SUMMARYBacteria can enter a transient state of reduced metabolic activity to survive temporary unfavorable conditions. This phenomenon, sometimes referred to as dormancy, growth arrest, or quiescence, enables pathogen survival inside and outside of their host, with major clinical consequences for the management of infections. From spores to persister cells, these states associated with bacterial dormancy share molecular mechanisms for controlling cellular activity and for responding to related environmental signals. In this review, we provide a synthesis of the diversity of dormant states in human pathogenic bacteria and their pathophysiology within a unifying framework of a dormant-to-active spectrum. We highlight recent developments in therapeutic strategies targeting growth-arrested bacteria and shed light on the role of dormancy in pathogen dissemination and transmission across compartments under a global health perspective. Finally, we discuss the role of dormancy as a microbial trait that shapes virulence and infection dynamics over the course of evolution. Overall, this work seeks to provide new insights into the links between bacterial dormancy and latency in microbial pathogenesis while alleviating the semantic boundaries of the field.

SUMMARYBrucella spp. are highly adapted intracellular bacterial pathogens that remain a substantial global cause of zoonotic disease. The globally distributed species Brucella melitensis, Brucella abortus, Brucella suis, and Brucella canis account for the majority of human infections, reflecting their efficient transmission across animal hosts, and their exceptional capacity to survive and replicate within the intracellular niche. Although animal infections are often clinically silent, human brucellosis can exhibit persistent intracellular infection and relapsing fever. Growing genomic data highlight expanding species diversity, including B. canis and marine Brucella. Progress in elucidating the intracellular life cycle of Brucella, including the maturation of Brucella-containing vacuoles, immune evasion strategies, and the role of the type IV secretion system, has refined our understanding of disease pathogenesis across hosts. At the same time, expanding molecular surveillance, global minimum-spanning-tree analyses, and One Health epidemiology have clarified transmission pathways among livestock, dogs, wildlife, and humans, revealing both cross-species connectivity and geographical hotspots of emergence. Given the limitations of existing livestock vaccines and the absence of human or canine vaccines, diverse next-generation platforms are now advancing toward translational evaluation. Unlike prior reviews focused primarily on livestock brucellosis or classical species, this review integrates emerging canine and marine Brucella lineages with advances in genomics, intracellular pathogenesis, and next-generation vaccine strategies within a unified One Health framework. In this review, we synthesize global trends in Brucella species diversity, zoonotic emergence, mechanisms of intracellular pathogenesis, and the status of current and experimental vaccines, while highlighting the One Health interventions needed to disrupt transmission and advance toward comprehensive brucellosis control.

SUMMARYThe treatment and prevention of HIV have undergone significant transformations in the 16 years since the last major review of HIV therapeutics published in ASM's Journal of Virology (A. M. N. Tsibris and M. S. Hirsch, J Virol 84:5458-5464, 2010, https://doi.org/10.1128/jvi.02524-09). First-generation antiretroviral medications, many now discontinued, have been replaced by integrase strand transfer inhibitor-based regimens that offer superior efficacy, higher genetic barriers to resistance, and the convenience of a single-tablet fixed-dose combination. Dolutegravir and bictegravir are now the anchors of most first-line therapies worldwide, and two-drug and nucleoside reverse transcriptase inhibitor (NRTI)-sparing strategies have emerged, allowing for simplification of treatment of patients who had been previously on complex regimens. The most consequential recent advance, though, has been the introduction of long-acting injectable medications, including cabotegravir-rilpivirine for treatment, standalone cabotegravir for pre-exposure prophylaxis (PrEP), and lenacapavir, a first-in-class capsid inhibitor for both treatment and PrEP. For people with multidrug-resistant HIV, new agents including fostemsavir, ibalizumab, and lenacapavir have made virologic suppression achievable in virtually all heavily treatment-experienced patients. An investigational and emerging pipeline that includes third-generation integrase inhibitors, nucleoside reverse transcriptase translocation inhibitors, maturation inhibitors, and broadly neutralizing antibodies promises further expansion of HIV therapeutic options. These advances, however, come with potential challenges, including emergent resistance to long-acting agents, metabolic consequences of lifelong therapy in an aging population, persistent inequities in global access to newer agents, and often insufficient safety data in pregnancy and breastfeeding. This review provides a clinical assessment of the current antiretroviral options, from legacy agents to investigational therapies, with attention to the resistance, implementation, and special population considerations that will shape HIV practice in the future.

SUMMARYThe traditional landscape of dermatophyte infections has changed over the past decade. The emergence and global expansion of Trichophyton indotineae have highlighted the impact of irrational and uncontrolled antifungal and topical corticosteroid use, presented treatment challenges, and highlighted the deficiencies of currently available diagnostic methods. Trichophyton mentagrophytes genotype VII, which has until recently been associated with animal reservoirs, is now associated with human-to-human transmission and is frequently related to sexual transmission. Infections associated with emerging dermatophytes are notable for atypical presentations that may include widespread, inflamed lesions, terbinafine resistance, and frequent relapse. The classic presentation of tinea lesions is frequently obscured by the application of topical corticosteroids, leading to delays in clinical recognition, diagnosis, and appropriate treatment, perpetuating further misuse of topical medications. Deep or invasive dermatophytoses, including Majocchi's granuloma, may occur in immunocompromised patients. The introduction of matrix-assisted laser desorption/ionization-time of flight mass spectrometry and molecular detection of dermatophytes has improved the diagnostic landscape for dermatophytes. However, currently, most assays do not specifically detect T. indotineae or T. mentagrophytes genotype VII, hindering the diagnosis and surveillance. Sequencing of the internal transcribed spacer (ITS) region is required for definitive identification. Terbinafine and azole resistance is common in T. indotineae and increasingly being reported for other species. While nomenclatural changes have been introduced and debated over many decades, the last decade has seen the introduction of new genera, e.g., Nannizzia, Paraphyton, and Lophophyton. An overview of currently recognized dermatophyte species, complexes, and genera is presented here, describing phylogenetic, ecological, and biochemical relatedness. The ethical conundrum of the name Trichophyton indotineae is also discussed.

SUMMARYAtypical pathogenic Neisseria infections, including disseminated gonococcal infection, primary meningococcal conjunctivitis, and urogenital meningococcal infection, are clinically important yet under-recognized syndromes that challenge traditional species-disease paradigms. The increasing use of whole-genome sequencing has revealed adaptive convergence within the Neisseria genus, providing new insights into the evolution, pathophysiology, and tissue tropism of these infections. This review aims to outline current epidemiological, clinical, and genomic evidence to define transmission, risk factors, and molecular determinants underpinning disease. Improved understanding of these conditions is essential to optimize diagnosis, treatment, and public health guidance.

SUMMARYScrub typhus, caused by Orientia tsutsugamushi, remains a major cause of acute undifferentiated febrile illness with an expanding global footprint. Early diagnosis is frequently delayed because of nonspecific systemic manifestations and geographic heterogeneity. The eschar, traditionally regarded as a characteristic but unreliable clinical sign, is better understood as a dynamic and biologically active lesion rather than a static cutaneous finding. Accumulating clinical, epidemiologic, and pathologic evidence demonstrates that eschar morphology and detectability vary widely with timing, anatomical location, host factors, and prior exposure, whereas its presence does not predict disease severity. Importantly, the eschar represents the primary site of pathogen inoculation, local amplification, and lymphatic dissemination preceding systemic endothelial infection. This biology has direct diagnostic implications: minimally invasive eschar swab-based molecular diagnostics consistently outperform blood-based assays during the early stages of illness and provide an optimal platform for emerging technologies. Furthermore, early eschar-based recognition dictates the timely initiation of targeted antimicrobial therapy, optimizing standard regimens and guiding safe treatment in vulnerable populations, while highlighting the need for novel therapeutics against drug-resistant strains. Reframing the eschar as a central clinical, diagnostic, and therapeutic axis offers a coherent framework for improving early recognition and future management strategies in scrub typhus.

SUMMARYTick-borne viral infections have emerged as a significant and growing public health concern. In East Asia, severe fever with thrombocytopenia syndrome (SFTS) has served as a prototypical disease in which pathological analyses have substantially advanced the understanding of disease pathogenesis. SFTS is characterized by profound immune dysregulation driven by viral tropism for plasmablast-lineage B cells, leading to cytokine storm and hemophagocytic syndrome. Complementary analyses of human clinical specimens and experimental animal models, including cats and ferrets, have provided critical insights into the immunopathogenesis of SFTS. The recent identification of additional tick-borne viruses, including Oz virus (OZV), Yezo virus (YEZV), and Alongshan virus (ALSV), has further expanded the spectrum of emerging infections in this region. Notably, pathological investigation of a fatal human case of OZV infection demonstrated direct viral localization within cardiomyocytes, establishing a causal link between infection and fulminant myocarditis and highlighting a distinct organ-specific pathogenic mechanism. Despite the advances in genomic technologies that enable rapid detection of novel viruses, establishing causal relationships between viral presence and disease remains a major challenge. Tissue-based pathological approaches, particularly in situ localization of viral components, are, therefore, essential for defining disease mechanisms and confirming etiological roles. This review provides a comprehensive synthesis of tick-borne viral infections in East Asia, with particular emphasis on Japan, integrating pathological, virological, and clinical perspectives. It also identifies key knowledge gaps and underscores the importance of a synergistic One Health framework that incorporates both human and veterinary pathology to advance the understanding and control of these emerging diseases.

SUMMARYHuman vascular pythiosis is a rare, life-threatening angioinvasive infection caused predominantly by the oomycete Pythium insidiosum. Unlike ocular or cutaneous pythiosis, the vascular form is defined by arterial wall invasion, long-segment thrombosis, limb ischemia, aneurysmal complications, and high risks of amputation and death. Although P. insidiosum is broadly distributed in freshwater environments, reported human vascular disease remains concentrated in Thailand, indicating that exposure alone is insufficient for disease development. Available evidence supports a multifactorial model centered on repeated freshwater exposure and host susceptibility, particularly hemoglobinopathies and iron dysregulation, while the rarity of comparable vascular disease elsewhere remains unexplained. Because vascular-specific mechanistic data are limited, evidence from animal pythiosis, nonvascular human disease, environmental studies, genomic analyses, and experimental models must be interpreted selectively and linked explicitly to vascular pathogenesis, diagnosis, or management. Infection usually begins at sites of skin disruption after freshwater exposure and progresses through soft tissue and perivascular planes into the arterial wall. Longitudinal intramural extension, rather than typical hematogenous dissemination, explains long-segment arterial occlusion, proximal progression, and relapse after incomplete source control. Diagnosis requires early suspicion, serology, vascular imaging, and tissue-based confirmation. Management depends on prompt and complete surgical removal of infected arterial tissue, supported by adjunctive protein-synthesis-inhibiting antibacterial therapy, particularly when residual disease is suspected. Conventional antifungals have limited activity, and Pythium antigen immunotherapy remains historically important but of uncertain independent benefit. Earlier recognition, better surgical-margin assessment, standardized diagnosis, and prospective treatment data are needed.

SUMMARYHighly pathogenic avian influenza (HPAI) viruses, especially subtype H5N1, have caused major outbreaks in poultry and serious human infections since the first description of "fowl plague" in 1878. Over time, these viruses have expanded their host range, causing huge losses in domestic poultry, spreading among wild bird populations, and occasionally infecting humans. Understanding how influenza viruses adapt and cross species barriers depends on analyzing their fundamental molecular characteristics. Key features such as the polybasic cleavage site within the hemagglutinin protein and the distinctive "1+7" ribonucleoprotein complex, which consists of a single polymerase core surrounded by seven RNA segments, enhance viral replication and broaden host range. Despite decades of intervention, including lessons from the 1997 Hong Kong outbreak and the continued global circulation of clade 2.3.4.4b, HPAI remains difficult to control. A major shift occurred in 2024, when H5N1 was detected in U.S. dairy cattle. This was the first confirmed instance of viral shedding into milk from a mammalian host, suggesting a new potential route of transmission beyond the traditional avian reservoirs. This review unites historical milestones, structural insights, epidemiological data, and recent cross-species findings to better define the current landscape of risk and transmission. We further discuss economic, public health, and agricultural impacts of these developments, particularly the 2024 cattle cases, and underscore the urgent need for an integrated One Health approach to better manage the growing risks posed by HPAI viruses.

SUMMARYStreptococcus suis is a swine pathogen causing significant economic losses and an important zoonotic agent in humans. Southeast Asia is a high-incidence region, where infection is strongly linked to consumption of raw or undercooked pork and occupational exposure to pigs or pork products. Thailand and Vietnam report the highest case numbers, with additional cases in Indonesia (Bali), Malaysia, Singapore, Lao PDR, and Cambodia. Serotype 2 predominates in both humans and pigs, followed by serotype 14, while other serotypes (1, 4, 5, 7, 9, 16, 24, and 31) are also reported in humans. In pigs, a broader serotype range is observed, including 1 or 14, 2, 4, 5, 6, 7, 8, 9, 15, 16, 18, 21, 29, 31, and nontypeable strains. Human infections involve multiple clonal complexes (CC1, CC16, CC25, CC28, CC94, CC104, CC233, CC221/234, and CC1688), several overlapping with porcine lineages. The region is also challenged by increasing antimicrobial resistance, with rising non-susceptibility to macrolides and tetracyclines and occasional reduced susceptibility to penicillin. Diagnostic limitations due to misidentification, limited molecular tools, and reliance on conventional methods further complicate surveillance. The economic burden is substantial, driven by swine losses, treatment costs, outbreaks, and severe human disease. Vaccination remains suboptimal due to limited protection against genetically and antigenically diverse strains across serotypes and CCs. An urgent One Health approach integrating animal health, food safety, and human health is needed to monitor S. suis dynamics. Control measures should target farms, slaughterhouses, and retail markets while promoting community-accepted behavioral changes to reduce transmission risk.

SUMMARYMycoplasma pneumoniae pneumonia (MPP) is an acute respiratory infection caused by Mycoplasma pneumoniae (MP) and constitutes the primary cause of community-acquired pneumonia (CAP) among children aged 5 years and older in China. The clinical manifestations of MP-associated respiratory disease in children are diverse, ranging from mild upper respiratory symptoms to life-threatening pneumonia. Notably, during the implementation of nonpharmaceutical interventions (NPIs) aimed at curbing SARS-CoV-2 transmission, there was a significant decline in MP infection rates. However, a pronounced global resurgence of MP infections was documented in 2023-2024. The increasing global prevalence of macrolide resistance, particularly in China, coupled with limited alternative antibiotic options for children, increasing rates of coinfections, and the absence of a preventive vaccine, collectively exacerbate treatment challenges and increase the disease burden. Furthermore, the insufficient availability of MP nucleic acid testing and antimicrobial resistance surveillance in primary healthcare settings, coupled with the absence of a comprehensive epidemiological monitoring network, results in a vicious public health cycle. Recent advances and emerging genomic data have provided new insights into its pathogenesis and clinical management. Therefore, in this narrative review, we aim to (i) synthesize the current understanding of the etiological characteristics of MP and the present status of MPP diagnosis and treatment; (ii) analyze recent advances and drivers behind the global resurgence of MP infections; and (iii) propose integrated prevention and control strategies to increase the recognition of MPP and prevent unanticipated outbreaks.

SUMMARYLoop-mediated isothermal amplification (LAMP) is a type of isothermal nucleic acid amplification test (NAAT). Compared to more traditional NAATs, like polymerase chain reaction (PCR), LAMP is run at one consistent temperature, utilizes four to six primers, and uses Bst polymerase. Some advantages that are provided by these differences are that LAMP has lower equipment requirements, resiliency to common PCR inhibitors, and a rapid time to result. Unfortunately, some disadvantages are also present due to these differences, such as more challenging primer design, reduced multiplexing capability, and difficulty with quantitation. Due to its unique characteristics, LAMP has proven to be an attractive option for molecular diagnostics in resource-limited, point-of-care, and near-patient testing settings. However, its adoption in clinical settings remains limited compared to its widespread use in research. In this review, we cover various detection methods within LAMP, recent advancements including extraction, multiplexing, and quantification, as well as key clinical applications of LAMP from a syndromic perspective. We also explore the commercial potential of LAMP and how it can be leveraged in resource-constrained settings and clinical laboratories, especially where early, affordable, and rapid diagnosis is essential.

SUMMARYDNA sequencing has revolutionized microbial surveillance in cystic fibrosis (CF), transforming pathogen identification from culture-dependent to total microbial community identification using molecular-based approaches. Techniques such as 16S rRNA gene sequencing have uncovered the complexity of the CF airway microbiome, while shotgun metagenomics, metatranscriptomics, and viromics now provide strain-level, functional, and viral insights beyond bacterial identification. Despite these advances, key technical and logistical challenges remain, including the processing of high-viscosity sputum samples, overwhelming host DNA contamination, managing large data sets, and the integration of complex bioinformatic outputs into clinical workflows. Emerging innovations such as host DNA depletion protocols, targeted enrichment panels, and adaptive sampling on Oxford Nanopore platforms are helping to overcome these barriers, improving microbial recovery and sequencing efficiency. As cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies are changing the lives of people with cystic fibrosis (pwCF), sequencing offers an unprecedented opportunity to track potential microbial adaptation in response. This review investigates current advances, limitations, and translational opportunities in DNA sequencing for CF airway microbiome surveillance, highlighting how these technologies can help reshape research and clinical microbiology in the post-modulator era.

SUMMARYIntra-amniotic infection is the main cause of spontaneous preterm birth and adverse maternal-fetal outcomes; therefore, rapid, robust, and accurate diagnosis remains a clinical priority. Conventional microbiological techniques, especially culture-based methods, are limited by long turnaround times and the inability to detect fastidious or unculturable organisms. This review summarizes the diagnosis, nomenclature, clinical significance, management, and laboratory approaches for diagnosing intra-amniotic infection. Targeted nucleic acid amplification methods, including species-specific polymerase chain reaction and broad-range 16S rRNA gene sequencing, have improved the detection of bacterial DNA and enabled the identification of organisms that evade routine culture in intra-amniotic infection. More recently, whole-genome sequencing and metagenomic next-generation sequencing have provided culture-independent strategies for comprehensive pathogen profiling, allowing simultaneous detection of bacteria, viruses, and fungi, as well as characterization of antimicrobial resistance determinants and virulence-associated genes. However, challenges remain, particularly in low-biomass samples such as amniotic fluid, where contamination, host DNA background, and data interpretation can compromise specificity. This review critically evaluates the advantages and limitations of each molecular modality and discusses pre-analytical, analytical, and bioinformatic considerations essential for reliable implementation. Integration of molecular diagnostics into clinical workflows holds promise for improving etiological diagnosis and guiding targeted therapy in intra-amniotic infection, thereby improving maternal and fetal outcomes.