AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Anthrax was described in the early literature of the Greeks, Romans, and Hindus. The fifth plague described in the book of Genesis may be among the earliest descriptions of anthrax.

Most of the terms associated with anthrax relate to cutaneous or respiratory anthrax. Cutaneous anthrax results from exposure to the spores of Bacillus anthracis after handling sick animals or contaminated wool, hair, or animal hides. Pulmonary anthrax results from inhaling anthrax spores. Intestinal anthrax results from ingesting meat products that contain anthrax. Anthrax is present in areas where animals, particularly herbivores, graze.

Pathophysiology

Anthrax is primarily a disease of herbivores (eg, cattle, sheep, goats, horses). Pigs are not immune, but they are more resistant, as are dogs and cats. Birds are usually naturally resistant to anthrax. Buzzards and vultures are naturally resistant to anthrax but may transmit the spores on their talons and beaks.

Humans are relatively resistant to cutaneous invasion by B anthracis, but the organisms may gain access through microscopic or gross breaks in the skin. In cutaneous anthrax, a malignant pustule develops at the infection site. This pustule is a central area of coagulation necrosis (ulcer) surrounded by a rim of vesicles filled with bloody or clear fluid. A black eschar forms at the ulcer site. Extensive edema surrounds the lesion. The organisms multiply locally and may spread to the bloodstream or other organs (eg, spleen) via the efferent lymphatics. Dissemination from the liver, spleen, and kidneys back into the bloodstream may result in bacteremia. In bacteremic anthrax, hemorrhagic lesions may develop anywhere on the body. Bacteremic anthrax with hematogenous spread most commonly follows inhalation anthrax.

B anthracis remains in the capillaries of invaded organs, and the local and fatal effects of the infection are due, in large part, to the toxins elaborated by B anthracis. Anthrax in the spore stage can exist indefinitely in the environment. Optimal growth conditions result in a vegetative phase and bacterial multiplication. Secondary hemorrhagic intestinal foci of anthrax result from B anthracis bacteremia.

Primary intestinal anthrax predominantly affects the cecum and produces a local lesion similar to the lesion produced in the cutaneous form. Oropharyngeal anthrax is a variant of intestinal anthrax and occurs in the oropharynx after ingesting meat products contaminated by anthrax. Oropharyngeal anthrax is characterized by throat pain and difficulty in swallowing. The lesion at the site of entry into the oropharynx resembles the cutaneous ulcer.

Inhalation anthrax occurs after inhaling spores into the lungs. Spores are ingested by alveolar macrophages and are carried to the mediastinal lymph nodes. Anthrax in the lungs does not cause pneumonia, but it does cause hemorrhagic mediastinitis and pulmonary edema. Hemorrhagic pleural effusions frequently accompany inhalation anthrax.

Anthrax meningitis may occur after bacteremic seeding from any form of anthrax.

Septicemic anthrax refers to overwhelming infection resulting from bloodstream invasion secondary to inhalation or intestinal anthrax. Death from anthrax occurs as a result of the effects of lethal toxins. Near death or just after death, animals bleed from all body orifices.

Frequency

United States

Natural incidence is rare, but infection is an occupational hazard among veterinarians, farmers, and individuals who handle animal wool, hair, hides, or bone meal products.

International

Anthrax is uncommon in Western Europe, but the disease is not uncommon in the Middle East, the Indian subcontinent, Africa, Asia, and Latin America. Anthrax used in bioterrorism (ie, weapon-grade anthrax) may be dispersed as an aerosol for mass effect or by focal spore contamination via letters or packages.

Mortality/Morbidity

Most cases of anthrax are the cutaneous type, are mild, and resolve with or without treatment. However, other forms of anthrax are potentially fatal.

• Septicemic anthrax and inhalation anthrax carry the highest mortality rates. Inhalation anthrax may be fatal with or without antibiotic therapy. In 2001, the mortality rate of treated inhalation anthrax was 45%.¹
• Cutaneous anthrax is readily curable if treated early with appropriate antibiotics (mortality rate <1%).
• Intestinal anthrax is difficult to diagnose and is associated with higher morbidity (mortality rate 20-60%).

Race

• No racial predilection for, or protection from, anthrax exists.

Sex

• No sex predilection exists.

Age

• No inherent age predilection exists, but, because anthrax is often related to industrial exposure and farming, the disease most often affects young and middle-aged adults.
• Persons of any age can be affected if anthrax is used as a bioterrorist weapon.

CLINICAL

Section 3 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

• Cutaneous anthrax
• • Cutaneous anthrax develops 1-7 days (usually 2-5) after skin exposure and penetration of B anthracis spores.
  • This form most commonly affects the exposed areas of the upper extremities and, to a lesser extent, the head and neck.
  • Hematogenous dissemination occurs in 5-10% of untreated cases.
• Oropharyngeal anthrax
• • Ingestion of B anthracis spores may result in oropharyngeal anthrax 2-7 days after exposure.
  • Patients with oropharyngeal anthrax may report unilateral sore throat and/or difficulty swallowing.
• Intestinal anthrax
• • Ingesting B anthracis spores may cause intestinal anthrax 2-5 days following ingestion.
  • Patients with intestinal anthrax report nausea, vomiting, malaise, anorexia, abdominal pain, hematemesis, and bloody diarrhea, which are accompanied by fever.
• Inhalation anthrax
• • Inhalation anthrax begins abruptly, usually 1-3 days (range, 1-60 d) after inhaling anthrax spores that are 1-5 µm in diameter. The number of spores needed to cause inhalation anthrax varies. As evidenced by recent anthrax cases in the United States, fewer spores of weapon-grade anthrax may be required to cause inhalation anthrax.
  • This form presents initially with nonspecific symptoms, including a low-grade fever and a nonproductive cough.
  • Patients may report substernal discomfort early in the illness.
  • Patients may improve temporarily before rapidly deteriorating clinically with hemorrhagic mediastinitis.
  • After the initial improvement, inhalation anthrax progresses rapidly, causing high fever, severe shortness of breath, tachypnea, cyanosis, profuse diaphoresis, hematemesis, and chest pain, which may be severe enough to mimic acute myocardial infarction.
• Septicemic anthrax
• • Septicemic anthrax refers to overwhelming infection by anthrax bacilli. This form of anthrax may complicate inhalation anthrax.
  • Internal organs become darkly colored with widespread petechiae and hemorrhage.
  • The anthrax bacilli multiply in the blood and proliferate to outnumber red blood cells. Another name for anthrax is black blood, which refers to the very dark color of the blood of animals or humans with overwhelming septicemic anthrax.
  • Because humans are relatively resistant to invasion by B anthracis, most cases of septicemic anthrax occur following inhalation anthrax. The number of organisms released from the liver or spleen into the bloodstream overwhelms host defenses and produces massive amounts of lethal toxin that cause shock and death.
• Anthrax meningitis: Anthrax meningitis may complicate any form of anthrax, with bacteremia and hematogenous spread to the CNS.

Physical

• Cutaneous anthrax
• • Cutaneous anthrax begins as a pruritic papule that enlarges within 24-48 hours to form an ulcer surrounded by a satellite bulbus/lesion edematous halo. The cutaneous anthrax lesion is usually approximately 2-3 cm in diameter and has a round, regular, and raised edge.
  • Regional lymphadenopathy of the nodes draining the infected area may occur.
  • The cutaneous anthrax ulcer is characteristically pruritic but not painful. The adenopathy associated with cutaneous anthrax may be painful.
  • The membrane/exudate of the ulcer contains numerous anthrax bacilli.
  • The anthrax ulcer and surrounding edema evolve into a black eschar within 7-10 days and last for 7-14 days before separating and leaving a permanent scar. The edema surrounding the ulcer may persist through the eschar stage.
  • Lymphadenopathy associated with cutaneous anthrax may persist long after disappearance of the ulcer/eschar.
  • If the lesions of cutaneous anthrax affect the neck, neck swelling due to edema and enlarged cervical lymph nodes may impinge on the trachea and cause stridor and respiratory distress and, if severe, may be accompanied by asphyxiation.
• Oropharyngeal anthrax
• • Oropharyngeal anthrax is the proximal GI manifestation of intestinal anthrax. Mouth lesions may affect the hard palate or pharyngeal walls.
  • The anthrax ulcer in the oropharynx may be accompanied by a membrane and is associated with local edema and cervical adenopathy.
  • Death may result from asphyxiation due to neck edema or toxemia.
• Intestinal anthrax
• • Patients with intestinal anthrax may have severe abdominal pain, hematemesis, and/or bloody diarrhea.
  • Multiple anthrax ulcerative lesions are found throughout the GI tract secondary to hematogenous spread.
  • Primary intestinal anthrax causes a local lesion that resembles the ulcer of oropharyngeal anthrax.
  • Intestinal anthrax is difficult to recognize, and shock and death may occur 2-5 days after onset.
• Inhalation anthrax
• • Chest radiographs and CT scans reveal a widened mediastinum.
  • In patients with potential inhalation anthrax exposure who have a flulike illness and substernal discomfort, obtain a chest CT scan.
  • Pulmonary infiltrates are usually absent because inhalation anthrax presents primarily as hemorrhagic mediastinitis, not pneumonia, which may be associated with bloody pleural effusions.
  • Inhalation anthrax is usually fatal; the patient often succumbs to shock and to the effects of lethal toxin.
• Septicemic anthrax: This is the most severe form and may complicate any other form of anthrax, particularly inhalation anthrax.
• Anthrax meningitis
• • Cerebrospinal fluid (CSF) anthrax is distinguished by hemorrhagic leptomeningitis.
  • Anthrax is present in other locations of the body, and patients develop hemorrhagic leptomeningitis (Cardinal's cap).

Causes

Anthrax is caused by B anthracis, a gram-positive bacillus. B anthracis measures 1 µm by 3 µm and is usually straight but may be slightly curved. The ends of the bacilli are truncated, not rounded. Anthrax bacilli tend to form into long chains and may appear similar to streptobacilli on cultures. B anthracis produces a capsule that is easily visualized using a methylene blue or India ink stain. Ground-glass–appearing colonies are adherent and appear gray or white on blood agar. B anthracis is catalase-positive. Bacilli grow optimally in enhanced carbon dioxide and are nonmotile. Capsule formation may help differentiate B anthracis from other nonpathogenic bacilli.

The most important presumptive test for B anthracis is the lack of motility in broth and hemolysis on blood agar.

Table 1. Microbiological Differences Between B anthracis and Non–B anthracis Bacilli

DIFFERENTIALS

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Other Problems to be Considered

Cutaneous anthrax

Physicians must differentiate cutaneous anthrax from bubonic plague or lymphocutaneous tularemia. Patients with plague have painful adenopathy, usually in the groin or axilla. No ulcer is present, and ulcer edema and eschar characteristic of anthrax are absent. Patients with bubonic plague appear more toxemic than patients with uncomplicated cutaneous anthrax. Patients with anthrax have an appropriate history of contact with animal products. In contrast, patients with bubonic plague have a history of contact with infected cats that may have been in contact with sylvatic rodents in plague-endemic areas. Patients with bubonic plague may also provide a history of contact with armadillos or infected prairie dogs in the western United States.

Ulceroglandular tularemia and primary syphilis

Ulceroglandular tularemia is characterized by purple ulcerative lesions that are painful, not pruritic, and not surrounded by a gelatinous edematous halo. Patients with anthrax, tularemia, or plague may report headache and have fever associated with shaking chills. The chancre of primary syphilis may also be confused with cutaneous anthrax. The chancre of primary syphilis is painless, as is the lesion of cutaneous anthrax, but the syphilitic chancre is not pruritic and is not surrounded by an edematous halo. Generalized rather than local adenopathy accompanies syphilis, which is the opposite of what is expected with cutaneous anthrax. Exudates from the ulcers of both ulceroglandular tularemia and cutaneous anthrax reveal organisms when properly stained. The ulcer of syphilis does not reveal organisms, but Treponema pallidum may be visualized using dark-field examination.

Inhalation anthrax

Do not confuse inhalation anthrax with the zoonotic atypical pneumonias. Pulmonary tularemia usually presents as a community-acquired pneumonia with bilateral hilar adenopathy and bloody pleural effusion. The primary clinical manifestation of inhalation anthrax is hemorrhagic mediastinitis with bloody pleural effusions. No pulmonary infiltrate is present, and a widened mediastinum is observed on early chest CT scans. Mediastinitis very closely resembles inhalation anthrax on chest radiographs, but their clinical presentations are different.

Bacterial mediastinitis is a serious infectious process usually secondary to thoracic surgery or esophageal perforation. The initial phase of inhalation anthrax may resemble bacterial mediastinitis, but it is associated with hemoptysis, severe substernal chest pain, and shock, which is very different from bacterial mediastinitis. Patients with bacterial mediastinitis give a history of previous esophageal tear or may have recently undergone a thoracic surgical procedure, which can result in mediastinitis. Patients with inhalation anthrax have a history of exposure to inhaling anthrax spores.

Intestinal anthrax

Intestinal anthrax is a difficult diagnosis that must be distinguished from dysentery. Dysentery may manifest as bloody diarrhea, as does intestinal anthrax, and may be accompanied by abdominal pain (ie, in cases of Shigella or amebic dysentery). A history of ingesting meat possibly contaminated with anthrax is helpful in suspected cases of intestinal anthrax. In tropical areas where bacillary and amebic dysentery are common, clinically differentiating intestinal anthrax from these endemic causes of dysentery is very difficult unless a cluster of dysentery cases or an outbreak is known to exist. Stool examination rapidly rules in bacillary or amebic dysentery. Stools negative for amebic cysts or trophs and for Shigella suggest the possibility of intestinal anthrax in patients residing near areas where anthrax is endemic (ie, in pastures where herbivores graze) or after ingestion of spores from hand/food contact.

WORKUP

Section 5 of 10  

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• References

Lab Studies

• The preferred diagnostic procedure for cutaneous anthrax is staining the ulcer exudate with methylene blue or Giemsa stain. B anthracis readily grows on blood agar, and staining microbiologically differentiates the organism from non–B anthracis bacilli. Warn laboratory personnel that contracting anthrax from specimens is possible and that they must take appropriate biohazard (level II) precautions.
• In patients with cutaneous anthrax who have fever and systemic symptoms that suggest extracutaneous spread, blood culture may be indicated. Treat blood cultures as biohazard II specimens.

Imaging Studies

• If inhalation anthrax is suspected, obtain a chest radiograph or CT scan. The appearance on chest radiograph or CT scan may suggest the diagnosis, especially if other predisposing disorders that might result in a widening mediastinum (eg, dissecting aortic aneurysm, bacterial mediastinitis) are absent.

Other Tests

• B anthracis is present in high numbers in the ulcer/eschar of cutaneous anthrax, bloody pleural fluid, the CSF in anthrax meningitis, or the blood in septicemic anthrax. Specimens may be stained or cultured to demonstrate the organism. Culture on sheep blood or peptone agar.
• The diagnosis of cutaneous anthrax is usually suggested by the characteristic appearance of skin lesions.
• Enzyme-linked immunosorbent assay (ELISA) serological diagnosis is also available. The ELISA measures titers to edema and lethal toxins, and the test is positive if a single acute-phase titer is highly elevated or if a 4-fold greater rise in the titer is observed between acute and convalescent specimens.

Procedures

• If anthrax meningitis is suspected, perform a lumbar puncture to obtain CSF for stain and culture. The CSF is grossly hemorrhagic with few PMN neutrophils and numerous gram-positive bacilli. Again, advise laboratory personnel to handle specimens with biohazard level II precautions.

Histologic Findings

The characteristic finding in anthrax is the presence of the organisms in the capillaries at the infection site; therefore, if a patient is infected, expect B anthracis in the capillaries of the skin, intestines, liver, spleen, lungs, or leptomeninges.

Pathological findings are not in proportion to the numbers of bacilli present, which is best explained by the effects of one or more of the toxins associated with B anthracis.

The histology of inhalation anthrax is that of hemorrhagic mediastinitis, with few, if any, PMN neutrophils. No endobronchial ulcers/eschars are present.

TREATMENT

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Medical Care

• The preferred agent used to treat nonbioterrorist anthrax is penicillin. Penicillin is the preferred agent to treat inhalational anthrax and anthrax meningitis. Use meningeal doses for inhalational anthrax because meningitis is often also present.
• For bioterrorist anthrax, use any quinolone or doxycycline for 1-2 weeks. Clindamycin may be added for its anti-exotoxin effect.
• Postexposure prophylaxis to prevent inhalation anthrax should be continued for 60 days.
• With doxycycline, a loading regimen should be used (200 mg PO/IV q12h for 72 h). In severely ill patients, 200 mg IV/PO q12h may be continued (without toxicity) for the duration of therapy.
• Oral doxycycline and quinolones have excellent bioavailability; the same blood/tissue levels are obtained with PO and IV therapy.
• Use any quinolone in patients who are unable to take penicillin or doxycycline.
• Use doxycycline or any quinolone (eg, ciprofloxacin, levofloxacin) for postexposure prophylaxis to prevent inhalation anthrax.

Consultations

Obtain consultation with an infectious disease specialist for any patient with suspected anthrax.

MEDICATION

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The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

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Further Inpatient Care

• Eighty percent of untreated individuals with cutaneous anthrax recover. However, fatal outcome is the rule in inhalation, meningeal, or septicemic anthrax.
• Antimicrobial therapy renders lesions culture-negative within hours, but the lethal effects of anthrax are related to the effects of the organism's toxin.
• Perform tracheostomy in patients with anthrax involving the head or neck who have respiratory compromise. This procedure ensures the patient has an adequate airway.
• Treat patients with hemorrhagic mediastinitis and pulmonary edema resulting from inhalation anthrax who are on a ventilator with cardiopulmonary supportive measures and appropriate antimicrobial therapy.

In/Out Patient Meds

• Treat patients with cutaneous anthrax as outpatients, using oral doxycycline.
• Alternatively, any quinolone can be used for a total course of 7-14 days.

Deterrence/Prevention

• Anthrax vaccine
• • A vaccine exists but is not readily available.
  • Administer human anthrax vaccine in a dose of 0.5 mL subcutaneously, and repeat at 2 weeks and at 1, 6, 12, and 18 months following the initial immunization.
  • Administer a booster of 0.5 mL of human anthrax vaccine annually. Administer to individuals who have exposure to anthrax-containing animals or animal products.
  • Assess the efficacy of the vaccine using the anthracin skin test.
• Chemoprophylaxis: To prevent infection from aerosolized spores of B anthracis, use any quinolone or doxycycline as chemoprophylaxis for 60 days following exposure.

Complications

• Patients with cutaneous anthrax have a persistent circular scar at the point of eschar formation.
• Patients with inhalation, oropharyngeal, or cutaneous (neck) anthrax may develop an airway obstruction.
• Patients with septicemic anthrax may develop overwhelming toxicity or shock.
• Patients with inhalation anthrax also often develop hemorrhagic leptomeningitis.

Prognosis

• If treated early, cutaneous anthrax carries a good prognosis.
• Inhalation anthrax carries the worst prognosis.
• Oropharyngeal or intestinal anthrax carries a less favorable prognosis than cutaneous anthrax but is more favorable than inhalation anthrax.

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Biological Warfare, Anthrax, and Personal Protective Equipment.

MULTIMEDIA

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Media file 1:  Polychrome methylene blue stain of Bacillus anthracis. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States.
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Media file 2:  Histopathology of mediastinal lymph node showing a microcolony of Bacillus anthracis on Giemsa stain. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 3:  Cutaneous anthrax. Image courtesy of Anthrax Vaccine Immunization Program Agency, Office of the Army Surgeon General, United States.
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Media file 4:  Skin lesion of anthrax on face. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 5:  Skin lesions of anthrax on neck. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 6:  Histopathology of large intestine showing marked hemorrhage in the mucosa and submucosa. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 7:  Histopathology of the large intestine showing submucosal thrombosis and edema. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 8:  Chest radiograph showing widened mediastinum resulting from inhalation anthrax. Image courtesy of P.S. Brachman, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 9:  Histopathology of mediastinal lymph node showing mediastinal necrosis. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 10:  Hemorrhagic meningitis resulting from inhalation anthrax. Image courtesy of the Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 11:  Histopathology of hemorrhagic meningitis in anthrax. Image courtesy of Marshall Fox, MD, Public Health Image Library, US Centers for Disease Control and Prevention, Atlanta, Georgia.
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Media file 12:  Microscopic picture of anthrax showing gram-positive rods. Image courtesy of Ramon E. Moncada, MD.
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Media file 13:  Bioterrorist Agents. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/bioterrorism.html.
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REFERENCES

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• Authors and Editors
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• Differentials
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• References

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