Dracunculiasis+Sp14

Dracunculiasis
 * DISEASE/DRUG OF INTEREST **:

Dracunculiasis, also known as Guinea Worm Disease (GWD), occurs in individuals that had drunk unfiltered water that is infected by the parasite Dracunculus medinensis. These parasitic nematode worms lay their eggs onto water fleas, which is consumed by humans. After a few months, the symptoms begin to show. The infected host starts experiencing a fiery feeling as the larvae develops, causing a painful swelling on the infected location of the host’s body. Dracunculiasis is an infectious disease that greatly affects underdeveloped parts of Asia and Africa. In the tropical parts of these regions, Dracunculiasis is very common due to the unsanitary drinking water and living conditions. One of the main reasons that Guinea Worm Disease is prevalent in Asia and Africa is because of the many unsanitary parts within the countries there [1]. Africa alone has about twenty different countries that are at risk of this disease. Therefore, populations that are most susceptible to Guinea Worm Disease are people living in more poor and undeveloped areas.
 * MOTIVATION AND BACKGROUND **:

Figure 1. The process of how Dracunculiasis spreads and infects others within a community.
 * TARGET INFORMATION and ****DRUG INFORMATION: **

After the larvae spreads and worms begin to develop within the host’s body, blisters and swollen spots start to surface upon the skin of the infected, making this disease a dermatosis type of infection [1]. The swelling spots on the skin cause a very painful and burning sensation [1]. Once the blisters are popped, the worm dwelling inside can be seen. These nematodes can be up to three feet long, engulfing the body from the inside. Although this disease is not life threatening, it can cause major irritants, pain, and disgust. Therefore, the spreading of this disease can cause an entire community a lot of suffering.

Although the only known way to cure dracunculiasis is through the surgical removal of the worm, there are a few drugs that, in theory, would be able to kill the worm within the body since they work against other types of similar nematodes. Some of these drugs are distributed to the World Health Organization through Eisai, a pharmaceutical company as a general way of fighting parasitic worms. One of these drugs is known as diethylcarbamazine (DEC) , a drug that inhibits an arachidonic acid in the worms, making them weaker against the immune system [2]. Diethylcarbamazine  was discovered in the 1940s as a method of preventing heartworm infections. However, how it was discovered or came across by scientists is unknown. Interestingly, the usage of DEC was operated on humans before that of animals. DEC is used mainly for the treatment of Filariasis, but due to the condition of this disease in relative to Dracunculiasis, DEC is thought to work against other types of nematode worms. There are other drugs similar to DEC that is used for parasitic worm controls, such as various types of anthelmintics. However, these other drugs serve more as a pain control rather than a treatment, making DEC the most generally used and most effective drugs against such parasites. Although DEC doesn’t directly kill the worms, it allows the immune system to be able to tolerate the damages that these parasites cause [2]. Unfortunately, the Dracunculus medinensis does not suffer as much of an effect as other nematodes, such as the filariae worms. However, inhibiting the arachidonic acid should have an effect on the larvae before any become full adults. Turning off the arachidonic acid would cause the parasites to lose a lot of its protein usage and muscle abilities, severely making them susceptible to either the immune system and white blood cells or other medication drugs. The arachidonic acid is majorly important for any life form because it is the essential fatty acid usage for the brain [3]. Likewise, it also serves as a major source of muscle nourishment and repair by converting to the prostaglandin PGF2alpha and  PGE2 after <span style="font-family: Arial,sans-serif; line-height: 1.5;">any form of muscle damage. <span style="background-color: #ffffff; font-family: Arial,sans-serif; line-height: 1.5;">Therefore, arachidonic acid is also necessary for the repair and growth of skeletal muscle tissue [3]. A lack of the acid or the inhibition of the acid would dramatically decrease the body’s ability to function. More specifically on arachidonic acid, it is a chain of 20 carbons with four double bonds. The bonds are classified as cis-bonds due to their relative location, making the carbon structures on opposite sides of each other. It is mostly found inside the brain, and body muscles where it is needed the most. Within the cells of these organs, this fatty acid chain is located within the phospholipids of the membranes. Arachidonic acid plays a major role in certain cell pathways, serving primarily as a second messenger for the activation of many enzymes such as PLCgamma, and PKCalpha and PKCbeta [3].

Figure 2. The carbon stick model of arachidonic acid.

<span style="font-family: Arial,sans-serif;">To inhibit the arachidonic acid, the <span style="background-color: #ffffff; font-family: Arial,sans-serif;">diethylcarbamazine ( <span style="font-family: Arial,sans-serif;">// N,N // <span style="background-color: #f9f9f9; font-family: Arial,sans-serif;">-diethyl-4-methylpiperazine-1-carboxamide) binds to the active site of the acid and prevents it from functioning [2,3]. From previous analysis of this drug, DEC works in many different age groups, ranging from infected kids to adults. DEC is easy to consume because of its crystalline form as a tablet, allowing easy consumption by people. These tablets induce its effect into the bloodstream and into the cells of the developing worms or larvae, hindering their ability to maintain growth and perform the parasitic functions. Figure 3. Diethylcarbamazine in its structural form.

<span style="background-color: #ffffff; font-family: Arial,sans-serif;">Diethylcarbamazine has a CAS Number of 90-89-1 and a formula of C10H21N3O, making this a very small substance. However, due to the direct attack on the parasites in the bloodstream and within the subcutaneous level, there are a few symptoms and side effects that are still at risk. These symptoms include irritant in the face, such as itchiness and swelling on the eyes. Likewise, headaches and fatigue could also be felt. These are common symptoms; however, many other rare symptoms also exist. These include a risk of fever and skin rash/pain and a very rare circumstance of vision reduction. With a molecular weight of 199 g/mol, Diethylcarbamazine is easily able to flow into the body. Some information about Diethylcarbamazine cannot be found, such as whether or not it is patented or how many times it has been clinically tested. However, Diethylcarbamazine, also known by its trade names: Hetrazan, Carbilazine, Caricide, Cypip, Ethodryl, Notezine, Spatonin, Filaribits, Banocide Forte, and Eofil, is manufactured by Zaneka Health Care and recently Eisai Company. These companies, especially Eisai, are majorly focused on eliminating worm diseases and other similar underdeveloped conditional illnesses.

<span style="font-family: Arial,sans-serif;">[1] S. Cairncross, R. Muller, N. Zagaria, Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative. //Microbiol Rev//. **2002**, (2), 223-246.
 * <span style="font-family: Calibri,sans-serif; font-size: 11pt;">REFERENCES: **

<span style="font-family: Arial,sans-serif;">[2] R.M. Maizels, D.A. Denham, Diethylcarbamazine (DEC): immunopharmacological interactions of an anti-filarial drug. //PubMed// **1992**(105), 49-60.

<span style="font-family: Arial,sans-serif;">[3] H. Meves, Arachidonic acid and ion channels: an update. //Br J Pharmacol// **2008**, 155, (1), 4-16.