Michael L. Rekart

Needle exchange is not enough: lessons from the Vancouver injecting drug use study

Objective: To describe prevalence and incidence of HIV‐1, hepatitis C virus (HCV) and risk behaviours in a prospective cohort of injecting drug users (IDU). Setting: Vancouver, which introduced a needle exchange programme (NEP) in 1988, and currently exchanges over 2 million needles per year. Design: IDU who had injected illicit drugs within the previous month were recruited through street outreach. At baseline and semi‐annually, subjects underwent serology for HIV‐1 and HCV, and questionnaires on demographics, behaviours and NEP attendance were completed. Logistic regression analysis was used to identify determinants of HIV prevalence. Results: Of 1006 IDU, 65% were men, and either white (65%) or Native (27%). Prevalence rates of HIV‐1 and HCV were 23 and 88%, respectively. The majority (92%) had attended Vancouvers NEP, which was the most important syringe source for 78%. Identical proportions of known HIV‐positive and HIV‐negative IDU reported lending used syringes (40%). Of HIV‐negative IDU, 39% borrowed used needles within the previous 6 months. Relative to HIV‐negative IDU, HIV‐positive IDU were more likely to frequently inject cocaine (72 versus 62%; P < 0.001). Independent predictors of HIV‐positive serostatus were low education, unstable housing, commercial sex, borrowing needles, being an established IDU, injecting with others, and frequent NEP attendance. Based on 24 seroconversions among 257 follow‐up visits, estimated HIV incidence was 18.6 per 100 person‐years (95% confidence interval, 11.1‐26.0). Conclusions: Despite having the largest NEP in North America, Vancouver has been experiencing an ongoing HIV epidemic. Whereas NEP are crucial for sterile syringe provision, they should be considered one component of a comprehensive programme including counselling, support and education.

The Unexpected Impact of a Chlamydia trachomatis Infection Control Program on Susceptibility to Reinfection

BACKGROUND After the introduction of a program to control Chlamydia trachomatis infection in British Columbia, Canada, case rates fell from 216 cases/100,000 population in 1991 to 104 cases/100,000 population in 1997. Since 1998, rates have increased, and case counts now exceed those recorded before the intervention. METHODS We used Cox proportional-hazards survival analysis and developed a compartmental mathematical model to investigate the cause of resurgence in chlamydia cases. RESULTS Cox proportional-hazards survival analysis showed that the relative risk of C. trachomatis reinfection has increased 4.6% per year since 1989, with the increased risk greatest among the young and greater among women than men. A compartmental mathematical model of C. trachomatis transmission showed that a control strategy based on shortening the average duration of infection results in an early reduction in prevalence followed by a rebound in prevalence, reproducing the observed trends. CONCLUSIONS We speculate that a C. trachomatis infection control program based on early case identification and treatment interferes with the effects of immunity on population susceptibility to infection and that, in the absence of strategies to alter sexual networks, a vaccine will be needed to halt the spread of infection at the population level.

Determinants of HIV seroconversion in drug users during a period of rising prevalence in Vancouver

To identify determinants of HIV seroconversion among injection drug users (IDUs) during a period of rising prevalence, a case-control investigation was conducted. Cases were IDUs with a new positive test after 1 January 1994, and a negative test within the prior 18 months. Controls required 2 negative tests during the same period. Subjects completed a questionnaire on demographic, psychosocial, and behavioural factors. Eighty-nine cases and 192 controls were similar with respect to gender, age, ethnicity and inter-test interval. Multivariate analyses of events during the inter-test interval showed borrowing syringes (adj. OR=2.96; P 0.006), unstable housing (adj. OR=2.01; P =0.03) and injecting 4 times daily (adj. OR=1.71; P =0.06) to be independently associated with seroconversion. Protective associations were demonstrated for sex with opposite gender (adj. OR=0.36; P =0.001) and tetrahydrocannabinol use (adj. OR=0.41; P =0.001). There is a need to evaluate programmes dealing with addiction, housing and the social underpinnings of risk behaviours in this population. <

Protective Immunity to Chlamydia trachomatis Genital Infection: Evidence from Human Studies

Background. Some screening and treatment programs implemented to control Chlamydia trachomatis genital infections and their complications have shown initial reductions in infection prevalence, followed by increases to preprogram levels or higher. One hypothesis is that treatment shortens duration of infection, attenuates development of protective immunity, and thereby, increases risk of reinfection. Methods. A literature review was undertaken to assess evidence supporting the concept of protective immunity,its characteristics, and its laboratory correlates in human chlamydial infection. The discussion is organized around key questions formulated in preparation for the Chlamydia Immunology and Control Expert Advisory Meeting held by the Centers for Disease Control and Prevention in April 2008. Results. Definitive human studies are not available, but cross-sectional studies show that chlamydia prevalence,organism load, and concordance rates in couples decrease with age, and organism load is lower in those with repeat infections, supporting the concept of protective immunity. The protection appears partial and can be overcome after reexposure, similar to what has been found in rodent models of genital infection. No data are available to define the duration of infection required to confer a degree of immunity or the time course of immunity after resolution of untreated infection. In longitudinal studies involving African sex workers, a group presumed to have frequent and ongoing exposure to chlamydial infection, interferon-g production by peripheral blood mononuclear cells in response to chlamydial heat-shock protein 60 was associated with low risk of incident infection.In cross-sectional studies, relevant T helper 1-type responses were found in infected persons, paralleling the studies in animal models. Conclusions. The data support the concept that some degree of protective immunity against reinfection develops after human genital infection, although it appears, at best, to be partial. It is likely that factors besides population levels of immunity contribute to trends in prevalence observed in screening and treatment programs.Future studies of protective immunity in humans will require longitudinal follow-up of individuals and populations,frequent biological and behavioral sampling, and special cohorts to help control for exposure.

A population-based approach to determine the prevalence of transmitted drug-resistant HIV among recent versus established HIV infections: results from the Canadian HIV strain and drug resistance surveillance program.

Objectives: Published results on primary or transmitted HIV drug resistance may be biased because they have been largely derived from specific cohort studies or higher risk individuals who present symptomatically. Here, we present results from a representative population-based study of newly diagnosed cases of HIV in Canada and compare the prevalence of transmitted drug resistance between recent and established infections. Methods: Available archived sera taken for the purpose of diagnostic HIV testing from all treatment-naive HIV-positive individuals who were newly diagnosed between 2000 and 2001 were tested for recency of infection, HIV-1 subtype, and mutations conferring reduced susceptibility to reverse transcriptase inhibitors and protease inhibitors (PIs). Recent infections were identified using the Organon Teknika Vironostika HIV-1-LS assay. After full-length sequencing of the pol gene, drug resistance mutations were identified using the 2004 International AIDS Society-USA mutations panel. Differences in drug resistance profiles between recent and prevalent infections were examined using the &khgr;2 test and the Fisher exact test. The variables examined included gender, age at diagnosis, year of diagnosis, exposure category, ethnicity, and HIV-1 subtype. Results: Among the study population, 8.1% had genotypic evidence of transmitted drug resistance: 4.1% against nucleoside reverse transcriptase inhibitors, 1.4% against nonnucleoside reverse transcriptase inhibitors, 1.5% against PIs, and 1% against ≥2 classes of drugs. A higher proportion of recent infections had genotypic evidence of transmitted drug resistance when compared with established infections (12.2% vs. 6.1%, respectively; P = 0.005). Transmitted drug resistance was identified mainly among recently infected Caucasian men who have sex with men but it was not limited to this group. Compared with the year 2000, a higher proportion of recently infected individuals with resistance-conferring mutations were diagnosed during the year 2001 (66.7% vs. 46.6%). Conclusions: In Canada, transmitted drug resistance is occurring within all 3 drug classes and across different population groups. The results suggest that the prevalence rates may be higher among recent versus established infections. Given the public health implications of transmitting drug-resistant HIV, it is important to continue population-based drug resistance surveillance to guide optimum prevention and treatment of HIV infection.

Epidemiology of chlamydial infection: are we losing ground?

Are we losing ground in our efforts to control sexually transmitted Chlamydia trachomatis infection? Before we can answer this question, we must first consider recent trends in Chlamydia from around the world to establish a baseline for understanding the possible explanations underlying these data.

Targeted mass treatment for syphilis with oral azithromycin

From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001<p<0.0044). This rate rebound and the absence of a sustained effect suggest that targeted mass treatment for syphilis, even though feasible, should not be done routinely.

Factors associated with frequent needle exchange program attendance in injection drug users in Vancouver, Canada

The objective of this study was to identify factors associated with frequent needle exchange program (NEP) attendance by injection drug users (IDUs) in Vancouver, Canada. Data were examined from a case control study of recent HIV infection. IDUs with documented HIV seroconversion after January 1, 1994 (n = 89) and seronegative controls with two documented HIV-negative test results in the same period (n = 192) were asked about demographic and social information, drug injection and sexual behavior, and NEP attendance. Logistic regression was used to examine the effect of multiple variables on NEP attendance while adjusting for HIV status and other potential confounders. Frequent (> 1 time/week) versus nonfrequent (< or = 1 time/week) NEP attenders did not differ with respect to gender, age, ethnicity, education, or HIV serostatus. For men, multivariate analysis showed that frequent cocaine injection was the only variable independently associated with NEP attendance (adjusted odds ratio [AOR] = 3.9; 95% confidence interval [CI] = 1.8-8.3); for women, independently associated variables were frequency of any drug injection (AOR = 5.5; 95% CI = 1.7-17), shooting gallery attendance (AOR = 11.5; 95% CI = 2.2-66), and having a nonlegal source of income (AOR = 3.4; 95% CI = 1.0-12). Borrowing used needles was associated with frequent NEP attendance in the univariate analysis. The NEP in Vancouver attracts IDUs who are frequent injectors (especially men using cocaine) and who have high-risk behaviors or an unstable lifestyle. This finding reinforces the role of NEPs as potential focal points for intervention in this hard-to-reach population.

Antenatal Seroprevalence of Herpes Simplex Virus Type 2 (HSV-2) in Canadian Women HSV-2 Prevalence Increases Throughout the Reproductive Years

Background Thisstudy sought to provide the first population estimates of herpes simplex type2 (HSV-2) seroprevalence inCanada. Goal Tomeasure the antenatal seroprevalence of HSV-2 antibodies in reproductive agewomen. StudyDesign An anonymous unlinked seroprevalence study usedstored sera collected from pregnant women in British Columbia during 1999.Randomized sampling within age strata selected a total of 1215 subjects, ages15 to 44 years. Serologic testing used the Gull Meridian Test. Overallprevalence was directly standardized to the 1999 Canadian femalepopulation. Results Theage-adjusted prevalence for HSV-2 was 17.3% (95% CI, 15.2–19.4).Prevalence ranged from 7.1% (ages, 15–19 years) to 28.1% (ages,40–44 years), with the largest increases after the age of 24years. Conclusions TheHSV-2 seroprevalence among pregnant women in British Columbia is similar tothat in the United States and other countries. Seroprevalence continues torise through the later reproductive years. This observation may relate tocontinued transmission, an age cohort effect, orboth.

Chlamydia Public Health Programs and the Epidemiology of Pelvic Inflammatory Disease and Ectopic Pregnancy

BACKGROUND Many countries have witnessed a disturbing increase in cases of Chlamydia trachomatis infection despite enhanced control programs. Since the goal of Chlamydia control is to prevent reproductive complications such as pelvic inflammatory disease and ectopic pregnancy, an understanding of recent trends in these conditions is needed to fully evaluate the effect of control efforts. METHODS We analyzed 2 provincial, comprehensive health services administrative databases (encompassing hospitalizations and all physician-delivered services) for pelvic inflammatory disease and ectopic pregnancy trends from 1992 through 2009 in women of reproductive age in British Columbia, Canada. Trends were compared to provincial Chlamydia surveillance data by time-series analysis, using the cross-correlation function method and Granger causality testing. RESULTS Chlamydia cases substantially increased from 1992 through 2009. Inpatient, outpatient, and total diagnoses of pelvic inflammatory disease and ectopic pregnancy declined from 1992 through 2003. After 2003, pelvic inflammatory disease rates continued to fall, while ectopic pregnancy rates significantly increased. The male Chlamydia urethritis rate increased from 39.4 to 173.6 cases/100,000 from 1996 to 2009. CONCLUSIONS In the context of increasing Chlamydia infection rates, the reproductive complications of Chlamydia infection in women are declining overall. A recent increase in rates of ectopic pregnancies is cause for concern.