Anthrax

Clinical Features

Anthrax presents as three somewhat distinct clinical syndromes in humans: cutaneous, gastrointestinal, and inhalational disease.

Cutaneous anthrax. The cutaneous form (also referred to as "malignant pustule") is the most common naturally occurring form of disease. It occurs most frequently on the hands and forearms of persons working with infected livestock or livestock products, but during epizootics it has been transmitted to humans by the bites of flies, and more recently occurred in as many as 11 people exposed to anthrax spores in the U.S. mail. After a 1 to 12 day (mean 7 days) incubation period, a painless or pruritic papule forms at the site of exposure, enlarging into a round ulcer by the next day. Vesicles or bullae containing clear or serosanguinous fluid and bacilli may form on the edge of the ulcer, which can be surrounded by various degrees of non-pitting edema. The ulcer subsequently dries and forms a coal-black scab (eschar), which falls off over the ensuing 1 to 2 weeks. Regional lymphadenopathy with associated systemic symptoms can occur. If untreated, this local infection may disseminate into a fatal systemic infection in 10-20 percent of cases. Treated, mortality is less than 1 percent.

Gastrointestinal (GI) anthrax is rare in humans, and is contracted by eating insufficiently cooked meat from infected animals. Infection is thought to occur as a result of the ingestion of viable vegetative organisms in contrast to spores. The two forms of GI anthrax, oropharyngeal and intestinal, have incubation periods of 1-6 days. Disease in oropharyngeal anthrax is heralded by the onset of fever and severe pharyngitis, followed by oral ulcers which progress from whitish patches to tan or gray pseudomembranes (often over a palatine tonsil and unilateral, but variable in location). Other signs and symptoms include dysphagia, regional lymphadenopathy (non-purulent), and severe neck swelling (often unilateral). Edema can lead to airway compromise, and disease can progress to sepsis, with case mortality rates of 10 to 50%. Intestinal anthrax begins with fever, nausea, vomiting, and focal abdominal pain. These symptoms can progress to hematemesis, hematochezia or melena, massive serosanguinous or hemorrhagic ascites, and sepsis. Overall mortality is greater than 50 percent. Some evidence exists for a mild, self-limited gastroenteritis syndrome associated with intestinal anthrax, but this is poorly described.

Inhalational (IA) anthrax. Endemic inhalational anthrax, known as Woolsorters' disease, is also an extremely rare infection contracted by inhaling the spores. It has historically occurred in an industrial setting, mainly among workers who handle infected hides, wool, and furs. Because of the rarity of human IA, a single case of this disease should be presumed to be as a result of intentional exposure to anthrax until proved otherwise. After an incubation period of 1 to 6 days*, presumably dependent upon the dose and strain of inhaled organisms, a non-specific febrile syndrome begins. Fever, malaise, headache, fatigue, and drenching sweats are often present, sometimes in association with nausea, vomiting, confusion, a nonproductive cough, and mild chest discomfort. Physical findings are typically non-specific in the early phase of the disease. Patients are often tachycardic, and despite normal lung physical exams, often have (albeit sometimes subtle at this stage) evidence of mediastinal widening (hemorrhagic mediastinitis) or pleural effusions on chest X-ray or CT scan. These initial symptoms generally last 2-5 days and can be followed by a short period of improvement (hours to 2-3 days), culminating in the abrupt development of severe respiratory distress with dyspnea, diaphoresis, stridor, and cyanosis. Septicemia, shock, and death usually follow within 24-36 hr after the onset of respiratory distress unless dramatic life-saving efforts are initiated. Historically, IA has been complicated by hemorrhagic meningitis in up to 50 percent of cases and GI hemorrhage in 80 percent of cases. For the attacks of 2001, mortality was only 45 percent, while before this time mortality rates for IA were > 85 percent. This improvement in outcomes is likely a reflection of advancements in intensive care medicine and the aggressive treatment of recent victims.

*During an outbreak of IA in the Soviet Union in 1979, persons are reported to have become ill up to 6 weeks after an aerosol release occurred. Studies performed in nonhuman primates confirm incubation periods which can be up to 100 days.

Clinical Features of Cutaneous Anthrax

Feature

Characteristics

Incubation period

1-7 days (more commonly 2-5 days; may be as long as 12 days)

Signs and symptomsa

—Initial lesion is small papule or vesicle, which may be pruritic.
—By second day, papule ulcerates with central necrosis and drying.
—Painless, localized, nonpitting edema surrounds ulcerated area.
—Fine vesicles may encircle ulcer; these enlarge over next 1- 2 days and may discharge serosanguinous fluid.
—After 1 to 2 days, painless black eschar forms over ulcerated area.
—Eschar sloughs off after 12-14 days.
—Lesions resolve without complications or scarring in 80%-90% of patients.
—Extensive nonpitting edema, lymphangitis, and painful lymphadenopathy may occur.
—Malignant edema is rare complication and is characterized by severe edema, multiple bullae, and shock.b
—Fever and malaise are common.a
—Lesions tend to occur on exposed areas of body (eg, face, hands, arms, neck).
—One outbreak in Thailand demonstrated the following cutaneous findings for 13 patients with cutaneous anthraxc:
   ~Eschar (85%)
   ~Blister (92%)
   ~Ulcer (23%)
   ~Edema around lesion (77%)
   ~Lymphadenopathy (100%)

Case-fatality rate

—Currently <1%a, g (most patients recover with appropriate antimicrobial therapy)
—In preantibiotic era, case-fatality rates of about 20% were reported.d
—A literature review of pediatric anthrax cases identified between 1900 and 2005 demonstrated an overall mortality rate for cutaneous disease of 14% (5 of 37 cases).e Not all cases in this report received antimicrobial therapy.

Laboratory findings

—Gram stain of lesion may reveal gram-positive rods; neutrophils are uncommon.
—WBC count often is normal or may be slightly elevated.a
—Histologic examination shows necrosis, edema, and lymphocytic infiltrate.f

Abbreviation: WBC, white blood cell.

aSee References: Gold 1955.
bSee References: Amadi 1974.
cSee References: Kunanusont 1990.
dSee References: Smyth 1941.
eSee References: Bravata 2007.
fSee References: Dixon 1999.


Clinical Features of Inhalational Anthrax

Feature

Characteristics

Incubation period

1-43 days (usually 1-6 days)a

Signs and symptoms

—Illness may be biphasic, with an initial prodrome (which includes symptoms such as fever, malaise, fatigue, anorexia) followed by sudden increase in fever, severe respiratory distress, diaphoresis and shock, if left untreated.
—Symptoms for 10 patients with inhalational anthrax identified during the 2001 US outbreakb:
   ~Fever, chills (100%) (7 were febrile on initial presentation)
   ~Sweats, often drenching (70%)
   ~Fatigue, malaise, lethargy (100%)
   ~Cough (minimally or nonproductive) (90%)
   ~Nausea or vomiting (90%)
   ~Dyspnea (80%)
   ~Chest discomfort or pleuritic pain (70%)
   ~Myalgias (50%)
   ~Headache (50%)
   ~Confusion (40%)
   ~Abdominal pain (30%)
   ~Sore throat (20%)
   ~Rhinorrhea (10%)
—In the 2001 US outbreak, no evidence of a mild form of inhalational anthrax was detected through follow-up serologic testing of exposed persons.b
—A systematic review of 82 inhalational anthrax cases reported between 1900 and 2005 found that the most common symptoms or findings on admission included the followingc:
 ~Abnormal lung findings (80%)
 ~Fever or chills (67%)
 ~Tachycardia (66%)
 ~Fatigue or malaise (64%)
 ~Cough (62%)
 ~Dyspnea (52%)
 ~All 26 patients who had chest radiography had abnormal findings, including pleural effusion (69%) or widened mediastinum (54%)

Case-fatality rate

—Sverdlovsk outbreak: 86%a
—US outbreak: 45%c (lower observed CFR in the US outbreak likely was due to early diagnosis and aggressive therapy)
—In a systematic review of 82 cases of inhalational anthrax, the overall CFR was 85%; however, patients in the US 2001 outbreak who received early antibiotic therapy (ie, during the prodromal phase [<4.7 days after illness onset]) had a CFR of 40% and those who received antibiotics >4.7 days after illness onset had a CFR of 75%c
—A literature review of pediatric anthrax cases identified between 1900 and 2005 demonstrated an overall mortality rate for inhalational disease of 60% (3 of 5 cases).e Not all cases in this report received antimicrobial therapy.

Laboratory findings

Findings for 10 patients with inhalational anthrax identified during 2001 US outbreakc:
—Median WBC count at presentation was 9,800/mm3 (range, 7,500/mm3 to 13,300/mm3)
—Differential WBC count >70% neutrophils (70%)
—Neutrophil band forms present (4 of 5; 80%)
—Peak WBC during illness was 26,400/mm3 (range, 11,900/mm3 to 49,600/mm3)
—Elevated transaminases (SGOT or SGPT) >40 (90%)
—Hypoxemiaf (60%)
—Metabolic acidosis (20%)
—Abnormal chest radiograph (100%):
   ~Mediastinal widening (70%)
   ~Infiltrates, consolidation (70%)
   ~Pleural effusion (80%)
—Abnormal CT scan (8 of 8; 100%):
   ~Mediastinal lymphadenopathy, widening (7 of 8; 88%)
   ~Pleural effusion (8 of 8; 100%)
   ~Infiltrates, consolidation (6 of 8; 75%)

Abbreviations: CFR, case-fatality rate; CT, chest-computed tomography; SGOT, serum glutamic oxalacetic transaminase; SGPT, serum glutamic pyruvic transaminase; WBC, white blood cell.

aSee References: Meselson 1994.
bSee References: Baggett 2005.
cSee References: Jernigan 2001.
dSee References: Holty 2006 : Systematic review: a century of inhalational anthrax cases from 1900 to 2005.
eSee References: Bravata 2007.
fAlveolar-arterial oxygen gradient >30 Hg on room air; O2 saturation <94%.


Clinical Features of Gastrointestinal and Oropharyngeal Anthrax

Feature

Characteristics

Incubation period

1-7 days (usually 2-5 days)

Signs and symptoms

—One outbreak of GI anthrax in Uganda demonstrated the following findings in 143 patientsa:
   ~Fever (may be low-grade) (70%)
   ~Abdominal tenderness (85%)
   ~Diarrhea (80%; bloody in only 5%)
   ~Vomiting (may be coffee-ground or blood-tinged) (90%)
   ~Headache (100%)
   ~Pharyngeal edema (10%)
—Ascites may develop 2-4 days after onset (fluid may be clear or purulent)b and in rare instances GI anthrax cases may present with progressive ascites without other classic symptoms. c
—Ulcerations can occur anywhere along the GI tract and may cause hemorrhage, obstruction, or perforation.d
—If the patient survives, symptoms last about 2 wk
—One outbreak of oropharyngeal anthrax in Thailand demonstrated the following findings for 24 patientse:
   ~Neck swelling (100%)
   ~Fever (96%)
   ~Sore throat, dysphagia (63%)
   ~Mouth or pharyngeal ulcerative or necrotic lesions (100%) (pseudomembranes also were noted in some patients)
   ~Respiratory distress (25%)
   ~Hoarseness (8%)
   ~Sensation of a "lump in throat" (8%)
   ~Diarrhea (4%)
   ~Bleeding from the mouth (4%)

Case-fatality rate

—Rate for GI anthrax is between 25% and 60%.f,j In outbreaks where patients received antibiotic therapy, rates have ranged from 0% to 29%.g
—A literature review of pediatric anthrax cases identified between 1900 and 2005 demonstrated an overall mortality rate for gastrointestinal disease of 65% (13 of 20 cases).h Not all cases in this report received antimicrobial therapy.
—In Thai outbreak of oropharyngeal disease, rate was 13%.e In another report of 6 cases of pharyngeal anthrax, rate was 50%.i

Laboratory findings

—Gram stain of peritoneal fluid or oropharyngeal ulcers may demonstrate gram-positive rods.
—Median WBC count for 13 patients with oropharyngeal anthrax in Thailand outbreak was 15,635/mm3 (range, 5,100/mm3 to 30,570/mm3). Mean percentage of neutrophils was 79.6% (range, 73% to 91%).e
B anthracis has been cultured from oropharyngeal swabs and stool specimens in patients with GI anthrax.g

Abbreviations: GI, gastrointestinal; WBC, white blood cell.

aSee References: Ndyabahinduka 1984.
bSee References: Dixon 1999.
cSee References: Hatami 2010.
dSee References: Sirisanthana 2002.
eSee References: Sirisanthana 1984.
fSee References: CDC 2001: Investigation of anthrax associated with intentional exposure and interim public health guidelines, October 2001.
gSee References: Beatty 2003.
hSee References: Bravata 2007.
iSee References: Doganay 1986.
jSee References: Doganay 2009.


Clinical Features of Anthrax Meningitis

Feature

Characteristics

Incubation period

Varies according to primary source of infection.

Signs and symptomsaa-d

—May occur as complication of cutaneous, inhalational, or gastrointestinal anthrax, and symptoms of primary site of infection usually will be present; however, meningitis may be the presenting illness.
—Characteristic features of bacterial meningitis usually present (eg, fever, nuchal rigidity, headache, change in mental status, seizures).
—Nausea and/or vomiting are common.
—Hemorrhagic meningoencephalitis is a characteristic presentation.

Case-fatality ratee

—Illness fatal in >90% of cases.
—A review of human anthrax in Turkey from 1990 to 2007 identified 5 cases of anthrax meningitis; 100% of cases died despite antibiotic and supportive therapy.f
—A literature review of pediatric anthrax cases identified between 1900 and 2005 demonstrated an overall mortality rate for meningoencephalitis of 100% (6 of 6 cases).g Not all cases in this report received antimicrobial therapy.
—Death usually occurs 1 to 6 days after illness onset, and 75% of patients die within 24 hr of presentation.

Laboratory findings

—Gram stain of CSF reveals many gram-positive rods.
—CSF is usually bloody.
—Report of 2 cases demonstrated elevated WBC counts in both patients at presentation (24,000 with 84% neutrophils and 18,000 with 90% neutrophils).b
—CT or MRI of head may show focal intracerebral hemorrhage, subarachnoid hemorrhage, diffuse cerebral edema, intraventricular hemorrhage, and/or leptomeningeal enhancement.d

Abbreviations: CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging; WBC, white blood cell.

aSee References: Dixon 1999.
bSee References: Rangel 1975.
cSee References: Meyer 2003.
dSee References: Sejvar 2005.
eSee References: Lanska 2002.
fSee References: Doganay 2009.
gSee References: Bravata 2007.

Find more information on this substance at: PubChem, PubMed