Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIMS: Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. METHODS: We conducted a systematic review, meta-analysis, and meta-regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random-effects meta-analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. RESULTS: Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (-9.97 mg/dL [95% CI: -15.08; -4.87], p < 0.0001), low-density lipoprotein (-6.29 mg/dL [95% CI: -9.25; -3.33], p < 0.0001), high-density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very-low-density lipoprotein (-4.52 mg/dL [95% CI: -6.36; -2.67], p < 0.0001) and triglyceride (-22.93 mg/dL [95% CI: -33.99; -11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. CONCLUSIONS: Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter-study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.

Epidemiology of gonorrhoea: systematic review, meta-analyses, and meta-regressions, World Health Organization European Region, 1949 to 2021.

BackgroundEpidemiology of Neisseria gonorrhoeae (NG) infection remains inadequately understood.AimWe aimed to characterise NG epidemiology in Europe.MethodsWe used Cochrane and PRISMA guidelines to systematically review, report, synthesise and analyse NG prevalence data from 1949 to 30 September 2021. Random-effects meta-analyses estimated pooled prevalence. Meta-regression analyses investigated associations and sources of heterogeneity.ResultsThe 844 included publications yielded 1,573 prevalence measures. Pooled prevalence of current urogenital infection was 1.0% (95% CI: 0.7-1.2%) among general populations, 3.2% (95% CI: 1.8-4.8%) among female sex workers, 4.9% (95% CI: 4.2-5.6%) among sexually transmitted infection clinic attendees and 12.1% (95% CI: 8.8-15.8%) among symptomatic men. Among men who have sex with men, pooled prevalence was 0.9% (95% CI: 0.5-1.4%), 5.6% (95% CI: 3.6-8.1%), and 3.8% (95% CI: 2.5-5.4%), respectively, for current urogenital, anorectal or oropharyngeal infection. Current urogenital, anorectal or oropharyngeal infection was 1.45-fold (95% CI: 1.19-1.77%), 2.75-fold (95% CI: 1.89-4.02%) and 2.64-fold (95% CI: 1.77-3.93%) higher among men than women. Current urogenital infection declined 0.97-fold (95% CI: 0.96-0.98%) yearly, but anorectal and oropharyngeal infection increased (1.02-fold; 95% CI: 1.01-1.04% and 1.02-fold; 95% CI: 1.00-1.04%), respectively.ConclusionsNeisseria gonorrhoeae epidemiology in Europe has distinct and contrasting epidemiologies for vaginal sex transmission in heterosexual sex networks vs anal and oral sex transmission in MSM sexual networks. Increased transmission may facilitate drug-resistant strain emergence. Europe is far from achieving the World Health Organization target of 90% incidence reduction by 2030.

Epidemiology of herpes simplex virus type 2 in the Middle East and North Africa: Systematic review, meta-analyses, and meta-regressions.

Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with poorly characterized prevalence in the Middle East and North Africa (MENA) region. This study characterized HSV-2 epidemiology in MENA. HSV-2 reports were systematically reviewed as guided by the Cochrane Collaboration Handbook and findings were reported following PRISMA guidelines. Random-effects meta-analyses and meta-regressions were performed to estimate pooled mean outcome measures and to assess predictors of HSV-2 antibody prevalence (seroprevalence), trends in seroprevalence, and between-study heterogeneity. In total, sixty-one overall (133 stratified) HSV-2 seroprevalence measures and two overall (four stratified) proportion measures of HSV-2 detection in laboratory-confirmed genital herpes were extracted from 37 relevant publications. Pooled mean seroprevalence was 5.1% (95% confidence interval [CI]: 3.6%-6.8%) among general populations, 13.3% (95% CI: 8.6%-18.7%) among intermediate-risk populations, 20.6% (95% CI: 5.3%-42.3%) among female sex workers, and 18.3% (95% CI: 3.9%-39.4%) among male sex workers. Compared to Fertile Crescent countries, seroprevalence was 3.39-fold (95% CI: 1.86-6.20) and 3.90-fold (95% CI: 1.78-8.57) higher in Maghreb and Horn of Africa countries, respectively. Compared to studies published before 2010, seroprevalence was 1.73-fold (95% CI: 1.00-2.99) higher in studies published after 2015. Pooled mean proportion of HSV-2 detection in genital herpes was 73.8% (95% CI: 42.2%-95.9%). In conclusion, MENA has a lower HSV-2 seroprevalence than other world regions. Yet, 1 in 20 adults is chronically infected, despite conservative prevailing sexual norms. Seroprevalence may also be increasing, unlike other world regions. Findings support the need for expansion of surveillance and monitoring of HSV-2 infection in MENA.

Epidemiology of herpes simplex virus type 1 and genital herpes in Australia and New Zealand: systematic review, meta-analyses and meta-regressions.

Herpes simplex virus type 1 (HSV-1) infection is a lifelong infection that is acquired primarily orally and during childhood. We aimed to characterise HSV-1 epidemiology in Australia and New Zealand. HSV-1-related data as recent as 6 December 2021 were systematically reviewed, synthesised and reported, following PRISMA guidelines. Pooled mean seroprevalence and proportions of HSV-1 detection in genital ulcer disease (GUD) and in genital herpes were calculated using random-effects meta-analyses. Meta-regressions were also conducted. HSV-1 measures were retrieved from 21 eligible publications. Extracted HSV-1 measures included 13 overall seroprevalence measures (27 stratified) in Australia, four overall proportions of HSV-1 detection in clinically diagnosed GUD (four stratified) in Australia, and ten overall proportions of HSV-1 detection in laboratory-confirmed genital herpes (26 stratified) in Australia and New Zealand. Pooled mean seroprevalence among healthy adults in Australia was 84.8% (95% confidence interval (CI) 74.3-93.1%). Pooled mean seroprevalence was 70.2% (95% CI 47.4-88.7%) among individuals <35 years of age and 86.9% (95% CI 79.3-93.0%) among individuals ≥35 years. Seroprevalence increased by 1.05-fold (95% CI 1.01-1.10) per year. Pooled mean proportion of HSV-1 detection in GUD was 8.2% (95% CI 0.4-22.9%). Pooled mean proportion of HSV-1 detection in genital herpes was 30.5% (95% CI 23.3-38.3%), and was highest in young individuals. Proportion of HSV-1 detection in genital herpes increased by 1.04-fold (95% CI 1.00-1.08) per year. Included studies showed heterogeneity, but 30% of the heterogeneity in seroprevalence and 42% of the heterogeneity in proportion of HSV-1 detection in genital herpes were explained in terms of epidemiological factors. HSV-1 seroprevalence is higher in Australia than in other Western countries. HSV-1 epidemiology in Australia and New Zealand appears to be transitioning towards less oral acquisition in childhood, but more genital acquisition among youth.

Wearable Artificial Intelligence for Detecting Anxiety: Systematic Review and Meta-Analysis.

BACKGROUND: Anxiety disorders rank among the most prevalent mental disorders worldwide. Anxiety symptoms are typically evaluated using self-assessment surveys or interview-based assessment methods conducted by clinicians, which can be subjective, time-consuming, and challenging to repeat. Therefore, there is an increasing demand for using technologies capable of providing objective and early detection of anxiety. Wearable artificial intelligence (AI), the combination of AI technology and wearable devices, has been widely used to detect and predict anxiety disorders automatically, objectively, and more efficiently. OBJECTIVE: This systematic review and meta-analysis aims to assess the performance of wearable AI in detecting and predicting anxiety. METHODS: Relevant studies were retrieved by searching 8 electronic databases and backward and forward reference list checking. In total, 2 reviewers independently carried out study selection, data extraction, and risk-of-bias assessment. The included studies were assessed for risk of bias using a modified version of the Quality Assessment of Diagnostic Accuracy Studies-Revised. Evidence was synthesized using a narrative (ie, text and tables) and statistical (ie, meta-analysis) approach as appropriate. RESULTS: Of the 918 records identified, 21 (2.3%) were included in this review. A meta-analysis of results from 81% (17/21) of the studies revealed a pooled mean accuracy of 0.82 (95% CI 0.71-0.89). Meta-analyses of results from 48% (10/21) of the studies showed a pooled mean sensitivity of 0.79 (95% CI 0.57-0.91) and a pooled mean specificity of 0.92 (95% CI 0.68-0.98). Subgroup analyses demonstrated that the performance of wearable AI was not moderated by algorithms, aims of AI, wearable devices used, status of wearable devices, data types, data sources, reference standards, and validation methods. CONCLUSIONS: Although wearable AI has the potential to detect anxiety, it is not yet advanced enough for clinical use. Until further evidence shows an ideal performance of wearable AI, it should be used along with other clinical assessments. Wearable device companies need to develop devices that can promptly detect anxiety and identify specific time points during the day when anxiety levels are high. Further research is needed to differentiate types of anxiety, compare the performance of different wearable devices, and investigate the impact of the combination of wearable device data and neuroimaging data on the performance of wearable AI. TRIAL REGISTRATION: PROSPERO CRD42023387560; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=387560.

Epidemiology of Herpes Simplex Virus Type 2 in Canada, Australia, and New Zealand: Systematic Review, Meta-Analyses, and Meta-Regressions.

BACKGROUND: This study characterized the epidemiology of herpes simplex virus type 2 (HSV-2) infection in Canada, Australia, and New Zealand. METHODS: Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2-related data up to January 21, 2021. Meta-analyses and meta-regressions were performed. RESULTS: In Canada, pooled mean seroprevalence was 10.0% (95% confidence interval [CI], 7.8-12.4%) among general populations, 44.5% (95% CI, 20.0-70.5%) among sexually transmitted infection clinic attendees and symptomatic populations, and 60.7% (95% CI, 49.8-71.1%) among human immunodeficiency virus (HIV)-positive individuals and individuals in HIV-discordant couples. In Australia and New Zealand, combined, pooled mean seroprevalence was 15.4% (95% CI, 9.6-22.2%) among general populations, 27.8% (95% CI, 12.0-47.2%) among men who have sex with men, and 37.2% (95% CI, 23.7-51.8%) among sexually transmitted infection clinic attendees and symptomatic populations. Men had 0.64-fold (95% CI, 0.47-0.86) lower seroprevalence compared with women. No evidence was found for a decline in seroprevalence over time. Pooled mean proportion of HSV-2 isolation in laboratory-confirmed genital herpes was 62.1% (95% CI, 53.8-70.1%) in Canada and 71.9% (95% CI, 64.2-78.9%) in Australia and New Zealand. Proportion of HSV-2 isolation in genital herpes declined by 0.98-fold (95% CI, 0.97-0.99) per year. Pooled mean proportion of HSV-2 isolation in genital ulcer disease was 17.4% (95% CI, 4.0-37.1%) in these countries. CONCLUSIONS: Over 10% of adults in these countries are infected, with no evidence for declining seroprevalence, unlike other global regions. Over 60% of genital herpes cases are caused by HSV-2 in these countries, yet HSV-2's role is declining by 2% per year.

The effect of microbiome-modulating probiotics, prebiotics and synbiotics on glucose homeostasis in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIM/HYPOTHESIS: The globally escalating diabetes epidemic is responsible for significant morbidity and mortality. Microbiome-modulating nutraceuticals have been investigated for their potential to restore metabolic and floral homeostasis in type 2 diabetic patients METHODS: A systematic review, meta-analyses and meta-regressions were conducted to investigate the effect of probiotics, prebiotics, and synbiotics on various biomarkers of glucose homeostasis based on a multi-database search of clinical trials published through April 10, 2022. Data was pooled using random effects meta-analyses and reported as mean differences with 95% confidence intervals (CIs), followed by univariate linear model meta-regression. RESULTS: Data from 68 trial comparisons across 58 studies (n = 3835) revealed that, compared to placebo/control group, administration of pro/pre/synbiotics was associated with statistically significant changes in fasting plasma glucose (-12.41 mg/dl [95% CI: -15.94; -8.88], p 0.0001), glycated hemoglobin (-0.38% [95% CI: -0.47; -0.30], p 0.0001), fasting insulin (-1.49 µU/mL [95% CI: -2.12; -0.86], p 0.0001), HOMA-IR (-0.69 [95% CI: -1.16; -0.23], p = 0.0031) and QUICKI (0.0148 [95% CI: 0.0052; 0.0244], p = 0.0025), but not C-peptide (-0.0144 ng/mL [95% CI: -0.2564; -0.2275], p = 0.9069). Age, baseline BMI, baseline biomarker value, pro/prebiotic dosage, trial duration, nutraceutical type, and recruitment region significantly affected the potential of pro/pre/synbiotics use as personalized diabetes adjunct therapy. Lastly, we discuss unexplained observations and directives for future trials, with the aim of maximizing our understanding of how microbiome-modulating nutraceuticals can treat various metabolic diseases CONCLUSIONS: Pro/pre/synbiotic supplementation improved glucose homeostasis in diabetic patients. Our results support their potential use as adjunct therapy for improving glycemia and insulinemia alongside pharmacological therapeutics.

Epidemiology of herpes simplex virus type 2 in Latin America and the Caribbean: systematic review, meta-analyses and metaregressions.

OBJECTIVE: To characterise epidemiology of herpes simplex virus type 2 (HSV-2) in Latin America and the Caribbean. METHODS: HSV-2 reports were systematically reviewed and synthesised, and findings were reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analyses and metaregressions were conducted. FINDING: 102 relevant reports were identified including 13 overall incidence measures, 163 overall (and 402 stratified) seroprevalence measures, and 7 and 10 proportions of virus detection in genital ulcer disease and in genital herpes, respectively. Pooled mean seroprevalence was 20.6% (95% CI 18.7% to 22.5%) in general populations, 33.3% (95% CI 26.0% to 41.0%) in intermediate-risk populations, 74.8% (95% CI 70.6% to 78.8%) in female sex workers, and 54.6% (95% CI 47.4% to 61.7%) in male sex workers, men who have sex with men and transgender people. In general populations, seroprevalence increased from 9.6% (95% CI 7.1% to 12.4%) in those aged <20 years to 17.9% (95% CI 13.6% to 22.5%) in those aged 20-30, 27.6% (95% CI 21.4% to 34.2%) in those aged 30-40 and 38.4% (95% CI 32.8% to 44.2%) in those aged >40. Compared with women, men had lower seroprevalence with an adjusted risk ratio (ARR) of 0.68 (95% CI 0.60 to 0.76). Seroprevalence declined by 2% per year over the last three decades (ARR of 0.98, 95% CI 0.97 to 0.99). Pooled mean proportions of HSV-2 detection in GUD and genital herpes were 41.4% (95% CI 18.9% to 67.0%) and 91.1% (95% CI 82.7% to 97.2%), respectively. CONCLUSIONS: One in five adults is HSV-2 infected, a higher level than other world regions, but seroprevalence is declining. Despite this decline, HSV-2 persists as the aetiological cause of nearly half of GUD cases and almost all of genital herpes cases.

Herpes simplex virus: global infection prevalence and incidence estimates, 2016.

OBJECTIVE: To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016. METHODS: To obtain data, we undertook a systematic review to identify studies up to August 2018. Adjustments were made to account for HSV test sensitivity and specificity. For each World Health Organization (WHO) region, we applied a constant incidence model to pooled prevalence by age and sex to estimate the prevalence and incidence of HSV types 1 and 2 infections. For HSV type 1, we apportioned infection by anatomical site using pooled estimates of the proportions that were oral and genital. FINDINGS: In 2016, an estimated 491.5 million people (95% uncertainty interval, UI: 430.4 million-610.6 million) were living with HSV type 2 infection, equivalent to 13.2% of the world's population aged 15-49 years. An estimated 3752.0 million people (95% UI: 3555.5 million-3854.6 million) had HSV type 1 infection at any site, equivalent to a global prevalence of 66.6% in 0-49-year-olds. Differing patterns were observed by age, sex and geographical region, with HSV type 2 prevalence being highest among women and in the WHO African Region. CONCLUSION: An estimated half a billion people had genital infection with HSV type 2 or type 1, and several billion had oral HSV type 1 infection. Millions of people may also be at higher risk of acquiring human immunodeficiency virus (HIV), particularly women in the WHO African Region who have the highest HSV type 2 prevalence and exposure to HIV.

The Epidemiology of Herpes Simplex Virus Type 1 in Asia: Systematic Review, Meta-analyses, and Meta-regressions.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) epidemiology in Asia was characterized by assessing seroprevalence levels and extent to which HSV-1 is isolated from clinically diagnosed genital ulcer disease (GUD) and genital herpes. METHODS: HSV-1 reports in Asia were systematically reviewed and synthesized, following PRISMA guidelines. Random-effects meta-analyses estimated pooled mean seroprevalence and proportion of HSV-1 detection in GUD and genital herpes. Random-effects meta-regressions identified predictors of seroprevalence and sources of between-study heterogeneity. RESULTS: Forty-nine relevant publications were identified. Fifty-four overall seroprevalence measures (182 stratified measures), and 8 and 24 proportions of HSV-1 detection in GUD and in genital herpes, respectively, were extracted. The pooled mean seroprevalence was 50.0% (n = 26; 95% confidence interval [CI], 41.3%-58.7%) for children and 76.5% (n = 151; 73.3%-79.6%) for adults. By age group, the pooled mean was lowest at 55.5% (n = 37; 95% CI, 47.5%-63.4%) in individuals aged <20 years, followed by 67.9% (n = 48; 62.4%-73.3%) in those aged 20-39 and 87.5% (n = 44; 83.4%-91.1%) in those aged ≥40 years. In meta-regression, age was the major predictor of seroprevalence. The mean proportion of HSV-1 detection was 5.6% (n = 8; 95% CI, 0.8%-13.6%) in GUD and 18.8% (n = 24; 12.0%-26.7%) in genital herpes. CONCLUSIONS: HSV-1 epidemiology is transitioning in Asia. HSV-1 is probably playing a significant role as a sexually transmitted infection, explaining one-fifth of genital herpes cases. There is a need for expanded seroprevalence monitoring and GUD/genital herpes etiological surveillance.

HIV epidemiology among female sex workers and their clients in the Middle East and North Africa: systematic review, meta-analyses, and meta-regressions.

BACKGROUND: HIV epidemiology among female sex workers (FSWs) and their clients in the Middle East and North Africa (MENA) region is poorly understood. We addressed this gap through a comprehensive epidemiological assessment. METHODS: A systematic review of population size estimation and HIV prevalence studies was conducted and reported following PRISMA guidelines. Risk of bias (ROB) assessments were conducted for all included studies using various quality domains, as informed by Cochrane Collaboration guidelines. The pooled mean HIV prevalence was estimated using random-effects meta-analyses. Sources of heterogeneity and temporal trends were identified through meta-regressions. RESULTS: We identified 270 size estimation studies in FSWs and 42 in clients, and 485 HIV prevalence studies in 287,719 FSWs and 69 in 29,531 clients/proxy populations. Most studies had low ROB in multiple quality domains. The median proportion of reproductive-age women reporting current/recent sex work was 0.6% (range = 0.2-2.4%) and of men reporting currently/recently buying sex was 5.7% (range = 0.3-13.8%). HIV prevalence ranged from 0 to 70% in FSWs (median = 0.1%) and 0-34.6% in clients (median = 0.4%). The regional pooled mean HIV prevalence was 1.4% (95% CI = 1.1-1.8%) in FSWs and 0.4% (95% CI = 0.1-0.7%) in clients. Country-specific pooled prevalence was < 1% in most countries, 1-5% in North Africa and Somalia, 17.3% in South Sudan, and 17.9% in Djibouti. Meta-regressions identified strong subregional variations in prevalence. Compared to Eastern MENA, the adjusted odds ratios (AORs) ranged from 0.2 (95% CI = 0.1-0.4) in the Fertile Crescent to 45.4 (95% CI = 24.7-83.7) in the Horn of Africa. There was strong evidence for increasing prevalence post-2003; the odds increased by 15% per year (AOR = 1.15, 95% CI = 1.09-1.21). There was also a large variability in sexual and injecting risk behaviors among FSWs within and across countries. Levels of HIV testing among FSWs were generally low. The median fraction of FSWs that tested for HIV in the past 12 months was 12.1% (range = 0.9-38.0%). CONCLUSIONS: HIV epidemics among FSWs are emerging in MENA, and some have reached stable endemic levels, although still some countries have limited epidemic dynamics. The epidemic has been growing for over a decade, with strong regionalization and heterogeneity. HIV testing levels were far below the service coverage target of "UNAIDS 2016-2021 Strategy."

Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment.

BACKGROUND: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR. METHODS: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software. RESULTS: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%]). CONCLUSION: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.

Epidemiology of herpes simplex virus type 1 in the United States: Systematic review, meta-analyses, and meta-regressions.

This study aimed to analytically describe the epidemiology of herpes simplex virus type 1 (HSV-1) infection in the United States through a systematic review and meta-analytics. We reviewed 159 publications, identifying 190 seroprevalence measures and 43 proportions of HSV-1 detection in genital herpes. The pooled mean HSV-1 seroprevalence was 38.0% (95% CI: 30.9-45.4) among general-population children and 63.5% (95% CI: 61.3-65.7) among general-population adults. Age explained 43% of the seroprevalence variation, with rates increasing progressively with age. Seroprevalence declined by 0.99-fold (95% CI: 0.99-0.99) per year. The pooled mean proportion of HSV-1 detection in genital herpes was 15.4% (95% CI: 10.8-20.6), increasing by 1.02-fold (95% CI: 1.00-1.04) per year. Recurrent genital herpes had a 0.17-fold (95% CI: 0.09-0.32) lower proportion of HSV-1 detection compared to first-episode cases. The epidemiology of HSV-1 is shifting, marked by a decline in oral acquisition during childhood and an increase in genital acquisition during adulthood.

Epidemiology of Trichomonas vaginalis infection in the Middle East and North Africa: systematic review, meta-analyses, and meta-regressions.

BACKGROUND: Trichomoniasis, caused by the parasite Trichomonas vaginalis (TV), remains an underappreciated sexually transmitted infection (STI), primarily due to inadequate understanding of its epidemiology and public health implications. This study aimed to characterize TV epidemiology in the Middle East and North Africa (MENA). METHODS: Systematic review and analysis of evidence sourced from international, regional, and national databases were conducted. Findings were reported following PRISMA guidelines. Random-effects meta-analyses and meta-regressions were performed to determine pooled mean prevalence, investigate associations with prevalence, and identify sources of between-study heterogeneity. FINDINGS: The review identified 263 relevant publications, encompassing 462 TV prevalence measures. The pooled mean TV prevalence was estimated as follows: 4.7% (95% CI: 3.9-5.6%) in the general population of women, 17.2% (95% CI: 5.4-33.6%) among intermediate-risk populations, 10.3% (95% CI: 6.2-15.3%) among female sex workers, 13.9% (95% CI: 12.3-15.6%) among symptomatic women, 7.4% (95% CI: 1.9-15.5%) among infertility clinic attendees, 2.3% (95% CI: 0.1-6.3%) among women with miscarriages or ectopic pregnancies, and 1.6% (95% CI: 0.8-2.7%) among STI clinic attendees. Limited data were found for men. Multivariable meta-regressions explained >40% of the prevalence variation, unveiling a hierarchical prevalence pattern by population type, an inverse correlation with national income, and a prevalence decline at a rate of 1% per calendar year. INTERPRETATION: Despite conservative sexual norms, MENA has a substantial TV prevalence, comparable to the global TV prevalence. The unexpectedly high prevalence of this curable infection may, in part, be attributed to limited access to and underutilization of STI screening and treatment services. FUNDING: This work was supported by the Qatar Research, Development, and Innovation Council [ARG01-0522-230273] and by the Biomedical Research Program at Weill Cornell Medicine-Qatar.

Epidemiology of herpes simplex virus type 1 in Canada: systematic review, meta-analyses, and meta-regressions.

Background: The objective of this study was to characterize herpes simplex virus type 1 (HSV-1) epidemiology in Canada. Methods: HSV-1 publications as recent as December 6, 2021 were systematically reviewed, synthesized, and reported following PRISMA guidelines. Meta-analyses and meta-regressions were conducted. Results: HSV-1 measures were extracted from 22 studies and included 32 overall seroprevalence measures (79 stratified), 2 overall proportions of HSV-1 detection in clinically diagnosed genital ulcer disease (2 stratified), and 8 overall proportions of HSV-1 detection in laboratory-confirmed genital herpes (27 stratified). Pooled mean seroprevalence was 19.1% [95% confidence interval (CI): 12.6-26.4%] among healthy children and 51.4% (95% CI: 47.3-55.5%) among healthy adults. Pooled mean seroprevalence among healthy general populations increased with age, with the lowest being 35.7% (95% CI: 29.1-42.6%) among individuals <20 years of age, and the highest being 70.0% (95% CI: 54.8-83.2) among individuals ≥40 years. Seroprevalence increased by 1.02-fold (95% CI: 1.01-1.04) per year. Pooled mean proportion of HSV-1 detection in genital ulcer disease was 30.8% (95% CI: 12.6-52.8%). Pooled mean proportion of HSV-1 detection in genital herpes was 37.4% (95% CI: 29.5-45.6%) and was highest in women and in young persons. Proportion of HSV-1 detection in genital herpes increased by 1.04-fold (95% CI: 1.00-1.08) per year. Conclusions: HSV-1 epidemiology in Canada appears to be shifting toward less oral acquisition in childhood and more genital acquisition in adulthood, particularly among youth. Both HSV-1 seroprevalence and proportion of HSV-1 detection in genital herpes are increasing with time.

Epidemiology of herpes simplex virus type 2 in Europe: systematic review, meta-analyses, and meta-regressions.

Background: Herpes simplex virus type 2 (HSV-2) infection is a globally prevalent, life-long, sexually transmitted infection. This study characterized HSV-2 seroprevalence in Europe for various at-risk populations and proportions of HSV-2 detection in genital ulcer disease (GUD) and in genital herpes. Data on neonatal herpes and HSV-2's contribution to HIV transmission were also reviewed. Methods: Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings. The search was conducted in PubMed and Embase databases up to February 20, 2022. Any publication reporting data on the outcome measures was included. Meta-analyses and meta-regressions were conducted. Findings: 211 relevant reports were identified, including 12 overall incidence measures, 294 overall (813 stratified by factors such as age and sex) seroprevalence measures, 13 overall (15 stratified by sex) proportions of HSV-2 detection in clinically diagnosed GUD, and 70 overall (183 stratified by factors such as age and sex) proportions of HSV-2 detection in laboratory-confirmed genital herpes. Pooled mean seroprevalence was 12.4% (95% CI: 11.5-13.3%) among general populations, 27.8% (95% CI: 17.5-39.4%) among men who have sex with men, 46.0% (95% CI: 40.1-51.8%) among people living with HIV and people in HIV discordant couples, and 63.2% (95% CI: 55.5-70.6%) among female sex workers. Most measures showed heterogeneity in HSV-2 seroprevalence. The pooled mean seroprevalence among general populations increased with age and was 0.65-fold (95% CI: 0.58-0.74) lower in men than women. Seroprevalence decreased by 1% per calendar year. Pooled mean proportions of HSV-2 detection in GUD and in genital herpes were 22.0% (95% CI: 15.3-29.6%) and 66.0% (95% CI: 62.9-69.1%), respectively. HSV-2 detection in genital herpes cases was 1.21-fold (95% CI: 1.10-1.32) higher in men compared to women and decreased by 1% per calendar year. Incidence of neonatal herpes indicated an increasing trend. Interpretation: Although seroprevalence is declining, a significant proportion of Europe's population is infected with HSV-2. HSV-2 accounts for approximately one-fifth of GUD cases and two-thirds of genital herpes cases. Findings support the need to invest in HSV-2 vaccine development, and sexual and reproductive health services. Funding: Qatar National Research Fund [NPRP 9-040-3-008] and pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar supported this study.

Epidemiology of herpes simplex virus type 2 in Asia: A systematic review, meta-analysis, and meta-regression.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection is a prevalent sexually transmitted infection worldwide. This systematic review was conducted to characterize HSV-2 epidemiology in Asia, including the World Health Organization regions of Southeast Asia and the Western Pacific. METHODS: Cochrane and PRISMA guidelines were followed to systematically review and report findings. Pooled mean seroprevalence and proportions of HSV-2 isolated in genital ulcer disease (GUD) and in genital herpes were calculated using random-effects meta-analyses. Meta-regressions were also conducted. Quality assessment was performed. FINDINGS: HSV-2 measures extracted from 173 publications included 15 seroconversion rates, 11 seroincidence rates, 272 overall seroprevalence measures (678 stratified), 14 proportions of HSV-2 isolation in GUD (15 stratified), and 27 proportions of HSV-2 isolation in genital herpes (36 stratified). Pooled mean seroprevalence was 12.1% (95% confidence interval (CI): 11.0-13.2%) among general populations, 23.6% (95% CI: 20.9-26.3%) among men who have sex with men and transgender people, 46.0% (95% CI: 39.2-52.9%) among HIV-positive individuals and individuals in HIV-discordant couples, and 62.2% (95% CI: 58.9-65.6%) among female sex workers. Among general populations, pooled mean seroprevalence increased gradually from 4.7% (95% CI: 3.3-6.3%) in <20-year-old individuals to 26.6% (95% CI: 19.2-34.7%) in >60-year-old individuals. Compared to women and across all populations, men had 0.60-fold (95% CI: 54.0-67.0) lower seroprevalence, that is women had 70% higher seroprevalence. Seroprevalence declined by 0.98-fold (95% CI: 0.97-0.99) per year, that is a 2% decline per year in the last three decades. Pooled mean proportions of HSV-2 isolation in GUD and in genital herpes were 48.2% (95% CI: 34.9-61.6%) and 75.9% (95% CI: 68.3-82.8%), respectively. INTERPRETATION: Over 1 in 10 individuals is infected with HSV-2, but seroprevalence is declining. HSV-2 accounts for half of GUD cases and three-quarters of genital herpes cases. These findings support the need for an HSV-2 vaccine and universal access to sexual and reproductive health services. FUNDING: This work was supported by the Qatar National Research Fund [NPRP 9-040-3-008] and by pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar.

Epidemiology of herpes simplex virus type 2 in sub-Saharan Africa: Systematic review, meta-analyses, and meta-regressions.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection is a prevalent, sexually transmitted infection with a sizable disease burden that is highest in sub-Saharan Africa. This study aimed to characterize HSV-2 epidemiology in this region. METHODS: Cochrane and PRISMA guidelines were followed to systematically review, synthesize, and report HSV-2 related findings up to August 23, 2020. Meta-analyses and meta-regressions were conducted. FINDINGS: From 218 relevant publications, 451 overall outcome measures and 869 stratified measures were extracted. Pooled incidence rates ranged between 2.4-19.4 per 100 person-years across populations. Pooled seroprevalence was lowest at 37.3% (95% confidence interval (CI): 34.9-39.7%) in general populations and high in female sex workers and HIV-positive individuals at 62.5% (95% CI: 54.8-70.0%) and 71.3% (95% CI: 66.5-75.9%), respectively. In general populations, pooled seroprevalence increased steadily with age. Compared to women, men had a lower seroprevalence with an adjusted risk ratio (ARR) of 0.61 (95% CI: 0.56-0.67). Seroprevalence has decreased in recent decades with an ARR of 0.98 (95% CI: 0.97-0.99) per year. Seroprevalence was highest in Eastern and Southern Africa. Pooled HSV-2 proportion in genital ulcer disease was 50.7% (95% CI: 44.7-56.8%) and in genital herpes it was 97.3% (95% CI: 84.4-100%). INTERPRETATION: Seroprevalence is declining by 2% per year, but a third of the population is infected. Age and geography play profound roles in HSV-2 epidemiology. Temporal declines and geographic distribution of HSV-2 seroprevalence mirror that of HIV prevalence, suggesting sexual risk behavior has been declining for three decades. HSV-2 is the etiological cause of half of genital ulcer disease and nearly all genital herpes cases with limited role for HSV-1. FUNDING: This work was supported by pilot funding from the Biomedical Research Program at Weill Cornell Medicine in Qatar and by the Qatar National Research Fund [NPRP 9-040-3-008].