Anthrax

Clinical Description

Identification

An acute bacterial enzootic disease that can occur in three forms: pulmonary, cutaneous, or gastrointestinal, depending on the route of exposure. Anthrax has been associated with state biological weapons programs and bioterrorism. More than 95% of naturally acquired human cases worldwide are cutaneous anthrax, manifested by initial itching of the affected site, followed by a lesion that becomes papular, then vesicular, developing in 2–6 days into a depressed black eschar. Moderate to severe and very extensive edema invariably surrounds the eschar, sometimes with small secondary vesicles. Pain is unusual and, if present, is due to edema or secondary infection. The head, neck, forearms and hands (exposed areas of the body) are common sites of infection. The lesion has been confused with human Orf (see ), early boils, arachnid bites, ulcers (especially tropical), and a variety of other infections, such as vaccinia, clostridial infection and more. Obstructive airway disease due to associated edema may complicate cutaneous anthrax of the face or neck, and tracheotomy may be needed. Untreated infections may spread to regional lymph nodes and the bloodstream with overwhelming septicemia. The meninges can become involved. Untreated cutaneous anthrax has a case-fatality rate of between 5% and 20%; with effective treatment, however, deaths from cutaneous anthrax are very rare. The lesion evolves through typical local changes even after the initiation of antimicrobial therapy.

Initial symptoms of inhalation anthrax are mild and nonspecific and may include fever, malaise, and mild cough or chest pain; acute symptoms of respiratory distress, including stridor, severe dyspnea, hypoxemia, diaphoresis, shock and cyanosis, and X-ray evidence of mediastinal widening, follow in 3–4 days, with death shortly thereafter. Pleural effusion is common, and infiltrates can sometimes be seen on chest X-ray. Maximum case fatality rate is estimated to be >85%, and early aggressive antimicrobial therapy along with supportive care may considerably reduce mortality. Anthrax is treatable in the early prodromal stage, but mortality remains high despite antimicrobial treatment if it is initiated after the onset of respiratory symptoms. In poor endemic countries, where the value of the meat from an animal that has died unexpectedly outweighs the perceived risks of illness that might result from eating it, ingestion anthrax is not uncommon and may take the form of oropharyngeal anthrax or, more commonly, gastrointestinal anthrax. In the former, the lesion is in the oral cavity, on the buccal mucosa, tongue, tonsils, or posterior pharynx wall. Sore throat and regional lymphadenopathy in the neck, with extensive edema that may lead to tracheal obstruction, are the predominant early features. In gastrointestinal anthrax, the lesion may lie at any point along the intestinal tract and is ulcerative and massively edematous, leading to hemorrhage, obstruction, perforation and extensive ascites. Ingestion anthrax is not invariably fatal, but, even with treatment mortality can be high, with development of septicemia, shock, coma and death. The incubation period is generally 3 to 7 days.

Gastrointestinal anthrax is rare and difficult to recognize; it tends to occur in explosive food poisoning outbreaks, where abdominal distress characterized by pain, nausea and vomiting is followed by fever, signs of septicemia, and death in typical cases. A rare oropharyngeal form of primary disease, characterized by edematous lesions, necrotic ulcers and swelling in the oropharynx and neck, has been described. Systemic illness, including fever, shock and dissemination to other organs, can occur with any form of anthrax, and may include meningitis that is usually fatal.

Causative agent

Bacillus anthracis, a Gram-positive, encapsulated, spore forming, non-motile rod. Specifically, the anthrax spores of B. anthracis are the infectious agent; vegetative B. anthracis rarely establish disease.


Diagnosis

Standard diagnosis remains culture of the organism from clinical specimens, but this may be difficult to achieve after antimicrobial treatment is initiated. Rapid detection can be achieved by PCR, and through immunodiagnostic testing; antigen detection methods include direct fluorescence antibody test (DFA), time-resolve fluorescence assay (TRF), and Immunohistochemistry (IHC). Most rapid assays are available only at reference laboratories, including laboratories participating in the laboratory response network. Commercially produced ELISA is available for antibody testing. Suspicion of anthrax in the case of both ingestion and inhalation depends on knowledge of the patient's history.


Epidemiology

Mode of Transmission

Contact with tissues of any parts of livestock or wild animals (cattle, sheep, goats, horses, pigs and others) dying of the disease, and/or hair, wool, hides or bone material taken for trade and products made from them (e.g. drums, brushes, and rugs); possibly also through biting flies that have fed on such animals; contact with soil contaminated by infected animals; or contact with contaminated bone meal used in gardening. Cutaneous infection requires a pre-existing lesion, and so is mostly seen on exposed areas of the body (hands, wrists, neck, face). Intestinal and oropharyngeal anthrax may arise from ingestion of inadequately cooked meat from such animals; there is no evidence that milk from infected animals transmits anthrax. Inhalation anthrax results from inhalation of B. anthracis spores in risky industrial processes—such as tanning hides and processing wool or bone—where spores are generated in an enclosed, poorly-ventilated area. Anthrax associated with the handling of animal hides outside of an industrial processing plant is rare, and is most often of the cutaneous form. Cases of both cutaneous and inhalation anthrax have been reported among drum makers.

Examples of laboratory-acquired infection exist, and an extensive outbreak with numerous deaths in both humans and animals occurred in the former USSR in 1979 as the result of an accidental release from a military research institute. Anthrax may also occur through deliberate release of spores. In 2001, spores deliberately released through the postal system in the USA resulted in 11 cutaneous and 11 inhalation cases, including 5 deaths. The distal proximity of some of the cases to original source suggests exposure to low concentrations of spores. The risk of inhalation anthrax is determined not only by bacillary virulence factors, but also by infectious aerosol production and removal rates, and by host factors.

The disease spreads among grazing animals through contaminated soil and feed, and probably by biting flies; in some endemic regions, non-biting flies, such as blowflies, are important in the spread of disease among omnivorous browsers (e.g. goats and various wild animal species), through depositing the organism on the leaves of shrubbery after feeding on the tissue or fluids of the anthrax carcass. Omnivorous and carnivorous animals acquire anthrax through contaminated meat, bone meal or other feeds derived from infected carcasses.

Incubation Period

From 1 to 7 days, although incubation periods of up to 60 days are possible. In the 1979 USSR outbreak, incubation periods extended to 43 days.

Period of Communicability
Person-to-person transmission is very rare. It has not been reported for inhalation or gastrointestinal forms of anthrax, and has only been rarely reported for cutaneous anthrax, where it requires direct contact with skin lesions. Articles and soil contaminated with spores may remain infective for several years.

Reservoir

Animals (normally herbivores, both livestock and wildlife) shed the bacilli in terminal hemorrhages or blood at death. On exposure to the air, vegetative cells sporulate and the B. anthracis spores, which resist adverse environmental conditions and disinfection, may remain viable in contaminated soil for years. The spores may be redistributed passively in the soil and adjacent vegetation through the action of water, wind and other environmental forces. Flies and scavengers feeding on infected carcasses may also disperse anthrax spores beyond the site of death, either through blood and viscera adhering to their fur, feathers or skin, or through excretion of viable anthrax spores in fecal matter. B. anthracis is not usually an invasive organism, however, and is not highly infectious even for herbivores, so there is a complex relationship between the number of spores a vector is likely to carry from a carcass and deposit at another site and the chance of another animal becoming infected from contact with that site. Dried or otherwise processed skins and hides, bones, etc. from infected animals may harbor spores for years, and are the fomites by which the disease is spread worldwide.

Susceptibility

Circumstantial evidence indicates humans are moderately resistant to anthrax infection. There is some evidence of inapparent infection, including by the ingestion and inhalation routes, among people in frequent contact with the infectious agent; second attacks can occur, but reports are rare.

Occurrence

Primarily a disease of herbivores; humans are incidental hosts. In most industrialized countries, anthrax is an infrequent and sporadic human infection, and is primarily an occupational hazard of workers who process hides, wool, hair (especially from goats), bone and bone products imported from endemic regions; and of veterinarians and agriculture and wildlife workers who handle infected animals. Human anthrax is endemic in the agricultural regions of the world where anthrax in animals is common, such as sub-Saharan Africa and Asia, south and central America, and southern and eastern Europe. New areas of infection in livestock may develop through introduction of animal feed containing contaminated bone meal.

Environmental events such as floods, or disruption of soil over previous burial sites of infected carcasses, may provoke epizootics. Anthrax has been deliberately used to cause harm; as such, it could present in epidemiologically unusual circumstances, exemplified by the recent deliberate spread of B. anthracis spores through the postal system in USA. In non-endemic countries in the past, effluent from tanneries processing imported hides from endemic countries have been notorious as sources of incidents and outbreaks. However this has become rare with the implementation of appropriate veterinary controls and good factory hygiene.


Prevention and Control

1. Preventive measures:

Immunize high-risk persons with a cell-free vaccine prepared from a culture filtrate containing the protective antigen (in the USA, marketed under the trade name Biothrax). This vaccine is effective in preventing cutaneous and inhalational anthrax: it is recommended for laboratory workers who routinely work with B. anthracis, and workers who handle potentially contaminated industrial raw materials and engage in activities with high potential for production of or exposure to B. anthracis spore-containing aerosols. It may also be used to protect military personnel against exposure to anthrax used as a biological warfare agent. Vaccination may be indicated for veterinarians and other persons handling potentially infected animals in areas with high incidence of epizootic anthrax. Annual booster injections are recommended if the risk of exposure continues. Vaccines for administration to humans are only produced in the USA and UK (protein-based non-living vaccines) and China and Russia (live spore vaccines analogous to livestock vaccines). They are restricted in availability outside these countries, and are essentially for administration to persons known to be in at-risk occupations as detailed above. The protein-based vaccines, requiring several doses over several weeks, are not really suitable for “after-the-event” response in incidents of naturally-acquired anthrax, but they could be administered together with prolonged antibiotic therapy after a substantial deliberate release exposure.

a. Prevention of naturally-acquired human anthrax begins with prevention in animals. Effective control centers around vaccination of livestock in endemic regions, and appropriate procedures in the event of incidents of livestock anthrax—correct disposal of carcasses; decontamination of carcass sites and items in contact with the carcasses or sites; vaccination of unvaccinated animals in the affected herd; treatment of symptomatic animals in such herds with penicillin or other suitable antibiotic; and quarantine. (Note: since the vaccine is a live vaccine, antibiotics and the vaccine should not be administered simultaneously).


b. Educate employees who handle potentially contaminated articles about modes of anthrax transmission, care of skin abrasions, and personal cleanliness.

c. Control dust and properly ventilate work areas in hazardous industries, especially those handling raw animal materials. Maintain continued medical supervision of employees, and provide prompt medical care for all suspicious skin lesions. Workers must wear protective clothing (gloves, boots, impermeable gowns, etc); adequate facilities must be provided for washing and changing clothes after work. Where possible, workers in at-risk occupations should be vaccinated. Locate eating facilities away from places of work. Vaporized formaldehyde has been used for disinfection of workplaces contaminated with B. anthracis.

d. Thoroughly wash, disinfect or sterilize hair, wool and bone meal—or other feed of animal origin—prior to processing, using disinfecting protocols demonstrated effective against B anthracis spores, such as the duckering process of irradiation.

e. Do not sell the hides of animals exposed to anthrax, or use their carcasses as food or feed supplements (bone or blood meal).

f. If anthrax is suspected in an animal, do not necropsy the animal; instead, aseptically collect a blood sample for smear and/or culture. Avoid contamination of the area. If a necropsy is inadvertently performed, autoclave, incinerate or chemically disinfect/fumigate all instruments or materials used.

Because anthrax spores may survive for years in the soil if carcasses are buried (there are many instances on record of outbreaks following disturbance of old burial sites), preferred disposal techniques are incineration at the site of death or removal to an incinerator or rendering plant, ensuring that no contamination occurs en route to the plant. Should these methods prove impossible, bury carcasses at the site of death as deeply as possible, without digging below the local water table level. Laboratory studies of close relatives of B. anthracis in the Bacillus genus have shown that exposure to elevated levels of calcium cations can extend the viable lifespan of spores. The same phenomenon could occur with B. anthracis spores, and so the addition of lye or quicklime to a carcass on burial (originally applied in the hope of speeding up putrefaction and discouraging scavengers) is now no longer recommended, as it is thought Ca++ ions may actually assist in the survival of anthrax spores.

g. Control effluents and wastes from rendering plants that handle potentially infected animals, and from factories that manufacture products from hair, wool, bones or hides likely to be contaminated. If appropriate, decontaminate.

h. Promptly immunize, and annually re-immunize, all domestic animals at risk. Treat symptomatic animals with penicillin or tetracyclines; immunize them after cessation of treatment. These animals should not be used for food until a few months have passed. Treatment in lieu of immunization may be used for animals exposed to a discrete source of infection, such as contaminated commercial feed.

i. The affected herd or flock should be quarantined for at least 14 days, preferably 20 days, after the last case.

2. Control of patient, contacts and the immediate environment:

a. Report to local health authority: Case report obligatory in most countries, Class 2. Also report to the appropriate livestock or agriculture authority. Even a single case of human anthrax, especially of the inhalation variety, is so unusual in industrialized countries and centers that it warrants immediate reporting to public health and law enforcement authorities for consideration of deliberate use.

b. Isolation: Anthrax is essentially non-contagious. Standard hygienic precautions (wearing disposable gloves; changing dressings; disinfecting clothing and bedding soiled with lesion fluid; washing hands after any of these procedures) for the duration of the lesion or illness in the living patient.

c. Concurrent disinfection: Of discharges from lesions and articles soiled therewith. Hypochlorite is sporicidal, and good when organic matter is not overwhelming and the item is not corrodable; to ensure adequacy of disinfection, free chlorine concentrations should be verified. Hydrogen peroxide, peracetic acid or glutaraldehyde may be alternatives; formaldehyde, ethylene oxide and cobalt irradiation have been used. Spores require steam sterilization, autoclaving or burning to ensure complete destruction. Fumigation and chemical disinfection may be used for valuable equipment.

In the event of death, the body fluids of the deceased person should be assumed to have very high concentrations of B. anthracis (although antibiotic treatment before death will probably have greatly reduced this) and suitable overclothing as well as gloves should be worn to place the body in a body bag. Bedding is probably best bagged and incinerated rather than simply disinfected. Whether the room should be fumigated depends on the perceived level of contamination beyond bedding.

d. Quarantine: Not applicable.

e. Immunization of contacts: Not applicable.

f. Investigation of contacts and source of infection: Search for history of exposure to infected animals or animal products and trace to place of origin. In a manufacturing plant, inspect for adequacy of preventive measures. There may be reason to consider deliberate use for all human cases of anthrax, but particularly those with no obvious occupational source of infection, or in other unusual circumstances.

g. Specific treatment: Ciprofloxacin is the recommended first-line treatment. Alternatives are doxycycline and amoxicillin (if isolate is susceptible). In inhalation anthrax, use of one or two additional antimicrobial agents, such as rifampicin, linezolid, macrolides, aminoglycosides, vancomycin, chloramphenicol, penicillin or ampicillin, clindamycin, and clarithromycin is recommended. Initial intravenous therapy with two or more antimicrobial agents effective against B anthracis is recommended for treatment of all forms of anthrax except localized cutaneous anthrax. Localized cutaneous anthrax can be treated with oral doxycycline or ciprofloxacin monotherapy, except in young children (<8 years), for whom initial therapy of cutaneous anthrax should be IV, and therapy with two or more additional antimicrobials should be considered.

In life-threatening cases, a combination of antibiotics, with at least one having good penetration to the CNS, may be appropriate, reverting to one drug when progression of symptoms ceases, and with overall duration 10–14 days. Supportive symptomatic (intensive care) treatment is also important.

3. Epidemic measures:

Outbreaks in livestock may be an occupational hazard of animal husbandry, with consequent risk to humans. Occasional epidemics in industrialized countries have been local industrial outbreaks among employees working with animal products, especially goat hair. These appear to be very rare in industrialized countries, although complacency is not advised. Outbreaks related to handling and consuming meat from infected cattle have occurred in Africa, Asia, and Russia.

4. Disaster implications:

None, except in case of floods in previously infected areas, which may raise the risk of new cases occurring in livestock.

5. International measures:

In line with The Terrestrial Animal Health Code (Organisation Mondiale de La Santé Animale (OIE), Paris, France, 2007), imported animals or animal products should be accompanied by international veterinary certificates that the animals involved were free from anthrax and were not on premises quarantined for anthrax at the time of harvesting. Imported bone meal should be sterilized if used as animal feed. Disinfect wool, hair hides, etc. when indicated and feasible.

6. Measures in case of deliberate use:

The general procedures for dealing with deliberate civilian release occurrences include the following:

a. Anyone who receives a threat about dissemination of anthrax organisms, or who receives a suspicious package or envelope, should immediately notify the relevant local criminal investigative authorities with responsibility for the investigation of such biological threats, including local police.

b. Other agencies must cooperate and provide assistance as requested.

c. Where appropriate, local and state health departments should also be notified, and should be ready to provide public health management and follow-up as needed.

d. Quarantine is not appropriate (see Quarantine, above).

e. If the threat of exposure to aerosolized anthrax is credible or confirmed, persons at risk should begin post-exposure prophylaxis (PEP) with both an appropriate antibiotic (Ciprofloxacin is the drug of choice; doxycycline is an alternative). If one of the non-living vaccines is available, because of uncertainty as to when or if inhaled spores may germinate or be cleared by the alveolar immune system, PEP consists of 3 doses of cell free vaccine at 0, 2, and 4 weeks in combination with 60 days of antimicrobials. The vaccine has not been evaluated for safety and efficacy in children under 18 or in adults aged 60 or older. Where it is known that the patient has had a substantial exposure to aerosolized anthrax spores, antibiotic treatment must be continued for about 6 weeks to allow development of adequate vaccine-induced immunity.

f. Responders should use an approved, pressure-demand self-contained breathing apparatus (SCBA) in conjunction with a Level A protective suit in responding to a suspected biological incident where any of the following information is unknown or the event is uncontrolled: the type(s) of airborne agent(s); the dissemination method; if aerosol dissemination is still occurring or it has stopped but there is no information on the duration of dissemination; or what the exposure concentration might be.

g. Responders may use a Level B protective suit with an exposed or enclosed, approved pressure-demand SCBA in a situation in which the suspected biological aerosol is no longer being generated, or in which other conditions may present a splash hazard.

h. Responders may use a full face piece respirator with a P100 filter or powered air-purifying respirator (PAPR) with high efficiency particulate air (HEPA) filters when it can be determined that: an aerosol-generating device was not used to create high airborne concentration; or dissemination was by a letter or package that can be easily bagged.

i. Persons who may have been exposed and may be contaminated should be decontaminated with soap and copious amounts of water in a shower. Bleach solutions are usually not required; a 1:10 dilution of household bleach (final hypochlorite concentration 0.5%) should be used only if there is gross contamination with the agent and it is impossible to remove the materials through soap and water decontamination. The bleach solution, to be used only after soap and water decontamination, must be rinsed off after 10 to 15 minutes.

j. All persons who are to be decontaminated should remove clothing and personal effects and place all items in plastic bags, which should be labeled clearly with the owner's name, contact telephone number, and inventory of contents. Personal items may be kept as evidence in a criminal trial or returned to the owner if the threat is unsubstantiated.

7. If the suspect item associated with an anthrax threat remains sealed (unopened), first responders should not take any action other than notifying the relevant authority and packaging the evidence. Quarantine, evacuation, decontamination and chemoprophylaxis will be dictated by subsequent epidemiologic and environmental investigation.

For more information on the deliberate use of infectious agents to cause harm, see the section on Deliberate use.

Source: Heymann (Ed.). (2008). Control of Communicable Diseases Manual, 19th edition. Washington, DC: American Public Health Association.

 

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