Anthrax

BY

NABEELA RAUF

OVERVIEW

Definition Problem statement History Epidemiology Pathogenesis of anthrax Types/Forms of anthrax Symptoms Of Anthrax Diagnosis Of Anthrax Treatment Prevention and control of anthrax Weaponizing anthrax

Definition

Anthrax is an acute bacterial infection of animals transmissible to man. It is also known as Malignant Pustule, Malignant Edema, Woolsorters Disease, Ragpickers Disease, Maladi Charbon, Splenic Fever

Problem statement

True incidence not known

World 20,000-100,000 in 1958 U.S. 235 total reported cases 1955-1994

18 cases inhalational since 1900, last one 1976 Until 2001, last previous case cutaneous 1992

Mortality

Inhalational 86-100% (despite treatment)

Era of crude intensive supportive care

Cutaneous <5% (treated) 20% (untreated) GI approaches 100%

Milestones in Anthrax History

Early history 1800s 1900s Recent years Outbreaks in Thailand and US

History of Anthrax (Early history)

Although anthrax dates back more than 3,000 years, it was not recognized as a disease until the 18th century. 1500 B.C - A plague of boils in Egypt affected the Pharaohs cattle. Boils are symptomatic of anthrax. 1600s - The Black Bane thought to be anthrax, in Europe kills over 60,000 cattle. 1700s - There are some accounts of human cases.

History (1800s)

Early 1800s - The first human cases of cutaneous anthrax in the US and UK were reported in men who contracted the disease after having been in contact with infected livestock. The disease was called Wool Sorters disease or Rag Pickers disease because it affected workers in those trades. 1868 - Anthrax was observed under a microscope. 1876 - German bacteriologist Robert Koch confirmed bacterial origin of anthrax.

History (1800s)

Early 1800s - The first human cases of cutaneous anthrax in the US and UK were reported in men who contracted the disease after having been in contact with infected livestock. The disease was called Wool Sorters disease or Rag Pickers disease because it affected workers in those trades. 1868 - Anthrax was observed under a microscope. 1876 - German bacteriologist Robert Koch confirmed bacterial origin of anthrax.

History (Late 1900s)

1950s and 60s - U.S. biological warfare program continues after WWII at Fort Detrick, Maryland

1969 - President Nixon ended United States' offensive biological weapons program, but defensive work still continues.
1970 - Anthrax vaccine for humans was approved by U.S. FDA. 1978-80 - The world's largest outbreak of human anthrax via insect vectors or contaminated meat struck Zimbabwe, Africa where more than 10,000 cases were recorded and over 180 people died. 1979 - In Soviet Union, aerosolized anthrax spores were released accidentally at a military facility, affecting 94 and killing 64 people.

History (Recent years)

1991 - About 150,000 U.S. troops were vaccinated for anthrax in preparation for Gulf War. 1990-93 - The cult group, Aum Shinrikyo, released anthrax spores in Tokyo, fortunately no one was injured. On February 27, 2004, the leader of this group was given a sentence of death at a district court in Tokyo. 1995 - Iraq produced 8,500 liters of concentrated anthrax as part of the biological weapon program under Saddam Husseins administration. 2001 - Letters containing anthrax spores were mailed to many places in the US such as NBC, New York Times, and Media in Miami. In Florida, a man died after inhaling anthrax at the office.

Epidemiology

Epidemological triangle Agent factors Host factors Envoirnmental & social factors

Agent factors

Agent

Bacillus anthracis.

Reservoir of infection

Infected cattle Sheep Goats horses

Source of infection

Tissue Skin Hides Hairs Whool of animals dying of anthrax

HOST FACTORS

AGE ,SEX, IMUNITY

All ages and genders affected Occurs worldwide Endemic areas - Africa, Asia

ENVIRONMENTAL & SOCIAL FACTORS

INCUBATION PERIOD

Time from exposure to symptoms Very variable for inhalational

2-43 days reported Theoretically may be up to 100 days Delayed germination of spores

TRANSMISSION
No human-to-human Naturally occurring cases

Skin exposure Ingestion Airborne

Bioterrorism
Aerosol (likely) Small volume powder (possible) Foodborne (unlikely)

INHALATIONAL ANTHRAX

Handling

hides/skins of infected

animals Microbiology laboratory Intentional aerosol release Small volume powdered form In letters, packages, etc Questionable risk, probably small

CUTANEOUS ANTHRAX
Handling

hides/skins of infected

animals Bites from arthropods (very rare) Handling powdered form in letters, etc. Intentional aerosol release May see some cutaneous if large-scale

GASTROINTESTINAL ANTHRAX
Ingestion

of meat from infected animal Ingestion of intentionally contaminated food Not likely in large scale Spores not as viable in large volumes of water Ingestion from powder-contaminated hands Inhalational of spores on particles >5 m Land in oropharynx

Mechanism of Infection

Anthrax spores enter body Germinate & multiple in lymph nodes PA, EF, LF excreted from bacteria PA binds to TEM8. PA nicked by protease furin 20-kDa segment off leaving 63-kDa peptide Heptamer forms EF and/or LF binds Complex internalized by endocytosis Acidification of endosome LF or EF crosses into cytosol via PA mediated ion-conductive channels LF cleaves MAPKK 1 & 2 EF stimulates cAMP

Pathogenesis

TYPES OF ANTHRAX

INHALATIONAL ANTHRAX CUTANEOUS ANTHRAX GASTROINTESTINAL ANTHRAX

Inhalation Anthrax

Disease immediately follows germination. Spores replicate in the lymph nodes.

The two lungs are separated by a structure called the mediastinum, which contains the heart, trachea, esophagus, and blood vessels. Bacterial toxins released during replication result in mediastinal widening and pleural effusions (accumulation of fluid in the pleural space).

Cutaneous Anthrax

95% of anthrax infections occur when the bacterium enters a cut or scratch on the skin due to handling of contaminated animal products or infected animals.

May also be spread by biting insects that have fed on infected hosts. After the spore germinates in skin tissues, toxin production initially results in itchy bump that develops into a vesicle and then painless black ulcer.

Gastrointestinal Anthrax

GI anthrax may follow after the consumption of contaminated, poorly cooked meat. There are 2 different forms of GI anthrax: 1) Oral-pharyngeal 2) Abdominal Abdominal anthrax is more common than the oral-pharyngeal form.

SYMPYOMS OF ANTHRAX

There are two phases of symptom. 1) Early phase - Many symptoms can occur within 7 days of infection 2) 2nd phase - Will hit hard, and usually occurs within 2 or 3 days after the early phase.

- Early Phase Symptoms

Fever (temperature > 100 degrees F) Chills or night sweats Headache, cough, chest discomfort, sore throat

Joint stiffness, joint pain, muscle aches

Shortness of breath Enlarged lymph nodes, nausea, loss of appetite, abdominal distress, vomiting, diarrhea Meningitis

- 2nd Phase Symptoms

Breathing problems, pneumonia Shock Swollen lymph glands Profuse sweating

Cyanosis (skin turns blue)

Death

Diagnosis Of Anthrax

Gram stain Culture of B. anthracis from the blood, skin lesions, vesicular fluid, or respiratory secretions X-ray and Computed Tomography (CT) scan Rapid detection methods - PCR for detection of nucleic acid - ELISA assay for antigen detection - Other immunohistochemical and immunoflourescence examinations - These are available only at certain labs

Treatment

Empiric Therapy

Children
Ciprofloxacin 10-15 mg/kg/d IV q12, max 1 g/d OR Doxycycline 2.2 mg/kg IV q12 (adult dosage if >8 yo and >45 kg) Add one or two antibiotics for inhalational Weigh risks (arthropathy, dental enamel)

Pregnant women
Same as other adults Weigh small risks (fetal arthropathy) vs benefit

Immunosuppressed

same as other adults

Alternative antibiotics

If susceptible, or cipro/doxy not possible

Penicillin*, amoxicillin *FDA Approved Gentamicin, streptomycin Erythromycin, chloramphenicol

Ineffective antibiotics
Trimethoprim/Sulfamethoxazole Third generation cephalosporins

Susceptibility testing should be done

Narrow antibiotic if possible Must be cautious

Multiple strains with engineered resistance to different antibiotics may be coinfecting Watch for clinical response after switching antibiotic

Antibiotic therapy

Duration

60 days

Risk of delayed spore germination Vaccine availability Could reduce to 30-45 days therapy Stop antibiotics after 3rd vaccine dose

Switch to oral

Clinical improvement Patient able to tolerate oral medications

Other therapies

Passive immunization
Anthrax immunoglobulin from horse serum Risk of serum sickness

Antitoxin

Mutated Protective Antigen

Blocks cell entry of toxin Still immunogenic, could be an alternative vaccine Animal models promising

Postexposure Prophylaxis

Who should receive PEP?

Anyone exposed to anthrax Not for contacts of cases, unless also exposed

Empiric antibiotic therapy Vaccination

Postexposure Prophylaxis

Avoid unnecessary antibiotic usage

Potential shortages of those who need them Potential adverse effects

Hypersensitivity Neurological side effects, especially elderly Bone/cartilage disease in children Oral contraceptive failure

Future antibiotic resistance

Individuals own flora Community resistance patterns

Postexposure Prophylaxis

Antibiotic therapy
Treat ASAP Prompt therapy can improve survival Continue for 60 days

30-45 days if vaccine administered

Postexposure Prophylaxis

Antibiotic therapy

Same regimen as active treatment

Substituting oral equivalent for IV Ciprofloxacin 500 mg po bid empirically Alternatives

Doxycycline 100 mg po bid Amoxicillin 500 mg po tid

Postexposure Prophylaxis

Antibiotic therapy

Children
Same dose adjustments as treatment Weigh benefits vs. risks Recommended switch if PCNsusceptible

Amoxicillin 80 mg/kg/day, max 500 mg tid

Methods of control & Prevention

1.Preventive measures

Isolation & treatment of infected animals. Carcases of animals dying of anthrax should be burnt or burried 6 feet deep with lime. A dead or living animal suffring from anthrax should not be bled or opened,for the bacilli do not produce spores except in the presence of oxygen. Vaccination of animals with an alum precipitated protective antigen Control of effluents & trade wastes of factories that handle wool,hides,hairs of animals,these effluents should be properly treated before discharge into streams.

Cont..

Health education of industrial workers handling potentially contaminated material ,they should wear gloves. Prompt medical care of all skin lesions of workers dealing with animal tissues and hides. Dust control and proper ventillation to carry off the dust where wool and hair are handled. If there is an out break in in a dairy herd,quarantine the herd for a10 days after the appearance of last case.during this period there milk should not be used. Immunization.

Cont..

Disinfection;anthrax spores are very resistant.steam disinfection is practicable for hair;wool may be disinfected by formaldehyde & hides by binchloride of mercury,formic acid or hcl Hair used for shaving brushes should be disinfected by boiling for 3 hrs,by exposure to saturated steam for 30 min or by dry heat at 200T for 24 hrs.

Duckering process

Most reliable method for disinfection of wool;it is done in 4 stages. 1.the wool is soaked insoap water solution containing some alkali at 102f and thoroughly mixed with rakes.this process cleans the wooland renders the spores of anthrax susceptible to disinfection. The material is thoroughly mixed with 21/2% formalin solution for 30 min.formalin destroys the spores. At this stage the wool or the material to be treated is dried in current of air at 106f.this drying further destroys the spores if any. The wool is then cooled by a current of air,where it is kept for several days to ensure complete destruction of spores

Control ofof infected persons,contacts,&envoirnment

Notify to local health authority. Isolate till the lesions are healed. Concurrent disinfection,steam sterilization of burning of all contaminated articles. Terminal disinfection. Quarantine;none. Immunization. Investigation of contacts and source of infection hx of exposure to infected animals. Treatment;penciline/tetracyclines.

Epidemic measures

Trace source of infection and remove it. In animals;vaccination,treatment,is olation,sterilization of animal products.

International measures

Sterilization of imported animal feed,of hair used for shaving brushes,animal hairs,hides and wool before being handled by workers

Vaccination

Cell-free filtrate Licensed in 1970 At risk

Wool mill workers Veterinarians Lab workers Livestock handlers Military personnel

Vaccine Side Effects

Injection site reactions

Mild: 30% men, 60% women Moderate:1-5% Large local:1%

5-35% experience systemic effects

Muscle or joint aches, headache, rash, chills, fever, nausea, loss of appetite, malaise

No long-term side effects noted

Vaccine Schedule

3 injections at two-week intervals 3 injections 6 months apart Annual booster

Weaponizing Anthrax: How is it made?

What Type of Anthrax to Use?

Inhalational (lungs)

Incredibly Lethal (untreated death rate >90%) Facile attack methods (silent, flu-like, spray dispersible, e Not near as lethal (untreated death rate ~20%) More difficult to administer (need cut or abrasion) Somewhat lethal (untreated death rate ~25-60%) More difficult to administer (one has to consume anthrax)

Cutaneous (skin)

Gastrointestinal (intestines)

Best Type of Anthrax for Use as Weapon: INHALATIONAL

Thanks