ANTHELMINTIC

Dr John Tiong
Overview
• Infections with helminths, or parasitic worms, affect more than two
billion people worldwide.

• In regions of rural poverty in the tropics, where prevalence is greatest,

simultaneous infection with more than one type of helminths is
common.

• Primarily as a result of stepped-up advocacy by the World Health

Organization (WHO), the World Bank, and smaller non-
governmental organizations such as the London-based Partnership
for Child Development (PCD), there is increasing appreciation for
the impact of helminth infections on the health and education of
school-aged children.

• These organizations have promoted the periodic and frequent use of

anthelmintic drugs in schools as a means to control morbidity caused
by soil-transmitted helminths in developing countries.
Overview
• Three major groups of helminths (worms) which infect humans:
1. Nematodes (roundworms)
2. Trematodes (flatworms also known as flukes)
3. Cestodes (tapeworms)

• These biologically diverse eukaryotes vary with respect to life cycle,

bodily structure, development, physiology, localization within the host,
and susceptibility to chemotherapy.

• Immature forms invade humans via the skin or gastrointestinal tract

and evolve into well-differentiated adult worms.

• Without treatment, infected individuals are most likely to become ill

and to perpetuate infection within their community.
NEMATODES
NEMATODES
• Nematodes are elongated roundworms that possess a
complete digestive system, including both a mouth and an
anus.

• The major infections include enterobiasis, ascariasis, filariasis,

hookworm diseases, strongyloidiasis and trichinosis

• The most widely used agents employed for reducing morbidity

are the benzimidazole anthelmintics (BZAs), either albendazole
(ALBENZA and ZENTEL) or mebendazole
ENTEROBIASIS (PINWORM DISEASE)
• Pinworm infection

• Causative agent: Enterobius vermicularis

• Most common helminthic infection in the United States.

• Infection usually occurs through the ingestion of pinworm eggs,

either through contaminated food, or less commonly water

• Pinworms are usually considered a nuisance rather than a serious

disease

• Pruritus ani occurs, with white worms visible in stools or perianal

region. A third of individuals with pinworm infection are totally
asymptomatic.
ENTEROBIASIS (PINWORM DISEASE)
• Pruritus in the perianal and perineal regions, however, can be severe,
and scratching may cause secondary infection. A considerable
proportion of children suffer from loss of appetite, weight loss and
irritability

• In female patients, worms may wander into the genital tract and
penetrate into the peritoneal cavity. Salpingitis or even peritonitis may
ensue.

• Therapy: Mebendazole, Albendazole or pyrantel pamoate.

ASCARIASIS (ROUNDWORM DISEASE)
• Causative agent: Ascaris lumbricoides

• People become infected by ingesting food or soil contaminated with

embryonated A. lumbricoides eggs.

• The highest ascaris worm burdens occur in school-aged children in

whom the parasite can cause intestinal obstruction or
hepatobiliary ascariasis.

• Ingested larvae grow in the intestine, causing abdominal symptoms,

including intestinal obstruction; roundworms may pass to blood
and infect the lungs.
ASCARIASIS (ROUNDWORM DISEASE)

• Therapy: Pyrantel pamoate or mebendazole or albendazole

• Cure with any of these drugs can be achieved in nearly 100% of

cases, and all infected persons should be treated.
FILARIASIS
• Causative agents: Wuchereria bancrofti or Brugia malayi.

• Adult worms that cause human filariasis dwell primarily in the

lymphatic system.

• Lymphatic filariasis (LF) affects nearly 120 million people, about 90%
of them infected with W. bancrofti and most of the rest with B. malayi.

• Spread through mosquito bites.

• Worms cause blockage of lymph flow and swelling (primarily in the

legs and genital areas) ultimate local inflammation and fibrosis of
the lymphatics occurs.

• After years of infestation, the arms, legs, and scrotum fill with fluid,
causing and elephantiasis.
FILARIASIS
• Therapy: A combination of diethylcarbamazine and albendazole.
These drugs clear circulating microfilariae from infected subjects
thereby reducing the likelihood that mosquitoes will transmit LF to
other individuals

• In long-standing elephantiasis, surgical measures are required to

improve lymph drainage and remove redundant tissues.
FILARIASIS
HOOKWORM DISEASE
• Causative agents: Ancylostoma duodenale (Old World hookworm),
Necator americanus (New World hookworm).

• Hookworm larvae live in the soils and penetrate exposed skin. After
reaching the lungs, the larvae migrate to the oral cavity and are
swallowed. After attaching to the jejunal mucosa, the worms feed on
host blood. This may result in anorexia, ulcer-like symptoms, and
chronic intestinal blood loss that leads to anemia.

• Therapy: Mebendazole or albendazole. Both benzimidazoles have

the advantage of effectiveness against other roundworms when there
is multiple infection. Albendazole is superior to mebendazole at
removing adult hookworms from the GI tract
HOOKWORM DISEASE
• Although iron supplementation often is helpful in individuals with
severe iron-deficiency anemia, the major treatment goal is to remove
blood-feeding adult hookworms from the intestines.
STRONGYLOIDIASIS (THREADWORM
DISEASE)
• Causative agent: Strongyloides stercoralis sometimes called the
threadworm.

• It is found in individuals living in unsanitary conditions and among

immigrants, travellers, and military personnel who lived in endemic
areas.

• Infective larvae in fecally contaminated soil penetrate the skin or

mucous membranes, travel to the lungs, and ultimately mature into
adult worms in the small intestine, where they reside.

• Most infected individuals are asymptomatic, while some experience

skin rashes and gastrointestinal symptoms.

• Life-threatening, systemic disease due to massive larval

hyperinfection can occur in immunosuppressed persons, even
decades after the initial infection.
STRONGYLOIDIASIS (THREADWORM
DISEASE)
• Most deaths caused by parasites in the United States probably are due
to Strongyloides hyperinfection.

• Strongyloides travels from the skin to the lungs and then to the
gastrointestinal (GI) tract of its host. In hyperinfection syndrome, this
classic life cycle is exaggerated (ie, the parasite burden and turnaround
increase and accelerate)

• Symptoms: gastrointestinal disturbances, weight loss, abdominal pain, GI

hemorrhage, cough, fever, and dyspnea.

• Patients with hyperinfection syndrome and disseminated disease

often have catastrophic clinical manifestations such as septic shock,
disseminated intravascular coagulation, meningitis, renal failure,
and/or respiratory failure
STRONGYLOIDIASIS (THREADWORM
DISEASE)
• Hyperinfection may require prolonged or repeated therapy.

• Ivermectin is the best drug for treating intestinal strongyloidiasis.

• Effective benzimidazole compounds, listed in order of decreasing

efficacy, are thiabendazole and albendazole.

• Thiabendazole shows efficacy comparable to that of ivermectin but is

far more toxic.
TRICHINOSIS
• Causative agent: Trichinella spiralis.

• T. spiralis is ubiquitous, regardless of climate, and can live outside its

hosts.

• The infection results from eating raw or insufficiently cooked flesh of

infected animals, especially pigs.

• When released by acid stomach contents, encysted larvae mature

into adult worms in the intestine.

• Adults then produce infectious larvae that invade tissues, especially

skeletal muscle and heart.

• Severe infection can be fatal, but more typically causes marked

muscle pain and cardiac complications.
TRICHINOSIS
• Fortunately, infection is readily preventable.

• All pork, including pork sausages, should be thoroughly cooked

before being eaten. The encysted larvae are killed by exposure to
heat of 60°C for 5 minutes.

• Albendazole and mebendazole appear to be effective against the

intestinal forms of T. spiralis that are present early in infection. The
efficacy of these agents or any anthelmintic agent on larvae that have
migrated to muscle is questionable.

• Glucocorticoids may be of considerable value in controlling the acute

and dangerous manifestations (i.e. inflammations) of established
infection.
Trematodes (Flukes)
Trematodes
• The trematodes (flukes) are flatworms that are generally
characterized by the tissues they infect.

• Their life-cycle occurs in at least two different hosts.

• Almost all trematodes infect mollusks (e.g. snail) as the first host in
the life cycle, and most have a complex life cycle involving
other hosts.
Schistosomiasis (New World)
• This disease is caused by the blood flukes Schistosoma mansoni and
Schistosoma japonicum.

• The primary site of infection is the gastrointestinal tract.

• Damage to the intestinal wall is caused by the host’s inflammatory

response to eggs deposited at that site.

• The eggs also secrete proteolytic enzymes that further damage the
tissue.
Schistosomiasis (New World)
• Clinical presentation includes GI bleeding, diarrhea, and liver
damage.

• The disease is transmitted by direct skin penetration.

• This form of schistosomiasis is diagnosed by identification of

characteristic eggs in the stool.
Schistosomiasis (Old World)
• This disease is caused by the blood fluke Schistosoma haematobium.

• The primary sites of infection are veins of the urinary bladder,

where the organism’s eggs can induce fibrosis, granulomas, and
hematuria.

• The disease is transmitted by direct skin penetration.

• This form of schistosomiasis is diagnosed by identifying characteristic

eggs in the urine or bladder wall.
Schistosomiasis treatment
• Praziquantel is the drug of choice for treating all species of
schistosomes that infect humans.

• The drug is safe and effective when given in single or divided oral
doses on the same day.

• These properties make praziquantel especially suitable for

population-based chemotherapy.

• Moreover, repeated chemotherapy with praziquantel is thought to

accelerate protective immune responses by increasing exposure
to antigens released from dying worms that induce a T-helper type-2
response
 Cestodes
(Tapeworms)
Cestodes (Tapeworms)
• The cestodes, or true tapeworms typically have a flat, segmented
body and attach to the host’s intestine.

• Like the trematodes, the tapeworms lack an alimentary canal

throughout their life cycle.

• The outer tegument of the body must serve not only as a protective
coating but also as a metabolically active layer through which nutritive
material can be absorbed, along with secretions and waste material to
be transported out of the body.

• Adult tapeworms usually inhabit the alimentary canal of their hosts

(though they occasionally are found in the bile or pancreatic ducts)
and attach themselves to the mucosa by means of a scolex.
Cestodes (Tapeworms)
• Despite the lack of a digestive system they do absorb food from the
hosts intestine  thereby providing the tapeworms a habitat that is
associated with high nutritional levels, feeding the tapeworms high
growth rate.

• Larvae on the other hand show a wide range of habitat preferences,

being found in almost any organ of both vertebrate and invertebrate
hosts. Though most larval species show a preference for a particular
site.
Taeniasis
• This form of the disease is caused by the adult Taenia solium (pork
tapeworm).

• Intestines are the primary site of infection.

• Most of these infections are asymptomatic but Pork tapeworm can

also cause diarrhea.

• The intestinal disease caused by the adult tapeworms is a result of

eating undercooked meat containing cysticerci (larva of tapeworm);
this can be prevented by proper cooking of infected meat.

• Therapy: Praziquantel is preferred for treatment of intestinal

infections with T. solium.
Cysticercosis
• More serious systemic disease caused by Taenia solium larvae.

• Infection produces cysticerci (larval enclosed within the fluid filled cyst) in
the brain (causing seizures, headache, and vomiting) and in the eyes.

• Cysticercosis is diagnosed by CT scan or biopsy.

• Albendazole and praziquantel are the drugs of choice for treating

cysticercosis, although some studies suggest that albendazole is more
effective.

• Pretreatment with glucocorticoids is advised strongly in this situation to

minimize inflammatory reactions to dying parasites.

• Anthelmintic treatment can shrink brain cysts but also can have adverse
consequences leading to seizures and hydrocephalus.
Cysticercosis
Anthelmintics
Benzimidazoles (BZAs)
• Examples: Thiabendazole, mebendazole and albendazole

Anthelmintic Action:
• BZAs produce many biochemical changes in susceptible nematodes
including inhibition of mitochondrial fumarate reductase, reduced
glucose transport, and uncoupling of oxidative phosphorylation, but
their primary action likely is to inhibit microtubule polymerization
by binding to β-tubulin.
• The selective toxicity of these agents results because the BZAs bind
parasite β-tubulin with much higher affinity than they do the
mammalian protein.
• Immobilization and death of susceptible gastrointestinal parasites
occur slowly, and their clearance from the GI tract may not be
complete until several days after treatment.
Benzimidazoles (BZAs)
Toxicity, side effects and contraindications:

• Thiabendazole: The clinical utility of thiabendazole in adults is

compromised by its toxicity. Side effects frequently encountered with
therapeutic doses include anorexia, nausea, vomiting, dizziness and
CNS side effects.

• Mebendazole: It does not cause significant systemic toxicity in

routine clinical use. This probably reflects its low systemic
bioavailability. Some patients may complain of abdominal pain and
diarrhea.

• Albendazole: It is relatively well- tolerated by most patients. Long

term treatment (3 months) has a risk of hepatotoxicity and, rarely,
agranulocytosis or pancytopenia. Blood counts and liver function
studies should be monitored during long-term therapy.
Pyrantel pamoate
• Pyrantel pamoate is a broad-spectrum anthelmintic highly effective for
the treatment of nematodes.

• Pyrantel pamoate is poorly absorbed from the gastrointestinal tract, a

property that contributes to its selective action on gastrointestinal
nematodes  major proportion of an administered dose is recovered
in the feces.

• Pyrantel and its analogs are depolarizing neuromuscular blocking

agents. They open non-selective cation channels and induce marked,
persistent activation of nicotinic acetylcholine receptors, which
results in spastic paralysis of the worm.The paralyzed worm is then
expelled from the host’s intestinal tract. Pyrantel also inhibits
cholinesterases.

• Transient and mild GI symptoms occasionally are observed in

humans, as are headache, rash and fever.
Ivermectin
• Ivermectin is the drug of choice for the treatment of strongyloidiasis.

• The drug immobilizes affected organisms by inducing a tonic

paralysis of the musculature. Ivermectin targets the parasite’s
glutamate-gated chloride channel receptors (found only in
invertebrate). Chloride influx is enhanced, and hyperpolarization
occurs, resulting in paralysis of the worm.

• Ivermectin is well tolerated by humans and other mammals. The

killing of the microfilaria can result in a Mazotti-like reaction (fever,
headache, dizziness, somnolence and hypotension).
Diethylcarbamazine
• Diethylcarbamazine is a first-line agent used in the treatment of
filariasis.

• Combined with albendazole, diethylcarbamazine is effective in the

treatment of Wuchereria bancrofti and Brugia malayi infections.

• The mechanism of action of diethylcarbamazine on susceptible

microfilariae is not well understood, but the drug appears to exert a
direct effect on microfilariae by causing organelle damage and
apoptosis

• Adverse effects are primarily caused by host reactions to the killed

organisms: fever, malaise, rash  Antihistamines or steroids may be
given to ameliorate many of the symptoms.
Praziquantel
• This drug is an agent of choice for the treatment of all forms of
schistosomiasis and for cestode infections like cysticercosis.

• Permeability of the cell membrane to calcium is increased, causing

contracture and paralysis of the parasite.

• Common adverse effects include drowsiness, malaise, and

gastrointestinal upsets.

• Praziquantel is contraindicated for the treatment of ocular

cysticercosis, because destruction of the organism in the eye may
damage the organ.
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