Are adolescents ready for tuberculosis vaccine trials?

Tuberculosis (TB) vaccine trials are planned in adolescents in a high tuberculosis burden rural area near Cape Town, South Africa. To determine the knowledge and attitudes of adolescents about tuberculosis, vaccines and vaccine trials, a representative sample of adolescent learners was chosen from high schools in the trial area. A questionnaire was administered and focus group discussions held with the group and a sample of their parents. The questionnaire response rate was 65%. Knowledge of tuberculosis was fair 63.7% but knowledge of vaccines poor 41.9% based on a TB and vaccine knowledge score, respectively. Willingness to participate in vaccine trials will be influenced by the type of procedures involved (60% willing to answer questions, 43% willing to be examined, 32% willing to undergo skin tests and 39% willing to undergo blood draw). In general, better knowledge was statistically associated with greater willingness to participate in study procedures except for the blood draw. The focus group discussions showed that adolescents and their parents were positive about participating in vaccine trials but concerns about safety and the provision of adequate information should be considered when planning TB vaccine trials. This study suggests that TB vaccine trials would be acceptable amongst adolescents in this community with certain provisos.     

Are HIV-infected injection drug users taking HIV tests?

OBJECTIVES. Knowledge of infection is essential for human immunodeficiency virus-type 1 (HIV-1) treatment initiation and epidemic control. This study evaluates infection knowledge among infected injection drug users and acceptance of confidential testing among injection drug users, particularly those infected with HIV-1. METHODS. A total of 810 injection drug users entering treatment in Contra Costa County, Calif, were examined. Clients were tested with unlinked (blinded) tests and simultaneously counseled and offered voluntary confidential HIV-1 antibody testing. Data on confidential testing acceptance, previous testing, drug use, and demographic information were collected. RESULTS. Of the 810 tested, 105 (13.0%) were infected. The current confidential test was accepted by 507 (62.6%). HIV seroprevalence in the unlinked survey was four times greater than in the voluntary survey (13% and 3.5%, respectively). HIV-1 infection was associated with refusal of a confidential test largely because most infected injection drug users (n = 58; 55.2%) already knew of their infection. Of the 47 injection drug users who were not aware of their infection, 12 (25.5%) accepted the test. Although African-American injection drug users presented with a higher infection rate (37.3%), they were three times less likely to know of their infection. CONCLUSIONS. "In-clinic" HIV-1 testing is highly accepted, and most infected clients in treatment will learn their status. Nevertheless, voluntary testing data are likely to yield considerable underestimates of the true rate of infection among injection drug users.     

Does bleach disinfection of syringes protect against hepatitis C infection among young adult injection drug users?

BACKGROUND: Hepatitis C virus (HCV) has emerged as a major public health problem among injection drug users. In this analysis we examine whether disinfection of syringes with bleach has a potentially protective effect on anti-HCV seroconversion. METHODS: We conducted a nested case-control study comparing 78 anti-HCV seroconverters with 390 persistently anti-HCV seronegative injection drug users. These data come from the Second Collaborative Injection Drug Users Study, a prospective cohort study that recruited injection drug users from five U.S. cities between 1997 and 1999. We used conditional logistic regression to determine the effect of bleach disinfection of syringes on anti-HCV seroconversion. RESULTS: Participants who reported using bleach all the time had an odds ratio (OR) for anti-HCV seroconversion of 0.35 (95% confidence interval = 0.08-1.62), whereas those reporting bleach use only some of the time had an odds ratio of 0.76 (0.21-2.70), when compared with those reporting no bleach use. CONCLUSIONS: These results suggest that bleach disinfection of syringes, although not a substitute for use of sterile needles or cessation of injection, may help to prevent HCV infection among injection drug users.     

Prevalence of hepatitis C among injection drug users in England and Wales: is harm reduction working?

OBJECTIVES: This study sought to establish the prevalence of hepatitis C antibodies (anti-HCV) and hepatitis B antibodies (anti-HBc) among injection drug users in England and Wales. METHODS: A voluntary cross-sectional survey collected oral fluid samples and behavioral information; 2203 injectors were recruited through drug agencies, and 758 were recruited in the community. RESULTS: Prevalence was 30% for anti-HCV, 21% for anti-HBc, and 0.9% for HIV antibodies. Anti-HCV prevalence rates were significantly greater among those with longer injecting careers, those in older age groups, those residing in London, those recruited in drug agencies, those positive for anti-HBc, and those with a previous voluntary HIV test. CONCLUSIONS: Anti-HCV prevalence rates among injectors in England and Wales, where comprehensive harm reduction programs exist, are lower than rates in other industrialized countries.     

How does tuberculosis relate to HIV positive and HIV negative drug users?

OBJECTIVES: (1) To compare the incidence of active tuberculosis in HIV positive and HIV negative drug users. (2) To describe the main characteristics of the tuberculosis cases. DESIGN: A prospective study was performed from 1986 to 1996 as part of an ongoing cohort study of HIV infection in Amsterdam drug users. METHODS: Data from the cohort study, including HIV serostatus and CD4-cell numbers, were completed with data from the tuberculosis registration of the tuberculosis department of the Amsterdam Municipal Health Service. Analyses were carried out with person time and survival methods. RESULTS: Of 872 participants, 24 persons developed culture confirmed tuberculosis during a total follow up period of 4000 person years (0.60 per 100 py, 95% CI: 0.40, 0.90). Nineteen cases were HIV positive (1.54 per 100 py, 95% CI: 0.86, 2.11) and five HIV negative (0.18 per 100 py, 95% CI: 0.08, 0.43). Multivariately HIV infection (relative risk: 12.9; 95% CI: 3.4, 48.8) and age above 33 years (RR: 6.8; 95% CI: 1.3, 35.0, as compared with age below 27) increased the risk for tuberculosis substantially. Additional findings were: (1) 13 of 22 pulmonary tuberculosis cases (59%) were detected by half yearly radiographic screening of the chest; (2) tuberculosis occurred relatively early in the course of HIV infection at a mean CD4 cell number of 390/microliter; (3) an estimated two thirds of the incidence of tuberculosis observed among HIV positive cases was caused by reactivation; (4) all but one patient completed the tuberculosis treatment. CONCLUSION: HIV infection increases the risk for active tuberculosis in Amsterdam drug users 13-fold. The incidence of tuberculosis in HIV negative drug users is still six times higher than in the overall Amsterdam population. In the absence of contact tracing and screening with tuberculin skin tests, periodic chest radiographic screening contributes substantially to early casefinding of active tuberculosis in Amsterdam drug users.     

What motivates minorities to participate in research?

This study investigates factors that facilitate and impede minority participation in medical and scientific research studies. Four focus group sessions involving 18 participants aged 18 to 55 years were conducted. Participants, all members of minority groups, were asked a series of questions about why minorities in the Twin Cities area might or might not participate in medical research. Focus group participants indicated they would be willing to participate as research subjects if study findings were shored with them and their primary care physician and if results would benefit their community. Participants cited 4 major barriers to their participation in research: limited knowledge of health studies, mistrust of researchers, limited community involvement in the design of health studies, and use of invasive procedures. Results from this study suggest that researchers seeking to include minority subjects need to use more participatory or community-centered approaches to research.     

Are phylogenetic position,virulence, drug susceptibility and in vivo response to treatment in mycobacteria interrelated?

Phylogenetic analyses on the basis of multiple house-keeping genes and whole genome sequences have offered new insights in the phylogeny of the genus Mycobacterium. This genus yields obligate pathogens, the M. tuberculosis complex and M. leprae, as well as opportunistic pathogens (e.g. M. avium, M. intracellulare, M. kansasii, M. marinum, M. malmoense) and saprophytes (e.g. M. phlei, M. sphagni, M. gordonae). The most virulent mycobacteria, the M. tuberculosis complex, M. leprae and the M. kansasii-M. szulgai-M. marinum-M. ulcerans group are phylogenetically related and infections by these organisms are better treatable than those caused by less virulent and phylogenetically more distantly related Mycobacterium species. The most virulent Mycobacterium species are also characterized by high levels of natural drug susceptibility. In this paper, we review studies of phylogeny, drug susceptibility, and clinical significance to support our hypothesis that drug susceptibility in mycobacteria is acquired and reflects the low level of competition in -and adaptation to- a closer-to-human (environmental) niche. In turn, mycobacteria that inhabit the most competitive environmental niches are the least adapted to humans, thus of low clinical significance, but most tolerant to antibiotics derived from microbes with which they share their habitat, lowering the chances of cure in case of infection.     

Screening for methicillin-resistant Staphylococcus aureus (MRSA) in community-recruited injection drug users: are throat swabs necessary?

We examined and described colonization of MRSA in the anterior nares and throat from 184 community-recruited injection drug users. Thirty-seven (20%) were positive for MRSA: most (34, 92%) were carriers in the nares; while only three (8%) were carriers detected by throat swabs alone. The majority (29, 78%) of MRSA isolates were PVL positive.     

Are Phase 2 screening trials in oncology obsolete?

Phase 2 studies in Oncology are controversial because on the one hand they are substantially underpowered for making assessments of activity and on the other hand they are used as a screen to determine whether a Phase 3 trial is warranted. In this paper, we undertake a systematic assessment of the properties of a Phase 2 study in the context of a drug development program. We will show that, when considering only the efficiency of a clinical trials program, Phase 2 screening trials can substantially increase the efficiency with which drugs that provide clinical benefit are identified. However, if there are substantial costs in identifying drug candidates to test in clinical trials as there are today, then Phase 2 screening trials as a prelude to Phase 3 trials may reduce the efficiency of the drug development process as a whole. .     

Are biomarkers harmful to recruitment and retention in Alzheimer’s disease clinical trials? An international perspective

Clinical trials in Alzheimer's disease (AD) do not only generate high costs but have also been of little success within recent years. The failure of several large phase III clinical trials on highly promising disease modifying compounds calls for a critical reflection on potential reasons and counter-measures. The recent introduction of new diagnostic criteria of AD and the development and validation of diagnostic and predictive AD biomarkers allows enriching study populations, reducing variance, and improving statistical power of trials while even opening the possibility to reduce total study costs. While CSF or extensive imaging biomarkers might adversely affect retention in clinical trials, their careful application will unlikely reduce adherence. Regulatory authorities are generally supportive of biomarker use in clinical trials but potential consequences of biomarker based patient selection on the generalizability of trial results need careful evaluation.     

Community participation in AIDS vaccine trials: empowerment or science?

For future AIDS vaccines to be successfully tested and implemented, extensive participation in vaccine trials will be necessary. Central to the challenges associated with such participation is concern for protection of participant wellbeing. This short report examines the tension that is sometimes found between the pragmatic need for recruitment into trials, and a more general social good concerning community participation in health. Community empowerment and trial participation are sometimes assumed to go hand in hand, but are potentially contradictory. Recognizing the possible disjunction between empowerment and trial participation allows for clearer discussion of and planning for ethical, scientifically valid trials.