In this article, we propose a metagenomic next-generation sequencing (mNGS) system for symptomatic clinical respiratory disease samples in Israel to enable detection early enough to contain novel pathogen outbreaks, limit international spread and expedite countermeasure development. We built an open-source, interactive SEIR (susceptible, exposed, infectious, recovered)-based model extending the work of Sharma et al (2023) for 7 representative known respiratory pathogens with pandemic potential, aiming to estimate costs and detection time for the identification of a novel respiratory pathogen in Israel through a network of mNGS monitoring in hospitals. We find that a novel pathogen with SARS-CoV-2-like characteristics could be detected within 68 days (interquartile range [IQR]: 53 to 80) after the first 2 emergency department presentations and 213 (IQR: 94 to 429) total infections across Israel. This surveillance system would cost US$24 million annually over 10 years when implemented in Israel's 6 largest hospitals, covering 37% of the population. Our open-source interactive model allows policymakers and experts to explore different system configurations and their associated tradeoffs between cost, detection speed, and population coverage.
随着肝细胞癌治疗进入以免疫联合治疗为代表的新时代，感染科在肝癌全程化管理中的角色正经历深刻且巨大的转变。文章基于国内多中心临床研究数据及广泛的临床实践现状，系统性地分析了感染科参与肝细胞癌管理的现有状况、面临的现实挑战以及未来的发展路径。感染科医生凭借对慢性肝病，特别是病毒性肝炎自然史和病理生理机制的深刻理解，在肝癌的预防、早期诊断、综合治疗决策、疗效评估及长期随访等全过程中，具备其他学科难以替代的独特优势。通过构建并践行“战略家-守护者-协调者”三维一体角色模型，加强在肿瘤学、免疫学及支持治疗等方面的关键技术能力建设，着力融入并积极贡献于多学科诊疗团队协作机制，感染科有望实现从传统、相对单一的抗病毒治疗专家，向全程化管理的主要参与者，肝癌筛查阶段的主导者的成功转型。文章进一步探讨了在精准医疗和个体化治疗理念日益深入的背景下，感染科如何主动突破传统学科壁垒，构建一套既符合国际前沿趋势、又契合中国国情的肝癌全程化管理新模式，旨在为全面提升我国肝癌防治水平提供坚实的理论依据和具有可操作性的实践路径。.
Since 2020, Infectious Diseases Society of America/American Thoracic Society/Centers for Disease Control and Prevention guidelines have preferentially recommended ≤4-month rifamycin-based regimens for tuberculosis infection. Since 2022, recommendations have included all-oral 6-month regimens (bedaquiline, pretomanid, and high-dose linezolid [BPaL] or BPaL plus moxifloxacin [BPaL-M]) for drug-resistant disease and a 4-month regimen (rifapentine, isoniazid, and moxifloxacin [HPMZ]) for drug-susceptible disease. Yet implementation of new regimens often lags behind guidelines. This survey aimed to characterize tuberculosis treatment practices of infectious disease clinicians and barriers to utilizing these regimens. A survey about tuberculosis treatment practices was distributed to 1501 North American adult infectious disease physician members of the IDSA's Emerging Infections Network. Percentages of respondents were calculated for each question. Open comment data were qualitatively analyzed. Three hundred forty-nine clinicians completed the survey. Ninety-three percent of respondents preferentially opted for ≤4-month regimens for tuberculosis infection, with only 12% expressing concerns about treatment effectiveness. In contrast, 1% selected HPMZ for pulmonary drug-susceptible disease, and 5% reported experience with HPMZ. For confirmed drug-resistant disease, 39% reported that they would use BPaL or BPaL-M, with 40% unsure about regimen choice. Forty-three percent reported uncertainty about effectiveness of 4- and 6-month regimens for drug-susceptible disease and drug-resistant disease. Qualitative analysis highlighted barriers to the use of newer regimens for tuberculosis disease, including concerns about treatment toxicities related to HPMZ or linezolid, medication interactions, and rifapentine and bedaquiline availability. While infectious disease physicians preferentially use shorter regimens for tuberculosis infection, uptake of newer regimens for tuberculosis disease is low due to concerns about effectiveness and treatment toxicities. Enhanced adverse effect management and monitoring and shared decision-making can optimize the implementation of newer tuberculosis disease treatment regimens.
Skin organoids are three-dimensional, self-organized in vitro models that recapitulate the architecture and function of skin tissue. This article comprehensively outlines the current progress and application prospects of skin organoids. Based on complexity, skin organoids can be classified into epidermal, appendage-specific, and full-thickness skin organoids. The construction of skin organoids highly depends on extracellular matrix capable of replicating tissue-specific microenvironment to provide essential physical scaffolding and biochemical cues. Construction strategies encompass natural/synthetic hydrogels scaffold and engineered approaches such as three-dimensional bioprinting, which provide tunable physicochemical and biological support. In terms of applications, skin organoids have been widely used to model physiological and pathological processes, including skin development, tumors, and infectious and inflammatory skin diseases, serving as valuable platforms for studying disease mechanisms and screening drug targets. In the field of wound repair, organoids not only serve as research models to uncover healing mechanisms, but also act as transplantable units that promote re-epithelialization, vascularization, and the regeneration of hair follicles and sweat glands, thereby achieving functional skin restoration. Although skin organoids are currently still facing challenges in terms of structural maturity, vascularization, recapitulation of the immune microenvironment, and heterogeneity, their potential in regenerative medicine, personalized therapy, and translational applications will continue to expand with the advances of technologies such as matrix biology, organ-on-a-chip systems, and automated culture. 皮肤类器官是在三维培养体系中通过细胞自组织形成的、能够模拟皮肤组织结构与功能的体外模型。该文系统概述了皮肤类器官的研究进展与应用前景。根据复杂程度，皮肤类器官可分为表皮类器官、附属器类器官及全层皮肤类器官。皮肤类器官的构建高度依赖能够复刻组织特异性微环境的细胞外基质，以提供关键的物理支撑与生物化学信号。在构建技术上，天然与合成水凝胶支架及三维生物打印等工程化策略为类器官提供了可调控的物理化学与生物学支撑。在应用方面，皮肤类器官已被成功用于模拟皮肤发育、肿瘤、感染性及炎症性皮肤病等生理病理过程，并成为疾病机制解析与药物靶点筛选的重要平台。在创伤修复领域，类器官不仅能作为研究模型揭示愈合机制，还可作为移植单元促进再上皮化、血管生成、毛囊与汗腺再生，实现功能性的皮肤修复。尽管当前皮肤类器官在结构成熟度、血管化、免疫微环境整合及异质性等方面仍面临挑战，但随着基质生物学、器官芯片与自动化培养等技术的发展，其在再生医学、个性化治疗与转化应用中的潜力将不断拓展。.
Candida auris (Candidozyma auris) is an emerging multidrug-resistant fungal pathogen that poses a significant global health threat. However, the molecular mechanisms underlying its virulence remain incompletely understood. In this study, we performed in vivo transcriptome analysis using an immunosuppressed mouse gastrointestinal infection model to identify genes associated with host-adaptation and virulence during infection. By comparing fungal transcriptomes obtained from colonization and dissemination sites with those from in vitro cultures, we identified genes that were consistently upregulated during infection. Among these genes, the unfolded protein response regulator HAC1 was selected as a candidate virulence-associated gene for further analysis. RT-PCR and sequencing analyses revealed that HAC1 mRNA in C. auris undergoes an unconventional splicing event of 287 bp that is enhanced under ER stress conditions. The excised region spans the annotated open reading frame boundary, suggesting that the translated region of HAC1 may require re-evaluation. Notably, a proportion of HAC1 transcripts appeared to be spliced even under non-stress conditions, indicating a detectable basal level of UPR activation. Differences in splicing dynamics were also observed among clade strains. Functional analyses demonstrated that deletion of HAC1 increased sensitivity to ER stress. The HAC1 deletion mutant also exhibited reduced virulence in both Galleria mellonella and immunosuppressed mouse infection models, as evidenced by delayed host mortality and decreased fungal burdens, respectively. These findings indicate that HAC1 contributes to ER stress adaptation and survival in the host environment and identify HAC1 as a virulence-associated gene in C. auris. Candida auris is an emerging multidrug-resistant fungal pathogen. Using in vivo transcriptome analysis, we identified HAC1 as a regulator of endoplasmic reticulum stress adaptation and virulence in infection models. This study provides new insight into stress-response pathways in C. auris virulence.
The first wave of Coronavirus disease 2019 (COVID-19), driven by the global emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), severely affected Spain with high infection and mortality rates across the country. Although numerous common and rare genetic variants affecting immune-related pathways have been associated with susceptibility to infection and severe disease, the contribution of complement system remains comparatively understudied. In this work, we analyzed the frequencies and severity associations of complotype-related common polymorphisms and rare complement variants in whole-exome sequencing data from a Spanish cohort accounting for 154 adults hospitalized due to severe COVID-19. Our results indicate that the CFHR4 rs7417769 (p.N209S) and CFH rs1061170 (p. Y402H) common polymorphisms are significantly associated with protection against acute respiratory distress syndrome (ARDS), while the C3 rs2230199 (p.R102G) and MASP2 rs7255087 (p.D120G) polymorphisms respectively correlated with low and high C3 levels. The marked over-representation of the C1R rs117402032 and C8A rs143523574 polymorphisms and increased frequency of heterozygous carriers of alleles previously associated with low FCN2 and FCN3 levels, suggest a link beween defective complement activation and increased rates of SARS-CoV-2 infection and support a pivotal role for the lectin pathway in the pathogenesis of COVID-19. Together, these results demonstrate that common variants in complement genes modulate susceptibility to severe COVID-19 and its clinical complications. They also identify promising, testable genetic biomarkers with potential utility not only for SARS-CoV-2, but also for preparedness against future emerging infectious threats.
Human T-cell leukemia virus 1 (HTLV-1) is a neglected retrovirus affecting 5-10 million persons worldwide. Most infections are asymptomatic, but HTLV-1 can cause adult T-cell leukemia or lymphoma and HTLV-1-associated myelopathy. Although mother-to-child transmission through breastfeeding is preventable, few countries have policies that include antenatal screening. The World Health Organization recommends integrating HTLV-1 into HIV and sexually transmitted infection strategies. HIV guidelines in high-income countries increasingly support breastfeeding under controlled conditions, creating increased risk for unrecognized HTLV-1 transmission. We reviewed existing policies for HTLV-1 mother-to-child transmission and considered integration of HTLV prevention into HIV response. We discovered inconsistent guidance across HIV, pediatric, and obstetric fields, leading to conflicting counseling of expectant mothers. Integration of HTLV-1 prevention into HIV guidelines and harmonization with maternal and child health policies is essential for awareness among providers. Prevention through screening and avoiding breastfeeding remains the cornerstone of HTLV-1 control.
Dalbavancin, a lipoglycopeptide with a half-life of 150-200 h, is a promising treatment option for prosthetic joint infections (PJIs) and other orthopaedic implant-associated infections (IAIs) caused by multidrug-resistant staphylococci. However, in vitro studies have shown that when exposed to low concentrations of dalbavancin, staphylococcal strains resistant to dalbavancin can emerge, potentially affecting its effectiveness in cases of recurrent infection. To investigate whether dalbavancin-resistant staphylococci emerge in vivo following long-term dalbavancin treatment for PJIs or orthopaedic IAIs. Nineteen patients who had received long-term dalbavancin treatment (≥12 weeks) following PJI or orthopaedic IAI and 25 control patients scheduled for elective prosthetic joint surgery were sampled from the nares and perineum. Each sample was subcultured on Mueller-Hinton II agar plates containing various concentrations of dalbavancin (0.0, 0.125, 0.5, and 2.0 mg/L). The growth of staphylococcal colonies was analysed using MALDI-TOF, and the MIC values of dalbavancin were determined using the gradient test method. Among dalbavancin-treated patients, 4 out of 19 displayed staphylococcal species resistant to dalbavancin (MIC value >0.25 mg/L according to EUCAST breakpoint tables). These four were all Staphylococcus epidermidis isolates, three from the nares and one from the perineum, and displayed MIC values of 0.38, 0.38, 0.5, and 0.75 mg/L. No resistant staphylococci were detected in the samples from the control group (P = 0.029, Fisher's exact test). The present study demonstrated the emergence of dalbavancin-resistant staphylococci following long-term treatment.
In an increasingly connected world a global One Health approach to the management of human, animal and ecosystem health will be critical to effective infectious disease responses. The emergence and rapid global spread of several emerging and re-emerging pathogens in the past decade has highlighted the need for rapid, sensitive and accurate diagnostics. Metagenomics, while commonly used for research purposes for almost two decades, entered the global spotlight during the COVID-19 pandemic. In this review we discuss the impacts that metagenomic studies have had on our understanding of origins, aetiology and ecology of infectious diseases within a One Health context. We also discuss the role of metagenomics in the future of diagnostics and disease surveillance, and outline the challenges and limitations of current metagenomic methods.
AbstractEmerging infectious diseases can cause abrupt demographic changes in wildlife populations. The 2023 outbreak of highly pathogenic avian influenza caused widespread mortality in pinnipeds along the South American coast. We evaluated the population-level impact of the outbreak on South American sea lions (Otaria flavescens) and South American fur seals (Arctocephalus australis) in Patagonia, Argentina. Censuses conducted during the 2024 breeding season using aircraft and drones were compared with long-term pre-outbreak data (1973-2023) using two complementary approaches: raw census comparisons and colony trend projections. Raw census comparisons indicated proportional declines in counts of 17.07% in South American sea lions and 31.31% in South American fur seals between the most recent pre-outbreak censuses and the 2024 breeding season. Colony trend projections based on historical growth trajectories suggested outbreak-associated mortality of about 43.67% in South American sea lions and 15.01% in South American fur seals. Adult males exhibited the largest proportional declines in counts in both species. Pup production in 2024 was 54.17% lower than expected in South American sea lions and 45.01% lower in South American fur seals relative to projected values based on pre-outbreak colony trends. Differences in colony density, spatial distribution, and seasonal timing of breeding and haul-out likely contributed to the observed interspecific variability in mortality and reproductive output. The magnitude of adult losses and reduced pup production suggests that the outbreak may influence short- to medium-term population trajectories. Our results highlight the value of long-term census programs for detecting large-scale demographic impacts of emerging infectious diseases in recovering pinniped populations.
Ultra-processed foods (UPFs) are industrial formulations characterized by high energy density, low nutritional quality, and the extensive use of additives, and their consumption has increased markedly worldwide. In many high-income countries, children and adolescents now derive up to 50-60% of their total daily energy intake from UPFs, raising major public health concerns. This narrative review synthesizes current evidence on UPF consumption across critical life stages, with a particular focus on pregnancy, childhood, and adolescence, and examines its potential implications for short- and long-term health outcomes. Available evidence consistently links high UPF intake in pediatric populations to excess weight gain, metabolic syndrome, and early cardiovascular risk. Additional adverse outcomes include dental caries and a higher prevalence of allergic diseases, such as atopic dermatitis and asthma. Several biological mechanisms may mediate these associations, including impaired satiety regulation, excessive intake of free sugars and saturated fats, disruption of the food matrix, and alterations in gut microbiota composition, immune function, and inflammatory pathways. Emerging research also indicates that exposure to UPFs may begin before birth, as maternal consumption during pregnancy and lactation has been associated with unfavorable offspring outcomes, including altered neurodevelopment, increased adiposity, and immune-related conditions. Familial, socioeconomic, and behavioral factors strongly influence early exposure to UPFs. Modifiable determinants such as breastfeeding duration, parental nutrition literacy, shared family meals, and screen time represent key targets for preventive interventions. Overall, the evidence highlights the urgent need for life-course-oriented nutritional strategies that promote unprocessed and minimally processed foods, reinforce family-based nutrition education, and support healthy dietary patterns from pregnancy through childhood and adolescence to reduce the long-term burden of non-communicable diseases.
Near-infrared photoimmunotherapy (NIR-PIT) is an innovative cancer treatment modality that was approved in Japan in 2020 for the treatment of unresectable locally advanced or locally recurrent head and neck cancer. This therapy uses an antibody-dye conjugate (Ab-IR700), which consists of a monoclonal antibody targeting a specific cell-surface antigen and a phthalocyanine-based near-infrared dye, IR700, that functions as a photosensitizer. After selective accumulation in tumor tissue, Ab-IR700 is irradiated with 690 nm NIR light, which initiates a photochemical reaction that selectively damages the cell membrane of target cells, thereby inducing immunogenic cell death. Its high tumor selectivity and therapeutic efficacy establish NIR-PIT as a promising next-generation cancer therapy. However, its further application to deep-seated solid tumors remains challenging, and will require IR700 analogs and novel dye scaffolds that can be activated by longer-wavelength light to achieve greater tissue penetration and that offer greater photochemical activation efficiency. This review covers the activation mechanism of IR700, the mechanisms of cytotoxicity of NIR-PIT, emerging applications of NIR-PIT in oncology and infectious diseases, the range of dye delivery vehicles, and the development of new dyes for NIR-PIT.
Emerging infectious diseases are one of the biggest challenges in a globalized world. To date, resources have been allocated to prevent and control the spread of zoonotic and livestock pathogens. We argue that, in line with the One Health approach, equitable efforts, financial resources, attention, and coordination are required for wildlife-only pathogens to halt biodiversity loss. Deploying the amphibian fungus Batrachochytrium salamandrivorans as a model, we demonstrate the unbalanced efforts among countries in Europe regarding surveillance, disease response, prevention, public outreach, and research. We compare investments with B. salamandrivorans l-free countries such as the United States, concluding that structural resources are urgently needed to curb the effects of this fungus within Europe and beyond. We encourage dialogue among authorities, researchers, and stakeholders and propose a coordinated European Union-level program of €6-10 million over 5-7 years to implement B. salamandrivorans action plans and define structural funding requirements for future wildlife disease mitigation.
Objective: Analyze the operation of the WeChat official account of the Chinese Journal of Epidemiology, so as to better use the WeChat official account platform to disseminate academic research results, improve the journal's influence and service ability for readers and authors. Methods: By searching all the tweets on the WeChat official account of the "Chinese Journal of Epidemiology" operated by the Chinese Journal of Epidemiology, we analyzed the tweets sent on the WeChat official account from May 2021 to March 31, 2026. Using metrics such as overall reach, average post reach, headline reach, peak reach, and WeChat communication index (WCI), we evaluated the performance of the official account. Linear regression was employed to analyze trends in key indicators, while VOSviewer 1.6.20 software was used for keyword co-occurrence analysis. Results: As of March 31, 2026, the WeChat official account of the "Chinese Journal of Epidemiology" had published 237 articles, with an average read count of 3 302.86 per article and a WCI of 154.66. Linear regression analysis revealed that the average read count, average "like" count, average "share" count, and average "star" count all showed an upward trend (all P<0.05). The "Standard-Protocol-Guideline" and "Expert Forum/Editorial" sections ranked highest in average read count (8 235.00 and 3 655.11 reads respectively), while articles on emerging infectious diseases achieved an average read count of 4 369.20. Articles from other sections also garnered significant attention through diverse presentation formats. Conclusions: The Chinese Journal of Epidemiology's WeChat official account tweets have high communication power and influence, and have become a mature and influential academic exchange platform for epidemiology. In addition to keeping an eye on the academic achievements of this journal, we should strengthen the operation and maintenance of WeChat official account, enrich the content and form of tweets, strengthen the operation and maintenance of WeChat official account, and further improve the ability to serve the readers and authors. 目的： 分析《中华流行病学杂志》微信公众号的运营情况，以更好地利用微信公众号平台传播学术研究成果、提升期刊影响力及为广大读者和作者服务的能力。 方法： 通过检索《中华流行病学杂志》微信公众号所有推文信息，分析微信公众号自2021年5月开通至2026年3月31日的推文情况。将整体传播力、篇均传播力、头条传播力、峰值传播力及微信传播指数（WCI）作为评估指标，分析该微信公众号的运营情况。采用线性回归分析主要指标的变化趋势，采用VOSviewer 1.6.20软件进行热词分析。 结果： 截至2026年3月31日，“中华流行病学杂志”微信公众号推文量为237篇，篇均阅读数为3 302.86次，WCI为154.66。线性回归分析结果显示，篇均阅读数、篇均在看数、篇均点赞数、篇均转发数均呈上升趋势（均P<0.05）。“标准·方案·指南”和“专家论坛/述评”栏目推文的篇均阅读数居前列，分别为8 235.00次和3 655.11次。新发传染病感染推文的篇均阅读数为4 369.20次，其他栏目推文通过多样化的展示方式也获得充分关注。 结论： 《中华流行病学杂志》微信公众号推文的传播力和影响力均较高，已成为较成熟且具有专业影响力的流行病学学术交流平台。应在保持关注学术成果推送展示外，加强微信公众号的运营与维护，丰富推文内容和形式，进一步提升为广大读者和作者服务的能力。.
RNA viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), flaviviruses, and alphaviruses, represent a major source of emerging human infectious diseases. They pose a persistent threat to public health; however, few therapeutic options are available for severe infections. Through a natural product screening campaign, we identified ansatrienin B as a broad-spectrum inhibitor of multiple RNA viruses, including SARS-CoV-2, flaviviruses (e.g., YFV, WNV, DENV), and alphaviruses (e.g., CHIKV). Time-of-drug-addition assays indicated that ansatrienin B acts at both the early (entry) and intermediate (replication) stages of the viral life cycle. Surface plasmon resonance (SPR) and molecular docking studies validated a direct interaction between ansatrienin B and the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and WNV. Combined RNA pull-down and RdRp enzymatic activity assays (in gel, solution, and cellular forms) further demonstrated that ansatrienin B disrupts both the binding of RdRp to viral RNA and its enzymatic activity. In vivo, ansatrienin B showed significant efficacy in mouse models infected with SARS-CoV-2 or WNV infection. To facilitate screening and elucidate the structure-activity relationship (SAR), we generated a focused ansatrienin library via a mutasynthetic approach. Supplementation of four 3,5-AHBA analogs into a ΔmycB1-B4 mutant strain of Streptomyces flaveolus yielded 30 novel ansatrienin derivatives. Evaluation of anti-SARS-CoV-2 activity identified four analogs with enhanced potency, enabling the establishment of a preliminary SAR. Collectively, these findings establish ansatrienin B as a novel inhibitor targeting RdRp and provide a foundation for the development alternative broad-spectrum antiviral agents.
Recombinant Listeriolysin O (rLLO), a cholesterol-dependent cytolysin (CDC) derived from Listeria monocytogenes, has gained increasing attention as a novel immunological adjuvant for next-generation vaccine development. rLLO enhances both innate and adaptive immune responses by facilitating controlled endosomal membrane permeabilization, promoting cytosolic antigen delivery, and enabling efficient antigen cross-presentation, leading to robust CD8⁺ T-cell activation. These immunological properties are particularly advantageous for vaccines targeting intracellular pathogens and malignancies. This narrative review synthesizes current experimental, preclinical, and translational evidence on the application of rLLO across diverse vaccine platforms in human and veterinary medicine, including DNA-, protein-, nanoparticle-, and vector-based formulations. Studies addressing infectious diseases, such as tuberculosis, HIV, dengue, and listeriosis, as well as cancer immunotherapy models, are critically examined. Emerging strategies involving fusion proteins, detoxified rLLO mutants, and recombinant delivery systems are highlighted to illustrate advances in formulation design and immunogenic optimization. Despite promising preclinical outcomes, several challenges remain, including the need for comprehensive safety evaluation, dosing and delivery strategy optimization, and regulatory pathway clarification. Addressing these limitations through standardized toxicological assessment and large-scale clinical and veterinary trials is essential for the successful translation of rLLO-based vaccine components. Overall, rLLO represents a versatile and potent immunological tool with significant potential to advance vaccine design in human and veterinary applications.
Trypanosomatids, including the genera Trypanosoma and Leishmania, are protozoan parasites of significant medical and veterinary relevance. These organisms cause African trypanosomiasis, Chagas disease, and leishmaniasis, which are classified as neglected tropical diseases (NTDs). NTDs continue to present major public health challenges, particularly in sub-Saharan Africa, Latin America, and parts of Asia, resulting in substantial morbidity, mortality, and socioeconomic impacts. Chemotherapeutic interventions remain constrained by toxicity, high cost, limited accessibility, and the increasing prevalence of drug resistance. Significantly, there is a tight relationship between pathogenesis and drug resistance because processes that facilitate intracellular persistence, immunological evasion, and metabolic adaptation can also decrease drug sensitivity and increase treatment failure. This interaction makes it easier for more pathogenic and resilient strains to arise, which makes disease treatment and control more difficult. The absence of effective vaccines underscores the urgent need for novel therapeutic strategies. Advances in molecular parasitology have elucidated unique organellar structures, immune evasion mechanisms, and metabolic pathways in trypanosomatids, providing new therapeutic targets. Additionally, artificial intelligence and computational methodologies are facilitating drug discovery, predicting resistance, and improving diagnostics. In this review, we provide a narrative overview of current knowledge of trypanosomatid biology, prevalence, drug resistance mechanisms, and emerging control strategies. By integrating classical parasitology with computational approaches, new opportunities are identified to address resistance, enhance therapy, and mitigate the global health burden of trypanosomatid infections.
Open-access drug discovery platforms have accelerated hit identification and lead prioritization across multiple diseases and enable systematic repurposing of bioactive compounds beyond their original indications. However, there remains a need for new chemotypes for African trypanosomiasis with improved efficacy and resilience to emerging drug resistance. In this study, we evaluated the antitrypanosomal potential and cellular effects of two Pathogen Box compounds, MMV667494 and MMV028694. The compounds were selected through a resazurin-based in vitro phenotypic viability screen that measures metabolic activity as a proxy for parasite viability against bloodstream-form Trypanosoma brucei brucei. To explore cellular phenotypes consistent with potential mechanisms of action, we applied cytological profiling using flow cytometry- and microscopy-based assays, including Annexin V/propidium iodide staining, cell-cycle DNA-content analysis, mitochondrial membrane potential (TMRE), and mitochondrial reactive oxygen species (MitoSOX) measurements. Both MMV667494 and MMV028694 (IC50 = 0.44 ± 0.05 µM and 0.33 ± 0.03 µM, respectively) displayed sub-micromolar antitrypanosomal potency and preferential toxicity toward trypanosomes over mammalian cells (selectivity indices >10). Growth profiling demonstrated dose-dependent inhibition of parasite proliferation, with evidence of trypanocidal activity at higher concentrations and longer exposure times. Treatment resulted in increased populations of phosphatidylserine-exposed and membrane-compromised cells, which is consistent with apoptosis-like phenotypes in trypanosomes. Although both compounds induced mitochondrial membrane depolarization in treated T. b. brucei cells, this effect was observed predominantly in a subpopulation of cells and is therefore unlikely to represent the primary cause of cell death. Increased mitochondrial production of reactive oxygen species and altered cell-cycle progression were also observed, which might indicate disruption of key cellular processes. These findings shows that MMV667494 and MMV028694 are selective antitrypanosomal compounds and their activities are associated with induce apoptosis-like features, cell-cycle disruption, and mitochondrial stress signatures in bloodstream-form T. b. brucei. These findings provide phenotypic insights into the activity of the compounds, warranting further target deconvolution and optimization, although validation in human-infective subspecies and in vivo systems will be required.
Ignatzschineria spp. bacteria are emerging pathogens whose vectors historically have not been clearly identified. We used molecular methods to establish a relationship between the black blow fly (Phormia regina) and human Ignatzschineria bacteremia in persons experiencing homelessness in Vancouver, British Columbia, Canada, validating a novel transmission pathway in a vulnerable urban population.
Candida auris (also referred to as Candidozyma auris) is an emerging multidrug-resistant fungal pathogen associated with high morbidity and mortality. Existing infection prevention and control (IPC) guidance has largely focused on adult populations, with limited recommendations for pediatric healthcare and non-healthcare settings. The Society for Healthcare Epidemiology of America (SHEA) convened a multidisciplinary expert panel to develop IPC recommendations for C. auris. The panel developed recommendations using a structured, iterative Delphi consensus process with rounds of discussion, refinement, and anonymous electronic voting with predefined consensus thresholds. Panelists reviewed relevant peer-reviewed and gray literature integrated with expert judgment and practical considerations. Preambles and remarks provide additional context and guidance. This consensus statement provides recommendations for prevention of C. auris in pediatric acute care settings, non-acute healthcare settings, and non-healthcare congregate settings. Recommendations incorporate pediatric risk factors and care and address screening practices, isolation precautions, caregiver-infant/child dyad considerations, room placement and rooming in, breastfeeding and skin-to-skin practices, visitation, use of shared spaces, environmental cleaning and disinfection, and management of medical and non-medical equipment, including toys. Recommendations emphasize coordination with local infection prevention and public health partners. This SHEA consensus statement addresses gaps in pediatric-specific IPC guidance for C. auris. The recommendations provide a practical framework to support prevention of transmission within the context of pediatric clinical, developmental, and family-centered care.