Botulism

=__**Disease/Drug of interest** : __=

[[image:botulism1.jpg width="257" height="306" caption="Figure 1: Molecular graphic representation of botulism neurotoxin [4]."]]
Botulism is a rare, but rather serious paralytic illness caused by a nerve toxin that is produced from the bacterium //Clostridium botulinum// [1]. It is also sometimes produced by strains of //Clostridium butyricum// and //Clostridium baratii// [1].

There are five main types of botulism: foodborne botulism, wound botulism, infant botulism, adult intestinal botulism, and latrogenic botulism. Foodborne botulism is caused by eating foods containing the botulinum toxin. This type of botulism is a considered public health emergency because many people can be poisoned by eating the contaminated food. The most common source of foodborne botulism is home-canned food, prepared in an unsafe manner [1]. In fact, the largest botulism outbreak over the past 40 years in the United States occurred due to unsafe preparation of home-canned food. This outbreak occurred at a church potluck in Ohio in which there were 29 confirmed cases of foodborne botulism [2].

Wound botulism occurs when the toxin is produced in an infected wound with //Clostridium botulinum//. Injection drug users are at an increased risk of this type of botulism [1]. Both infant botulism and adult intestinal toxemia are caused by consuming the spores of the botulinum bacteria, which then grow in the intestines and release toxins [1]. Finally, latrogenic botulism occurs from the overdose of botulism toxin. Every single one of these types of botulism can be fatal and they are all considered medical emergencies.

What are the symptoms of Botulism?
The symptoms of botulism include: double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness [1]. In addition, infants with botulism may appear lethargic, feed poorly, be constipated, have a weak cry, and have poor muscle tone [1]. Each of these symptoms are characteristics of muscle paralysis caused by the bacterial toxin and if left untreated, these symptoms may progress to cause paralysis of the respiratory muscles, arms, legs, and trunk [1]. In the case of foodborne botulism, symptoms generally begin 18 to 36 hours after eating a contaminated food, but they can occur as early as 6 hours or as late as 10 days [1].

Why should I care?
The spores that cause botulism can be weaponized and use as a biological weapon much like the anthrax in the 2001 attacks. While there is an antitoxin, preventative measures should be taken which is why as vaccine is underdevelopment however at the moment there are significant adverse side effects.

[1] CDC. Botulism https://www.cdc.gov/botulism/index.html (accessed Feb 4, 2017). [2] McCarty, C.L.; Angelo, K.; Beer, K.D.; White, K.; Quinn, K.; Fijter, S.; Bokanyi, R.; Germain, E.; Baransi, K.; Barlow, K.; Shafer, G.; Hanna, L.; Spindler, K.; Walz, E.; DiOrio, M.; Jackson, B.; Luquez, C.; Mahon, B.; Basler, C.; Curran, K.; Matanock, A.; Walsh, K.; Slifka, K.; Rao, A., Notes from the Field: Large Outbreak of Botulism Associated with a Church Potluck Meal – Ohio, 2015. //Morbidity and Mortality Weekly Report// 2015, 64(29), 802-3. [3] Food and Drug Administration (FDA). Highlights of prescribing information. Available online: http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-bio-gen/documents/document/ucm345147.pdf (accessed on 02 February 2017). [4] Wilson, B.A.; Ho, M., Cargo-delivery platforms for targeted delivery of inhibitor cargos against botulism. //Curr Top Med Chem// 2014, 14(18), 2081-2093.
 * References: **

**External links:**
https://www.cdc.gov/botulism/index.html https://www.fda.gov/ucm/groups/fdagov-public/@fdagov-bio-gen/documents/document/ucm345147.pdf

=__**Target Information** : __=

How is botulism treated?
Botulism is treated with botulism antitoxin or Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)- (Equine)] [3]. This antitoxin is a mixture of immune globulin fragments indicated for the treatment of symptomatic botulism in adults and pediatric patients [3]. Botulism serotypes A and B, and somewhat E and F are associated with human botulism while serotypes C and D are more prevalent in bird and animal botulism [4].

=How does the antitoxin work? =

Botulism antitoxin is administered intravenously only [3]. Its mechanism of action is through passive immunization with equine polyclonal antibody fragment (mainly F(ab’)2 and Fab) against the botulinum neurotoxin (Botulism neurotoxin) A, B, C, D, E, F, and G [3]. While in the bloodstream, the polyclonal antibody fragments bind to free Botulism neurotoxin thus preventing the Botulism neurotoxin from interacting with the ganglioside anchorage sites and protein receptors on the cholinergic nerve ending [3]. As a result, the Botulism neurotoxin is prevented from internalizing into the target cells. Finally, the antibody/antigen complexes are cleared from the bloodstream by the organs involved in processing immune complexes [3].


 * Function in a normal cell ** : None, the antitoxin targets the botulism neurotoxin that has entered bloodstream.

=__**Drug Information**** : **__=


 * Schematic figure of drug ** :


 * Delivery method ** : Intravenously only
 * Side effects ** :

Some side effects of botulism antitoxin include: headache, fever, rash, hives, chills, nausea, and swelling [3]. In addition, some people have a chilly feeling, difficulty breathing, and have a quick rise in body temperature within the first 20 to 60 minutes after getting botulism antitoxin [3]. Lastly, botulism antitoxin can cause allergic reactions.


 * Maker or company ** : Cangene Corporation
 * Is it patented ** ? Yes

__** Origin ** : __ The heptavalent botulism antitoxin is manufactured by Cangene Corporation [3]. It consists of a sterile solution of F(ab’)2 and Fab- related antibody fragments prepared from plasma obtained from horses that have been immunized with a specific serotype of botulinum toxoid and toxin [3]. The antitoxin for infants is available from the California Department of Public Health, and the antitoxin for older children and adults is available through the CDC [1].

What are complications associated with botulism?
Despite the availability of an antitoxin, complications can always arise. Botulism can result in death due to respiratory failure. However, the past 50 years the proportion of patients with botulism who die has fallen from 50% to 3-5% [1]. In some cases of severe botulism, the patient may be required to be on a breathing machine (ventilator) for weeks or months, plus intensive medical and nursing care due to the respiratory failure and paralysis that can occur [1]. Over time the paralysis will slowly improve. Some patients die from infections or other problems related to remaining paralyzed for weeks or months. Often times patients who survive an episode of botulism poisoning may have fatigue and shortness of breath for years and long-term therapy may be needed to aid recovery. In the case of infant botulism, a human antitoxin called “Baby-BIG” is available in order to reduce the risk of anaphylaxis [4]. This antitoxin is derived from human donors who received the pen-tavalent (Botulism neurotoxin/A, B, C, D and E) vaccine [4].

When it comes to botulism prevention is key and there are many measures that can be taken to prevent infection by the botulism neurotoxin. Foodborne botulism is caused by the failure to follow proper canning methods and is associated with home-canned foods with low acid content, such as asparagus, green beans, beets, and corn. Some prevention tips include keeping oils infused with garlic or herbs refrigerated, keep potatoes which have been baked while wrapped in aluminum hot until served or refrigerated [1]. Also, boil home-processed, low-acid, tomato, and canned foods in a saucepan for 10 minutes before serving, even if no signs of spoilage are detected [1]. Wound botulism can be prevented by immediately seeking medical care for infected wounds and by not using injectable street drugs. Unfortunately, most infant cases of botulism cannot be prevented because the bacteria that because infant botulism is found in soil and dust [1]. Thus, the bacteria can be found inside homes on floors, carpet, and countertops even after cleaning. In addition, honey, can contain the bacteria, so children younger than 12 months old should not be fed honey however it is fine for everyone else [1].
 * How can botulism be prevented? **