Research Articles (Pharmacology)

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Tackling migraines head-on : insights into pathophysiology, management and treatment
Balmith, Marissa; Mare, M.; Basson, Charlize; Nyane, N.; Ditshego, Rebotile; Flepisi, B. (Medpharm Publications, 2025-10)
Migraines are complex neurological disorders characterised by recurrent episodes of moderate-to-severe headaches, often accompanied by sensory disturbances. Globally, migraine is one of the leading causes of disability and is classified into various subtypes based on individual characteristics and symptoms. Clinical presentation and diagnosis rely on the identification of specific symptoms and stages of migraine attacks, distinguishing them from other types of headache disorders. The pathophysiology of migraine involves a complex interplay between neurological, vascular, and biochemical factors, with the trigeminovascular system playing a central role. Migraine management includes both non-pharmacological and pharmacological approaches. Non-pharmacological strategies involve lifestyle modifications, dietary adjustments, and sleep and stress management. Pharmacological treatment involves therapies such as triptans, nonsteroidal anti-inflammatory drugs (NSAIDs), and calcitonin gene-related peptide (CGRP) antagonists, as well as preventive medications such as antihypertensives, antidepressants, antiepileptics, and newer biological therapies. Key challenges in migraine treatment include the accessibility of advanced therapies, the role of pharmacogenomics in personalised treatment, and the development of emerging therapies through clinical trials. Further research is needed to better understand the complex pathophysiology of migraine for the development of more effective and targeted treatment strategies.
Overview and management of colds and flu
Dlamini, Z.; Kupa, K.; Schellack, Natalie (Medpharm Publications, 2025-04)
In South Africa deaths related to colds and flu are at least three times higher when compared to the USA. The burden of HIV and tuberculosis in our country heightens the risk of severe flu-related illness. The common cold and flu are caused by very different viruses that share very similar symptoms. The common cold is a self-limiting upper respiratory tract viral infection and it is caused by the rhinovirus, coronavirus or the adenovirus. It usually resolves within 7–10 days. Flu is caused by the influenza virus and usually presents with headaches, myalgia, fever and body aches. There is no place for antibiotic usage in colds and flu management, and there is no clinical evidence which suggests that using antibiotics alters the course of the disease or prevents secondary infection. Treatment is mainly symptomatic and includes many over the counter-medicines, specific antiviral agents and herbal treatment.
Atrial fibrillation in South Africa : anti-arrhythmic and anticoagulation therapy-clinical considerations for pharmacists
Jordaan, Beatrice; Bronkhorst, E. (Medpharm Publications, 2025-10)
BACKGROUND d: Atrial fibrillation (AF) represents the most prevalent persistent cardiac rhythm disorder encountered in routine clinical care and is a leading contributor to stroke, systemic embolic events, and heart failure. In South Africa, the occurrence of AF is currently lower than anticipated, though it is showing an upward trend, driven in part by the substantial prevalence of hypertension, obesity, and valvular heart disease, frequently linked to rheumatic heart disease (RHD). Furthermore, the risk for arrhythmias is increased with structural heart disease due to fibrotic scar formation caused by myocardial infarction. Pharmacological and non-pharmacological treatments are used to limit the effect of arrhythmias on morbidity and potential mortality. The therapeutic approach to AF typically includes strategies for rhythm or rate regulation using anti-arrhythmic agents, in combination with anticoagulation agents to reduce the risk of thromboembolic events. In the public healthcare sector, warfarin continues to be the predominant anticoagulant, whereas direct oral anticoagulants (DOACs) are being adopted with increasing frequency in private healthcare settings. OBJECTIVES : This review summarises current epidemiology of AF in South Africa, outlines anti-arrhythmic and anticoagulation strategies, and highlights key considerations for pharmacists, including drug interactions, adverse effects, and patient counselling. RESULTS : While beta-blockers, calcium channel blockers, amiodarone, and sotalol remain mainstays for rate/rhythm control, newer agents have improved tolerability profiles. Anticoagulation decisions should be guided by the CHA₂DS₂-VA and HAS-BLED scores, in line with the 2024 ESC guideline, balancing stroke prevention with bleeding risk. DOACs offer practical advantages but cost, accessibility, and reversal agent availability remain limiting factors in public healthcare. CONCLUSION : Pharmacists play a critical role in AF management through patient education, adherence support, adverse effect monitoring, and optimisation of therapy in line with national and international guidelines.
SGLT2 inhibitors in type 2 diabetes mellitus : a pharmacist’s guide to optimised care
Jordaan, Beatrice; Outhoff, Kim (Medpharm Publications, 2025-09)
OBJECTIVES : To review current evidence on sodium–glucose co-transporter-2 (SGLT2) inhibitors in the management of type 2 diabetes mellitus (T2DM), highlighting their mechanisms, efficacy, safety, and relevance to the growing burden of diabetes mellitus within the South African healthcare context, where high rates of undiagnosed disease and limited specialist access amplify the importance of pharmacist-led interventions. This review underscores the vital role of pharmacists as frontline diabetes care providers – facilitating optimal use of SGLT2 inhibitors such as empagliflozin and dapagliflozin through patient counselling, safety monitoring, and therapeutic guidance. METHODS : A narrative literature review was conducted by searching PubMed, Google Scholar, and local databases. Key articles on SGLT2 inhibitors, their effects on cardiovascular and renal outcomes, and prevalence data on T2DM in South Africa were included. Relevant clinical trials and meta-analyses published in English were appraised, with a focus on recent developments and guidelines. RESULTS : Burden of diabetes in South Africa: T2DM prevalence can reach 12.9% or higher in certain urban black populations, exceeding the overall International Diabetes Federation (IDF) estimate of 10.8%. Nearly half (45.4%) of those affected remain undiagnosed. Mechanism and benefits: SGLT2 inhibitors lower blood glucose by enhancing urinary excretion of glucose, providing insulin-independent glycaemic control. They induce weight loss and mild blood pressure reductions. Cardiorenal protection: Large-scale trials conducted in T2DM patients with either established chronic kidney disease or cardiovascular disease or high cardiovascular risk demonstrate meaningful reductions in cardiovascular events, hospitalisation for heart failure, and progression of chronic kidney disease. Safety profile: While generally well tolerated, key adverse effects include genitourinary infections and rare euglycaemic ketoacidosis, especially during acute illness or low-carbohydrate intake. CONCLUSION : SGLT2 inhibitors address both the escalating rates of T2DM in South Africa and its serious complications. Their robust cardiorenal benefits, combined with modest weight loss and minimal hypoglycaemia risk, make them an essential component of contemporary diabetes pharmacotherapy. Pharmacists play a central role in identifying appropriate candidates, advising on safety precautions, and improving patient outcomes in an increasingly burdened healthcare landscape.
Hypertension in South Africa : a growing epidemic and evolving treatment paradigms
Jordaan, Beatrice; Theron, B.; Owusu, E.; Bronkhorst, E. (Medpharm Publications, 2025-06)
BACKGROUND : Hypertension is a major public health concern in South Africa, affecting 40–50% of adults, with control rates below 50% despite available treatments. It is a key driver of cardiovascular morbidity and mortality, particularly in populations with limited healthcare access, poor medication adherence, and high rates of comorbidities such as diabetes and obesity. This review examines the epidemiology, pathophysiology, diagnosis, treatment strategies, and public health approaches to hypertension in South Africa, highlighting gaps in care and opportunities for intervention. RESULTS : Pharmacological interventions such as fixed-dose combinations (FDCs) improve adherence but remain underutilised in public healthcare due to cost constraints. Community-based screening programmes (e.g. HealthRise South Africa) have successfully identified high-risk individuals, yet less than 30% of screened patients attend follow-ups due to referral challenges. Primary healthcare (PHC) infrastructure is overburdened, with workforce shortages, inconsistent medication availability, and weak referral systems limiting hypertension management. Public health policies targeting salt and sugar reduction have been implemented, but enforcement remains weak, and public awareness is insufficient. CONCLUSION AND POLICY IMPLICATIONS : Addressing hypertension in South Africa requires a multi-pronged strategy focusing on: 1. Expanding access to cost-effective FDCs in public clinics to improve adherence and BP control. 2. Strengthening PHC capacity through workforce training, task-shifting, and improved referral pathways. 3. Scaling up community-based screening and linkage-to-care programmes for early detection. 4. Enhancing enforcement of dietary policies and launching nationwide awareness campaigns on lifestyle modifications. 5. Implementing national BP monitoring registries to track trends and guide policy adjustments. A patient-centred, equity-driven approach that integrates pharmacological advances with robust public health interventions is critical to reversing the current trends of uncontrolled hypertension in South Africa.
Haemoglobin A1c (HbA1c) : clinical relevance, history, and role in diabetes mellitus management – a South African perspective
Jordaan, Beatrice; Outhoff, Kim (Medpharm Publications, 2025-06)
BACKGROUND : Diabetes mellitus (DM) is a growing health challenge in South Africa, with an increasing prevalence driven largely by urbanisation and lifestyle changes. Haemoglobin A1c (HbA1c) has emerged as a pivotal biomarker for diagnosing and monitoring diabetes. Its clinical utility is well established globally, yet its optimal use in the South African healthcare landscape remains an area of interest. This article provides a comprehensive review of HbA1c, outlining its historical discovery, biochemical basis, clinical applications, and interpretation challenges. Emphasis is placed on its role in South Africa, where access to laboratory testing and point-of-care diagnostics influences diabetes care. METHODS : A literature review was conducted using PubMed, Google Scholar, and local healthcare databases to evaluate HbA1c’s effectiveness in DM diagnosis and monitoring. International and South African guidelines were analysed to assess the standardisation and applicability of HbA1c testing in diverse populations. RESULTS : HbA1c is vital in diabetes management, though its accuracy may be affected by haemoglobinopathies, ethnicity, age, and medical conditions. Technological advances, such as point-of-care testing (POCT), have improved accessibility, particularly in underserved areas. Personalised HbA1c targets are increasingly recommended to enhance patient-centred care. CONCLUSION : While HbA1c is a valuable diagnostic and monitoring tool, healthcare professionals (HCPs) must be aware of its limitations in specific populations. Expanding access to HbA1c testing and integrating individualised glycaemic targets can improve diabetes management outcomes in South Africa.
Depression unveiled : a comprehensive review of pathophysiology and treatment advances
Skosana, P.; Naidoo, Mivasha; Nabyoma, J.; Mushipe, T. (Medpharm Publications, 2025-09)
Depression is one of the most commonly diagnosed mental health disorders among adults and is currently the third leading cause of disease worldwide. Depression, also referred to as major depressive disorder (MDD), poses a significant global health challenge, affecting over 300 million individuals worldwide. In sub-Saharan Africa, neuropsychiatric conditions account for nearly 10% of the disease burden, with depression being the most frequently diagnosed disorder. Clinically, depression manifests through symptoms such as feelings of worthlessness, cognitive and sleep disturbances, and suicidal ideation, with major depression representing the predominant subtype. Its complex pathogenesis has been extensively investigated, incorporating hypotheses related to genetic predisposition, neurotransmitter dysregulation, and hypothalamic-pituitary-adrenal (HPA) dysfunction, among others. While both pharmacological and non-pharmacological interventions demonstrate efficacy, antidepressant medications remain the cornerstone of treatment. Untreated depression can lead to widespread emotional, behavioural, and physical health complications, significantly impairing quality of life. This review reports current hypotheses regarding the underlying pathophysiology of depression and evaluates therapeutic strategies with an emphasis on the pharmacological profile of the classes used to treat depression.
The role of pharmacists in optimising patient outcomes to reduce the burden of tonsillitis
Majeed, Ramsha; Outhoff, Kim (Medpharm Publications, 2025)
Tonsillitis is a common upper respiratory tract infection frequently encountered in pharmacy practice, with significant implications for antimicrobial stewardship. It typically involves inflammation of the palatine tonsils, most often caused by viral infections, but occasionally by bacterial pathogens such as Streptococcus pyogenes (Group A Streptococcus, GAS). This article reviews the anatomy, epidemiology, aetiology, complications, and management of tonsillitis, with an emphasis on evidence-based pharmacological and supportive care. It also highlights the essential role pharmacists play in optimising treatment, counselling patients and promoting rational antibiotic use to reduce antimicrobial resistance.
The mechanism of action of oral corticosteroids in relation to short- and long-term-burst therapy
Cordier, Werner; Rossouw, Theresa M. (Allergy Society of South Africa, 2025-03)
Corticosteroids, potent anti-inflammatory agents, are broadly used in various inflammatory and immune-dependent pathologies, which include asthma. Through non-genomic and genomic mechanisms of action, corticosteroids reduce pro-inflammatory mediators while promoting anti-inflammatory molecule expression. Furthermore, in the context of asthma treatment, they also promote the expression of β2 adrenergic receptors which increase the therapeutic potential of β2-receptor agonists to promote bronchodilation. However, corticosteroids also precipitate a variety of adverse events which reduce the quality of life of patients and predispose them to further pathological alterations. Given the ubiquitous expression of the glucocorticoid receptor, alongside the non-genomic and genomic mechanisms of corticosteroids, a myriad interconnecting physiological processes are altered upon receptor modulation. Both long- and short-course treatment has been linked to immune suppression, metabolic and cardiovascular disease, cerebrovascular accidents, osteoporosis, ophthalmic disorders, pneumonia and mood disorders. Consequently, clinical decision-making should consider the potential risks involved in short- and long-term use of corticosteroids because pathophysiological changes may be precipitated in both.
Vascular endothelial growth factor receptors in the vascularization of pancreatic tumors : implications for prognosis and therapy
Grobbelaar, C.W. (Craig); Steenkamp, Vanessa; Mabeta, Peaceful Lucy (MDPI, 2025-03)
In pancreatic cancer (PC), vascular endothelial growth factor (VEGF) and its primary receptor, vascular endothelial growth factor receptor (VEGFR)-2, are central drivers of angiogenesis and metastasis, with their overexpression strongly associated with poor prognosis. In some PC patients, VEGF levels correlate with disease stage, tumor burden, and survival outcomes. However, therapies targeting VEGF and VEGFR-2, including tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have demonstrated limited efficacy, partly due to the emergence of resistance mechanisms. Resistance appears to stem from the activation of alternative vascularization pathways. This review explores the multifaceted roles of VEGFRs in pancreatic cancer, including VEGFR-1 and VEGFR-3. Potential strategies to improve VEGFR-targeting therapies, such as combination treatments, the development of more selective inhibitors, and the use of biomarkers, are discussed as promising approaches to enhance treatment efficacy and outcomes.
Advancing cervical cancer treatment : integrating cannabinoids, combination therapies and nanotechnology
Mathibela, Sanele Priscilla; Ncube, Keith Ntokozo; Lebelo, Maphuti Tebogo; Steenkamp, Vanessa (Springer, 2025-10)
BACKGROUND : Cervical cancer remains a major global health challenge, with the highest incidence and mortality rates observed in sub-Saharan Africa. Despite progress in prevention and treatment, the management of advanced and recurrent disease remains difficult. AIM : This review explores the potential role of cannabinoids in cervical cancer therapy, with a focus on their integration into existing treatment strategies, combination therapies, and nanotechnology-based delivery systems. METHODS : A critical synthesis of preclinical studies and emerging therapeutic approaches was conducted, examining the anticancer properties of cannabinoids, their mechanisms of action, and their application within combination and nanotechnology-based treatment modalities. RESULTS : Cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD) demonstrate anticancer effects by inducing apoptosis, inhibiting cell proliferation, and suppressing metastasis. Mechanistic studies highlight their ability to promote oxidative stress, modulate key signalling pathways, and influence immune responses in cervical cancer cells. Combination therapies involving cannabinoids with chemotherapy, radiotherapy, and immunotherapy show enhanced efficacy and reduced drug resistance. Furthermore, nanotechnology-based delivery systems offer advantages including targeted drug release, improved solubility, controlled dosing, and decreased systemic toxicity. CONCLUSION : Cannabinoids represent a promising adjunct in cervical cancer management. However, successful clinical translation requires optimisation of formulations, establishment of dosing protocols, and comprehensive safety evaluation. Future research should also explore biomarker-driven personalised medicine approaches. Standardisation, along with addressing regulatory and ethical challenges, will be crucial for the integration of cannabinoid-based therapies into mainstream cervical cancer treatment.
Advances in hypothyroidism management : rethinking therapy beyond levothyroxine
Ditshego, Rebotile; Pick, Jessica; Ncube, Keith Ntokozo (Medpharm Publications, 2025-10)
Hypothyroidism, a prevalent neuroendocrine disorder characterised by insufficient thyroid hormone production and a wide spectrum of clinical manifestations, affects approximately 5% of the population, with an additional 5% remaining undiagnosed. While levothyroxine remains the golden standard of care, its inability to resolve persistent symptoms in a subset of patients highlights the need for alternative approaches. Combination levothyroxine+liothyronine therapy, though unpopular and underutilised by most physicians, offers potential benefits, particularly when tailored to mimic natural thyroid hormone ratios. Furthermore, emerging therapies show promise in reducing pharmacokinetic fluctuations that limit current advances in hypothyroidism therapy. By addressing the shortcomings of traditional therapies, these innovative approaches aim to improve the quality of life and clinical outcomes for patients with hypothyroidism, especially when the golden standard fails. This review highlights current viable options and explores emerging therapeutic strategies that could potentially optimise current treatment and quality of life, catering for all hypothyroidism patients.
Exploring the ex vivo effects of Bitis arietans snake venom on the coagulation, ultrastructure, and viscoelastic properties of human blood
Hill, Courtney; Megaw, Christie; Potgieter, Johan; Strydom, Morne A.; Bester, Janette (Elsevier, 2025-08)
BACKGROUND : Snakebite envenoming represents a significant and frequently overlooked public health challenge affecting tropical and subtropical regions. Bitis arietans venom toxins have cytotoxic effects and result in coagulopathy. However, there is limited literature on coagulopathies associated with B arietans envenomation or comparing traditional diagnostic tests with point-of-care (POC) methods. OBJECTIVES : This study investigated the effects of B arietans venom on the coagulation of human blood, with a focus on comparing the 20-minute whole blood clotting test (20-WBCT) to other POC coagulation tests. METHODS : This study exposed human blood to 2 ng/μL B arietans venom ex vivo. Clot formation was studied using the 20-WBCT. Prothrombin time, activated partial thromboplastin time, thrombin time, and fibrinogen levels were measured to obtain hematological clotting profiles of each participant. Viscoelastic properties of whole blood clot kinetics were quantified using thromboelastography (TEG). Red blood cell morphology and clot architecture were analyzed using scanning electron microscopy. RESULTS : Bitis arietans venom had significant effects on red blood cell morphology and clot structure. Both the 20-WBCT and clinical coagulation assays revealed notable differences in the results of venom-exposed samples; however, they were still in the normal range. TEG indicated hypocoagulation and decreased clot stability. Morphological studies of venom-exposed samples revealed echinocytes with varying degrees of morphological abnormalities and membrane blebbing. In addition, venom-exposed blood clots had sparse, disorganized fibrin networks and limited crosslinking. CONCUSION : Bitis arietans venom contains various hemotoxins that disrupt normal clot formation and affect TEG parameters. These insights provide a necessary link between clinical and laboratory analysis of B arietans venom. The study demonstrates the value of TEG as a POC test in snakebite management as it could provide a better indication of coagulopathy associated with envenomation. ESSENTIALS • Current research focusing on the hemotoxic effects of Bitis arietans venom is limited. • Small, unstable clot formation with disrupted fibrin networks were observed in the venom-exposed samples. • Venom-exposed samples also displayed changes in red blood cell morphology and ultrastructure. • The study findings expand the understanding of the effects of B arietans venom on human blood coagulation.
Mapping evidence on the regulations affecting the accessibility, availability, and management of snake antivenom globally : a scoping review
Majeed, Ramsha; Bester, Janette; Kgarosi, Kabelo; Strydom, Morne A. (MDPI, 2025-08)
The World Health Organization (WHO) declared snakebite envenoming (SBE) as a neglected tropical disease in 2017. Antivenom is the gold standard of treatment, but many healthcare barriers exist, and hence, affected populations are often unable to access it. The challenge is further perpetuated by the lack of attention from national health authorities, poor regulatory systems and policies, and mismanagement of antivenom. This study aims to map the evidence regarding snake antivenom regulations globally and identify gaps in the literature to inform future research and policy. This review was conducted using the original Arksey and O’Malley framework by three independent reviewers, and the results were reported using the Preferred Reporting Items for Systematic reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). A search strategy was developed with assistance from a librarian, and six databases were searched: PubMed, SCOPUS, ProQuest Central, Africa Wide Web, Academic Search Output, and Web of Science. Screening was conducted independently by the reviewers, using Rayyan, and conflicts were resolved with discussions. A total of 84 articles were included for data extraction. The major themes that emerged from the included studies were regarding antivenom availability, accessibility, manufacturing, and regulations. The study revealed massive gaps in terms of policies governing antivenom management, especially in Asia and Africa. The literature does not offer sufficient evidence on management guidelines for antivenom in the endemic regions, despite identifying the challenges in supply. However, significant information from Latin America revealed self-sufficient production, involvement of national health bodies in establishing efficient regulations, effective distribution nationally and regionally, and technology sharing to reduce SBE-related mortality.
Utility of multicellular spheroids for investigating mechanisms of chemoresistance in triple-negative breast cancer
Ncube, Keith Ntokozo; Van den Bout, Iman; Willers, Clarissa; Gouws, Chrisna; Cordier, Werner (MDPI, 2025-08)
Chemoresistance is a major challenge in the treatment of triple-negative breast cancer (TNBC). Multicellular spheroids are an attractive platform for investigating chemoresistance in TNBC, as they replicate the cues of the tumour microenvironment in vivo. We conducted a comprehensive literature search to summarise the multifactorial and interlinked mechanisms driving chemoresistance in TNBC spheroids. These mechanisms include spatial heterogeneity, hypoxia, extracellular matrix remodelling, tumour–stroma crosstalk, drug efflux, apoptotic resistance, and cancer stem cell signalling. Strategies for overcoming chemoresistance in TNBC spheroids include nanocarrier systems to overcome spatial diffusion limitations, pathway inhibition, and targeting tumour–microenvironment interactions. Despite their advantages, some spheroid models face challenges such as low reproducibility, a lack of heterogeneity, variability in size and shape, limited vascularisation, and constraints in long-term culture. Advanced culturing platforms such as clinostat bioreactors allow for extended culture periods, enabling mature spheroid drug testing. Furthermore, advanced analytical techniques provide spatially resolved spheroid data. These multifactorial and interlinked mechanisms reflect the tumour microenvironment in vivo that spheroids recapitulate, rendering them valuable models for studying chemoresistance. The incorporation of stromal components and advanced analytical workflows will enhance the utility and translational relevance of spheroids as reliable preclinical models for drug discovery in TNBC.
The global landscape of neuropsychiatric prescribing practices of nurses : a scoping review
Naidoo, M.; Filmalter, Cecilia Jacoba; Cordier, Werner (Wiley, 2025-07)
Mental healthcare service access in South Africa is currently strained due to, among others, shortages of specialised mental healthcare professionals. The National Strategic Plan for HIV, TB and STIs (2023-2028) recommends enabling nurses to diagnose, prescribe and dispense neuropsychiatric medication for promoting mental health services. The aim was to explore and describe the existing practices, strengths and challenges for nurses prescribing neuropsychiatric medication globally through a scoping and document review. A standardised search was conducted across PubMed, CINAHL and EBSCOHost electronic databases. An online Google search was conducted across governmental legislative and regulatory websites. The Joanna Briggs Institute scoping review framework was followed using relevant MeSH terms and free-text words. South African governmental and parastatal documentation relating to relevant regulatory frameworks affecting such prescribing authorisation in South Africa was analysed following Bowen (2009) guidelines. Of 817 citations identified, 20 reports were included. The included reports originated mostly from developed countries, with only one from South Africa. Patients and healthcare professionals were mostly positive towards including the prescription of neuropsychiatric medication in the nursing care model. Prescription of Schedule 5 and 6 controlled substances by nurses is already authorised in the USA and UK. In South Africa, nurses are not yet permitted and will require amendments to the legislative framework that guides nursing practice. Nurses can prescribe neuropsychiatric medications in certain developed countries; however, contextual research is necessary to ascertain whether South African stakeholders will support such an authorisation. Educational and interprofessional concerns will need to be thoroughly assessed to ensure that appropriate competencies are obtained, ensuring the boundaries of the scope of practice. Investigation of potential professional overlap of responsibilities and perceptional biases, as well as transformation of educational platforms, will be needed should such a recommendation come to pass. Furthermore, legislative changes will be required to authorise the prescription of neuropsychiatric medications.
WHO global research priorities for antimicrobial resistance in human health
Bertagnolio, Silvia; Dobreva, Zlatina; Centner, Chad M.; Olaru, Ioana Diana; Donà, Daniele; Burzo, Stefano; Huttner, Benedikt D.; Chaillon, Antoine; Gebreselassie, Nebiat; Wi, Teodora; Hasso-Agopsowicz, Mateusz; Allegranzi, Benedetta; Sati, Hatim; IVanovska, Verica; Kothari, Kavita U.; Balkhy, Hanan H.; Cassini, Alessandro; Hamers, Raph L.; Van Weezenbeek, Kitty; Aanensen, David; Alanio, Alexandre; Alastruey-Izquierdo, Ana; Alemayehu, Tinsae; Al-Hasan, Majdi; Allegaert, Karel; Al-Maani, Amal Saif; Al-Salman, Jameela; Alshukairi, Abeer Nizar; Amir, Afreenish; Applegate, Tanya; Araj, George F.; Villalobos, Marlen Arce; Årdal, Christine; Ashiru-Oredope, Diane; Ashley, Elizabeth A.; Babin, François-Xavier; Bachmann, Laura H.; Bachmann, Till; Baker, Kate Susan; Balasegaram, Manica; Bamford, Colleen; Baquero, Fernando; Barcelona, Laura Isabel; Bassat, Quique; Bassetti, Matteo; Basu, Sulagna; Beardsley, Justin; Vásquez, Grey Benoit; Berkley, James A.; Bhatnagar, Anuj K.; Bielicki, Julia; Bines, Julie; Bongomin, Felix; Bonomo, Robert A.; Bradley, John S.; Bradshaw, Catriona; Brett, Ana; Brink, Adrian; Brown, Colin; Brown, Jeremy; Buising, Kirsty; Carson, Carolee; Carvalho, Anna Cristina; Castagnola, Elio; Cavaleri, Marco; Cecchini, Michele; Chabala, Chishala; Chaisson, Richard E.; Chakrabarti, Arunaloke; Chandler, Clare; Chandy, Sujith John; Charani, Esmita; Chen, Lisa; Chiara, Francesca; Chowdhary, Anuradha; Chua, Arlene; Chuki, Pem; Chun, Doo Ryeon; Churchyard, Gavin; Cirillo, Daniela; Clack, Lauren; Coffin, Susan E.; Cohn, Jennifer; Cole, Michelle; Conly, John; Cooper, Ben; Corso, Alejandra; Cosgrove, Sara E.; Cox, Helen; Daley, Charles L.; Darboe, Saffiatou; Darton, Tom; Davies, Gerry; De Egea, Viviana; Dedeić-Ljubović, Amela; Deeves, Miranda; Denkinger, Claudia; Dillon, Jo-Anne R.; Dramowski, Angela; Eley, Brian; Roberta Esposito, Susanna Maria; Essack, Sabiha Y.; Farida, Helmia; Farooqi, Joveria; Feasey, Nicholas; Ferreyra, Cecilia; Fifer, Helen; Finlayson, Heather; Frick, Mike; Gales, Ana Cristina; Galli, Luisa; Gandra, Sumanth; Gerber, Jeffrey S.; Giske, Christian; Gordon, Bruce; Govender, Nelesh; Guessennd, Nathalie; Guindo, Ibrehima; Gurbanova, Elmira; Gwee, Amanda; Hagen, Ferry; Harbarth, Stephan; Haze, John; Heim, Jutta; Hendriksen, Rene; Heyderman, Robert Simon; Holt, Kathryn Elizabeth; Hönigl, Martin; Hook, Edward W.; Hope, William; Hopkins, Heidi; Hughes, Gwenda; Ismail, Ghada; Issack, Mohammad Iqbal; Jacobs, Jan; Jasovský, Dušan; Jehan, Fyeza; Pearson, Antonieta Jimenez; Jones, Makoto; Joshi, Mohan P.; Kapil, Arti; Kariuki, Samuel; Karkey, Abhilasha; Kearns, Gregory L.; Keddy, Karen Helena; Khanna, Nina; Kitamura, Akiko; Kolho, Kaija-Leena; Kontoyiannis, Dimitrios P.; Kotwani, Anita; Kozlov, Roman S.; Kranzer, Katharina; Kularatne, Ranmini; Lahra, Monica M.; Langford, Bradley J.; Laniado-Laborin, Rafael; Larsson, Joakim; Lass-Flörl, Cornelia; Le Doare, Kirsty; Lee, Hyukmin; Lessa, Fernanda; Levin, Anna S.; Limmathurotsakul, Direk; Lincopan, Nilton; Lo Vecchio, Andrea; Lodha, Rakesh; Loeb, Mark; Longtin, Yves; Lye, David Chien; Mahmud, Asif Mujtaba; Manaia, Célia; Manderson, Lenore; Mareković, IVana; Marimuthu, Kalisvar; Martin, Irene; Mashe, Tapfumanei; Mei, Zeng; Meis, Jacques F.; Lyra Tavares De Melo, Flávio Augusto; Mendelson, Marc; Miranda, Angelica Espinosa; Moore, David; Morel, Chantal; Moremi, Nyambura; Moro, Maria Luisa; Moussy, Francis; Mshana, Stephen; Mueller, Arno; Ndow, Francis J.; Nicol, Mark; Nunn, Andrew; Obaro, Stephen; Obiero, Christina W.; Okeke, Iruka N.; Okomo, Uduak; Okwor, Tochi J.; Oladele, Rita; Omulo, Sylvia; Ondoa, Pascale; Ortellado de Canese, Juana Medarda; Ostrosky-Zeichner, Luis; Padoveze, Maria Clara; Pai, Madhukar; Park, Benjamin; Parkhill, Julian; Parry, Christopher M.; Peeling, Rosanna; Sobreira Vieira Peixe, Luísa Maria; Perovic, Olga; Pettigrew, Melinda M.; Principi, Nicola; Pulcini, Céline; Puspandari, Nelly; Rawson, Timothy; Reddy, Denasha LaVanya; Reddy, Kessendri; Redner, Paulo; Rodríguez Tudela, Juan Luis; Rodríguez-Baño, Jesús; Rogers Van Katwyk, Susan; Roilides, Emmanuel; Rollier, Christine; Rollock, Leslie; Ronat, Jean-Baptiste; Ruppe, Etienne; Sadarangani, Manish; Salisbury, David; Salou, Mounerou; Samison, Luc Hervé; Sanguinetti, Maurizio; Sartelli, Massimo; Schellack, Natalie; Schouten, Jeroen; Schwaber, Mitchell J.; Seni, Jeremiah; Senok, Abiola; Shafer, William M.; Shakoor, Sadia; Sheppard, Donald; Shin, Jong-Hee; Sia, Sonia; Sievert, Dawn; Singh, Ishwar; Singla, Rupak; Skov, Robert Leo; Soge, Olusegun O.; Sprute, Rosanne; Srinivasan, Arjun; Srinivasan, Subasree; Sundsfjord, Arnfinn; Tacconelli, Evelina; Tahseen, Sabira; Tangcharoensathien, Viroj; Tängdén, Thomas; Thursky, Karin; Thwaites, Guy; Tigulini de Souza Peral, Renata; Tong, Deborah; Tootla, Hafsah Deepa; Tsioutis, Constantinos; Turner, Katy M.; Turner, Paul; Omar, Shaheed Vally; Van de Sande, Wendy W.J.; Van den Hof, Susan; Van Doorn, Rogier; VeeraraghaVan, Balaji; Verweij, Paul; Wahyuningsih, Retno; Wang, Hui; Warris, Adilia; Weinstock, Hillard; Wesangula, Evelyn; Whiley, David; White, Peter J.; Williams, Phoebe; Xiao, Yonghong; Moscoso, Martin Yagui; Yang, Hsu Li; Yoshida, Sachiyo; Yu, Yunsong; Żabicka, Dorota; Zignol, Matteo (Elsevier, 2024-11)
The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR.
Antiretroviral-induced toxicity in umbilical cord blood-derived haematopoietic stem/progenitor cells
Hendricks, Candice Laverne; Ellero, Andrea Antonio; Mellet, Juanita; Stivaktas, Voula; Pepper, Michael Sean (Wiley, 2025-04)
Improvements in administration and efficacy of antiretroviral therapy (ART) have reduced rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) to < 2%. However, in utero exposure to antiretrovirals (ARVs) leads to abnormalities in HIV-exposed uninfected (HEU) infants. We determined the effect of five ARVs on human umbilical cord blood (UCB)-derived haematopoietic stem/progenitor cells (HSPC) with the aim of exploring a potential causal relationship with haematological abnormalities. Efavirenz (EFV) was cytotoxic to HSPCs alone and in combination with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). Dolutegravir (DTG) had a biphasic effect on HSPC expansion. Immunophenotypic analysis showed increased erythroid and granulocyte precursors after 7-day culture with these drugs. Finally, using colony forming unit (CFU) assays, we observed impairment in the formation of CFU-GEMM and CFU/Burst forming unit (BFU) erythroid (E) in the presence of DTG, lamivudine (3TC) and TDF, both visually and immunophenotypically. We conclude that multiple potential HSPC toxicities exist with ARVs commonly used in pregnancy, prompting the need for further research to confirm the safety of these drugs in this vulnerable group.
Combining an OSMAC approach and untargeted metabolomics to profile compounds exhibiting anti-HIV-1 activities in an endophytic fungus, Penicillium Rubens P03MB2
Moloi, Neo; Khumalo, Mothusi C.; Nxumalo, Wonder Praise-God; Mtambo, Sphamandla E.; Mkhwanazi, Nompumelelo P.; Ndlovu, Sizwe I. (Nature Research, 2025-07)
The persistent burden of HIV-1 in Sub-Saharan Africa underscores the need for innovative treatments, as current antiretroviral therapies cannot eliminate latent proviral reservoirs and face challenges from multidrug-resistant strains. This study investigates the potential of Penicillium rubens P03MB2, an endophytic fungus from the Albizia adianthifolia plant, as a source of novel anti-HIV-1 compounds. The fungus was cultivated in various media (malt extract broth, oats, and rice), with oat media yielding crude extracts exhibiting significant anti-HIV-1 activity. Active fractions were further analyzed using an untargeted metabolomics and molecular networking approach, revealing clusters of secondary metabolites, including coumarins and other anti-HIV-1-associated compounds. A virtual screening workflow was employed to assess the binding affinities of these metabolites against HIV-1 protease. Furthermore, molecular dynamics simulations were used to analyze ligand-protein complex stability. Binding free energy calculations highlighted diosgenin as a promising candidate, with a binding free energy of -34.59 kcal/mol, outperforming the co-crystallized ligand ORV. This research demonstrates the potential of secondary metabolites from Penicillium rubens as novel anti-HIV-1 agents, offering a foundation for further developing effective antiviral therapies.
Air travel and the risk of venous thromboembolism
Schellack, G.; Schellack, Natalie; Agyepong-Yeboah, Amma (Medpharm Publications, 2025-04-01)
Passenger air travel is a convenient and frequently used mode of transportation across the globe. However, certain health risks are associated with commercial flights, many of which are inherent to this distinctive method of transportation. It has been shown that air travel innately carries an increased risk of the development of venous thromboembolism (VTE), and although small, this risk is significantly higher than in the general, healthy, non-flying population. Individual air travellers are strongly encouraged to consult a suitable healthcare professional for an individual risk assessment and guidance on suitable or required prophylactic measures prior to undertaking either frequent or long-distance travel via aeroplane.

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