OBJECTIVES: Bloodstream infections (BSI) are a leading cause of sepsis, necessitating early risk stratification during the critical window for effective management. We aimed to develop a model that leverages early-phase...OBJECTIVES: Bloodstream infections (BSI) are a leading cause of sepsis, necessitating early risk stratification during the critical window for effective management. We aimed to develop a model that leverages early-phase clinical data to predict 28-day mortality by integrating longitudinal trends and addressing comorbidity-driven heterogeneity. METHODS: The BSI Heterogeneity Score (BHScore) was developed using machine learning on longitudinal clinical data (first 7 days post-culture) from 2524 BSI patients at Xijing Hospital. The model uses interpretable methods to establish comorbidity-stratified thresholds (global, renal disease, liver disease, metastatic malignancy) to enhance prediction accuracy. RESULTS: The BHScore demonstrated superior discriminatory performance (area under the receiver operating characteristic curve: 0.81-0.91) and temporal stability compared to established scores including the Sequential Organ Failure Assessment (SOFA), representing an improvement of 10% to 25%. Our analysis revealed that coagulation biomarkers have greater prognostic significance in the malignancy subgroup, inflammatory thresholds are more sensitive in the liver disease subgroup, and urea levels exhibit U-shaped mortality curves in the renal disease subgroup. To support clinical application, a freely accessible web tool has been developed. CONCLUSIONS: The BHScore enables the early identification of high-risk BSI patients with diverse comorbidities using straightforward clinical indicators, facilitating timely and targeted interventions to reduce mortality.
BACKGROUND: Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. In critically ill patients, iron biomarkers are closely linked to outcomes; yet the mechanistic role of iron metab...BACKGROUND: Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. In critically ill patients, iron biomarkers are closely linked to outcomes; yet the mechanistic role of iron metabolism in sepsis progression remains unclear. METHOD: To address this knowledge gap, we conducted a longitudinal clinical study in 20 sepsis patients, tracking plasma iron biomarkers together with monocyte function and iron content over five consecutive days following sepsis onset. Some patients required red blood cell transfusions during the study period. RESULTS: We show that anemia of inflammation is an early and prominent feature of sepsis hallmarked by iron sequestration in blood monocytes, reduced plasma iron levels and anemia. Importantly, increased iron levels in monocytes are detected already at day one following the sepsis diagnosis and the degree of iron accumulation directly correlates with sepsis severity. High monocytic iron levels further correlate with decreased human leukocyte antigen DR (HLA-DR) expression on day one, suggestive of monocyte immunosuppression. Furthermore, in iron-loaded septic monocytes mRNA levels of the non-transferrin bound iron (NTBI) transporter ZRT/IRT-like Protein 8 were significantly increased, suggesting enhanced uptake of non-transferrin bound iron that may arise from hemolysis. Interestingly, we also show that the total iron binding capacity is an important predictor of sepsis mortality, while transfusions did not correlate with an altered iron and/or inflammatory status. CONCLUSIONS: The study highlights that early iron accumulation in monocytes is a hallmark of sepsis and is closely linked to disease severity and progression. We expect that improved insights into iron metabolism in sepsis patients may pave the way to improving therapeutic options that balance iron levels and their effects on organ functions in the future.
OBJECTIVES: We aimed to compare host response profiles between sepsis patients who develop cytomegalovirus (CMV) reactivation (reactivators) and those who do not (non-reactivators). METHODS: We performed a nested case-co...OBJECTIVES: We aimed to compare host response profiles between sepsis patients who develop cytomegalovirus (CMV) reactivation (reactivators) and those who do not (non-reactivators). METHODS: We performed a nested case-control study in CMV-seropositive sepsis patients from two Dutch ICUs. Reactivators (plasma CMV ≥100 IU/ml) were matched 1:1 to non-reactivators, based on length of stay until reactivation, disease severity, and other relevant criteria. We analysed 32 plasma biomarkers and whole-blood gene expression on the day of CMV reactivation (or matched time point for non-reactivators), three days prior, and at ICU admission. RESULTS: We compared 81 reactivators with 81 matched non-reactivators. In reactivators, six soluble immune checkpoint regulators increased longitudinally from three days before to the day of CMV viraemia onset. In contrast, biomarkers reflecting cytokine release, endothelial activation, coagulation, inflammation and organ damage remained stable. Structural equation modelling identified inhibitory checkpoint regulation as the only variable independently associated with CMV reactivation. Gene expression analysis three days before reactivation revealed upregulation of innate immunity, haemostasis, and CMV-related pathways, alongside downregulation of adaptive immunity and cytokine signalling pathways. CONCLUSIONS: CMV reactivation in sepsis is preceded by broad immune dysregulation. These data provide insight into antiviral immune mechanisms that are impaired prior to reactivation and may inform preventive strategies.
Wulffraat MT, van de Weijer NG, Wijmenga-Monsuur AJ
… +8 more, Badoux P, Steens A, Smit D, Mariman R, Trzciński KP, van Sorge NM, Rots NY, van Houten MA
OBJECTIVES: Since pneumococcal conjugate vaccines (PCVs) were introduced into the Dutch childhood National Immunization Program in 2006, colonization and invasive disease of Streptococcus pneumoniae have declined, alongs...OBJECTIVES: Since pneumococcal conjugate vaccines (PCVs) were introduced into the Dutch childhood National Immunization Program in 2006, colonization and invasive disease of Streptococcus pneumoniae have declined, alongside shifts in serotype prevalence towards non-vaccine serotypes (NVTs). To monitor changes and estimate the added value of higher-valent PCVs, serotype-specific carriage, invasive pneumococcal disease (IPD) and invasive disease potential were analyzed. METHODS: During the winters of 2018/2019 and 2022/2023 pneumococcal carriage was determined among 24-month-old children and parents, and compared to carriage studies from 2005 to 2016. IPD data from Dutch surveillance (2004-2024) were included. Pneumococcal isolates were serotyped using agglutination and Quellung. Serotype-specific disease potential determined as odds ratios (OR) for IPD versus carriage. RESULTS: Pneumococcal carriage in children decreased from 66% in 2005 to 49% in 2018/2019 and 46% in 2022/2023. In 2022/2023, 29% of children carried NVTs, followed by PCV20- (11%), PCV13- (4%), PCV15- (2%) and PCV10- (0%) specific serotypes. Among parents, carriage declined from 17% in 2005 to 2% by 2022/2023. IPD incidence increased from 6·7 to 8·4 per 100,000 children under 5 years between 2018-2020 and 2022-2024, predominantly caused by an increase in serotype 19A. Serotypes 8 and 3 have the highest invasive disease potential. CONCLUSIONS: This study shows stabilized pneumococcal carriage from 2018 to 2023 with low invasive disease potential for common serotypes, except for serotype 19A. However, rising IPD incidence from other non-vaccine serotypes highlights the need for higher-valency vaccines. The newly introduced PCV15 covers 58% of IPD cases, while PCV20 could cover 73%.
Cummings BE, Stucke EM, Coulibaly D
… +38 more, Lawton JG, Sobota RS, Kone AK, Kane B, Guindo B, Tangara B, Sissoko M, Maiga F, Traore K, Diawara A, Traore A, Thera A, Dara A, Niangaly A, Daou M, Diarra I, Tolo Y, Sebastian S, Jain A, Nakajima R, Jasinskas A, Silzel EK, Shrestha B, Ouattara A, Munro JB, Laurens MB, Lyke KE, Tebben K, Bogale H, Plowe CV, Sissoko MS, Kouriba B, Takala-Harrison S, Felgner PL, Silva JC, Doumbo OK, Thera MA, Travassos MA
Plasmodium falciparum is the most virulent Plasmodium species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined par...Plasmodium falciparum is the most virulent Plasmodium species, responsible for the life-threatening severe malaria syndromes of cerebral malaria and severe malarial anemia. In a Mali case-control study, we determined parasite gene expression in cerebral malaria, severe malarial anemia, and concurrent disease featuring both syndromes by comparing RNA-seq data from severe malaria cases to matched uncomplicated malaria controls with or without a history of cerebral malaria. While severe malarial anemia comparisons produced comparatively low levels of differential expression, the comparisons of cerebral malaria and concurrent disease yielded significant differential expression of multigene families (fikk, phist, and surf) implicated in processes that escalate disease severity, such as cytoadherence and erythrocytic remodeling. We probed custom microarrays featuring these antigens with acute and convalescent sera. Children with severe malaria developed antibody responses to subsets of these proteins following severe malaria infection, suggesting exposure to these antigens during illness and their potential as targets in the development of natural protective immunity against severe malaria. Our findings address knowledge gaps surrounding parasite gene expression in severe malarial anemia. Further, these results broaden the scope of multigene families implicated in severe malaria pathogenesis and underscore the utility of transcriptome-wide approaches for a comprehensive understanding of severe disease, particularly when developing therapeutics or vaccines.
OBJECTIVE: The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was...OBJECTIVE: The preventive effect of nirsevimab, a long-acting monoclonal antibody, on infants with respiratory syncytial virus (RSV) infection beyond six months has rarely been evaluated. The objective of this study was to evaluate the preventive effects of nirsevimab beyond 6 months after RSV infection using a global database. METHODS: This was a multi-centre retrospective study using a global database (TriNetX). The participants were children under 24 months of age who required nucleic acid testing for RSV between July 2023 and June 2025. Children who received the last dose of nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months were compared with those who did not receive any nirsevimab dose by epidemic season after propensity score matching. RESULTS: A total of 4627, 861, and 532 children aged <24 months who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before RSV testing, respectively, and 210,626 children who did not receive any nirsevimab were identified. Compared with those who did not receive nirsevimab, the odds ratios (OR) of a positive RSV test result among those who received nirsevimab within 6 months, between 6 and 11 months, and beyond 12 months before testing were 0.49 [95% confidence interval (CI) 0.42, 0.57] (p<0.001), 0.67 [0.48, 0.94] (p<0.020), and 1.21 [0.89, 1.65] (p=0.234) in the last epidemic season, respectively. CONCLUSION: This study indicated that the preventive effect of nirsevimab against RSV infection was maintained for up to 12 months following administration, whereas a preventive effect beyond 12 months was not observed. The results of this study need to be interpreted with caution owing to some important limitations.
Ambrosioni J, de Lazzari E, Sánchez-Palomino S
… +15 more, Bailón L, Suanzes P, Busca C, Ramos-Ruperto L, Orviz E, Rivero Á, Mothe B, Romero JD, Falcó V, Vicens-Artés S, Moraga E, Cruceta A, Mallolas J, Miró JM, BIC-PHI Study Group
OBJECTIVES: We evaluated the efficacy, safety and impact on viral reservoir of rapid bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) initiation during primary HIV infection (PHI). METHODS: Multicenter, sing...OBJECTIVES: We evaluated the efficacy, safety and impact on viral reservoir of rapid bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) initiation during primary HIV infection (PHI). METHODS: Multicenter, single-arm clinical trial in participants with PHI of <3 months (seroconversion or incomplete serological pattern), starting BIC/FTC/TAF in 6 Spanish centers between January-2021 and September-2022. Primary endpoint was proportion of participants with viral load (VL)<50 copies/mL at 48-weeks on the Intention-to-treat-exposed population (ITTe). Cases were compared with randomly-matched retrospective PHI controls, starting other 3-drug Integrase-Strand-Transfer-inhibitor-based regimens. Reservoir was evaluated in PHI cases by Intact Proviral DNA Assay (IPDA). RESULTS: We included 64 participants, 94% cis-male, aged 32 (26;41) years.; 78% men-who-have-sex-with-men. At BIC/FTC/TAF initiation, Fiebig stages were II (14%), III (11%); IV (5%), V (54%) and VI (16%); VL was 496,520 (110,000;1,285,000) copies/mL; 62% were subtype B; median (IQR) CD4 T cell count was 406 (322;535) cells/µL; 6% had active hepatitis B virus co-infection. All participants started BIC/FTC/TAF at first specialist consultation. 81% (ITTe) and 93% (On-Treatment, OT) had VL<50 copies/mL at 48-weeks. 72% had adverse events, only 3% were grade 3/4; 91% were not-related, none led to BIC/FTC/TAF-discontinuation. 92% of controls (OT) had VL<50 copies/mL at 48-weeks (p=0.914), 11% (17%) modified initial antiretroviral regimen (p>0.001). Intact and defective proviral DNA levels significantly decreased at 48-weeks. CONCLUSIONS: BIC/FTC/TAF showed rapid viral decay, high suppression rates, good tolerability, and reservoir decline in PHI, making it an appealing regimen in this setting.
OBJECTIVES: Human adenovirus 55 (HAdV-55), a highly pathogenic double-stranded DNA virus, presents a serious global public health challenge due to its rapid transmission and complex pathogenesis. Current antiviral treatm...OBJECTIVES: Human adenovirus 55 (HAdV-55), a highly pathogenic double-stranded DNA virus, presents a serious global public health challenge due to its rapid transmission and complex pathogenesis. Current antiviral treatment options for HAdV-55 are limited, with no specific antiviral drugs available. The CRISPR-Cas system, capable of precisely targeting viral genomes, has emerged as a novel approach for antiviral therapy. This study aimed to leverage targeted DNA cleavage activity of the CRISPR-Cas12a system to develop a therapeutic strategy for effectively inhibiting HAdV-55 replication. METHODS: We developed a rapid and efficient screening platform for identifying antiviral targets by integrating CRISPR-Cas12a fluorescence detection technology with bioinformatics analysis. Using this platform, we systematically screened 194 candidate targets against HAdV-55. RESULTS: The E1B-crRNA6-Cas12a system was identified, demonstrating a highly potent antiviral activity with 99.17% inhibitory efficiency and a selectivity index (SI) of 2482.80. This target significantly outperformed the clinical broad-spectrum anti-adenovirus drug cidofovir in both inhibitory efficacy and duration. CONCLUSIONS: This study not only holds promise for providing safe and highly effective antiviral candidate targets for HAdV-55 therapy but also, through the construction of an interdisciplinary technical platform, is expected to enhance the translational potential of CRISPR antiviral technology for preclinical applications.
Tóth GE, Petersen M, Chevenet F
… +13 more, Sikora M, Tomazatos A, Bialonski A, Baum H, Horváth B, Siriyasatien P, Heitmann A, Jansen S, Offergeld R, Lachmann R, Schmidt M, Schmidt-Chanasit J, Cadar D
BACKGROUND: West Nile virus (WNV) has emerged as a public health concern in Germany since its first detection in 2018, with evidence of expanding geographic spread. Genomic surveillance is critical for tracking viral evo...BACKGROUND: West Nile virus (WNV) has emerged as a public health concern in Germany since its first detection in 2018, with evidence of expanding geographic spread. Genomic surveillance is critical for tracking viral evolution, identifying introductions, and monitoring local transmission. However, genome recovery from low-viremia samples such as those obtained through blood donor screening remains technically challenging. AIM: To develop and validate a sensitive amplicon-based sequencing protocol optimized for WNV lineage 2 and apply it to low-titer samples to support genomic surveillance in Germany. METHODS: A novel primer scheme was designed for WNV lineage 2 and applied to 43 nucleic acid testing (NAT)-positive blood donor samples collected between 2020 and 2024. Amplicon-based sequencing performance was benchmarked against metagenomic next-generation sequencing (mNGS). Recovered genomes were subjected to phylogenomic analysis to assess viral diversity and transmission dynamics. RESULTS: The amplicon protocol enabled genome recovery (>70% coverage) from samples with viral loads as low as ∼10¹ RNA copies/µL, outperforming metagenomic NGS (mNGS). Of the 43 samples, 30 yielded complete or near-complete genomes. Six distinct WNV subclades (2A-2F), including German strains, were identified, indicating multiple introductions into Germany from Central Europe. Subclade 2F emerged as the dominant and widely distributed group. Berlin, Brandenburg, Saxony, and Saxony-Anhalt were identified as persistent transmission hubs. CONCLUSION: This study highlights blood donors as valuable sentinels for WNV genomic surveillance. The validated amplicon-based sequencing approach enables sensitive, scalable genome recovery from low-viremia samples, and when integrated with routine blood donor screening, provides a robust framework for early detection, transmission dynamics, and public health preparedness.
BACKGROUND: Some studies have suggested an association between Enterococcus faecalis blood stream infection (BSI) and colorectal cancer (CRC) suggesting that screening for CRC could be reasonable. However, these studies...BACKGROUND: Some studies have suggested an association between Enterococcus faecalis blood stream infection (BSI) and colorectal cancer (CRC) suggesting that screening for CRC could be reasonable. However, these studies were limited by small numbers with low generalizability. METHODS: Danish nationwide registries were used to identify patients with first-time E. faecalis BSI from 2010 to 2021 without previous colorectal neoplasia (CRN). Age-, sex- and calendar-matched comparators from the general population were identified (1:5). We estimated the six-month cumulative incidence of CRC and CRN and a multivariable adjusted Cox analysis was used for relative comparison between groups. RESULTS: We identified 4664 patients with E. faecalis BSI (median age: 74.9 years, 73.4% males) and 23,320 comparators from the general population. For patients with E. faecalis BSI the six-month incidence of CRC was 0.45% (95% CI: 0.28-0.72%) and of CRN 2.34% (95% CI: 1.88-2.88). For matched comparators the incidence of CRC was 0.12% (95% CI: 0.08-0.17) and of CRN 0.48% (95% CI: 0.39-0.57). In adjusted analysis, patients with E. faecalis BSI had a higher HR of CRC (HR=3.70 (95% CI: 1.91-7.19) and CRN (HR=4.64 (95% CI: 3.40-6.34) than matched comparators. The six-month mortality was 36.3% in patients with E. faecalis BSI while this was 1.7% among comparators. CONCLUSION: In patients with first-time E. faecalis BSI the six months incidence of CRC was around 0.5% and 2.3% for the diagnosis of CRN, which were 3-4 times higher than in a matched cohort from the general population. Nevertheless, the absolute risks do not justify systematic screening for CRC or CRN in patients with E. faecalis BSI.
OBJECTIVES: Fluoroquinolones (FQ) are one of the most prescribed broad-spectrum antibiotics and a cornerstone of tuberculosis (TB) treatment. TB patients may have had FQ resistance before treatment initiation. However, t...OBJECTIVES: Fluoroquinolones (FQ) are one of the most prescribed broad-spectrum antibiotics and a cornerstone of tuberculosis (TB) treatment. TB patients may have had FQ resistance before treatment initiation. However, the association between pre-diagnostic FQ exposure and acquired FQ-resistant TB remains unclear. METHODS: A case-control study was conducted among all pulmonary TB patients in Shanghai during 2022-2023. Cases were TB patients who had possible acquired FQ resistance identified through whole-genome sequencing (WGS), while controls were FQ susceptible patients. Pre-diagnostic FQ prescriptions were extracted from the Shanghai Electronic Health Record (EHR) platform. RESULTS: Among 3496 patients, 7.4% had FQ-resistant TB, with 93.5% (243/260) phylogenetically inferred as possible acquired resistance. Multivariate analysis revealed FQ exposure was the strongest predictor of possible acquired FQ resistance with an aOR of 4.31 for a single prescription and 13.18 for multiple prescriptions. A nonlinear dose-response relationship between resistance probability and prescription number was found. Most prescriptions to cases were from non-TB-designated tertiary hospitals for non-TB respiratory diseases, with an exposure interval of ≥61 days prior to TB diagnosis. CONCLUSION: Acquired resistance dominates FQ resistance in Shanghai TB patients. The dose-response relationship between pre-diagnostic FQ exposure and possible acquired resistance underscores the need for judicious FQ use.
Cryptococcus neoformans and Cryptococcus gattii are World Health Organization critical and medium priority pathogens, respectively. These mainly impact people with human immunodeficiency virus residing in low- and middle...Cryptococcus neoformans and Cryptococcus gattii are World Health Organization critical and medium priority pathogens, respectively. These mainly impact people with human immunodeficiency virus residing in low- and middle-income countries, but other patient groups and settings are also affected. The high global morbidity and mortality and the limitations of current treatments provided an impetus for the development of a target product profile (TPP) for new anti-cryptococcal agents. Key attributes of the TPP include improved safety, superior (or at least comparable) activity to current treatments against all syndromes across the full disease spectrum (cryptococcal meningitis, cryptococcal pneumonia, etc.), relevance for C. neoformans and C. gattii, suitability for all age groups, oral and intravenous formulations, an acceptable treatment regimen, minimal/manageable drug-drug interactions, thermostability, and a barrier to resistance at least as high as current options. The aim of this TPP, along with the suggested discovery and development paths, is to assist all stakeholders in the development of novel cryptococcal disease treatments.
OBJECTIVE: To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs). METHODS: Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inc...OBJECTIVE: To assess whether GLP-1 RA treatment influences infection risk in randomized clinical trials (RCTs). METHODS: Systematic searches were conducted across PubMed, EMBASE, Cochrane Library, and Web of Science (inception to September 24, 2024), and reference lists of eligible articles. RCTs comparing GLP-1 RA treatment with placebo or non-GLP-1 RA treatments were included. Dual reviewer resolved disagreements by consensus. Two reviewers independently extracted data following PRISMA recommendations and assessed risk of bias via Cochrane tool. RESULTS: A total of 136 RCTs (n = 164,322) were included. GLP-1 RA treatment was associated with a significant reduction in serious infections (RR, 0.89; 95% CI, 0.86-0.93; absolute risk difference, -30 per 10,000 persons/year; I² = 0%), non-serious (RR, 0.90; 95% CI, 0.85-0.97; I² = 77%), and total infections (RR, 0.89; 95% CI, 0.84-0.94; I² = 77%). Reductions were observed for serious respiratory (RR, 0.84; 95% CI, 0.79-0.90), skin and subcutaneous (RR, 0.77; 95% CI, 0.68-0.87), musculoskeletal (RR, 0.79; 95% CI, 0.65-0.97), vascular (RR, 0.65; 95% CI, 0.47-0.90), and COVID-19 infections (RR, 0.82; 95% CI, 0.72-0.92), all with I² = 0%. Meta-regression showed greater weight loss (β = -0.011; P =.045), hemoglobin A1c reduction (β = -0.229; P =.026), and higher GLP-1 RA doses (RR, 0.87; 95% CI, 0.83-0.92) were associated with lower risk. CONCLUSION: GLP-1 RA use was associated with reduced risk of serious infections, particularly in respiratory, skin, musculoskeletal, vascular systems and COVID-19, partially explained by weight loss and improved glycemic control.
Mycoplasma pneumoniae (MP) infection in children has recently re-emerged with a higher rate of hospitalization in the post-COVID-19 period. However, understanding of how the adaptive immunity plays a role in the bacteria...Mycoplasma pneumoniae (MP) infection in children has recently re-emerged with a higher rate of hospitalization in the post-COVID-19 period. However, understanding of how the adaptive immunity plays a role in the bacterial pneumonia is often restrained by recurrent infection and complex co-infection with M. pneumoniae. Herein, we took advantage of the single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry to characterize the impairment of peripheral T and B lymphocytes in pediatric patients with mild Mycoplasma pneumonia (MMPP). These patients were M. pneumoniae mono-infected at hospitalization, and showed an expansion of both effector and memory CD8 T cells, with exhausted KLRG1 CD8 T compartments prevailed. Moreover, they exhibited a hyperactivation of IgM plasma cells and unswitched memory B cells, which could partly explain the IgM seroconversion routinely diagnosed in MMPP. Therefore, the hypo-functional CD8 T cells and polarization of IgM secreting cells might help explain the ill-controlled bacterial replication in MMPP. Furthermore, compared to the healthy controls, IL-17A producing Th17 cells were reduced in MMPP, but cytotoxic granzymes increased significantly. Reduced IL-17A would suggest elevated M. pneumoniae colonization and reduced bacterial clearance in the respiratory tract, whereas cytotoxic property of this pathogenic Th17 cells might play a role in the pulmonary hyper inflammation. Therefore, this work managed to characterize the landscape of dysfunctional T and B lymphocytes that associates with the immune evasion and immunopathogenesis of MMPP.
Genital herpes (GH), historically associated with herpes simplex virus type 2 (HSV-2), is changing its etiology. Since the last few decades, there has been an increase in genital infections caused by herpes simplex virus...Genital herpes (GH), historically associated with herpes simplex virus type 2 (HSV-2), is changing its etiology. Since the last few decades, there has been an increase in genital infections caused by herpes simplex virus type 1 (HSV-1). In fact, in several countries, preferably in high-income regions such as North America or Western Europe, HSV-1 has become the leading cause of first-episode GH, especially among adolescents and young adults. However, the epidemiological trend varies geographically, with slower changes observed in Africa, Latin America, and Southeast Asia, where GH HSV-2 remains dominant. This epidemiological shift may be mainly due to the decline in HSV-1 seroprevalence, decreased childhood exposure to the virus, and changes in sexual practices. Despite the global decline in HSV-1 seroprevalence, GH caused by HSV-1 is rising by 1-2% annually in many areas. This review summarizes the seroprevalence of HSV-1/-2 worldwide in recent decades and discusses the changes in GH etiology and contributing factors. Despite the substantial global burden of the disease and its psychosocial impact, no vaccine or curative treatment exists. Active surveillance, health and sexual health education, and targeted interventions are vital to manage this changing landscape and to mitigate the public health issue posed by GH and HSV-1.