Multidrug-resistant tuberculosis.
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Baltimore↗
Biomedical subjects
K E Nelson
Publications and source records attributed to K E Nelson.
Transmission of retroviruses from seronegative donors by transfusion during cardiac surgery. A multicenter study of HIV-1 and HTLV-I/II infections.
OBJECTIVE: To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and II (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors. DESIGN: A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991. SETTING: Cardiac surgery services of three large tertiary care hospitals. PATIENTS: The study included 11,532 patients in three hospitals who had cardiovascular surgery. MEASUREMENTS: Incident HIV-1 and HTLV-I or HTLV-II infection. RESULTS: We detected two new HIV-1 infections among patients transfused with 120,312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% CI of 0.0053%. Before donor screening for HTLV-I, transfusion of 51,026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69,272 units, a rate of 0.0014%. A corresponding HTLV-I/II-infected donor was found for this patient. CONCLUSION: Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmitted HIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60,000 units.
Aged↗
The declining risk of post-transfusion hepatitis C virus infection.
BACKGROUND: The most common serious complication of blood transfusion is post-transfusion hepatitis from the hepatitis C virus (HCV). Blood banks now screen blood donors for surrogate markers of non-A, non-B hepatitis and antibodies to HCV, but the current risk of post-transfusion hepatitis C is unknown. METHODS: From 1985 through 1991, blood samples and medical information were obtained prospectively from patients before and at least six months after cardiac surgery. The stored serum samples were tested for antibodies to HCV by enzyme immunoassay, and by recombinant immunoblotting if positive. RESULTS: Of the 912 patients who received transfusions before donors were screened for surrogate markers, 35 seroconverted to HCV, for a risk of 3.84 percent per patient (0.45 percent per unit transfused). For the 976 patients who received transfusions after October 1986 with blood screened for surrogate markers, the risk of seroconversion was 1.54 percent per patient (0.19 percent per unit). For the 522 patients receiving transfusions since the addition in May 1990 of screening for antibodies to HCV, the risk was 0.57 percent per patient (0.03 percent per unit). The trend toward decreasing risk with increasingly stringent screening of donors was statistically significant (P less than 0.001). After we controlled for the method of donor screening, the risk of seroconversion was strongly associated (P less than 0.001) with the volume of blood transfused, but not with the use of particular blood components. CONCLUSIONS: The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV. The current risk of post-transfusion hepatitis is about 3 per 10,000 units transfused.
Alanine Transaminase↗
Changes in T-lymphocyte subsets in intravenous drug users with HIV-1 infection.
OBJECTIVE: To evaluate changes in T-cell subsets in prevalent human immunodeficiency virus type 1 (HIV-1) seronegative and seropositive intravenous drug users (IVDUs) and in HIV-1 seropositive IVDUs with known time of seroconversion. DESIGN: Cohort study with a median 18-month follow-up. SETTING: Community-based clinic established to study the natural history of HIV infection in IVDUs. SUBJECTS: Eight hundred fifty-nine self-referred IVDUs aged 18 through 49 years who injected drugs within the last 10 years and who did not have an AIDS (acquired immunodeficiency syndrome)--defining illness; 152 were seronegative for HIV-1, 621 were seropositive, and 86 seroconverted during the study. OUTCOME MEASURES: Proportions and absolute numbers of lymphocytes and CD3, CD4, and CD8 T cells as determined at 6-month intervals by flow cytometry and complete blood cell counts with automated differential. RESULTS: Median numbers of CD4 lymphocytes at enrollment were 1061/microL (1.06 x 10(9)/L) for seronegative IVDUs, 508/microL for seropositive IVDUs, and 733/microL for those who seroconverted (enrolled a median of 4.5 months after seroconversion); the corresponding figures for CD8 lymphocytes were 628, 894, and 889/microL, respectively. Median rates of decline in absolute numbers and percentages of CD4 lymphocytes per 6 months were 7.6/microL (0.0%) for seropositive IVDUs and 55.1/microL (1.9%) for IVDUs who seroconverted (median follow-up after seroconversion was 12 months). Multivariate regression analysis that incorporated the within-individual correlation of the CD4 lymphocyte counts showed no significant change in these cells over time and no change due to use of drugs. CONCLUSION: Our data suggest that progression of HIV-1 infection in IVDUs, as reflected in decline of CD4 cell counts, is no more rapid than that reported for other risk groups.
Adult↗
Prevalence of tuberculin positivity and skin test anergy in HIV-1-seropositive and -seronegative intravenous drug users.
OBJECTIVES: --To identify differences in purified protein derivative (PPD) tuberculin positivity and skin test anergy rates by human immunodeficiency virus (HIV) serostatus, CD4+ lymphocyte count, and other risk factors in intravenous drug users (IVDUs); and to evaluate the appropriateness of the Centers for Disease Control (CDC)--recommended definition for a positive PPD tuberculin skin test result in HIV-1-seropositive patients. DESIGN: --Nested case-control and cross-sectional analyses. SETTING: --Community-based cohort of IVDUs. PATIENTS: --Two hundred sixty HIV-1-seropositive and -seronegative IVDUs, drawn from an unselected cohort, were skin-tested for sensitivity to PPD tuberculin, mumps, and Candida antigens using the Mantoux method. OUTCOME MEASURES: --Positivity to PPD tuberculin, skin test anergy. RESULTS: --Even using the CDC definition of an induration 5 mm or greater in diameter in HIV-1 seropositives, this group was substantially less likely to be PPD tuberculin positive than HIV-1 seronegatives (13.8% vs 25.2%; P = .02). In the HIV-1 seropositives the relative odds of being PPD positive varied depending on whether 10 mm or greater (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.2 to 0.7), 5 mm or greater (OR, 0.5; 95% CI, 0.2 to 0.9), or 2 mm or greater (OR, 0.7; 95% CI, 0.4 to 1.3) was used to define a positive test result. The mean diameter induration in the HIV-1-seropositive group was 2.6 mm vs 5.4 mm in the seronegative group (P = .005). Skin test anergy (to mumps and Candida) appeared to explain the differential. Anergy was substantially higher in the HIV-1 seropositive group and increased as the CD4+ lymphocyte count fell (chi 2 for linear trend, 24.5; P less than .0001). An inverse linear trend for PPD positivity and CD4+ lymphocyte count was also observed (chi 2 for trend, 6.1; P = .01). In multivariate analyses, being 35 years of age or older and being HIV-1 seronegative were significantly associated with PPD positivity, while history of previous police arrest was of borderline significance. Only HIV-1 seropositivity was significantly associated with anergy. CONCLUSIONS: --These findings show that CDC-recommended definition of an induration 5 mm or greater in diameter for PPD tuberculin positivity in HIV-1 seropositives significantly underestimates the "true" infection rate (using the PPD positivity rate in HIV-1 seronegatives as the criterion standard). A definition of 2 mm or greater would appear to be a better cutoff for reducing misclassification in HIV-1 seropositives. This study also confirms that delayed-type hypersensitivity is seriously depressed in HIV-1 seropositive IVDUs and that anergy testing is mandatory to properly assess a negative PPD test result.
Adolescent↗
Penicillium marneffei infection in patients infected with human immunodeficiency virus.
From June 1990 to August 1991, 21 patients infected with the human immunodeficiency virus (HIV) presented with systemic mycosis caused by Penicillium marneffei. Between August 1987 and August 1991, only five patients were observed who had P. marneffei infection but not HIV infection. The clinical presentation included fever, cough, and generalized papular skin lesions. For 11 of these 21 patients, the presumptive diagnosis of P. marneffei infection could be made by microscopic examination of Wright's-stained bone marrow aspirate and/or touch smears of skin specimens obtained by biopsy several days before the results of culture were available. Initial clinical response to treatment with either parenteral amphotericin B or oral itraconazole was favorable in most patients. Epidemiological and clinical evidence suggest that this systemic mycosis is caused by an important opportunistic pathogen and that it should be included in the differential diagnosis of AIDS, at least for countries in areas of endemicity, i.e., Southeast Asia and China.
Adult↗
Needle-cleaning practices among intravenous drug users who share injection equipment in Baltimore, Maryland.
In Baltimore, Maryland, between 1988 and 1989, 2,921 intravenous drug users were recruited into a study of drug injection practices and human immunodeficiency virus (HIV) infection. Sixty-three percent reported both current use and sharing of needles; almost all these (N = 1,757) reported using injection equipment immediately after it was used by another intravenous drug user. Of the 1,757, 62% said that they "typically" cleaned the used equipment with bleach or alcohol before injecting. These data suggest that information about disinfecting needles has disseminated into this population and identifies several groups to target for interventions.
Adult↗
Immune serum markers and CD4 cell counts in HIV-infected intravenous drug users.
We examined the association of three serum immune markers with CD4 cell counts in a large cohort of i.v. drug users with and without human immunodeficiency virus (HIV) infection. Levels of beta 2-microglobulin and neopterin were significantly elevated in HIV-infected subjects and increased in association with decline in CD4 cell counts (all p less than 0.001). Serum IgA levels in HIV-seropositive individuals were significantly elevated only when the CD4 cell count was less than 200/microliters (p less than 0.001). After controlling for HIV status and CD4 count, recent history of hepatitis was associated with significantly higher beta 2-microglobulin (p = 0.028) and marginally higher neopterin (p = 0.052) levels. There was no association of race, gender, or drug use patterns with levels of serum immune markers after controlling for HIV status and CD4 count. These data indicate that immune activation is coupled with immunosuppression in HIV-infected i.v. drug users. In addition, beta 2-microglobulin and neopterin levels are elevated in persons with a recent history of hepatitis but not in those with recent non-AIDS-defining bacterial infections. Markers of immune activation do not vary by race, gender, or drug use patterns among i.v. drug users.
Biomarkers↗
Evaluation of four semi-synthetic Mycobacterium leprae antigens with sera from healthy populations in endemic and non-endemic areas.
In order to determine the frequency of occurrence of antibodies to semisynthetic antigens of Mycobacterium leprae in clinically healthy nonpatient populations and to establish a 'baseline' for comparison with antibody frequencies in both patients with a history of leprosy and their contacts, ELISAs were conducted using representative sera from two areas: a leprosy endemic area, Cebu City, Philippines and a nonendemic area for leprosy Chicago, Illinois, USA. These sera were tested, by an indirect IgM ELISA, for the presence of antibodies reacting with four semisynthetic antigens based on the phenolic glycolipid I antigen of M. leprae: ND-O-BSA (natural disaccharide with octyl linkage to bovine serum albumin), NT-O-BSA (natural trisaccharide with octyl linkage to BSA), ND-P-BSA (natural disaccharide with phenolic ring linkage to BSA) and NT-P-BSA (natural trisaccharide with phenolic ring linkage to BSA). Using an OD reading > or = 0.16 as positive, the antigen with the lowest background seroreactivity was ND-O-BSA, which reacted with 5/398 (1.3%) sera from Cebu, and 3/426 (0.7%) sera from Chicago. A total of 10 (2.5%) of 398 sera from the endemic area reacted with at least one antigen and 5 (1.3%) sera reacted with all four semisynthetic antigens. Of the 426 sera from Chicago, 12 (2.8%) were reactive with at least one antigen and 3 (0.7%) were reactive with all four semisynthetic antigens. Mean ELISA values for the 22 positive sera for each antigen ranged from 0.17 to 0.3 OD units, while the mean values for all sera in each area ranged from 0.01 to 0.04 OD units for all four antigens. Reactivity of 14 of the positive sera to some antigens, but not all four semisynthetic antigens, indicated that the carrier and linker arms might be associated with this background reactivity. Investigation of alternative linker arms and carriers is warranted. We conclude that nonspecific background reactivity to the semisynthetic antigens representing the PG-I molecule of M. leprae is 0.7-1.3%, based on a > or = 0.16 OD cutoff value. From these data it was concluded that reactivity in individuals free of leprosy was low enough to warrant use of these antigens in a diagnostic setting, such as screening household contacts and highly endemic populations. When incidence and prevalence of leprosy are low, testing with these antigens would not be cost effective, unless applied to high risk individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Prognostic indicators for development of AIDS among intravenous drug users.
A cohort of 544 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) was recruited in 1988 and early 1989; data on laboratory markers, clinical symptoms, intravenous drug use, and demographics were collected. Forty-one IVDUs developed AIDS within 2 years of enrollment. Data were analyzed using methods of survival analysis. None of the individuals reported use of antiviral agents or Pneumocystis carinii prophylaxis at baseline. A very strong (p less than 0.001) dose-response relationship was identified between CD4 cell count at baseline and the subsequent development of AIDS. In multivariate analysis, both the presence of more than one clinical HIV-1-related symptom and serum neopterin greater than 12 nmol/L showed significant associations with the relative hazard (95% confidence interval) of AIDS after controlling for CD4 of 2.9 (1.6, 5.6) and 2.0 (1.0, 3.7), respectively. In these IVDUs, serum beta 2-microglobulin did not add predictive power for progression to AIDS. The effect of clinical symptoms was stronger for high CD4 cell counts, indicating the need to monitor HIV seropositive IVDUs with both laboratory studies and clinical evaluation.
Acquired Immunodeficiency Syndrome↗
Antibody responses to Haemophilus influenzae type B vaccines in men with human immunodeficiency virus infection.
BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at increased risk for serious infections caused by Haemophilus influenzae, yet there are few data on their antibody responses to the H. influenzae type b vaccines. METHODS: We evaluated antibody responses in 248 men who were randomly assigned to receive a single dose of either the H. influenzae type b polysaccharide (PRP) vaccine or the polysaccharide-mutant diphtheria toxoid conjugate vaccine (PRP-CRM). The subjects were stratified into four groups: seronegative men (67 subjects), men with asymptomatic HIV infection (79), men with symptomatic HIV infection (47), and men with the acquired immunodeficiency syndrome (AIDS) (55). RESULTS: Before immunization, the subjects with AIDS had the lowest PRP-antibody titers; 40 percent had titers below the putative protective level (less than 0.15 micrograms per milliliter). In the seronegative subjects, those with asymptomatic HIV infection, and those with symptomatic HIV infection, the PRP-CRM vaccine led to a threefold greater increase in geometric mean antibody titers than did the PRP vaccine (P less than 0.01). However, the subjects with AIDS had a greater antibody response to the PRP vaccine. The antibody response of HIV-seropositive men to the PRP-CRM vaccine correlated significantly with the number of CD4 lymphocytes (r = 0.47, P less than 0.0001, as compared with r = -0.01 for the PRP vaccine). In these HIV-infected men, both vaccines elicited the dominant anti-PRP idiotype described previously in populations not infected with HIV. CONCLUSIONS: Immunization with the PRP-CRM conjugate vaccine early in the course of HIV infection is likely to confer protection against disease caused by H. influenzae type b.
AIDS Vaccines↗
New evidence on intravenous cocaine use and the risk of infection with human immunodeficiency virus type 1.
To examine whether recent intravenous use of cocaine might be associated with increased risk of human immunodeficiency virus type 1 (HIV) infection, the authors studied 2,597 active intravenous drug users: 2,399 with recent cocaine injection and 198 with recent injection of heroin or other drugs but not cocaine. These subjects were adult residents of Baltimore City and the surrounding Maryland counties, recruited via outreach into the community between February 1988 and March 1989. In contrast to the first report on the cocaine-HIV association, the present study sample was not recruited solely from drug treatment programs. In the present study, estimated HIV seroprevalence was 26.4% for recent cocaine injectors as compared with 10.6% among all other recent intravenous drug users; the relative odds estimate was 3.03. In the untreated segment of the sample, HIV seroprevalence was 26.0% for recent cocaine injectors as compared with 8.9% among others (relative odds (RO) = 3.61). The estimated degree of association did not change appreciably when multiple logistic regression was used to hold constant potentially confounding and/or mediating variables such as receptive anal intercourse, number of sex partners, and use of injection equipment obtained at shooting galleries (RO = 2.64). Augmenting these cross-sectional data, preliminary prospective data showed excess risk of HIV seroconversion among recent cocaine injectors (estimated relative risk = 2.11). While other research has examined the cocaine-HIV association, the present study differs in that it has allowed a test for whether the association was a spurious artifact of studying drug users recruited solely from drug treatment programs, a broad array of alternative determinants of HIV infection have been held constant, and the association has been examined with seroconversion data. The results lend support to the abiding concern about the risk of HIV infection among cocaine users.
Adolescent↗
Antibody to hepatitis C virus among cardiac surgery patients, homosexual men, and intravenous drug users in Baltimore, Maryland.
In order to define the risk factors for infection with hepatitis C virus, the authors determined the prevalence and incidence of antibodies to hepatitis C in three cohorts in Baltimore, Maryland, enrolled in prospective studies of human immunodeficiency virus (HIV-1) infection. Among 500 multi-transfused patients who underwent cardiac surgery in 1985 and 1986, 12 (2.4%) were hepatitis C seropositive before surgery while 19 (3.9%) developed antibodies in the 8-12 months after surgery. The seroprevalence of hepatitis C virus among 225 intravenous drug users followed since 1988 was 85%, which did not vary by HIV-1 status. Longer duration of intravenous drug use was significantly associated with hepatitis C seropositivity. Among 926 homosexual/bisexual men followed since 1984, 15 (1.6%) were hepatitis C seropositive; only intravenous drug use and a history of hepatitis A were marginally associated with hepatitis C in this population. No association was found between hepatitis C virus and HIV-1 or sexual behavior variables in this population. These data suggest that hepatitis C is readily transmitted by blood exposure, but is transmitted inefficiently by sexual means.
Adult↗
Sexually transmitted diseases in a population of intravenous drug users: association with seropositivity to the human immunodeficiency virus (HIV).
The association between human immunodeficiency virus (HIV) seropositivity and a history of sexually transmitted diseases (STDs), evidence of STDs on physical examination, and sexual and drug use practices was studied in a population of 2921 intravenous drug users (IVDUs) in Baltimore during 1988 and 1989. Overall, 24.1% were HIV-seropositive at baseline, and 60% reported a history of an STD. A significant association was found between HIV seropositivity and a history of syphilis (P = .04); both were more frequent among homosexual/bisexual men than among heterosexual IVDUs. In multivariate analysis, a history of syphilis was independently associated with HIV seroprevalence in homosexual/bisexual male IVDUs, of whom 90% reported a history of sexual intercourse with women. Cocaine injection was independently associated with HIV seropositivity but not a history of syphilis on multivariate analysis. STDs, indicative of unsafe sex practices, are common in this population; efforts are needed to prevent sexual transmission of HIV infection among IVDUs and their sex partners.
Baltimore↗
HIV seroconversion and disinfection of injection equipment among intravenous drug users, Baltimore, Maryland.
To examine the putative protective effect of disinfectant use on HIV seroconversion among intravenous drug users, we conducted a nested case-control study comparing 22 black heterosexual HIV seroconverters with 95 persistent seronegatives matched on gender, use of cocaine, date of study entry, and duration of follow-up. For intravenous drug users who reported using disinfectant all the time, the odds of seroconversion was 0.77 (95% CI: 0.25-2.38) compared with those who reported no use of disinfectants; for those who used disinfectants some of the time, the corresponding odds ratio was 0.91 (95% CI: 0.26-3.31). The odds ratio for use of disinfectant all the time was 0.63 (95% CI: 0.10-3.91) for those injecting at galleries and 1.08 (95% CI: 0.35-3.11) for those not injecting at galleries. These data suggest a limited protective effect of disinfectant use in the field which may be more beneficial to those injecting in shooting galleries.
Adult↗
Risk factors for shooting gallery use and cessation among intravenous drug users.
BACKGROUND: Shooting galleries, locations where intravenous drug users (IVDUs) can rent or borrow needles and syringes, are a high-risk environment for HIV-1 transmission. This study investigates risk factors for lifetime attendance at shooting galleries and differentiates characteristics of those who continue to frequent shooting galleries and those who have stopped. METHODS: We interviewed 2615 active IVDUs in Baltimore in 1988 and 1989 and determined patterns of IV drug use, sociodemographics, and HIV-1 serostatus as related to persistence vs cessation of shooting gallery use. RESULTS: Over half (52%) of active IVDUs reported ever using a shooting gallery, with 33% reporting use within the prior 3 months. In multivariate analysis, lifetime shooting gallery use was associated with male gender, homosexuality/bisexuality, low socioeconomic status, Black race, and heavier drug involvement. Persistent shooting gallery users were more frequently male, homosexual/bisexual, homeless, less educated, and started IV drug use more recently compared with those who ceased going to shooting galleries. CONCLUSIONS: Shooting gallery attendance may be pragmatic from a sociological and economic perspective, but it carries with it a heightened risk of acquiring HIV-1 infection.
Adult↗
The ALIVE study, a longitudinal study of HIV-1 infection in intravenous drug users: description of methods and characteristics of participants.
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Acquired Immunodeficiency Syndrome↗
Effect of glucocorticoids and interferon-gamma on the oxidative responses of monocytes from leprosy patients and normal donors.
Leprosy patients suffering from erythema nodosum leprosum are frequently treated with glucocorticosteroids. The role glucocorticosteroids and interferon-gamma (IFN-gamma) play in regulating the interaction of phagocytic cells with Mycobacterium leprae was examined. Monocytes from leprosy patients receiving prednisone therapy responded to lower concentrations of IFN-gamma in vitro with enhanced superoxide anion release when challenged with M. leprae or M. bovis BCG than did monocytes from healthy subjects and other leprosy patients. Although the number of patients was small and the population heterogeneous, the data suggested that prednisone could alter IFN-gamma efficacy and led to the examination of the effect of glucocorticosteroids on IFN-gamma activation of monocytes. IFN-gamma treatment following in vitro dexamethasone pretreatment of monocytes from healthy subjects resulted in a greater enhancement of superoxide anion generation than that observed with IFN-gamma treatment alone. These findings are important considerations in evaluating patient immune function because IFN-gamma is being used in a number of clinical trials with leprosy patients.
Adult↗