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Biomedical subjects

M P Busch

Publications and source records attributed to M P Busch.

At least 91 records · Page 5Linked to original sources
PubMed1997

Comparative rates of disease progression among persons infected with the same or different HIV-1 strains. The Transfusion Safety Study Group.

Rates of HIV-1 progression vary widely. To investigate the relative effects of viral and host characteristics on course, we compared persons infected by the same and different subtype B strains. Forty-three infection chain clusters were identified, each defined by an infected blood donor, that donor's recipients, and the recipients' sexual partners, representing second and third generations of infection. Analysis of levels and rates of change in CD4 lymphocyte counts and viral load showed that members within a cluster were no more alike in their rates of change in CD4+ lymphocyte counts or viral RNA levels than among clusters. Differences in entry viral RNA levels by cluster were marginal and markedly smaller than interindividual differences. These results argue that, in general, host factors outweigh differences in viral strain in determining HIV-1 disease progression.

Blood Donors↗
PubMed1997

Time course of viremia and antibody seroconversion following human immunodeficiency virus exposure.

Rational application of diagnostic assays in the management of healthcare workers (HCWs) following occupational exposure is needed to rule out pre-existing human immunodeficiency virus (HIV) infection, detect HIV infection or seroconversion as early as possible in the small proportion individuals who become infected, and to rule out infection in the high proportion of individuals who remain uninfected following occupational exposure to HIV. An understanding of the time course of viremia and seroconversion following HIV exposure is essential in developing recommendations for management of occupational exposure among HCWs. Several data sources that address the timing and dynamics of HIV viremia and seroconversion following primary infection are reviewed. The implications of each data source for management of occupational exposure among HCWs is assessed. Although the majority of infected HCWs seroconvert within 2 months of exposure, the possibility of delayed seroconversion is well established, with approximately 5% of infected HCWs estimated to seroconvert >6 months after exposure. In contrast, the period of viremia (detectable by p24 antigen or RNA assays) preceding antibody seroconversion is consistently brief (1-3 weeks). Animal inoculation studies indicate that a variable period of localized viral replication in lymphoid tissue draining inoculation sites exists prior to systemic viremia and subsequent seroconversion.

Animals↗
PubMed1997

Divergence of HIV-1 quasispecies in an epidemiologic cluster.

BACKGROUND: During treatment with blood components prepared from an HIV-infected donation, two recipients became infected in 1985. One recipient infected her sexual partner. OBJECTIVE: To evaluate the evolution of the originally-shared HIV-1 quasispecies in different human hosts over time, sequence data were obtained from serum from the actual donation sample of blood, and from plasma samples collected from the four members of the epidemiologic cluster over a period extending from 1986 to 1993. METHODS: The V3 hypervariable region of env and the gag p17 gene were analysed. CD4 and CD8 counts, as well as HIV RNA burden data, were collected. RESULTS: One patient died from AIDS during the study. This patient showed a greater degree of diversity in the V3 region, with a higher positive charge over time, than the other individuals. Phylogenetic analysis revealed that the V3 sequences from each of the four individuals occupied separate branches of a phylogenetic reconstruction (tree). Two distinct subgroups evolved in the donor, one with GPGR and the other with GSGR/GSGK at the tip of the V3 loop. This latter group was not detected in the other individuals. The sequences in the sexual partner were no more related to those in the infecting transfusion recipient than to sequences from the other members of the cluster, consistent with sexual transmission having occurred at a time shortly after the recipient was infected. CONCLUSION: The shared HIV-1 quasispecies in this epidemiologic cluster diverged in an individual-specific manner.

Amino Acid Sequence↗
PubMed1997

Potential increased risk of virus transmission due to exclusion of older donors because of concern over Creutzfeldt-Jakob disease. The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study.

BACKGROUND: Concern over the theoretical possibility of disease transmission via blood from donors who develop Creutzfeldt-Jakob disease has led to proposals to exclude older individuals from donating plasma for further manufacture into pooled plasma donations. The impact of extending this age-deferral policy to blood donors was examined with respect to the risk for known transmissible viruses. STUDY DESIGN AND METHODS: Demographic characteristics and confirmed prevalence rates (/10(5) first-time donations) and incidence rates (/10(5) person-years for repeat donors) for viral markers were compared for donors < 50 years old (n = 1,259,805 [85%]) and > or = 50 years old (n = 219,856 [15%]) and for donors < 60 years old (n = 1,409,176 [95%]) and > or = 60 years old (n = 70,485 [5%]). Incidence rates were combined with infectious window-period estimates for each virus, to calculate the risk of virus transmission per 10(6) donations. RESULTS: Unadjusted prevalence rates were significantly greater for younger than for older donor groups for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) (p < or = 0.05). Incidence rates (and transmission risk estimates) for HBsAg were significantly higher in the < 50 donor group than in the > or = 50 group (p < or = 0.05), and those for HIV, human T-lymphotropic virus, and HCV were not significantly higher (p > 0.05). Blanket removal of donors over the age of 50 would potentially lead to the following significant increases in the risk of infected units: HIV, 12 percent; HCV, 21 percent; and hepatitis B virus (HBsAg), 22 percent. CONCLUSION: Removal of donors over the age of 60 would not significantly affect the risk of infected units. Deferral of donors > or = 50 years of age from whole-blood donations for unfounded concerns about Creutzfeldt-Jakob disease could have adverse effects on both blood availability and safety.

Aging↗
PubMed1997

Value and cost-effectiveness of screening blood donors for antibody to hepatitis B core antigen as a way of detecting window-phase human immunodeficiency virus type 1 infections. The HIV Blood Donor Study Group.

BACKGROUND: The value of screening donors for antibody to hepatitis B core antigen (anti-HBc) for the prevention of posttransfusion hepatitis has declined markedly. However, anti-HBc screening may still be useful as a surrogate marker for the window period (WP) of human immunodeficiency virus type 1 (HIV-1) infection. STUDY DESIGN AND METHODS: First, the relationship between anti-HBc reactivity and HIV-1 WP infections was examined among 225 donors who had seroconverted to anti-HIV-1 positivity between 1987 and 1990. In addition, data from 1654 HIV-1 seropositive donors were analyzed to characterize the relationship among anti-HBc reactivity, donor demographics, and HIV-1-related risk factors. The yield and cost-effectiveness of anti-HBc for HIV-1 prevention were then projected on the basis of a published decision analysis model. RESULTS: Forty (18%) of 225 HIV-1-seroconverting donors tested anti-HBc-reactive on the donation preceding anti-HIV-1 seroconversion; in contrast, 341 (34%) of 1014 HIV-1-seropositive donors interviewed tested anti-HBc-reactive (chi-square test; p < 0.001). Anti-HBc reactivity was more common among HIV-1-seropositive donors reporting male-to-male sexual contact (169/360, 47%) and injection drug use (44/83, 53%) than among those with heterosexual contacts known to be HIV-1-positive (31/190, 16%) or transfusion exposure (3/21, 14%) or among females with no identified risk factors (21/124, 17%). The estimates of 18 to 34 percent sensitivity for anti-HBc in detecting HIV-1 WP donations and a current rate of 1 in 676,000 HIV-1 WP donations (after p24 antigen screening) suggest that continued use of anti-HBc screening could result in the transfusion of 5 to 12 fewer HIV-1-infected units per year in the United States, which would add 19 to 48 quality-adjusted years of life for the 3.5 million annual transfusion recipients at a cost of $992,020 to $2,345,000 per quality-adjusted life-year saved. CONCLUSION: The low yield and very poor cost-effectiveness of anti-HBc screening indicate that this test is not an effective screening test for HIV-1 WP donations.

Blood Donors↗
PubMed1997

Automatic volumetric capillary cytometry for counting white cells in white cell-reduced plateletpheresis components.

BACKGROUND: As the benefits of white cell (WBC)-reduced blood components become increasingly apparent, the need has arisen for a simple, automated WBC-counting technique that is sensitive to low WBC concentrations. Automated volumetric capillary cytometry was evaluated for its ability to quantify residual WBCs in WBC-reduced plateletpheresis components. STUDY DESIGN AND METHODS: The volumetric capillary cytometry system evaluated uses a laser to excite fluorescent dye-labeled nucleated cells. The number of nucleated cells per microliter is reported. Four studies were performed: linearity, precision of results near the value of 5 x 10(6) WBCs per unit, the limit of detection, and correlation to the Nageotte manual counting method. RESULTS: Assay values correlated to expected values (range, 0-125 WBC/microliter) with an r2 > 0.99. In the range of 5 x 10(5) WBCs per unit the CV was 8.5 percent, and concentration differences of 0.15 log10 were detectable. The limit of detection was 1.0 WBCs per microliter (95% upper confidence limit). The assay correlated to the Nageotte method with an r2 of 0.98, slope of 1.0, and y-intercept of 2.0 WBCs per microliter. Assay results were 10 to 15 percent higher than Nageotte results, in samples with values near 5 x 10(6) WBCs per unit. Technician time per sample was 2 to 3 minutes. CONCLUSION: Volumetric capillary cytometry is precise and sensitive to small differences in WBC concentration in the range of clinical interest. The device provides an efficient new method for quality assurance and control of WBC-reduced plateletpheresis products.

Blood Component Removal↗
PubMed1997

Cost-effectiveness of expanded human immunodeficiency virus-testing protocols for donated blood.

BACKGROUND: This study was designed to estimate the cost-effectiveness of expanding the human immunodeficiency virus (HIV)-testing protocol for donated blood beyond screening for HIV antibodies to further reduce the risk of HIV transmission through transfusion. STUDY DESIGN AND METHODS: A Markov decision analysis model was developed to estimate the cost-effectiveness of HIV antibody testing (at a cost of $5/unit) and of adding to that protocol a second HIV test, either plasma p24 antigen detection or RNA polymerase chain reaction (PCR) (at costs of $5/unit and $8/unit, respectively). Test efficacy was projected from anticipated window-period reductions (6 days for p24 antigen, 11 days for RNA PCR), and donor seroconversion rates were derived from the Retrovirus Epidemiology Donor Study. RESULTS: On the basis of current estimates of HIV prevalence rates in blood donors (1/10,000) and 16 million annual transfusions in the United States HIV antibody testing prevents 1568 cases of transfusion-acquired HIV infection each year at a cost of $3600 per quality-adjusted year of life saved. The addition of p24 antigen testing would prevent 8 more cases at a net additional cost of $60 million annually ($2.3 million/quality-adjusted life year); RNA PCR testing would prevent 16 more cases at a net additional cost of $96 million annually ($2.0 million/ quality-adjusted life year). CONCLUSION: Although expanding the donor HIV screening protocol with p24 antigen or RNA PCR testing will prevent rare cases of transfusion-associated HIV, the cost-effectiveness of such an addition is predicted to be far below that of most medical interventions. Thus, HIV test protocol additions are unlikely to provide cost-effective improvements to blood safety in the United States.

Blood Donors↗
PubMed1997

Loss of volunteer blood donors because of unconfirmed enzyme immunoassay screening results. Retrovirus Epidemiology Donor Study.

BACKGROUND: Blood donors who test repeatably reactive on enzyme immunoassay (EIA) and are not confirmed as positive are a continuing problem for blood banks. Units are discarded and donors are deferred, in spite of multiple studies indicating that such donors are very rarely infected with the transmissible agents. Few data are available, however, with which to evaluate whether the discarded units are more likely to come from particular demographic subgroups. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study database of over 2 million allogeneic whole-blood donations collected in the years 1991 through 1993 was utilized. The prevalence of false-positive and indeterminate test results within demographic subgroups was computed for antibodies to human immunodeficiency virus, hepatitis C virus, and human T-lymphotropic virus (anti-HIV, anti-HCV, anti-HTLV, respectively) and hepatitis B surface antigen (false-positive only) as the proportion of donations that were repeatably reactive on EIA but negative or indeterminate on the confirmatory or supplemental test. RESULTS: Several demographic groups with increased prevalence of false-positive and indeterminate anti-HIV results were the same females, younger age groups, blacks, and first-time donors. Likewise, many of the demographic subgroups with increased prevalence of false-positive and indeterminate anti-HCV results were similar: older age groups, non-whites, lower education levels, first-time donors, donors making directed donations, and donors who had received transfusions. For anti-HTLV, by contrast, the oldest group had the highest prevalence of false-positive results but the lowest prevalence of indeterminate results: blacks had the lowest prevalence of false positive results but the highest prevalence of indeterminate results. CONCLUSION: If units that test repeatably reactive on EIA but that are not confirmed as positive are almost always from individuals not infected with the virus in question, then these results indicate that there may be sex-, race-, and/or age-linked proteins cross-reacting with the test kit materials. Elucidation of these antigenic determinates and their subsequent removal should be a priority.

Blood Donors↗
PubMed1997

A method for estimating hepatitis B virus incidence rates in volunteer blood donors. National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study.

BACKGROUND: Calculations of the incidence of hepatitis B virus (HBV) infections in the blood donor setting that are based solely on data for seroconversion to hepatitis B surface antigen (HBsAg) will underestimate the incidence due to the transient nature of antigenemia. Estimates based on antibody to hepatitis B core antigen will overestimate the incidence due to false-positive results caused by the nonspecificity of the test. STUDY DESIGN AND METHODS: Serologic test results were obtained from multiple-time volunteer donors at five United States blood centers from January 1991 through December 1993. The observed HBsAg seroconversion rate was multiplied by an adjustment factor, derived from the weighted average probability of a positive HBsAg test for HBV-infected donors who become chronic carriers, for donors with a primary antibody response without detectable antigenemia, and for donors who develop transient antigenemia. RESULTS: Among 586,507 multiple-time donors giving 2,318,356 donations and observed for 822,426 person-years, the HBsAg incidence rate was 4.01 per 100,000 person-years. On the basis of prior reports of the duration of HBsAg positivity and the observed distribution of interdonation intervals among the study group, there was an estimated 53-percent chance that an HBV-infected donor with transient antigenemia would have a positive HBsAg test result. If 70 percent of newly HBV-infected adults have transient antigenemia, 25 percent have a primary antibody response without primary antigenemia, and 5 percent become chronic carriers, the overall chance of being detected by the HBsAg test was 42 percent, for an adjustment factor of 2.38. The total HBV incidence rate, therefore, was estimated to be 9.54 per 100,000 person-years. CONCLUSION: The crude HBV incidence rate observed from HBsAg test results will underestimate the true rate. The adjusted HBV incidence rate should be used in applications such as estimations of residual HBV risk to the blood supply and projections of the benefits of screening for HBV DNA.

Adult↗
PubMed1997

Use of human immunodeficiency virus (HIV) type 1 and 2 recombinant strip immunoblot assay to resolve enzyme immunoassay anti-HIV-2-repeatably reactive samples after anti-HIV-1/2 combination enzyme immunoassay screening.

BACKGROUND: With the implementation of combination human immunodeficiency virus types 1 and 2 (HIV-1/2) antibody enzyme immunoassay (EIA) in donor screening in 1992, the supplemental testing algorithm changed to require the use of a Food and Drug Administration (FDA)-licensed HIV-1 Western blot (WB) or immunofluorescence assay, as well as an FDA-licensed HIV-2 EIA. When HIV-2 EIA-reactive specimens are identified, further testing to confirm HIV-2 infection is recommended. Currently, a licensed HIV-2 supplemental assay is not available. STUDY DESIGN AND METHODS: The sensitivity of an HIV-1/2 recombinant strip immunoblot assay (SIA) for HIV-2 was determined on the basis of the analysis of 65 HIV-2-positive samples identified by the Centers for Disease Control and Prevention (CDC). Anti-HIV-1/2 combination EIA-repeatably reactive (RR) specimens from seven blood centers and their affiliated hospitals were tested in parallel by HIV-1 WB and HIV-2 EIA. Anti-HIV-2 EIA-RR specimens were further tested by HIV-1/2 SIA. Specimens interpreted as positive for HIV-2 or HIV-1/2 were referred to the CDC for final resolution of antibody status. RESULTS: Ninety-seven percent (63/65) of known HIV-2-positive samples tested positive for HIV-2 only or HIV-1/2 on the HIV-1/2 SIA. A total of 1048 anti-HIV-1/2 combination-EIA-RR specimens were evaluated. Sixty-nine percent (75/109) of the WB-positive specimens were HIV-2 EIA-RR, while only 9 percent (84/939) of WB-indeterminate or WB-negative specimens tested HIV-2 EIA-RR. The HIV-1/2 SIA resolved 91 percent of HIV-2 EIA-RR samples as negative. Four HIV-2 EIA-RR specimens (all HIV-1 WB-positive) were classified as positive for HIV-1 and HIV-2 in the HIV-1/2 SIA. Final interpretation of these specimens by CDC was that they were reactive for HIV-1 with cross-reactivity to HIV-2. CONCLUSION: No confirmed HIV-2-positive specimens were detected. The HIV-1/2 SIA is currently useful for resolving HIV-2 EIA-RR specimens.

AIDS Serodiagnosis↗
PubMed1997

Host-specific driving force in human immunodeficiency virus type 1 evolution in vivo.

To investigate the process of human immunodeficiency virus type 1 (HIV-1) evolution in vivo, a total of 179 HIV-1 V3 sequences derived from cell-free plasma were determined from serial samples in three epidemiologically linked individuals (one infected blood donor and two transfusion recipients) over a maximum period of 8 years. A systematic analysis of pairwise comparisons of intrapatient sequences, both within and between each sample time point, revealed a preponderance and accumulation of nonsynonymous rather than synonymous substitutions in the V3 loop and flanking regions as they diverged over time. This strongly argues for the dominant role that positive selection for amino acid change plays in governing the pattern and process of HIV-1 env V3 evolution in vivo and nullifies hypotheses of purely neutral or mutation-driven evolution or completely chance events. In addition, different rates of evolution of HIV-1 were observed in these three different individuals infected with the same viral strain, suggesting that the degree of positive pressure for HIV-1 amino acid change is host dependent. Finally, the observed similar rate of accumulation in divergence within and between infected individuals suggests that the process of genetic divergence in the HIV epidemic proceeds regardless of host-to-host transmission events, i.e., that transmission does not reset the evolutionary clock.

Amino Acid Sequence↗
PubMed1997

History of posttransfusion hepatitis.

The risk of hepatitis virus transmission from tranfusions has declined dramatically from that of the 1940s when posttransfusion hepatitis (PTH) was first appreciated. Introduction of hepatitis B surface antigen screening and conversion to volunteer donors for whole-blood donations in the late 1960s and early 1970s led to substantial reduction in PTH cases. However, up to 10% of the recipients continued to develop PTH, most cases of which were attributed to an unknown non-A, non-B viral agent. Implementation of surrogate marker testing (i.e., alanine aminotransferase and anti-hepatitis B virus core antigen) for residual non-A, non-B hepatitis in the late 1980s reduced the per unit risk of PTH from 1 in 200 to about 1 in 400. Hepatitis C virus was discovered in 1989 and quickly was established as the causative agent of > 90% of non-A, non-B PTH. Introduction of progressively improved antibody assays in the early 1990s reduced the risk of PTH due to hepatitis C virus to about 1 in 100000. Although additional hepatitis viruses exist (e.g., hepatitis G virus), these appear to be minor contributors to clinical PTH, which has been virtually eradicated.

Alanine Transaminase↗