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Biomedical subjects

J W Mosley

Publications and source records attributed to J W Mosley.

At least 37 records · Page 2Linked to original sources
PubMed1995

Donor screening for antibody to hepatitis B core antigen and hepatitis B virus infection in transfusion recipients.

BACKGROUND: Testing for antibody to hepatitis B core antigen (anti-HBc) as a surrogate for hepatitis C viremia is no longer needed for blood donor screening. Currently, the important question is how much its use supplements hepatitis B surface antigen (HBsAg) donor screening in preventing transfusion-transmitted hepatitis B virus (HBV) infection. STUDY DESIGN AND METHODS: In a study conducted in the 1970s, 64 blood donors were associated with 15 cases of HBV (1.0%) in 1533 transfusion recipients. Sera from 61 donors at donation and 29 follow-up visits were available for present-day assays for HBsAg, HBV DNA, anti-HBc, and antibody to HBsAg (anti-HBs). RESULTS: HBsAg was found in four previously negative blood donors; HBV DNA was limited to three of these four. Anti-HBc was detected in six HBsAg-negative donors. Two other donors were negative in all assays at donation, but positive for anti-HBc and anti-HBs 2 to 4 months later. The remaining donors were negative for all HBV markers, which left five recipient cases unexplained. No HBV transmission was observed when anti-HBs sample-to-negative control values were > or = 10. CONCLUSION: Some 33 to 50 percent of cases of hepatitis B that could be transmitted by transfusion of blood from HBsAg-negative donors are prevented by anti-HBc screening. Anti-HBc-positive donors unequivocally positive for anti-HBs should be considered noninfectious for HBV and should be allowed to donate. Anti-HBc screening of paid plasmapheresis donors, supplemented by anti-HBs testing, would reduce the amount of HBV to be processed by virus inactivation and increase the content of anti-HBs in plasma pools.

Blood Donors↗
PubMed1995

Rapid molecular epidemiology of human immunodeficiency virus transmission.

Close sequence homology between strains of HIV-1 have been used to corroborate cases of epidemiologically identified transmission. As an alternative to extensive DNA sequence analysis, genetic relateness between pairs of HIV quasispecies was estimated using the reduced electrophoretic mobilities of HIV-1 envelope DNA heteroduplexes through polyacrylamide gels. All six infections acquired in a dental practice in the late 1980s and four of six infections acquired through blood product transfusions and sexual contact in 1984-1985 could be rapidly identified. A rising level of genetic diversity within HIV-1 subtype B facilitated the detection of later transmission events. Transmission linkages could be detected up to 4 years following infection. The simple and rapid technique of DNA heteroduplex tracking can therefore assist epidemiological investigations of HIV transmission and potentially of other genetically variable infectious agents.

Base Sequence↗
PubMed1995

Human immunodeficiency virus type 1 infection: relationship of risk group and age to rate of progression to AIDS. Transfusion Safety Study Group.

Age differences among risk groups may account for rate differences in progression of human immunodeficiency virus type 1 (HIV-1) infection to AIDS. Institutions in 6 US cities used a common protocol to study infected homosexual blood donors, recipients of blood components, and factor VIII-treated hemophiliacs. Follow-up was every 6 months. Actuarial risk for AIDS 8 years after infection was 51% among blood recipients, 36% among homosexual donors, and 24% among hemophiliacs. Significant risk group differences were explained by age differences among cohorts (medians of 61, 29, and 22 years, respectively). When age was adjusted for and both CD4 cell value and zidovudine treatment were used as time-dependent covariates, homosexual donors had more rapid progression than the other groups. Omitting Kaposi's sarcoma as an AIDS-defining condition removed any significant differences among risk groups except CD4 cell count and age. Thus, major factors in AIDS progression are age-related.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Dual human immunodeficiency virus type 1 infection and recombination in a dually exposed transfusion recipient. The Transfusion Safety Study Group.

We studied a case in which a 2-month-old premature infant was concurrently transfused with packed erythrocytes from two different human immunodeficiency virus type 1 (HIV-1)-seropositive donors in late 1984. The two donors also each singly infected a second infant. Inspection of sequences from portions of the HIV-1 genomes in each of the two donors showed a close relationship to the strain in their respective singly exposed recipients. Inspection of sequences from the dually exposed recipient provided evidence of an individual simultaneously infected with two distinct HIV-1 strains, as well as recombination of the two strains in vivo.

Amino Acid Sequence↗
PubMed1994

Effect of low- and intermediate-purity clotting factor therapy on progression of human immunodeficiency virus infection in congenital clotting disorders. Transfusion Safety Study Group.

Low- and intermediate-purity clotting-factor therapies are believed to accelerate human immunodeficiency virus (HIV) progression in hemophiliacs through adverse immune effects of the other plasma proteins in the preparations. To investigate this postulate, we evaluated data from six clinical centers that observed persons with congenital factor deficiencies at 6-month intervals. The present analysis is based on HIV-infected subjects who received intermediate purity factor VIII or factor IX concentrates, or cryoprecipitate. For long-term outcome, we classified 374 subjects by the type and amount of treatment during our first year of observation, and determined the subsequent rate of progression to a CD4 count less than 200 cells/microL. A second analysis of this group used a repeated-measures, random-effect model that allowed for individual differences in CD4 decline. Finally, we compared short-term rates of change in CD4 count in each treatment interval of 525 subjects with the type and amount of factor therapy received in the same interval. There was no overall or dose-related deleterious effect of any form of treatment on CD4 trend. The CD4 decrease was less when cryoprecipitate was administered alone or combined with concentrate, but not significantly so. Our results counter the assertion that low- and intermediate-purity products accelerate the rate of CD4 decrease in HIV-1-infected hemophiliacs.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Naturally occurring hepatitis B virus mutants with deletions in the core promoter region.

A novel class of hepatitis B virus mutants in patients with chronic hepatitis B is described. The predicted effect of the mutations is to disrupt the X open reading frame. The location of the genetic alterations within the putative precore promoter also suggests that they may ameliorate precore transcription, which would provide an alternate mechanism for HBeAg(-) escape variation. Definitive conclusions regarding the effects of these mutations must await additional in vitro and in vivo studies.

Adult↗
PubMed1994

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group.

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1-infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high-risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Has hepatitis A virus been transmitted by clotting factor concentrates among hemophiliacs in the United States?

Hepatitis A virus (HAV) infection occurred after administration of factor VIII concentrate in Europe associated with one manufacturing process. We determined if there was an excess prevalence of anti-HAV among hemophiliacs in the United States, and whether any infections here were potentially concentrate-associated. We observed clotting disorder patients and household members for up to 7 years at 6-month intervals. Selected specimens were titered for anti-HAV-immunoglobulin G content to distinguish whether they were passively or actively acquired. Our results show that anti-HAV prevalence was 20-25%, but males with clotting deficiencies had a 44% rate (p < 0.001). Passive anti-HAV (> or = 30 to < 950 mIU/ml) from intermediate-purity factor VIII may have protected against community HAV exposure. Factor IX concentrates, which contain no anti-HAV, did not protect and a few instances of past transmission are possible. Criteria for present-day concentrate-associated cases were developed; no subject conclusively met these criteria during the period between late 1985 and May 1993. In conclusion, the excess of anti-HAV prevalence in male clotting disorders is attributable to both passive administration in concentrate, and past therapy prior to concentrates. No untoward HAV event related to concentrate was found in our population, but measures to prevent transmission of nonenveloped viruses should be instituted.

Drug Contamination↗
PubMed1994

Hepatitis A virus transmission by blood products in the United States. Transfusion Safety Study Group.

To address the question of HAV prevalence and seroconversion in relation to clotting factor concentrates, we assayed an early serum for 339 hemophiliacs followed every 6 months by the Transfusion Safety Study in the period from mid-1985 until mid-1992. We found 58.4% positive around entry, with an age-specific prevalence that did not vary with age. In comparison to rates for anti-HIV-negative blood donors, they were significantly higher. Based on testing of subsequent sera, 11 hemophiliacs (7.8% of 141 susceptibles) changed their anti-HAV status from negative to positive. In 9 instances, positivity immediately followed the first dose of intravenous immune globulin. A possible seroconversion followed treatment with blood components, and a possible seroconversion followed intermediate-purity, solvent/detergent(SD)-treated factor VIII concentrate. Neither of these 2 patients was anti-HAV IgM positive, so that passively transferred antibody is possible. The high prevalence among hemophiliacs at entry must be further investigated by determining the expected background rate in a US population similar to the hemophilia patients, and by comparing anti-HAV prevalence associated with SD-treated and heat-inactivated concentrates.

Adolescent↗
PubMed1993

Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B virus infection.

OBJECTIVE: To investigate the possible interference with acute hepatitis B virus infection by co-infection with hepatitis C virus. DESIGN: Analysis of stored sera collected for transfusion transmitted viruses study in 1970s. SETTING: Four major medical centres in the United States. PATIENTS: 12 recipients of blood infected with hepatitis B virus. MAIN OUTCOME MEASURES: In 1970s, presence of antibodies in hepatitis B virus and raised serum alanine aminotransferase concentration; detection of antibodies to hepatitis C virus with new enzyme linked immunoassays. RESULTS: Five of the 12 patients were coinfected with hepatitis C virus. Hepatitis B surface antigen was first detected at day 59 in patients infected with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C virus (p = 0.01); median durations of antigenaemia were 83 and 21 days respectively (p = 0.05), and the antigen concentration was lower in the coinfected patients. Alanine aminotransferase patterns were uniphasic when hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four coinfected recipients developed chronic hepatitis C virus infection. The fifth patient was followed for only four months. CONCLUSIONS: Acute coinfection with hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in humans, and onset of hepatitis B may reduce the severity of hepatitis C virus infection but not frequency of chronicity. Alanine aminotransferase concentration showed a biphasic pattern in dual infection.

Acute Disease↗
PubMed1993

Effect on lymphocyte subsets of clotting factor therapy in human immunodeficiency virus-1-negative congenital clotting disorders. The Transfusion Safety Study Group.

Patients with hemophilia A without human immunodeficiency virus type 1 (HIV-1) infection have lower CD4+ counts and CD4+/CD8+ ratios than controls. This is usually interpreted as a therapy-induced immunodeficiency. Our data re-examine the effect of therapy on peripheral blood mononuclear cell immunophenotypic subpopulations in all congenital clotting disorders. Since late 1985 we have prospectively observed HIV-1 uninfected persons with all types and severity of disorder. Controls were household members without clotting disorders or HIV-1 infection. Analyses of immunophenotype and treatment included a longitudinal random effects model. Compared with controls, age-adjusted CD4+ counts were significantly lower in treated patients (P < .0001) and in patients with all types of clotting disorders who were seldom or never treated (P = .0005). Significantly lower values among both treated and untreated clotting disorder subjects (P < .05) were likewise found for total lymphocytes, several other T-cell subsets, and the CD4+/CD8+ ratio. For most indexes, including the CD4+ count and CD4+/CD8+ ratio, the type of clotting deficiency was not a significant variable. Comparing persons who had no or minimal therapy with those having the most showed increases in CD8+ (P = .0017) and CD20+ CD21- counts (P = .0255), and a lower CD20+ CD21+/CD20+ ratio (P = .0106) in the latter. Controls and persons with clotting disorders differ in CD4+ count. Among those with clotting factor disorders, there is no difference attributable to type of clotting disorder or factor therapy. Large amounts of treatment increased CD8+ and CD20+ CD21- counts, but were not associated with a change in CD4+ count.

Antigens, CD↗
PubMed1993

Purity of factor VIII concentrates and serial CD4 counts. The Transfusion Safety Study Group.

Whether expensive high-purity factor VIII concentrates are required to slow CD4 decline in HIV-infected haemophiliacs is controversial. We examined CD4 counts among such cases treated with intermediate-purity and high-purity factor VIII. 36 subjects treated with high-purity concentrate for 6 months or more had a smaller decline in CD4 than 72 matched controls on intermediate-purity concentrate (two-sided p = 0.08). In a more complex analysis with 226 subjects, CD4 counts declined 3% less per 6 months with high-purity material than with intermediate product (p = 0.04). Thus concentrate purity may affect rate of CD4 change.

CD4-Positive T-Lymphocytes↗
PubMed1993

Nucleotide sequence analysis of the precore region in patients with fulminant hepatitis B in the United States.

BACKGROUND: A precore defective hepatitis B virus (HBV) mutant unable to produce hepatitis B e antigen (HBeAg) has been associated with fulminant hepatitis B. We have studied the etiologic contribution of precore mutants among North American patients with this disorder. METHODS: We studied 39 patients with fulminant hepatitis B. The precore and proximal core regions of HBV from 37 of 39 patients were sequenced. RESULTS: Four patients (10.8%) harbored nonsense mutants likely to produce an HBeAg negative HBV infection; two such mutants had a G to A substitution at position 1896, one lost the precore initiation codon, and one harbored a stop codon immediately downstream of the precore initiation codon. Recovered sequences from seven additional patients displayed silent or missense mutations in these regions. All delta coinfected patients harbored known wild type strains of HBV. A significantly poorer survival was associated with antibody to HBe positivity and presence of nucleotide substitutions in the precore/core region. CONCLUSIONS: The prevalence of precore mutations in 37 patients from the United States was lower than reported elsewhere; only two patients were found to have the G to A transition mutation in the precore region at position 1896. We conclude that HBeAg negative HBV mutants do not play a predominant etiologic role among North American patients with fulminant hepatitis B.

Adenine↗