Editor's Note: Anthrax is a zoonotic infectious disease caused by Bacillus anthracis infection, which still occurs sporadically in some areas of China. Anthrax can manifest in various clinical forms, with pulmonary anthrax having a mortality rate of over 80% and requiring management as a Class A infectious disease. In order to further standardize the clinical diagnosis and treatment of anthrax, the National Health Commission issued the "Anthrax Diagnosis and Treatment Plan (2023 Edition)." At the recent Fourth National Congress of the Chinese Society of Infectious Diseases (BISC 2024), Professor Junyan Qu, the secretary-general of the conference and from the Infectious Diseases Center of West China Hospital, Sichuan University, interpreted the diagnosis and treatment plan based on case studies. The summary is presented below.Background
Anthrax (Anthrax) is a zoonotic infectious disease caused by Bacillus anthracis, mainly occurring in herbivorous animals such as cattle, sheep, and horses. Humans mainly become infected with anthrax by contacting infected animals or their products, or inhaling anthrax spores in the environment. In recent years, the overall incidence of anthrax in China has been low, with an annual incidence rate below 0.05/100,000 and a mortality rate of 0.2% to 2.7%, but local outbreaks still occur.
Anthrax is classified as a Class B infectious disease under the “Law of the People’s Republic of China on the Prevention and Treatment of Infectious Diseases,” with pulmonary anthrax managed as a Class A infectious disease. In order to further standardize the clinical diagnosis and treatment of anthrax, this diagnosis and treatment plan was formulated based on domestic and international research progress and clinical experience.
Epidemiology
Anthrax has the following epidemiological characteristics: (1) Regional distribution: Anthrax is prevalent in pastoral areas worldwide, resulting in endemic outbreaks, with approximately 2,000 to 20,000 reported cases globally each year. From 1880 to 1915, most reported cases of anthrax came from Europe, from 1916 to 1950 mostly from North America, and since 1950, most cases have been reported from Asia. The overall trend of anthrax in China is declining, mainly distributed in western and northern regions, with the highest incidence in provinces including Sichuan, Gansu, Qinghai, Xinjiang, and Inner Mongolia. (2) Seasonal: Anthrax is more common in summer and less common in autumn and winter.
The main source of anthrax transmission is infected herbivorous animals such as cattle, sheep, horses, camels, followed by omnivorous animals such as pigs and dogs. Fur, meat, and their products from carrier animals may carry anthrax bacilli. The transmission routes of anthrax include direct contact transmission, respiratory transmission, and digestive tract transmission. The population is generally susceptible, but individuals involved in the breeding, slaughter, processing, and sale of animals and their products are at high risk. Infected individuals usually acquire lasting immunity.
Pathogeny
Bacillus anthracis belongs to the Bacillaceae family, Bacillus genus, appearing as large Gram-positive rods, arranged in chains with no flagella, and unable to move. It grows well on common nutrient agar medium, forming white rough colonies.
Bacillus anthracis can form spores (refractile, unstained, endospores) in the external environment, with extremely strong resistance. Spores can survive for over 20 years in dry ambient conditions and for decades in fur; Bacillus anthracis, once spores are formed, enters a dormant state without consuming energy. Due to the strong vitality and pathogenicity of Bacillus anthracis, it has been used as a biological weapon since the two World Wars.
The second pathogenic feature of Bacillus anthracis is the exotoxin protein, composed of protective antigen (PA), lethal factor (LF), and edema factor (EF). Each protein alone is inactive, but when combined, they form a composite toxin that damages endothelial cells in microvessels, leading to septic shock, death, tissue edema, and necrosis. For example, the combination of PA and EF forms edema toxin (LeTx), causing tissue edema and necrosis; PA combined with LF forms lethal toxin (EdTx), causing systemic symptoms of sepsis.
The third pathogenic feature of Bacillus anthracis is the capsule polysaccharide antigen, mainly composed of D-glutamic acid peptides, with a single antigenicity and phagocytosis resistance, which is related to bacterial virulence.
Pathogenic Mechanism
Bacillus anthracis spores invade through damaged skin, mucous membranes, or alveoli, causing local edema and necrosis. When phagocytes ingest spores, it leads to local lymph node edema, hemorrhage, and necrosis.
Furthermore, bacteria can spread through the bloodstream and lymphatics, producing large amounts of exotoxins that cause septicemia, shock, disseminated intravascular coagulation (DIC), and death. By passing through the lymph or blood-brain barrier, it can cause meningeal involvement. Pulmonary anthrax is usually due to hemorrhagic lymphadenitis around bronchi, leading to obstructed lymphatic drainage and pulmonary edema.
Patients generally develop septicemia, septicemia, or pulmonary complications leading to death within 1-7 days after exposure.
Pathology
The main pathological changes are hemorrhage, edema, and necrosis in invaded tissues and organs.
Clinical Manifestations
The incubation period of anthrax is several hours to 14 days, with cutaneous anthrax generally appearing in 2 to 7 days, while pulmonary and intestinal anthrax can have an incubation period as short as several hours.
According to the site of Bacillus anthracis infection, it can be divided into cutaneous anthrax, intestinal anthrax, pulmonary anthrax, meningeal anthrax, and septicemic anthrax.
(1) Cutaneous Anthrax
Accounts for over 95% of all anthrax cases, lesions often occur on exposed areas such as the face, neck, forearms, hands, and feet. It typically presents as a single skin lesion but can also be multiple. Initially, it appears as pruritic papules, progressing to painless vesicles, hemorrhagic vesicles, vesicular rupture to shallow ulcers, with blood exudate forming black eschars. The eschar gradually falls off around 10 days after the appearance of the papule.
The typical features of cutaneous anthrax skin lesions include no obvious pain or tenderness, slight itching, and no abscess formation. Lymphadenopathy and fever may accompany cutaneous anthrax.
(2) Intestinal Anthrax
Intestinal anthrax usually occurs after ingesting undercooked meat contaminated with Bacillus anthracis spores. It is rare and highly fatal, with an incubation period of 1-7 days. It presents as abdominal pain, vomiting, fever, bloody diarrhea, and ascites, with a mortality rate of 25%-75%.
(3) Pulmonary Anthrax
Pulmonary anthrax is caused by inhaling Bacillus anthracis spores, with a high mortality rate of over 80%. The incubation period is usually 1-7 days. It initially presents as nonspecific upper respiratory symptoms such as fever, headache, malaise, and mild cough. As the disease progresses, respiratory distress, cyanosis, mediastinal widening, and pleural effusion may occur. Hemorrhagic mediastinitis and hemorrhagic pleurisy often lead to death.
(4) Meningeal Anthrax
Meningeal anthrax is extremely rare, occurring in less than 1% of cases. It results from the hematogenous spread of Bacillus anthracis to the meninges, leading to symptoms of meningeal irritation such as headache, neck stiffness, photophobia, and positive Kernig’s sign. The cerebrospinal fluid usually shows a marked increase in pressure, with purulent exudate, increased white blood cells, and decreased glucose content.
(5) Septicemic Anthrax
Septicemic anthrax is characterized by acute onset, high fever, hypotension, sepsis, DIC, and multiple organ failure, with a high mortality rate.
Diagnosis
The diagnosis of anthrax should be based on epidemiological history, clinical manifestations, laboratory tests, and imaging examinations.
(1) Epidemiological history: Occupational exposure, contact with infected animals or their products, consumption of undercooked meat, living or traveling in endemic areas, and history of biological warfare.
(2) Clinical manifestations: Specific clinical features such as painless black eschar, mediastinal widening, hemorrhagic pleural effusion, hemorrhagic meningeal exudate, and skin biopsy culture for Bacillus anthracis.
(3) Laboratory tests: Isolation and identification of Bacillus anthracis from clinical specimens (blood, skin tissue, cerebrospinal fluid, respiratory secretions, etc.) using bacterial culture, PCR, immunohistochemistry, and other methods.
(4) Imaging examinations: Chest X-ray or CT scan may show mediastinal widening, pleural effusion, and pulmonary edema.
Treatment
Early diagnosis and treatment are critical for improving the prognosis of anthrax. The treatment principles are as follows:
(1) Prompt initiation of antibiotic therapy: Empirical antibiotics should be started immediately upon suspicion of anthrax. Recommended antibiotics include ciprofloxacin, doxycycline, penicillin, and amoxicillin-clavulanate. Antimicrobial susceptibility testing should guide antibiotic selection.
(2) Supportive therapy: Patients with anthrax should receive supportive care including fluid resuscitation, vasopressor therapy for septic shock, and respiratory support for pulmonary anthrax.
(3) Surgical debridement: Surgical debridement may be necessary for cutaneous anthrax to remove necrotic tissue and eschar.
(4) Prophylactic treatment: Close contacts of patients with anthrax should receive prophylactic antibiotic therapy.
Prevention and Control
Anthrax prevention and control measures include:
(1) Animal vaccination: Immunization of susceptible animals with live attenuated or inactivated vaccines can effectively prevent anthrax outbreaks in livestock.
(2) Surveillance and early warning: Strengthening surveillance of animal anthrax cases and establishing an early warning system for anthrax outbreaks are essential for timely prevention and control.
(3) Occupational protection: Individuals at high risk of anthrax exposure, such as livestock breeders, slaughterhouse workers, and laboratory personnel, should use personal protective equipment and practice strict biosafety measures.
(4) Public health education: Public health education campaigns should raise awareness of anthrax prevention and control measures among the general population, especially in endemic areas.
In conclusion, anthrax is a severe infectious disease with high mortality, requiring prompt diagnosis, and treatment to improve patient outcomes. Standardized prevention and control measures are essential for reducing the incidence and impact of anthrax outbreaks.
