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Biomedical subjects

K E Nelson

Publications and source records attributed to K E Nelson.

At least 73 records · Page 4Linked to original sources

A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus.

BACKGROUND: In Southeast Asia, disseminated infection with Penicillium marneffei is common among patients with human immunodeficiency virus (HIV) infection. Even after successful primary treatment, the relapse rate for this potentially fatal systemic fungal infection is about 50 percent. METHODS: We conducted a double-blind trial in Thailand to evaluate itraconazole as secondary prophylaxis against P. marneffei infection in patients with the acquired immunodeficiency syndrome (AIDS) who were in complete remission after treatment for culture-proved P. marneffei infection. The patients were randomly assigned to receive either oral itraconazole (200 mg daily) or placebo as maintenance therapy. RESULTS: Of the 72 HIV-infected patients who completed initial treatment for P. marneffei infection, 71 were enrolled in the maintenance study. None of the 36 patients assigned to itraconazole had a relapse of P. marneffei infection within one year, whereas 20 of the 35 patients assigned to placebo (57 percent) had relapses (P<0.001). Among the 20 patients who had relapses, P. marneffei was cultured from blood (15 patients), lymph-node tissue (3 patients), skin (3 patients), and sputum (1 patient). The median time to relapse was 24 weeks after the completion of the initial treatment (95 percent confidence interval, 19.0 to 36.1). Survival and toxic effects were similar in the two groups. CONCLUSIONS: In patients infected with HIV who have completed successful primary treatment of P. marneffei infection, secondary prophylaxis with oral itraconazole is well tolerated and prevents relapses of this opportunistic infection.

AIDS-Related Opportunistic Infections↗

Reliability of self-reported sexual behavior in human immunodeficiency virus (HIV) concordant and discordant heterosexual couples in northern Thailand.

A partner study was conducted in northern Thailand between March 1992 and June 1996 which included data that allowed an assessment of the reliability of self-reports of sexual behavior and contraceptive use among heterosexual couples. The authors enrolled 529 couples among whom all male subjects were human immunodeficiency virus (HIV) seropositive voluntary blood donors and their female sexual partners were either HIV infected (n=246) or HIV seronegative (n=283). The levels of agreement within couples were assessed for recency of last sexual intercourse, sexual activity in the prior year, and contraceptive practices. For HIV discordant couples, a prospective study was conducted to examine risk factors for HIV transmission, the primary goal of the study. This allowed assessment of reliability of inter-partner reports over 6-12 months. Overall, agreement among couples was good for common sexual practices, especially vaginal intercourse and time since last intercourse, but was lower for condom use. Anal and oral sex were infrequently reported by these couples and there was greater disagreement for the occurrence of these practices. Partner agreement for contraceptive histories was good to excellent. Prospective data showed less frequent intercourse and more condom use but reliability remained good. Common sexual practices may be reliable for both HIV concordant and discordant couples in studies estimating prevalent infection. Estimates of incident heterosexually transmitted HIV may be made with greater reliability by studies which include assessment of reports of risk behavior by each member of a couple than studies of individuals.

Adult↗

Decreasing incidence of HIV and sexually transmitted diseases in young Thai men: evidence for success of the HIV/AIDS control and prevention program.

OBJECTIVE: To determine whether HIV and sexually transmitted disease (STD) incidence rates among young men in northern Thailand have declined since the establishment of the '100% Condom Program', and to prospectively document changes in the association between behavioral risk factors and incident HIV and STD infections. SETTING: Thirteen military bases in northern Thailand. METHODS: Serial prospective cohorts of 19-23-year-old male conscripts (n = 4086) inducted into military service from six northern Thai provinces between 1991 and 1993 were followed at 6-month intervals for incident HIV and STD through May 1995. HIV incidence was determined by serology, and incident STD were reported by conscripts as diagnosed by health-care providers. RESULTS: HIV incidence declined from a rate of 2.48 per 100 person-years during 1991-1993 to 0.55 per 100 person-years during 1993-1995. STD incidence showed an even greater decline, with a 10-fold decrease from 1991-1993 to 1993-1995. Behavioral risk factors for incident STD infections included a history of prior STD and sex with girlfriends and sex workers. Inconsistent condom use remained a strong predictor of incident STD among brothel visitors. Other previously-reported risk factors in 1991-1993 such as illicit drug use, frequency and cost of brothel visits, and low socioeconomic status were not associated with incident STD or HIV in 1993-1995. CONCLUSIONS: Although several studies have recently reported decreased prevalence of HIV and STD infections in Thailand, these data demonstrate that a dramatic decrease in the incidence rates of STD, including HIV infection, has occurred among young men in military service in northern Thailand. The Thai AIDS prevention and control program might be implemented by other countries experiencing major epidemics of heterosexually transmitted HIV infections. Similar prevention programs targeted at other populations in Thailand and elsewhere in Asia are needed to decrease the spread of the HIV epidemic.

Adult↗

Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count.

CONTEXT: Plasma human immunodeficiency virus type 1 (HIV-1) viral load and CD4+ cell count are used to predict prognosis of persons infected with HIV. However, whether combining these markers improves prognostic accuracy and whether they predict prognosis for injection drug users (IDUs) and nonwhite persons infected with HIV has not been extensively investigated. OBJECTIVE: To evaluate plasma viral load and CD4+ cell count as prognostic indicators for the acquired immunodeficiency syndrome (AIDS) and infectious disease deaths. DESIGN: Cohort study initiated in 1988 and 1989 with follow-up for up to 7.9 years. PARTICIPANTS: Injection drug users infected with HIV recruited from the community in Baltimore, Md. MAIN OUTCOME MEASURES: Plasma HIV-1 RNA and CD4+ cell count measured at baseline compared with time to first clinical AIDS diagnosis and death due to an infectious disease. RESULTS: Of 522 subjects, 96% were African American, 80% were male, 96% injected drugs within the past 6 months, and the median age was 33 years. A total of 146 cases of AIDS and 119 infectious disease deaths were seen during a median follow-up period of 6.4 years. Time-fixed baseline levels of viral load and CD4+ cell count were independent predictors of progression to AIDS and infectious disease deaths, but in proportional hazards models, viral load had better predictive value than CD4+ cell count. Kaplan-Meier analysis of time to AIDS and to infectious disease deaths by viral load (<500, 500-9999, 10000-29 999, > or =30000 copies/mL) at 3 levels of CD4+ cell count (<0.20, 0.20-0.49, and > or =0.50x10(9)/L [<200,200-499, and > or =500/microL]) was reduced to a 5-stage classification scheme using a backward stepwise regression procedure. The 5-year cumulative probabilities for AIDS and infectious disease deaths ranged from 0% and 0%, respectively, for group I (viral load, <500 copies/mL; CD4+ cell count, 0.50x10(9)/L) to 81.2% and 76.1% respectively, for group V (viral load, > or =10000 copies/mL; CD4+ cell count, 0.20x10(9)/L). CONCLUSIONS: In this study, plasma HIV-1 viral load independently and in combination with CD4+ cell count measurements provided powerful prognostic information for progression to AIDS and death caused by infectious disease in a population of predominantly African American IDUs. Combining categories of both markers provided a simple method for prognostically staging HIV disease.

AIDS-Related Opportunistic Infections↗

Epidemiology of HIV-1 infection in opiate users in Northern Thailand.

Characterizing the epidemiology of HIV-1 infection in Northern Thai opiate users is important in developing control strategies in this ethnically diverse and culturally distinct region. A cross-sectional survey of drug users first admitted between 1993 and 1995 at the Northern Drug Dependence Treatment Center, Mae Rim, Thailand, was conducted. Patients (n = 4197) were interviewed at intake about their history of drug use when they provided serum specimens for HIV-1 antibody testing. The HIV-1 prevalence was 18.6%, with men having a fourfold higher prevalence than women. Wide diversity in HIV-1 prevalence was seen by ethnicity; the HIV-1 prevalence among Thai lowlanders was four times greater than that among ethnic minorities (hill tribes). Differences in HIV-1 prevalence were the result of differences in opiate use; hill tribes frequently smoked or ingested opium, whereas Thai lowlanders injected heroin. The high HIV-1 prevalence suggests that preventive interventions for risk reduction are urgently needed in these populations. Education about the risks of injection drug use (IDU) as well as information concerning needle disinfection and expansion of drug treatment are required to reduce the risk of HIV-1 transmission associated with sharing injection equipment. Further, increasing sources of sterile needles should be considered for active users, especially for those in more remote settings.

Adolescent↗

Association of antibody to GB virus C (hepatitis G virus) with viral clearance and protection from reinfection.

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.

Adult↗

Molecular methods for the diagnosis of genital ulcer disease in a sexually transmitted disease clinic population in northern Thailand: predominance of herpes simplex virus infection.

A multiplex polymerase chain reaction (M-PCR) assay that simultaneously detects the three major causes of genital ulcer disease (GUD), Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus, was used to evaluate swab specimens for 38 sequential patients with GUD at a Thai sexually transmitted disease clinic. Subjects received clinical diagnoses and syndromic treatment. Swab specimens for H. ducreyi cultures and M-PCR were obtained. No H. ducreyi cultures were positive. Of 38 M-PCR specimens, 31 (81.6%) were positive for HSV, 1 (2.3%) for both HSV and T. pallidum, and none for H. ducreyi or T. pallidum alone; 6 (15.8%) were negative for all 3 pathogens. Clinical diagnoses corresponded poorly to M-PCR findings; none of 5 suspected cases of chancroid were positive by M-PCR and none of 1 for syphilis, but 21 of 24 suspected herpes lesions were confirmed by M-PCR. Human immunodeficiency virus infection status was known for 24 of 38 subjects; 11 (45.8%) were seropositive, and all 11 had HSV by M-PCR. HSV appeared to be the most common pathogen overall.

Chancroid↗

Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients.

Disseminated infection with Penicillium marneffei is common in patients infected with human immunodeficiency virus (HIV) in Southeast Asia. Treatment with amphotericin B alone is effective but requires a prolonged hospital stay. We conducted an open-label nonrandomized study to evaluate the efficacy and safety of treatment with amphotericin B at a dosage of 0.6 mg/(kg.d) intraveneously for 2 weeks, followed by a 400-mg/d dosage of oral itraconazole for 10 weeks. Of the 74 HIV-infected patients we studied who had disseminated P. marneffei infection, diagnosed by positive fungal culture and clinical evidence of infection, 72 (97.3%) responded to the treatment. There were no serious adverse drug effects. It was concluded that the regimen was effective and safe for treatment of disseminated P. marneffei infection in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Prevalence and incidence of hepatitis C virus infection among young adult injection drug users.

Through community-based outreach, young adult injection drug users (IDUs) were enrolled in a prospective study of the prevalence, incidence, and risk factors for hepatitis C virus (HCV) infection. Demographics and information on sexual and injecting practices were collected during semiannual interviews, and HCV infection was evaluated using a second-generation antibody assay. Of the 229 participants, 86 (37.6%) were HCV-seropositive at baseline. After adjusting for injecting frequency and duration by logistic regression, HCV seroprevalence was independently associated with reusing syringes at least once in the past 6 months (odds ratio [OR]=3.81, 95% confidence interval [CI] 1.39-11.00), injecting the first time with someone > or =5 years older (OR=2.99; 95% CI, 1.43-6.23) or alone (OR=4.02; 95% CI, 1.12-14.43) versus with someone <5 years older, and injecting cocaine or speedball exclusively (OR=4.29; 95% CI, 1.53-12.01) or with other drugs (OR=5.27; 95% CI, 2.62-10.64) versus injecting no cocaine in the past 6 months. Of the 105 originally HCV-seronegative participants who returned for follow-up, 13 seroconverted (incidence rate=16.0/100 person-years). On bivariate analysis, HCV seroconversion was significantly associated with injecting for <2 years (relative risk [RR]=7.3; 95% CI, 1.6-32.8) and continuing to inject during follow-up (RR=4.4; 95% CI, 1.0-19.9). Young adult IDUs are at high risk for HCV infection. These data support the need for wider legal access to sterile syringes, as well as expanded community outreach education to this population to prevent transmission of HCV.

Adult↗

Phenotypic and phylogenetic characterization of ruminal tannin-tolerant bacteria.

The 16S rRNA sequences and selected phenotypic characteristics were determined for six recently isolated bacteria that can tolerate high levels of hydrolyzable and condensed tannins. Bacteria were isolated from the ruminal contents of animals in different geographic locations, including Sardinian sheep (Ovis aries), Honduran and Colombian goats (Capra hircus), white-tail deer (Odocoileus virginianus) from upstate New York, and Rocky Mountain elk (Cervus elaphus nelsoni) from Oregon. Nearly complete sequences of the small-subunit rRNA genes, which were obtained by PCR amplification, cloning, and sequencing, were used for phylogenetic characterization. Comparisons of the 16S rRNA of the six isolates showed that four of the isolates were members of the genus Streptococcus and were most closely related to ruminal strains of Streptococcus bovis and the recently described organism Streptococcus gallolyticus. One of the other isolates, a gram-positive rod, clustered with the clostridia in the low-G+C-content group of gram-positive bacteria. The sixth isolate, a gram-negative rod, was a member of the family Enterobacteriaceae in the gamma subdivision of the class Proteobacteria. None of the 16S rRNA sequences of the tannin-tolerant bacteria examined was identical to the sequence of any previously described microorganism or to the sequence of any of the other organisms examined in this study. Three phylogenetically distinct groups of ruminal bacteria were isolated from four species of ruminants in Europe, North America, and South America. The presence of tannin-tolerant bacteria is not restricted by climate, geography, or host animal, although attempts to isolate tannin-tolerant bacteria from cows on low-tannin diets failed.

Animals↗

Gynaecological conditions associated with HIV infection in women who are partners of HIV-positive Thai blood donors.

Women who were partners of HIV-positive blood donors were enrolled in a study of heterosexual HIV transmission between March 1992 and December 1996 and were interviewed and examined. Gynaecological conditions, including cervical dysplasia, human papillomavirus (HPV) infection, gonorrhoea, chlamydial infection, trichomoniasis, bacterial vaginosis, vaginal candidiasis and syphilis were assessed in addition to HIV status and CD4 level. Of 481 women enrolled, 224 (46.6%) were HIV seropositive. HIV-infected women were more likely to have abnormal vaginal discharge on physical examination (OR=2.6, P <0.01), HPV infection with a high-risk type (OR=6.9, P <0.01), and cervical dysplasia (OR=5.3, P <0.01). The prevalence of other gynaecological conditions detected at the enrolment visit did not differ by HIV status. History of prior STD (OR=2.0, P <0.01) was more common among HIV-infected women. The median CD4 count was 400 cells/microl among HIV-infected women. The prevalence of abnormal vaginal discharge and bacterial vaginosis increased significantly with decreasing CD4 count. The prevalence of ectopy, vaginal candidiasis, and cervical dysplasia increased with decreasing CD4 count, but these trends were not significant. We conclude that HIV-infected Thai women appear to have increased prevalences of abnormal vaginal discharge, squamous intraepithelial lesions and self-reported history of STD.

Adult↗

Specific identification of Penicillium marneffei by a polymerase chain reaction/hybridization technique.

Penicillium marneffei has been described recently as a cause of an emerging mycotic infection in HIV-infected patients. A PCR/hybridization assay was developed to rapidly identify this pathogen. The nucleotide sequence of the 631-bp region of 18S ribosomal DNA of P. marneffei was determined using the standard dideoxy chain termination method. An oligonucleotide probe was designed on the basis of the analysed sequences of P. marneffei and 18S rDNA sequences of other fungi in the GenBank database. A 631-bp PCR product was amplified using primers RRF1 and RRH1 from P. marneffei and seven other fungi, Penicillium spp., Aspergillus fumigatus, A. flavus, Histoplasma capsulatum, Cryptococcus neoformans, Candida albicans and C. krusei. A 15 oligonucleotide segment (Pm3) which was specific for P. marneffei was synthesized and used as a probe. Only the PCR products of P. marneffei isolates hybridized with the Pm3 oligonucleotide probe. The sensitivity of the assay was approximately 0.5 pg/microl and 0.1 pg/microl of DNA by PCR and Southern hybridization, respectively. The usefulness of this method as a diagnostic tool will require further studies.

AIDS-Related Opportunistic Infections↗

The association of herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and syphilis with HIV infection in young men in northern Thailand.

To evaluate the association between sexually transmitted diseases that commonly may cause genital ulceration and prevalent and incident HIV infections, we conducted three case control studies in a cohort of 21-year-old male military conscripts in northern Thailand. The men were evaluated at baseline in 1991 and semiannually until their discharge 2 years later. Serologic evidence of infection with herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and HIV were more frequent at baseline in 83 men with a history of genital ulcer than in 97 men without such a history. Seropositivity to H. ducreyi (odds ratio [OR] = 3.46), HSV-2 (OR = 3.83), and syphilis (OR = 1.53) were more common in HIV-positive than HIV-negative men. Men (N = 45) who seroconverted to HIV while in the military were more often seropositive for H. ducreyi and HSV-2 before HIV seroconversion and also were more likely to seroconvert to HSV-2 and H. ducreyi during the same interval as their HIV seroconversion compared with men who remained HIV-negative. These data suggest that HSV-2 and H. ducreyi may be both markers for high-risk sexual behavior and risk factors for HIV infection among young men in Thailand.

AIDS-Related Opportunistic Infections↗

The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus.

Archaeoglobus fulgidus is the first sulphur-metabolizing organism to have its genome sequence determined. Its genome of 2,178,400 base pairs contains 2,436 open reading frames (ORFs). The information processing systems and the biosynthetic pathways for essential components (nucleotides, amino acids and cofactors) have extensive correlation with their counterparts in the archaeon Methanococcus jannaschii. The genomes of these two Archaea indicate dramatic differences in the way these organisms sense their environment, perform regulatory and transport functions, and gain energy. In contrast to M. jannaschii, A. fulgidus has fewer restriction-modification systems, and none of its genes appears to contain inteins. A quarter (651 ORFs) of the A. fulgidus genome encodes functionally uncharacterized yet conserved proteins, two-thirds of which are shared with M. jannaschii (428 ORFs). Another quarter of the genome encodes new proteins indicating substantial archaeal gene diversity.

Archaeoglobus fulgidus↗

Risk factors for HIV-1 transmission from HIV-seropositive male blood donors to their regular female partners in northern Thailand.

OBJECTIVE: To describe risks for HIV transmission from male blood donors to their regular female sex partners in Chiang Mai, Thailand. DESIGN: Cross-sectional study. METHODS: From March 1992 through September 1995, 405 HIV-seropositive male blood donors (index cases) and their regular female partners were enrolled in the study. Women with risk factors for HIV infection other than sexual contact with the index male were excluded. Couples were interviewed and examined; specimens were collected for laboratory analysis. RESULTS: Overall, 46% of the 405 women enrolled were HIV-positive. Ninety-eight per cent of male index cases had a history of sex with a female prostitute; 1.5% reported always using condoms with their regular partner. History of sexually transmitted disease (STD) and swollen inguinal lymph nodes in the female partner were associated with an increased risk of HIV infection in the female. History in the female of genital herpes [odds ratio (OR), 3.46; 95% confidence interval (CI), 1.50-8.78], gonorrhea or chlamydia infection (OR, 2.71; 95% CI, 1.39-5.53), and stable relationship of longer than 24 months (OR, 2.28; 95% CI, 1.02-5.09) were associated with an increased risk of HIV infection in the female. Consistent condom use in the past 2 years (OR, 0.10; 95% CI, 0.01-0.79) was associated with a decreased risk of HIV infection in the female. CONCLUSIONS: Married women in northern Thailand who appear otherwise to be at low risk for HIV infection may be exposed to this virus by their husbands. High rates of sex with commercial sex workers among men and low use of condoms within stable relationships may be important factors promoting the transmission of HIV in married couples. Programs to increase the regular use of condoms among married couples could be an important public health intervention to prevent transmission of HIV and other types of STD in northern Thailand.

Adolescent↗