Prithwish De

Sexual network analysis of a gonorrhoea outbreak.

Objectives: Sexual partnerships can be viewed as networks in order to study disease transmission. We examined the transmission of Neisseria gonorrhoeae in a localised outbreak in Alberta, Canada, using measures of network centrality to determine the association between risk of infection of network members and their position within the sexual network. We also compared risk in smaller disconnected components with a large network centred on a social venue. Methods: During the investigation of the outbreak, epidemiological data were collected on gonorrhoea cases and their sexual contacts from STI surveillance records. In addition to traditional contact tracing information, subjects were interviewed about social venues they attended in the past year where casual sexual partnering may have occurred. Sexual networks were constructed by linking together named partners. Univariate comparisons of individual network member characteristics and algebraic measures of network centrality were completed. Results: The sexual networks consisted of 182 individuals, of whom 107 were index cases with laboratory confirmed gonorrhoea and 75 partners of index cases. People who had significantly higher information centrality within each of their local networks were found to have patronised a popular motel bar in the main town in the region (p = 0.05). When the social interaction through the bar was considered, a large network of 89 individuals was constructed that joined all eight of the largest local networks. Moreover, several networks from different communities were linked by individuals who served as bridge populations as a result of their sexual partnering. Conclusion: Asking clients about particular social venues emphasised the importance of location in disease transmission. Network measures of centrality, particularly information centrality, allowed the identification of key individuals through whom infection could be channelled into local networks. Such individuals would be ideal targets for increased interventions.

Risk of hepatitis C virus transmission through drug preparation equipment: a systematic and methodological review

Summary.  The use of blood‐contaminated drug preparation equipment is believed to be associated with the transmission of hepatitis C virus (HCV) among injection drug users (IDUs), but the extent of HCV infection risk is unclear. The objective of this review was to appraise the evidence regarding HCV incidence associated with the use of drug preparation equipment such as drug mixing containers, filters and water. In June 2007, cohort and case–control studies examining the association of HCV incidence with the sharing of drug preparation equipment were identified by searching electronic reference databases as well as the reference lists of published papers. Ten studies (seven cohort and three nested case–control) met the inclusion criteria for the review. The relative risk of HCV infection associated with drug preparation equipment were mainly between 2.0 and 5.9; however, the precision of the estimates from individual studies were marked by wide confidence intervals. Few studies exist to allow an adequate assessment of the individual contributions of containers, filters and water to HCV incidence. The major methodological limitations of reviewed studies were short follow‐up times, inadequate control of confounders and lack of exclusion of periods when IDUs were not at risk for HCV infection through drug injection. Current evidence implicating the association of drug preparation equipment with HCV incidence is limited by several methodological concerns.

Primary Syphilis: Serological Treatment Response to Doxycycline/Tetracycline versus Benzathine Penicillin

BACKGROUND Benzathine penicillin G is the treatment of choice for infectious syphilis, but tetracycline and doxycycline are believed to be effective second-line treatments. The objective of this study was to assess the serological response from treatment of primary syphilis with benzathine penicillin compared with doxycycline or tetracycline. METHODS We examined rapid plasma reagin serological test results of all first-time primary syphilis patients in Alberta, Canada from 1980 to 2001 and compared treatment with single dose of penicillin with 14-day course of oral doxycycline (100 mg twice a day) or oral tetracycline (500 mg 4 times a day). Serological treatment success was defined as a minimum 4-fold decrease in baseline rapid plasma reagin test antibody titer within 6 months, or > or =8-fold decrease within 12 months, or > or =16-fold decrease by 24 months. The median time to successful response was estimated, and factors associated with treatment success were identified by unadjusted logistic regression. RESULTS Of the 445 primary syphilis cases with available treatment outcome data, 420 (94.4%) received penicillin and 25 (5.6%) received doxycycline/tetracycline. The serological treatment success rate was 97.4% in the penicillin group (409/420) and 100% in the doxycycline/tetracycline group (25/25), and not significantly different. The estimated median time to serological treatment success was 72.0 days (mean=101.7, range 10-603) in penicillin and 43.0 days (mean=78.6, range 15-334) in doxycycline/tetracycline-treated patients; however, this difference was not statistically significant (P=0.16). CONCLUSION Doxycycline/tetracycline had a similarly high serological treatment success rate when compared with penicillin in the treatment of primary syphilis.

Predictors of Gonorrhea Reinfection in a Cohort of Sexually Transmitted Disease Patients in Alberta, Canada, 1991–2003

Objective: The objective of this study was to identify characteristics associated with reinfection in sexually transmitted disease (STD) patients in Alberta, Canada. Methods: A retrospective cohort of 5,701 STD patients with gonorrhea diagnosed between 1991 and 2003 were followed for incident gonorrhea. Rates of reinfection were estimated and multivariate logistic regression was used to identify patient characteristics associated with reinfection. Results: There were 568 reinfections in 460 individuals, with reinfection occurring at a median of 9.2 months with an incidence rate of 2.34 per 100 person-years (95% confidence interval [CI], 2.09–2.59). The highest risk of reinfection was found in patients of black ethnicity (adjusted hazard ratio [aHR], 3.31; 95% CI, 2.27–4.81), aboriginal ethnicity (aHR, 2.64; 95% CI, 1.96–3.56), those reporting homo-/bisexual practice (aHR, 2.05; 95% CI, 1.40–3.02), or treated at an STD clinic (aHR, 1.49; 95% CI, 1.15–1.94). Conclusion: The recognition of key demographic and behavioral characteristics can help focus interventions for patients at higher risk of gonorrhea reinfection.

Rethinking approaches to risk reduction for injection drug users: differences in drug type affect risk for HIV and hepatitis C virus infection through drug-injecting networks.

Objective: To identify and compare the drug-injecting network characteristics of cocaine and heroin injectors associated with a risk of HIV and hepatitis C virus (HCV). Methods: Active injectors were recruited from syringe exchange and methadone programs. Characteristics of all participants and their social networks were elicited. Regression analysis using generalized estimating equations examined the network characteristics of injection drug users (IDUs) relative to cocaine or heroin use in the past 6 months. Results: Of 282 IDUs, 228 (81%) used cocaine and 54 (19%) used heroin as their primary injected drug. In analyses adjusted for age and gender, cocaine injectors compared with heroin injectors were more likely to live in unstable housing (odds ratio [OR] = 3.55, 95% confidence interval [CI]: 1.49 to 8.40), self-report HCV infection (OR = 4.69, 95% CI: 2.14 to 10.31), and have a greater number of IDUs in their social network (OR = 1.61, 95% CI: 1.14 to 2.28) and were less likely to be polydrug users (OR = 0.06, 95% CI: 0.02 to 0.16) and to have social support (OR = 0.97, 95% CI: 0.95 to 0.99). The injecting networks of cocaine users were more likely to have members who were older (OR = 1.08, 95% CI: 1.04 to 1.12), had a history of shooting gallery use (OR = 2.27, 95% CI: 1.08 to 4.76), and had shorter relationships with the subject (OR = 0.91, 95% CI: 0.85 to 0.97). Conclusions: Beyond personal behaviors, HIV and HCV infection risk seems to be linked to social network traits that are determined by drug type. Prevention efforts to control the spread of bloodborne viruses among IDUs could benefit from tailoring interventions according to the type of drug used.

HIV and HCV discordant injecting partners and their association to drug equipment sharing

Our objective was to examine the association between HIV and HCV discordant infection status and the sharing of drug equipment by injection drug users (IDUs). IDUs were recruited from syringe exchange and methadone treatment programmes in Montreal, Canada. Characteristics of participants and their injecting partners were elicited using a structured questionnaire. Among 159 participants and 245 injecting partners, sharing of syringes and drug preparation equipment did not differ between concordant or discordant partners, although HIV-positive subjects did not share with HIV-negative injectors. Sharing of syringes was positively associated with discordant HIV status (OR=1.85) and negatively with discordant HCV status (OR=0.65), but both results were not statistically significant. Sharing of drug preparation equipment was positively associated with both discordant HIV (OR=1.61) and HCV (OR=1.18) status, but both results were non-significant. Factors such as large injecting networks, frequent mutual injections, younger age, and male gender were stronger predictors of equipment sharing. In conclusion, IDUs do not appear to discriminate drug equipment sharing partners based at least on their HCV infection status. The results warrant greater screening to raise awareness of infection status, post-test counselling to promote status disclosure among partners, and skill-building to avoid equipment sharing between discordant partners.

Social Network-Related Risk Factors for Bloodborne Virus Infections Among Injection Drug Users Receiving Syringes through Secondary Exchange

Secondary syringe exchange (SSE) refers to the exchange of sterile syringes between injection drug users (IDUs). To date there has been limited examination of SSE in relation to the social networks of IDUs. This study aimed to identify characteristics of drug injecting networks associated with the receipt of syringes through SSE. Active IDUs were recruited from syringe exchange and methadone treatment programs in Montreal, Canada, between April 2004 and January 2005. Information on each participant and on their drug-injecting networks was elicited using a structured, interviewer-administered questionnaire. Subjects’ network characteristics were examined in relation to SSE using regression models with generalized estimating equations. Of 218 participants, 126 were SSE recipients with 186 IDUs in their injecting networks. The 92 non-recipients reported 188 network IDUs. Networks of SSE recipients and non-recipients were similar with regard to network size and demographics of network members. In multivariate analyses adjusted for age and gender, SSE recipients were more likely than non-recipients to self-report being HIV-positive (OR = 3.56 [1.54–8.23]); require or provide help with injecting (OR = 3.74 [2.01–6.95]); have a social network member who is a sexual partner (OR = 1.90 [1.11–3.24]), who currently attends a syringe exchange or methadone program (OR = 2.33 [1.16–4.70]), injects daily (OR = 1.77 [1.11–2.84]), and shares syringes with the subject (OR = 2.24 [1.13–4.46]). SSE is associated with several injection-related risk factors that could be used to help focus public health interventions for risk reduction. Since SSE offers an opportunity for the dissemination of important prevention messages, SSE-based networks should be used to improve public health interventions. This approach can optimize the benefits of SSE while minimizing the potential risks associated with the practice of secondary exchange.

The Emergence of Extensively Drug-Resistant Tuberculosis (TB): TB/HIV Coinfection, Multidrug-Resistant TB and the Resulting Public Health Threat from Extensively Drug-Resistant TB, Globally and in Canada

Resistance to anti-tuberculosis (TB) drugs continues to present a major challenge to global public health. Resistance usually develops due to inadequate TB management, including improper use of medications, improper treatment regimens and failure to complete the treatment course. This may be due to an erratic supply or a lack of access to treatment, as well as to patient noncompliance. However, the emergence and transmission of drug-resistant TB, including the recently detected extensively drug resistant TB (XDR-TB), is driven, in part, by the synergistic relationship between TB and HIV (TB/HIV coinfection). There is evidence that persons infected with HIV are more likely to experience XDR-TB. XDR-TB is virtually untreatable with available TB medications. XDR-TB presents a grave global public health threat, particularly in high HIV prevalence settings. The present commentary discusses the current status of XDR-TB and draws attention to the urgency in addressing this problem, for both the global and Canadian public health networks. XDR-TB and the apparent XDR-TB and HIV association warrants further study.

Is H9N2 Avian Influenza Virus a Pandemic Potential

To the Editor: H1N1 and H3N2 influenza virus subtypes continue to cause human disease (1,2), while avian influenza A H5 and H7 subtypes spread globally among birds with limited an inefficient transmission to humans (3,4). Results from recent ferret research on the H9N2 subtype has demonstrated an increased theoretical threat to humans from the potential emergence of novel subtypes of avian influenza. In North America, there is no evidence of fixed lineages of the H9N2 avian influenza virus in land-based poultry; it is found in wild ducks and shore birds (5). In contrast, H9N2 remains endemic across Asia, mainly limited to outbreaks in domestic land-based poultry, but overshadowed as a pandemic threat by H5N1 bird flu, which has spread from Asia into Africa and Europe (6–9). However, there is evidence of interspecies transmission of H9N2 from land-based poultry to mammals, such as pigs and swine (10–13). Further evidence of an expanded mammalian host range includes efficient replication of H9N2 in mice without adaptation (14). H9N2 has already caused mild respiratory disease in humans in Hong Kong and mainland China in 1999 and 2003 (10,13,15,16). The six genes encoding the internal components of the H9N2 virus are similar to those found in a previous 1997 outbreak of H5N1 that caused several human deaths in Hong Kong (15). Furthermore, circulating H9N2 strains show human-like receptor specificity with amino acid leucine at position 226 at the receptor-binding site of human airway epithelial cells cultured in vitro (17). H9N2 isolated from live bird markets in Hong Kong possessed receptor specificity similar to human H3N2 viruses (18) and mutations similar to human H2N2 and H3N2 viruses, so the glycoproteins of the Hong Kong H9N2 viruses may potentially promote human infection. In a ferret model of transmission (9), the H9N2 avian reassortment subtype appears to be evolving. The H9N2 virus replicates in the respiratory tract of ferrets and can spread to noninfected ferrets (9). The amino acid leucine residue located at position 226 in the hemagglutinin receptor-binding site (instead of glutamine), plays a key role in human virus-like receptor specificity, and promotes transmission of the H9N2 virus in ferrets. Airborne transmission has not been detected. Mixing the H9N2 viral genes containing the surface glycoprotein and the six internal genes of a human H3N2 virus resulted in increased transmissibility. The model and reassortment mixing results raises concern about viral evolution as well as efficient pandemic transmission, and suggests that the H9N2 avian virus could be of pandemic importance (19). To conclude that H9N2 is the next human pandemic strain is premature at this time given the unfolding evidence. Yet, the possibility for competent nonavian intermediate reassorters generating novel and virulent pandemic strains of H9N2 (or other avain influenza strains) has increased given the recent raccoon influenza transmission findings (20). Additional study and timely surveillance of H9N2 is needed to identify any increments in viral adaptation to human beings. Studies should consider the widespread prevalence of the H9N2 virus in poultry, and co-circulation and mixing of avian H9N2 with human H3N2, H5, H7 and other avian and mammalian viruses.

Access to Sterile Injecting Equipment is More Important Than Awareness of HCV Status for Injection Risk Behaviors Among Drug Users

Awareness of hepatitis C virus (HCV) infection status is expected to influence risk behaviors. In 2004–2005, injection drug users (IDUs) recruited from syringe exchange programs (SEPs) and methadone clinics in Montreal, Canada, were interviewed on drug use behaviors (past 6 months) and HCV testing. Subjects (n = 230) were classified as low/intermediate risk (20.4% borrowed drug preparation equipment only) and high risk (19.6% borrowed syringes), and 54.5% reported being HCV positive. Logistic regression modeling showed that compared to no risk (60% borrowed nothing), low/intermediate risk was associated with fewer noninjecting social network members, poor physical health, and problems obtaining sterile injecting equipment. High risk was associated with all of these factors except social networks. HCV status was not associated with any level of risk. Improved access to sterile injecting equipment may be more important than knowledge of HCV status in reducing injection risks among this IDU population. The study limitations are noted and recommendations discussed.