Anthrax is a bacterial disease
caused by the bacterium Bacillus anthracis (a large non-motile,
aerobic, encapsulated, Gram-positive rod which has the capacity to make
heat & dry-resistant spores (1 to 2 ?m in diameter) under adverse conditions.
Oxygen is required for sporulation but not for germination of spores. Sporulation
does not take place in living animals, so the disease is not transmissible
from person to person, nor from animal to animal). In the environment,
the bacteria exist as spores, which stay in topsoil and are ingested by
the animals when grazing. Spores are very resistant to adverse conditions
and can survive in the dry earth for years. By contrast spores are
destroyed by:
-boiling for ten minutes,
(ingestion of water infected by spores may transmit gastrointestinal form
of anthrax)
-by potassium permanganate
or hydrogen peroxide
-by diluted formaldehyde
Virulence is caused by three
toxins, three proteins called anthratoxins, and an antiphagocytic capsular
polypeptide. This is of some relevance for the production of vaccines
Incubation Period :
The period between exposure
to infection and manifestation of symptoms, incubation, is usually within
2-7 days. However inhalation anthrax incubation may be up to six weeks
(clinical observation) or even 8 weeks in the experimental infection in
macacus.
Epidemiology and Transmission
:
It is mainly a zoonotic
disease (a disease of animals which can affect human beings) that occurs
in domestic herbivores, goat, sheep, cow & wild animals. Human disease
is most likely to occur in endemic regions by direct contact with infected
carcasses or animal products. Anthrax occurs worldwide, endemic regions
are Turkey, Iran, and part of Iraq. Industrial cases may occur anywhere
& reflect exposure to wool (woolsorters disease) , imported animal
carcass product such as bone meal (used for making glues) & hides.
Natural infection in humans
is almost invariably acquired from exposure to infected animals or contaminated
animal products. Infection occurs by the cutaneous route, this includes
handling contaminated carcasses, wool, hides, bones, hair ,etc (95% of
the cases); and only rarely(5% of the cases) by the inhalation route (usually
seen only during generation of aerosols in an enclosed space associate
with processing contaminated wool or hair ) or extremely rarely by gastrointestinal
routes (ingesting contaminated meat). Inhalation anthrax is of military
concern because of its potential for use as a biological warfare agent.
Human-to-human transmission is extremely unlikely and only reported with
skin anthrax.
Some of the data reported
are informations acquired from two sources :
-the Sverdlovsk accident
in 1979, in the former Soviet Union, due to accidental release of spores
held in a military base (66 people died).
-from a naturally occurring
epidemic which took place in Rhodesia-Zimbabwe in 1978-1980 where in those
years there were a total of 9700 cases. This epidemic was caused by a disruption
of the veterinary infrastructure and cessation of anthrax vaccination in
animal because of the war.
Clinical Disease :
Cutaneous Anthrax :
More than 95% of cases of
anthrax are cutaneous. After inoculation (the spores penetrate through
small wounds or abrasions, apparently they do not penetrates intact skin),
the incubation period is 1-5 days. The disease first appears as a small
papule that progress over a day or two to a vesicle which may be of 1 to
2 cm in diameter, ruptures, leaving a necrotic ulcer. The ulcer base develops
a characteristic black eschar and after a period of 2 to 3 weeks the eschar
separates leaving a scar. The lesion is usually painless, & not discharges
pus, and varying degree of edema may be present around it. Anthrax lesions
are common on the head & neck and exposed arms but rarely on the hands.
Patient usually has fever, malaise, and headache, which may be sever in
those with extensive oedema. The lesion always resolves slowly, over a
period of 2-6 weeks, despite appropriate antimicrobial treatment, and with
treatment the mortality should be less than 1%. .
Inhalational Anthrax :
Naturally acquired pulmonary
anthrax is a very rare occupational disease affecting those handling
infected animal products, for instance wool and hides workers, and dock
workers. Wool sorters & workers who are continuously exposed become
relatively resistant to infection. Pulmonary Anthrax starts initially with
low fever, dry cough, feeling unwell, tiredness, muscle pain, marked sweating,
discomfort in the chest, and 1-5 days later, may have sudden onset of high
fever and very severe stridor and cyanosis of lips and fingers. Chest X
Ray examination usually shows the characteristic widening of the mediastinum
(caused by hemorrhagic mediastinitis) and often pleural effusion, but no
pulmonary infiltrates. Shock may occur with death in 24-36 hours. Meningitis
is present in 50% of cases & mortality has been essentially 100% despite
appropriate treatment. Inhalation anthrax study in experimental animals
has shown spores are transported by lymphatics to mediastinal lymph nodes,
where germination occurs up to 60 days later. These observations were the
basis for the recommendation that antibiotics prophylaxis be given for
60 days. In the Serdlovsk accident all cases occurred within six weeks
from the accidental discharge of anthrax spores. In the two known outbreaks
of inhalation anthrax, mortality rate was 86% in Sverdlovsk and and 45%
in the US postal service. Chest x rays of 8 US patients showed enlarged
mediastinum ((7 of 8) but also infiltrates and consolidation (6 of 8) confirming
autopsy report of Sverdlovsk cases of 75 % pulmonary infiltrates.
Gastrointestinal Anthrax:
It is very rare, thought
to arise by consumption of contaminated meat that has not been sufficiently
cooked. Ingestion of contaminated water can be a source as well. The presentation
is non-specific with feeling sick, vomiting, loss of appetite, fever leading
to severe stomach pain, haematemesis and bloody diarrhoea. Sudden death
can occur within 2-5 days of onset.
Diagnosis :
The most critical aspect
in making a diagnosis of anthrax is a high index of suspicion associated
with a compatible history of exposure.
Cutaneous Anthrax should
be considered following the development of a painless pruritic papule ,
vesicle or ulcer – often with surrounding oedema- that develops into a
black eschar. Gram’s stain & culture of the lesion will usually confirm
the diagnosis. Serological testing and punch biopsy at the edge of the
lesion, are useful in diagnosis of anthrax in patients who received antibiotic
therapy.
The diagnosis of inhalational
anthrax is difficult , but the disease should be suspected with a history
of exposure to B anthracis – containing aerosol. The early symptoms are
entirely nonspecific. However (1) the development of respiratory distress
in association with radiographic evidence of a widened mediastinum due
to hemorrhagic mediastinitis, and (2) the presence of hemorrhagic pleural
effusion or hemorrhagic meningitis should suggest the diagnosis.
Blood culture and B.anthracis
– specific polymerase chain reaction (PCR) of sterile fluid (e.g., blood
and pleural fluid ) are important in the diagnosis of inhalational anthrax.
Serological tests , immunohistochemical examination of pleural fluid or
transbronchial biopsy specimens, has an important role in the diagnosis
of inhalational anthrax. None of these are presently available in North
Iraqi Kurdistan
Treatment :
Early treatment of all forms
is important for recovery. Antibiotic therapy usually results in recovery
of the individual or infected animal if given before onset or immediately
after onset of illness. Penicillin remains the proven drug of choice for
anthrax. Provided there is early treatment of skin anthrax, with oral penicillin;
the outcome is very good. If evidence of spreading infection or systemic
symptoms present, then i.v. therapy with high dose penicillin ( 2 million
units administered every 6 h ) may be initaiated until a clinical response
is obtained. Treatment should be continued for 7 to 10 days. Inhalational
, oropharyngeal , and gastrointestinal anthrax should be treated with large
doses of i.v. Penicillin (2 million units administered every 2 h) with
appropriate vasopressors, oxygen, and other supportive therapy ( chest
tube drainage of the recurrent hemorrhagic pleural effusions often leads
to a dramatic clinical improvement). However concern for Penicillin resistance
has been raised regarding the military uses of spores because is very easy
to produce Penicillin resistant strain in laboratory. Therefore inhalation
Anthrax caused by military use of spores A must be considered caused by
Penicillin resistant strains, and treatment should be with ciprofloxacine
per os, 1000 mg initially followed by 750 mg bid (twice daily) or doxycycline,
200 mg initially followed by 100 mg bid (twice daily).
Precautions , Prevention
& Prophylaxis :
Prevention of anthrax in
both humans and animals is based on enforcement of regulatory methods in
endemic areas. The population should be encouraged not to eat the meat
of animals that become ill or die. Burying their carcasses in lime can
reduce the spread of the disease from animals, which have died of anthrax.
The most efficient method of disposal is incineration in a manner that
ensures heat sterilization of the soil. Bandages, clothing and other contaminated
materials should be disposed of, preferably by burning, as spores are very
resistant to normal decontamination methods. Once a case is suspected,
the local health authorities must be informed immediately. In case of military
use of spore, an anthrax attack, the situation is different because of
the possibility of Penicillin resistance of the strain. Experimental evidence
has demonstrated that treatment with antibiotics beginning 1 day after
exposure to lethal aerosol challenge with anthrax spores can provide significant
protection against death. During recent bioterrorist attack, interim CDC
(Center for Diseases control) recommendations for anthrax prophylaxis include
Ciproflaxacin or Doxycycline. Amoxicillin is an option for children &
pregnant or lactating women to avoid the potential toxicity of quinolones
& tetracyclines. However in the case of inhalation anthrax from military
use amoxicillin will not be appropriate and one has to balance the risk
of cyprofloxacin for pregnat womency against the risk of a lethal disease.
The dose options of prophylaxis for anthrax attack is therefore : Ciprofloxacin
500 mg bid, or doxycycline 100 mg bid. If the attack is confirmed vaccination,
if available, should be given, while antibiotics should be continued for
four weeks.
Where possible three options
are now offered regarding duration of prophylaxis: