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Vaccine-induced immune thrombotic thrombocytopaenia (VITT) is a rare adverse effect of COVID-19 adenoviral vector vaccines 1 – 3 . VITT resembles heparin-induced thrombocytopaenia (HIT) in that it is associated with platelet-activating antibodies against platelet factor 4 (PF4) 4 ; however, patients with VITT develop thrombocytopaenia and thrombosis without exposure to heparin. Here we sought to determine the binding site on PF4 of antibodies from patients with VITT. Using alanine-scanning mutagenesis 5 , we found that the binding of anti-PF4 antibodies from patients with VITT ( n  = 5) was restricted to eight surface amino acids on PF4, all of which were located within the heparin-binding site, and that the binding was inhibited by heparin. By contrast, antibodies from patients with HIT ( n  = 10) bound to amino acids that corresponded to two different sites on PF4. Biolayer interferometry experiments also revealed that VITT anti-PF4 antibodies had a stronger binding response to PF4 and PF4–heparin complexes than did HIT anti-PF4 antibodies, albeit with similar dissociation rates. Our data indicate that VITT antibodies can mimic the effect of heparin by binding to a similar site on PF4; this allows PF4 tetramers to cluster and form immune complexes, which in turn causes Fcγ receptor IIa (FcγRIIa; also known as CD32a)-dependent platelet activation. These results provide an explanation for VITT-antibody-induced platelet activation that could contribute to thrombosis. Alanine-scanning mutagenesis is used to identify the PF4 epitope that is recognized by anti-PF4 antibodies in patients with vaccine-induced immune thrombotic thrombocytopaenia, revealing that the epitope corresponds to the heparin-binding site on PF4.

VITT is caused by antibodies to PF4 that recognize the heparin-binding site. Thrombocytopenia and thrombosis associated with VITT-like antibody specificity developed in a child and an adult after adenovirus infection.

Background: Zambia, like many low- and middle-income countries, faces a growing burden of antimicrobial resistance (AMR), driven by the misuse of antimicrobials in both human and animal health, a limited diagnostic capacity, and weak regulatory enforcement. To address this challenge, Standard Treatment Guidelines (STGs) were developed for the veterinary sector, which represents a major milestone in the country’s AMR containment strategy. STGs are evidence-based protocols that guide veterinary professionals in consistently and appropriately diagnosing and treating animal diseases. They promote the rational use of veterinary medicines, and can mitigate AMR and improve animal health outcomes. By translating the best evidence into best practices, STGs also provide a practical foundation for antimicrobial stewardship (AMS) programs. Until 2023, Zambia lacked nationally adopted STGs for the veterinary sector. The introduction and standardization of these guidelines are expected to promote prudent antimicrobial use and raise the standard of care delivered to animal patients across the country. Objective: The aim of this paper is to provide a practical reference for future revisions of STGs and outline the successful methodology used to create STGs in the Zambian animal sector. Methods: A situational analysis was conducted to identify priority animal health conditions and existing treatment gaps within the veterinary sector. A multidisciplinary expert committee was then formed, comprising veterinarians, veterinary paraprofessionals, academics, regulatory authorities, and private sector stakeholders, to lead the development of the STGs. The process was guided by the WHO methodology for developing treatment guidelines, including a comprehensive review of the clinical evidence, local disease patterns, antimicrobial resistance data, and existing treatment practices. Draft STGs were developed with clearly defined, species-specific treatment protocols tailored to the Zambian context. For the validation process, the AGREE II instrument was used to assess the quality, clarity, and applicability of the guidelines. Structured stakeholder consultations with practitioners, policy-makers, and technical experts were held to ensure that the guidelines were practical, evidence-based, and aligned with national priorities. The validated drafts were then disseminated and piloted in selected districts. Conclusions: The development of the species-specific STGs represents an essential turning point in the country’s efforts to promote responsible veterinary care and contain AMR. STGs have become a prominent key support in the delivery of quality animal care. Further, the guidelines will assist in the optimization of antimicrobial use in animal health in Zambia.

Background/Objectives: Antimicrobial Resistance (AMR) remains a growing public health threat, underscoring the need for robust surveillance of Antimicrobial Consumption (AMC) and Antimicrobial Use (AMU). This study analysed AMC and AMU trends in Zambia’s human and animal health sectors, identifying priority areas for antimicrobial stewardship (AMS) under a One Health framework. Methods: A retrospective study was conducted in February 2025, utilising data from 2018 to 2023. Sources of data included the Zambia Medicines Regulatory Authority (ZAMRA) and the WOAH Animal Antimicrobial Use (ANIMUSE) Global Database platform. AMC was analysed using the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) methodology. Antimicrobials were classified using the WHO Anatomical Therapeutic Chemical (ATC) system, and consumption was measured in Defined Daily Doses (DDDs) per 1000 inhabitants per day (DID). Antibiotics were further categorised using the WHO Access, Watch, and Reserve (AwaRe) classification. Data analysis was performed using IBM SPPS version 25.0. Results: In the human health sector, oral antibiotics accounted for 88% of total consumption. Penicillins (33%), cephalosporins (19.2%), and macrolides (12.4%) were the most consumed classes. In 2023, 98,651,882.42 DDDs per 1000 inhabitants/day were recorded, with amoxicillin, ceftriaxone, and sulfamethoxazole/trimethoprim leading as the most consumed antibiotics. According to the consumption of antibiotics by the WHO AwaRe classification, 47% were Access, 40% Watch, and 3% Reserve group antibiotics. In animal health, tetracyclines dominated (63%), followed by sulphonamides (26%) and penicillins (11%). AMU in animal health peaked in 2023. Conclusions: This study found high AMC and AMU, especially Watch-group antibiotics and tetracyclines, highlighting the need for strengthened antimicrobial stewardship, regulatory oversight, and integrated One Health surveillance to mitigate AMR risks in Zambia.