A REVIEW ON PARASITIC WORMS AND ANTHELMENTIC DRUG

About author:
Priya Diwedi
M.Pharm
Bhopal institute of technology and science-pharmacy, Bhopal (M.P)
Priya.diwedi07@gmail.com

ABSTRACT:
Anthelmintics or antihelminthics are drugs that expel helminth parasitic worms (helminths) from the body, either by stunning or killing them. They may also be called vermifuges (stunning) or vermicides (killing). They belong to two major groups of animals, the flatworms or Platyhelminthes (flukes and tapeworms) and the roundworms or Nematoda. Albendazole, mebendazole and praziquantel are the commonly used drugs acting as anthelmintics having broad spectrum activity and high cure rates due to the sustainability of the periodic emergence of resistance. This article reviews the worm infection, their lifecycle and its outcome, symptoms of worm infection and its prevention,marketed formulation for anthelmentic activity and their limitation and herbal drug used for anthelmentic activity.

REFERENCE ID: PHARMATUTOR-ART-1819

Introduction to anthelmintics
Anthelmintics are drugs that are used to treat infections with parasitic worms. This includes both flat worms, e.g., flukes and tapeworms and round worms, i.e., nematodes. They are of huge importance for human tropical medicine and for veterinary medicine. The World Health Organization estimates that a staggering 2 billion people harbour parasitic worm infections. Parasitic worms also infect livestock and crops, affecting food production with a resultant economic impact. Also of importance is the infection of domestic pets. Indeed, the companion animal market is a major economic consideration for animal health companies undertaking drug discovery programmer. ^[2]

Key drugs registered for the treatment of parasitic worms in humans. ^[2]

Schistosomiasis (blood fluke)	Intestinal round worms
Antimonials	Piperazine
Metrifonate	Benzimidazoles
Oxamnaquine	Morantel
Praziquantel	Pyrantel
	Levamisole
Cestodiasis (tape worm)	Avermectins and milbemycins
Niclosamide	Closantel (and halogenated salicylamides)
Benzimidazoles	Emodepside
Praziquantel
Fasciolasis (liver fluke)	Filariasis (tissue round worms)
Praziquantel	Diethylcarbmazine
Closantel	Suramin
(and halogenated salicylamides)	Ivermectin

Despite the prevalence of parasitic worms, anthelmintic drug discovery is the poor relation of the pharmaceutical industry. The simple reason is that the nations which suffer most from these tropical diseases have little money to invest in drug discovery or therapy. This prompts concern, as anthelmintic resistance has been widely reported in livestock and it may also only be a matter of time before this phenomenon occurs in parasites of humans.

Broad spectrum anthelmintics are effective against parasitic flat worms and nematodes. However, the majority of drugs are more limited in their action, e.g., praziquantel, a drug used in the treatment of schistosomiasis and thought to act by disrupting calcium homeostasis, has no activity against nematodes  for the purpose of this review we will focus on drugs used in human and veterinary medicine to treat parasitic nematode infection. ^[2]

Various plants were used in veneral diseases, to promote healing of wounds, swellings, abscesses, rheumatism and treating pain in lower extremities, skin diseases, leucorrhoea, dysentery, dysuria and fever 10, 11. Natural anthelmintic includes the following list of components: ^[1]

Tobbacco	Garlic
Walnut	Male fern
Wormwood	Pineapple
Clove	Diatomaceous earth
Kalonji  seeds	Soya and other legumes
Male fern	Honey, water and vinegar are mixed with warm water act as vermifuges.

WORM INFECTION AND ITS LIFECYCLE
Parasitic worms, often referred to as helminths are a division of eukaryotic parasites.^[1]They are worm-like organisms that live and feed off living hosts, receiving nourishment and protection while disrupting their hosts' nutrient absorption, causing weakness and disease. Those that live inside the digestive tract are called intestinal parasites. They can live inside humans as well as other animals. ^[6]

Helminthology is the study of parasitic worms and their effect on their hosts. The word helminth comes from Greek helmins, a kind of worm.

Helminths - worms - are some of the world's commonest parasite. They belong to two major groups of animals, the flatworms or Platyhelminthes (flukes and tapeworms) and the roundworms or Nematoda. All are relatively large and some are very large, exceeding one meter in length. ^[6]

Their bodies have well-developed organ systems, especially reproductive organs, and most helminths are active feeders. The bodies of flatworms are flattened and covered by a plasma membrane, whereas roundworms are cylindrical and covered by a tough cuticle. Flatworms are usually hermaphroditic whereas roundworms have separate sexes; both have an immense reproductive capacity. ^[6]

The most serious helminth infections are acquired in poor tropical and subtropical areas, but some also occur in the developed world; other, less serious, infections are worldwide in distribution. Exposure to infection is influenced by climate, hygiene, food preferences, and contact with vectors. Many potential infections are eliminated by host defenses; others become established and may persist for prolonged periods, even years. Although infections are often asymptomatic, severe pathology can occur. Because worms are large and often migrate through the body, they can damage the host's tissues directly by their activity or metabolism. Damage also occurs indirectly as a result of host defense mechanisms. Almost all organ systems can be affected. ^[6]

Host defense can act through nonspecific mechanisms of resistance and through specific immune responses. Antibody-mediated, cellular, and inflammatory mechanisms all contribute to resistance. However, many worms successfully avoid host defenses in a variety of ways, and can survive in the face of otherwise effective host responses. ^[6]

Roundworms
The migration of the larval forms and eggs transmission through skin contact in moist soil and in tropical areas causes migraine, eosinophilia and pulmonary related problems. The common infections occurring with intestinal worms include Ascaris, Lumbricoides, Trichuris Trichiura, Necator americanus and Ancylostoma duodenal with the house hold aggregation of infection. The eggs are deposited on perianal area that is due to self infection. These infections also occur due to the contaminated surfaces like carpets, curtains etc. The airborne and inhalation of the small number of eggs are transmitted through ingestion of the infected food because the humans are the accident hosts. After the ingestion of the infected products the immunological lungs, liver and central nervous system damages occur. 

Lifecycle of Roundworm ^[7]
Eggs
The female roundworm can produce roughly 200,000 eggs per day, some fertile, some not. The fertilized eggs embryonate and become infectious after about 18 days, depending on the temperature.

Larval Stage
Some fertile eggs hatch into larvae before entering a person's body. After the larvae are swallowed, they feed and grow until they reach the molting process. The molting process occurs in four stages before the nematode reaches the adult stage.

Process
The larvae invade the intestinal mucosa and circulate to the lungs, where they grow for 10 to 14 days. They then penetrate the alveolar walls, travel by way of the bronchial tree to the throat and are swallowed. When they reach the small intestine, they develop into adult worms.

Adult
Adult worms live in the lumen of the small intestine. The adult male is 15 to 30 cm in length by 0.3 to 0.8 cm in diameter and has a curved tail. The adult female is 20 to 35 cm in length by 0.5 cm in diameter. Adult worms can live one to two years.

Reproduction
At the final stage of the life cycle, genders are established and the adults are capable of sexual reproduction. The female can produce around 6 million eggs during her lifetime.

The process from swallowing theeggs to having mature worms develop in the intestine takes between two and three months.

Tapeworms
Humans are the intermediate host for the Taenia solium with the development of the tissue cysts. After the ingestion of the uncooked beef (T. saginata) orporkit develops the cysts and it causes them mild abdominal symptoms. The infestations of the central nervous systems caused due to the pork tapeworm or flukes are known as neurocysticercosis which is treated through albendazole and praziquantel.

Life cycle of Tapeworm ^[7]
This infection is caused by ingestion of eggs shed in the feces of a human tapeworm carrier. Pigs and humans become infected by ingesting eggs or gravid proglottids. Humans are infected either by ingestion of food contaminated with feces containing eggs, or by auto infection. In the latter case, a human infected with adult T. solium can ingest eggs produced by that tapeworm, either through fecal contamination or, possibly, from proglottids carried into the stomach by reverse peristalsis. Once eggs are ingested, oncospheres hatch in the intestine, invade the intestinal wall, and migrate to striated muscles, as well as the brain, liver, and other tissues, where they develop into cysticerci. In humans, cysts can cause serious sequelae if they localize in the brain, resulting in neurocysticercosis. The parasite life cycle is completed, resulting in human tapeworm infection, when humans ingest under cooked pork containing cysticerci. Cysts evaginate and attach to the small intestine by their scolex. Adult tape worms develop, (up to 2 to 7 m in length and produce less than 1000 proglottids, each with approximately 50,000 eggs) and reside in the small intestine for years.

PINWORM
The pinworm, or Enterobius vermicularis, is a parasite that commonly infects the intestines of humans. The male is 2 to 5 millimeters long and lives in the lower gastrointestinal tract. Females can be twice as long as males. Eggs take 1 to 2 months to mature in the gastrointestinal tract and become large enough to migrate. Pregnant females typically migrate to the rectal area to lay eggs, often during the night. Pinworms may also deposit their eggs along the perineum and even in the vagina. The females usually die after depositing their eggs. Humans are the only known natural hosts; pinworms do not live in dogs and cats. ^[5]

Lifecycle of Pinworm ^[7]

Eggs
The adult female pinworm travels to the rectum to lay her eggs. She moves at night, depositing her eggs around the rim of the anus, and then she dies.

Human Host
The human host scratches the anus; itching is triggered by the movement of the female and the presence of her eggs. The eggs are caught under fingernails, transferred to skin, linens and objects in the home, and eventually the eggs may be carried to the mouth.

Transmission
Pinworm eggs take six hours to mature. When the eggs are swallowed, they hatch in the digestive tract of a human (animals are not considered a source of infection); when they hatch on the surface of the skin, the larvae make their way into the nearest orifice (the vagina or the anus).

Immature Worms
Pinworms begin their lives in the small intestine. The larvae migrate to the large intestine and attach to the intestinal wall.

Adult Worms
Adult worms live in the large intestine or colon. It is suspected that they consume human fecal matter as a source of food.

Reproduction
Pin worms reproduce through sexual contact; pregnant females can lay 10,000 to 15,000 eggs. The time from initial ingestion of eggs to the first incidence of adult egg-laying takes about a month.

Flukes
Flukes are the parasitic trematodes of Schistosoma species which are transmitted through      direct contact with fresh water. They penetrate into the intact human skin and enter the  capillaries and then migrate to the central and portal system where they mature. Acute schistosomiasis also known as Katayama fever, which is a form of visceral larval migraines. The adult male and female pairs ultimately migrate to the superior mesenteric veins and ureteric vesicles. The eggs are then shed in the faeces and urine.

Lifecycle of Liverfluke ^[7]

• The adult flukes (Fasciola hepatica: up to 30 mm by 1v3 vemm; F. gigantica: up to 75 mm) reside in the large biliary ducts of the mammalian host. Immature eggs are discharged in the biliary ducts and in the stool.
• After development in water, each egg releases a miracidium which invades a suitable snail intermediate host.
• In the snail the parasites undergo several developmental stages (sporocysts, rediae, and cercariae).
• The cercariae are released from the snail and encyst as metacercariae on aquatic vegetation or other surfaces.
• Mammals acquire the infection by eating vegetation containing metacercariae.
• After ingestion, the metacercariae excyst in the duodenum and migrate through the intestinal wall, the peritoneal cavity and the liver parenchyma into the biliary ducts, where they develop into adults.
• Fasciola hepatica infect various animal species, mostly herbivores.
• Humans can become infected by ingesting metacercariae-containing freshwater plants, especially watercress.In humans, maturation from metacercariae into adult flukes takes approximately 3 to 4 months

WORM INFECTION AND ITS OUTCOME

TAPEWORM INFECTION
A tapeworm infection starts after ingestion of tapeworm eggs or larvae.

• Ingestion of eggs.If you eat food or drink water contaminated with feces from a person or animal with tapeworm, you ingest microscopic tapeworm eggs. For example, a pig infected with tapeworm will pass tapeworm eggs in its feces, which gets into the soil. If this same soil comes in contact with a food or water source, it becomes contaminated. You can then be infected when you eat or drink something from the contaminated source. Once inside your intestines, the eggs develop into larvae. At this stage, the larvae become mobile. If they migrate out of your intestines, they form cysts in other tissues, such as your lungs, central nervous system or liver.

• Ingestion of larvae cysts in meat or muscle tissue.When an animal has a tapeworm infection, it has tapeworm larvae in its muscle tissue. If you eat raw or undercooked meat from an infected animal, you ingest the larvae, which then develop into adult tapeworms in your intestines. Adult tapeworms can measure up to 50 feet (15.2 meters) long and can survive as long as 20 years in a host. Some tapeworms attach themselves to the walls of the intestines, where they cause irritation or mild inflammation, while others may pass through to your stool and exit your body.

LIVERFLUKE INFECTION
Liver fluke is caused by a parasite Fasciloa hepatica. Fluke eggs, which are passed in the faeces of a mammalian host, develop and hatch into motile ciliated miracidia - a process which takes nine days at the optimal temperature of 22 to 26^o. Development will not occur below 10^o. These miracidia have a short lifespan and must come into contact with the host (snail) within three hours. Development of the parasite continues in infected snails, until cercaria are shed from the snail as motile forms and attach themselves to firm surfaces, such as grass blades, where they become the infective metacercariae. These are then reingested by the final host, completing the life cycle. Once inside cattle, metacercaiae migrate through the gut wall, cross the peritoneum and penetrate the liver capsule and bile ducts. An adult fluke can be up to 3cm long and can survive in cattle anything between six months to two years. Mild temperatures and above average rainfall provide optimum conditions for fluke development. Wet areas on dry farms are high risk.

Roundworm infection
According to the National Institute of Allergy and Infectious Diseases, many roundworm parasitic diseases are caused by poor sanitation and hygiene. Most roundworms or their eggs are found in the dirt and can be picked up on the hands and transferred to the mouth. Or they can get into the body through the skin. Different species of roundworms cause different infections. ^[8]

The various roundworm infections include:

• Ascariasis:People become infected when they eat food or drink that contains the eggs of the roundworm Ascaris lumbricoides. That can happen when people eat food grown in soil that has been mixed with human feces. Once in the body, the larvae enter the lungs and then the throat, where they are coughed up and swallowed. Once they swallowed, larvae enter the intestines and become adults. They can produce eggs for a year or more. ^[8]
• Guinea worm disease (dracunculosis):People can become infected with Guinea worm disease when they drink contaminated water. Larvae grow into adults in the intestines, where they can grow to be 3 feet long. Then the adult moves to another area of the body (usually the legs) and emerges through a painful blister. The tip of the worm comes out through the skin to lay its eggs whenever the skin is immersed in water. This type of roundworm infects 10 - 40 million people annually worldwide, mostly in the Indian subcontinent, West and Central Africa, and some Middle Eastern countries. ^[8]
• Hookworm (ancylostomiasis):A hookworm infection occurs when larvae come into contact with human skin, through contaminated soil or feces. They penetrate the skin, making their way through the lungs to the small intestine, where they latch on and grow into adults, laying more eggs. They feed off the blood of the infected person, which can lead to anemia. Children are especially vulnerable to this kind of infection. These roundworms infect about 25% of the world's population.
• Loiasis:Loiasis is an infection caused by the roundworm Loa loa. Like river blindness, loiasis is spread by day-biting flies. An estimated 3 - 13 million people in equatorial Africa have been infected with Loa loa. ^[8]
• Lymphatic filariasis:A lymphatic filariasis infection occurs when a person is bitten by a mosquito containing the roundworms Wucheria bancrofti, Brugia malayi, or Brugia timori. Over 6 - 12 months, adult worms mature and live in human lymph vessels and nodes. Eggs are released and circulate through the blood. About 90 million people worldwide have been infected with these roundworms. ^[8]
• Pinworm (enterobiasis):A pinworm infection occurs when a person consumes food or drink contaminated with feces containing the worm. The eggs hatch in the small intestine, and adult worms ultimately live in the large intestine. The pregnant female worms move to the anus and deposit large numbers of eggs in the skin around that area. Pinworm, which is commonly spread in day care centers, schools, and camps, affects as many as 1/3 of all American children. ^[8]
• River blindness (onchocerciasis):River blindness is an infection of the eyes caused by the roundworm Onchocerca volvulus. River blindness is spread by day-biting flies, and is the leading cause of blindness worldwide. It affects about 20 million people, mostly in Africa. ^[8]
• Threadworm (strongyloidiasis):Threadworm usually occurs when someone walks barefoot on contaminated soil, and larvae get into the skin. Inside the body, they move to the lymph nodes and then to the lungs and throat. When the person coughs, the larvae are swallowed and move to the intestines. There they grow into adults and produce eggs. About half of the population of some African countries has been infected with threadworm. ^[8]
• Trichinosis (trichiniasis):Trichinosis is an infection caused by the roundworm Trichinella spiralis. These larvae live in pigs and other wild carnivores, such as bears. People can get infected when they eat meat (particularly pork) that is undercooked. The larvae mature in the small intestine and move to muscle cells where they can live for months or years. ^[8]
• Visceral larva migrans, or VLM (toxocariasis):VLM is an infection caused by the roundworms Toxocara canis, Toxocara cati, or Baylisascaris procyonis. These parasites usually infect dogs, cats, and raccoons, respectively. People can get infected by ingesting soil contaminated by animal feces. While the larvae do not grow to be adults in people, they penetrate the intestinal wall and move to various parts of the body, particularly the lungs and liver. ^[8]
• Whipworm (trichuriasis):A whipworm infection occurs when a person eats food contaminated with soil containing eggs of the worm. After eggs are eaten, larvae hatch and attach themselves to the large intestine. ^[8]

SYMPTOM OF WORM  INFECTION

Tapeworm Infection

•   Abdominal Discomfort
•   Diarrhea
•   Constipation
•   Malnutrition
•   Muscle Weakness
•   Neurological Damage
•   Seizures
•   Weight loss
•   Tapeworm Segments on Clothes or in Feces

Pinworm  infection
The most common symptom is anal itching, but most people with pin-worms show no symptoms at all. Because female pinworms usually lay their eggs at night, this is when itching can be most intense, and it may interfere with sleep or may cause restless sleep. Sometimes, anal itching is so minor that it is not recognized as a symptom. In females, pinworms can migrate to the vagina, causing itching and vaginal discharge.

Roundworm infection
The signs and symptoms of roundworm infection include:

Ascariasis

• Cough
• Shortness of breath
• Abdominal pain
• Nausea and diarrhea
• Blood in the stool
• Weight loss
• Fatigue
• Presence of worm in vomit or stool

Guinea worm disease
Symptoms start about one year after infection. When the adult worm is ready to lay eggs, it comes out through the skin. A blister develops, usually on the legs of feet, and becomes an open wound. When the wound is submerged in water, the tip of the worm emerges to lay its eggs. Symptoms include pain and swelling at the site of the wound.

Hookworm
Often no symptoms are present. Or they may include:

• Itchy rash
• Cough
• Wheezing
• Difficulty breathing
• Abdominal pain
• Weight loss
• Diarrhea
• Loss of appetite

Loiasis

• Watery or itchy eyes
• Blurred vision
• Some people may see the worm move across the eyes

Lymphatic filariasis

• Swelling and scarring, especially of the legs and groin
• Infections

River blindness

• Itchy rash
• Sores on the skin
• Swollen lymph nodes
• Skin turns white (loss of pigmentation)
• Loss of vision

Threadworm

• Itch where the worm enters the skin (similar to a bug bite)
• Nausea and diarrhea
• Fever
• Blood in the stool
• Dry cough or coughing up blood
• Difficulty breathing

Trichinosis

• Diarrhea
• Abdominal pain
• High fever
• Muscle pain
• Sensitivity to light (photosensitivity)
• Headache
• Pink eye (conjunctivitis)

Whipworm

• Abdominal pain
• Diarrhea (sometimes bloody)
• Anemia

Fluke infection

Abdominal Pain
Liver fluke infection can cause pain in the upper right abdomen where the liver is located. Pain is this area is particularly common in the early stages of infection, especially with Fasciola hepatica. The pain corresponds to the flukes making their way from the intestine into the liver. The immature flukes burrow through the liver surface causing pain. Later in the illness, heavy infestation with any of the liver flukes may cause episodic obstruction of the biliary system. Pain in the right upper abdomen is a characteristic symptom during these episodes.

Fever
Infection with liver flukes may cause episodic fevers. Fevers are most common early in the infection, and may reach as high as 104F. Fevers also occur if the liver flukes cause obstruction of the biliary system.

Nausea, Vomiting and Diarrhea
Nausea, vomiting and diarrhea may occur with liver fluke infections. These symptoms are prominent early in the infection and may last for weeks to months. Gastrointestinal symptoms typically wane after the initial phase of the infection but may recur later due to inflammation or obstruction of the biliary tract.

Hives
Parasitic infections, including those caused by liver flukes, may cause hives. This symptom is triggered by the immune system's response to invasion by the parasites. Hives are most common early in the illness.

Malaise
Liver fluke infection may cause a general feeling of being unwell; this symptom is called malaise. It is common in the early phase of liver fluke infection. Malaise may recur later in the illness if long-standing infection causes permanent liver damage.

Decreased Appetite and Weight Loss
Long-standing liver fluke infection may cause decreased appetite and weight loss. Infections with liver flukes, especially Fasciola hepatica, may cause liver cirrhosis after many years. Weight loss, jaundice (yellowing of the skin and whites of the eyes), and other signs and symp toms are common with cirrhosis of the liver.

WORM INFECTION PREVENTION

Fluke infection
No vaccines have been developed that are effective against lung or liver fluke infections. Prevention of these infections includes the following measures:

• Boiling or purifying drinking water.
• Avoiding raw or undercooked fish or salads made from fresh aquatic plants. All food eaten in areas with fluke infestations should be cooked thoroughly. Pickling or smoking will not kill fluke cysts in fish or shellfish.
• Control or eradication of the snails that serve as the flukes' intermediate hosts

Roundworm infection
It is easier to prevent roundworms than to cure them. The steps to preventing roundworm infection include: ^[8]

• Practice good personal hygiene -wash hands and avoid contact with fecal matter.
• Don’t eat uncooked or unwashed fruits and vegetables.
• Stay away from mosquito or fly-infested areas; don’t drink unfiltered water; and dotouch the soil in areas where roundworm infections are common.
• Wear protective clothing, and use insect repellant.
• Cook or freeze meat thoroughly.
• Keep children away from pet feces.
• Ask a veterinarian about deworming  pets.
• Public health measures include improving general sanitation, especially sewage disposal, and reducing mosquito and fly populations.

Tapeworm infection
To prevent tapeworm infection:

• Wash your hands with soap and water before eating or handling food and after using the toilet.
• When traveling in areas where tapeworm is more common, wash and cook all fruits and vegetables with safe water before eating.
• Eliminate livestock exposure to tapeworm eggs by properly disposing of animal and human feces.
• Thoroughly cook meat at temperatures of at least 125 F (52 C) to kill tapeworm eggs or larvae.
• Freeze meat for at least 12 hours and fish for at least 24 hours to kill tapeworm eggs and larvae.
• Avoid eating raw or undercooked pork, beef and fish.
• Promptly treat dogs infected with tapeworm.

Pinworm infection

• Bath first thing in the morning.
• Change underwear daily and nightclothes regularly.
• Change bed sheets after every treatment.
• Wash your hands after using the washroom, after changing diapers, and before eating.
• Open curtains in the bedroom during the day, as pinworm eggs are sensitive to light.
• Cut fingernails short, avoid nail biting, and do not scratch the anal area.

MARKETED FORMULATION FOR ANTHELMENTIC ACTIVITY ^[15]
The Generic Anthelmintics Drugs available are commonly used to cure the ailment caused by parasitic worms. These drugs either destroy parasitic worms or expel them from the body. ^[13]

* Albendazole (Albenza, Zentel)
Oral: 200 mg tablets; 100 mg/5ml suspension
Note: Albendazole is approved in the USA for the treatment of cysticercosis and hydatid   disease

* Bithionol (Bitin)
Oral: 200 mg tablets
Note: Bithionol is not marketed in the USA but is available from the Parasitic Disease Drug Service, Centers for Disease Control and Prevention, Atlanta; 404-639-3670.

* Diethylcarbamazine (Hetrazan)
Oral: 50 mg tablets
Note: Diethylcarbamazine is no longer marketed in the USA but is available from the Parasitic Disease Drug Service, Centers for Disease Control and Prevention, Atlanta; 404-639-3670.

* Ivermectin (Mectizan, Stromectol)
Oral: 3, 6 mg tablets
Note: Ivermectin is approved for use in the USA for the treatment of onchocerciasis and strongyloidiasis.

* Levamisole (Ergamisol)
Oral: 50 mg tablets

* Mebendazole (generic, Vermox)
Oral: 100 mg chewable tablets; outside the USA, 100 mg/5 mL suspension

* Metrifonate (trichlorfon, Bilarcil)
Oral: 100 mg tablets
Note: Metrifonate is not available in the USA.

* Niclosamide (Niclocide)
Oral: 500 mg chewable tablets
Note: Niclosamide is not available in the USA.

* Oxamniquine (Vansil, Mansil)
Oral: 250 mg capsules; outside the USA, 50 mg/ml syrup.

* Oxantel pamoate (Quantrel); oxantel/pyrantel pamoate (Telopar)
Oral: tablets containing 100 mg (base) of each drug; suspensions containing 20 or 50 mg (base) per ml.
Note: Oxantel pamoate and oxantel/pyrantel pamoate are not available in the USA.

* Piperazine (generic, Vermizine)
Oral: piperazine citrate tablets equivalent to 250 mg of the hexahydrate; piperazine citrate syrup equivalent to 500 mg of the hexahydrate per 5 ml.

* Praziquantel (Bactericide; others outside the USA)
Oral: 600 mg tablets (other strengths outside the USA)

* Pyrantel pamoate (Antiminth, Combantrin, Pin-rid, Pin-X)
Oral: 50 mg (base)/ml suspension; 180 mg tablets; 62.5 mg (base) capsules (available without prescription in the USA)

* Suramin (Bayer 205, others)
Parenteral: ampules containing 0.5 or 1 g powder to be reconstituted as a 10% solution and used immediately
Note: Suramin is not marketed in the USA but can be obtained from the Parasitic Disease Drug Service, Centers for Disease Control, Atlanta, 404-639-3670.

* Thiabendazole (Mintezol)
Oral: 500 mg chewable tablets; suspension, 500 mg/Ml.

LIMITATION OF MARKETED FORMULATION USED FOR ANTHELMINTIC ACTIVITY

ALBENDAZOLE ^{[15, 16]}
When used for 1-3 days, albendazole is nearly free of significant adverse effects. Mild and transient epigastric distress, diarrhea, headache, nausea, dizziness, lassitude, and insomnia can occur. In long-term use for hydatid disease, albendazole is well tolerated, but it can cause abdominal distress, headaches, fever, fatigue, alopecia, increases in liver enzymes, and pancytopenia.

Blood counts and liver function studies should be followed during long-term therapy. The drug should not be given to patients with known hypersensitivity to other benzimidazole drugs or to those with cirrhosis. The safety of albendazole in pregnancy and in children younger than 2 years of age has not been established.

BITHIONOL ^{[15, 16]}
Adverse effects, which occur in up to 40% of patients, are generally mild and transient, but occasionally their severity requires interruption of therapy. These problems include diarrhea, abdominal cramps, anorexia, nausea, vomiting, dizziness, and headache. Skin rashes may occur after a week or more of therapy, suggesting a reaction to antigens released from dying worms.

Bithionol should be used with caution in children younger than 8 years of age because there has been limited experience in this age group.

DIETHYLCARBAMAZINE CITRATE ^{[15, 16]}
Reactions to diethylcarbamazine, which are generally mild and transient, include headache, malaise, anorexia, weakness, nausea, vomiting, and dizziness. Adverse effects also occur as a result of the release of proteins from dying microfilariae or adult worms. Reactions are particularly severe with onchocerciasis, but diethylcarbamazine is no longer commonly used for this infection, as ivermectin is equally efficacious and less toxic. Reactions to dying microfilariae are usually mild in W bancrofti, more intense in B malayi, and occasionally severe in L loa infections. Reactions include fever, malaise, papular rash, headache, gastrointestinal symptoms, cough, chest pain, and muscle or joint pain. Leukocytosis is common. Eosinophilia may increase with treatment. Proteinuria may also occur. Symptoms are most likely to occur in patients with heavy loads of microfilariae. Retinal hemorrhages and, rarely, encephalopathy have been described.

IVERMECTIN ^{[15, 16]}
In strongyloidiasis treatment, infrequent side effects include fatigue, dizziness, nausea, vomiting, abdominal pain, and rashes. In onchocerciasis treatment, the adverse effects are principally from the Mazotti reaction, due to killing of microfilariae. The reaction includes fever, headache, dizziness, somnolence, weakness, rash, increased pruritus, diarrhea, joint and muscle pains, hypotension, tachycardia, lymphadenitis, lymphangitis, and peripheral edema. This reaction starts on the first day and peaks on the second day after treatment. The Mazotti reaction occurs in 5-30% of persons and is generally mild, but it may be more frequent and more severe in individuals who are not long-term residents of onchocerciasisendemic areas. A more intense Mazotti reaction occurs in 1-3% of persons and a severe reaction in 0.1%, including high fever, hypotension, and bronchospasm. Corticosteroids are indicated in these cases, at times for several days. The Mazotti reaction diminishes with repeated dosing. Swellings and abscesses occasionally occur at 1-3 weeks, presumably at sites of adult worms.

Some patients develop corneal opacities and other eye lesions several days after treatment. These are rarely severe and generally resolve without corticosteroid treatment.

It is best to avoid concomitant use of ivermectin and other drugs that enhance GABA activity, eg, barbiturates, benzodiazepines, and valproic acid. Ivermectin should not be used in pregnancy. Safety in children younger than 5 years has not been established.

MEBENDAZOLE ^{[15, 16]}
Short-term mebendazole therapy for intestinal nematodes is nearly free of adverse effects. Mild nausea, vomiting, diarrhea, and abdominal pain have been reported infrequently. Rare side effects, usually with high-dose therapy, are hypersensitivity reactions (rash, urticaria), agranulocytosis, alopecia, and elevation of liver enzymes.

Mebendazole is teratogenic in animals and therefore contraindicated in pregnancy. It should be used with caution in children younger than 2 years of age because of limited experience and rare reports of convulsions in this age group. Plasma levels may be decreased by concomitant use of carbamazepine or phenytoin and increased by cimetidine. Mebendazole should be used with caution in patients with cirrhosis.

METRIFONATE (TRICHLORFON) ^{[15, 16]}
Some studies note mild and transient cholinergic symptoms, including nausea and vomiting, diarrhea, abdominal pain, bronchospasm, headache, sweating, fatigue, weakness, dizziness, and vertigo. These symptoms may begin within 30 minutes and persist up to 12 hours. Metrifonate should not be used after recent exposure to insecticides or drugs that might potentiate cholinesterase inhibition. Metrifonate is contraindicated in pregnancy.

NICLOSAMIDE ^{[15, 16]}
Infrequent, mild, and transitory adverse events include nausea, vomiting, diarrhea, and abdominal discomfort.

The consumption of alcohol should be avoided on the day of treatment and for 1 day afterward.

The safety of the drug has not been established