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Biomedical subjects

K E Nelson

Publications and source records attributed to K E Nelson.

At least 109 records · Page 6Linked to original sources

Effect of isoniazid chemoprophylaxis on HIV-related mycobacterial disease.

OBJECTIVES: The aims of this study were to (1) identify trends and risk factors for mycobacterial disease and (2) determine the effect of expanded access to isoniazid chemoprophylaxis on tuberculosis incidence. METHODS: A prospective observational cohort study was conducted among community-based injecting drug users (IDUs); 2960 IDUs (942 human immunodeficiency virus [HIV] seropositive) were followed up from January 1988 to June 1994. Directly observed chemoprophylaxis with twice-weekly isoniazid (10 to 15 mg/kg) was offered to purified protein derivative (PPD) tuberculin-positive (> or = 5-mm induration diameter in HIV-seropositive subjects and > or = 10-mm diameter in HIV-seronegative subjects) individuals but not to those with cutaneous anergy. Overall and annual incidence rates of disease due Mycobacterium tuberculosis, Mycobacterium avium complex, and other atypical mycobacteria were estimated using Poisson regression. RESULTS: HIV seropositivity was the strongest risk factor for tuberculosis, M avium complex, and other mycobacterial disease (relative risk [RR], 3.8, 17.2, and 6.9, respectively). Median CD4 lymphocyte cell counts for the three groups of mycobacterial disease were 0.17, 0.03, and 0.02 x 10(9)/L (167/microL, 30/microL, 18/microL) within 6 months of diagnosis (before or after). Overall incidence rates of tuberculosis, M avium complex disease, and other mycobacterial disease were 1.9, 8.8, and 2.7 per 1000 person-years, respectively. Tuberculosis incidence peaked in 1991 at six per 1000 person-years. However, after access to directly observed preventive therapy was expanded for tuberculin-positive subjects, incidence fell to only one case in 1992 and zero cases for 24 months from mid-1992 to mid-1994. During this period the number of PPD-positive patients who completed at least 26 weeks of therapy (or were still receiving isoniazid) more than tripled (from 21 to 70). None of the 12 patients with tuberculosis diagnosed during follow-up had received any preventive therapy. In addition, no tuberculosis developed among participants with cutaneous anergy. Calendar trends in risk for M avium complex and tuberculosis diverged after expanded access to isoniazid prophylaxis. Compared with 1988-1989, risk of M avium complex increased sevenfold. Tuberculosis risk fell 83% from the peak risk in 1990-1991. CONCLUSIONS: Expanded access to directly observed isonazid therapy for tuberculin-positive IDUs with and without HIV infection was associated with an 83% drop in tuberculosis incidence, while in the same period M avium complex incidence significantly increased. These population-based data are consistent with those obtained from clinical trials of isoniazid prophylaxis and were obtained without offering chemoprophylaxis to HIV-infected patients with cutaneous energy.

AIDS-Related Opportunistic Infections↗

Hepatitis B immunization: a potential incentive to HIV vaccine trial participation in Thailand?

To assess the effectiveness of hepatitis B immunization as an incentive to retention in HIV seroincidence studies and future HIV vaccine trials in northern Thailand, subjects enrolled in three HIV seroincidence cohorts were screened for hepatitis B markers and seronegatives were offered free hepatitis B immunization. Cohorts studied included female commercial sex workers (CSWs), male sexually transmitted disease (STD) patients, and recently discharged military conscripts. Subjects who agreed to the immunization program were compared with those not enrolled to determine the utility of immunization as an incentive to cohort retention. Full immunization was achieved for 273 (89.5%) of 305 vaccinees; only 323 (60.6%) of 533 subjects not immunized completed the same follow-up visits (OR = 1.49, 95% and CI = 1.27, 1.75). Hepatitis B vaccination was a significant incentive for completion of the follow-up program. The vaccination program had the greatest effect on the CSWs; a similar effect was seen for male STD patients, but not for discharged conscripts. Despite the immunization program, follow-up rates at 12 months were similar in the immunized and nonimmunized groups.

AIDS Vaccines↗

Risk factors for HIV-1 seroconversion among young men in northern Thailand.

OBJECTIVE: To identify behavioral and sociodemographic risk factors for incident human immunodeficiency virus-1 (HIV-1) infection among healthy young men in northern Thailand. DESIGN: Men inducted into military service in northern Thailand in May and November 1991 were followed at 6-month intervals until discharge 2 years later. Trained nonmilitary interviewers identified risk factors for HIV-1 infection through interviews with the men. SETTING: Thirteen military bases in northern Thailand. PARTICIPANTS: A total of 1932 seronegative men, aged 19 to 23 years (average age, 21 years) at enrollment, conscripted into the Royal Thai Army and Air Force from six upper-northern Thai provinces. MAIN OUTCOME MEASURES: Human immunodeficiency virus-1 seroincidence as determined through enzyme-linked immunosorbent assay and verified by Western blot, and univariate and multivariate analyses of risk factors related to HIV-1 incidence. RESULTS: A total of 85 men seroconverted to HIV-1 over the period of observation, giving an incidence rate of 2.43 per 100 person-years. Factors strongly associated with HIV-1 seroconversion were frequency of visits to female commercial sex workers (CSWs), sex with men, and incident sexually transmitted diseases (STDs). High frequency of condom use showed a significant (P < .001) protective effect for HIV-1 incidence among men with a history of recent sex with female CSWs in univariate analysis, but a multivariate model demonstrated no difference in HIV-1 seroconversion rates by consistency of condom use. Multivariate analysis incorporating condom use showed that having sex with men (adjusted relative risk [RR], 2.59; 95% confidence interval [CI], 1.08 to 6.25), having sex with CSWs (adjusted RR ranged from 2.54 [95% CI, 1.81 to 3.58] to 2.74 [95% CI, 1.56 to 4.81]), and incident STDs (adjusted RR, 2.38 [95%, CI, 1.31 to 4.32]) to be predictors of incident HIV-1 infection. Substance use was not associated with HIV-1 seroconversion rates in multivariate analysis. CONCLUSION: The HIV-1 incidence in this cohort of young men appears to be primarily attributable to having sex with female CSWs. Condom use provided some protection, although not in multivariate analysis; however, condom use has previously been shown likely to be useful in preventing HIV-1 transmission. Thus, programs to increase effective condom use in brothels are essential. Efforts to extend condom use to non-CSW partners are especially needed. More effective prevention and treatment of STDs may also be necessary to decrease HIV-1 infection in this population.

AIDS Serodiagnosis↗

Effects of imitative and conversational recasting treatment on the acquisition of grammar in children with specific language impairment and younger language-normal children.

The purpose of the study was to compare the relative effectiveness of imitative treatment and conversational recast treatment in children with language impairment and in a group of children with normal language skills. Language treatment outcomes were compared between a group of older (4.7 to 6.7) specifically-language-impaired (SLI) children and a group of younger (2.2 to 4.2) language-normal (LN) children matched on language levels and on intervention targets. The results indicated: (a) Target acquisition was more rapid under conversational recast treatment for both groups: (b) This outcome held for targets absent initially (in pretreatment sampling and probing) as well as for initially partially mastered targets. (c) SLI children sometimes can learn grammatical structures as efficiently as language-normal children if similar language input is tailored to their specific developmental language levels. Implications of these findings for language treatment strategies with SLI children are discussed. Theoretical models compatible with the data also are considered.

Age Factors↗

Changes in phosphorylation of tau during ischemia and reperfusion in the rabbit spinal cord.

The microtubule-associated protein tau plays an important role in the dynamics of microtubule assembly necessary for axonal growth and neurite plasticity. Ischemia disrupts the neuronal cytoskeleton both by promoting proteolysis of its components and by affecting kinase and phosphatase activities that alter its assembly. In this study the effect of ischemia and reperfusion on the expression and phosphorylation of tau was examined in a reversible model of spinal cord ischemia in rabbits. tau was found to be dephosphorylated in response to ischemia with a time course that closely matched the production of permanent paraplegia. Dephosphorylation of tau was limited to the caudal lumbar spinal cord. In a similar manner, Ca2+/calmodulin-dependent kinase II activity was reduced only in the ischemic region. Thus, dephosphorylation of tau is an early marker of ischemia as is the rapid loss of Ca2+/calmodulin-dependent kinase II activity. tau, however, was rephosphorylated rapidly during reperfusion at site(s) that cause a reduction in its electrophoretic mobility regardless of the neurological outcome. Alterations in phosphorylation or degradation of tau may affect microtubule stability, possibly contributing to disruption of axonal transport but also facilitating neurite plasticity in a regenerative response.

Animals↗

Donation deferral criteria for human immunodeficiency virus positivity among blood donors in northern Thailand.

BACKGROUND: The purpose of this study was to develop human immunodeficiency virus (HIV) infection donation deferral criteria for blood donors in an HIV-epidemic area of northern Thailand, where the predominant means of transmission of HIV is through heterosexual contact. STUDY DESIGN AND METHODS: In a preliminary study, 2242 blood donors were interviewed, and their blood was tested for HIV antibodies between September 1993 and April 1994. The risk factors associated with HIV positivity were identified. Criteria to identify HIV-positive persons on the basis of a logistic equation were developed and applied to another group of 5769 prospective blood donors. RESULTS: A multivariate analysis showed the following odds ratios (OR) for traits that were independently associated with HIV positivity: younger age (OR = 0.93 for each additional year of age), male gender (OR = 2.41), having no more than a primary school education (OR = 2.00), being in the military (OR = 1.78), being unsure of one's own blood safety (OR = 2.00), history of injecting drug use (OR = 5.36), diagnosis of syphilis or positive syphilis serologic test in the past 12 months (OR = 2.67), and genital ulcer in the past 12 months (OR = 4.56). On the basis of the model, with a limit of <10 percent loss of uninfected donors, predicted probabilities of HIV positivity alone or of markers of infection with HIV, hepatitis B virus, or Treponema pallidum were calculated. With a cutoff of 6.5-percent estimated probability of HIV infection, derived from the logistic equation, the donor deferral criteria have 33.6-percent sensitivity and 8.3-percent positive predictive value for HIV positivity and 15.5-percent sensitivity and 18.4-percent positive predictive value for markers of infection with one of the three pathogens. CONCLUSION: The proposed donor deferral system provides a more flexible, sensitive, and predictive tool for averting donation by those who, though HIV antibody-negative, are at a higher risk of being infected with HIV.

Adult↗

Effect of human immunodeficiency virus type 1 infection on the antibody response to a glycoprotein conjugate pneumococcal vaccine: results from a randomized trial.

Adults (n = 282) were randomized to receive either a pneumococcal glycoprotein conjugate vaccine, composed of pneumococcal serotypes 6B, 14, 18C, 19F, and 23F linked to CRM197, or a 23-valent pneumococcal polysaccharide vaccine. Among human immunodeficiency virus (HIV)-uninfected persons, conjugate vaccine elicited significantly higher IgG antibody geometric mean titers (GMTs) than did polysaccharide vaccine for serotypes 6B, 18C, and 23F: IgG GMTs were 9.0 versus 4.8, 23.2 versus 5.9, and 15.3 versus 4.4 micrograms/mL, respectively. In contrast, the two vaccines elicited similar antibody GMTs in HIV-infected persons: GMTs ranged from 1.3 to 10.8 micrograms/mL for all serotypes. Of note, among persons receiving polysaccharide vaccine, antibody GMTs in HIV-uninfected and -infected persons with CD4 lymphocytes > or = 500/microL were similar. These data underscore the importance of controlled clinical evaluations of newer pneumococcal vaccines in all high-risk groups for whom pneumococcal immunization is recommended and highlight the need for early immunization of HIV-infected persons with currently available polysaccharide vaccines.

AIDS-Related Opportunistic Infections↗

Differences in the incidence of hepatitis B and human immunodeficiency virus infections among injecting drug users.

Both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) type 1 seroconversions have been considered as outcome measures to evaluate the effectiveness of needle exchange programs. To assess the relationships between incident HBV and HIV infections among injecting drug users (IDUs), seroconversions were prospectively studied among a cohort of 240 HBV- and HIV- seronegative IDUs. The incidence of HBV seroconversion declined from 24.41/100 person-years in 1988 to 0 seroconversions in 1992. In contrast, HIV seroconversion rates varied little from the overall rate of 3.29/100 person-years. HBV seroconversion predicted subsequent HIV seroconversion among male IDUs (relative incidence [RI]= 4.23) but not among female IDUs (RI=0.86). Because of different transmission dynamics, HBV seroconversion probably has limited utility as a surrogate outcome measure for incident HIV. However, HBV seroconversion itself is an appropriate and important outcome measure for evaluation of prevention programs among IDUs.

Adult↗

Seasonal variation of disseminated Penicillium marneffei infections in northern Thailand: a clue to the reservoir?

Disseminated Penicillium marneffei infections are common AIDS-defining opportunistic infections among persons with human immunodeficiency virus (HIV) infection in northern Thailand. Penicilliosis due to P. marneffei is the third most frequent AIDS-defining infection in this population, after tuberculosis and cryptococcosis. Very little is known about the epidemiology and natural reservoir of P. marneffei. The seasonal distribution of two common AIDS-defining fungal infections was compared among patients diagnosed between 1991 and 1994 at Chiang Mai University Hospital. There were 550 cases (492 male, 58 female patients) of P. marneffei and 793 cases (685 male, 108 female patients) of Cryptococcus neoformans infection diagnosed. In each year, P. marneffei but not C. neoformans infections were more frequent in the rainy than the dry season. Seasonal variation of P. marneffei infections in AIDS patients in northern Thailand may provide valuable information in determining the important reservoirs and exposures to this organism that lead to disseminated disease in these patients.

AIDS-Related Opportunistic Infections↗

Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users.

To assess the effect of human immunodeficiency virus (HIV) immunosuppression on ongoing hepatitis C virus (HCV) infection, CD4 lymphocyte counts and serum concentrations of HCV RNA, HIV RNA, and alanine aminotransferase (ALT) were evaluated among members of a cohort of injecting drug users (IDUs). With 100 participants randomly selected at various stages of HIV-related immunosuppression, serum HCV RNA concentrations increased with age (P = .007) and were higher in HIV-positive IDUs with 201-500 (P = .026) and 51-200 (P = .004) CD4 cells/mL than in HIV-negative participants. Among 27 HCV-infected IDUs who acquired HIV infection, serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs, increasing by 0.60 logs after HIV seroconversion (P < .0001), by 0.12 logs each subsequent year (P = .006), and by 0.36 logs per log increase in CD4 cells (P = .01). Serum ALT levels were similar between HIV-positive (40.1 IU/mL) and HIV-negative (45.4 IU/mL) patients (P > .10). While HIV infection and possibly HIV progression are associated with increased HCV RNA levels, other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons.

Adolescent↗

An estimate of the number of human immunodeficiency virus (HIV)-positive blood donations by HIV-seronegative donors in a northern Thailand HIV epicenter.

Despite mandatory antibody testing, human immunodeficiency virus (HIV) can be transmitted from HIV-infected blood that is seronegative. The objective of this study was to estimate the probability of HIV-infected blood donations during the seronegative "window period" in a northern Thailand HIV epicenter. Thus, a retrospective cohort of repeat blood donors was created. With the assumptions that the probability of HIV seroconversion is distributed uniformly between the last HIV-negative and the first HIV-positive donation and that the seronegative window is 45 days, the rate of window-period donations was calculated by multiplying the incidence by the window duration. Of 11,232 repeat donors, 273 seroconverted during 9,518,863 person-days of observation (i.e., a window-period donation rate of 1/775). There were more window-period donations among 21- to 30-year-old men and in donors replacing blood of friends or relatives. Additional measures are needed to reduce the high number of HIV-infected window-period donations.

Adolescent↗

Human immunodeficiency virus infection and infective endocarditis among injecting drug users.

Human immunodeficiency virus (HIV) infection and infective endocarditis are serious complications of injection drug use. To determine whether HIV infection may increase the risk of endocarditis beyond that associated with drug injection, we performed a nested case-control study among injecting drug users taking part in an ongoing cohort. We identified 26 participants with infective endocarditis between cohort enrollment (in 1988-1989) and June 1992, through reviews of medical records and death certificates. We matched each endocarditis case with up to five controls (N = 120) on enrollment date, race/ethnicity, and follow-up time. Data were taken from baseline and from the one follow-up visit: the last visit before the endocarditis occurred for cases and the closest visit (+/- 3 months) for controls. We used conditional logistic regression to quantify the association between HIV serostatus at follow-up and subsequent endocarditis, after adjusting for a history of endocarditis or sepsis before enrollment, injection duration, current injection frequency, and a recent history of abscess at injection sites. Among current injectors at follow-up, the adjusted odds ratio (OR) of developing endocarditis for HIV-seropositive subjects with > or = 350 CD4 cells per microliter, compared with HIV-seronegative subjects, was 2.31 [95% confidence interval (CI) = 0.61-8.78]; the corresponding OR for HIV-seropositive subjects with < 350 CD4 cells per microliter was 8.31 (95% CI = 1.23-56.37). These data indicate that HIV-related immunodeficiency may independently increase the risk of infective endocarditis among injecting drug users.

Adult↗

Restriction endonuclease analysis of Penicillium marneffei.

Forty-six isolates of Penicillium marneffei were differentiated into two DNA types on the basis of their restriction fragment length polymorphisms. Of the 22 human isolates of P. marneffei, 16 (72.7%) were type I and 6 (27.3%) were type II. Of the 23 bamboo rat isolates, 20 from Rhizomys sumatrensis were type I and 3 from Cannomys badius were type II. The soil isolate was type II. These data represent the first molecular epidemiological study of this important emerging fungal pathogen.

AIDS-Related Opportunistic Infections↗

Diversity of the envelope glycoprotein among human immunodeficiency virus type 1 isolates of clade E from Asia and Africa.

Human immunodeficiency virus type 1 isolates of clade E, known to be largely responsible for the fulminating epidemic in Southeast Asia, have been derived exclusively from Asia and Africa. Here we provide full or partial sequences of the envelope glycoprotein gene from 13 additional clade E isolates from Asia representing patients in both early and late stages of disease. More extensive comparison of isolates within clade E by geographic locale, stage of disease, and year of isolation is now possible. The genetic diversity of clade E isolates from Asia, particularly among those derived from early-stage patients, is restricted compared with African isolates (mean interisolate distances in gp120, 5.4 and 20.2%, respectively). However, patients hospitalized with AIDS-related illnesses in Thailand harbored clade E isolates exhibiting broader interisolate diversity and with highly heterogeneous third hypervariable loop sequences. An additional pair of cysteine residues, predicting a novel disulfide bridge and present in 80% of clade E isolates from Asia, was uniformly absent from six African isolates. Clade E isolates in Thailand from early-stage subjects continue to be genetically similar to potential vaccine prototype strains, providing a favorable environment for the evaluation of genotype E candidate vaccines. However, evidence of increasing interisolate diversity is appearing among late-stage patients in Asia. This diversification of the clade E virus, if sustained, may impact preventive vaccine development strategies.

Africa↗

Viral infections in short-term injection drug users: the prevalence of the hepatitis C, hepatitis B, human immunodeficiency, and human T-lymphotropic viruses.

OBJECTIVES: The purpose of this study was to estimate the prevalence and correlates of four blood-borne viral infections among illicit drug injectors with up to 6 years of injecting experience. METHODS: We analyzed data from 716 volunteers recruited in 1988 and 1989. Test results for hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus, type 1 (HIV), and human T-lymphotropic virus types I and II (HTLV) were examined across six sequential cohorts defined by duration of drug injection. RESULTS: Overall, seroprevalence of HCV, HBV, HIV, and HTLV was 76.9%, 65.7%, 20.5% and 1.8%, respectively, and 64.7%, 49.8%, 13.9%, and 0.5%, respectively, among those who had injected for 1 year or less. Among the newest initiates, HCV and HBV were associated with injecting variables, and HIV was associated with sexual variables. CONCLUSIONS: The high rates of HCV, HBV, and HIV infections among short-term injectors emphasizes the need to target both parenteral and sexual risk reduction interventions early. Renewed efforts at primary prevention of substance abuse are indicated.

Adolescent↗

Feasibility of northern Thai factory workers as participants in HIV vaccine trials.

To determine the feasibility of establishing a cohort of HIV-1 seronegative factory workers for potential HIV vaccine trials, and other HIV preventive interventions, we enroled and followed 499 male and female industrial workers in Lamphun Province, northern Thailand. A baseline demographic and HIV seroprevalence survey was conducted by a mobile team at worker's housing units in Lamphun Province in 1994. Follow-up HIV and syphilis incidence rates were measured 6 months later. The study was voluntary, anonymous, and included HIV pre- and post-test counseling, HIV and syphilis serology, and a self-administered fact sheet. A total of 106 men and 393 women were recruited. The median age was 22 years, and the mean 23.4 years. Educational levels were moderate; 41.9% had some secondary school and 23.6% had completed secondary school. HIV prevalence was 2.4% overall but differed by sex; among men it was 7/106, 6.6%, among women 5/393, 1.3%, OR = 5.49 (95% CI = 1.52, 20.39). Low educational levels were associated with HIV infection, OR = 7.2 (95% CI = 2.2, 23.4). Syphilis prevalence was 3.8%. Follow-up at 6 months was successful for 420/499 subjects, 84.2%, and varied by sex: 73/106 men, 68.9%, returned while 347/393 women, 88.3%, did so, RR = 1.21 (95% CI = 1.07, 1.37). There were 5 incident HIV-1 infections, a rate of 2.1/100 person years. The HIV seroconversion rate differed by sex, but not significantly; it was 4.1/100 person years for men and 1.5/100 person years for women. This population is largely young, female, and at considerable HIV risk. If follow-up could be improved, factory workers in northern Thailand could be an appropriate population in which to mount HIV preventive efficacy studies, including vaccine trials.

AIDS Vaccines↗