Large scale analysis of the SARS-CoV-2 main protease reveals marginal presence of nirmatrelvir-resistant SARS-CoV-2 Omicron mutants in Ontario, Canada, December 2021-September 2023.

Background: In response to the COVID-19 pandemic, a new oral antiviral called nirmatrelvir-ritonavir (PaxlovidTM) was authorized for use in Canada in January 2022. In vitro studies have reported mutations in Mpro protein that may be associated with the development of nirmatrelvir resistance. Objectives: To survey the prevalence, relevance and temporal patterns of Mpro mutations among SARS-CoV-2 Omicron lineages in Ontario, Canada. Methods: A total of 93,082 Mpro gene sequences from December 2021 to September 2023 were analyzed. Reported in vitro Mpro mutations were screened against our database using in-house data science pipelines to determine the nirmatrelvir resistance. Negative binomial regression was conducted to analyze the temporal trends in Mpro mutation counts over the study time period. Results: A declining trend was observed in non-synonymous mutations of Mpro sequences, showing a 7.9% reduction (95% CI: 6.5%-‬9.4%; p<0.001) every 30 days. The P132H was the most prevalent mutation (higher than 95%) in all Omicron lineages. In vitro nirmatrelvir-resistant mutations were found in 3.12% (n=29/929) Omicron lineages with very low counts, ranging from one to 19. Only two mutations, A7T (n=19) and M82I (n=9), showed temporal presence among the BA.1.1 in 2022 and the BQ.1.2.3 in 2022, respectively. Conclusion: The observations suggest that, as of September 2023, no significant or widespread resistance to nirmatrelvir has developed among SARS-CoV-2 Omicron variants in Ontario. This study highlights the importance of creating automated monitoring systems to track the emergence of nirmatrelvir-resistant mutations within the SARS-CoV-2 virus, utilizing genomic data generated in real-time.

Testing for extragenital Neisseria gonorrhoeae and Chlamydia trachomatis: At-home pharyngeal and rectal self-swabs are non-inferior to those completed in healthcare settings.

INTRODUCTION: The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the oropharynx and rectum for men who have sex with men (MSM), and because at-home self-collected swabs for these infections are not licensed by Health Canada or the United States Food and Drug Administration, decreased accessed to in-person care during and since the COVID19 pandemic potentially means missed case findings. OBJECTIVES: To evaluate the performance of at-home self-collected pharyngeal and rectal swabs for gonorrhea and chlamydia nucleic acid amplification testing. METHODOLOGY: All persons who contacted our Sexual Health Clinic and who had a clinical indication to complete oral and/or rectal swabs for gonorrhea and chlamydia were invited to complete at-home swabs in advance of their scheduled appointments. We mailed swabs and instructions to those who consented. Participants brought these swabs to their scheduled in clinic appointments, where we repeated the same swabs. All matching swabs were sent to the laboratory for analysis to determine concordance. RESULTS: From September 8, 2022 to July 18, 2023, we enrolled 296 eligible participants who provided 1184 swabs. For analysis, cancelled specimens and specimens with invalid results were excluded, leaving 1032 swabs for comparison. We identified 66 STI diagnoses in 47 unique participants. Overall accuracy was high (exceeding 99%), except for rectal chlamydia, which was 96.0%. While the performance of self-swabs for chlamydia was lower compared to gonorrhea, at-home swabs identified six chlamydia infections that were missed by in-clinic collected swabs (two pharyngeal, four rectal). Removing these six cases as "false positives" increased overall accuracy for chlamydia detection to 99.7% (pharyngeal) and 97.8% (rectal). CONCLUSION: Self-collected at-home swabs had good performance acceptable for gonorrhea and chlamydia nucleic acid amplification testing.

Longitudinal Analysis of Mpox Virus DNA Detectability From Multiple Specimen Types During Acute Illness: A Cohort Study.

Background: Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce. Methods: We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation. Results: Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75-45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0-47.9) and 22.4 (16.6-29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0-12.1) and 0 (0-0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P > .05). Conclusions: MPXV DNA detectability varies by specimen type and persists for over 3-4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study.

2023/24 mid-season influenza and Omicron XBB.1.5 vaccine effectiveness estimates from the Canadian Sentinel Practitioner Surveillance Network (SPSN).

The Canadian Sentinel Practitioner Surveillance Network reports mid-season 2023/24 influenza vaccine effectiveness (VE) of 63% (95% CI: 51-72) against influenza A(H1N1)pdm09, lower for clade 5a.2a.1 (56%; 95% CI: 33-71) than clade 5a.2a (67%; 95% CI: 48-80), and lowest against influenza A(H3N2) (40%; 95% CI: 5-61). The Omicron XBB.1.5 vaccine protected comparably well, with VE of 47% (95% CI: 21-65) against medically attended COVID-19, higher among people reporting a prior confirmed SARS-CoV-2 infection at 67% (95% CI: 28-85).

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.

Mpox outbreak control indicators used in Ontario, Canada: May 21-December 10, 2022.

Since May 2022, over 91 000 cases of mpox have been reported globally with the majority of cases occurring among adult males who identify as gay, bisexual, or men who have sex with men (gbMSM). Given the rapid emergence of the global mpox outbreak, many public health authorities did not have established mpox outbreak control indicators or criteria for declaring an mpox outbreak over. Expert consensus in Ontario, Canada, set thresholds for five key indicators of mpox outbreak control as follows: estimated number of currently infectious cases < 5; effective reproductive number < 1.0; doubling time > 42 days; weekly test positivity < 5%; and sporadic non-gbMSM cases (i.e., female and pediatric cases). Once all indicators were achieved, a 52-day period based on two incubation periods for mpox and a 10-day reporting delay was employed to monitor for indicator stability. After all five indicators remained at expected levels, the mpox outbreak in Ontario was declared over on December 10, 2022. Despite current low levels of mpox activity globally, some jurisdictions may benefit from utilizing or modifying these outbreak control indicators during a future localized mpox outbreak.

Monkeypox-Associated Disciform Keratitis.

PURPOSE: The purpose of this study was to describe a case of monkeypox (MPX)-associated disciform keratitis. METHODS: This is a case report. RESULTS: A 36-year-old male patient presented to the infectious diseases clinic with a 1-week history of disseminated pustular skin lesions, a 4-day history of constitutional symptoms, and redness in the left eye. Testing of blood, 2 skin lesions, and a conjunctival swab confirmed the presence of MPX virus by polymerase chain reaction. On ophthalmologic examination on the 17th day of illness, there was a corneal epithelial ridge that stained with fluorescein with disciform corneal edema and underlying keratic precipitates. The patient was treated with oral tecovirimat 600 mg twice a day for 14 days and topical prednisolone acetate 1% 4 times daily, starting 2 days later. On completion of oral treatment, his corneal findings had resolved except for a small subepithelial scar at which time topical steroids were tapered. CONCLUSIONS: MPX may cause disciform keratitis and scarring that closely resembles other ocular viral infections. Clinical trials are urgently needed to define the optimal management of human MPX infections and reduce vision loss.

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.

Atypical Clinical Presentation of Monkeypox Complicated by Myopericarditis.

We present a case of monkeypox infection in a man presenting with genital and labial ulcers, followed by submandibular lymphadenopathy, fever, and constitutional symptoms. His course was complicated by myopericarditis and an ongoing pleomorphic skin eruption. Viral deoxyribonucleic acid was detected by polymerase chain reaction in skin swabs, nasopharyngeal swab, saliva, and semen.