Carolyn Z. Grimes

Real-Time Polymerase Chain Reaction Detection of Asymptomatic Clostridium difficile Colonization and Rising C. difficile –Associated Disease Rates

OBJECTIVE To evaluate the accuracy of real-time polymerase chain reaction (PCR) for Clostridium difficile-associated disease (CDAD) detection, after hospital CDAD rates significantly increased following real-time PCR initiation for CDAD diagnosis. DESIGN Hospital-wide surveillance study following examination of CDAD incidence density rates by interrupted time series design. SETTING Large university-based hospital. PARTICIPANTS Hospitalized adult patients. METHODS CDAD rates were compared before and after real-time PCR implementation in a university hospital and in the absence of physician and infection control practice changes. After real-time PCR introduction, all hospitalized adult patients were screened for C. difficile by testing a fecal specimen by real-time PCR, toxin enzyme-linked immunosorbent assay, and toxigenic culture. RESULTS CDAD hospital rates significantly increased after changing from cell culture cytotoxicity assay to a real-time PCR assay. One hundred ninety-nine hospitalized subjects were enrolled, and 101 fecal specimens were collected. C. difficile was detected in 18 subjects (18%), including 5 subjects (28%) with either definite or probable CDAD and 13 patients (72%) with asymptomatic C. difficile colonization. CONCLUSIONS The majority of healthcare-associated diarrhea is not attributable to CDAD, and the prevalence of asymptomatic C. difficile colonization exceeds CDAD rates in healthcare facilities. PCR detection of asymptomatic C. difficile colonization among patients with non-CDAD diarrhea may be contributing to rising CDAD rates and a significant number of CDAD false positives. PCR may be useful for CDAD screening, but further study is needed to guide interpretation of PCR detection of C. difficile and the value of confirmatory tests. A gold standard CDAD diagnostic assay is needed.

Relationship of cosmetic procedures and drug use to hepatitis C and hepatitis B virus infections in a low‐risk population

We conducted an anonymous cross‐sectional seroprevalence study of a population with a low frequency of injection drug use to determine whether persons with a history of cosmetic procedures, such as tattooing and body piercing, or intranasal drug use were at increased risk for hepatitis C virus (HCV) or hepatitis B virus (HBV) infection. Students 18 years and older from eight college campuses in Houston, Texas, were invited to participate in the study. Of the 7,960 who completed a self‐administered questionnaire and provided a blood sample, 5,282 U.S.‐ or Canadian‐born participants were analyzed. Their median age was 21, 62% were female, 42% were white, 26% black, 22% Hispanic, and 10% Asian or other. Two percent reported injection drug use, 13.7% intranasal drug use, 21.2% body piercings, and 25.2% tattoos. The overall prevalence of HCV infection was 0.9% and of HBV infection was 5.2%. Higher HCV prevalence was independently associated with increasing age (odds ratio [OR] per year = 1.11; 95% confidence interval [CI] = 1.08‐1.14), history of injection drug use (OR = 18.24; 95% CI = 7.74‐42.92), blood transfusion before 1991 (OR = 3.21; 95% CI = 1.02‐10.12), and incarceration (OR = 3.48; 95% CI = 1.45‐8.37). Among 5,066 students who denied injecting drugs, HCV prevalence was 0.8% in those who reported intranasal drug use and 0.6% each in those who reported tattoos and those who reported body piercing. Increased HBV prevalence was associated with high‐risk sexual behaviors and black or Asian race. In conclusion, there was no increased risk for HCV or HBV infection in low‐risk adults based solely on history of cosmetic procedures or snorting drugs. However, proper infection control practices for cosmetic procedures should be followed, illegal drug use discouraged, and hepatitis B vaccination provided to adolescents and sexually active adults. (HEPATOLOGY 2006;44:341–351.)

Accelerated hepatitis B vaccination schedule among drug users: a randomized controlled trial.

BACKGROUND Hepatitis B vaccine provides a model for improving uptake and completion of multidose vaccinations in the drug-using community. METHODS The Drugs, AIDS, STDs, and Hepatitis (DASH) project conducted a randomized controlled trial among not-in-treatment current drug users in 2 urban neighborhoods. Neighborhoods were cluster-randomized to receive a standard behavioral intervention (which provided information on human immunodeficiency virus [HIV]) or an enhanced behavioral intervention (designed to increase acceptance of or adherence to the hepatitis B vaccination protocol). Participants within clusters were randomized to a standard vaccination schedule (vaccines at 0, 1, and 6 months) or an accelerated vaccination schedule (vaccines at 0, 1, and 2 months). The outcomes were completion of the 3-dose vaccine and seroprotection against hepatitis B virus (HBV). RESULTS Of participants with negative screening results for HIV and HBV, 77% accepted hepatitis B vaccination, and 75% of vaccinees received all 3 doses. Injection drug users (IDUs) on the accelerated schedule were significantly more likely to receive 3 doses (76%) than those on the standard schedule (66%; P = .04), although for drug users as a whole the corresponding adherence rates were 77% and 73%, respectively. No difference in adherence was observed between the behavioral intervention groups. Predictors of adherence were older age, African American race, stable housing, and alcohol use. Cumulative HBV seroprotection (≥10 mIU/mL) was gained within 12 months by 65% of those completing the schedule. Seroprotection at 6 months was greater for those on the accelerated schedule. CONCLUSION The accelerated vaccination schedule improves hepatitis B vaccination adherence among IDUs.

Demographics, Socio-behavioral Factors and Drug Use Patterns: What Matters in Spontaneous HCV Clearance?

Hepatitis C virus (HCV), an emerging bloodborne pathogen, causes chronic liver disease frequently except in about 10–20% of infections which undergo spontaneous resolution. Investigating factors that influence viral clearance is essential to understand the natural history of this infection and establishing novel strategies for prevention and treatment. HCV clearance was estimated in a unique cohort of 1,260 HIV and HBV negative current drug users enrolled for a hepatitis B vaccination study. It was defined as the inability to detect viral RNA using a PCR method in presence of serum anti‐HCV antibody EIA. Associated demographic and socio‐behavioral factors including drug use patterns were identified from the enrolled subjects using multivariate regression analysis. 33.3% (420/1260) of drug users were found positive for anti‐HCV antibodies and 14.8% (62/420) of these individuals achieved viral clearance (negative PCR test). Race or ethnicity of the participants was the only significant factor associated with HCV clearance. Hispanics (OR = 3.4, 95% CI: 1.3–8.5, P = 0.01) and Caucasians (OR = 3.1, 95% CI: 1.5–6.6, P = 0.003) had significantly higher odds of clearing the virus compared to African Americans when adjusted for age and gender. None of the socio‐behavioral factors including alcohol intake and drug use patterns were significant determinants of HCV clearance. Racial or ethnic differences in HCV clearance were observed in this study suggesting an important role of host genetic susceptibility factors in determining the clinical course of this disease. Further research is needed to examine these genetic associations of host–virus relationships. J. Med. Virol. 84:235–241, 2012.

Latent tuberculosis infections in hard-to-reach drug using population - detection, prevention and control

Interferon-gamma release assays (IGRAs) need be evaluated for effectiveness as screening tests for tuberculosis (TB) infection in drug users. These tests have demonstrated improved sensitivity and specificity, but have not been studied in drug users. These one step blood tests are intended to replace the tuberculin skin test (TST), which is difficult to use and requires 48 hour follow-up, so they are expected to be particularly suitable for risk groups, like drug users, in whom follow-up is problematic. Drug users have traditionally been identified as being at increased risk for acquiring TB disease. The results of our pilot study using the TST and simpler and more sensitive interferon-gamma release assays showed that about 45% of current drug users in Houston tested have at least one test positive for latent tuberculosis infection (LTBI). These preliminary data suggest that there is an important reservoir of LTBI in drug using populations, and the risk of progression to active TB disease with other infections is great. However, LTBI in drug using populations has not been studied in depth and deserves further investigation. We need to evaluate the validity of IGRAs for detection of latent TB infection, the factors associated with LTBI, the incidence and risk for developing active TB disease in drug users and the effectiveness of early treatment of LTBI. We believe that using better tuberculosis screening tools will allow us to more accurately measure the prevalence of latent TB infection and incidence of active TB disease in drug using populations and develop more effective TB prevention and treatment interventions in the community.

Effect of age and frequency of injections on immune response to hepatitis B vaccination in drug users

Despite the high immunogenicity of the hepatitis B vaccine, evidence suggests that immunological response in drug users is impaired compared to the general population. A sample of not-in-treatment adult drug users from two communities in Houston, TX, USA, susceptible to hepatitis B virus (HBV), was sampled via outreach workers and referral methodology. Participants were randomized to either the standard multi-dose hepatitis B vaccine schedule (0, 1, and 6 months) or to an accelerated (0, 1, and 2 months) schedule. The participants were followed for 1 year. Antibody levels were measured at 2, 6 and 12 months after enrollment in order to determine the immune responses. At 12 months, cumulative adequate protective response was achieved in 65% of the HBV susceptible subgroup using both the standard and accelerated schedules. The standard group had a higher mean antibody titer (184.6 mIU/mL vs 57.6 mIU/mL). But at 6 months, seroconversion at the adequate protective response was reached by a higher proportion of participants and the mean antibody titer was also higher in the accelerated schedule group (104.8 mIU/mL vs. 64.3 mIU/mL). Multivariate analyses indicated a 63% increased risk of non-response for participants 40 years or older (p=0.046). Injecting drugs more than once a day was also highly associated with the risk of non-response (p=0.016). Conclusions from this research will guide the development of future vaccination programs that anticipate other prevalent chronic conditions, susceptibilities, and risk-taking behaviors of hard-to-reach populations.

Long-term effectiveness of accelerated hepatitis B vaccination schedule in drug users

OBJECTIVES We demonstrated the effectiveness of an accelerated hepatitis B vaccination schedule in drug users. METHODS We compared the long-term effectiveness of accelerated (0-1-2 months) and standard (0-1-6 months) hepatitis B vaccination schedules in preventing hepatitis B virus (HBV) infections and anti-hepatitis B (anti-HBs) antibody loss during 2-year follow-up in 707 drug users (HIV and HBV negative at enrollment and completed 3 vaccine doses) from February 2004 to October 2009. RESULTS Drug users in the accelerated schedule group had significantly lower HBV infection rates, but had a similar rate of anti-HBs antibody loss compared with the standard schedule group over 2 years of follow-up. No chronic HBV infections were observed. Hepatitis C positivity at enrollment and age younger than 40 years were independent risk factors for HBV infection and antibody loss, respectively. CONCLUSIONS An accelerated vaccination schedule was more preferable than a standard vaccination schedule in preventing HBV infections in drug users. To overcome the disadvantages of a standard vaccination schedule, an accelerated vaccination schedule should be considered in drug users with low adherence. Our study should be repeated in different cohorts to validate our findings and establish the role of an accelerated schedule in hepatitis B vaccination guidelines for drug users.

Epidemiologic characterization of culture positive Mycobacterium tuberculosis patients by katG-gyrA principal genetic grouping.

Molecular typing techniques make it possible to genetically characterize Mycobacterium tuberculosis isolates. Public health strategies to control the spread of tuberculosis are enhanced by the use of molecular data to study tuberculosis transmission dynamics within populations. This study compared epidemiological and clinical characteristics of three M. tuberculosis groups based on polymorphisms at katG codon 463 and gyrA codon 95 in 1893 culture-positive patients by a retrospective nested case-comparison design. Study participants, diagnosed from 1995 to 2001 in the Houston, Texas metropolitan area, were >/= 18 years old, 70% male, 66% U.S.-born, 40% Black, 29% Hispanic, 19% White, and 12% Asian/Pacific Islander. The prevalence of each principal genetic group (GG) was 30% (GG1), 52% (GG2), and 18% (GG3). Multiple logistic regression analysis showed that GG1 participants were more likely to be Asian, male, and have a history of homelessness, as compared with participants with either GG2 or GG3 isolates. GG2 participants were more likely to be Hispanic, have streptomycin-resistant isolates, and be infected with HIV than either GG1 or GG3 participants. GG3 participants were more likely to be Black or Hispanic, report illicit drug use, and live in a congregative facility at the time of diagnosis, than GG1 or GG2 participants. Ethnicity and sociodemographic findings were significant, prompting additional research into social networks, genetic susceptibility, immunology, and virulence factors.