Anthrax has generated a great deal of interest as a weapon for biological
terrorism. An inhalational variant is the most deadly form of the disease.
A World Health Organization report estimated that 3 days after the release
of 50 kg of anthrax spores along a 2-km line upwind of a city of 500,000 population,
125,000 infections would occur, producing 95,000 deaths. An aerial spray of
anthrax along a 100-km line under ideal meteorologic conditions could produce
50% lethality rates as far as 160 km downwind.
It is important for physicians and other healthcare providers to understand
the proper culture and isolation techniques. It is important to remember that
human to human transmission has not been documented to occur.
Notifiy Department of Health regarding suspected anthrax case and for any
additional instructions before doing diagnostic tests.
Diagnosis: Physicians should maintain universal precautions when evaluating
patients with suspected cutaneous anthrax. Although contact with exudated
should be avoided, as should contact with any blood or bodily fluid, physicians
evaluating patients with suspected cutaneous anthrax are not considered to
be at risk for contracting pulmonary anthrax. The laboratory workup should
include:
| EPIDEMIOLOGY |
CHARACTERIZATION |
Human anthrax in Iran: an epidemiological study of 468 cases.
Parvizpour D. |
Int J Zoonoses 1978 Dec;5(2):69-74 Abstract quote
The study of 468 cases of cutaneous anthrax admitted to the Firoozabadi Hospital during the 13 years show that 59.83% of cases were male and 40.17% female. 42.93% of patients were below the age 30. As occupational background concerned 27.86% belongs to industrial workers. On the other hand 20.73% of cases have contracted the disease through contact with sick animals whereas 74.24% have the history of contacts with animal products and 5% have infected due to the use of spidab. All patients were treated by penicillin or other antibiotics. 78 cases having massive oedema were additionally treated with cortisone.
The death rate was slightly higher in females when compared with males. |
| Spore distribution |
The spore form of this organism can survive in the environment for many decades.
Anthrax zones is where the soil is heavily contaminated-here the soil is rich in organic matter (pH <6.0) and dramatic changes in climate, such as abundant rainfall following a prolonged drought
Domestic herbivores
Bite of certain flies
Vultures
Closely parallel the cattle drive trails of the 1800s in the USA |
Fatal Inhalational Anthrax With Unknown Source of Exposure in a 61-Year-Old Woman in New York City
Bushra Mina, MD; J. P. Dym, MD; Frank Kuepper; Raymond Tso, MD; Carmina Arrastia, MD; Irina Kaplounova, MD; Hasan Faraj, MD; Agnieszka Kwapniewski, MD; Christopher M. Krol, MD; Mayer Grosser, MD; Jeffrey Glick, MD; Steven Fochios, MD; Athena Remolina, MD; Ljiljana Vasovic, MD; Jeffrey Moses, MD; Thomas Robin, M(ASCP); Maria DeVita, MD; Michael L. Tapper, MD
|
JAMA. 2002;287:858-862 Abstract quote
A 61-year-old woman who was a New York City hospital employee developed fatal inhalational anthrax, but with an unknown source of anthrax exposure. The patient presented with shortness of breath, malaise, and cough that had developed 3 days prior to admission. Within hours of presentation, she developed respiratory failure and septic shock and required mechanical ventilation and vasopressor therapy. Spiral contrast–enhanced computed tomography of the chest demonstrated large bilateral pleural effusions and hemorrhagic mediastinitis. Blood cultures, as well as DNA amplification by polymerase chain reaction of the blood, bronchial washings, and pleural fluid specimens, were positive for Bacillus anthracis.
The clinical course was complicated by liver failure, renal failure, severe metabolic acidosis, disseminated intravascular coagulopathy, and cardiac tamponade, and the patient died on the fourth hospital day.
The cause of death was inhalational anthrax. Despite epidemiologic investigation, including environmental samples from the patient's residence and workplace, no mechanism for anthrax exposure has been identified. |
Fatal Inhalational Anthrax in a 94-Year-Old Connecticut Woman
Lydia A. Barakat, MD; Howard L. Quentzel, MD; John A. Jernigan, MD; David L. Kirschke, MD; Kevin Griffith, MD, MPH; Stephen M. Spear, MD; Katherine Kelley, PhD; Diane Barden, MT; Donald Mayo, ScD; David S. Stephens, MD; Tanja Popovic, MD, PhD; Chung Marston; Sherif R. Zaki, MD, PhD; Jeanette Guarner, MD; Wun-Ju Shieh, MD, PhD; H. Wayne Carver II, MD; Richard F. Meyer, PhD; David L. Swerdlow, MD; Eric E. Mast, MD, MPH; James L. Hadler, MD; for the Anthrax Bioterrorism Investigation Team |
JAMA. 2002;287:863-868 Abstract quote
We describe the 11th case of bioterrorism-related inhalational anthrax reported in the United States.
The presenting clinical features of this 94-year-old woman were subtle and nondistinctive. The diagnosis was recognized because blood cultures were obtained prior to administration of antibiotics, emphasizing the importance of this diagnostic test in evaluating ill patients who have been exposed to Bacillus anthracis. The patient's clinical course was characterized by progression of respiratory insufficiency, pleural effusions and pulmonary edema, and, ultimately, death. Although her B anthracis bacteremia was rapidly sterilized after initiation of antibiotic therapy, viable B anthracis was present in postmortem mediastinal lymph node specimens.
The source of exposure to B anthracis in this patient is not known. Exposure to mail that was cross-contaminated as it passed through postal facilities contaminated with B anthracis spores is one hypothesis under investigation. |
LABORATORY/
RADIOLOGIC/
OTHER |
CHARACTERIZATION |
| RADIOLOGY |
|
|
Radiological changes in inhalation anthrax. A report of radiological
and pathological correlation in two cases.
Vessal K, Yeganehdoust J, Dutz W, Kohout E.
|
Clin Radiol 1975 Oct;26(4):471-4 Abstract quote
The radiological changes in two cases of inhalation anthrax are correlated
with pathological findings.
The earliest radiological sign was widening of the mediastinum, followed
by prominent lung markings with peribronchial infiltration due to pulmonary
oedema and haemorrhage. Associated pleural effusions are common, and
non-specific super-imposed pulmonary infiltration may also be present.
Inhalation anthrax must be considered in any case of mediastinal widening
in a patient coming in contact with imported animal products or with
livestock in endemic areas.
|
| LABORATORY |
Catalase production and aerobic endospore formation distinguish Bacillus
species from clostridia
May be identified on routine blood agar as typical gray-white nonhemolytic
colonies and circular white colonies
Selective media is polymyxin-lysozyme EDTA-thallous acetate agar (PLET)
Deomtamination may be carried out with either 5% hypochlorite or 5%
phenol (carbolic acid)-instruments and equipment may be autoclaved
|
|
Comparison of noninvasive sampling sites for early detection of
Bacillus anthracis spores from rhesus monkeys after aerosol exposure.
Hail AS, Rossi CA, Ludwig GV, Ivins BE, Tammariello RF, Henchal
EA.
Veterinary Medicine Division, U.S. Army Medical Research Institute
of Infectious Diseases, Fort Detrick, MD 21702-5011, USA.
|
Mil Med 1999 Dec;164(12):833-7 Abstract quote
Bacillus anthracis, a spore-forming bacterium, is the etiologic agent
of anthrax. B. anthracis spores can be aerosolized, are relatively easy
to produce, and are capable of producing high mortality when inhaled.
The prompt use of postexposure antibiotics combined with vaccination
greatly increases the survival rate. Rapid detection of exposure is
critical to effective case management.
Using common collection swabs, culture medium, and culturing equipment,
we compared six different noninvasive sampling sites to determine which
might best be used to rapidly detect the presence of B. anthracis spores
on rhesus monkeys after aerosolization.
The results indicate that the greatest number of spores were deposited
in the nares, on the face, and on the haired portions of the head, suggesting
that these locations are the most effective sampling sites when attempting
to detect B. anthracis aerosol exposure.
|
|
Rapid recovery and identification of anthrax bacteria from the environment.
Kiel JL, Parker JE, Alls JL, Kalns J, Holwitt EA, Stribling LJ,
Morales PJ, Bruno JG.
Directed Energy Bioeffects Division, Air Force Research Laboratory,
Brooks Air Force Base, Texas 78235, USA.
|
Ann N Y Acad Sci 2000;916:240-52 Abstract quote
Bacillus anthracis has been recognized as a highly likely biological
warfare or terrorist agent. We have designed culture techniques to rapidly
isolate and identify "live" anthrax from suspected environmental release.
A special medium (3AT medium) allows for discrimination between closely
related bacilli and non-pathogenic strains. Nitrate was found to be
a primary factor influencing spore formation in Bacillus anthracis.
Nitrate reduction in anthrax is not an adaptation to saprophytic environmental
existence, but it is a signal to enhance environmental survival upon
the death of the anthrax host, which can be mimicked in culture.
|
GROSS APPEARANCE/
CLINICAL VARIANTS |
CHARACTERIZATION |
| GENERAL |
|
|
Clinical aspects, diagnosis and treatment of anthrax
Friedlander AM.
|
J Appl Microbiol 1999 Aug;87(2):303 Abstract quote
There are three clinical presentations of anthrax in humans: cutaneous
(>95% of cases), orogastric and inhalational.
The infectious form, the spore, enters the body and is thought to germinate
within macrophages either at the site of inoculation (cutaneous or orogastric)
or in the regional lymph node (inhalational). The bacillus then synthesizes
its antiphagocytic capsule and the lethal and oedema toxins which interfere
with the non-specific host defences leading to the characteristic locally
destructive lesion and spread by lymphatics to the systemic circulation
and other organs. The cutaneous form begins as a papule which progresses
over several days to a vesicle and then ulcerates. There is often oedema,
sometimes massive, probably due to the oedema toxin that surrounds the
lesions which then develop a characteristic black eschar. The patient
may be febrile with mild to severe systemic symptoms of malaise, headache
and toxicity. Oropharyngeal anthrax presents with severe sore throat
or an ulcer in the oropharyngeal cavity associated with neck swelling,
fever, toxicity and dysphagia.
Gastrointestinal anthrax begins with anorexia, nausea, vomiting and
abdominal pain which may be similar to an acute abdomen. There may be
diarrhoea and ascites, both of which may be haemorrhagic.
Inhalational anthrax begins with non-specific symptoms of malaise,
fever, myalgia and non-productive cough. After a period of 2-3 days,
this is followed by a sudden onset of severe respiratory distress associated
with diaphoresis, cyanosis and increased chest pain. There may be a
widened mediastinum and pleural effusions on chest X-ray. Death follows
in 24-36 h from respiratory failure, sepsis and shock.
The diagnosis of anthrax is easy if it is considered. The organism
is readily observed by Gram or Wright stain in local lesions or blood
smear and can be easily cultured from the blood and other body fluids.
However, because of its rarity, it is not often included in the differential
diagnosis and in inhalational disease the diagnosis is rarely made until
the patient is moribund. More rapid diagnostic tests are under development.
Penicillin, combined with supportive care, remains the mainstay of
treatment, although the organism is susceptible in vitro to many antibiotics.
In recent years, there have been significant advances in our knowledge
of the organism and its toxins and it is anticipated that similar progress
will be made in the future in developing more rapid diagnostic tests
and new modalities of treatment.
|
|
CUTANEOUS
|
Close contact of abraded skin with products derived from infected herbivores,
principally cattle, sheep, and goats
Products might include hides, hair, wool, bone, and meal.
|
|
Appearance
|
Modified from the American Academy of Dermatology Ad Hoc Task Force
on Bioterrorism (October 2001)
Approximately a 1-12 day incubation period, the lesion usually begins
as a papule on an exposed area on upper extremity, head or neck. The
lesion may be pruritic and may mimic an insect or spider bite
The lesion enlarges and develops a central vesicle or bulla with surrounding
brawny, non-pitting edema.
Vesicle beomes hemorrhagic, depressed and then necrotic and may be
surrounded by satellite vesicles
Edema increases, a central, black eschar forms and the surrounding
erythema increases. The necrotic ulcer is usually painless, which is
an important differentiating feature from a brown recluse spider bite
Pustules are rarely, if ever, present in anthrax lesions, and a primary
pustular lesion is very unlikely to be cutaneous anthrax
lesions may be solitary or multiple, and if multiple, usually on the
same part of the body.
|
|
Indigenous human cutaneous anthrax in Texas.
Taylor JP, Dimmitt DC, Ezzell JW, Whitford H.
Epidemiology Division, Texas Department of Health,
Austin 78756.
|
South Med J 1993 Jan;86(1):1-4 Abstract quote
In December 1988 an indigenous case of cutaneous anthrax was identified
in Texas. The patient, a 63-year-old male Hispanic from southwest Texas,
was a sheep shearer and had a recent history of dissecting sheep that
had died suddenly. He experienced an illness characterized by left arm
pain and edema. A necrotic lesion developed on his left forearm, with
cellulitis and lymphadenopathy. After treatment with oral and intravenous
penicillins, the patient fully recovered. Western blot testing revealed
a fourfold or greater rise in antibody titer to Bacillus anthracis protective
antigen and lethal factor.
This represents the first case of indigenous anthrax in Texas in more
than 20 years.
|
|
Cutaneous anthrax in eastern Turkey.
Caksen H, Arabaci F, Abuhandan M, Tuncer O, Cesur
Y.
Department of Pediatrics, Yuzuncu Yil University
School of Medicine, Van, Turkey.
|
Cutis 2001 Jun;67(6):488-92 Abstract quote
Anthrax, caused by the spore-forming bacterium Bacillus anthracis,
is rarely seen in industrial nations but is common in developing countries.
Cutaneous anthrax (CA), the most common form of the disease, accounts
for 95% of cases and usually develops on exposed sites.
This study reviews the clinical and laboratory findings of 21 patients
diagnosed with CA during 2 separate epidemics in the Van region of Turkey.
All patients had a history of direct contact with infected cattle. The
patients, aged 1.5 to 64 years, included 13 females and 8 males. Of
the patients, 9 were 15 years or younger. Skin lesions were localized
on the hands and fingers in 15 patients, on the face in 3 patients,
on the face and finger in 1 patient, on the chest and finger in 1 patient,
and on the eyelid in 1 patient. Gram-positive bacillus were noted on
Gram stains of material obtained from skin lesions in 2 patients.
All but one patient was successfully treated with penicillin; the unresponsive
patient was treated with cefuroxime and required plastic reconstructive
surgery because of a skin defect on the eyelid.
|
|
Toxemic shock, hematuria, hypokalemia, and hypoproteinemia
in a case of cutaneous anthrax.
Khajehdehi P.
Department of Medicine, Shiraz University of Medical
Sciences, Iran.
|
Mt Sinai J Med 2001 May;68(3):213-5 Abstract quote
A 20-year-old woman who had daily contact with domestic herbivores
presented with a painless and pruritic lesion in her neck; the lesion
ulcerated to a black necrotic eschar from which Bacillus anthracis grew.
Rapidly expanding edema at the site of the ulcer was followed by shock,
hematuria, hypokalemia, and hypoproteinemia. The latter symptoms - unusual
for cutaneous anthrax - responded to intravenous penicillin therapy.
|
|
INHALATIONAL (PULMONARY)
|
Also known as Woolsorters' disease
Occupational hazard of slaughterhouse and textile workers
|
| |
Adopted from Texas Department of Health
1-6 days (CDC's treatment recommendation is based on a possible 60-day
window).
Usually have a biphasic illness with a benign initial phase followed
by an acute second phase. Initially, nonspecific symptoms appear, resembling
a common upper respiratory infection.
Three to five days later fever, fatigue, malaise, myalgia, mild chest
pain, and a nonproductive cough appear.
The patient may show signs of improvement after 2-4 days. These symptoms
are then followed by a sudden onset of severe respiratory distress with
dyspnea, diaphoresis, stridor, and cyanosis. Chest wall edema may be
observed.
Physical findings are nonspecific except that rhonchi may be present.
Without treatment, shock and death follow within 24-36 hours of onset
of severe symptoms.
|
|
Anthrax pneumonia.
Penn CC, Klotz SA.
University of Kansas School of Medicine, Kansas City,
USA.
|
Semin Respir Infect 1997 Mar;12(1):28-30 Abstract quote
Inhalation anthrax is a rare and almost uniformly fatal form of human
anthrax caused by the inhalation of spores of Bacillus anthracis. A
clue to the diagnosis is provided by taking a work history which will
disclose patient exposure to contaminated animal products, most often
animal hair and wool used in the textile industry. It is an illness
with a biphasic course marked by the presence of a widened mediastinum
on chest radiograph and often accompanied by hemorrhagic meningitis.
The pathogenesis of this disease as well as the differential diagnosis
of inhalation anthrax in the context of other zoonotic pneumonias is
discussed. Therapy has been ineffectual probably because it has begun
too late, but includes intravenous high dose penicillin G and perhaps
vaccination to prevent relapse.
|
|
Inhalational anthrax: epidemiology, diagnosis, and
management.
Shafazand S, Doyle R, Ruoss S, Weinacker A, Raffin
TA.
Division of Pulmonary and Critical Care Medicine,
Department of Medicine, Stanford University Medical Center, Stanford,
CA 94305-5236, USA.
|
Chest 1999 Nov;116(5):1369-76 Abstract quote
Anthrax, a disease of great historical interest, is once again making
headlines as an agent of biological warfare. Bacillus anthracis, a rod-shaped,
spore-forming bacterium, primarily infects herbivores. Humans can acquire
anthrax by agricultural or industrial exposure to infected animals or
animal products. More recently, the potential for intentional release
of anthrax spores in the environment has caused much concern. The common
clinical manifestations of anthrax are cutaneous disease, pulmonary
disease from inhalation of anthrax spores, and GI disease.
The course of inhalational anthrax is dramatic, from the insidious
onset of nonspecific influenza-like symptoms to severe dyspnea, hypotension,
and hemorrhage within days of exposure. A rapid decline, culminating
in septic shock, respiratory distress, and death within 24 h is not
uncommon. The high mortality seen in inhalational anthrax is in part
due to delays in diagnosis. Classic findings on the chest radiograph
include widening of the mediastinum as well as pleural effusions. Pneumonia
is less common; key pathologic manifestations include severe hemorrhagic
mediastinitis, diffuse hemorrhagic lymphadenitis, and edema.
Diagnosis requires a high index of suspicion. Treatment involves supportive
care in an intensive care facility and high doses of penicillin. Resistance
to third-generation cephalosporins has been noted. Vaccines are currently
available and have been shown to be effective against aerosolized exposure
in animal studies.
|
|
GASTROINTESTINAL
|
Rare
Ingestion of contaminated meat |
| VARIANTS |
|
|
Anthrax of the eyelids.
Amraoui A, Tabbara KF, Zaghloul K.
Centre Hospitalier, Universitaire De Casablanca,
Morocco.
|
Br J Ophthalmol 1992 Dec;76(12):753-4 Abstract quote
The disease affects primarily herbivores including sheep, cattle, horses,
and other domestic animals. Humans may rarely be affected. We examined
one male and two female patients with a localised itchy erythematous
papule of the eyelid. A necrotising ulcer formed in each of the three
cases resulting in a black lesion. Scraping in each case showed Gram
positive rods and culture grew Bacillus anthracis. All three patients
responded to the intravenous administration of penicillin G, and the
lesion resolved leaving scars in two cases.
Anthrax is a rare disease but should be considered in the differential
diagnosis of ulcers or pustules of the eyelids.
|
|
Anthrax as the cause of preseptal cellulitis.
Celebi S, Celebi H, Celiker UO, Kandemir B, Alagoz G, Esmerligil
S.
Department of Ophthalmology, Firat University Medical Faculty, Elazig,
Turkey.
|
Acta Ophthalmol Scand 1997 Aug;75(4):462-3 Abstract quote
Anthrax is an infectious disease caused by Bacillus anthracis. It is
primarily a disease of domestic animals such as cattle, goats, and sheep;
but humans can rarely be infected by contact with infected animals or
contaminated animal products.
Our case is a 4-year-old boy who was initially diagnosed as preseptal
cellulitis, but later he showed the characteristic anthrax lesions with
a black necrotic eschar. Scrapings from the necrotic tissue showed gram
positive rods and culture grew Bacillus anthracis. The patient responded
to intravenous administration of penicillin G, and the lesions resolved,
leaving a scar on the right upper eyelid.
Eyelid involvement of anthrax is rarely seen in clinical practice,
but should be considered in differential diagnosis.
|
|
Familial outbreak of agricultural anthrax in an area of northern
Italy.
de Lalla F, Ezzell JW, Pellizzer G, Parenti E, Vaglia A, Marranconi
F, Tramarin A.
Divisione Malattie Infettive, Ospedale San Bortolo, Vicenza, Italy.
|
Eur J Clin Microbiol Infect Dis 1992 Sep;11(9):839-42 Abstract quote
Three cases of cutaneous anthrax are reported which occurred in a farming
family in northern Italy.
Epidemiological studies revealed contact with an infected cow (delivery
of a stillborn fetus and slaughter). The cow was slaughtered soon after
the delivery; cultures of carcass specimens yielded growth of Bacillus
anthracis. The origin of the animal infection was not known. Serum samples
were obtained from all 11 members of the family group and randomly from
10 of the 75 cows on the farm, which appeared to be in good health.
Tests for antibodies against protective antigen and lethal factor using
EIA and Western blot techniques were positive in three subjects (in
paired sera) with cutaneous anthrax and in one subject who neither had
had direct contact with the infected cow nor showed any sign of anthrax.
|
| HISTOLOGICAL TYPES |
CHARACTERIZATION |
| General |
|
|
Pathology of inhalational anthrax in 42 cases from the Sverdlovsk
outbreak of 1979.
Abramova FA, Grinberg LM, Yampolskaya OV, Walker DH.
Department of Pathology, Hospital 40, Ekaterinburg, Russia.
|
Proc Natl Acad Sci U S A 1993 Mar 15;90(6):2291-4 Abstract quote
A large epidemic of anthrax that occurred in Sverdlovsk (now Ekaterinburg),
Russia, in 1979 resulted in the deaths of many persons.
A series of 42 necropsies, representing a majority of the fatalities
from this outbreak, consistently revealed pathologic lesions diagnostic
of inhalational anthrax, namely hemorrhagic necrosis of the thoracic
lymph nodes in the lymphatic drainage of the lungs and hemorrhagic mediastinitis.
Bacillus anthracis was recovered in bacterial cultures of 20 cases,
and organisms were detected microscopically in the infected tissues
of nearly all of the cases. A novel observation was primary focal hemorrhagic
necrotizing pneumonia at the apparent portal of entry in 11 cases. Mesenteric
lymphadenitis occurred in only 9 cases.
This remarkably large series demonstrated the full range of effects
of anthrax bacteremia and toxemia (edema especially adjacent to sites
of extensive infection and pleural effusions) and hematogenously disseminated
infection [hemorrhagic meningitis (21 cases) and multiple gastrointestinal
submucosal hemorrhagic lesions (39 cases)].
|
|
Quantitative Pathology of Inhalational Anthrax I: Quantitative
Microscopic Findings
Lev M. Grinberg, etal.
|
Mod Pathol 2001;14:482-495 Abstract quote
Forty-one cases of documented inhalational anthrax from the Sverdlovsk
epidemic of 1979 traced to release of aerosols of Bacillus anthracis
at a secret biologic-agent production facility were evaluated by semiquantitative
histopathologic analysis of tissue concentrations of organisms, inflammation,
hemorrhage, and other lesions in the mediastinum, mediastinal lymph
nodes, bronchi, lungs, heart, spleen, liver, intestines, kidneys, adrenal
glands, and central nervous system. These data were correlated with
clinical, epidemiologic, and demographic data. The patients’ courses,
with a variable incubation period and short nonspecific course (4 days
before hospitalization) with rapid demise (1 day of hospitalization
before death), correlated with systemic bacterial infection and lesions.
Bacillus anthracis were identified in all cases in which there was no
antibiotic treatment or there was treatment for fewer than 21 hours.
The lesions that were the most severe and apparently of longest duration
were in the mediastinal lymph nodes and mediastinum. There and elsewhere,
peripheral transudate surrounded fibrin-rich edema; necrosis of arteries
and veins was the most likely source of large hemorrhages displacing
tissue or infiltrating tissue, respectively; and apoptosis of lymphocytes
was observed. Respiratory function was compromised by mediastinal expansion,
large pleural effusions, and hematogenous and retrograde lymphatic vessel
spread of B. anthracis to the lung with consequent pneumonia. The central
nervous system and intestines manifested similar hematogenous spread,
vasculitis, hemorrhages, and edema. These pathologic findings are consistent
with previous experimental studies showing transport of inhaled spores
to mediastinal lymph nodes, where germination and growth lead to local
lesions and systemic spread, with resulting edema and cell death, owing
to the effects of edema toxin and lethal toxin.
The identification of the vascular lesions as a basis for the prominent
hemorrhages is a novel observation for human inhalational anthrax.
|
| VARIANTS |
|
|
Extraordinary case report: cutaneous anthrax.
Mallon E, McKee PH.
Department of Dermatopathology, UMDS (St. Thomas's Hospital) London,
England.
|
Am J Dermatopathol 1997 Feb;19(1):79-82 Abstract quote
Anthrax is a very rare disease in the United Kingdom. It is caused
by the spore-forming bacterium Bacillus anthracis. Humans become infected
when they come into contact with infected animals or their products.
Cutaneous anthrax, the most common form of the disease, accounts for
95% of cases, and the disease usually developing on exposed sites.
We present a patient who developed cutaneous disease after exposure
to untreated leather.
Owing to the initial clinical information, the biopsy specimen was
misinterpreted as representing a severe acute insect bite reaction.
The subsequent involvement by the Department of Microbiology established
the correct diagnosis. Because today the disease is so rare in Europe
and the United States, sporadic cases of anthrax are easily overlooked
as the diagnosis often is not considered.
Cutaneous anthrax should be considered in any patient with a painless
ulcer with vesicles, edema, and a history of exposure to animals or
animal products.
|
| PROGNOSIS AND TREATMENT |
CHARACTERIZATION |
| PROGNOSIS |
|
| |
Death is universal in untreated cases and may occur in as
many as 95% of treated cases if therapy is begun more than 48 hours after
the onset of symptoms. |
| TREATMENT |
Emer Infect Dis 1999;5:553-555
Ciprofloxacin (400 mg intravenously (i.v.) q 12 h) the drug of choice
Doxycycline (100 mg i.v. q 12 h) is an acceptable alternative, although
rare doxycycline-resistant strains of B. anthracis are known
In cases of endemic anthrax, or where organisms are known to be susceptible,
penicillin G (2 million units i.v. q 2 h or 4 million units i.v. q 4
h) is recommended.
|
| GENERAL |
|
|
Anthrax as a biological weapon, 2002: updated recommendations for management.
Inglesby TV, O'Toole T, Henderson DA, Bartlett JG, Ascher MS, Eitzen
E, Friedlander AM, Gerberding J, Hauer J, Hughes J, McDade J, Osterholm
MT, Parker G, Perl TM, Russell PK, Tonat K.
Johns Hopkins Center for Civilian Biodefense Strategies, Johns Hopkins
University, Candler Bldg, Suite 830, 111 Market Pl, Baltimore, MD 21202.
|
JAMA 2002 May 1;287(17):2236-52 Abstract quote
OBJECTIVE: To review and update consensus-based recommendations for
medical and public health professionals following a Bacillus anthracis
attack against a civilian population.
PARTICIPANTS: The working group included 23 experts from academic medical
centers, research organizations, and governmental, military, public
health, and emergency management institutions and agencies.
EVIDENCE: MEDLINE databases were searched from January 1966 to January
2002, using the Medical Subject Headings anthrax, Bacillus anthracis,
biological weapon, biological terrorism, biological warfare, and biowarfare.
Reference review identified work published before 1966. Participants
identified unpublished sources.
CONSENSUS PROCESS: The first draft synthesized the gathered information.
Written comments were incorporated into subsequent drafts. The final
statement incorporated all relevant evidence from the search along with
consensus recommendations.
CONCLUSIONS: Specific recommendations include diagnosis of anthrax
infection, indications for vaccination, therapy, postexposure prophylaxis,
decontamination of the environment, and suggested research. This revised
consensus statement presents new information based on the analysis of
the anthrax attacks of 2001, including developments in the investigation
of the anthrax attacks of 2001; important symptoms, signs, and laboratory
studies; new diagnostic clues that may help future recognition of this
disease; current anthrax vaccine information; updated antibiotic therapeutic
considerations; and judgments about environmental surveillance and decontamination.
|
|
Post-exposure prophylaxis
|
Oral ciprofloxacin (500 mg orally q 12 h) or doxycycline (100 mg orally
q 12 h), and all persons exposed to a bioterrorist incident involving
anthrax should be administered one of these regimens at the earliest
possible opportunity
In cases of threatened or suspected release of anthrax, chemoprophylaxis
can be delayed 24 to 48 hours, until the threat is verified
Chemoprophylaxis can be discontinued if the threat is found to be
false
Levofloxacin and ofloxacin would be acceptable alternatives to ciprofloxacin
In addition to receiving chemoprophylaxis, exposed persons should
be immunized
Chemoprophylaxis is best continued until the exposed persons has received
at least three doses of vaccine (thus, for a minimum of 4 weeks)
If vaccine is unavailable, some recommend that chemoprophylaxis be
continued for 8 weeks
It is given in a preexposure regimen at 0, 2, and 4 weeks, and at 6,
12, and 18 months
Persons at continuing risk for exposure should receive yearly boosters.
Exposed persons should receive at least three doses (at 0, 2, and 4
weeks), assuming no further exposure is likely, before discontinuing
chemoprohylaxis.
|
|
Pediatic
|
California Hospital Planning Guides List
Ciprofloxaxin 15 mg/kg/ q12 hours, maximum dose 1 gram per day in children
Switch to the following therapy if strain is sensitive:
Penicillin G 400,000 units/kd/d in divided doses IV, when stable switch
to PO Amoxicillin-If <20 kg, 40 mg/kd divided into 3 doses taken
q 8 hours; if >20 kg, 500 mg po q 8 hours (adult dose)
Doxycycline also first line alternative pending sensitivities-if >8
year and >45 kg-same as adult dose
All other children-4.4 mg/kg loading dose then 4.4 mg/kg/d in 2 divided
doses
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| VACCINE |
Not generally approved since no large scale human trials
have been performed
Recommended for patients at high risk for exposure |
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Molecular basis for improved anthrax vaccines.
Brey RN.
DOR BioPharma, Inc., 1691 Michigan Avenue, Suite 435, Miami, FL 33139, United States.
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| Adv Drug Deliv Rev. 2005 Jun 17;57(9):1266-92. Epub 2005 Apr 21. Abstract quote |
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The current vaccine for anthrax has been licensed since 1970 and was developed based on the outcome of human trials conducted in the 1950s. This vaccine, known as anthrax vaccine adsorbed (AVA), consists of a culture filtrate from an attenuated strain of Bacillus anthracis adsorbed to aluminum salts as an adjuvant. This vaccine is considered safe and effective, but is difficult to produce and is associated with complaints about reactogenicity among users of the vaccine.
Much of the work in the past decade on generating a second generation vaccine is based on the observation that antibodies to protective antigen (PA) are crucial in the protection against exposure to virulent anthrax spores. Antibodies to PA are thought to prevent binding to its cellular receptor and subsequent binding of lethal factor (LF) and edema factor (EF), which are required events for the action of the two toxins: lethal toxin (LeTx) and edema toxin (EdTx). The bacterial capsule as well as the two toxins are virulence factors of B. anthracis. The levels of antibodies to PA must exceed a certain minimal threshold in order to induce and maintain protective immunity. Immunity can be generated by vaccination with purified PA, as well as spores and DNA plasmids that express PA. Although antibodies to PA address the toxemia component of anthrax disease, antibodies to additional virulence factors, including the capsule or somatic antigens in the spore, may be critical in development of complete, sterilizing immunity to anthrax exposure.
The next generation anthrax vaccines will be derived from the thorough understanding of the interaction of virulence factors with human and animal hosts and the role the immune response plays in providing protective immunity.
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Combining anthrax vaccine and therapy: a dominant-negative inhibitor of anthrax toxin is also a potent and safe immunogen for vaccines.
Aulinger BA, Roehrl MH, Mekalanos JJ, Collier RJ, Wang JY.
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
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| Infect Immun. 2005 Jun;73(6):3408-14. Abstract quote |
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Anthrax is caused by the unimpeded growth of Bacillus anthracis in the host and the secretion of toxins. The currently available vaccine is based on protective antigen (PA), a central component of anthrax toxin. Vaccination with PA raises no direct immune response against the bacilli and, being a natural toxin component, PA might be hazardous when used immediately following exposure to B. anthracis. Thus, we have sought to develop a vaccine or therapeutic agent that is safe and eliminates both secreted toxins and bacilli.
To that end, we have previously developed a dually active vaccine by conjugating the capsular poly-gamma-d-glutamate (PGA) with PA to elicit the production of antibodies specific for both bacilli and toxins. In the present report, we describe the improved potency of anthrax vaccines through the use of a dominant-negative inhibitory (DNI) mutant to replace PA in PA or PA-PGA vaccines. When tested in mice, DNI alone is more immunogenic than PA, and DNI-PGA conjugate elicits significantly higher levels of antibodies against PA and PGA than PA-PGA conjugate.
To explain the enhanced immunogenicity of DNI, we propose that the two point mutations in DNI may have improved epitopes of PA allowing better antigen presentation to helper T cells. Alternatively, these mutations may enhance the immunological processing of PA by altering endosomal trafficking of the toxin in antigen-presenting cells.
Because DNI has previously been demonstrated to inhibit anthrax toxin, postexposure use of DNI-based vaccines, including conjugate vaccines, may provide improved immunogenicity and therapeutic activity simultaneously.
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Study of immunization against anthrax with the purified recombinant
protective antigen of Bacillus anthracis.
Singh Y, Ivins BE, Leppla SH.
Centre for Biochemical Technology, Delhi, India.
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Infect Immun 1998 Jul;66(7):3447-8 Abstract quote
Protective antigen (PA) of anthrax toxin is the major component of
human anthrax vaccine.
Currently available human vaccines in the United States and Europe
consist of alum-precipitated supernatant material from cultures of toxigenic,
nonencapsulated strains of Bacillus anthracis. Immunization with these
vaccines requires several boosters and occasionally causes local pain
and edema. We previously described the biological activity of a nontoxic
mutant of PA expressed in Bacillus subtilis.
In the present study, we evaluated the efficacy of the purified mutant
PA protein alone or in combination with the lethal factor and edema
factor components of anthrax toxin to protect against anthrax. Both
mutant and native PA preparations elicited high anti-PA titers in Hartley
guinea pigs. Mutant PA alone and in combination with lethal factor and
edema factor completely protected the guinea pigs from B. anthracis
spore challenge.
The results suggest that the mutant PA protein may be used to develop
an effective recombinant vaccine against anthrax.
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Anthrax vaccine: increasing intervals between the first two doses
enhances antibody response in humans.
Pittman PR, Mangiafico JA, Rossi CA, Cannon TL, Gibbs PH, Parker
GW, Friedlander AM.
Division of Medicine, U.S. Army Medical Research Institute of Infectious
Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.
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Vaccine 2000 Sep 15;19(2-3):213-6 Abstract quote
The influence of dosing interval on the human antibody response to
anthrax vaccine adsorbed (AVA) was evaluated in two retrospective serological
studies.
In both studies, the interval between the first two doses was 2, 3
or 4 weeks. In the first study, banked sera were selected from 89 at-risk
individuals at a mean time of 13 days after the second dose of vaccine.
In the second study, banked sera were selected from 51 at-risk individuals
at a mean time of 48 days following the first dose of AVA. In both studies,
the geometric mean anti-protective antigen IgG antibody titer increased
significantly as the interval between the two doses increased from 2
to 4 weeks (p=0.0005-0.029). In the first study, the seroconversion
rate also increased as the interval between the first two doses increased
(p=0. 0034).
A prospective, randomized study has been completed and is being analyzed
to confirm these findings.
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Relationship between prepregnancy anthrax vaccination and pregnancy
and birth outcomes among US Army women.
Wiesen AR, Littell CT.
Department of Preventive Medicine, Madigan Army Medical Center,
Tacoma, WA 98431, USA.
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JAMA 2002 Mar 27;287(12):1556-60 Abstract quote
CONTEXT: Substantial concern surrounds the potential health effects
of the anthrax vaccine, particularly the potential adverse effects on
reproductive processes.
OBJECTIVE: To determine whether receipt of anthrax vaccination by reproductive-aged
women has an effect on pregnancy rates.
DESIGN, SETTING, AND PATIENTS: Cohort study, based on information from
a computer database, of women aged 17 to 44 years who were stationed
at Fort Stewart, Ga, or Hunter Army Airfield, Ga, from January 1999
through March 2000.
MAIN OUTCOME MEASURES: Pregnancy and birth rates and adverse birth
outcomes.
RESULTS: Of a total of 4092 women, 3136 received at least 1 dose of
the anthrax vaccine. There was a total of 513 pregnancies, with 385
following at least 1 dose of anthrax vaccine. The pregnancy rate ratio
(before and after adjustment for marital status, race, and age) comparing
vaccinated with unvaccinated women was 0.94 (95% confidence interval
[CI], 0.8-1.2; P =.60). There were 353 live births and 25 pregnancies
lost to follow-up. The birth odds ratio after anthrax vaccination (before
and after adjustment for marital status and age) was 0.9 (95% CI, 0.5-1.4;
P =.55). After adjusting for age, the odds ratio for adverse birth outcome
after receiving at least 1 dose of anthrax vaccination was 0.9 (95%
CI, 0.4-2.4; P =.88). However, this study did not have sufficient power
to detect adverse birth outcomes.
CONCLUSION: Anthrax vaccination had no effect on pregnancy and birth
rates or adverse birth outcomes.
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| Other |
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Surgical management of cutaneous anthrax.
Aslan G, Terzioglu A.
Department of Plastic Surgery, Numune Hospital, Ankara, Turkey.
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Ann Plast Surg 1998 Nov;41(5):468-70 Abstract quote
Cutaneous anthrax in humans is a very rare disease caused by Bacillus
anthracis. Humans become infected with this spore-forming bacterium
when they come into contact with an infected animal. The disease usually
develops on exposed sites like the hands and the face.
The authors present 4 patients with cutaneous anthrax: 2 of the hands
and 2 of the eyelids. All patients needed plastic surgical help via
skin grafting after excision of the black eschar. No complications occurred
after surgery. Because they are so rare in Europe and the United States,
sporadic cases of anthrax are easily overlooked because the diagnosis
often is not considered.
Cutaneous anthrax should be considered in any patient with a painless
ulcer or black eschar who has a history of exposure to animals.
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