Infectious Diseases

Data evaluating human papillomavirus (HPV) vaccine impact in Spain remain limited. We aimed to assess HPV and cytology findings among vaccinated and unvaccinated women as an early indicator of its effectiveness. During April 2024-January 2026, a total of 908 women participating in a population-based cervical cancer screening in three regions of Spain were recruited (58% vaccinated). Cervical samples and epidemiological and vaccination data were obtained. HPV was detected in 37% (337/908) and high-risk HPV in 24% (221/908). High-grade cytological lesions (1.2%, 11/907) were more frequent in unvaccinated women (2.4% vs 0.38%, p=0.011) and showed higher prevalence of HPV 16/18 (5.5% vs 0.76%; aOR: 4.9; 95% CI: 1.4-17) and HPV31 (3.4% vs 1.3%; aOR: 2.7; 95% CI: 1.0-6.9) compared with vaccinated women. HPV51 and HPV70 were more frequent among vaccinated women; however, both were associated with factors unrelated to vaccination. HPV51 was linked to a higher number of sexual partners (aOR: 2.6; 95% CI: 1.2-5.6), while HPV70 to smoking (aOR: 0.36; 95% CI: 0.13-0.99). Lower detection of HPV 16/18, HPV31 and high-grade lesions among vaccinated women supports vaccine effectiveness and cross-protection, highlighting the importance of continuous comprehensive surveillance of HPV genotype, including epidemiological and sexual behavioral factors.

Background Ecological surveillance indicates (regional) establishment of West Nile virus (WNV) and Usutu virus (USUV) in the Netherlands. However, the incidence of human infections remains unknown. Methods We identified WNV and USUV infections in the Netherlands in 2020-2023, using a longitudinal, nationwide population-based cohort, applying a two-tiered serology approach based on protein micro-array and virus neutralization. IgG data were used to estimate overall seroprevalence and infection incidence, and to study antibody longevity. Study set-up enabled tracking of the period of seroconversion and linking of self-reported travel history. The analyses took account of the survey design and weights were incorporated to match the Dutch population distribution following census data. Findings Among 4290 participants, we identified 113 probable WNV and/or USUV cases, including 55 seroconversions. Thirty-six cases were confirmed by antibody neutralization, of which 12 seroconverted. Six confirmed seroconverters were identified as autochthonous infections. The overall weighted seroprevalence was estimated at 0.54% (0.21-0.87%) for WNV and 0.25% (0.09-0.40%) for USUV. The weighted incidence for autochthonous WNV and USUV infection was estimated as respectively 0.06% (95% CI 0-0.12%) and 0.04% (95% CI 0-0.09%). Interpretation The estimated infection incidence and seroprevalence of WNV and USUV indicate a substantial underdiagnosis of clinical cases in the Netherlands in 2020-2023. These observations highlight the need for increased awareness among physicians to identify cases and the need for continued paired syndromic-laboratory surveillance for these viruses.

The continued circulation of H5 clade 2.3.4.4b highly pathogenic avian influenza virus (HPAIV) has caused extensive mortality in wild bird populations worldwide with increasing spillover to mammals. In 2022, H5 HPAIV emerged in Svalbard, Norway, with subsequent detections in wild birds, walruses, polar bears, and arctic foxes. To understand the population-level exposure among Svalbard arctic foxes, we analysed body fluids from carcasses trapped in 2006-2015 (n = 56), 2023-2024 (n = 112), and 2024-2025 (n = 94) for antibodies to H5 avian influenza (anti-H5), influenza A nucleoprotein (anti-NP), and neuraminidase subtypes using ELISAs, haemagglutination inhibition (HI), and a multiplex assay. Only three samples from 2006-2015 tested positive for anti-H5 and were interpreted as false positives. In 2023-2024, seropositivity for anti-H5 was high (95%), supported by a lower anti-NP seropositivity (85%) and antibody profiles consistent with mixed H5N1 (42%) and H5N5 (52%) exposure. In 2024-2025, anti-H5 and anti-NP seroprevalences remained high (83% and 57%), with H5N5 (87%) exposure predominating over H5N1 (3%). A subset of anti-H5-positive samples tested positive by HI (2023-2024: 30%; 2024-2025: 14%). Juveniles with exposure limited to the previous season had higher odds of anti-H5 seropositivity in 2023-2024 than in 2024-2025 (OR 5.5). Analysis of paired lung extracts from a subset of individuals (n = 63) yielded results concordant with body fluids, using an indirect anti-H5 ELISA adapted for carnivores. Our findings demonstrate widespread H5 virus exposure. Together with occasional reports of progression to fatal HPAI, this highlights the need for continued population monitoring to evaluate ecological consequences.

Background. The objective was through an analysis of longitudinal data from the DepIST-H cohort to estimate the incidence, describe the dynamics and factors associated with CT/NG infection in MSM in Togo. Methods. A total of 200 MSM in Lome, Togo, were included in the ANRS I MIE 12400/DepIST-H cohort, half living with HIV. After inclusion in the study, participants received follow-up clinical visits at 6 and 18 months, and laboratory tests were performed at baseline (M0) and at 12 and 24 months (M12 and M24). PCR tests for CT and NG were performed from pharyngeal, anal and urine samples collected using the Xpert(R) CT/GC kit (Sunnyvale, CA, USA). To identify the factors associated with anal bacterial STIs, offset term Poisson regression models were performed. Results. Among 200 MSM (median age 24 years), CT and NG incidence rates were high ({approx}22 cases per 100 person-years), particularly at the anal site. Multiple partners significantly increased anal NG incidence (aIRR 2.35). Anal NG incidence was significantly lower among participants with income-generating activity (aIRR 0.57). Trends suggested higher anal CT and NG incidence in the presence of pharyngeal infection, but associations were not statistically significant Conclusion. This study confirms that MSM remain highly exposed to STIs in Togo and highlights the need to strengthen prevention efforts within this population. Postexposure doxycycline prophylaxis and multisite pooled-sample screening represent promising avenues to strengthen prevention efforts within these populations.

Background: Olfactory dysfunction is a recognised but poorly characterised comorbidity of Primary Ciliary Dyskinesia (PCD). No prior systematic review has synthesised its prevalence or clinical correlates. Methodology: A PRISMA compliant systematic review and meta-analysis was conducted. Five databases were searched to February 2026. Observational studies reporting olfactory function in confirmed PCD were included. Risk of Bias was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis using the Freeman-Tukey double arcsine transformation was performed to calculate pooled prevalence with 95% confidence intervals (CI) and prediction intervals (PI). Results: Twelve studies (n=865) were included. Overall pooled prevalence of olfactory dysfunction was 43.4% (95% CI 25.2-62.5%; 95% PI 0.1-99.0%). Objective psychophysical testing yielded a significantly higher pooled prevalence of 66.1% (95% CI 55.5-76.0%; 95% PI 38.4-88.9%) compared to patient-reported outcome measures (30.5%; 95% CI 11.4-54.0%). Older age, greater sinonasal disease burden, and specific ciliary ultrastructural defects were associated with worse olfactory function. A striking discordance between objective dysfunction and subjective awareness was observed across multiple studies. Conclusions: Olfactory dysfunction is highly prevalent in PCD and substantially under-recognised by patients. Routine objective olfactory screening should be integrated into standard multidisciplinary PCD care.

Tick-borne encephalitis virus (TBEV) is a zoonotic flavivirus maintained in complex enzootic cycles involving ticks and vertebrate hosts. While vector-mediated transmission has been extensively studied, host-associated mechanisms, including vertical transmission and prolonged viral carriage in natural reservoir populations, remain poorly understood. Here, we investigated TBEV circulation, genetic diversity, and evidence for vertical transmission in bank voles (Clethrionomys glareolus) from a highly endemic region of North-eastern Poland. A total of 258 wild rodents were screened using molecular and serological approaches. TBEV RNA was detected in 14.3% of individuals, whereas seroprevalence was substantially lower (6.6%), revealing limited concordance between viral presence and humoral response under natural conditions. Near-complete genome sequences were obtained from 10 TBEV-positive individuals, representing the first near-complete TBEV genomes generated from wild rodents in Poland. All isolates belonged to the European subtype (TBEV-Eu), and phylogenetic analysis revealed two genetically distinct viral clades co-circulating within a narrow spatiotemporal window. Importantly, TBEV RNA and/or envelope protein were detected in embryos from naturally infected females, providing evidence consistent with vertical transmission in a wild reservoir host. Together, these findings suggest that vertical transmission and complex host infection dynamics may be underappreciated components of TBEV maintenance in natural reservoir populations. Our results highlight the need to integrate vertebrate host dynamics into models of TBEV ecology and support expanded wildlife-based surveillance to better understand and predict zoonotic risk.

Background The phase 3 ADVOCATE trial evaluated the efficacy and safety of avacopan in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Concerns raised regarding the 2019 primary endpoint adjudication process prompted a blinded, independent readjudication of all participants' primary outcomes, the results of which are described here. Methods Patients with GPA or MPA were randomized 1:1 to receive oral avacopan 30 mg twice daily or oral prednisone on a scheduled taper, each in combination with rituximab- or cyclophosphamide-based standard of care. In 2026, the Duke Clinical Research Institute Clinical Events Classification group conducted an independent, blinded committee re-adjudicated the Birmingham Vasculitis Activity Score (BVAS), relapse, and remission from weeks 26 through 52 using procedures aligned with the original adjudication charter. The primary endpoints were remission at week 26 and sustained remission at week 52. As per the original analysis plan, noninferiority and superiority were declared if the lower bounds of the 95% confidence interval (CI) for the difference in the primary outcome rates between avacopan and a prednisone taper were greater than -20.0 and 0.0 percentage points, respectively. Results Among 330 participants in the intent-to-treat population, remission at week 26 was achieved by 68.1% (113/166) and 67.1% (110/164) of participants in the avacopan and prednisone taper groups, respectively, in the 2026 readjudication (adjusted difference: 2.2%; 95% CI, -7.5, 11.9), compared with 72.3% (120/166) and 70.1% (115/164) in the 2019 primary outcome adjudication (adjusted difference: 3.4%; 95% CI, -6.0, 12.8). Sustained remission at week 52 was achieved by 61.4% (102/166) and 52.4% (86/164) of participants, respectively, in the 2026 readjudication (adjusted difference: 9.8%; 95% CI, -0.3, 19.9), compared with 65.7% (109/166) and 54.9% (90/164) in the 2019 readjudication (adjusted difference: 12.5%; 95% CI, 2.6, 22.3). Concordance between the 2019 and 2026 adjudications was 95.2% for remission and 93.6% for sustained remission. Conclusion The re-analysis of ADVOCATE based on the 2026 readjudication further supports the efficacy of avacopan for GPA/MPA. Non-inferiority of avacopan versus a prednisone taper was confirmed at weeks 26 and 52 despite a median 81% reduction in glucocorticoid exposure observed in the avacopan versus prednisone taper groups. While a consistent numerical difference favoring avacopan at week 52 was observed in the 2019 and 2026 analyses, this difference did not reach statistical superiority.

Aim: Brucellosis remains endemic throughout the Mediterranean basin, the Middle East and Central Asia. Genitourinary involvement is an uncommon but clinically consequential focal complication that closely mimics urological emergencies and may precipitate unnecessary surgery. Contemporary data describing its frequency, laboratory signature and treatment outcomes in endemic settings remain limited. Material-Methods: We retrospectively screened all adults ([≥]18 years) with confirmed brucellosis managed at a tertiary infectious diseases unit between January 2008 and December 2020. Genitourinary involvement was defined as epididymo-orchitis, orchitis, epididymitis and/or brucellar pyelonephritis. Clinical, laboratory, ultrasonographic, therapeutic and outcome variables were abstracted using a standardised form. Proportions are reported with Wilson score 95% confidence intervals (CI). Reporting followed the STROBE statement. Result: Genitourinary involvement was identified in 18 of 125 patients with brucellosis (14.4%; 95% CI 9.3-21.6); 16 (88.9%) were men and the mean age was 35.2 years (range 22-62). Scrotal disease dominated the male presentation: epididymo-orchitis in 10 of 16 men (62.5%; 95% CI 38.6-81.5), orchitis in 4 (25.0%) and epididymitis in 2 (12.5%). Both women presented with pyelonephritis, one of whom developed a tubo-ovarian abscess requiring drainage. Constitutional features were near-universal (fatigue 100%, night sweats 88.9%, fever 77.8%). Leukocyte counts remained within the reference interval in every patient (mean 5,680/mm3), whereas erythrocyte sedimentation rate (mean 32 mm/h) and C-reactive protein (mean 24.2 mg/L) were only mildly to moderately raised. The Coombs anti-Brucella test was positive in 18 of 18 patients (100%) and the standard agglutination test in 17 of 18 (94.4%), whereas blood culture yielded Brucella melitensis in only 1 of 18 (5.6%). Concomitant extragenitourinary focal disease was present in 8 patients. All patients received doxycycline plus rifampicin; none required modification of the regimen or orchiectomy, and no treatment failure occurred (0 of 18; 95% CI 0-17.6). Median follow-up was 12 weeks (range 6-52) and no relapse was documented within this interval. Conclusions: In endemic regions, genitourinary brucellosis should be suspected in any patient with acute scrotal or flank symptoms accompanied by constitutional complaints, even when the leukocyte count is normal and acute-phase reactants are only marginally elevated. Coombs anti-Brucella serology rather than blood culture is the diagnostic cornerstone, and prompt doxycycline-rifampicin therapy averts surgical intervention.

ABSTRACT Background Cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) may involve parasite dissemination from the primary skin lesion to clinically healthy mucosal sites, a process potentially relevant to the development of mucosal leishmaniasis. Parasite burden and Leishmania RNA Virus 1 (LRV1) have been proposed as factors influencing parasite persistence, dissemination, and treatment response. We investigated whether parasite load and LRV1 detection in skin lesions were associated with Leishmania in clinically healthy nasal mucosa and, in a subset of patients, with therapeutic outcome. We also assessed the relationship between LRV1 and parasite load. Methodology/Principal findings We conducted a prospective observational cohort study. Parasite load and LRV1 were assessed by qPCR in skin lesions and clinically healthy nasal mucosa from patients with localized cutaneous leishmaniasis in Rondonia, Brazilian Amazon. Samples were evaluated before treatment (D0), at the end of treatment (D20), and during follow-up (D90-180). Among 178 patients screened, CL was confirmed in 113. LRV1 was detected in skin lesions in 34.51% of patients and in nasal mucosa in 24.13%. Leishmania DNA was detected in clinically healthy nasal mucosa in 12.38% of patients. LRV1 detection in the skin lesion was associated with detection of Leishmania in the nasal mucosa. Higher parasite loads were observed in more recent lesions. Among patients evaluated for therapeutic outcome, higher parasite load before treatment was associated with treatment failure and was the factor most strongly associated with an unfavorable response in multivariate analysis. Conclusions/Significance LRV1 detection in cutaneous lesions was associated with Leishmania in clinically healthy nasal mucosa, although the significance of this association and its relationship with parasite dissemination require further investigation. In contrast, parasite burden was associated with therapeutic outcome, with higher pre-treatment loads observed in patients who experienced treatment failure. The absence of an association between LRV1 and parasite load suggests that these two parameters may provide distinct information regarding parasite detection at mucosal sites and therapeutic response.

Background Following the emergence of a novel Shamonda-like virus (SHAV) in Europe, suspected clinical cases in dairy cattle were reported in Northeastern Italy. Investigation was required in dairy cattle in Northeastern Italy. Methods Samples were collected from 28 farms displaying fever and reduced milk yield and were screened using molecular methods (PanSimbu real-time RT-PCR followed by Sanger sequencing and differential PCRs for SBV/BTV). Positive samples were subsequently confirmed by Sanger sequencing and selected samples underwent whole-genome sequencing using a metagenomic approach. Results Twenty-four among sera and blood samples from 12 farms tested positive for SHAV. WGS confirmed that Italian strains share maximum identity with the European SHAV-EU1 clade. Limitations This study concerns the results of clinical investigations on suspected cases in the two autonomous provinces of Trento and Bolzano. At present, it is not possible to infer on the circulation of the virus in other Italian provinces. Conclusions This study documents the first detection and genetic characterization of SHAV-EU1 in Italian cattle, indicating active circulation of this virus across Europe. Its identification in two north-eastern Italian provinces does not rule out wider, undetected circulation. In this regard, assessing its geographical extent requires careful evaluation, just as much remains to be discovered about its host range and the severity of symptoms.

Objectives To evaluate the impact of COVID-19 vaccination on the prevention of long COVID (LC) in the Omicron era through an updated systematic review and meta-analysis. Methods We performed an update of our previously published systematic review and meta-analysis of vaccination and LC risk (searches between 1 January 2022 and 1 March 2024). Databases (Embase, MEDLINE, PubMed, Europe PMC, LILACS, Cochrane COVID-19 Study Register) were searched for studies published between 1 March 2024 and 13 July 2026. Observational studies assessing the impact of vaccination on the risk of LC four or more weeks after SARS-CoV-2 infection were included. Vaccines were restricted to those centrally authorised in the European Union. Random-effects meta-analyses, restricted to adults, were performed to calculate pooled odds ratios (OR) of LC in three comparisons: vaccinated (any dose) versus unvaccinated; booster vaccination versus unvaccinated; and booster vaccination versus primary course vaccination only. Results Nineteen new studies were identified, of which ten were included in the updated meta-analyses alongside eight studies from the original review. The pooled OR of LC in vaccinated adults (any dose) versus unvaccinated was 0.75 (95% confidence interval [CI] 0.67-0.84; 13 studies). ORs were also lower for booster vaccination versus unvaccinated (0.73; 95% CI 0.65-0.82; 6 studies), and booster vaccination versus primary course vaccination (0.63; 95% CI 0.53-0.75; 6 studies). Significant associations between vaccination and lower LC odds were observed in subgroup analyses of mRNA-only vaccination and LC outcomes three or more months after infection. Conclusions This updated review and meta-analysis reinforces our previous finding that vaccination may reduce the burden of LC in the Omicron era, with booster doses potentially providing additional protection. Although evidence in high-risk groups now prioritised for vaccination in most countries remains limited, these findings clearly demonstrate the benefits of vaccination and support current seasonal vaccination strategies.

Objectives: To evaluate the epidemiological evolution of unique pneumococcal serotypes covered by either PCV20 or PCV21, common serotypes by both vaccines and non-vaccine serotypes in adults. Methods: We characterized all national IPD clinical isolates from January 2009 to June 2026. Results: The highest burden of IPD was caused by serotypes shared between PCV20 and PCV21 with serotypes 3 and 8 the most prevalent in adults of all ages. During the pre-pandemic period, IPD caused by unique-PCV20 serotypes declined probably due to herd protection by paediatric vaccination with PCVs. In contrast, unique-PCV21 serotypes increased in incidence accounting for more cases than unique-PCV20 serotypes. However, after the COVID-19 pandemic, a different pattern was observed with unique-PCV20 serotypes increasing in incidence due a marked rise in IPD caused by serotypes 4 and 14 that has progressively reduced the gap in disease coverage. In adults aged 18-64 years, the fraction of disease that could be prevented with PCV20/PCV21 changed from 5% in favour of PCV21 (years 2022/2023) to 15% in favour of PCV20 (year 2026) whereas in adults [≥]65 years the vaccine contribution declined from 20% in favour of PCV21 (year 2022) to 8% in 2026. Conclusions: IPD trends in adults have changed after the COVID-19 pandemic, especially in recent years. Our study emphasizes the rapid re-emergence of infections caused by traditional PCV7 serotypes especially serotypes 4 and 14 and reinforce the idea that the use of broader PCVs must be accompanied by an increase in the uptake rates in adults of all ages.

Since mid-June 2026, an acute, non-fatal syndrome with high herd morbidity, reduced milk yield, diarrhea, fever and lethargy affected dairy cattle in southern Germany and Switzerland. Major viral pathogens were excluded. Pan-Simbuvirus PCR first detected an orthobunyavirus, subsequently confirmed by metagenomic sequencing, which enabled recovery of a complete "Shamonda-like" genome. One sentence summary lineMore than a decade after the emergence of Schmallenberg virus in 2011, a novel "Shamonda-like" orthobunyavirus of the Simbu serogroup has now emerged in Central Europe.

Computer vision models that estimate body mass index (BMI) from facial features offer a non-invasive, low-cost alternative to physical measurement, with uses in telemedicine, emergency care where a scale or measuring tools arent available, automated self-monitoring, and large-scale epidemiological research. Most of these models, however, are trained on government records, social media images, and celebrity photographs, sources that introduce dataset biases and fail to represent the general public. This study tests how well a face-to-BMI machine learning model generalizes across populations, specifically how morphological diversity and population-specific training data affect cross-cultural accuracy. We trained and evaluated Vision Transformer (ViT-H/14) models on paired BMI measurements and facial photographs from four Indigenous populations: the Orang Asli of Malaysia, the Ju/hoansi of Southern Africa, the Sama residing in the Philippines, and the Tsimane of Bolivia. To evaluate how training data composition affects predictions, we compared four training strategies, from single-population models (focal models) to models trained on the full combined global dataset (global models). In-distribution training always produced the best performance. Models exposed to a target populations morphology, whether focal or global, consistently predicted BMI most accurately for that population. But when a target population differed from the training sample, adding more cross-cultural variation to training improved out-of-distribution predictions. Therefore, training on a populations own data works best when that data exists, and training on data spanning a wide range of human morphology is the strongest fallback when it doesnt. These findings suggest that while target population training data produces the most accurate results, training on datasets that capture global morphological variation substantially improves performance in unrepresented populations. Broader diversity in training data is essential for developing machine learning health tools that generalize reliably across human populations.

BackgroundOutbreaks of fluconazole-resistant Candida parapsilosis have recently emerged worldwide. In Spain, this phenomenon has been reported since 2020, mainly involving isolates from different clones harbouring the Y132F mutation at Erg11. MethodsWe analysed the expansion of fluconazole resistant C. parapsilosis strains within the national antifungal resistance surveillance program. Genetic clustering and relationships were assessed using microsatellite typing and whole genome sequencing. FindingsWe identified the expansion of three distinct clones carrying the Y132F mutation. Additionally, there was an increase in strains harbouring the G458S mutation, most of which belonged to a clonal complex, although other less prevalent clones were also detected. G458S isolates showed higher resistance to azoles than Y132F strains, particularly to voriconazole and isavuconazole. This increased resistance was associated with mutations in the Tac1 transcriptional regulator and duplication of a chromosomal region containing Tac1 and Erg11. One G458S isolate without mutation at Tac1 exhibited lower MIC values. Furthermore, two isolates carried the K143R mutation, and a distinct group of resistant strains without detectable ERG11 mutations was also identified. Resistant cases were detected across 31 hospitals in 12 autonomous regions. InterpretationOur findings indicate a concerning nationwide expansion of antifungal-resistant C. parapsilosis in Spain, involving multiple resistance mechanisms and clonal lineages, with implications for antifungal treatment and infection control strategies.

The recent large-scale circulation of High Pathogenicity Avian Influenza (HP AI) viruses H5Nx of clade 2.3.4.4b has been responsible for massive die-offs in wild species, notably in long-lived seabirds, with unknown implications for the immunity of surviving individuals. In the North Atlantic, northern gannet colonies were heavily affected in 2022, with more than 40% mortality observed among breeding adults and some surviving individuals developing dark irises. Using samples collected in 2023 and 2024 on Rouzic colony (France), we report persistent individual anti-AI antibody levels and seroneutralisation titres, with most of the immune individuals showing dark irises. A modelling approach further stressed the importance of long-lasting immunity in such species by showing that the proportion of individuals which kept their immunity between years strongly limited decreases in population size in case of repeated outbreaks. Overall, our results highlight the existence and importance of long-lasting immunity in long-lived species for population persistence.

Long COVID (LC) is a broad label encompassing the heterogeneous long-term consequences of SARSCoV2 infection that persist for at least 3 months post-infection. Despite its substantial global burden, there is still a lack of reliable biomarkers or panels capable of distinguishing individuals with Long COVID from healthy individuals or from those who have recovered from acute COVID-19. We previously characterized a biomarker panel comparing 85 adults with WHO-defined Long COVID against 85 age- and sex-matched controls who had recovered within three months of acute COVID-19 in 2020, at between 12 and 24 months post-infection. That initial profile evaluated blood cell counts, coagulation status, routine SARS-CoV-2 serology, immune cell populations, and basic cytokine levels based on Luminex assays. We have enhanced our biomarker panel by incorporating more precise cytokine quantification using the high-precision ELLA automated immunoassay system. To assess potential ongoing peripheral systemic inflammation, we measured classical inflammatory markers in blood, including C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha), interleukin (IL)1beta, and IL6. In this manuscript, we present data that confirm age- and gender-matching between the LC and control group; and compared differences in cytokine levels and comorbidities.

Background: In England, a national school-based human papillomavirus (HPV) vaccination programme was introduced in September 2008. Routine vaccination against HPV16/18 is offered to girls aged 12-13 and a 'catch-up' offer ran for girls aged 14-18 during the programme's first two years. Methods: Data from 19,407 women aged 25-29yrs attending cervical screening across England 2016-2025 were collected and residual samples from 4,837 high-risk (HR) HPV-screening-positive women were genotyped to monitor type-specific HR-HPV prevalence and evaluate vaccination impact. Results: Type-specific HR-HPV results were available for 3,683 HR-HPV-screen-positive samples. Estimated age-adjusted prevalence of HPV16 and HPV18 was 91% (95% confidence interval [CI]: 87-94%) and 84% (95%CI: 65-93%) lower respectively among routine-eligible women than vaccination-ineligible women. Large declines were also observed for HPV31 (85% [95%CI: 72-92%]) and HPV45 (84% [95%CI: 73-90%]) but not for other HR-HPV types. Among 618 women with cytological abnormalities, HPV16/18 was present in samples from 53.9% (95%CI: 34.8-73.1%) of vaccination-ineligible, 18.1% (95%CI: 13.5-22.7%) of catch-up-eligible, and 6.5% (95%CI: 3.6-9.3%) of routine-eligible women. Conclusions: The early years of the HPV vaccination programme in England conferred strong protection against HPV16, 18, 31 and 45, and dramatically changed the target remaining for screening strategies to detect and reduce cervical disease.

Phage Display Immunoprecipitation sequencing (PhIP-Seq) is a high throughput method allowing to measure antibody binding against hundreds of thousands of potential antigens. Typically, blood samples of hundreds to thousands of individuals are measured in 96-well plates, necessitating distribution of samples on multiple plates and processing in batches. To correctly interpret PhIP-Seq results, it is crucial to understand its nature and technical limitations. Here, we analyzed 195 technical replicates of controls (anchor samples) from 49 plates measured in 13 immunoprecipitation runs to gauge technical variability and replicability. While there were few false-positive enriched peptides, we observed a substantial fraction of false negatives. The total number of enriched peptides can be affected by batch effects. Additionally, the type of biological material used (serum or plasma) influences enrichment profiles with an antigen library containing bacterial proteins due to the interaction of phages with plasma proteins. Finally, replicating measurements in different labs produces comparable enrichment profiles, but slight differences in a subset of peptides are noticeable. These results suggest best practices for PhIP-Seq experiments. Most importantly, due to batch effects, samples of cases and controls should be evenly distributed between 96-well plates to avoid confounding with biological effects. Also, for highly complex libraries, the total number of enriched peptides can be a technical artifact and potentially not a feature useful in comparisons.

Background Human papillomavirus (HPV) is the primary cause of cervical cancer, with women living with HIV at increased risk of HPV infection and HPV related disease. Data on HPV prevalence and genotype distribution among adolescent girls and young women (AGYW) in rural South African settings remain limited. We estimated HPV prevalence, genotype distribution, and factors associated with HPV infection among AGYW in a high HIV prevalence district of KwaZulu Natal, South Africa. Methods This cross-sectional study was nested within the baseline survey of the Thetha Nami population-based trial among young people aged 15 to 30 years in rural uMkhanyakude District, KwaZulu-Natal. Survey participants were asked to provide dried blood spots for HIV testing and genital swabs for STI testing. For this study, we selected AGYW living with HIV with available vaginal swabs and a frequency-matched sample of AGYW without HIV. HPV genotyping was done using the HPV Direct Flow Chip Kit (Master Diagnostica, Spain). Genotype-specific HPV prevalence was described overall and by HIV status. Logistic regression was used to identify factors associated with HPV infection. Results Among 187 AGYW with valid HPV results, 90 (48.1%) were living with HIV. Overall HPV prevalence was 69.1% (95% confidence interval (CI)=54.5 to 80.7%) and high-risk (hr)HPV prevalence was 57.3% (95%CI=44.1 to 69.6%). HPV prevalence was higher among AGYW living with HIV than among AGYW without HIV (84.6% vs 64.6%, p=0.02). HPV genotype distribution varied by HIV status: HPV35, HPV45 and HPV58 were the most prevalent hrHPV genotypes among AGYW living with HIV, vs HPV52, HPV56 and HPV31 among AGYW without HIV. No HPV16 or HPV18 infections were detected among participants who were age-eligible for the national HPV vaccination programme. Reported condomless sex (adjusted odds ratio (aOR)=2.23, 95%CI=1.06 to 4.70) and the presence of another sexually transmitted infection (aOR=4.30, 95%CI=1.52 to 12.20) were associated with HPV infection. Conclusions AGYW in rural uMkhanyakude experience a high burden of hrHPV infection, especially those living with HIV. Regardless of HPV vaccination status not being confirmed, no HPV 16/18 was detected among vaccine-eligible AGYW. The higher prevalence of non-HPV16/18 hrHPV genotypes covered by the nonavalent vaccine highlights the potential value of vaccines with broader genotype coverage. These findings support expanding HPV screening and cervical cancer prevention programmes in high HIV prevalence settings.