Sustained Reduction in Sexual Behavior that May Pose a Risk of HIV Transmission Following Diagnosis During Early HIV Infection Among Gay Men in Vancouver, British Columbia.

Increased viral load during early HIV infection (EHI) disproportionately contributes to HIV transmission among gay men. We examined changes in sexual behavior that may pose a risk of HIV transmission (condomless anal sex (AS) with a serodiscordant or unknown status partner, CAS-SDU) in a cohort of 25 gay men newly diagnosed during EHI who provided information on 241 sexual partners at six time points following diagnosis. Twenty-two (88%) participants reported ≥1 AS partner (median time to first AS 80 days) and 12 (55%) reported ≥1 partnership involving CAS-SDU (median 116 days). In hierarchical generalized linear mixed effects models, AS was significantly less likely in all time periods following diagnosis and more likely with serodiscordant partners. The likelihood of CAS-SDU decreased three months after diagnosis and was higher in recently versus acutely infected participants. Most men in our study abstained from sex immediately after diagnosis with sustained longer-term reduction in CAS-SDU, confirming the importance of timely diagnosis during EHI.

A double-edged sword: does highly active antiretroviral therapy contribute to syphilis incidence by impairing immunity to Treponema pallidum?

BACKGROUND AND HYPOTHESIS: Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic. METHODS: We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects. CONCLUSIONS AND IMPLICATIONS: Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. pallidum. This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such as T. pallidum.

Diagnostic technologies in practice: gay men's narratives of acute or recent HIV infection diagnosis.

Diagnosing HIV-positive gay men through enhanced testing technologies that detect acute HIV infection (AHI) or recent HIV infection provides opportunities for individual and population health benefits. We recruited 25 men in British Columbia who received an acute (n = 13) or recent (n = 12) HIV diagnosis to engage in a longitudinal multiple-methods study over one year or longer. Our thematic analysis of baseline qualitative interviews revealed insights within men's accounts of technologically mediated processes of HIV discovery and diagnosis. Our analysis illuminated the dialectic of new HIV technologies in practice by considering the relationship between advances in diagnostics (e.g., nucleic acid amplification tests) and the users of these medical technologies in clinical settings (e.g., clients and practitioners). Technological innovations and testing protocols have shifted experiences of learning of one's HIV-positive status; these innovations have created new diagnostic categories that require successful interpretation and translation to be rendered meaningful, to alleviate uncertainty, and to support public health objectives.

HIV-negative gay men's accounts of using context-dependent sero-adaptive strategies.

We enrolled 166 gay and bisexual men who tested HIV-negative at a community sexual health clinic in Vancouver, British Columbia, into a year-long mixed-methods study. A subsample of participants who reported recent condomless anal sex (n = 33) were purposively recruited into an embedded qualitative study and completed two in-depth qualitative interviews. Analysis of baseline interviews elicited three narratives relevant to men's use of context- or relationally-dependent HIV-risk management strategies: (1) seroadaptive behaviours such as partner testing and negotiated safety agreements used with primary sexual partners, (2) serosorting and seroguessing when having sex with new partners and first-time hookups and (3) seroadaptive behaviours, including one or more of seropositioning/strategic positioning, condom serosorting and viral load sorting, used by participants who knowingly had sex with a serodiscordant partner. Within men's talk about sex, we found complex and frequently biomedically-informed rationale for seroadaptation in men's decisions to have what they understood to be various forms of safe or protected condomless anal sex. Our findings support the need for gay men's research and health promotion to meaningfully account for the multiple rationalities and seroadaptive strategies used for having condomless sex in order to be relevant to gay men's everyday sexual decision-making.

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.

Genetic diversity as a marker for timing infection in HIV-infected patients: evaluation of a 6-month window and comparison with BED.

BACKGROUND: It has been reported that the increase in human immunodeficiency virus (HIV) sequence diversity in drug resistance surveillance specimens may be used to classify the duration of HIV infection as <1 or >1 year. We describe a mixed base classifier (MBC) optimized to categorize the duration of subtype B infections as <6 or >6 months on the basis of sequences for drug resistance surveillance specimens and compared MBC findings with those of serologic methods. METHODS: The behavior of the MBC was examined across a range of thresholds for calling mixed bases. MBC performance was then evaluated using either complete pol sequences or sites reflecting evolutionary pressures (HLA selection sites, sites that increased in entropy over the course of infection, and codon positions). RESULTS: The MBC performance was optimal when secondary peaks on the sequencing chromatogram accounted for at least 15% of the area of primary peaks. A cutoff of <0.45% mixed bases in the pol region best identified recent infections (sensitivity = 82.7%, specificity = 78.8%), with improvement achieved by analyzing only sites that increased in entropy. CONCLUSIONS: In an extended data set of 1354 specimens classified by BED, the optimized MBC performed significantly better than a simple MBC (agreement, 68.98% vs 67.13%). If further validated, the MBC may prove beneficial for detecting recent infection and estimating the incidence of HIV infection.

Detection of Mycobacterium tuberculosis Complex Using the Xpert MTB/RIF Ultra Assay on the Stool of Pediatric Patients in Dushanbe, Tajikistan.

We report the findings of a prospective laboratory diagnostic accuracy study to evaluate the sensitivity, specificity, and predictive values of the Xpert MTB/RIF Ultra assay for Mycobacterium tuberculosis detection in fresh stool specimens from children under 15 years of age with confirmed tuberculosis (TB) disease from Dushanbe, Tajikistan. Six hundred eighty-eight (688) participants were enrolled from April 2019 to October 2021. We identified 16 participants (2.3%) with confirmed TB disease, defined as ≥1 TB sign/symptom plus microbiologic confirmation. With the Xpert MTB/RIF Ultra assay for stool, we found a sensitivity of 68.8% (95% CI, 46.0 to 91.5) and a specificity of 98.7% (95% CI, 97.8 to 99.5) in confirmed TB disease. Our results are comparable to other published studies; however, our cohort was larger and our confirmed TB disease rate lower than most. We also demonstrated that this assay was feasible to implement in a centralized hospital laboratory in a low-middle-income Central Asian country. However, we encountered obstacles such as lack of staffing, material ruptures, outdated government protocols, and decreased case presentation due to COVID-19. We found eight patients whose only positive test was an Xpert Ultra stool assay. None needed treatment during the study; however, three were treated later, suggesting such cases require close observation. Our report is the first from Central Asia and one of a few from a low-middle-income country. We believe our study demonstrates the generalizability of the Xpert MTB/RIF Ultra assay on fresh stool specimens from children and provides further evidence supporting WHO's approval of this diagnostic strategy. IMPORTANCE The importance of this report is that it provides further support for WHO's recent recommendation that fresh stool is an acceptable sample for GeneXpert TB testing in children, especially small children who often cannot produce an adequate sputum sample. Diagnosing TB in this age group is difficult, and many cases are missed, leading to unacceptable rates of TB illness and death. In our large cohort of children from Dushanbe, Tajikistan, the GeneXpert stool test was positive in 69% of proven cases of TB, and there were very few false-positive tests. We also showed that this diagnostic strategy was feasible to implement in a low-middle-income country with an inefficient health care delivery system. We hope that many more programs will adopt this form of diagnosing TB in children.

Using centralized laboratory data to monitor trends in herpes simplex virus type 1 and 2 infection in British Columbia and the changing etiology of genital herpes.

OBJECTIVES: Understanding the regional epidemiology of genital Herpes Simplex Virus (HSV) infections is important for clinical and public health practice, due to the increasing availability of type-specific serologic testing in Canada and the contribution of genital HSV-2 infection to ongoing HIV transmission. We used centralized laboratory data to describe trends in viral identifications of genital HSV in BC and assess the utility of these data for ongoing population surveillance. METHODS: Records of viral identifications (1997-2005) were extracted from the Provincial Public Health Microbiology & Reference Laboratory database. Classification as genital or other site was based on documented specimen site. We conducted a descriptive analysis of trends over time, and calculated odds of HSV-1 infection among individuals with genital herpes. RESULTS: Of 48,183 viral identifications, 56.8% were genital, 10.0% were peri-oral and 9.1% cutaneous; site was unknown for 22.9%. Among genital identifications, HSV-1 infection was more likely in females, younger age groups, and later time periods. The proportion of genital herpes due to HSV-1 increased over time from 31.4% to 42.8% in BC. CONCLUSIONS: Our analysis of population-level laboratory data demonstrates that the proportion of genital herpes due to HSV-1 is increasing over time in BC, particularly among women and younger age groups; this has implications for clinical practice including the interpretation of type-specific serology. Provincial viral identification data are useful for monitoring the distribution of genital HSV-1 and HSV-2 infections over time. Improving clinical documentation of specimen site would improve the utility of these data.

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.

Prediction of disease severity in young children presenting with acute febrile illness in resource-limited settings: a protocol for a prospective observational study.

INTRODUCTION: In rural and difficult-to-access settings, early and accurate recognition of febrile children at risk of progressing to serious illness could contribute to improved patient outcomes and better resource allocation. This study aims to develop a prognostic clinical prediction tool to assist community healthcare providers identify febrile children who might benefit from referral or admission for facility-based medical care. METHODS AND ANALYSIS: This prospective observational study will recruit at least 4900 paediatric inpatients and outpatients under the age of 5 years presenting with an acute febrile illness to seven hospitals in six countries across Asia. A venous blood sample and nasopharyngeal swab is collected from each participant and detailed clinical data recorded at presentation, and each day for the first 48 hours of admission for inpatients. Multianalyte assays are performed at reference laboratories to measure a panel of host biomarkers, as well as targeted aetiological investigations for common bacterial and viral pathogens. Clinical outcome is ascertained on day 2 and day 28.Presenting syndromes, clinical outcomes and aetiology of acute febrile illness will be described and compared across sites. Following the latest guidance in prediction model building, a prognostic clinical prediction model, combining simple clinical features and measurements of host biomarkers, will be derived and geographically externally validated. The performance of the model will be evaluated in specific presenting clinical syndromes and fever aetiologies. ETHICS AND DISSEMINATION: The study has received approval from all relevant international, national and institutional ethics committees. Written informed consent is provided by the caretaker of all participants. Results will be shared with local and national stakeholders, and disseminated via peer-reviewed open-access journals and scientific meetings. TRIAL REGISTRATION NUMBER: NCT04285021.

A population-based study of infectious syphilis rediagnosis in British Columbia, 1995-2005.

BACKGROUND: The Canadian province of British Columbia has experienced an ongoing heterosexual infectious syphilis epidemic since July 1997. In this study, we sought to characterize individuals who received a diagnosis of syphilis more than once in a cohort of reported cases from 1995 through 2005 in British Columbia. METHODS: Data for all cases of primary, secondary, and early latent syphilis from 1 January 1995 through 31 December 2005 were extracted from the British Columbia Provincial Sexually Transmitted Disease Surveillance Database. A descriptive analysis was conducted on all variables from the cases, and the incidence density of syphilis rediagnosis was calculated. Bivariate and multivariate analyses were conducted using Cox proportional hazards regression techniques to compare those who received a syphilis diagnosis once with those who received a syphilis diagnosis more than once within the 10-year period. RESULTS: By 2006, up to 10% of new cases of syphilis in the province were attributed to individuals who had received a previous diagnosis of syphilis within the preceding 10 years. In Cox proportional hazards regression analysis, individuals with the following characteristics were associated with an increased risk of becoming reinfected with syphilis: human immunodeficiency virus seropositivity, history of ever having gonorrhea or chlamydia, aboriginal ethnicity, and being a man who had sex with men. CONCLUSIONS: In this study, an increasing proportion of syphilis cases in British Columbia were attributed to a rediagnosis during the previous decade. Individuals with syphilis rediagnosis may represent a core group of transmitters who continue to engage in risky behavior and sustain the epidemic. Policies for prevention need to better consider the role of interventions to decrease rates of repeat diagnoses of sexually transmitted infections.

Priorities, Barriers, and Facilitators towards International Guidelines for the Delivery of Supportive Clinical Care during an Ebola Outbreak: A Cross-Sectional Survey.

During the Ebola outbreak, mortality reduction was attributed to multiple improvements in supportive care delivered in Ebola treatment units (ETUs). We aimed to identify high-priority supportive care measures, as well as perceived barriers and facilitators to their implementation, for patients with Ebola Virus Disease (EVD). We conducted a cross-sectional survey of key stakeholders involved in the response to the 2014⁻2016 West African EVD outbreak. Out of 57 email invitations, 44 responses were received, and 29 respondents completed the survey. The respondents listed insufficient numbers of health workers (23/29, 79%), improper tools for the documentation of clinical data (n = 22/28, 79%), insufficient material resources (n = 22/29, 76%), and unadapted personal protective equipment (n = 20/28, 71%) as the main barriers to the provision of supportive care in ETUs. Facilitators to the provision of supportive care included team camaraderie (n in agreement = 25/28, 89%), ability to speak the local language (22/28, 79%), and having treatment protocols in place (22/28, 79%). This survey highlights a consensus across various stakeholders involved in the response to the 2014⁻2016 EVD outbreak on a limited number of high-priority supportive care interventions for clinical practice guidelines. Identified barriers and facilitators further inform the application of guidelines.

Seeking sexual partners on the internet: a marker for risky sexual behaviour in men who have sex with men.

OBJECTIVE: In order to generate a generalizable estimate regarding risk for STI and HIV acquisition in men who have sex with men (MSM) who seek partners on the internet, we examined the sexual practices of MSM who seek partners on the internet compared to MSM who do not, using a community-based sample of MSM from British Columbia. METHODS: 'Sex Now', a questionnaire that was developed to examine trends in sexual behaviour in gay men, was offered to men attending Gay Pride events throughout the province of British Columbia, Canada between May and August 2004. Logistic regression analysis was used to model the association between seeking sexual partners online and other variables of interest, using odds ratio as the measure of association. RESULTS: Of the 2,312 MSM who completed the survey, 766 (33.1%) had used the internet to find a partner in the past year. In logistic regression analyses, MSM who found partners on the internet were more likely to have had more than 10 sexual partners in the past year (overall, insertive and receptive), and to engage in sexual activities in public venues. They were also more likely to agree with the statement "I think most guys in relationships have condom-free sex." MSM who sought partners on the net were more likely to be from specific geographic regions, including non-urban regions. Demographic characteristics, HIV status, and use of drugs were not significantly different between men who found partners on the internet and those who did not in multivariable modeling. DISCUSSION: MSM who sought to meet partners online had significantly more sexual partners, were more likely to be from specific geographic regions of the province and to have participated in seeking sexual partners in venues known to be associated with HIV and STI acquisition. This study confirms from a community-based sample of MSM that programming for prevention and treatment of HIV and STI need to be available and offered in the cyber setting, to ensure effective messaging and interventions reach this population.

Feasibility of self-collection of specimens for human papillomavirus testing in hard-to-reach women.

To study the feasibility of self-collected specimens for testing human papillomavirus (HPV) status among hard-to-reach women, outreach nurses recruited women in women's centres, shelters and alleys in Vancouver's Downtown Eastside. Of the 151 participants for whom samples were available, 43 (28.5%) tested positive for high-risk HPV. Outreach nurses were able to recontact 81.4% of the participants who tested positive and referred them for further testing. About 14% (21/151) of participants had never received a Papanicolaou smear in British Columbia, as compared with 8.3% (608/7336) of women in the BC general population (p < 0.05). This difference suggests that self-collection of specimens for HPV testing is a feasible method to reach women who have not previously participated in cervical cancer screening programs.

Sex-work harm reduction.

Sex work is an extremely dangerous profession. The use of harm-reduction principles can help to safeguard sex workers' lives in the same way that drug users have benefited from drug-use harm reduction. Sex workers are exposed to serious harms: drug use, disease, violence, discrimination, debt, criminalisation, and exploitation (child prostitution, trafficking for sex work, and exploitation of migrants). Successful and promising harm-reduction strategies are available: education, empowerment, prevention, care, occupational health and safety, decriminalisation of sex workers, and human-rights-based approaches. Successful interventions include peer education, training in condom-negotiating skills, safety tips for street-based sex workers, male and female condoms, the prevention-care synergy, occupational health and safety guidelines for brothels, self-help organisations, and community-based child protection networks. Straightforward and achievable steps are available to improve the day-to-day lives of sex workers while they continue to work. Conceptualising and debating sex-work harm reduction as a new paradigm can hasten this process.

The impact of syphilis mass treatment one year later: self-reported behaviour change among participants.

In 2000, syphilis mass treatment using oral azithromycin was delivered to at-risk British Columbians during a sex trade-related outbreak. The initiative included education, counselling and referral. This cross-sectional, observational study examines knowledge, attitudes and self-reported behaviour after one year among mass treatment participants compared with eligible non-participants. Participants self-reported positive changes: reduction in sexual partners overall (P=0.001) and for sex workers (P<0.01), decrease in unprotected oral sex (P=0.03), knowledge of asymptomatic syphilis (P=0.02), positive attitudes to mass treatment (P=0.02) and to the street nurses (P=0.01). Increased awareness was associated with increased condom use for vaginal sex overall (P=0.02) and for sex workers (P=0.03) and increased condom use for oral sex (P=0.05). There was no difference in syphilis incidence. Syphilis outbreak interventions that include education, support and referral can result in long-term positive behaviour changes.

STD and HIV counseling practices of British Columbia primary care physicians.

This study evaluated British Columbian primary care physicians' use of sexually transmitted disease (STD) and HIV counseling guidelines. The authors sought to assess barriers to integrated HIV and STD testing and counseling, with the objective of developing and revising practice guidelines to meet the needs of primary care physicians in diverse settings. The BC College of Physicians and Surgeons membership of general practice/family medicine practitioners was stratified by practitioner location; 1200 physicians were randomly selected to receive a mailed self-administered questionnaire. Four hundred seven completed questionnaires were returned. Female physicians reported better adherence to practice guidelines on many items than their male counterparts. A minority of primary care physicians routinely integrated HIV and STD testing and counseling. Physicians in nonurban areas were more likely to report that they lacked sufficient information on HIV and STD risk and prevention. Although male primary care physicians in British Columbia were more likely to provide care for people with HIV infection, female physicians were more likely to undertake ongoing screening for sexual risk behavior and sexually transmitted infections (STIs) among their HIV-positive patients. Clinical practice guidelines are theoretically equally available to all physicians, but they are not universally used. Physicians may not receive adequate training in sexual health during their medical education; continuing education opportunities may be limited to physicians outside of urban centres. Accessible and relevant continuing medical education in novel formats are needed to address the gap between ideal and actual practice in HIV and STD prevention, treatment, and care in Canada.

Prenatal and congenital syphilis in British Columbia.

OBJECTIVE: To describe the incidence of maternal syphilis and the corresponding rate of infection in exposed neonates in British Columbia before and after a serious outbreak of infectious syphilis in the heterosexual population. METHODS: We conducted a retrospective chart review of pregnant women with positive syphilis serology and reported cases of congenital syphilis in British Columbia from 1994 to 2003. Clinical charts were reviewed for demographic information, staging of maternal syphilis, and stage of pregnancy when treatment was received. The primary outcome measure was the number of cases of congenital syphilis. We conducted a 2-sided z-test and Fisher's exact test to determine differences in the proportion of infectious syphilis in mothers and the number of cases of congenital syphilis before and during the major outbreak. RESULTS: In 389 478 live births in British Columbia between 1994 and 2003, 77% of mothers had prenatal syphilis serology. A diagnosis of syphilis was made in 183 mothers, resulting in 5 cases of congenital syphilis. Four of these were in infants whose mothers did not undergo prenatal syphilis testing. The proportion of pregnant women with infectious syphilis was significantly higher after the onset of a major outbreak of syphilis in the community than it was before (P = 0.001), but there was no significant difference in the number of cases of congenital syphilis (3 before and 2 after the outbreak, P = 0.36). CONCLUSION: Although syphilis rates in British Columbia during the study period rose steadily, the prevalence of congenital syphilis remained low. Our findings suggest that, in the context of a major outbreak, universal screening and prenatal syphilis testing may contribute to controlling rates of congenital syphilis.