THE DEVELOPMENT OF AN ORAL VACCINE AGAINST ANTHRAX

摘要

Bacillus anthracis, a sporulating gram-positive rod, is the causative agent of the disease anthrax, which commonly occurs among herbivores but can also affect humans. The disease is still prevalent in many parts of Africa, Central and South America, the Indian subcontinent, Indonesia, Australia, the Middle East and certain regions of the former USSR. The disease in humans occurs primarily in a cutaneous form, but also as pulmonary or gastro-intestinal manifestations, depending upon the route of infection by anthrax spores (Table 1). In endemic countries anthrax occurs mainly as an occupational disease. Its normal spread among herbivores causes accidental infection to people whose occupation brings them into contact with animal products. For this reason anthrax is also called "wool sorter's disease". The cutaneous form is transmitted through a break in the skin and is manifested as a painless carbuncle or pustule. The infection may spread through the bloodstream and can cause shock, cyanosis, sweating and collapse. Without treatment 10-20% of all cases of cutaneous infection progress to fatal septi-cemia. With hospital treatment (antibiotics) this figure drops to 0-3%. The gastro-intestinal form is transmitted by consumption of meat from animals that have died from anthrax. Symptoms are nausea, vomiting, fever, chills, abdominal pain, bloody diarrhea, general discomfort, malaise and shock. Finally, a comatose stage is reached, eventually leading to death. Gastro-intestinal anthrax is far more often fatal than the cutaneous form. The pulmonary form of anthrax is transmitted by inhalation of spores in dust clouds created by handling dry hides, wool and bone meal. Airborne spores that are >5 micron in size pose a reduced threat, as they are either physically trapped in the nasopharynx or are cleared by the mucociliary system. Spores between 1 and 5 micron in size are more likely to penetrate and be deposited on alveolar ducts or alveoli. They are phagocytosed by alveolar macrophages and are transported to the mediastinal lymph nodes where they germinate and multiply rapidly, causing hemorrhagic mediastinitis. Illness begins insidiously with mild fever, fatigue and malaise. This mild initial phase is terminated by the sudden onset of acute illness. The rapid development of dyspnoea, cyanosis, severe pyrexia is quickly followed by coma and death. The fatality rate of the pulmonary form is or is near 100%. Human anthrax is not considered contagious and there is no evidence of person-to-person transmission.