Biology and Life Sciences

Abstract: Respiratory viral infections impose a substantial global health burden. Among these, respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in young children, immunocompromised individuals, and older adults. During the COVID-19 pandemic, co-circulation of RSV and COVID-19 led to increasing reports of coinfections, which continue to occur in endemic settings. In this study, we employed a physiologically relevant in vitro model comprising human primary respiratory epithelial cells cultured at an air–liquid interface (ALI), together with the A549-ACE2 cell line model, to investigate the impacts of sequential RSV and SARS-CoV-2 infection. This platform enabled us to examine how host responses primed by an initial RSV infection influence subsequent SARS-CoV-2 infection. Our findings demonstrate that RSV-induced host response significantly restricted SARS-CoV-2 gene expression. Notably, we identified that RSV induced phospholipid scramblase 1 (PLSCR1), an interferon-stimulated gene previously implicated in antiviral defense against SARS-CoV-2, as a novel potential mediator of this effect. Together, these mechanisms are consistent with the phenomenon of viral interference, whereby one respiratory virus transiently reduces susceptibility to another, providing a biologically plausible explanation for cross-protective effects observed in sequential infections.

Abstract: Chronic obstructive pulmonary disease (COPD) and inflammatory bowel disease (IBD) are heterogeneous inflammatory disorders. COPD can be classified into emphysema and chronic bronchitis, whereas IBD can be classified into Crohn’s disease and ulcerative colitis. We hypothesize that COPD, like IBD, is also an autoimmune disease. However, the detailed immunopathogenesis of these diseases remains unclear. In this review, we summarize experimental, epidemiological, and clinical evidence linking autoimmunity to these disorders. Emphysema and Crohn’s disease are proposed to be TH1-dominant autoimmune disorders, whereas chronic bronchitis and ulcerative colitis are proposed to be TH22-dominant autoimmune disorders. A more detailed understanding of the immunopathogenesis of these diseases may support more specific and effective therapeutic strategies.

Abstract: Background: To determine the molecular relationship between pyrazinamide (PZA) and bedaquiline (BDQ) resistance mechanisms in multidrug-resistant tuberculosis (MDR-TB) and drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) isolates to improve treatment strategies. Methods: Phenotypic drug susceptibility testing (DST), resistance gene amplification and sequencing (pncA, panD, hadC, and Rv0678), and efflux pump gene expression (mmpS5 and mmpL5) by qRT-PCR were performed on 71 clinical MTBC isolates from seven provinces in Southern Türkiye (2022-2023). Results: PZA resistance was closely associated with MDR-TB (χ² = 38.0, p < 0.0001), exclusively detected in MDR isolates (42% overall; 73% of MDR). pncA mutations were detected in 77% of PZA-resistant isolates with strong genotype-phenotype correlation (p = 0.009, r = 0.45), while panD mutations were present in 40% and showed less association (p = 0.14). No hadC or Rv0678 mutations were identified despite significant overexpression of efflux genes mmpS5 and mmpL5 in MDR strains (p < 0.001). Conclusions: PZA and BDQ resistance arise through distinct, non-overlapping mechanisms. PZA-resistant MDR-TB without Rv0678 mutations confirms bedaquiline's independent therapeutic value and success in treating PZA-resistant cases.

Abstract: Background: Bedaquiline (BDQ), delamanid (DLM), and linezolid (LZD) are core drugs for multidrug-resistant tuberculosis (MDR-TB) treatment. Comprehensive regional data on phenotypic susceptibility and genotypic resistance-associated mutations are essential to guide optimized therapy. This study aimed to characterize phenotypic and genotypic resistance in treatment-naïve MTBC isolates by determining MICs of BDQ, DLM, and LZD and identifying associated genetic mutations. Methods: Minimum inhibitory concentrations (MICs) of BDQ, DLM, and LZD were determined for 71 Mycobacterium tuberculosis isolates (30 fully drug-susceptible and 41 MDR-TB) collected in the Cukurova region of Southern Türkiye between 2021 and 2023 using the MGIT 960/EpiCenter system. Sequencing of resistance-associated genes was analyzed: atpE and Rv0678 for BDQ, ddn and fbiA for DLM, and rrl and rplC for LZD. Results: MICs ranged from ≤0.025–6.4 µg/mL for BDQ, 0.005–0.32 µg/mL for DLM, and 0.125–2 µg/mL for LZD. According to WHO breakpoints, resistance rates were 7.0% for BDQ, 4.2% for DLM, and 7% for LZD, all confined to MDR-TB isolates. Nine MDR-TB isolates (12.7%) harbored atpE mutations, including both previously reported and putatively novel substitutions. A single ddn mutation was detected in a DLM-susceptible isolate. No mutations were observed in Rv0678, fbiA, rrl, or rplC. Conclusion: BDQ, DLM and LZD showed strong activity against MDR-TB isolates. However, the presence of atpE variants in both resistant and susceptible isolates demonstrated genotype-phenotype discordance of resistance. These results underline the necessity of the combination of genetic and phenotypic testing for detection of resistance and guidance for treatment.

Abstract: Background. Occupational contact dermatitis (OCD) is a significant occupational health concern among healthcare workers (HCWs) due to frequent exposure to irritants and allergens, impacting their quality of life and work performance. Objective. The study aimed to determine the prevalence, clinical presentation, sensitization profile and associated factors of OCD among HCWs in a tertiary hospital, Northern Tanzania. Methodology. A cross-sectional study was conducted from February 2025 to May 2025 at Kilimanjaro Christian Medical Centre (KCMC). A total of 368 HCWs were screened using a pre-tested, validated, interview questionnaire adapted from Nordic Occupational Skin Questionnaire (NOSQ-2002). Patch test baseline series was done for participants with occupational contact dermatitis. Data were analyzed using SPSS version 28. Results. A 12- month prevalence of OCD was 25.5%. The most common clinical presentations of self-reported skin symptoms were dry skin with scaling (67.0%), itching (35.1%), and papules (18.1%). Factors significantly associated with OCD included frequent hand washing, occasional moisturizer use, and history of allergy. The most frequent patch test positive reactions were nickel (26.1%) followed by methyl dibromo glutaronitrile, and fragrance mix II. Conclusion. OCD is an issue that requires attention and resolution and Patch test should performed for HCW with suspected cases of contact dermatitis.

Abstract: Immune cell migration from lymphoid organs to inflamed tissues is regulated by cell-surface receptors sensitive to environmental changes. G protein-coupled receptors involved in immune cell trafficking have been used in the design of anti-inflammatory drugs providing large datasets of active compounds deposited in e.g. ChEMBL. Here, we evaluated these datasets in terms of their applicability to machine learning (ML) aimed at compound activity prediction. Mixed-receptor datasets selected based on sequence homology were used in training of deep neural networks (DNNs) and gradient boosting machines (GBMs) to develop accurate ML classifiers for receptors with sparse ligand datasets in ChEMBL such as CCR6, CCR7, CCR8, CCR9, CCR10, CXCR5, and CCRL2. This ligand-based approach to drug design was compared with structure-based virtual screening (SBVS) using refined, ready-for-VS, structural models of immune cell trafficking receptors recently implemented in GPCRVS. The strengths and weaknesses of DNNs, GBMs, and SBVS were described in terms of applicability of various data schemes. As a result, a comprehensive, multi-level approach based on publicly accessible repositories has been proposed to facilitate immunomodulatory drug design.

Abstract: Major histocompatibility complex class II antigen presentation enables professional antigen-presenting cells to display endogenous and exogenous antigens to CD4⁺ T cells, linking antigen acquisition to the induction and regulation of adaptive immunity. While MHC II-mediated antigen presentation is defined as MHC II-peptide display at the cell surface, its outcome is determined by a coordinated series of regulatory checkpoints that control antigen entry, MHC II expression, intracellular routing, peptide loading, surface stability, and costimulatory signals that provide context to the presented antigen. The regulation of antigen presentation on MHC II is governed by multiple mechanisms — some universal, and some utilized selectively by dendritic cells, macrophages, or B cells. Herein we review the structural and cellular basis of MHC II function, antigen uptake mechanisms, MHC II transcriptional regulation, MHC II intracellular trafficking, and the processes regulating peptide editing, loading, and surface presentation. Together, these regulatory layers determine not only how much MHC II is displayed, but also which peptides are presented, where antigen loading occurs, and how long peptide–MHC II complexes remain available for CD4⁺ T cell recognition. Critically, disruption of these checkpoints contributes to immunodeficiency, autoimmunity, cancer immune evasion, and pathogen-mediated immune evasion. Across these areas, important gaps remain, including how pAPCs select between indirect and direct MHC II trafficking routes, how cargo-sorting mediators distinguish innocuous from infected materials, and how anti-inflammatory regulators directly regulate MHC II expression, peptide loading, or peptide-MHC II surface stability. Addressing these gaps would further clarify how pAPCs calibrate antigen presentation at the intersection of immunity, tolerance, and inflammatory resolution.

Abstract: Polyamine metabolism has emerged as an important determinant of pathogen survival, proliferation, and persistence, highlighting polyamine-associated proteins and metabolic pathways as promising therapeutic targets. This is particularly relevant to major infectious diseases, including tuberculosis, malaria, leishmaniasis, and trypanosomiasis, in which pathogens exploit and remodel host cellular processes to evade immune responses and establish intracellular survival. Increasing evidence indicates that alterations in host–pathogen polyamine metabolism contribute to pathogen adaptation and persistence, providing opportunities for therapeutic intervention. Over the past decade, several components of polyamine biosynthesis, transport, and utilization have been identified and validated as potential drug targets in clinically relevant pathogens. Concurrently, advances in medicinal chemistry have led to the development of polyamine-derived compounds with enhanced specificity toward pathogen-associated polyamine proteins and metabolic pathways. These findings have strengthened the rationale for target-based drug discovery as a complementary strategy to conventional antimicrobial development, particularly in the context of the increasing prevalence of multidrug-resistant pathogens. In this review, we summarize recent advances in the identification and validation of polyamine-related drug targets in pathogens responsible for tuberculosis, malaria, leishmaniasis, and trypanosomiasis. We further discuss emerging strategies for the design and optimization of polyamine-derived therapeutic compounds, with emphasis on their molecular targets, mechanisms of action, and potential for overcoming antimicrobial resistance. Finally, we highlight current challenges and future opportunities for exploiting polyamine metabolism in the development of next-generation therapeutics against these major infectious diseases.

Abstract: Plant microbiome research is a rapidly developing and productive field, with substantial attention directed toward the identification of the major determinant of plant growth, nutrient acquisition, stress tolerance, disease resistance and associated agricultural productivity. Advances in high-throughput sequencing and multi-omics technologies have generated large and complex datasets describing plant-associated microbial communities. However, the high dimensionality, sparsity, compositionality and heterogeneity of microbiome datasets create substantial analytical challenges for conventional statistical approaches. Machine learning (ML) and artificial intelligence (AI) provide new opportunities to identify microbial biomarkers, predict plant phenotypes, characterize plant–microbe interactions and design beneficial microbial communities. Applications include plant disease prediction, crop productivity, abiotic-stress tolerance, nutrient cycling, biomarker discovery, microbiome-assisted breeding and synthetic microbial community (SynCom) design. Recent studies increasingly combine AI with multi-omics, synthetic biology and predictive modelling, indicating a transition from descriptive microbiome analysis toward microbiome engineering. Nevertheless, model generalizability remains constrained by small sample sizes, compositional data, technical variation, batch effects, environmental heterogeneity and insufficient external validation. The combination of microbiome science and AI has considerable potential to support sustainable, climate-resilient crop production, but successful translation will require rigorous biological validation and field-scale testing.

Abstract: Background/Objectives: Lumpy skin disease, a highly contagious Capripoxvirus infection, causes significant economic losses in cattle worldwide. In Ethiopia, diagnosis primarily relies on virus neutralization tests and PCR, highlighting the need for scalable serological tools suitable for large-volume surveillance. The objective of this study was to produce and functionally characterize egg-yolk-derived IgY antibodies against the lumpy skin disease virus (LSDV) vaccinal strain as a proof-of-concept for future serological assay development. Methods: An experimental study was conducted from January to May 2024 over 42 days. The vaccinal virus was adapted on the Vero cell line and titrated after two passages in Minimum Essential Medium. Chickens (n = 10) were allocated into two groups (six experimental and four control). The experimental group received the LSDV vaccinal strain with a booster on day 15, while the control group received a placebo. Weekly serum and egg samples were collected. IgY was extracted from egg yolk using polyethylene glycol precipitation followed by dialysis purification. The protein concentration, molecular weight, and functional activity were assessed using NanoDrop spectrophotometry, SDS-PAGE, and virus neutralization tests (VNTs), respectively. A statistical analysis was performed using linear regression, repeated-measures ANOVA, and a linear mixed-effects model in R (version 4.4.1), with p < 0.05 considered statistically significant. Results: Total protein concentration increased significantly over time (p = 0.0239), with significant differences observed across weeks (p < 0.0001). The virus neutralization assays demonstrated a significantly higher neutralizing activity of egg-yolk-derived IgY compared to serum-derived antibodies (p < 0.0002). Conclusions: This study demonstrates the feasibility of producing functionally active IgY antibodies against LSDV in egg yolk. However, as the protein quantification was based on total protein measurement and antigen-specific validation was not performed, further studies are required to confirm specificity and optimize their application in diagnostic assay development.

Abstract: Despite effective antiretroviral therapy (ART), people with HIV (PWH) continue to experience chronic oral mucosal disease characterized by persistent T-cell inflammation, regulatory T cell (Treg) dysfunction, impaired CD8+ tissue resident cell (TRM) immunity and microbial dysbiosis. Emerging evidence identifies dysregulated polyamine metabolism and mucosal T cell dysregulation as key mediators of these pathological processes. The paradoxical dose-dependent effects of polyamines on epithelial barrier integrity are critically discussed, and a unified mechanistic model is proposed. It also highlights single-cell transcriptomic data from our laboratory that implicates epithelial cell barrier dysfunction in PWH and offers a perspective of how it may worsen persistent inflammation even after combined anti-retroviral treatment. This hypothesis report reviews current knowledge on how HIV-induced polyamine overload and Fusobacterium-derived putrescine could drive oral epithelial barrier disruption through interconnected mechanisms involving oxidative stress, α6β4 integrin–laminin-332 signaling, HIF-1α stabilization, tight junction disorganization, and innate immune dysregulation. Finally, we outline key future research directions, including therapeutic targeting of polyamine oxidation to restore oral mucosal homeostasis in PWH.

Abstract: Background/Objectives: The global crisis of antimicrobial resistance and limited discov-ery of new antimicrobial classes have intensified the search for alternative sources of bio-active natural products. Environmental bacteria harbor largely unexplored biosynthetic diversity, much of which is encoded in biosynthetic gene clusters (BGCs). This review examines current strategies for genome-guided BGC bioprospecting, emphasizing antimi-crobial and environmental applications, and the transition from computational prediction to experimental validation. Methods: We review advances in bacterial genome mining, protein structure prediction, molecular docking, and experimental approaches for evalu-ating antimicrobial and bioremediation potential. Emphasis is placed on representative environmental bacterial genera and the integration of genomic, structural, metabolomic, microbiological, and environmental approaches. Results: Genome mining has revealed substantial biosynthetic potential across diverse environmental bacteria. Comparative ge-nomics and BGC similarity analyses support dereplication and prioritization, while AI-based approaches can expand the search toward atypical and poorly characterized bi-osynthetic systems. Protein structure prediction and molecular docking provide mecha-nistic hypotheses but cannot independently demonstrate metabolite production or biolog-ical activity. Experimental approaches, including One Strain-Many Compounds, heterol-ogous expression, metabolomics, functional genetics, antimicrobial assays, and environ-mentally relevant microcosms, are therefore essential for linking genomic potential to me-tabolite production and biological function. Conclusions: BGC-driven bioprospecting pro-vides a powerful framework for expanding microbial natural product discovery beyond conventional screening. Its greatest potential lies in multi-omics approaches and experi-mental validation. Future progress will depend on improving the prioritization and acti-vation of cryptic BGCs and establishing stronger gene-to-metabolite-to-function relation-ships, ultimately supporting the development of novel antimicrobials and environmental-ly relevant biotechnological applications.

Abstract:

Avian cholera and typhoid are major bacterial diseases in the poultry industry, causing reduced productivity and economic losses. Here, we developed a single-dose, bivalent, inactivated vaccine containing Pasteurella multocida and Salmonella spp. antigens adsorbed to an aqueous matrix based on chitosan, aluminum hydroxide, and saponin. Different concentrations of the experimental vaccine were evaluated in mice to determine the optimal single-dose concentration. Vaccine efficacy was assessed by survival rates; the experimental vaccine provided complete protection, whereas 60% of animals immunized with a commercial vaccine survived a challenge with 1×10¹⁰ CFU/mL of P. multocida and 5×10¹⁰ CFU/mL of Salmonella spp. Subsequently, experiments were conducted to determine the cytokine profiles of animals immunized with the experimental vaccine (single-dose vs. double-dose regimens) followed by a challenge. Pre-challenge cytokine analysis revealed similar profiles for IL-2, IL-4, IL-10, IL-17, IFN-γ, and TNF-α across groups; however, IL-6 levels were significantly higher in the single-dose experimental vaccine group (G1) than in the commercial vaccine group (G2). In the post-challenge comparative study, the cytokine response induced by the single-dose vaccine was robust and stable, showing no negative interference following the Salmonella spp. challenge, although the double-dose regimen did boost cellular and regulatory cytokines (IFN-γ, TNF-α, and IL-10) specifically against Salmonella spp. Conversely, no significant differences in cytokine profiles were observed among the treatments for groups challenged with P. multocida or for unchallenged groups. The single-dose regimen proved fully sufficient to confer complete protective immunity against both pathogens. The results demonstrated the potential of the single-dose bivalent inactivated vaccine as a promising strategy for the simultaneous prevention of avian typhoid and cholera.

Abstract: Wnt signaling plays central roles in embryogenesis/development, skeletal homeostasis, tumour development, and other diseases. The pathway is initiated by Wnt ligands which can be bound and inhibited by sFRP1. Regulation of sFRP1 in lung inflammation needs increased study, and little is known about which cytokines can induce sFRP1, nor the role of gp130 cytokines in its modulation. Here we used AdOSM (Advector expressing mouse Oncostatin M [OSM]) administration to overexpress the gp130 cytokine OSM in mice in vivo, and applied Nanostring, RT-PCR, and immunoblots to measure mRNA and protein levels. OSM induced robust increases in mRNA for sFRP-1 in context of reduced Wnt ligand and receptor mRNA (Wnt10B, Wnt3A, Wnt2, Wnt11, LRP5 and LRP6). Axin-2 mRNA, as a b-catenin target gene, was also suppressed suggesting an inhibition of Wnt signaling pathways. AdOSM could induce sFRP1 in IL-6KO mice, while overexpression of IL-6 (AdIL-6 vector) did not. Immunoblots of total lung extracts showed increases in the 35Kd sFRP1 protein species. In situ hybridization of mouse lung histological sections using specific sFRP1 probes showed staining in the subepithelial layer of the airways, consistent with fibroblast or myofibroblast locations in lung mucosa. In vitro, recombinant OSM stimulated sFRP1 mRNA in cultures of mouse lung fibroblasts and NIH-3T3 cells. The results support the novel observation that OSM can induce sFRP1 in vitro and in vivo, and suggest this axis contributes to the control of Wnt signaling pathways in lung inflammation.

Abstract: Acinetobacter baumannii (A. baumannii) is a major nosocomial pathogen that poses a significant threat to global health owing to its remarkable capacity for antimicrobial resistance, environmental persistence, and virulence. These adaptive traits are closely associated with its quorum-sensing (QS) network, particularly the AbaI/AbaR system. Current evidence indicates that AbaI/AbaR-mediated signalling coordinates biofilm formation, surface-associated motility, antimicrobial tolerance via modulation of efflux pump activity, oxidative stress responses, and membrane integrity, as well as biofilm-associated antibiotic resistance and stress adaptation, thereby enhancing bacterial survival and fitness. Furthermore, QS signalling contributes to epithelial cell injury and to the modulation of innate immune responses during infection, whereas its effects on adaptive immunity remain poorly understood. This review summarises current knowledge of the molecular mechanisms underlying AbaI/AbaR-mediated signalling, its role in regulating A. baumannii infection-relevant phenotypes and host–pathogen interactions, as well as the therapeutic potential of quorum quenching (QQ) strategies in attenuating A. baumannii virulence, while highlighting key knowledge gaps that warrant further mechanistic and translational investigation.

Abstract: Background/Objectives: Escherichia coli is one of the most problematic bacterial species in hospital and community settings and a leading cause of resistant infections worldwide. This reinforces the need of new antibacterial tools like phage therapy. This study aimed to isolate and characterise lytic bacteriophages (phages) targeting clinical E. coli strains with different resistance profiles and to assess their potential for future therapeutic development. Methods: Environmental and clinical samples were used to isolate lytic phages active against clinical E. coli strains, and to evaluate their potential for future therapeutic applications. A phage collection was tested against E. coli strains from human bloodstream infections to determine their bacteriolytic activity, host range and specificity. Two phages were selected for further phenotypic and genomic characterisation. Their infectivity and antibacterial activity were evaluated under growth medium- and filtered human urine-related conditions and across different temperature and pH ranges. Results: Both phages demonstrated consistent antimicrobial activity against susceptible clinical strains, exhibiting a narrow host range and specificity. They retained infectivity under growth medium- and filtered human urine-related conditions, significantly reducing bacterial populations, and maintaining lytic activity across a range of temperatures and pH values. Genomic characterisation confirmed their lytic nature and supported their safety. Taxonomic analysis revealed that one phage was classified as a new podovirus-morphotype species within the genus Xuquatrovirus. The other displayed characteristics consistent with a novel genus, showing myovirus morphology. Conclusions: Environmental reservoirs represent a source of lytic phages active against clinically relevant E. coli strains. The new coliphages provide a basis for future development of phage-based strategies against multidrug-resistant E. coli strains.

Abstract: Background: Neutrophils play an essential role in pathogen clearance and can also contribute to pathogenesis and inflammation. Phenotypic changes of neutrophils during infection or inflammation may be associated with their functional activity. However, investigation of neutrophil phenotypes and functions in clinical studies is challenging because of their short viability ex-vivo and difficulties in effectively cryopreserving neutrophils for subsequent analyses. Methods: We isolated neutrophils from human peripheral blood and evaluated different approaches for cryopreservation. We examined labelling of cell surface receptors of interest, including CD64, CD32, CD16, CD54, CD66b, CD62L and CD14, on fresh versus cryopreserved neutrophils by flow cytometry. Trypan blue staining was used to assess cell membrane integrity. Results: We developed a neutrophil cryopreservation protocol that preserved membrane integrity and enabled subsequent investigation of phenotypes. All cell surface receptors tested could be labelled and quantified using flow cytometry. There were some differences in levels of surface staining for some receptors comparing fresh and cryopreserved cells, but these differences did not prevent the evaluation of neutrophil phenotypes. Discussion: Overall, data suggests that our neutrophil cryopreserving and thawing protocols can preserve neutrophil surface receptors relevant to functions and phenotypes and are methods suitable for use in clinical studies.

Abstract: The immune system is a dynamic, energy-dependent network regulated by temporal biology. Advances in circadian biology have revealed that the molecular transcription–translation feedback loop coordinates approximately 15% of the human transcriptome, synchronizing metabolism, immune surveillance, tissue repair, and adaptation to environmental cycles. Here, we propose a metabolomic, endocrine, neurological chromodynamic model of immune health, based on time of day rhythms. Immune resilience is defined by synchronization among four “wheels”: i) the central circadian clocks, ii) food-entrainable metabolic oscillators, iii) peripheral cellular clocks, and iv) neuroimmune regulatory pathways. The model provides a framework to optimize these interconnected systems to maintain metabolic efficiency, minimize unnecessary inflammation, and enable precise immune responses through temporal gating. External factors of modern lifestyle disruptions, including irregular feeding patterns, sleep deprivation, and chronic stress, induce internal circadian desynchrony, contributing to persistent low-grade inflammation, metabolic dysfunction, immune aging, and chronic non-communicable diseases. We propose that immune health is characterized not merely by the absence of disease, but by stable circadian phase coherence, low inflammatory noise, and adaptive immune flexibility. A propose a panel of chrono-biomarkers of metabolomic and endocrine parameters, that may provide a functional assessment of immune resilience, defined by inflammatory tone, immune adaptability, metabolic integrity, and repair capacity. This framework integrates chronobiology, endocrine and immunometabolism to shift medicine from reactive disease management toward proactive assessment and restoration of biological resilience.

Abstract: Genotype-resolved data on human papillomavirus (HPV) are almost absent for Venezuelan indigenous populations. We conducted a multi-site cross-sectional study of 260 indigenous women from La Guajira (Wayuu, n = 94), Maniapure (Eñepa, n = 141), and Delta Amacuro (Warao, n = 25), Venezuela. All samples were processed under a single protocol, with real-time PCR resolving 21 genotypes individually; conventional cytology was available in 144 women. Overall HPV prevalence was 55.4% (95% CI 49.3–61.3) and high-risk HPV prevalence was 51.2% (95% CI 45.1–57.2); positivity differed across communities (χ² = 13.40, df = 2, p = 0.001), reaching 80.0% in Delta Amacuro versus 59.6% in Maniapure and 42.6% in La Guajira. Nineteen genotypes were detected. HPV-31 was the most frequent overall (15.8%), then HPV-16 (11.5%) and HPV-18 (9.2%). The profiles differed markedly between communities: HPV-68 (48.0%) and HPV-56 (40.0%) in Delta Amacuro, HPV-51 (9.6%) in La Guajira, and HPV-31 (20.6%) in Maniapure. Multiple genotypes were found in 51.4% of infected women. Agreement between cytology and qPCR was negligible (Cohen’s κ = 0.056), with a cytology sensitivity of 25.6%. HPV is highly prevalent in these communities; the circulating genotype spectrum extends well beyond HPV-16/18, and cytology alone is not an adequate screening strategy. In conclusion, the nonavalent vaccine is preferred, as it covers 69.4% of infected women of the indigenous community, compared to 30.6% for the bivalent formulation.

Abstract: Mesangial proliferative glomerulonephritis (MesPGN) refers to the light microscopic description of increased mesangial cells (greater than 3 cells per mesangial area) without endocapillary proliferation, necrosis, and crescents in the absence of another primary glomerulopathy (e.g., IgA nephropathy) or systemic illness (e.g., lupus). Immunofluorescence may be negative or contain mesangial IgM +/- complement (IgM nephropathy) or C1q + immunoglobulin (C1q nephropathy). The presence of either immune deposits or mesangial proliferation per se connotes a worse prognosis compared to minimal changes. Segmental sclerosis may be present and imparts a worse prognosis regardless of mesangial proliferation or immune deposits. Primary MesPGN may present clinically as nephrotic syndrome, non-nephrotic proteinuria +/- hematuria, or isolated hematuria. If nephrotic, MesPGN may be considered nosologically as a primary podocytopathy with secondary mesangial cell activation, especially when immunofluorescence is negative. Such podocyte injury may be driven by circulating factors and/or antibodies directed against podocyte-specific antigens. Alternatively, IgM or complement deposits suggest an antibody-driven immune-complex etiology primarily affecting the mesangium with secondary podocyte injury analogous to IgA nephropathy, especially when presenting as non-nephrotic proteinuria or hematuria. No randomized controlled trials have addressed immunosuppression in primary MesPGN. If non-nephrotic or isolated hematuria, supportive care is indicated. If nephrotic, initial immunosuppression should mimic that of the primary podocytopathies (high-dose oral steroids), although tacrolimus may substitute if concern for steroid toxicity. For frequently relapsing/steroid dependent cases, rituximab is our choice for adults, probably with maintenance dosing. Steroid resistant cases may be treated with calcineurin inhibition.