CURRENT STATUS AND TRENDS IN THE PREVENTION AND TREATMENT OF ANTHRAX

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 68 CURRENT STATUS AND TRENDS IN THE PREVENTION AND TREATMENT OF ANTHRAX N.K. Burxanova1, P.O. Sa’dinov2 PhD candidate at the Tashkent Research Institute of Vaccines and Serums, Tashkent1 PhD.in Medical Sciences, Senior Researcher of the Immunology Laboratory at the Tashkent Research Institute of Vaccines and Serums, Tashkent2 https://doi.org/10.5281/zenodo.17920328 Abstract. Anthrax is a dangerous infectious disease caused by the pathogen Bacillus anthracis, which can manifest itself in pulmonary, cutaneous, and intestinal forms. Successful clinical treatment depends on the timely initiation of antibacterial therapy and the appropriate selection of medications. One of the important components of biological defense is drug prophylaxis aimed at preventing the development of the disease in patients exposed to the spores of these microorganisms. This article provides a general overview of modern approaches to the treatment and prevention of anthrax, the groups of drugs used, their mechanisms of action, and a detailed analysis of the literature by local and international authors. Keywords: anthrax, antibiotics, Bacillus anthracis, post-exposure prophylaxis, antitoxin, toxin, lethal toxin, protective antigen (PA), virulence, FDA. Introduction Anthrax is a zoonotic disease caused by Bacillus anthracis, which continues to occur in agricultural regions of the Americas, sub-Saharan Africa, Central and Southwestern Asia, and Southern and Eastern Europe [16]. Primarily, sheep, goats, cattle, and other herbivores are affected. Humans become infected secondarily through contact with infected animals, consumption of contaminated animal products (such as meat or hides), or, more rarely, through injection of illicit drugs [17]. The symptoms, treatment, and prognosis of anthrax in humans depend on the route of infection. Gastrointestinal anthrax develops after consuming inadequately cooked meat from animals that have ingested naturally occurring anthrax spores in soil. Cutaneous anthrax, the most common form, results from direct inoculation of spores through the skin and accounts for more than 95% of cases. Inhalational anthrax is acquired by inhaling aerosolized spores of B. anthracis [1]. Among the three major forms, inhalational anthrax represents a serious bioterrorism threat due to the ability of infectious spores to remain airborne over long distances and because the mortality rate reaches 100% if timely treatment is not provided [2, 3]. A relatively new form, injection anthrax, has been reported following the injection of heroin contaminated with B. anthracis spores. Anthrax meningitis may complicate any form of the disease. Due to its ability to remain airborne while preserving infectivity and the extremely high mortality rate in the absence of prompt treatment, inhalational anthrax is considered a serious bioterrorism hazard. [2, 3] The general principles of anthrax therapy include: 1. Combined antibacterial therapy 2. Anthrax antitoxin 3. Symptomatic therapy Combined Antibacterial Therapy SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 69 In 2008, the World Health Organization (WHO) updated its recommendations on the treatment and prevention of anthrax [4]. Penicillin G is widely used in many countries for the treatment of naturally occurring anthrax. The WHO recommends antibacterial therapy and supportive therapy for inhalational and gastrointestinal forms of anthrax, as well as for the cutaneous form with systemic manifestations. In severe cases, the WHO recommends the combination of penicillin with either a fluoroquinolone (ciprofloxacin or levofloxacin) or a macrolide (clindamycin or clarithromycin). The main recommendations for the treatment of gastrointestinal anthrax include a combination of penicillin with an aminoglycoside (streptomycin). Penicillin is selected as the antibiotic of choice for children. For post-exposure prophylaxis following contact with B. anthracis spores in inhalational anthrax, four antibiotics have been approved: doxycycline, ciprofloxacin, levofloxacin, and parenteral procaine-penicillin G. Levofloxacin for post-exposure prophylaxis of anthrax was approved by the FDA for adults in 2004 and for children in 2008 [5]. Recommendations regarding the duration of treatment are not clearly defined. In general, the WHO recommends 3 to 7 days for uncomplicated cutaneous anthrax and 10 to 14 days for systemic infections [6]. Although timely and appropriate antimicrobial therapy may reduce morbidity and mortality, research on additional treatment modalities continues. Anthrax Antitoxin Anthrax is a toxin-mediated disease, and anthrax toxins together with the antifagocytic polyglutamic capsule are the two major virulence factors of B. anthracis. These virulence factors are encoded by genes located on the PXO1 and PXO2 plasmids, respectively. The lethal toxin is formed when the protective antigen (PA) binds to the lethal factor (LF), and the edema toxin is formed when the protective antigen binds to the edema factor [18, 19]. Lethal toxin (LT) and edema toxin (ET) enter the cell by endocytosis. LF and EF escape from the endocytic vesicle and reach their targets in the cytosol. The lethal toxin suppresses immune function and is responsible for vasomotor instability. LF is a protease that catalyzes the hydrolysis of MAPKK (mitogen-activated protein kinase kinase), ultimately leading to cell death through apoptosis. The edema toxin causes cell and tissue swelling. ET is a calmodulin-dependent adenylate cyclase that markedly increases the intracellular level of cAMP. Elevated cAMP results in disturbance of water homeostasis (leading to edema) and disruption of intracellular signaling pathways, reducing macrophage function. This allows the bacteria to evade the immune system. Currently, three antitoxin preparations have been approved by the Food and Drug Administration (FDA) for the treatment of anthrax: Anthrasil (Anthrasil, Intravenous Anthrax Immune Globulin), a purified polyclonal human immunoglobulin G (IgG). Human plasma obtained from individuals vaccinated with the BioThrax vaccine was used for the production of Anthrasil. To support licensing, a passive transfer model was used, in which animals were administered purified anthrax immune globulin (AIGIV, Anthrasil). [8, 9] Raxibacumab (Abthrax) is a recombinant monoclonal antibody belonging to the IgG1 class, produced using recombinant DNA technology in a mouse cell expression system. This antibody binds to the protective antigen of anthrax and blocks the activity of the toxin. Raxibacumab was approved by the FDA in 2012 for the treatment of patients with inhalational anthrax in combination with antibiotics, as well as for post-exposure prophylaxis when alternative treatment methods are unavailable or inappropriate. [10] SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 12 DECEMBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 70 Obiltoxaximab (Anthim) is a chimeric, de-immunized monoclonal immunoglobulin G produced in a human cell line. Although it was developed in parallel with raxibacumab, it was approved by regulatory authorities in 2016 and recommended for the treatment of inhalational anthrax. Its use in combination with antibiotics was approved in cases where no alternative therapeutic options are available [11]. Both Raxibacumab and Obiltoxaximab are also indicated for use in post-exposure prophylaxis (PEP). All three approved agents exert their effect by binding to the protective antigen, thereby preventing the formation of lethal and edema toxin. The Centers for Disease Control and Prevention (CDC) recommends the use of antitoxin as an adjunct to antimicrobial agents for the treatment of systemic anthrax. This applies to all age groups and special populations. [12,13,14] CONCLUSION Anthrax has been described for more than two thousand years. [15] Despite the availability of vaccines as a preventive measure, it remains a serious public health problem for people and livestock in many parts of developing countries. The spore-forming ability of the bacterium and its capacity to survive various environmental challenges provide a strong rationale for developing effective therapeutic agents for post-exposure prophylaxis (PEP). Limited evidence in humans and animals suggests that adjunctive antitoxin therapy may improve survival in cases of systemic anthrax infection. When used as treatment, early administration of antitoxin significantly improves survival, and when used for post-exposure prophylaxis, it reduces the likelihood of infection. The FDA has approved raxibacumab and obiltoxaximab for PEP; these agents reduce the risk of disease development by binding protective antigen and preventing toxin formation, and when used in combination with antibiotics in systemic anthrax, they improve survival outcomes. REFERENCES 1. 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