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Biomedical subjects

R Y Dodd

Publications and source records attributed to R Y Dodd.

At least 37 records · Page 2Linked to original sources
PubMed1998

Transmission of parasites by blood transfusion.

A number of parasitic diseases are known, or suspected to be transmitted by blood transfusion. Of greatest concern are malaria and Chagas' disease, but babesia, leishmania and toxoplasmosis also offer risk in particular locations or circumstances. Some of these parasites may be imported into non-endemic areas as a result of population movements and in some cases, the natural range of the parasite is increasing as a result of environmental change. Recent research, particularly on Chagas disease and babesiosis will be discussed, along with measures to minimize transmission of these and other parasites via transfusion.

Animals↗
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

A retrospective analysis of microbial contaminants in outdated random-donor platelets from multiple sites.

BACKGROUND: Platelet components contaminated with bacteria are an important source of transfusion-associated bacterial sepsis. Estimates of contamination rates vary widely (0-10%) and are highly controversial. The present study, designed with stringent testing regimens, retrospectively determined the prevalence of microbial contaminants in platelets from four collection regions. STUDY DESIGN AND METHODS: During a 9-month period, outdated platelet units were assayed by spreading aliquots from the unit, and from thioglycollate broth medium inoculated with part of the unit, onto 5-percent sheep blood agar media. Cultures were examined after 72-hour incubation at 37 degrees C, and, if bacterial growth was present, the assay processes were repeated with fresh inocula. Units were considered contaminated only if repeatedly positive. RESULTS: Four (0.08%) of 4995 units sampled were contaminated, two with Corynebacterium sp. and one each with Propionibacterium acnes and Aspergillus terreus. Contaminants were present at low, subclinical levels and were detected only after amplification in thioglycollate. The contaminated units were cultured 1, 2, 3, and 7 days after expiration. CONCLUSION: Contamination rates were low and did not vary by region. The identification of A. terreus suggests the role that transfusion may play in transmitting fungal infections should be reassessed. The persistent detection of contaminated platelet units supports the need for a test to detect clinically relevant levels of microbial contaminants in blood components.

Aspergillus↗
PubMed1997

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors.

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T-lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window-period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window-period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window-period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.

Biomarkers↗
PubMed1997

Seroepidemiology of Trypanosoma cruzi, etiologic agent of Chagas' disease, in US blood donors.

A comprehensive seroepidemiologic study was conducted in two Red Cross regions (Los Angeles and Miami) to determine the prevalence of Trypanosoma cruzi antibodies in at-risk blood donors, to identify additional risk factors, and to assess the likelihood of transmitting T. cruzi by transfusion. At-risk and control donors were stratified by a broad risk question, tested for T. cruzi antibodies, and if confirmed as seropositive, enrolled in case-control and lookback investigations. A total of 299,398 donors were queried; 23,978 at-risk and 25,587 control donations were tested, and T. cruzi antibodies were confirmed in 34 donors (33 and 1, respectively). Seropositive donors shared one risk factor; birth/extensive time in a T. cruzi-endemic area. Lookback studies identified 11 recipients, all negative for T. cruzi antibodies. Screening strategies that use a question are unlikely to identify all seropositive donors. The lack of definitive data on the risk of transmission by transfusion indicates additional studies of donors and recipients are needed.

Adolescent↗
PubMed1996

False-positive human immunodeficiency virus type 1 western blot tests in noninfected blood donors.

BACKGROUND: The manufacturers' criteria for a positive human immunodeficiency virus type 1 (HIV-1) Western blot (WB) test were recently revised to require reactivity to only two of the following bands: p24, gp41, and gp120/160. In a recent report, low-risk blood donors were identified in whom nonspecific reactivity to multiple env antigens in WB testing resulted in apparently false-positive WBs by these criteria. The present study was conducted to verify the existence of false-positive WBs among noninfected donors and to assess the extent of this problem. STUDY DESIGN AND METHODS: Four donors classified as WB-positive on the basis of env-only (3 cases) or p24/env-only (1 case) patterns were investigated. Index and/or follow-up specimens were tested by polymerase chain reaction (PCR), by overlapping recombinant env antigens and synthetic peptides in enzyme immunoassays, and by deglycosylated and denatured antigen WBs. WB records from American Red Cross blood centers were reviewed to determine the frequency of env-only and p24/env-only patterns, relative to all positive WBs, from 1988 through 1993. RESULTS: The four index-case donors denied risk and had stable WB reactivity during follow-up. HIV PCR was negative in all. Env reactivity was restricted to nonglycosylated gp41 epitopes; no gp120-specific reactivity was detected. For three of the four donors, env reactivity was mapped to a 20-amino acid N-terminal epitope of gp41. The rate of detecting WBs with these false-positive patterns increased from 0.6 percent of all positive WBs from 1988 to 1990 (4/776) to 8 percent in 1991 and 1992 (52/683), and then it declined to 6 percent in 1992 and 1993 (47/783). Env-only patterns predominated in 1991 and 1992, whereas p24/env-only patterns were more frequent following implementation of combined anti-HIV-1/HIV type 2 enzyme immunoassays in 1992. CONCLUSION: Low-risk blood donors can have false-positive results on WB tests. Increased detection of env-only and p24/env-only WBs appears related to the enhanced sensitivity of newer enzyme immunoassays to gp41 and p24 antibodies. Donors with these patterns should undergo follow-up testing to document the presence or absence of HIV infection.

Adult↗
PubMed1996

Infectious risk of plasma donations: relationship to safety of intravenous immune globulins.

Although intravenous immune globulin (IVIG) preparations may be derived from tens of thousands of donations, the residual risk of viral contamination of recovered plasma appears remarkably low, at least for human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Consequently, most pools are unlikely to contain these viruses although the situation is not as well understood for US-derived source plasma. In addition, routine preparation methods are likely to eliminate infectivity from the relatively fragile HIV. Current plasma screening measures are generally designed to maintain reasonable titres of anti-HBs in pools, perhaps contributing to the absence of HBV infection. The situation with respect to hepatitis C virus (HCV) is not well understood and it appears that sensitive screening for anti-HCV may have had an impact on the safety of at least one IVIG preparation. The implementation of effective viral inactivation procedures is expected to eliminate any further risk of HCV infection from IVIG preparations.

Blood Donors↗
PubMed1995

Estimated risk of transmission of the human immunodeficiency virus by screened blood in the United States.

BACKGROUND: In the United States, transmission of the human immunodeficiency virus (HIV) by blood transfusion occurs almost exclusively when a recently infected blood donor is infectious but before antibodies to HIV become detectable (during the "window period"). We estimated the risk of HIV transmission caused by transfusion on the basis of the window period associated with the use of current, sensitive enzyme immunosorbent assays and recent data on HIV incidence among blood donors. METHODS: We analyzed demographic and laboratory data on more than 4.1 million blood donations obtained in 1992 and 1993 in 19 regions served by the American National Red Cross, as well as the results of HIV-antibody tests of 4.9 million donations obtained in an additional 23 regions. RESULTS: We estimated that, in the 19 study regions, 1 donation in every 360,000 (95 percent confidence interval, 210,000 to 1,140,000) was made during the window period. In addition, it is estimated that 1 in 2,600,000 donations was HIV-seropositive but was not identified as such because of an error in the laboratory. We estimated that 15 to 42 percent of window-period donations were discarded because they were seropositive on laboratory tests other than the HIV-antibody test. When these results were extrapolated to include the additional 23 Red Cross service regions, there was a risk of one case of HIV transmission for every 450,000 to 660,000 donations of screened blood. If the Red Cross centers are assumed to be representative of all U.S. blood centers, among the 12 million donations collected nationally each year an estimated 18 to 27 infectious donations are available for transfusion. CONCLUSIONS: The estimated risk of transmitting HIV by the transfusion of screened blood is very small and nearly half that estimated previously, primarily because the sensitivity of enzyme immunosorbent assays has been improved.

Blood Banks↗
PubMed1995

Time course of detection of viral and serologic markers preceding human immunodeficiency virus type 1 seroconversion: implications for screening of blood and tissue donors.

BACKGROUND: Almost all human immunodeficiency virus (HIV) transmission via blood or tissues that has occurred since anti-HIV screening was implemented in 1985 is traceable to blood given after infection but before antibody seroconversion, a time that is referred to as the window period. In this study, the performance of newer assays designed to detect viral and serologic markers soon after infection is assessed, and the reduction in the window period achieved by these assays is estimated. STUDY DESIGN AND METHODS: Three cohort studies of persons at high risk for acquiring HIV infection were identified. These studies included well-controlled HIV type 1 (HIV-1) polymerase chain reaction (PCR) analyses of serial preseroconversion specimens from HIV-1-seroconverting homosexual men or intravenous drug users. Of 81 enrollees with anti-HIV-1 seroconversion documented by a viral lysate anti-HIV-1 enzyme immunosorbent assay (EIA) available in 1989, 13 (16%) had PCR-positive preseroconversion specimens. In the present study, sera from these 13 PCR-positive samples were further tested for anti-HIV by 10 contemporary EIAs and 6 supplemental assays, as well as being tested for plasma p24 antigen and HIV-1 RNA. Preseroconversion sera from 38 HIV-1 DNA PCR-negative cohort participants were also tested by selected anti-HIV EIAs and tested for p24 antigen and HIV-1 RNA. On the basis of these laboratory data and the intervals between blood drawing in all 81 men, the reduction in the preseroconversion window period achieved by these new assays was estimated with a mathematical model developed to analyze seroconversion data. RESULTS: Nine (69%) of the 13 preseroconversion PCR-positive samples had anti-HIV that was detectable by one or more contemporary anti-HIV-1 or anti-HIV type 2 EIA. Supplemental antibody assays were negative on all four EIA-nonreactive preseroconversion samples and negative or indeterminate on a high proportion of the nine EIA-reactive PCR-positive samples. Eight (61%) of the 13 samples were p24 antigen-positive, and 11 (85%) were HIV-1 RNA-positive. The estimated reductions in the window period (relative to the index viral lysate-based anti-HIV EIA) were as follows: contemporary anti-HIV-1/2 EIAs, 20.3 days (95% Cl, 8.0-32.5); p24 antigen and DNA PCR, 26.4 days (95% Cl, 12.6-38.7); and RNA PCR, 31.0 days (95% Cl, 16.7-45.3). CONCLUSION: Recent improvement in the sensitivity of anti-HIV assays has resulted in significant shortening of the preseroconversion window period. Consequently, the incremental reduction in the window period that could be achieved by implementing direct virus-detection assays has diminished significantly.

Blood Donors↗
PubMed1995

Mammalian genotoxicity assessment of methylene blue in plasma: implications for virus inactivation.

BACKGROUND: The risk of adverse consequences of virus-inactivation procedures for plasma and cellular blood components must be less than the risk of transfusion-associated viral disease. Previous studies demonstrated that methylene blue, which is currently used in Europe for virus inactivation in fresh-frozen plasma, can elicit mutations in bacterial test systems. This study investigates the potential for methylene blue genotoxicity in two mammalian test systems. STUDY DESIGN AND METHODS: Different concentrations of methylene blue were prepared in plasma (heat-treated at 56 degrees C for 1 hour to reduce cytotoxicity) and used, without illumination, in an in vitro mouse lymphoma cell assay designed to detect forward mutations in the gene encoding thymidine kinase. The assay was performed in the presence or absence of rat liver S9 microsomal fraction. Similarly prepared samples of methylene blue in heat-treated plasma were used in an in vivo mouse micronucleus assay. Each system included a negative vehicle control (heat-treated plasma without methylene blue) and a positive control consisting of a known genotoxic agent. RESULTS: Intravenous administration to mice of 62 mg per kg of methylene blue did not increase the frequency of micronuclei in polychromatic red cells harvested from bone marrow. However, methylene blue concentrations of 10 micrograms per mL (with S9 activation) and 30 micrograms per mL (without S9 activation) significantly increased the thymidine kinase mutation frequency of mouse lymphoma cells to approximately 110 x 10(-6), from a spontaneous frequency of 28 x 10(-6). CONCLUSION: Methylene blue is mutagenic in cultured mammalian cells. In contrast, results from the mouse micronucleus assay suggest that the genotoxicity is not expressed in vivo. Considerably more investigation will be required to assess the genotoxic potential of intravenously administered methylene blue used in virus-inactivation procedures, because of the likelihood of the formation of methylene blue photoproducts or the impact of metabolic conversion of methylene blue to leukomethylene blue in vivo.

Animals↗
PubMed1995

Prevalence of antibodies to hepatitis C virus and other markers in Jamaica.

Three population groups, 1500 blood donors, 513 antenatal women representing a normal population group and 250 sicklers representing a multiply transfused group were studied to determine the prevalence of hepatitis C viral (HCV) infection in Jamaica. The relationship to liver enzyme levels, hepatitis B infection, syphilis and HIV infection was also investigated. Sera were screened by enzyme-linked immunoassay (EIA) for anti-HCV C100-3 and subsequently tested by a supplementary second generation recombinant immunoblot assay (RIBA). In the blood donors, the prevalence of anti-HCV was low, 0.3%-0.4%, the same level as that reported by several European countries. In the multiply transfused sicklers, the prevalence was more than seven times higher. No HCV infection was detected in the antenatal group. There was little correlation between HCV infection and surrogate markers alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti-HBc) and no correlation with sexually transmitted diseases.

Adult↗
PubMed1995

Transfusion-transmitted hepatitis virus infection.

For many years, viral hepatitis has been considered to be a frequent and serious adverse outcome of blood transfusion. The majority of cases have been due to hepatitis B and C viruses, which, respectively, are DNA and RNA viruses. Both are lipid enveloped and are susceptible to viral inactivation procedures. Careful donor screening and the use tests for HBsAg and anti-HBc have essentially eliminated the risk of transfusion-transmitted HBV infection.

Blood Donors↗