Anthrax

DR. ANVESH NARIMETI INTERNALMEDICINE

• The anthrax bacillus, Bacillus anthracis, was the first bacterium shown to be the cause of a disease

• In 1877, Robert Koch grew the organism in pure culture, demonstrated its ability to form endospores, and produced experimental anthrax by injecting it into animals

Introduction

Introduction

• Bacillus anthracis is very large, Gram-positive, sporeforming rod

• Anthrax is caused by exposure to the spores of the bacteria Bacillus anthracis that become entrenched in the host body and produce lethal poisons

• It is primarily a disease of grazing animals such as cattle, sheep, goats, and horses

The cells have characteristic squared ends. The endospores are ellipsoidal shaped and located centrally in the sporangium

It may exist as an individual bacterium or be grouped into short chains

Anthrax bacteria in Gram stain

Introduction

• The bacteria that cause anthrax are able to go into a dormant phase, in which they form spores.

• Spores can exist in the environment for decades.

• Under the right conditions, the dormant spores can germinate and multiply.

• People of any age may be affected

• Humans are relatively resistant to cutaneous invasion by B anthracis, but the organisms may gain access through microscopic or gross breaks in the skin

Introduction

• 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

Introduction

• B anthracis remains in the capillaries of invaded organs, and the local and fatal effects result due to the toxins elaborated

• Septicemic anthrax refers to overwhelming infection resulting from bloodstream invasion

Introduction

PATHOGENESIS• Researchers found that there are three

proteins that are created by the anthrax bacteria.

• These proteins are harmless individually, but together can be deadly.

Protective antigen (PA) Edema factor (EF) Lethal factor (LF)

• The edema factor, when combined with the protective antigen, forms a toxin known as the edema toxin ( EF + PA )

• The lethal factor, when combined with the protective antigen, forms a toxin known as the lethal toxin ( LF + PA )

PATHOGENESIS

Frequency

• In the US: Natural incidence is rare

• Internationally: 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 are cutaneous anthrax, are mild, and resolve with/without treatment

• However, other forms of anthrax are potentially fatal

• Septicemic anthrax and inhalational anthrax highest mortality ( >90% )

• Intestinal anthrax higher mortality ( 20 - 60% )

• Cutaneous anthrax lowest mortality ( <1% )

Mortality / Morbidity

Cutaneous anthrax ( 95% )

• occurs 1-7 days after skin exposure and penetration of spores

• Hematogenous dissemination occurs in 5-10% of untreated cases

Cutaneous anthrax

• begins as a pruritic papule that enlarges in 24-48 hours to form an ulcer surrounded by a halo

• ulcer characteristically is pruritic but not painful

• painful Regional lymphadenopathy may occur

• exudate of the ulcer contains numerous anthrax bacilli

• ulcer and surrounding edema evolve into a black eschar in 7-10 days and last for 7-14 days before separating and leaving a permanent scar

Cutaneous anthrax

MALIGNANT

PUSTULE

MALIGNANT

PUSTULE

Oropharyngeal anthrax

• Ingestion of spores may result in oropharyngeal anthrax 2-7 days after exposure

• complain of unilateral sore throat/difficulty swallowing

• proximal GI manifestation of intestinal anthrax

• accompanied by a membrane and is associated with local edema and cervical adenopathy

• Death may result from asphyxiation due to edema

Oropharyngeal anthrax

Intestinal anthrax

• Ingesting spores may cause intestinal anthrax 2-5 days following ingestion

• complain of nausea, vomiting, malaise, anorexia, abdominal pain, hematemesis, and bloody diarrhea, which are accompanied by fever

Intestinal anthrax

• Multiple anthrax ulcerative lesions are found throughout the GI tract secondary to hematogenous spread

• Intestinal anthrax is difficult to recognize, and shock and death may occur 2-5 days after onset

Inhalational anthrax

• begins abruptly, 1-3 days after inhaling large concentrations of anthrax spores

• initially with nonspecific symptoms, low-grade fever and a nonproductive cough

• substernal discomfort early in the illness

• progresses rapidly with high fever, severe shortness of breath, tachypnea, cyanosis, and chest pain, which may be so severe as to mimic an acute myocardial infarction

Inhalational anthrax

Inhalational anthrax

• Chest percussion or radiographs reveal a widened mediastinum

• presents as hemorrhagic mediastinitis, not pneumonia, which may be associated with bloody pleural effusions

Septicemic anthrax

• Internal organs become darkly colored with widespread petechiae and hemorrhage

• most cases of septicemic anthrax occur following inhalational anthrax

• massive amounts of lethal toxin result in shock and death

Anthrax meningitis

• may complicate any form of anthrax

• bacteremia and hematogenous spread to the CNS

• Cerebrospinal fluid (CSF) is distinguished by hemorrhagic leptomeningitis

• patients develop hemorrhagic leptomeningitis (Cardinal's cap)

Anthrax meningitis

Causes

• Anthrax is caused by B anthracis, a gram-positive bacillus

• B anthracis produces a capsule that is easily visualized using a methylene blue or India ink stain

• Capsule formation may help differentiate B anthracis and other nonpathogenic bacilli.

Lab Studies

• staining the ulcer exudate with methylene blue or Giemsa stain

• B anthracis readily grows on blood agar, and staining will microbiologically differentiate the organism and nonanthracis bacilli species

Imaging Studies

• If inhalational anthrax is suspected, obtain a chest radiograph or CT scan

• a widening mediastinum appearance on chest x-ray/CT scan may suggest the diagnosis

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/cultured to demonstrate the organism

• Enzyme-linked immunosorbent assay (ELISA) serological diagnosis also is available

• If anthrax meningitis is suspected, obtain CSF for stain and culture.

• The CSF is grossly hemorrhagic with few PMN neutrophils

Other Tests

Histologic Findings

• The characteristic finding in anthrax is the presence of the organisms in the capillaries at the infection site

• histology of inhalational anthrax is that of hemorrhagic mediastinitis

Complications

• Septicemia

• Shock

• Hemorrhagic leptomeningitis

Prognosis

• cutaneous anthrax - good prognosis

• inhalational anthrax - worst prognosis

TREATMENT

• The preferred agent used to treat anthrax is penicillin

• Ampicillin (meningeal doses), doxycycline, and chloramphenicol penetrate the CSF, which is important in meningeal anthrax

• Use any quinolone for patients unable to take penicillin or doxycycline

• Treatment ordinarily for 1-2 weeks

• Other antibiotics that may be useful include erythromycin, first-generation cephalosporins, chloramphenicol, clindamycin, vancomycin, carbapenems, cefoperazone, and extended-spectrum penicillins or trimethoprim-sulfamethoxazole (TMP-SMX)

TREATMENT

postexposure prophylaxis

• Amoxicillin, doxycycline, or any quinolone (eg, ciprofloxacin, levofloxacin, gatifloxacin) for postexposure prophylaxis to prevent inhalation anthrax

• Postexposure prophylaxis should be continued for 60 days

Prevention - Anthrax vaccine

• 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