic HCV infection (odds ratio [OR], 0.25; P < 0.0001), but this inverse relationship was much stronger in the oldest (>50 years; OR = 0.15) than the youngest (18-29 years; OR = 0.81) participants (P(trend) = 0.03). Similar results were obtained when duration of injection drug use was substituted for age (P(trend) = 0.05). Among IDUs who have acquired both HBV and HCV, chronic HBV infection is much less common among those with chronic HCV infection, but this inverse relationship increases markedly with increasing years of age and injection drug use. Co-infection with HCV may enhance the resolution of HBsAg during the chronic phases of these infections.
  Journal of Viral Hepatitis 06/2008; 15(9):690-8. · 4.09 Impact Factor
• Article: Biobanks of blood from donors and recipients of blood products.

  H W Reesink, C P Engelfriet, C A Hyland, P Coghlan, B Tait, M Wsolak, A J Keller, G Henn, W R Mayr, I Thomas, [......], R Norda, C Prowse, B Dow, L Jarvis, F Davidson, S Kleinman, C Bianco, S L Stramer, R Y Dodd, M P Busch
  Vox Sanguinis 05/2008; 94(3):242-60. · 2.86 Impact Factor
• Article: Biobanks of blood from donors and recipients of blood products

  H. W. Reesink, C. P. Engelfriet, C. A. Hyland, P. Coghlan, B. Tait, M. Wsolak, A. J. Keller, G. Henn, W. R. Mayr, I. Thomas, [......], R. Norda, C. Prowse, B. Dow, L. Jarvis, F. Davidson, S. Kleinman, C. Bianco, S. L. Stramer, R. Y. Dodd, M. P. Busch
  Vox Sanguinis 01/2008; 94(3):242 - 260. · 2.86 Impact Factor
• Article: The course of hepatitis C viraemia in transfusion recipients prior to availability of antiviral therapy

  J. W. Mosley, E. A. Operskalski, L. H. Tobler, Z. J. Buskell, W. W. Andrews, B. Phelps, J. Dockter, C. Giachetti, L. B. Seeff, M. P. Busch, for the Transfusion-transmitted Viruses Study and Retrovirus Epidemiology Donor Study Groups
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  ABSTRACT:   Knowing the likely distribution of intervals from hepatitis C infection to first RNA-negativity is important in deciding about therapeutic intervention. Prospectively collected sera and data from the Transfusion-transmitted Viruses Study (1974–1980) provide specific dates of infection and pattern of alanine aminotransferase (ALT) elevations. We examined frequency, timing and correlates of spontaneous resolution for 94 acutely infected transfusion recipients followed for a median of 9.5 months. Later, follow-up sera (>10 years) were available for 27 of the 94 cases from a Veterans Administration (VA) Study (1989–1990). Twenty-five (27%) of the 94 cases were classified as probably resolved during the episode itself. First RNA negativity occurred at 6–50 weeks (median, 19.5 weeks) after infection, and 5–43 weeks (median, 11 weeks) after ALT elevation. Thirteen of the 25 cases remained RNA-negative subsequently; 12 others had 1–6 RNA-positive sera intercalated between first and last RNA-negative results. RNA negativity, therefore, began variably and was interrupted in 12 cases of 25 (48%) by transient RNA-positive sera. Five of these 25 patients who were RNA-negative in the last study specimen had late, Veterans Administration Study follow-up; none showed viraemia. Of the remaining 69 transfusion transmitted virus study recipients, whose last serum was RNA-positive, two cleared viraemia after the last study serum but before late follow-up. Eleven (16%) had 23 intercalated RNA-negative sera before last positivity. RNA status, therefore, needs monitoring for many months before judging the spontaneous outcome as transient negativity may occur. Resolution was significantly more common in women and symptomatic cases; it was not associated with viral load in the infectious donation, HCV genotype, or the recipient’s age.
  Journal of Viral Hepatitis 12/2007; 15(2):120 - 128. · 4.09 Impact Factor
• Source

  Available from: Leslie H Tobler

  Article: Antibodies to a novel antigen in acute hepatitis C virus infections.

  L H Tobler, S L Stramer, D Y Chien, S Lin, P Arcangel, B H Phelps, S L Cooper, M P Busch
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  ABSTRACT: Conformational viral proteins potentially play an important role in the immunobiology of acute hepatitis C virus (HCV) infection and may enable earlier antibody detection. HCV RNA was detected using nucleic acid testing. Early antibody production was evaluated using three enzyme immunoassays (EIAs) containing antigenic proteins not present in licensed EIAs. Respectively, these contained: (1) multiple-epitope fusion antigen (MEFA) 7.1-NS3/4a, (2) F and Core, and (3) E1/E2 proteins. NS3/4a is a conformational antigen retaining protease and helicase enzymatic activities. MEFA 7.1 contains the linear epitopes used in licenced EIAs, including the latest EIA-3.0, in combination with genotype 1-3 specific epitopes. Forty-two RNA positive, EIA-3.0 negative samples, including two persistently serosilent cases, were used to evaluate these research EIAs. As controls, 54 EIA-3.0 negative/RNA negative and three HCV RNA+/antibody positive specimens were included. Only the MEFA 7.1-NS3/4a EIA was positive in seven (17%) of the 42 HCV RNA + specimens, in all three EIA-3.0 positive controls but in none of 54 EIA-3.0 negative/HCV RNA negative controls. Notably, six of the seven (86%) specimens had evidence of active hepatitis (ALT > 210 IU/l). The two serosilent cases were research EIA negative. A novel EIA with conformational and linear epitopes detected HCV antibodies in 17% of viraemic specimens missed by the standard reference EIA-3.0. Our research EIA appears to detect HCV antibodies closer to the initiation of acute hepatitis. Given that the average RNA-positive, antibody-negative window period is 56.4 days, this 17% yield would translate into a 10-day earlier detection of antibodies.
  Vox Sanguinis 01/2007; 92(1):1-7. · 2.86 Impact Factor
• Article: Performance of ORTHO HCV core antigen and trak-C assays for detection of viraemia in pre-seroconversion plasma and whole blood donors.

  L H Tobler, S L Stramer, S R Lee, D Baggett, D Wright, D Hirschkorn, I Walsh, M P Busch
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  ABSTRACT: Logistics and cost of nucleic acid amplification testing (NAT) screening preclude its current use in many developing countries. Development of hepatitis C virus (HCV) core antigen assays offer an alternative to NAT. We evaluated two specimen populations to assess the sensitivity, relative to NAT, of the HCV core antigen (HCVcAg) ELISA (enzyme-linked immunosorbent assay) test system and the trak-C assay: (1) plasma donor HCV NAT-conversion panels and (2) cross-sectional whole blood donor NAT yield specimens. Differential sensitivities among NAT (NGI; Chiron/Gen-Probe) and both HCVcAg assays (Ortho-Clinical Diagnostics, Rochester, NY) were evaluated using: (1) 102 serial ramp-up phase specimens from 37 plasma donor NAT-conversion panels (Alpha Therapeutic/BioClinical Partners); and (2) 42 cross-sectional whole blood donor NAT yield specimens (confirmed RNA positive, antibody negative) plus 54 NAT false-positive specimens (American Red Cross). Viral load among the plasma donor NAT-conversion panels at the cutoffs for HCVcAg and trak-C assays were 32 000 copies/ml (95% confidence interval [CI] 8000-120 000) and 8000 copies/ml (95% CI: 2200-28 000), respectively. The mean (95% CI) difference in window period reduction compared to routine mini-pool NAT screening (estimated sensitivity 100 copies/ml) was delayed 5.2 days (2.2-7.6 days) for HCVcAg assay and 3.8 days (2.1-5.5 days) for the trak-C assay. Among the 42 NAT yield specimens, the HCVcAg assay detected 31 (74%) as core antigen-positive while the trak-C assay detected 37 (88%) as core antigen-positive. Viral loads for the five specimens not detected by the trak-C HCVcAg assay ranged from 100 to 7770 copies/ml. All 54 NAT false-positive specimens were non-reactive on both HCV core antigen assays. These data indicate that the trak-C assay has sensitivity approaching routine mini-pool NAT screening for the detection of seronegative HCV infection. In the absence of routine NAT screening for early HCV infection, the use of an HCV core antigen assay should be considered.
  Vox Sanguinis 12/2005; 89(4):201-7. · 2.86 Impact Factor
• Article: Does prevalence of transfusion-transmissible viral infection reflect corresponding incidence in United States blood donors?

  Baoguang Wang, G B Schreiber, S A Glynn, Steven Kleinman, D J Wright, E L Murphy, M P Busch
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  ABSTRACT: Calculation of viral residual risk is dependent on estimating incidence, which is not easily obtainable by most blood centers. Prevalence, however, is readily available. Understanding whether prevalence reflects corresponding incidence may help blood centers monitor disease risks. With data on 12 million allogeneic donations, prevalence and incidence of transfusion-transmitted viral infections (TTVIs) were calculated. Relationships between prevalence (in total, first-time, and repeat donations) and incidence were analyzed for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) relative to temporal and donor demographic stratifications, respectively. Overall prevalence of HIV, HBV, and HCV did not consistently reflect corresponding incidence. The relationship between prevalence and incidence varied with time and donors' age and was virus-specific. Incidence of TTVIs cannot be easily predicted from overall prevalence. Accurate assessment of TTVI risk necessitates knowledge about donation histories and person-years at risk. Establishing comprehensive frameworks for monitoring blood donations and infectious disease markers remains a key to monitoring blood safety.
  Transfusion 08/2005; 45(7):1089-96. · 3.22 Impact Factor
• Article: Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology: update to 2003.

  J Coste, H W Reesink, C P Engelfriet, S Laperche, S Brown, M P Busch, H T Cuijpers, R Elgin, B Ekermo, J S Epstein, [......], W K Roth, S Sauleda, C R Seed, D Sondag-Thull, S L Stramer, M Strong, E C Vamvakas, C Velati, M A Vesga, A Zanetti
  Vox Sanguinis 06/2005; 88(4):289-303. · 2.86 Impact Factor
• Article: International Forum: 1

  J. Coste, H. W. Reesink, C. P. Engelfriet, S. Laperche, S. Brown, M. P. Busch, H. T. Cuijpers, R. Elgin, B. Ekermo, J. S. Epstein, [......], W. K. Roth, S. Sauleda, C. R. Seed, D. Sondag‐Thull, S. L. Stramer, M. Strong, E. C. Vamvakas, C. Velati, M. A. Vesga, A. Zanetti
  Vox Sanguinis 05/2005; 88(4):289 - 298. · 2.86 Impact Factor
• Article: International Forum: 2

  M. P. Busch, S. L. Stramer, D. M. Strong, I. K. Hewlett, J. S. Epstein
  Vox Sanguinis 05/2005; 88(4):298 - 301. · 2.86 Impact Factor
• Article: Detection of West Nile virus RNA and antibody in frozen plasma components from a voluntary market withdrawal during the 2002 peak epidemic.

  L H Tobler, C Bianco, S A Glynn, G B Schreiber, B J Dille, H E Prince, R S Lanciotti, J M Linnen, J Gallarda, V Shyamala, D Smith, S H Kleinman, M P Busch
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  ABSTRACT: The US West Nile virus (WNV) epidemic in the summer and fall of 2002 included the first documented cases of transfusion-transmitted WNV infection. In December 2002, the FDA supported a voluntary market withdrawal by the blood banking community of frozen blood components collected in WNV high-activity areas. At the time, the prevalence of viremia and serologic markers for WNV in the blood supply was undefined. In collaboration with America's Blood Centers, 1468 frozen plasma components (of approx. 60,000 frozen units voluntarily withdrawn from the market) were selectively retrieved from the peak epidemic regions and season (June 23, 2002-September 28, 2002). These units were unlinked, subaliquoted, and tested by WNV enzyme immunoassays (EIAs; Focus Technologies and Abbott Laboratories) and nucleic acid amplification tests (NATs; Gen-Probe Inc. and Roche Molecular Systems). Of the 1468 EIA results from Abbott and Focus, 7 were anti-immunoglobulin M (IgM)- and anti-immunoglobulin G (IgG)-reactive by both assays, 8 and 1 were IgM-only-reactive, and 8 and 23 were IgG-only-reactive, respectively. NAT by Gen-Probe and Roche Molecular Systems yielded one RNA-positive, antibody-negative unit containing approximately 440 RNA copies per mL. An additional 10-fold replicate NAT testing by Gen-Probe on 14 of 15 IgM-reactive specimens yielded 2 additional IgM- and IgG-reactive units with low-level viremia (i.e., 7/10 and 2/10 replicates tested reactive). The prevalence of acute (RNA-positive) and recent (IgM-seroreactive) WNV infections indicates that transfusion risk in high-risk areas could have been considerable and that voluntary market withdrawal of frozen components likely averted some WNV transfusion transmissions. The existence of very-low-level viremic units raises concerns, because WNV minipool NAT screening will miss such units and individual NAT may not completely correct this situation.
  Transfusion 05/2005; 45(4):480-6. · 3.22 Impact Factor
• Article: Analytical and clinical sensitivity of West Nile virus RNA screening and supplemental assays available in 2003.

  M P Busch, L H Tobler, J Saldanha, S Caglioti, V Shyamala, J M Linnen, J Gallarda, B Phelps, R I F Smith, M Drebot, S H Kleinman
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  ABSTRACT: Transfusion-transmitted West Nile virus (WNV) infections were first reported in 2002, which led to rapid development of investigational nucleic acid amplification tests (NAT). A study was conducted to evaluate sensitivities of WNV screening and supplemental NAT assays first employed in 2003. Twenty-five member-coded panels were distributed to NAT assay manufacturers. Panels included five pedigreed WNV standards (1, 3, 10, 30, and 100 copies/mL), 15 or 16 donor units with very-low-level viremia identified through 2003 screening, and four or five negative control samples. Samples were tested neat in 10 replicates by all assays; for NAT screening assays, 10 replicates were also performed on dilutions consistent with minipool (MP)-NAT. The viral load distribution for 142 MP-NAT yield donations was characterized, relative to the analytical sensitivity of MP-NAT systems. Analytical sensitivities (50% limits of detection [LoD] based on Poisson model of detection of WNV standards) for screening NAT assays ranged from 3.4 to 29 copies per mL; when diluted consistent with MP pool sizes, the 50 percent LoD of screening NAT assays was reduced to 43 to 309 copies per mL. Analytical sensitivity of supplemental assays ranged from 1.5 to 7.7 copies per mL (50% LoD). Detection of RNA in donor units varied consistent with analytical LoD of assays. Detection of low-level viremia after MP dilutions was particularly compromised for seropositive units, probably reflecting lower viral loads in the postseroconversion phase. Based on the viral load distribution of MP-NAT yield donations (median, 3519 copies/mL; range, < 50-690,000), 13 to 24 percent of units had viral loads below the 50 percent LoD of screening NAT assays run in MP-NAT format. WNV screening and supplemental assays had generally excellent analytical sensitivity, comparable to human immunodeficiency virus-1 and hepatitis C virus NAT assays. The presence of low-level viremic units during epidemic periods and the impact of MP dilutions on sensitivity, however, suggest the need for further improvements in sensitivity as well as a role for targeted individual-donation NAT in epidemic regions.
  Transfusion 04/2005; 45(4):492-9. · 3.22 Impact Factor
• Article: Analytical and clinical sensitivity of West Nile virus RNA screening and supplemental assays available in 2003

  M.P. Busch, L.H. Tobler, J. Saldanha, S. Caglioti, V. Shyamala, J.M. Linnen, J. Gallarda, B. Phelps, R.I.F. Smith, M. Drebot, S.H. Kleinman
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Transfusion-transmitted West Nile virus (WNV) infections were first reported in 2002, which led to rapid development of investigational nucleic acid amplification tests (NAT). A study was conducted to evaluate sensitivities of WNV screening and supplemental NAT assays first employed in 2003.STUDY DESIGN AND METHODS: Twenty-five member-coded panels were distributed to NAT assay manufacturers. Panels included five pedigreed WNV standards (1, 3, 10, 30, and 100 copies/mL), 15 or 16 donor units with very-low-level viremia identified through 2003 screening, and four or five negative control samples. Samples were tested neat in 10 replicates by all assays; for NAT screening assays, 10 replicates were also performed on dilutions consistent with minipool (MP)-NAT. The viral load distribution for 142 MP-NAT yield donations was characterized, relative to the analytical sensitivity of MP-NAT systems.RESULTS: Analytical sensitivities (50% limits of detection [LoD] based on Poisson model of detection of WNV standards) for screening NAT assays ranged from 3.4 to 29 copies per mL; when diluted consistent with MP pool sizes, the 50 percent LoD of screening NAT assays was reduced to 43 to 309 copies per mL. Analytical sensitivity of supplemental assays ranged from 1.5 to 7.7 copies per mL (50% LoD). Detection of RNA in donor units varied consistent with analytical LoD of assays. Detection of low-level viremia after MP dilutions was particularly compromised for seropositive units, probably reflecting lower viral loads in the postseroconversion phase. Based on the viral load distribution of MP-NAT yield donations (median, 3519 copies/mL; range, < 50-690,000), 13 to 24 percent of units had viral loads below the 50 percent LoD of screening NAT assays run in MP-NAT format.CONCLUSION: WNV screening and supplemental assays had generally excellent analytical sensitivity, comparable to human immunodeficiency virus-1 and hepatitis C virus NAT assays. The presence of low-level viremic units during epidemic periods and the impact of MP dilutions on sensitivity, however, suggest the need for further improvements in sensitivity as well as a role for targeted individual-donation NAT in epidemic regions.
  Transfusion 03/2005; 45(4):492 - 499. · 3.22 Impact Factor