Modular Nanosensing Platforms for Tuberculosis and Beyond: Engineering Biomaterials Toward Cross‐Pathogen Diagnostic Universality

Clinical microbiology laboratories in low-resource settings, it is not only about equipment and reagents, but also good governance for sustainability

Equity in Global Health Research.

Antimicrobial resistance (AMR) in Mycobacterium tuberculosis (M. tuberculosis) has emerged as one of the most pressing challenges in global public health. The development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of tuberculosis (TB) has rendered conventional treatment regimens less effective, leading to increased morbidity, mortality, and treatment costs. This paper explores the mechanisms behind antimicrobial resistance in M. tuberculosis, the contributing factors such as improper treatment adherence and diagnostic delays, and global strategies for managing resistant TB. Furthermore, it discusses current diagnostic tools, therapeutic advancements, and the importance of surveillance and policy frameworks in mitigating the spread of resistant TB strains. The increasing incidence of drug resistance has made it necessary to reassess traditional TB control programs and adapt new evidence-based approaches. The implementation of rapid diagnostics, patient-centered treatment plans, community education, and international collaboration has become pivotal in achieving long-term control and eventual elimination of drug-resistant TB. Through detailed case studies and review of current literature, this research underscores the urgency of addressing antimicrobial resistance in TB through a multidisciplinary and globally coordinated effort. Keywords: Mycobacterium tuberculosis, antimicrobial resistance, MDR-TB, XDR-TB, global health, tuberculosis treatment, drug susceptibility, public health, TB diagnosis, WHO strategies

Background Antimicrobial resistance (AMR) is a pressing global health concern, responsible for millions of deaths every year. Overuse and misuse of antimicrobials is a significant driver of AMR and is partly driven by a lack of decision-relevant and timely diagnostic tests to guide treatment. Point of care tests (POCT) would be of great public health benefit for neonatal sepsis, which refers to systemic life-threatening infections in newborns in their first 28 days of life. Neonatal sepsis, for which over- and inappropriate prescription of antibiotics are very high, affects 1.3 to 3.9 million neonates and accounts for nearly a quarter of all neonatal deaths. However, due to insufficient market incentives and revenue guarantee for developers, research and development pipelines are stagnant and no such POCT exists. One proposed solution is an advanced market commitment (AMC), a form of ‘pull incentive’ that would aim to ‘pull’ a new POCT to market. In an AMC, donors commit to a fund from which a specified subsidy is paid per unit purchased by low income countries until the fund is exhausted. This aims to strengthen suppliers’ incentives to invest in research, development and capacity. Methods This study modelled the costs and outcomes of an AMC for a neonatal sepsis POCT that would seek to identify the presence or absence of sepsis. Modelled for the Indian public healthcare system, the test was conceived as an adjunct to clinical judgement where there is diagnostic uncertainty if a neonate has sepsis. The POCT was compared with current best practice. Benefits of increased identification of neonatal sepsis and decreased burden of AMR were considered; cost of diagnostic tests and antibiotic treatment were considered. Cost-effectiveness and incremental cost-effectiveness were calculated in cost per disability adjusted life year (DALY), from both the perspective of the Indian healthcare system and investors to an AMC. Results From our cost-effectiveness model, a POCT would have an incremental cost-effectiveness of $93.56/DALY (compared with current clinical practice) for the Indian healthcare system, with a cost-effectiveness of $5.9/DALY for donors to an AMC. On sensitivity analysis, the cost benefit analysis is contingent on a test with sufficiently high specificity and sensitivity and varies depending on estimated AMR burden. Conclusions Although a novel market incentive with some uncertainty in model parameters, an AMC for a neonatal sepsis POCT may be highly effective and cost-effective from both a global health and AMR perspective.

The fifth annual Global Health 50/50 report, Boards for all?, presents our first-ever analysis of the gender and geography of who governs global health. Through an examination of the demographics of over 2,000 board members of the most influential organisations active in global health, the report warns that global health is not living up to its name. The report further presents its annual review of the equality- and gender-related policies and practices of 200 global organisations. Building on five years of evidence, it finds signs of rapid progress in building more equitable and gender-responsive global health organisations, while also revealing stagnating progress among a large subset of global health organisations. For the first time, the Index categorises all organisations by performance and presents dedicated pages for each organisation to explore and compare findings. Boards for all? is a call to realise a globally representative and equitable global health governance that can deliver health for all. "Ensuring the leadership and influence of people from low- and middle-income countries, and especially women, is not only a question of equity - however essential - but of the very relevance, effectiveness and impact of the global health enterprise." Elhadj As Sy, Chair of the Kofi Annan Foundation

Microbial Pathogenesis of Mycobacterium tuberculosis: Dawn of a Discipline

Leveraging the positives from the pandemic to strengthen infectious disease care in low-income and middle-income countries

The escalating rise of antimicrobial resistance (AMR) casts a grave shadow over global public health, making once manageable infections increasingly difficult to treat. Despite advancements in combination chemotherapy for multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (TB), this pathogen remains a formidable foe. TB is now the second leading cause of death worldwide from infectious diseases, only surpassed by COVID-19. It is the primary driver of AMR-related deaths, particularly among HIV co-infected individuals. A significant challenge lies in TB's resistance to β-lactam antibiotics, the most widely used class, comprising about 65% of global antibiotic consumption. This resistance is driven by the bacterium's β-lactamase enzyme (BlaC) production, which neutralizes the antibiotic by hydrolyzing the β-lactam ring. Although BlaC remains susceptible to β-lactamase inhibitors (MBIs) like sulbactam, tazobactam, and clavulanate, resistance mutations in secondary catalytic sites pose an emerging threat, potentially undermining these inhibitors. To combat this evolving challenge, a comprehensive study explored BlaC's role in AMR. The research spanned six phases, from gene and protein sequence analysis to dynamic protein modelling and mutational landscape exploration. Homology modelling was employed to generate structures for all 40 BlaC variants, with stability assessed through Ramachandran plots. Drug-protein interactions with six β-lactam agents and MBIs were investigated via automated docking and simulation studies. These insights provide a deeper understanding of BlaC-mediated resistance in TB and offer a promising foundation for future drug development to address this global health crisis.

1The Review on AMR was an expert panel commissioned by the UK Government in 2014 tasked with analysing the economic and social impacts of AMR and proposing solutions to these. 2NICE is a UK non-departmental public body that sponsored by but separate from the Department of Health that produces evidence-based guidance for health practitioners. 3NHS England is a non-departmental public body sponsored by the Department of Health that oversees planning and delivery of health services in England. 4Note that circulation of the News of the World ceased in July 2011; the Sun on Sunday was launched by the same newsgroup in 2012, but is unavailable on the Nexis database.

Artificial intelligence (AI), as an emerging interdisciplinary field dedicated to simulating and extending human intelligence, is increasingly integrating into the domain of infectious disease medicine with unprecedented depth and breadth. This narrative review is based on a systematic literature search in databases such as PubMed and Web of Science for relevant studies published between 2018 and 2025, with the aim of synthesizing the current landscape. It demonstrates transformative potential, particularly in the realm of diagnostic assistance. Confronting global challenges such as pandemic control, emerging infectious diseases, and antimicrobial resistance, AI technologies offer innovative solutions to these pressing issues. Leveraging its robust capabilities in data mining, pattern recognition, and predictive analytics, AI enhances diagnostic efficiency and accuracy, enables real-time monitoring, and facilitates the early detection and intervention of outbreaks. This narrative review systematically examines the application scenarios of AI within infectious disease diagnostics, based on an analysis of recent literature. It highlights significant technological advances and demonstrated practical outcomes related to high-throughput sequencing (HTS) for pathogen surveillance, AI-driven analysis of digital and radiological images, and AI-enhanced point-of-care testing (POCT). Simultaneously, the review critically analyzes the key challenges and limitations hindering the clinical translation of current AI-based diagnostic technologies. These obstacles include data scarcity and quality constraints, limitations in model generalizability, economic and administrative burdens, as well as regulatory and integration barriers. By synthesizing existing research findings and cataloging essential data resources, this review aims to establish a valuable reference framework to guide future in-depth research, from model development and data sourcing to clinical validation and standardization of AI-assisted infectious disease diagnostics.

Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.

Tuberculosis remains a major global public health problem despite the modest infectious disease control efforts. Timely and accurate diagnosis is pivotal to the reduction in tuberculosis related morbidity and mortality. In addition, drug resistant form of tuberculosis is a serious threat to the efforts at tuberculosis control and eradication. Hence; there is the need for efficient methods of Mycobacterium tuberculosis infection diagnosis and treatment. There are major advances in the laboratory diagnostic methods for detection of Mycobacterium tuberculosis which seeks to complement or replace the existing conventional methods in a view to reduction in under-diagnosis and improved infectious disease management. Chest computer tomographies, Cephid GeneXpert, Line probe are some of the Mycobacterium tuberculosis diagnostic advances while chest x-ray, sputum microscopy/culture represent some of the conventional methods of evaluation of both Mycobacterium tuberculosis infection and its multi-resistant strain. Intriguingly, the conventional tuberculosis diagnostics though time consuming and inefficient, its use still predominates in high disease burden settings. Meanwhile, the slow transition to use of advanced tuberculosis diagnostic methods seems to have an economic undertone. The seemingly lack of cutting edge advanced Mycobacterium tuberculosis diagnostics in high disease burden countries is attributable to their suboptimal health financing model and over reliance on the donor organizations thereby retarding progress in tuberculosis eradication.

Objectives: Equitable global health partnerships are recognized as critical for health equity; however, power imbalances and structural inequities continue to undermine these partnerships and ultimately their ability to achieve equitable health outcomes. As individuals within a US‑based academic institution engaged in global health partnerships during the current, complicated political moment, we recognize our responsibility to critically examine what it means for us to seek to engage equitably, both locally and globally. We therefore undertook an initiative to develop and adopt a set of principles to serve as internal guidance for how individuals within our institution engage in partnerships. We present our approach to promoting equity within our local and global research, education, and community partnerships, informed by existing literature, as an example of how academic institutions based in the Global North might seek to address power imbalances and to engage with others involved in similar efforts. Methods: We reviewed similar initiatives and existing principles. An internal, departmental committee coalesced around eight principles and drafted and iteratively refined their components. As part of ongoing, broader conversations with our partners, during this process, we engaged and sought the perspectives of our external partners, including from Brazil, India, and Kenya, to ensure the guidance was both informed by and resonated with their concerns about engaging with a US‑based institution. Findings: The principles of sustainability, mutual benefit and reciprocity, equitable governance, do no harm, locally identified priorities, compliance with ethical reviews and legal standards, information sharing, and accountability were elaborated and ultimately adopted by the full department faculty. Conclusions: Despite the best of intentions, we foresee challenges that may impact both implementation and outcomes. Continued reflection and dialogue with our partners and others engaged in similar initiatives is needed to address these challenges and the broader structural inequities embedded in global health.

Despite a gendered approach being increasingly applied across global health challenges, this has been a notable oversight in antimicrobial resistance (AMR) research. Failing to consider the complexity of human behaviours and roles in healthcare, animal production, and environmental settings compromises programmatic effectiveness and sustainability, while risking entrenching or widening existing social disparities. Research demonstrates how gender norms influence health-related behaviours across various sectors, from accessing healthcare to livestock rearing, with strong implications for antimicrobial stewardship and zoonotic disease transmission. The sparse literature connecting and investigating gender, equity and AMR – especially in a One Health context – hampers our ability to comprehensively address this global issue. The responsibility is however shared. This commentary advocates for funders to propel the inclusion of gender and equity-focused perspectives in AMR research and to set expectations in research landscapes, thus fostering a more equitable global health landscape and strengthening strategies against AMR. We outline our rationale and recommendations for other funders to support an ecosystem in AMR that supports gender and equity as a common aspect of AMR research and not an exception. One Health impact statement While AMR is increasingly recognised as a One Health challenge encompassing humans, animals, plants and the environment, sector-specific and cross-sectoral solutions needed to address AMR too often lack the multidisciplinary approach needed for a holistic response to this challenge. To date, AMR research has been largely biomedical, with limited social investigation including on gender and its interplay with factors that drive AMR in different settings such as healthcare, community or farm settings. Intentionally integrating gender analysis that informs AMR research design and implementation across sectors, including with supportive research funding opportunities, will help build the evidence base on how research projects and public programs should integrate and address gender disparities in AMR across the One Health spectrum. This is needed to ensure contextually relevant gender-informed solutions with sustainable impact.

Antibiotic stewardship and point-of-care testing for children in 25 low-income and lower-middle-income countries: a systematic review and meta-analysis