Can laboratory HIV and infectious syphilis data inform future pre-exposure prophylaxis use in women in Ontario, Canada?

OBJECTIVES: Infectious syphilis has been proposed as an indication for HIV pre-exposure prophylaxis (PrEP) in women. We explored how many women experienced HIV seroconversion after being diagnosed with syphilis in Ontario between 20 April 2010 and 31 December 2021. METHODS: Through deterministic linkage of laboratory data at the Public Health Ontario laboratory, which conducts the vast majority of syphilis and HIV testing in Ontario, we quantified the number of females with positive syphilis diagnoses who subsequently exhibited HIV seroconversion between April 2010 and December 2021. New HIV cases were identified by diagnostic serology or HIV viral load test result of ≥20 copies/mL at least 60 days after the positive syphilis test. We report aggregate numbers of women with new laboratory evidence of HIV infection after their first positive syphilis test. RESULTS: Among 7957 women with positive syphilis tests during the study period, 6554 (82.4%) had linkable HIV serology tests and 133 (1.7%) ever tested HIV positive. With further linkage to viral load data, the number of women who ever had laboratory evidence of HIV infection increased to 184 (2.3%). However, when restricting to women whose first positive HIV test or HIV viral load occurred after their first positive syphilis test, this number decreased to 34 (0.4%). The median (IQR) time between the positive syphilis test and the first laboratory evidence of HIV was 551 (IQR=226-1159) days. CONCLUSION: Although it is clinically appropriate to recommend HIV PrEP to women with syphilis, Ontario surveillance data suggest that the population-level impact of this strategy on the HIV epidemic in Ontario would have been modest during this 11-year period. Future studies should explore additional ways of prioritising women for PrEP.

Association Between Cycle Threshold Value and Vaccination Status Among Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant Cases in Ontario, Canada, in December 2021.

Background: Increased immune evasion by emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and occurrence of breakthrough infections raise questions about whether coronavirus disease 2019 vaccination status affects SARS-CoV-2 viral load among those infected. This study examined the relationship between cycle threshold (Ct) value, which is inversely associated with viral load, and vaccination status at the onset of the Omicron wave onset in Ontario, Canada. Methods: Using linked provincial databases, we compared median Ct values across vaccination status among polymerase chain reaction-confirmed Omicron variant SARS-CoV-2 cases (sublineages B.1.1.529, BA.1, and BA.1.1) between 6 and 30 December 2021. Cases were presumed to be Omicron based on S-gene target failure. We estimated the relationship between vaccination status and Ct values using multiple linear regression, adjusting for age group, sex, and symptom status. Results: Of the 27 029 presumed Omicron cases in Ontario, the majority were in individuals who had received a complete vaccine series (87.7%), followed by unvaccinated individuals (8.1%), and those who had received a booster dose (4.2%). The median Ct value for post-booster dose individuals (18.3 [interquartile range, 15.4-22.3]) was significantly higher than that for unvaccinated (17.9 [15.2-21.6]; P = .02) and post-vaccine series individuals (17.8 [15.3-21.5]; P = .005). Post-booster dose cases remained associated with a significantly higher median Ct value than cases in unvaccinated individuals (P ≤ .001), after adjustment for covariates. Compared with values in persons aged 18-29 years, Ct values were significantly lower among most age groups >50 years. Conclusions: While slightly lower Ct values were observed among unvaccinated individuals infected with Omicron compared with post-booster dose cases, further research is required to determine whether a significant difference in secondary transmission exists between these groups.

Pulmonary Nontuberculous Mycobacteria, Ontario, Canada, 2020.

We measured annual prevalence of microbiologically defined nontuberculous mycobacterial lung disease in Ontario, Canada. Mycobacterium avium prevalence was 13 cases/100,000 persons in 2020, a 2.5-fold increase from 2010, indicating a large increase in true M. avium lung disease. During the same period, M. xenopi decreased nearly 50%, to 0.84 cases/100,000 persons.

Evaluating HIV Rapid/Point of Care Testing among Risk Factor Groups in Ontario, 2011 to 2018.

OBJECTIVES: In 2014, Ontario's Point-of-Care (POC) test providers were advised to focus efforts on provincially defined priority populations who experience a greater risk of HIV. Our objective was to describe the POC program before, during and after this change, including tester characteristics, follow-up testing results, positive predictive value (PPV) over time, and trends and characteristics of those with reactive test results without a confirmatory serological specimen. METHODS: Test-level data of POC screening and confirmatory results were extracted from the Public Health Ontario HIV Datamart. Final test results were defined based on results of the confirmatory blood sample, or the POC test for "non-reactive" tests. Testing volumes, percent of total tests, percent positivity and PPV were calculated overall, annually, and by exposure group. RESULTS: Overall testing volumes decreased by 39.8% between 2014 and 2018. The majority of confirmed positive tests were in the men who have sex with men (MSM) exposure category, followed by HIV-endemic and heterosexual - no identified risk (heterosexual-NIR). Overall percent positivity decreased from 0.59% in 2011 to 0.42% in 2015 (change of 0.17%, 95% CI 0.03% to 0.31%), increasing to 0.69% in 2018 (change of 0.27%, 95% CI 0.20% to 0.34%). Increases in percent positivity corresponded with a decrease in the overall proportion of tests conducted in low-risk populations. When compared to the heterosexual-NIR category, PPV was significantly higher for men who have sex with men - people who use injection drugs (MSM-PWID) (52.7% compared to 100%, P < .001), MSM (52.7% compared to 95.4%, P < .001), HIV-endemic (52.7% compared to 91.5%, P < .001), heterosexual - partner with identified risk (heterosexual-PIR) (52.7% compared to 77.3%, P = .042), and people who use injection drugs (PWID) (52.7% compared to 81.3%, P = 0.007). A total of 13.5% of reactive POC results did not have a serological sample submitted. CONCLUSIONS: Targeted testing towards populations at higher risk of HIV improved the overall test performance characteristics of Ontario's POC testing program. While not unexpected, the large discrepancies between PPV in higher-risk, compared to lower-risk populations, suggests the need for greater awareness and messaging of the likelihood of false positive test results in different populations.

Monkeypox Virus Detection in Different Clinical Specimen Types.

A global monkeypox outbreak began in May 2022. Limited data exist on specimen type performance in associated molecular diagnostics. Consequently, a diverse range of specimen sources were collected in the initial weeks of the outbreak in Ontario, Canada. Our clinical evaluation identified skin lesions as the optimal diagnostic specimen source.

Real-Time RT-PCR Allelic Discrimination Assay for Detection of N501Y Mutation in the Spike Protein of SARS-CoV-2 Associated with B.1.1.7 Variant of Concern.

The N501Y amino acid mutation caused by a single point substitution A23063T in the spike gene of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is possessed by three variants of concern (VOCs), B.1.1.7, B.1.351, and P.1. A rapid screening tool using this mutation is important for surveillance during the coronavirus disease 2019 (COVID-19) pandemic. We developed and validated a single nucleotide polymorphism real-time reverse transcription PCR assay using allelic discrimination of the spike gene N501Y mutation to screen for potential variants of concern and differentiate them from SARS-CoV-2 lineages without the N501Y mutation. A total of 160 clinical specimens positive for SARS-CoV-2 were characterized as mutant (N501Y) or N501 wild type by Sanger sequencing and were subsequently tested with the N501Y single nucleotide polymorphism real-time reverse transcriptase PCR assay. Our assay, compared to Sanger sequencing for single nucleotide polymorphism detection, demonstrated positive percent agreement of 100% for all 57 specimens displaying the N501Y mutation, which were confirmed by Sanger sequencing to be typed as A23063T, including one specimen with mixed signal for wild type and mutant. Negative percent agreement was 100% in all 103 specimens typed as N501 wild type, with A23063 identified as wild type by Sanger sequencing. The identification of circulating SARS-CoV-2 lineages carrying an N501Y mutation is critical for surveillance purposes. Current identification methods rely primarily on Sanger sequencing or whole-genome sequencing, which are time consuming, labor intensive, and costly. The assay described herein is an efficient tool for high-volume specimen screening for SARS-CoV-2 VOCs and for selecting specimens for confirmatory Sanger or whole-genome sequencing. IMPORTANCE During the coronavirus disease 2019 (COVID-19) pandemic, several variants of concern (VOCs) have been detected, for example, B.1.1.7, B.1.351, P.1, and B.1.617.2. The VOCs pose a threat to public health efforts to control the spread of the virus. As such, surveillance and monitoring of these VOCs is of the utmost importance. Our real-time RT-PCR assay helps with surveillance by providing an easy method to quickly survey SARS-CoV-2 specimens for VOCs carrying the N501Y single nucleotide polymorphism (SNP). Samples that test positive for the N501Y mutation in the spike gene with our assay can be sequenced to identify the lineage. Thus, our assay helps to focus surveillance efforts and decrease turnaround times.

Detection of the novel SARS-CoV-2 European lineage B.1.177 in Ontario, Canada.

Background: Travel-related dissemination of SARS-CoV-2 continues to contribute to the global pandemic. A novel SARS-CoV-2 lineage (B.1.177) reportedly arose in Spain in the summer of 2020, with subsequent spread across Europe linked to travel by infected individuals. Surveillance and monitoring through the use of whole genome sequencing (WGS) offers insights into the global and local movement of pathogens such as SARS-CoV-2 and can detect introductions of novel variants. Methods: We analysed the genomes of SARS-CoV-2 sequenced for surveillance purposes from specimens received by Public Health Ontario (Sept 6 - Oct 10, 2020), collected from individuals in eastern Ontario, which comprised the study sample. Taxonomic lineages were identified using pangolin (v2.08) and phylogenetic analysis incorporated publicly available genomes covering the same time period as the study sample. Epidemiological data collected from laboratory requisitions and standard reportable disease case investigation was integrated into the analysis. Results: Genomic surveillance identified a COVID-19 case with SARS-CoV-2 lineage B.1.177 from an individual in eastern Ontario in late September, 2020. The individual had recently returned from Europe. Genomic analysis with publicly available data indicate the most closely related genomes to this specimen were from Southern Europe. Genomic surveillance did not identify further cases with this lineage. Conclusions: Genomic surveillance allowed for early detection of a novel SARS-CoV-2 lineage in Ontario which was deemed to be travel related. This type of genomic-based surveillance is a key tool to measure the effectiveness of public health measures such as mandatory self-isolation for returned travellers, aimed at preventing onward transmission of newly introduced lineages of SARS-CoV-2.

Global trends in incidence rates of childhood liver cancers: A systematic review and meta-analysis.

BACKGROUND: Childhood liver cancers are relatively rare, hence inferences on incidence trends over time are limited by lack of precision in most studies. OBJECTIVE: To conduct a systematic review and meta-analysis of published contemporary trends on childhood liver cancer incidence rates worldwide. DATA SOURCES: PubMed, EMBASE, CINAHL, Web of Science. STUDY SELECTION AND DATA EXTRACTION: English-language peer-reviewed articles published from 1 January 2008 to 1 December 2019 that presented quantitative estimates of incidence trends for childhood liver cancer and diagnostic subgroups. Review was conducted per PRISMA guidelines. Two authors independently extracted data and critically assessed studies. SYNTHESIS: Random effects meta-analysis models were used to estimate pooled incidence trends by diagnostic subgroups. Heterogeneity was measured using the Q and I2 statistics and publication bias evaluated using Egger's test. RESULTS: Eighteen studies were included, all based on population-based cancer registries. Trends were reported on average for 18 years. Overall pooled estimates of the annual percentage change (APC) were 1.4 (95% confidence interval [CI] 0.5, 2.3) for childhood liver cancers, 2.8 (95% CI 1.8, 3.8) for hepatoblastoma and -3.0 (95% CI -11.0, 4.9) for hepatocellular carcinoma. Sub-group analysis by region indicated increasing trends for childhood liver cancers in North America/Europe/Australia (APC 1.7, 95% CI 0.7, 2.8) whereas corresponding trends were stable in Asia (APC 1.4, 95%CI -0.3, 2.7). Publication bias was not detected for any of these analyses. The I2 statistic indicated that the heterogeneity among included studies was low for combined liver cancers, moderate for hepatoblastoma and high for hepatocellular carcinoma. CONCLUSIONS: Incidence is increasing for childhood liver cancers and the most commonly diagnosed subgroup hepatoblastoma. Lack of knowledge of the etiology of childhood liver cancers limited the ability to understand the reasons for observed incidence trends. This review highlighted the need for ongoing monitoring of incidence trends and etiological studies.

Cohort profile: Development and profile of a population-based, retrospective cohort of diagnosed people living with HIV in Ontario, Canada (Ontario HIV Laboratory Cohort).

PURPOSE: Population-based cohorts of diagnosed people living with HIV (PLWH) are limited worldwide. In Ontario, linked HIV diagnostic and viral load (VL) test databases are centralised and contain laboratory data commonly used to measure engagement in HIV care. We used these linked databases to create a population-based, retrospective cohort of diagnosed PLWH in Ontario, Canada. PARTICIPANTS: A datamart was created by integrating diagnostic and VL databases and linking records at the individual level. These databases contain information on laboratory test results and sociodemographic/clinical information collected on requisition/surveillance forms. Datamart individuals enter our cohort with the first record of a nominal HIV-positive diagnostic test (1985-2015) or VL test (1996-2015), and remain unless administratively lost to follow-up (LTFU; no VL test for >2 years and no VL test in later years). Non-nominal diagnostic tests are excluded as they lack identifying information to permit linkage to other tests. However, individuals diagnosed non-nominally are included in the cohort with record of a VL test. The LTFU rule is applied to indirectly censor for death/out-migration. FINDINGS TO DATE: As of the end of 2015, the datamart contained 40 372 HIV-positive diagnostic tests and 23 851 individuals with ≥1 VL test. Almost half (46.3%) of the diagnostic tests were non-nominal and excluded, although this was lower (~15%) in recent years. Overall, 29 587 individuals have entered the cohort-contributing 229 302 person-years of follow-up since 1996. Between 2000 and 2015, the number of diagnosed PLWH (cohort individuals not LTFU) increased from 8859 to 16 110, and the percent who were aged ≥45 years increased from 29.1% to 62.6%. The percent of diagnosed PLWH who were virally suppressed (<200 copies/mL) increased from 40.7% in 2000 to 79.5% in 2015. FUTURE PLANS: We plan to conduct further analyses of HIV care engagement and link to administrative databases with information on death, migration, physician billing claims and prescriptions. Linkage to other data sources will address cohort limitations and expand research opportunities.

Trends in HIV care cascade engagement among diagnosed people living with HIV in Ontario, Canada: A retrospective, population-based cohort study.

BACKGROUND: The HIV cascade is an important framework for assessing systems of care, but population-based assessment is lacking for most jurisdictions worldwide. We measured cascade indicators over time in a population-based cohort of diagnosed people living with HIV (PLWH) in Ontario, Canada. METHODS: We created a retrospective cohort of diagnosed PLWH using a centralized laboratory database with HIV diagnostic and viral load (VL) test records linked at the individual-level. Individuals enter the cohort with record of a nominal HIV-positive diagnostic test or VL test, and remain unless administratively lost to follow-up (LTFU, >2 consecutive years with no VL test and no VL test in later years). We calculated the annual percent of diagnosed PLWH (cohort individuals not LTFU) between 2000 and 2015 who were in care (≥1 VL test), on ART (as documented on VL test requisition) or virally suppressed (<200 copies/ml). We also calculated time from diagnosis to linkage to care and viral suppression among individuals newly diagnosed with HIV. Analyses were stratified by sex and age. Upper/lower bounds were calculated using alternative indicator definitions. RESULTS: The number of diagnosed PLWH increased from 8,859 (8,859-11,389) in 2000 to 16,110 (16,110-17,423) in 2015. Over this 16-year period, the percent of diagnosed PLWH who were: in care increased from 81% (63-81%) to 87% (81-87%), on ART increased from 55% (34-60%) to 81% (70-82%) and virally suppressed increased from 41% (23-46%) to 80% (67-81%). Between 2000 and 2014, the percent of newly diagnosed individuals who linked to care within three months of diagnosis or achieved viral suppression within six months of diagnosis increased from 67% to 82% and from 22% to 42%, respectively. Estimates were generally lower for females and younger individuals. DISCUSSION: HIV cascade indicators among diagnosed PLWH in Ontario improved between 2000 and 2015, but gaps still remain-particularly for younger individuals.

Spatial epidemiology of the syphilis epidemic in Toronto, Canada.

BACKGROUND: Urban centers across Canada and the United States have battled syphilis epidemics with high rates of human immunodeficiency virus (HIV) coinfection for over a decade. We examined the spatial epidemiology of syphilis over time for Toronto (Canada) with the intention of forming new insights and strategies for restoring low syphilis rates. METHODS: Syphilis incidence rates, HIV-syphilis coinfection, and sexual risk behavior prevalences were estimated and mapped from primary, secondary, early latent syphilis cases reported to Toronto Public Health between January 1, 2006, and December 31, 2010, using ArcGIS 9.0. Geographic clusters of significantly elevated syphilis incidence rates were identified using SaTScan 9.0. The relationship between syphilis incidence rates and sociocultural factors was modeled using the Besag, York, and Mollie model. RESULTS: Between 2006 and 2010, syphilis incidence rates were high in Toronto's downtown core area, intensified, and spread outward initiating 3 independent outbreak areas. HIV coinfection was high (47%); however, no spatial clustering was identified. Syphilis incidence rates, HIV coinfection, and behavioral risk factors promoting sexually transmitted infection transmission were high outside the core area, suggesting that peripheral sexual networks may be influencing high syphilis infection rates both inside and outside the core. CONCLUSIONS: Toronto's syphilis epidemic is mature. Response, resources, and intervention activities should target core and noncore areas.

Does core area theory apply to sexually transmitted diseases in rural environments?

BACKGROUND: Our objective was to determine the extent to which geographical core areas for gonorrhea and syphilis are located in rural areas as compared with urban areas. METHODS: Incident gonorrhea (January 1, 2005-December 31, 2010) and syphilis (January 1, 1999-December 31, 2010) rates were estimated and mapped by census tract and quarter. Rurality was measured using percent rural and rural-urban commuting area (rural, small town, micropolitan, or urban). SaTScan was used to identify spatiotemporal clusters of significantly elevated rates of infection. Clusters lasting 5 years or longer were considered core areas; clusters of shorter duration were considered outbreaks. Clusters were overlaid on maps of rurality and qualitatively assessed for correlation. RESULTS: Twenty gonorrhea core areas were identified: 65% were in urban centers, 25% were in micropolitan areas, and the remaining 10% were geographically large capturing combinations of urban, micropolitan, small town, and rural environments. Ten syphilis core areas were identified with 80% in urban centers and 20% capturing 2 or more rural-urban commuting areas. All 10 (100%) of the syphilis core areas overlapped with gonorrhea core areas. CONCLUSIONS: Gonorrhea and syphilis rates were high for rural parts of North Carolina; however, no core areas were identified exclusively for small towns or rural areas. The main pathway of rural sexually transmitted disease (STI) transmission may be through the interconnectedness of urban, micropolitan, small town, and rural areas. Directly addressing STIs in urban and micropolitan communities may also indirectly help address STI rates in rural and small town communities.

Sexually transmitted disease core theory: roles of person, place, and time.

The authors' purpose was to expand sexually transmitted disease core theory by examining the roles of person, place, and time in differentiating geographic core areas from outbreak areas. The authors mapped yearly census-tract-level syphilis rates for San Francisco, California, based on new primary and secondary syphilis cases reported to the San Francisco City sexually transmitted disease surveillance program between January 1, 1985, and December 31, 2007. SaTScan software (Information Management Services, Inc., Silver Spring, Maryland) was used to identify geographic clusters of significantly elevated syphilis rates over space and time. The authors graphed epidemic curves for 1) core areas, 2) outbreak areas, 3) neither core nor outbreak areas, and 4) noncore areas, where noncore areas included outbreaks, and stratified these curves according to demographic characteristics. Five clusters of significantly elevated primary and secondary syphilis rates were identified. A 5-year threshold was useful for differentiating core clusters from outbreak clusters. Epidemic curves for core areas, outbreak areas, neither core nor outbreak areas, and noncore areas were perfectly synchronized in phase trends and wavelength over time, even when broken down by demographic characteristics. Between epidemics, the occurrence of syphilis affected all demographic groups equally. During an epidemic, a temporary disparity in syphilis occurrence arose and a homogeneous core group of cases could be defined.

Are neighborhood sociocultural factors influencing the spatial pattern of gonorrhea in North Carolina?

PURPOSE: To determine if the spatial pattern of gonorrhea observed for North Carolina was influenced by neighborhood-level sociocultural determinants of health, including race/ethnicity. METHODS: A generalized linear mixed model with spatially correlated random effects was fit to measure the influence of socio-cultural factors on the spatial pattern of gonorrhea reported to the North Carolina State Health Department (January 1, 2005 to March 31, 2008). RESULTS: Neighborhood gonorrhea rates increased as the percent single mothers increased (25th to 75th neighborhood percentile Relative Rate 1.18, 95% CI 1.12, 1.25), and decreased as socioeconomic status increased (Relative Rate 0.89, 95% CI 0.84, 0.95). Increasing numbers of men in neighborhoods with more women than men did not change the gonorrhea rate, but was associated with decreased rates in neighborhoods with more men than women. Living in the mountains was protective for all race/ethnicities. Rurality was associated with decreased rates for Blacks and increased rates for Native Americans outside the mountains. PURPOSE: Neighborhood-level sociocultural factors, primarily those indicative of neighborhood deprivation, explained a significant proportion of the spatial pattern of gonorrhea in both urban and rural communities. Race/ethnicity was an important proxy for social and cultural factors not captured by measures of socioeconomic status.

HIV mortality and infection in India: estimates from nationally representative mortality survey of 1.1 million homes.

OBJECTIVE: To determine the rates of death and infection from HIV in India. DESIGN: Nationally representative survey of deaths. SETTING: 1.1 million homes in India. Population 123,000 deaths at all ages from 2001 to 2003. MAIN OUTCOME MEASURES: HIV mortality and infection. RESULTS: HIV accounted for 8.1% (99% confidence interval 5.0% to 11.2%) of all deaths among adults aged 25-34 years. In this age group, about 40% of deaths from HIV were due to AIDS, 26% were due to tuberculosis, and the rest were attributable to other causes. Nationally, HIV infection accounted for about 100,000 (59,000 to 140,000) deaths or 3.2% (1.9% to 4.6%) of all deaths among people aged 15-59 years. Deaths from HIV were concentrated in the states and districts with higher HIV prevalence and in men. The mortality results imply an HIV prevalence at age 15-49 years of 0.26% (0.13% to 0.39%) in 2004, comparable to results from a 2005/6 household survey that tested for HIV (0.28%). Collectively, these data suggest that India had about 1.4-1.6 million HIV infected adults aged 15-49 years in 2004-6, about 40% lower than the official estimate of 2.3 million for 2006. All cause mortality increased in men aged 25-34 years between 1997 and 2002 in the states with higher HIV prevalence but declined after that. HIV prevalence in young pregnant women, a proxy measure of incidence in the general population, fell between 2000 and 2007. Thus, HIV mortality and prevalence may have fallen further since our study. CONCLUSION: HIV attributable death and infection in India is substantial, although it is lower than previously estimated.