Pentavalent toxoid

Drugs There is an antitoxin stored at the CDC. To arrange to use this antitoxin, call your state health department (or CDC at 404-639-2206 or 404-639-3753 workdays, or call weekends or evenings at 404-639-2888). This chemotherapy (antitoxin) available from CDC is a licensed trivalent equine antitoxin for serotypes A, B, and E. There is no reversal of botulism disease with this drug, but the antitoxin does usually prevent further nerve damage. The U.S. Department of Defense (DOD) has a heptavalent equine despeciated antitoxin for serotypes A - G (IND). DOD also has pentavalent toxoid (vaccine) for serotypes A - E (IND). The currently recommended schedule is for use at zero, two, and twelve weeks with a one year booster. This vaccine is supposed to induce solidly protective antitoxin levels in greater that 90 percent of those vaccinated after one year. Contact USAMRIID, (U.S. Army Medical Research Institute of Infectious Diseases), Fort Detrick, Maryland. Tel. 301-619-2833. 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

Since aerosol dispersal of BoNT can create a toxic cloud over large areas, it is considered to be a likely route for use by terrorists. Consequently, a critical question for effective medical management of potential bioterrorist attacks is whether the conventional vaccine and antitoxin would be effective in treating patients following an inhalation exposure of BoNT. In experiments where guinea pigs were immunized with the pentavalent toxoid, the vaccine was found to be as protective against an... 

There is an investigational pentavalent toxoid available for special cases, but because the disease is not contagious and the toxoid would not help those already exposed, there are few indications for its use unless repeated attacks are feared. 

However, severe constraints do exist on DoD use of IND drugs and vaccines for CBW defense in military combat. The issue of IND use arose in the Gulf War in the case of pyridostigmine bromide (PB), which was regarded as the most effective pretreatment against exposure to the nerve gas Soman, and pentavalent botulinum toxoid (BT)... 

There are as yet no FDA-approved vaccines to prevent botulism. An investigational pentavalent botuliniun toxoid (PBT) product, developed at Fort Detrick, is available for persons at risk for botulism (i.e. laboratory workers, warfighters). While determined to be safe and immunogenic, PBT is not useful or recommended for post-exposure prophylaxis. Antitoxin titers do not develop until a month after the third dose in the vaccine schedule. PBT is reserved for employees at high risk for BoNT exposure but not the general population. Several factors limit the usefrdness of PBT as a vaccine for inoculating the general population. 

A pentavalent botulinum toxoid (botulinum toxin in different antigenic types) has been used for more than 30 years in some countries to prevent the disease in laboratory workers and to protect troops against attack. Pre-exposure immunization for the general population is neither feasible nor desirable the vaccine is ineffective for postexposure prophylaxis. Treatment of botulism consists of passive immunization and supportive care. Most licensed antitoxins contain antibodies against the most common toxin types A, B, and E. About 9% of recipients of equine antitoxin developed urticaria, serum sickness, or other hypersensitivity reactions. In 2% of recipients anaphylaxis occurred within 10 minutes of antitoxin... 

Active immunization, capable of permanently eliminating the hazard posed by botulinum toxin, is available in the United State, but limited to certain popnlations. The CDC distributes an investigational pentavalent (ABCDE) botnlinnm toxoid to... 

Although more than 3,000 laboratory workers have received the pentavalent vaccine over the past 30 years, it is not administered broadly for several reasons. The toxoid is relatively scarce, expensive, requires several injections, has the side effects described previonsly, and the natnral disease is very rare. The drawbacks of immunizing the entire popnlation clearly outweigh the expense of preventing a very small number of cases. In addition, active immunity to botulinum toxin would preclude the use of the toxin for other medicinal purposes (36). The heptavalent vaccine wonld not be helpfnl postexposure in an ontbreak scenario, because the toxoid requires several injections over several months to induce immunity. A recombinant vaccine, which may overcome these limitations, is in development (36). 

Fiock, M.A., Cardella, M.A., and Gearinger, N.F. 1963. Studies on immunity to toxins of Clostridium botulinum. IX. Immunologic response of man to purified pentavalent ABCDE botulinum toxoid. J. Immunol. 90 697-702. 

Vaccines. Anthrax and smallpox vaccines can be used before exposure and also for postexposuie prophylaxis. A pentavalent (ABODE) botulinum toxoid is currently used for laboratory workers at high risk of exposure. It is not effective for postexposure prophylaxis. Vaccines are not currently available for plague, tularemia, or viral hemorrhagic fevers. 

Siegel, L.S., 1988, Human response to botulinum pentavalent (ABCDE) toxoid detennined by a neutralization test and by an enzyme-linked immunosorbent assay, J. Clin. Microbiol. 26 2351-2356. 

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