Gayatri C. Jayaraman

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.

Estimating the size of hard-to-reach populations: a novel method using HIV testing data compared to other methods.

Objective: To estimate population size of hard-to-reach groups such as injecting drug users and men who have sex with men. Design: Several different methods were used to estimate the size of these populations in Canadas three largest cities (Toronto, Montreal and Vancouver). Methods: A novel method (referred to as the indirect method) was developed for use in Toronto and Vancouver that combines HIV serodiagnostic information with data on HIV testing behavior. Population size estimates were obtained by dividing the number of injecting drug users or men who have sex with men recorded in HIV serodiagnostic databases in a given year by the proportion of the corresponding group that reported being tested in a 1-year period. Results of this method were compared with four other methods: (1) population surveys; (2) capture-recapture (for injecting drug users only); (3) a modified Delphi technique; and (4) a method based on the proportion of never-married men aged 45 and over (for men who have sex with men only). Only these other methods were used in Montreal. Results: The survey method gave the lowest estimates which are best viewed as minimum estimates given the relative inability of surveys to access these populations and the reluctance of participants to admit to sensitive behaviors. The indirect method produced results more closely comparable with those obtained by other methods, but they are probably slight overestimates, at least for injecting drug users, due to possible underestimation of the proportion tested for HIV. Point estimates using the indirect method were 17 700 and 17 500 for injecting drug users in Toronto and Vancouver, respectively, and 39 100 and 15 900 for men who have sex with men. In Toronto, results for the other methods ranged from 12 300-13 360 for injecting drug users and 18 800-35 000 for men who have sex with men. For Vancouver, these ranges were 6400-11 670 and 7000-26 500, respectively. In Montreal, ranges were 4300-12 500 for injecting drug users and 18 500-40 000 for men who have sex with men. Conclusions: This novel method provides estimates of population size of hard-to-reach groups such as injecting drug users and men who have sex with men that are comparable with results derived by other methods. These estimates may be useful for the purposes of planning, implementing and evaluating prevention and care services, especially when they are combined with the results of other estimation methods to improve the degree of confidence in the resulting estimates.

Nucleic Acid Testing for West Nile Virus RNA in Plasma Enhances Rapid Diagnosis of Acute Infection in Symptomatic Patients

Although nucleic acid amplification testing (NAAT) for West Nile virus (WNV) is useful in screening blood donors, such methods have not been studied in symptomatic patients. For diagnosis of WNV infection, 1.0 mL of plasma was tested by NAAT, and WNV-specific immunoglobulin M was assayed. Of 276 WNV cases, 191 were tested by both serology and NAAT. Of these, 86 (45.0%), 111 (58.1%), and 180 (94.2%) were detected by NAAT, serology, and combined NAAT and serology, respectively. NAAT-based screening was most useful within 8 days of the onset of symptoms. Viremia is common in early symptomatic WNV infection, and NAAT enhances diagnostic yield.

Trends in antimicrobial resistance in Neisseria gonorrhoeae isolated in Canada: 2000-2009.

Background: Canada conducts surveillance of penicillin, tetracycline, erythromycin, spectinomycin, ciprofloxacin, cefixime, and ceftriaxone susceptibilities in Neisseria gonorrhoeae isolates to support development of national treatment guidelines for sexually transmitted infections. Methods: N. gonorrhoeae isolates were collected by Canadian provincial public health laboratories and included isolates from males and females ranging in age from 1 to 86 years. Minimum inhibitory concentrations (MICs) were determined by agar dilution at the National Microbiology Laboratory, Public Health Agency of Canada, and MIC interpretations were based on the criteria of the Clinical Laboratory Standards Institute. Results: From 2000 to 2009, 40,875 isolates of N. gonorrhoeae were tested by provincial laboratories and 10,993 of these were characterized by the Public Health Agency of Canada. There was an increasing incidence of N. gonorrhoeae isolates that were chromosomally resistant to penicillin, tetracycline, and erythromycin while the plasmid-mediated resistance strains (penicillinase-producing N. gonorrhoeae, tetracycline-resistant N. gonorrhoeae, and PP/tetracycline-resistant N. gonorrhoeae strain all had a declining trend. The percentage of isolates resistant to ciprofloxacin significantly increased from 1.3% in 2000 to 25.5% in 2009. Only 0.17% of isolates tested were azithromycin resistant. Between 2000 and 2009, the modal MICs for ceftriaxone increased from 0.016 &mgr;g/mL to 0.063 &mgr;g/mL. Conclusions: Ciprofloxacin resistance in N. gonorrhoeae within Canada has increased to a level where quinolones are no longer the preferred drugs for the treatment of gonococcal infections and the modal MICs for the third-generation cephalosporins have increased over time. Close monitoring of antibiotic susceptibilities are required to inform treatment options.

Characteristics of individuals with male-to-male and heterosexually acquired infectious syphilis during an outbreak in Calgary, Alberta, Canada.

Background Eliminating syphilis is important not only to prevent the sequelae of infection but also to control the spread of HIV. Current prevention and control efforts in Canada have been ineffective in eliminating this disease. Goal The goal of the study was to determine the characteristics of individuals with infectious syphilis due to male-to-male and heterosexual contact, diagnosed during an outbreak in Calgary, Alberta, Canada. Study Design This was a prospective study of individuals with infectious syphilis diagnosed at the STD clinic in Calgary between January 2000 and April 2002. Results The outbreak reported here (September 2000 to April 2002) involves 32 cases of infectious syphilis, corresponding to rates of 0.9/100,000 population during 2000 and 1.8/100,000 population during 2001. Between September 2000 and June 2001, the cases diagnosed were among men who have sex with men (MSM); between May 2001 and April 2002, they were due to locally acquired infections among heterosexuals, including one case of congenital syphilis. Compared to the heterosexuals, MSM tended to be older, be coinfected with HIV, and report excessive alcohol use (versus injection drug use) and had infectious syphilis diagnosed earlier. MSM used the Internet and bars or bathhouses to initiate sexual contact, whereas heterosexually acquired infections were largely among sex workers and their clients. Contact tracing was more successful among the heterosexuals than among MSM. The public health staff at the STD clinic initiated a series of multifaceted interventions in response to the outbreak. These interventions were moderately successful, as measured by the increased numbers of individuals seeking counseling and testing services at the clinic. Conclusion The results highlight key differences in the risk factor-specific characteristics of the outbreak that should be taken into account when designing prevention and control strategies.

Time to Testing and Accessing Care among a Population of Newly Diagnosed Patients with HIV with a High Proportion of Canadian Aboriginals, 1998–2003

Early HIV diagnosis and treatment are important for decreasing HIV transmission and morbidity. By using initial CD4 counts and time to first viral load test, we examined the stage of disease at the time of diagnosis and the time to accessing medical care after diagnosis, respectively. Initial CD4 count, first HIV viral load test, demographics and exposure risks were obtained for all newly diagnosed HIV cases in Northern Alberta from 1998-2003. Time to accessing care was determined as the time between diagnosis and the first viral load test. Correlates were determined using simple descriptive statistics and survival analysis methods. Of 526 HIV cases, median age was 36 years (interquartile range [IQR]: 31-43), 69% were males and 41% were Aboriginal. At diagnosis, 28% of the population had CD4 counts less than 200 cells=mm3. After diagnosis, 92.2% accessed care and median time to care for the entire population was 29 days. In multivariate analysis, age at diagnosis less than 45 years was independently associated with longer median time to care (versus age 45 years or more; adjusted hazard ratio [AHR]: 0.69; 95% confidence interval [CI] 0.55-0.88), while Aboriginal ethnicity (versus Caucasian; AHR: 0.82; 95% CI 0.68-1.01), and nonmetropolitan residence (versus metropolitan; AHR: 0.81; 95% CI 0.65-1.00) were marginally significant correlates for longer times to care. Although more than one quarter of cases were diagnosed at relatively advanced stages of infection, the majority of new HIV cases in Northern Alberta accessed care within 2 months of diagnosis. We need to explore new strategies to facilitate and promote earlier access to testing among individuals at risk.

Estimation of the burden of disease and costs of genital Chlamydia trachomatis infection in Canada.

Background: Rates of Chlamydia trachomatis (CT) infection in Canada have been increasing since the mid-1990s. We sought to estimate the burden of CT in this population. Methods: We developed an age- and sex-structured mathematical model parameterized to reproduce trends in CT prevalence between 1991 and 2009 in the Canadian population aged 10 to 39 years. Costs were identified, measured, and valued using a modified societal perspective and converted to year 2009 Canadian dollars. Cost-effectiveness of the implemented policy of enhanced screening for asymptomatic infections was estimated by comparison with model-projected trends in the absence of increased screening. Main outcome measures were current net cost and burden of illness attributable to CT infection, and incremental cost-effectiveness ratios. Results: Under base case model assumptions, there was a trend of increasing detection of CT cases (due to increases in screening), despite an underlying stabilization of actual CT infections. Average estimated costs associated with CT infection over this period were

Trends in age disparities between younger and middle-age adults among reported rates of chlamydia, gonorrhea, and infectious syphilis infections in Canada: findings from 1997 to 2007.

51.4 million per year. Costs of screening and treatment of asymptomatic infections as a proportion of total CT costs were estimated to have increased over time, whereas costs of long-term sequelae associated with untreated infections declined over the same period. Compared with no change in screening, enhanced screening was estimated to be highly cost-effective, with an incremental cost-effectiveness ratio of

Clinical utility of commercial enzyme immunoassays during the inaugural season of West Nile virus activity, Alberta, Canada.

2910 per quality-adjusted life year. Conclusions: Despite increases in screening, the economic burden of CT in Canada remains high. Further investigation of trends in chlamydia-associated complications is required to better understand the impact of screening on incidence.

A Protocol for the Secure Linking of Registries for HPV Surveillance

Background: The objective was to determine trends in age disparities between reported rates of chlamydia, gonorrhea, and infectious syphilis among younger versus middle-age Canadians. Methods: We examined age- and sex-specific reported rates of chlamydia, gonorrhea, and infectious syphilis between 1997 and 2007. Sexually transmitted infection (STI) rates in the younger age group (15–29 years) were compared to the middle-age group (40–59 years) over the 11-year period. We used Poisson regression to examine trends in age-specific (younger:middle-age) rate ratios. Results: Between 1997 and 2007, both the number and rate of reported cases increased for all 3 nationally notifiable STIs. Although chlamydia and gonorrhea rates continued to be higher among younger adults, rates of all 3 STIs increased more dramatically among middle-age adults. Between 1997 and 2007, chlamydia rates increased by 86.8% among adults aged 15 to 29 (P <0.0001) and 165.9% among adults 40- to 59-years-old (P <0.0001). The corresponding increases for gonorrhea were 133.3% (P <0.0001) and 210.2% (P <0.0001) respectively. Infectious syphilis rates increased 5-fold among younger adults compared to an increase of 11-fold among middle-age adults (P <0.0001) since 1997. The reported rate ratios (younger:middle-age) decreased over time for chlamydia (P <0.0001), gonorrhea (P <0.0001), and syphilis (P = 0.005). Males were disproportionately represented among reported chlamydia, gonorrhea, and infectious syphilis cases, constituting 59.8%, 87.6%, and 93.0% of middle-age adult cases, respectively, in 2007. Conclusions: Middle-age adults may be increasingly affected by chlamydia, gonorrhea and infectious syphilis. There is a need for sexual health information targeting Canadas middle-age adults and their health care providers.