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Biomedical subjects

E Donegan

Publications and source records attributed to E Donegan.

At least 19 recordsLinked to original sources

HIV, syphilis infection, and sexual practices among transgenders, male sex workers, and other men who have sex with men in Jakarta, Indonesia.

OBJECTIVES: To establish the prevalence of HIV, syphilis, and sexual risk behaviour among three groups of men who have sex with men in Jakarta, Indonesia, and to investigate sexual links between these men and broader heterosexual populations. METHODS: Anonymous, cross sectional surveys among community recruited transgender and male sex workers and self recognised men who have sex with men (MSM) were undertaken in mid-2002 in Jakarta, Indonesia. Places where transgender and male sex workers sell sex and where men go to meet non-commercial male sex partners were mapped. Probability samples were selected for the sex worker populations, while a mixed probability and convenience sample was drawn for self recognised MSM. Blood was drawn for HIV and syphilis serology and community interviewers administered a standardised questionnaire. RESULTS: HIV prevalence was 22% among transgender sex workers, 3.6% among male sex workers, and 2.5% among self recognised MSM, and syphilis prevalence was 19.3%, 2.0% and 1.1% respectively. 59.3% of transgender sex workers and 64.8% of male sex workers reported recent unprotected anal intercourse with clients, and 53.1% of other MSM reported unprotected anal sex with male partners. Some 54.4% of male sex workers and 18.3% of other MSM reported female partners in the preceding year. CONCLUSION: HIV has reached substantial levels among transgender sex workers, and is not negligible in other MSM groups. Risk behaviour is high in all subpopulations, and bisexual behaviour is common, meaning the threat of a wider epidemic is substantial. Prevention programmes targeting male-male sex are needed to reduce this threat.

Adult↗

Importation of multiple HIV type 1 strains into West Papua, Indonesia (Irian Jaya).

HIV-1 from 16 sexually transmitted disease clinic patients in Timika, West Papua, Indonesia was amplified by RT-PCR and subtyped by a combination of envelope and gag region heteroduplex mobility analysis (HMA) and direct PCR DNA sequencing. HMA showed the presence of 14 subtype E (CRF01_AE) and 2 subtype B HIV-1. Phylogenetic analysis of a 540-bp V3-V4 region of gp120 showed that 9 of 10 CRF01_AE variants clustered tightly with a median distance of 1.3% (range, 0.5 to 2.2%) whereas 1 CRF01_AE variant diverged significantly from the others (median distance, 10.7%; range, 10.1 to 11.8%). One subtype B virus envelope was typical of United States/European strains whereas the other appeared to be related to Thai subtype B' variants. These results reflect the independent introduction of multiple HIV-1 strains into West Papua, with the rapid spread in the majority of infected patients tested of a single strain of HIV-1E (CRF01_AE).

Adolescent↗

Adverse reactions to isosulfan blue during selective sentinel lymph node dissection in melanoma.

BACKGROUND: Selective sentinel lymph node (SLN) dissection can spare about 80% of patients with primary melanoma from radical lymph node dissection. This procedure identifies the SLN either visually by injecting isosulfan blue dye around the primary melanoma site or by handheld gamma probe after radiocolloid injection. METHODS: During selective SLN mapping, 1 to 5 ml of isosulfan blue was injected intradermally around the primary melanoma. From November 1993, to August 1998, 406 patients underwent intraoperative lymphatic mapping with the use of both isosulfan blue and radiocolloid injection. Three cases of selective SLN dissection, in which adverse reactions to isosulfan blue occurred, were reviewed. RESULTS: We report three cases of anaphylaxis after intradermal injection with isosulfan blue of 406 patients who underwent intraoperative lymphatic mapping by using the procedure as described above. The three cases we report vary in severity from treatable hypotension with urticaria and erythema to severe cardiovascular collapse with or without bronchospasm or urticaria. CONCLUSIONS: In our series, the incidence of anaphylaxis to isosulfan blue was approximately 1%. Anaphylaxis can be fatal if not recognized and treated rapidly. Operating room personnel who participate in intraoperative lymphatic mapping where isosulfan blue is used must be aware of the potential consequences and be prepared to treat anaphylaxis.

Adult↗

Risk factors for plasma cell endometritis among women with cervical Neisseria gonorrhoeae, cervical Chlamydia trachomatis, or bacterial vaginosis.

OBJECTIVE: We sought to determine potential risk factors for upper genital tract inflammation in women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis. STUDY DESIGN: In a case-controlled study we compared 111 women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis (the study group) with 24 women who had negative tests for each of these infections (the control group). We evaluated potential risk factors for upper genital tract inflammation by use of bivariate and then logistic regression analysis. RESULTS: We found plasma cell endometritis in 53 of 111 women in the study group and 3 of 24 controls (odds ratio = 6.4, 95% confidence interval 1.7 to 35.0). On logistic regression, the study group women who were in the proliferative phase had increased likelihood of plasma cell endometritis (odds ratio = 4.5, 95% confidence interval 1.6 to 12.4). CONCLUSION: The proliferative phase of the menstrual cycle seems to be the primary risk factor for ascending infection by organisms associated with pelvic inflammatory disease. This may be due to a hormonal effect or to the loss of the cervical barrier during menstruation.

Adolescent↗

Role of viral load in heterosexual transmission of human immunodeficiency virus type 1 by blood transfusion recipients. Transfusion Safety Study Group.

Eighteen transfusion recipients infected with human immunodeficiency virus type 1 (HIV-1) were followed prospectively with their 19 long-term sexual partners from 1986 to 1993 in California, Florida, and New York. Follow-up included clinical, behavioral, immunologic, serologic, and virologic evaluations. Two partners were already infected when seen 18 and 34 months after sexual contact began following the infectious transfusion. Four of 17 initially seronegative partners seroconverted during 23 person-years of observation. The recipient's clinical status, mononuclear cell subset variations, and time trend in CD4+ counts had no association with transmission. Individual plasma HIV-1 ribonucleic acid (RNA) loads were stable during observation, and sexual transmission was not attributable to an upward trend or transient burst in viremia. However, recipients who transmitted HIV-1 to their sexual partners had higher mean viral RNA levels than did nontransmitting recipients (4.3 vs. 3.6 log10 copies/ml; p = 0.05). Although this series was small, the prospective observations suggest that viral load was the only characteristic in the recipient that contributed to heterosexual infectiousness.

Acquired Immunodeficiency Syndrome↗

Development of oral lesions in human immunodeficiency virus-infected transfusion recipients and hemophiliacs.

The authors used multivariate repeated-measures transition models to identify risk factors for two oral lesions related to human immunodeficiency virus (HIV)-candidiasis and hairy leukoplakia-in 152 HIV-infected blood transfusion recipients and hemophiliacs. Subjects were examined for occurrences of these lesions every 6 months from July 1985 through March 1993, yielding 1,076 study visits. It was found that, after adjustment for the CD4:CD8 T-lymphocyte ratio, patients with a history of candidiasis in the previous 18 months were at high risk of lesion recurrence. This risk increased with the number of prior episodes and with the recency of the episode(s). A history of hairy leukoplakia was less predictive of persistence of that lesion after adjustment for significant risk factors (including candidiasis and use of antifungal agents at the current examination, a low CD4:CD8 cell ratio, and age less than 40 years). The authors also found a high coprevalence of candidiasis and hairy leukoplakia in these subjects. These results suggest that HIV-infected patients with oral candidiasis should be carefully monitored for subsequent episodes over the next 12-18 months, and patients with either oral candidiasis or hairy leukoplakia and a low CD4:CD8 cell ratio should be carefully examined for the other type of lesion as well.

Adolescent↗

Screening potential corneal donors for HIV-1 by polymerase chain reaction and a colorimetric microwell hybridization assay.

PURPOSE: Current screening of potential corneal donors for human immunodeficiency virus type 1 (HIV-1) involves serologic detection of antibodies to the virus. However, this approach cannot detect infection during the seronegative window period of the disease. We therefore evaluated the polymerase chain reaction (PCR) assay for viral nucleic acid as a possible alternative to screening cadaveric blood for HIV-1. METHODS: Blood specimens from cadavers diagnosed at autopsy with acquired immunodeficiency syndrome (AIDS) (n = 21), at high risk for HIV-1 infection (n = 47), and at no known risk (n = 350) were screened by PCR for HIV-1 proviral DNA and human leukocyte antigen (HLA)-DQ alpha sequences, and for HIV antibodies. RESULTS: All AIDS group samples were seropositive; of these, 18 (86%) and 20 (95%) of 21 were positive for HIV by PCR of proteinase K- and Chelex-extracted pellets, respectively. The seropositive samples negative by PCR testing were shown to inhibit PCR amplification. Nine (19%) of 47 high-risk specimens were HIV-positive. The no-known-risk group yielded negative results. The overall sensitivities for PCR in the proteinase K- and Chelex-treated groups were 90% and 97%, respectively, compared with Western blot reactivity. If PCR-inhibitory samples and HLA-DQ alpha-negative samples had been eliminated, sensitivity would have been 100%. Specificity was 100% for each group. CONCLUSIONS: Screening cadaveric blood by PCR may be feasible, but further refinement of the assay and blood specimen collection practices will be necessary for it to become routine. Future studies should focus on optimizing specimen procurement and preparation to reduce or eliminate specimens that inhibit PCR.

AIDS Serodiagnosis↗

Complementary therapies in HIV disease.

This study was designed to determine whether a standardized program of complementary therapies combined with appropriate standard medical care would have a measurable influence on the course of HIV disease when compared with data from other groups. All 10 participants began this study in 1988 with a diagnosis of asymptomatic HIV-positive. They received a 1-month orientation to the program and were then seen at 3-month intervals for follow-up data collection. Data were compared with two groups that had not been trained in the comprehensive treatment program. After 30 months, the mean CD4 cell count of our study group declined by 4% (406 to 391). The mean red and white blood cell counts remained stable at 96% and 105% of baseline, respectively. The mean CD8 cell number rose by 28%. No mortality occurred. One opportunistic infection (pneumocystis carinii pneumonia) developed in the study group. No other significant symptoms, serious infections, or disease progression developed in the other 9 participants during the study period. At long-term follow-up 8 of the 10 study participants remained alive 7 years after beginning the study protocol. These data suggest that patients who are presented counseling on good nutrition, vitamin supplementation, stress reduction, exercising, and involving oneself in community potentially can continue to live asymptomatic lives that in quality and length exceed the lives of those HIV-positive individuals not presented such counseling.

Adult↗

Transient increase in circulating donor leukocytes after allogeneic transfusions in immunocompetent recipients compatible with donor cell proliferation.

Donor leukocytes in therapeutic blood components are implicated in transfusion-related complications ranging from alloimmunization to graft-versus-host disease (GVHD) to viral transmission and reactivation. To further characterize the kinetics of donor leukocyte clearance after allogeneic transfusion, we developed allele-specific polymerase chain reaction (PCR) assays directed at a single-copy Y chromosome gene and HLA class II alleles. These assays enable sensitive detection and quantitation of donor leukocytes at concentrations ranging from one cell to greater than 1,000 cells per 125 microL of recipient blood. When applied to serial samples from five consecutive orthopedic surgery patients who met study criteria, we observed 99.9% clearance of donor leukocytes over the initial 2 days posttransfusion, followed by a transient, 1-log increase in circulating donor leukocytes on days 3 to 5. This phenomenon was reproduced in a canine transfusion model, where the transient donor leukocyte expansion phase was prevented by gamma irradiation of donor blood, and was not observed after transfusions into alloimmunized dogs. We hypothesize that this transient increase in circulating allogeneic donor cells represents one arm of an in vivo mixed lymphocyte reaction, with activated donor T lymphocytes proliferating in an abortive GVHD reaction to HLA-incompatible recipient cells. Further investigation of this phenomenon should provide insight into the mechanisms involved in donor-recipient leukocyte interactions posttransfusion and the relationship of these interactions to leukocyte-induced complications.

Animals↗

Detection of hepatitis C after liver transplantation. Four serologic tests compared.

To determine the best method for detecting HCV infection in immunosuppressed patients, stored frozen serum from 101 liver transplant recipients was tested for hepatitis C virus. Each sample was tested by four assays. HCV RNA was detected by both polymerase chain reaction (PCR) and branched DNA signal amplification. Antibody to HCV was determined using second-generation enzyme-linked immunoassay (EIA) and recombinant immunoblot assay. Forty one transplant recipients met the working definition for true positives of HCV infection. Of these "true positives," 98% were positive by HCV RNA PCR assay, 88% by b-DNA signal amplification assay, 88% by anti-HCV EIA, and 63% demonstrated two or more reactive bands on recombinant immunoblot. Five of 57 (9%) HCV-antibody negative recipients had HCV RNA detected by both methods. Of 44 HCV enzyme-linked immunoassay (EIA) repeatedly reactive samples, the recombinant immunoblot was negative in 2 and indeterminate in 13. HCV RNA was present in 9 of 13 recombinant immunoblot indeterminate sera. Nine EIA repeatedly reactive sera were negative by both tests for HCV RNA. In liver transplant recipients, HCV infection is best determined by measurement of HCV RNA. Antibody formation may be delayed or suppressed in a minority of patients despite > 10(9) equivalents/L (> 10(6)/mL) of HCV RNA in serum. Recombinant immunoblots with a single reactive band pattern often indicate HCV infection in immunosuppressed patients.

Hepacivirus↗

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↗

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↗

Transfusion transmission of retroviruses: human T-lymphotropic virus types I and II compared with human immunodeficiency virus type 1.

BACKGROUND: The incidence of transfusion transmission of human T-lymphotropic virus type I (HTLV-I) and HTLV type II (HTLV-II) has not been compared directly or to that of human immunodeficiency virus type 1 (HIV-1). The effects of refrigerator storage of the blood component on infectivity of the viruses needs definition. STUDY DESIGN AND METHODS: The circumstances influencing the transmission of HTLV-I, HTLV-II, and HIV-1 via blood of donors whose sera were stored in a repository and who were retrospectively documented as having been infected at blood donation were examined. Confirmation and typing of anti-HTLV positivity in donors and recipients used polymerase chain reaction, supplemented by specific peptide testing. RESULTS: Overall, 27 percent (26/95) of the recipients of blood components from anti-HTLV-I- and -II-positive donors became infected (9 with HTLV-I and 17 with HTLV-II). No recipients of acellular blood components became infected with HTLV-I or -II. There was no probable transmission by components stored > 10 days. The rates of transmission for both viruses were similar: 0 to 5 days' storage, 17 (74%) of 23; 6 to 10 days, 8 (44%) of 18; and 11 to 14, 0 (0%) of 10 (trend, p = 0.0002). In comparison, 89 percent (112/126) of the recipients of anti-HIV-1-positive blood were infected regardless of component type, and no effect on transmission occurred with storage for < 26 days. CONCLUSION: Transfusion-transmitted HTLV-I and -II are similar. The data suggest that a donor's lymphocytes become noninfectious when they lose the ability to be activated or to proliferate.

Acquired Immunodeficiency Syndrome↗

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↗

Heterosexual transmission of human immunodeficiency virus type 1 from transfusion recipients to their sex partners.

Using lookback procedures and other methods, we identified and then prospectively followed human immunodeficiency virus type 1 (HIV-1)-infected transfusion recipients and their sex partners to determine AIDS incidence and risks of heterosexual transmission of HIV-1. At enrollment, 7 of 32 (21.9%) female partners of male recipients were themselves infected with HIV-1, as compared with none of 14 male partners of female recipients (p = 0.08). No additional episodes of transmission were observed. The prevalence of advanced immunodeficiency at enrollment was similar in male and female recipients. Male recipients with advanced immunodeficiency (CD4+ lymphocyte count < or = 0.20 x 10(9)/L or a history of clinical AIDS) at enrollment were more likely to have infected their female partners (odds ratio = 7.9; p = 0.03) than men with neither condition. Similarly, AIDS-free survival, as estimated by the product-limit method, was lower among male transmitters than among male nontransmitters (p = 0.01). Transmission was not associated with frequency of unprotected vaginal intercourse. Our data suggest that HIV-1-infected men who develop immunodeficiency rapidly are more likely to infect their sex partners and that the greater efficiency of male-to-female HIV-1 transmission is not explained by a greater number of sexual contacts or more advanced immunodeficiency in index subjects.

Adult↗

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↗