Hepatitis B virus infection and immunization status in a new generation of injection drug users in San Francisco.

Hepatitis B virus (HBV) infection is common among injection drug users (IDU). Younger IDU, however, may be less susceptible to infection due to the implementation of public health interventions, such as universal immunization programs and syringe exchange programs. To investigate the current epidemiology of HBV infection and control among a new generation of drug users in the United States, we conducted interviews and examined HBV serologic markers in a cross-section of street-recruited IDU under age 30 in San Francisco, CA. Of the 831 persons studied, 21% showed serologic evidence of current or past infection; 22% had isolated antibodies to hepatitis B surface antigen consistent with vaccine-mediated immunity; and 56% had no HBV markers. In multivariate analyses, HBV infection was associated with drug use behaviour in heterosexual males; sexual behaviour in males who have sex with males; and both drug use and sexual behaviour in females. Vaccine-mediated immunity was independently associated with female sex and younger age. In conclusion, HBV transmission persists among young IDU in San Francisco. Few young injectors show evidence of successful immunization and the majority remains susceptible to disease. Until the broad effects of universal vaccination are seen, targeted and innovative approaches to immunizing young IDU in the US are needed to prevent a substantial number of new HBV infections.

Propionate precursors and other metabolic intermediates as possible alternative electron acceptors to methanogenesis in ruminal fermentation in vitro.

Fifteen potential precursors of propionate were tested for their ability to decrease CH4 production by ruminal fluid in vitro. Sodium acrylate and sodium fumarate produced the most consistent effects in batch cultures, with 50 % of the added precursors being fermented to propionate and CH4 production decreasing by between 8 and 17 %, respectively. Additives were more effective when added as free acids, but this also decreased the pH and may have inhibited fibre digestion. Changing the dietary substrate from predominantly grass hay to predominantly concentrate had no influence on the effectiveness of acrylate and fumarate. In an in vitro fermentor (the rumen simulating technique, Rusitec) with a grass hay-concentrate (50:50, w/w) diet as substrate, both compounds were again fermented to propionate (33 and 44 % conversion to propionate, respectively). However, fumarate appeared more effective as a H2 sink compound. It was calculated to capture 44 % of the H2 previously used for CH4 formation compared with a 22 % capture of H2 with acrylate. Fumarate also caused a stimulation in fibre digestion. Thus, sodium fumarate was the preferred propionate precursor for use as a feed ingredient to decrease CH4 emissions from ruminants.

Prevalence of antiretroviral drug resistance in the HIV-1-infected urban indigent population in San Francisco: a representative study.

We determined the prevalence of antiretroviral (ARV) resistance in HIV-1 infected indigent persons in San Francisco, California. Three hundred and twenty-seven subjects (159 (49%) ARV naïve, and 168 (51%) ARV-experienced), were recruited during 1996-97 and 1999-2000. Plasma HIV-1 viral load quantification and genotypic resistance testing were performed. Twice as many subjects received nucleoside reverse transcriptase inhibitors (NRTIs) as non-nucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs); resistance mutation prevalences were 30%, 14% and 16% respectively. Risk of any resistance mutations was strongly and independently associated with prior ARV exposure (OR = 1.3 per year of exposure, P < 0.0001) and with ARV exposure prior to HAART (OR = 2.5, P = 0.015). Prevalences of primary ARV resistance mutations among both treatment-naive and treatment-experienced subjects in this indigent urban population are low compared to other observational cohorts, are directly related to length and type of prior ARV exposure, and did not increase significantly between recruitment periods.

Modeling the impact of modified directly observed antiretroviral therapy on HIV suppression and resistance, disease progression, and death.

A simulation model that used Markov assumptions with Monte Carlo uncertainty analysis was evaluated 1500 times at 10,000 iterations. Modified directly observed therapy (MDOT) for human immunodeficiency virus was assumed to improve adherence to therapy to 90% of prescribed doses. The impact of MDOT interventions on modeled biological and clinical outcomes was compared for populations with mean rates of adherence (i.e., the mean percentage of prescribed doses taken by each member of the population who had not discontinued therapy) of 40%, 50%, 60%, and 70%. MDOT reduced the risk of virological failure, development of opportunistic infections, and death, yet increased the risk of drug resistance, for each adherence distribution among persons with detectable plasma virus loads. Over 1500 trials, for a population with 50% adherence to therapy and a 12-month period, MDOT increased the median rate of virological suppression from 13.2% to 37.0% of patients, decreased the rate of opportunistic infection from 5.7% to 4.3% of patients, and decreased the death rate from 2.9% to 2.2% of patients. In the same population, however, MDOT increased the rate of new drug resistance mutations from 1.00 to 1.41 per person during the 12-month period. The impact of MDOT was smaller in populations with higher levels of adherence. MDOT interventions will likely improve clinical outcomes in populations with low levels of adherence but may not be effective at preventing drug resistance in treatment-experienced populations. MDOT may be more effective in preventing drug resistance with potent regimens in treatment-naive patients.

Can the poor adhere? Incentives for adherence to TB prevention in homeless adults.

SETTING: Community-based population of homeless adults living in San Francisco, California. OBJECTIVE: To compare the effect of cash and non-cash incentives on 1) adherence to treatment for latent tuberculosis infection, and 2) length of time needed to look for participants who missed their dose of medications. DESIGN: Prospective, randomized clinical trial comparing a 5 dollar cash or a 5 dollar non-cash incentive. All participants received directly observed preventive therapy and standardized follow-up per a predetermined protocol. Completion rates and amount of time needed to follow up participants was measured. RESULTS: Of the 119 participants, 102 (86%) completed therapy. There was no difference between the cash and non-cash arms. Completion was significantly higher among males (OR 5.65, 95%CI 1.36-23.40, P = 0.02) and persons in stable housing at study entry (OR 4.86, 95%CI 1.32-17.94, P = 0.02). No substance use or mental health measures were associated with completion. Participants in the cash arm needed significantly less follow-up to complete therapy compared to the non-cash arm (P = 0.03). In multivariate analysis, non-cash incentive, use of crack cocaine, and no prior preventive therapy were associated with more follow-up time. CONCLUSION: Simple, low cost incentives can be used to improve adherence to TB preventive therapy in indigent adults.

Reliability and validity of the SF-36 in HIV-infected homeless and marginally housed individuals.

OBJECTIVE: To assess the reliability and validity of the Short-Form 36 (SF-36) health survey as a health status indicator among HIV-infected homeless and marginally housed (HMH) individuals. METHODS: Between July 1996 and May 2000, a sample of HMH individuals completed interviews that included the SF-36. Responses to the SF-36 were analyzed for missing data, range, internal consistency, and construct validity. RESULTS: Among 330 individuals interviewed, 83% were male, 43% were African-American, and the median age was 39 years. All internal consistency reliability coefficients exceeded 0.70, all item-scale correlations exceeded 0.40, all items were more strongly correlated with their hypothesized scale than any other scale, and all reliability coefficients exceeded inter-scale correlations for the same scale. Three of four physical health scales were significantly associated with CD4 cell count and HIV viral load. All scales were significantly associated with depression. DISCUSSION: We found that scales were internally consistent, items correlated to an acceptable degree with their hypothesized scales, items were distinct from other scales, physical scales were associated with CD4 cell count and viral load, and all scales were associated with depression. These analyses provide evidence for the reliability and validity of the SF-36 as a measure of health status in HIV-positive HMH individuals.

Overdosing among young injection drug users in San Francisco.

Heroin overdoses increased sharply in the US in the 1990s, but few studies have addressed overdose risk. We examined overdosing and injection-related risk behavior in young injection drug users (IDUs). We interviewed all consenting injectors under age 30 at needle exchanges and youth outreach sites in San Francisco. Their median age was 22, and their median number of years of injecting was 4. About 48% reported at least one overdose, with a median of two overdoses reported. Overdosing was associated with injecting "speedballs" (i.e. mixtures of heroin and cocaine), with borrowing syringes, and (with P-values of borderline statistical significance) with heroin injection and with gay or bisexual behavior. It was not associated with age, sex, years of injecting, or frequency of injecting. In multivariate analysis, only borrowing syringes and gay or bisexual behavior were independent statistically significant predictors, probably because gay and bisexual subjects were more likely to be heroin or "speedball" injectors. Most subjects (65%) reported that they had not received medical attention at time of last overdose. Risk of overdose in young injectors is acute and closely associated with HIV risk. HIV interventions should include overdose prevention. Emergency response protocols should minimize risk of arrest. Injectors and providers should be trained in overdose prevention, and developing overdose interventions should be a priority among drug educators.

Hepatitis C virus infection and needle exchange use among young injection drug users in San Francisco.

Young injection drug users (IDUs) in San Francisco may be at high risk for hepatitis C virus (HCV) infection despite access to several needle exchange venues. The authors conducted a cross-sectional study from 1997 to 1999 in San Francisco to estimate the prevalence and incidence of antibody to HCV (anti-HCV) among street-recruited IDUs under age 30, and to examine risk behaviors and sources of sterile needles. Among 308 participants, the prevalence of anti-HCV was 45%. Using statistical modeling, incidence of HCV infection was estimated to be 11 per 100 person years. Independent risk factors for anti-HCV included age (odds ratio [OR], 1.17 per year; 95% confidence interval [CI], 1.05-1.30), years injecting (OR, 1.21 per year; 95% CI, 1.10-1.34), years in San Francisco (OR, 1.06 per year; 95% CI, 1.00-1.14), first injected by a sex partner (OR, 4.06; 95% CI, 1.74-9.52), injected daily (OR, 3.85; 95% CI, 2.07-7.17), ever borrowed a needle (OR, 2.56; 95% CI, 1.18-5.53), bleached last time a needle was borrowed (OR, 0.50; 95% CI, 0.24-1.02), snorted or smoked drugs in the prior year (OR, 0.48; 95% CI, 0.26-0.89), and injected by someone else in the prior month (OR, 0.50; 95% CI, 0.25-0.99). In the prior month, 88% used at least 1 of several needle exchange venues, and 32% borrowed a needle. We conclude that anti-HCV prevalence is lower than in previous studies of older IDUs, but 11% incidence implies high risk of HCV infection in a long injecting career. Despite access to sterile needles, borrowing of needles persisted.

The role of dairy products in supplying conjugated linoleic acid to man's diet: a review.

Health benefits for man have been associated with conjugated linoleic acid (CLA) and dairy products are highlighted as offering the best opportunity to increase CLA consumption. CLA is synthesised in the rumen as an intermediate in the biohydrogenation of linoleic acid to stearic acid. The supplies of both intermediates and endproducts of biohydrogenation are affected by the substrate supply and extent of biohydrogenation, thus influencing the CLA content of milk from ruminants. The majority of CLA is present in the rumen in the form of the cis-9,trans-11 isomer. The transfer efficiency of CLA to milk fat is affected by the presence of different isomers of CLA. Ruminant mammary and adipose cells are able to synthesise cis-9,trans-11-CLA from trans-11-18:1 (vaccenic acid) by the action of the Delta9-desaturase enzyme. Plant oils are high in both linoleic and linolenic acids, which results in increased CLA production in the rumen and in the mammary gland. The CLA content of milk increases when cows are offered grazed grass. Many published studies examining the CLA concentration of processed milk were confounded by variations in the concentration of CLA in the raw milk.

Tuberculosis in the homeless. A prospective study.

We set out to determine tuberculosis incidence and risk factors in the homeless population in San Francisco. We also examined the transmission of tuberculosis by molecular methods. We followed a cohort of 2,774 of the homeless first seen between 1990 and 1994. There were 25 incident cases during the period 1992 to 1996, or 270 per 100,000 per year (350/100,000 in African Americans, 450/100,000 in other nonwhites, 60/100,000 in whites). Ten cases were persons with seropositive HIV. Independent risk factors for tuberculosis were HIV infection, African American or other nonwhite ethnicity, positive tuberculin skin test (TST) results, age, and education; 60% of the cases had clustered patterns of restriction fragment length polymorphism, thought to represent recent transmission of infection with rapid progression to disease. Seventy-seven percent of African-American cases were clustered, and 88% of HIV-seropositive cases. The high rate of tuberculosis in the homeless was due to recent transmission in those HIV-positive and nonwhite. African Americans and other nonwhites may be at high risk for infection or rapid progression. Control measures in the homeless should include directly observed therapy and incentive approaches, treatment of latent tuberculous infection in those HIV-seropositive, and screening in hotels and shelters.

Risk of hepatitis B infection among young injection drug users in San Francisco: opportunities for intervention.

OBJECTIVE: To compare the demographic characteristics and risk behaviors for hepatitis B infection among injection drug users younger than 30 years with those aged 30 or older and to evaluate participants' knowledge, attitudes, and experiences of infection, screening, and vaccination against hepatitis B virus. DESIGN: A systematic sample of injection drug users not currently in a treatment program were recruited and interviewed at needle exchange programs and community sites. PARTICIPANTS: 135 injection drug users younger than 30 years and 96 injection drug users aged 30 or older. RESULTS: Injection drug users younger than 30 were twice as likely as drug users aged 30 or older to report having shared needles in the past 30 days (36/135 [27%] vs 12/96 [13%]). Injection drug users younger than 30 were also twice as likely to report having had more than two sexual partners in the past 6 months (80/135 [59%] vs 29/96 [30%]). Although 88 of 135 (68%) young injection drug users reported having had contact with medical providers within the past 6 months only 13 of 135 (10%) had completed the hepatitis B vaccine series and only 16 of (13%) perceived themselves as being at high risk of becoming infected with the virus. CONCLUSION: Few young injection drug users have been immunized even though they have more frequent contact with medical providers and are at a higher risk for new hepatitis B infection than older drug users. Clinicians caring for young injection drug users and others at high risk of infection should provide education, screening, and vaccination to reduce an important source of hepatitis B infection.

Adherence to isoniazid prophylaxis in the homeless: a randomized controlled trial.

OBJECTIVES: To test 2 interventions to improve adherence to isoniazid preventive therapy for tuberculosis in homeless adults. We compared (1) biweekly directly observed preventive therapy using a $5 monetary incentive and (2) biweekly directly observed preventive therapy using a peer health adviser, with (3) usual care at the tuberculosis clinic. METHODS: Randomized controlled trial in tuberculosis-infected homeless adults. Outcomes were completion of 6 months of isoniazid treatment and number of months of isoniazid dispensed. RESULTS: A total of 118 subjects were randomized to the 3 arms of the study. Completion in the monetary incentive arm was significantly better than in the peer health adviser arm (P = .01) and the usual care arm (P = .04), by log-rank test. Overall, 19 subjects (44%) in the monetary incentive arm completed preventive therapy compared with 7 (19%) in the peer health adviser arm (P = .02) and 10 (26%) in the usual care arm (P = .11). The median number of months of isoniazid dispensed was 5 in the monetary incentive arm vs 2 months in the peer health adviser arm (P = .005) and 2 months in the usual care arm (P = .04). In multivariate analysis, independent predictors of completion were being in the monetary incentive arm (odds ratio, 2.57; 95% CI, 1.11-5.94) and residence in a hotel or other stable housing at entry into the study vs residence on the street or in a shelter at entry (odds ratio, 2.33; 95% CI, 1.00-5.47). CONCLUSIONS: A $5 biweekly cash incentive improved adherence to tuberculosis preventive therapy compared with a peer intervention or usual care. Living in a hotel or apartment at the start of treatment also predicted the completion of therapy.

A molecular epidemiologic analysis of tuberculosis trends in San Francisco, 1991-1997.

BACKGROUND: To decrease tuberculosis case rates and cases due to recent infection (clustered cases) in San Francisco, California, tuberculosis control measures were intensified beginning in 1991 by focusing on prevention of Mycobacterium tuberculosis transmission and on the use of preventive therapy. OBJECTIVE: To describe trends in rates of tuberculosis cases and clustered cases in San Francisco from 1991 through 1997. DESIGN: Population-based study. SETTING: San Francisco, California. PATIENTS: Persons with tuberculosis diagnosed between 1 January 1991 and 31 December 1997. MEASUREMENTS: DNA fingerprinting was performed. During sequential 1-year intervals, changes in annual case rates per 100,000 persons for all cases, clustered cases (cases with M. tuberculosis isolates having identical fingerprint patterns), and cases in specific subgroups with high rates of clustering (persons born in the United States and HIV-infected persons) were examined. RESULTS: Annual tuberculosis case rates peaked at 51.2 cases per 100,000 persons in 1992 and decreased significantly thereafter to 29.8 cases per 100,000 persons in 1997 (P < 0.001). The rate of clustered cases decreased significantly over time in the entire study sample (from 10.4 cases per 100,000 persons in 1991 to 3.8 cases per 100,000 persons in 1997 [P < 0.001]), in persons born in the United States (P < 0.001), and in HIV-infected persons (P = 0.003). CONCLUSIONS: The rates of tuberculosis cases and clustered tuberculosis cases decreased both overall and among persons in high-risk groups. This occurred in a period during which tuberculosis control measures were intensified.

Street talk: knowledge and attitudes about tuberculosis and tuberculosis control among homeless adults.

OBJECTIVES: To measure knowledge and perceived susceptibility to tuberculosis among homeless adults in San Francisco and attitudes toward control measures used to improve adherence to treatment for tuberculosis. DESIGN: A cross-sectional survey via interview of homeless shelter residents was done at five shelters. RESULTS: Of 292 persons interviewed, 21.6% reported a positive skin test, and 57.1% of the positives had received preventive therapy. Over 60% had misconceptions about transmission, in particular confusion with transmission of the human immunodeficiency virus (HIV). Knowledge of skin testing procedures and symptoms was generally good, and most reported health care providers as the main source of information. Over half reported concern about catching tuberculosis and over 80% favored controls to ensure adherence, in particular directly observed therapy. Higher TB knowledge score (P = 0.0155) and male sex (P = 0.0357) were associated with a favorable attitude toward directly observed therapy. CONCLUSIONS: Health care providers should expand educational messages beyond skin testing. Greater knowledge about tuberculosis may increase acceptance of control measures. Targeted education plus social norms favoring completion of therapy may improve screening and treatment outcomes in this population.

Differences in contributing factors to tuberculosis incidence in U.S. -born and foreign-born persons.

To determine the factors contributing to tuberculosis incidence in the U.S.-born and foreign-born populations in San Francisco, California, and to assess the effectiveness of tuberculosis control efforts in these populations, we performed a population-based molecular epidemiologic study using 367 patients with strains of Mycobacterium tuberculosis recently introduced into the city. IS6110-based and PGRS-based restriction fragment length polymorphism (RFLP) analyses were performed on M. tuberculosis isolates. Patients whose isolates had identical RFLP patterns were considered a cluster. Review of public health and medical records, plus patient interviews, were used to determine the likelihood of transmission between clustered patients. None of the 252 foreign-born cases was recently infected (within 2 yr) in the city. Nineteen (17%) of 115 U. S.-born cases occurred after recent infection in the city; only two were infected by a foreign-born patient. Disease from recent infection in the city involved either a source or a secondary case with human immunodeficiency virus (HIV) infection, homelessness, or drug abuse. Failure to identify contacts accounted for the majority of secondary cases. In San Francisco, disease from recent transmission of M. tuberculosis has been virtually eliminated from the foreign-born but not from the U.S.-born population. An intensification of contact tracing and screening activities among HIV-infected, homeless, and drug-abusing persons is needed to further control tuberculosis in the U.S.-born population. Elimination of tuberculosis in both the foreign-born and the U.S. -born populations will require widespread use of preventive therapy.

Incidence of tuberculosis in injection drug users in San Francisco: impact of anergy.

Between 1990 and 1994, we conducted a prospective study in five methadone maintenance clinics in San Francisco to determine the rate of tuberculosis (TB) in injection drug users, including those who were anergic. Of the 1,745 persons seen in the clinics, 1,109 completed an evaluation that included skin testing with tuberculin and at least two other antigens (mumps, tetanus, and/or Candida), as well as HIV testing. All persons with a positive tuberculin skin test (TST) and anergic individuals who had radiographic evidence of tuberculous infection (i.e., calcified granulomas) were offered isoniazid (INH) preventive therapy. The median follow-up was 22.0 mo. There were 338 (30.5%) human immunodeficiency virus (HIV)-seropositive patients and 771 (69.5%) HIV-seronegative patients; 96 (28.0%) and 336 (44.0%), respectively, had positive TSTs. Of the HIV-seropositive subjects, 108 (31.9%) had no reaction to any of the three antigens, and were therefore classified as anergic. The rate of TB among the HIV-seropositive, TST-positive patients who did not take INH preventive therapy was 5.0 per 100 person-yr, compared with 0.4 per 100 person-yr among the HIV-seronegative, TST-positive patients (p = 0.007). There were no cases of TB among the anergic subjects. These data indicate that INH preventive therapy is not routinely indicated in anergic, HIV-seropostive patients.

Cancer screening in homeless women: attitudes and behaviors.

Little is known about the use of cancer-screening services in homeless women and their attitudes about early detection programs. Face-to-face interviews were conducted with homeless women in San Francisco to determine rates of clinical breast exams, mammograms, and Pap smears. A total of 105 women were randomly selected from two homeless shelters. By self-report, 51 percent were current on clinical breast exams, 47 percent on mammograms, and 54 percent on Pap smears. These women had very positive attitudes toward receiving cancer-screening exams. In multivariate analyses, discussion about cancer prevention with a health care provider predicted current clinical breast exams and mammograms. More medical visits predicted being current on mammograms and Pap smears. Although homeless women represent a unique group of the urban poor, they are accessing cancer-screening exams at rates comparable to the general population.