Epigenetic Changes in Cerebrospinal Fluid and Blood of People with Neurosyphilis.

Epigenetic changes within immune cells may contribute to neuroinflammation during bacterial infection, but its role in neurosyphilis pathogenesis and response has not yet been established. We longitudinally analyzed DNA methylation and RNA expression changes in cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMCs) from 11 participants with laboratory-confirmed NS (CSF VDRL positive) and 11 matched controls with syphilis without NS (non-NS). DNA methylation profiles from CSF and PBMCs of participants with NS significantly differed from those of participants with non-NS. Some genes associated with these differentially methylated sites had corresponding RNA expression changes in the CSF (111/1097, 10.1%), which were enriched in B-cell, cytotoxic-compounds, and insulin-response pathways. Despite antibiotic treatment, approximately 80% of CSF methylation changes persisted; suggesting that epigenetic scars accompanying NS may persistently affect immunity following infection. Future studies must examine whether these sequelae are clinically meaningful.

Polypharmacy Is Associated With Slow Gait Speed and Recurrent Falls in Older People With HIV.

BACKGROUND: Older people with human immunodeficiency virus (HIV, PWH) are prone to using multiple medications due to higher rates of medical comorbidities and the use of antiretroviral therapy (ART). We assessed the prevalence and clinical impact of polypharmacy among PWH. METHODS: We leveraged clinical data from the AIDS Clinical Trials Group A5322 study "Long-Term Follow-up of Older HIV-infected Adults: Addressing Issues of Aging, HIV Infection and Inflammation" (HAILO). We included PWH aged ≥40 years with plasma HIV RNA levels <200 copies/µL. We assessed the relationship between polypharmacy (defined as the use of 5 or more prescription medications, excluding ART) and hyperpolypharmacy (defined as the use of 10 or more prescription medications, excluding ART) with slow gait speed (less than 1 meter/second) and falls, including recurrent falls. RESULTS: Excluding ART, 24% of study participants had polypharmacy and 4% had hyperpolypharmacy. Polypharmacy was more common in women (30%) than men (23%). Participants with polypharmacy had a higher risk of slow gait speed (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.27-2.50) and increased risk of recurrent falls (OR = 2.12; 95% CI = 1.06-4.23). The risk for recurrent falls was further increased in those with hyperpolypharmacy compared with those without polypharmacy (OR = 3.46; 95% CI = 1.32-9.12). CONCLUSIONS: In this large, mixed-sex cohort of PWH aged ≥40 years, polypharmacy was associated with slow gait speed and recurrent falls, even after accounting for medical comorbidities, alcohol use, substance use, and other factors. These results highlight the need for increased focus on identifying and managing polypharmacy and hyperpolypharmacy in PWH.

The International Sexual Health And REproductive Health during COVID-19 (I-SHARE) Study: A Multicountry Analysis of Adults from 30 Countries Prior to and During the Initial Coronavirus Disease 2019 Wave.

BACKGROUND: There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium. METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence. RESULTS: Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. CONCLUSIONS: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.

Neurosyphilis is characterized by a compartmentalized and robust neuroimmune response but not by neuronal injury.

BACKGROUND: Neurosyphilis is increasing in prevalence but its pathophysiology remains incompletely understood. This study assessed for CNS-specific immune responses during neurosyphilis compared to syphilis without neurosyphilis and compared these immune profiles to those observed in other neuroinflammatory diseases. METHODS: Participants with syphilis were categorized as having neurosyphilis if their cerebrospinal fluid (CSF)-venereal disease research laboratory (VDRL) test was reactive and as having syphilis without neurosyphilis if they had a non-reactive CSF-VDRL test and a white blood cell count <5/µL. Neurosyphilis and syphilis without neurosyphilis participants were matched by rapid plasma reagin titer and HIV status. CSF and plasma were assayed for markers of neuronal injury and glial and immune cell activation. Bulk RNA sequencing was performed on CSF cells, with results stratified by the presence of neurological symptoms. FINDINGS: CSF neopterin and five CSF chemokines had levels significantly higher in individuals with neurosyphilis compared to those with syphilis without neurosyphilis, but no markers of neuronal injury or astrocyte activation were significantly elevated. The CSF transcriptome in neurosyphilis was characterized by genes involved in microglial activation and lipid metabolism and did not differ in asymptomatic versus symptomatic neurosyphilis cases. CONCLUSIONS: The CNS immune response observed in neurosyphilis was comparable to other neuroinflammatory diseases and was present in individuals with neurosyphilis regardless of neurological symptoms, yet there was minimal evidence for neuronal or astrocyte injury. These findings support the need for larger studies of the CSF inflammatory response in asymptomatic neurosyphilis. FUNDING: This work was funded by the National Institutes of Health, grants K23MH118999 (S.F.F.) and R01NS082120 (C.M.M.).

Pay-it-forward influenza vaccination among older adults and children: A cost-effectiveness analysis in China.

A quasi-experimental study was conducted to evaluate the effectiveness of a pay-it-forward strategy for increasing influenza vaccination among children and older adults compared to a self-paid vaccination strategy in China. Pay-it-forward is an innovative community-engaged intervention in which participants receive a free influenza vaccination and are then asked if they would like to donate or create a message to support subsequent vaccinations. This economic evaluation used a decision-tree model to compare pay-it-forward to a standard of care arm in which patients had to pay for their own influenza vaccine. The analysis was performed from the healthcare provider perspective and costs were calculated with 2020 United States dollars. The time horizon was one year. In the base case analysis, pay-it-forward was more effective (111 vs 55 people vaccinated) but more costly than standard-of-care ($4477 vs $2725). Pay-it-forward spurred 96.4% (107/111) of individuals to voluntarily donate to support influenza vaccination for high-risk groups in China. Further costing and implementation research is needed to inform scale up.

Intimate Partner Violence During COVID-19 Restrictions: A Study of 30 Countries From the I-SHARE Consortium.

Intimate partner violence (IPV) causes substantial physical and psychological trauma. Restrictions introduced in response to the COVID-19 pandemic, including lockdowns and movement restrictions, may exacerbate IPV risk and reduce access to IPV support services. This cross-sectional study examines IPV during COVID-19 restrictions in 30 countries from the International Sexual HeAlth and REproductive Health (I-SHARE) study conducted from July 20th, 2020, to February, 15th, 2021. IPV was a primary outcome measure adapted from a World Health Organization multicountry survey. Mixed-effects modeling was used to determine IPV correlates among participants stratified by cohabitation status. The sample included 23,067 participants from 30 countries. A total of 1,070/15,336 (7.0%) participants stated that they experienced IPV during COVID-19 restrictions. A total of 1,486/15,336 (9.2%) participants stated that they had experienced either physical or sexual partner violence before the restrictions, which then decreased to 1,070 (7.0%) after the restrictions. In general, identifying as a sexual minority and experiencing greater economic vulnerability were associated with higher odds of experiencing IPV during COVID-19 restrictions, which were accentuated among participants who were living with their partners. Greater stringency of COVID-19 restrictions and living in urban or semi-urban areas were associated with lower odds of experiencing IPV in some settings. The I-SHARE data suggest a substantial burden of IPV during COVID-19 restrictions. However, the restrictions were correlated with reduced IPV in some settings. There is a need for investing in specific support systems for survivors of IPV during the implementation of restrictions designed to contain infectious disease outbreaks.

The International Sexual Health And Reproductive Health Survey (I-SHARE-1): A Multi-Country Analysis of Adults from 30 Countries Prior to and During the Initial COVID-19 Wave.

BACKGROUND: The COVID-19 pandemic forced billions of people to shelter in place, altering social and sexual relationships worldwide. In many settings, COVID-19 threatened already precarious health services. However, there is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of COVID-19 disease. To address this gap, our team organized a multi-country, cross-sectional online survey as part of a global consortium. METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service utilization, and we compared three months prior to and three months after policy measures to mitigate COVID-19. We used established indicators and analyses pre-specified in our protocol. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence using Cochrane methods. Descriptive analyses included 22,724 individuals in 25 countries. Five additional countries with sample sizes <200 were included in descriptive meta-analyses. RESULTS: Respondents were mean age 34 years; most identified as women (15160; 66.7%), cis-gender (19432; 86.6%) and heterosexual (16592; 77.9%). Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%) people and 640 (14.1%) people reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063/15144, 7.0%) compared to the period before COVID-19 measures (1469/15887, 9.3%). COVID-19 measures impeded access to condoms (933/10790, 8.7%), contraceptives (610/8175, 7.5%), and HIV/STI testing (750/1965, 30.7%). Pooled estimates from meta-analysis indicate during COVID-19 measures, 32.3% (95% CI 23.9-42.1) of people needing HIV/STI testing had hindered access, 4.4% (95% CI 3.4-5.4) experienced partner violence, and 5.8% (95% CI 5.4-8.2) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy. CONCLUSION: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.

Self-Reported Neuropsychiatric Post-COVID-19 Condition and CSF Markers of Neuroinflammation.

This case-control study assesses cerebrospinal fluid markers of neuroinflammation and blood-brain barrier disruption in individuals with post­COVID-19 condition who reported neuropsychiatric symptoms.