HUMAN HELMINTHES INFECTIONS

INTRODUCTION

Helminthes (worm) are among the major parasites of humans and are classified under two phyla;

1. Nemathelminthes ( Nematodes or Round worms)
2. Platyhelminthes (Cestodes or tape worms and Trematodes or flukes)

Majority of helminthes that infect humans belong to the following three classes.

1. Nematoda (round worms). They are elongated, cylindrical worms. The sexes are separate. A complete alimentary canal is present with some species having well developed buccal capsules. They possess a body cavity ( pseudocele)
2. Cestoda (tapeworms). They are flattened tape-like segmented worms. Sexes are not separate, each segment having a set of male and female reproductive organs. Alimentary canal is absent. The head end possesses suckers, often with hooks. The body cavity is absent.
3. Trematoda (flukes). They are flattened and leaf-like. Each fluke has a set of male and female reproductive organs (except blood flukes where sexes are separate). The alimentary canal is incomplete and there is no body cavity. They possess oral and ventral suckers.

NEMATODES

This is a large and highly successful group of organisms found living in all types of habitats. Some are important parasites of human and animals. The parasitic nematodes are remarkable being similar to each other but vary widely in size. They are cylindrical with unsegmented bodies and have false body cavities (pseudocoelomes). The multi-layered cuticle is non-nucleated and allows contraction and expansion of the body. Inner to the cuticle is the muscle layer. Among the major organs are the alimentary, excretory and the reproductive systems, which are suspended in the ‘body cavity’. They have separate sexes.

The cuticle is shed (moulting) four times during development from egg to adult worm. Some species have direct life cycles while others need intermediate hosts. Nematodes do not multiply in humans (except in the form of auto infection with Strongyloides). Parasitic nematodes of humans are found in various tissues such as subcutaneous, muscle, lymphatic tissue and in organs such as the intestinal tract.

Nematode parasites of humans

Small intestine

1. Ascaris lumbricoides ( The large roundworm)
2. Necator americanus (Hook worm)
3. Ancylostoma duodenale (Hook worm)
   
4. Strongyloides stercoralis (Thread worm)
   
5. Trichinella spiralis (Trichina worm)

Large intestine

1. Trichuris trichiura (Whip worm)
2. Enterobius vermicularis (Pin worm)

Tissue nematodes

1. Subcutaneous tissue (filarial worm, Dracanculosis and animal hookworm larvae)
2. Muscle ( Trichinella spiralis)
3. Lymphatics ( Filarial worm)
4. Visceral organs (Toxocara)
5. CNS ( Angiostrongylus cantonensis and Toxocara)

Infections due to other nematodes

1. Dracunculus medinensis (Dracanculosis or Guinea worm disease)
2. Trichinella spiralis (Trichinosis)
3. Larva migrans

• Cutaneous larva migrans
• Visceral larva migrans

CESTODES

They are flat, ribbon-like worms inhabiting the intestinal tract of vertebrates. Their bodies are formed of chains of segments (proglottids) of varying sizes and shapes. The whole chain is called strobila. At the anterior end is the scolex or the ‘holdfast’ organ which is used for the attachment of the worm to the intestinal mucosa. Suckers aid the attachment to the mucosa in some while others use sucking grooves. Hooks also help when present. Behind the scolex is the undifferentiated ‘neck’ region from which growth of new segments takes place continuously. The end of the worm is comprised of gravid (pregnant) segments. They have no alimentary canals and nutrition is getting through the cuticle of the segments. Each segment has male and female reproductive organs (testes, ovaries and uteri).

In the life cycle the larval stages are found in the intermediate hosts. Some have only one intermediate host while others have two intermediate hosts. In humans pathology is caused by either adult worms or by larval stages.

Cestodes parasites in human

Human infection due to adult worms

1. Taenia saginata (beef tapeworm)
2. Taenia solium (pork tapeworm)
3. Hymenolepis diminuta (rat tapeworm)
4. Hymenolepis nana (The dwarf tapeworm)
5. Diphyllobothrium latum (fish tapeworm)
6. Dipylidium caninum (cat/dog tapeworm)
7. Bertiella studeri (monkey tapeworm)

Human infection due to larval stages

1. Cysticercosis cellulose (Cysticercosis)
2. Echinococcus garnulosus (Echinococcosis/Hadatid disease)

TREMATODES

Several trematodes (also known as flukes) are capable of parasiting man. The most important of these are the schistosomes. Other trematodes are also of major medical significance, especially in the Far East, as parasites of the liver, lung and the intestinal tracts.

Trematodes are flat, leaf-like hermaphrodite helminthes (excluding schistosomes). These parasites vary in size from a few millimeters to around 7cm in length. They possess two suckers, one for attachment, and another into which the alimentary tract opens. The rest of the body is occupied by the gut, testes, uterus and yolk glands. The morphology of these structures is used in identification.

In all trematodes infections, man acts as the definitive host harbouring the adult worms. The life cycle is complex, with alternating sexual and asexual reproduction in different hosts. The first intermediate host, however, is always a freshwater snail. Each parasite is specific in the choice of a snail host. The life cycles of trematodes (excluding the schistosomes) are similar: the egg which is excreted by a definitive host needs to reach water/moisture, where the ciliated larva inside the egg (called the miracidium) escapes and finds its way into a snail host. There is prolonged development multiplication in the snail with the formation of sporocysts and radia (2^nd stage larvae) stages. The final larval stages, which are known as cercaria, emerge from the snail and encyst as metacercaria on fish, crustacean or water plants. Human infection follows ingestion of these infected second intermediate hosts.

Trematodes parasites in human

Lung flukes

1. Paragonimus westermani

Liver flukes

1. Ophisthorchis (Clonorchis) sinensis (Chinese liver fluke)
2. Fasciola hepatica (sheep liver fluke)

Intestinal flukes

1. Fasciolopsis buski

Blood schistosomiasis

1. Intestinal schistosomiasis

• Schistosoma mansoni
• Schistosoma japonicum

2. Urinary schistosomiasis

• Schistosoma haematobium

HYMENOLEPIS NANA (The dwarf tapeworm)

GEOGRAPHICAL DISTRIBUTION

The infection is commoner in both temperate and tropical regions of the world such as Egypt, Sudan, Thailand, India, Japan, South America and Southern Europe.

LOCATION IN HOST

The worm is found attached to the mucosa of the small intestine.

MORPHOLOGY

The worm is small and measures 25-45mm*0.5-0.9mm. It consists of 100-200 segments. The small scolex measures 140-480µm and has a rostellum with single row of hooks

There are four suckers on the scolex. The neck is usually long. The segments close to the neck are short while the mature segments are broader than long. The eggs are globular and have thin outer vitelline membranes; 40-60µm separated from the inner which measures about 20-30µm.The latter is the embryophore and encloses the embryo which is ‘lemon’ shaped. On either end is polar thickening from which a few filaments extend.

LIFE CYCLE

Man is the definitive host. This is the only tapeworm known to have no intermediate host. The gravid segments are generally disrupted and eggs are passed in the faeces of the infected person. When ingested by man the onchosphere penetrates the small intestinal villi to form the cysticercoid stage. Within a short time (4 days) the cysticercoid re-enter the lumen and mature into adults. Autoinfection is possible.

PATHOGENESIS AND CLINICAL FEATURES

Mild infections are generally asymptomatic. But when large numbers of worms are found (>1000) enteritis with abdominal pain, diarrhea, nausea and vomiting may occur. These symptoms are probably due to the toxemia or allergic reactions to metabolic products of the worms.

EPIDEMIOLOGY

The infection is common in children than adults. The transmission is usually hand to mouth and via food and water. Infection is common in institutionalized children.

DIAGNOSIS

This is done by demonstrating characteristics eggs in the faeces.

PREVENTION AND CONTROL

Treatment of diagnosed cases and improvement of personal hygiene help to reduce the infection prevalence.

TREATMENT

Niclosamide is the drug of choice. The dose should be repeated after 10 days. Large number of persisting cysticercoids makes it difficult to obtain a radical cure. Other option is praziquantel, as it acts against both the adult worms and the cysticercoids in the intestinal villi.

CYSTICERCUS CELLULOSAE (Cysticercosis)

GEOGRAPHICA DISTRIBUTION

This is common where Taenia solium infection is prevalent especially south and Central America, South and east Africa, India and former Russian Federation countries.

LOCATION IN HOST

Cysticerci may be found in any organ or tissue of the body as they carried by the blood stream on hatching of the onchosphere in the small intestine. Common sites are the brain, skeletal muscles, heart and the eye.

MORPHOLOGY

Cysticercus cellulosae (commonly called ‘bladder worm’) are ovoid white and measure 8*5 mm and are easily visible to the naked eye. Each Cysticercus cellulosae consists of a fluid filled bladder with a small protoscolex invaginated into the lumen. The protoscolex has four suckers and two rows of hooks (Cysticercus bovis of Taenia saginata has no hooks).

TRANSMISSION

Accidental ingestion of Taenia solium eggs which are passed in infected person’s faeces may take place via contaminated green vegetables, fruits or drinking water. Since about 25% of patients with Cysticercosis also harbour adult Taenia solium in small intestine it is possible that autoinfection takes place following regurgitation of segments or eggs into stomach. The eggs need to pass through the stomach, as gastric acid is responsible for the dissolution of the thick wall of the eggs. Infection may take place from anus to fingers to mouth.

PATHOGENESIS

This is related to the organ affected. Generally the cysts are distributed throughout the body roughly in proportion to the weight of the organ. The living cysts cause only mild symptoms unless the path of CSF flow is blocked (cerebral infection). Severe pathology is seen following the death of the cysts due to inflammatory reactions. Allergic manifestations due to leakage of fluid also occur.

CLINICAL FEATURES

The clinical presentation of Cysticercosis depends on the number and location of cysticerci as well as the extent of associated inflammatory responses or scarring.

1. Cerebral Cysticercosis; minors symptoms related to the Central Nervous System are common but the most serious manifestations are epileptiform fits. These seizures may be generalized, focal, or Jacksonian. Hydrocephalus results from obstruction of cerebrospinal fluid (CSF) flow by cysticerci and accompanying inflammation or by CSF outflow obstruction from arachnoiditis. Signs of increased intracranial pressure, including headache, nausea, vomiting, changes in vision, dizziness, ataxia, or confusion, are often evident. Cysticerci in different part of the brain could give rise to motor, sensory and psychological symptoms. The cysticerci may get calcified.

2. Muscle Cysticercosis; this is common site. They could sometimes be felt as nodules. Muscle cysts are usually more elongate than others. These cysts get calcified earlier.

3. Ocular Cysticercosis; The cysts lodged in the eye cause pain and blurring of vision. With time and with encapsulation these cause severe damage to the eye.

4. Cardiac Cysticercosis; in the heart the cysts can be found in the epicardium, myocardium and endorcadium.

DIAGNOSIS

There are different types of diagnostic methods are available. The method which should be employed depends on the organ system which is suspected be affected. Radiological, histological and serological tests are useful.

1. Radiological: X-rays are useful to demonstrate calcified cysts in muscles. CT scan is important to detect the cerebral Cysticercosis.

2. Histological: Palpable cysts in the muscles can be identified by following biopsy.

3. Serological: Several specific serological tests, including PCR are now available.

PREVENTION AND CONTROL

This is same as for Taenia solium. Improvement of sanitary habits and environmental hygiene are important.

TREATMENT

There is no specific treatment. Various drugs such as albendazole and praziquantel have been used. However, praziquantel can evoke an inflammatory response in the central nervous system. Niclosamide (2 g) is also effective but is not widely available.

The management of neurocysticercosis focuses primarily on symptom-based treatment of seizures or hydrocephalus. Seizures can usually be controlled with antiepileptics. If parenchymal lesions resolve without development of calcifications and patients remain free of seizures, antiepileptic therapy can usually be discontinued after 2 years. High-dose Glucocorticoids can be used during treatment or if symptoms worsen. Since glucocorticoids induce first-pass metabolism of praziquantel and may decrease its antiparasitic effect, cimetidine should be coadministered to inhibit praziquantel metabolism.

For patients with hydrocephalus, the emergent reduction of intracranial pressure is the mainstay of therapy. In the case of obstructive hydrocephalus, the preferred approach is removal of the cysticercus via endoscopic surgery. However, this intervention is not always possible. An alternative approach is initially to perform a diverting procedure, such as ventriculoperitoneal shunting. Historically, shunts have usually failed, but low failure rates have recently been attained with treatment with antiparasitic drugs, chronic administration of glucocorticoids, or use of flow-sensitive shunts. Open craniotomy to remove the cysticerci is now required only infrequently. For patients with subarachnoid cysts or giant cysticerci, glucocorticoids are needed to reduce arachnoiditis and accompanying vasculitis.

HYMENOLEPIS DIMINUTA (The rat tapeworm)

GEOGRAPHICAL DISTRIBUTION

This is a common parasite rats and mice in many parts of the world. It is an occasional accidental parasite of humans, particularly children.

LOCATION IN HOST

The worm is found in upper part of the ileum. It may move up or down as it is known in rats.

MORPHOLOGY

The worm measures about 300-600 mm* 4 mm. It has about 800-1000 segments. The scolex is small (0.2-0.4 mm). It has a retractable rostellum but no hooks. Four small suckers are also present on the scolex. The mature segments is broader than length and measures 0.75*0.25 mm.

The eggs are ovoid (60-80 µm) and have thick yellowish outer shells and thin colourless inner membranes. The intermediate layer appears granular. The embryo has three pairs of hooklets.

LIFE CYCLE

The adult worm is in the small intestine of rat which is the definitive host. Larval rat fleas ingest the eggs passed in the rat faeces. The embryo grows into a cysticercoid larva (cysticercus like) in the flea. When humans accidentally ingest the rat flea the released cysticercoid larva matures into an adult worm. Four beetles may also act as intermediate hosts.

PATHOGENESIS

Multiple infections are not uncommon. The scolices may damage the mucosa leading to inflammation. Frequent movements of worm may also cause pathology. Metabolic products of the worm mar also cause different clinical manifestations.

CLINICAL FEATURES

Most of the time patients are asymptomatic. Some patients may experience abdominal pain. High degree of clinical suspicious is needed for the diagnosis.

DIAGNOSIS

Demonstration of the characteristics eggs in the stool is the most reliable method.

PREVENTION AND CONTROL

Improvement of personal and environmental sanitation is important. Elimination of household rats helps to reduce the disease.

TREATMENT

Identification of the infected persons is very important. There are few treatments methods available. Praziquantel and Niclosamide can be used as treatment.

DRACANCULUS MEDINENSIS (Dracanculosis/ dracunculiasis/guinea worm disease)

GEOGRAPHICAL DISTRIBUTION

The infection was, at one time, widely but patchily spread across tropical Africa, some parts of the Middle-east countries and India. The involved countries exerted a concerted effort in order to eradicate the infection by 1995. The program has been a success although sporadic cases still occur. The parasite also infects a wide range of animals particularly in North America. There are historical reports on the infection in South America.

MORPHOLOGY

It is a subcutaneous worm closely related to filarial worms. The female is long and appears as a long piece of twine (a piece of white coloured thread), about 60-100cm.The male is small and measures 2-3 cm.

LIFE CYCLE

The adult worms are found in humans (definitive host) while larval stages are found in the Cyclops (a water flea belongs to crustacean group) which is the intermediate host.

Male dies soon after fertilizing the female. The gravid female (uterus filled with larvae) migrates from its usual habitat in connective tissue (eg. Retro-periobital connective tissue) to areas of the skin which usually come in contact with water. As the head end approaches the surface of the skin, a blister develops. This causes intense burning pain. Infected persons tend to place their infected parts (eg. Foot) in water to get rid the pain. On contact with water the blister ruptures and the uterus of the worm protrudes through the ulcer. The contact with water is the stimulus for the uterus to discharge larvae into water.

The larvae (500-700µm) are swallowed by Cyclops. The larvae can live in clean water for about six days while it can last for nearly three weeks in muddy water. After two moults, the larvae develop into the infective stage inside the Cyclops (within2-4 weeks). When the infected Cyclops is ingested via drinking water the larvae penetrate the gut wall to reach suitable site. They become mature in about a year’s time.

Life cycle

PATHOGENESIS AND CLINICAL FEATURES

The adult worms living in the connective tissue of limbs and trunk cause minimal reactions. The blisters formed by migrating gravid females are commonly seen on the feet. They may appear around the knee joint in some and rarely around the scrotal area. In water carriers the blister may appear on the shoulder. A major pathology is seen after the worm dies when a sterile abscess is formed. Secondary infection often leads to inflammation and debility. The blister causes intense burning pain. Patients may experience itching, rash, nausea and vomiting with the appearance of blisters.

Few or no clinical manifestations of dracunculiasis are evident until just before the blister forms, when there is an onset of fever and generalized allergic symptoms, including periorbital edema, wheezing, and urticaria.

a ruptured blister

COMPLICATIONS

Complications include abscesses following secondary infection, arthritis, synovitis and abdominal symptoms due to adult worms migrating to the peritoneal cavity.

DIAGNOSIS

In endemic areas the clinical features are well known. Traditional way of diagnose this condition is by placing a drop of water on the blister or ulcer. This drop of water becomes cloudy due to the extrusion of larvae by the gravid female. A smear made on a slide will show the rapidly moving larvae.

EPIDEMIOLOGY

Although many animals are infected, the human infection is not considered a zoonosis as humans are the main reservoirs of the infection. Cyclops is a crustacean usually found in fresh water and some times in water storage tanks. Infected persons introduce larvae to water when the affected part of the body is immersed in water. Step wells played a major role in the transmission of the infection India.

PREVENTION AND CONTROL

The infection could easily be eradicated by improving drinking water supplies so that dependence on surface is removed. Boiling, filtering and chlorination of drinking water will remove Cyclops if they present in water. The insecticide ‘Temephos’ is an organophosphorus compound that is harmless to man that can be added to wells and storage tanks as slow release granules.

TREATMENT

The removal of the worm quickly is nit possible without chemotherapeutic support. The traditional way is to tie the anterior end of the worm to a stick or a matchstick and roll the worm out gradually over period of several days or weeks. Drugs such as Tinidazole, metronidazole and thiabendazole help with smooth extraction of the worm.

removing of an adult worm

TAENIA SOLIUM (Pork tapeworm)

GEOGRAPHICAL DISTRIBUTION

The infection is prevalent in places where pork or pork products are eaten raw or under-cooked. It is common in East Europe, South and Central America, South Africa, China, India, Korea and Indonesia.

LOCATION IN HOST

The scolex is attached to the mucosa of the jejunum with the rest of the strobila in the intestinal lumen.

MORPHOLOGY

The scolex has a rostellum with two rows of hooks. The segments are similar to those of Taenia saginata. Mature segments are roughly square in shape. Gravid segments have less than 13 primary uterine branches as oppose to the Taenia saginata, which the number of uterine segments are more than 13.

LIFE CYCLE

Man is the only definitive host whereas pig is the only intermediate host. Life cycle is similar to that of Taenia saginata. The larval stage in the pig muscle is called Cysticercus cellulosae. Human infection occurs when pork containing Cysticercus cellulosae is eaten raw or under-cooked.

CLINICAL FEATURES

Clinical features are similar to those of Taenia saginata. Often the infection is asymptomatic except noticing whitish segments in faeces or experience of segments actively moving out of the anus. Vague abdominal symptoms such as pain, nausea, weight loss and anorexia may be present. In some the symptoms are relieved by ingestion of food.

COMPLICATIONS

Unlike in Taenia saginata, if an individual ingests eggs (usually accidentally) life cycle will continue as in the intermediate host, pig. Therefore humans can develop Cysticercosis, a complication due to the presence of pork worm larvae (Cysticercus cellulosae) in the skeletal muscles.

DIAGNOSIS

This is also similar to that of Taenia saginata.

1. The gravid segments passed in the faeces could be injected with Indian ink to show the lateral uterine branches of the uterus. In Taenia solium there are less than 13 primary branches of the uterus (compare with Taenia saginata).

2. If the scolex is passed following treatment, presence of hooks distinguishes it from Taenia saginata

3. If the gravid segments are ruptured eggs may be found in faeces (taenid egg).

EPIDEMIOLOGY

Prevalence of the infection is lower than that of beef tape worm infection. This is because some communities do not eat pork and in others when pork is eaten it is usually well cooked. While Taenia saginata infection occurs both in highly develop and developing countries, Taenia solium infection and its major complication, Cysticercosis, are prevalent in poor communities in which people live in close contact with pigs and eat improperly cooked pork. Uncooked or partially cooked pork products can transmit the infection.

PREVENTION AND CONTROL

Thorough cooking of pork is very important. Heating meat to 50ºC kills the cysticerci but those in the inside of large pieces may not reach the require temperature. At 0ºC the cysticerci can live for 70 days. Freezing at -10ºC for 4 days kills the cysticerci.

TREATMENT

A single dose of praziquantel (10 mg/kg) is highly effective. Niclosamide can also be given. The dose is 2gm for adults and lower doses for the children. The tablets are chewed and washed down with a little water.

TAENIA SAGINATA (Beef tapeworm)

GEOGRAPHICAL DISTRIBUTION

Infection is common in countries where beef is often eaten raw or under-cooked such as African countries, Brazil, Argentina, USA, former Russian federation countries and Europe.

LOCATION IN HOST

The worm is found attached to the mucosa of the small intestine (ileum) with its scolex. The rest of the worm is free in the lumen of the intestine.

MORPHOLOGY

They are flat, ribbon-like worms. Their bodies are formed of chains of segments (proglottids) of varying sizes and shapes. At the anterior end is the scolex or the ‘holdfast’ organ which is used for the attachment of the worm to the intestinal mucosa.

The scolex is 1-2mm and is pear shaped. There are four suckers on the scolex but no rostellum or hooks. The fully grown worm is exceptionally long, sometimes reaching 20 meters. Usually it measure about 5 meters and has about 1000-2000 segments. The mature segments measure approximately 12 mm wide and 10 mm long. In the mature segments both male and female reproductive organs are found. On the lateral margin are the genital pores, one on each segment. In gravid segments (the last segments of the strobila) the uterus occupies the whole space with primary and secondary uterine branches (twenty uterine branches at one side).

LIFE CYCLE

Humans are the only definitive host of the parasite and cattle are the only intermediate host.

The gravid segments are dislodged and are passed in the faeces of the infected person. The detached gravid segments also have their inherent movement and may actively move down the lumen and out of the anus and sometimes along the thighs.

When the segments are deposited on the ground the eggs are scattered on the soil. Eggs deposited on vegetation can live for months to years until they are ingested by cattle.

Eggs measure 30-45 µm. Each egg has an outer vitelline membrane which is usually lost in the faeces. The inner, thick wall is made up of keratin blocks and appears striated. This is called the embryaosphore. Inside is the embryo and now it is called the onchosphere. It has six embryonic hooklets and because of this it is also known as the hexacanth larva.

The egg when ingested by cattle, the onchosphere hatches out in the duodenum. With the help of the hooklets it penetrates the intestinal mucosa and enters the venous capillaries (or mesenteric lymphatics) within half an hour. Then they reach skeletal muscles. There they lose their hooklets and grow into infective cysticercus bovis larva in about 10-12 weeks. The infective cysticercus bovis is ovoid, white in colour and measures 8*5 mm. It has an invaginated scolex and four suckers but no hooks. Humans acquire the infection when infected beef containing cysticercus bovis is eaten raw or under-cooked.

PATHOGENESIS AND PATHOLOGY

The scolex does not cause much damage to the mucosa. Sometimes inflammation may be present. Several cases of intestinal obstruction and perforation have been reported. The symptoms are often due to metabolic products of the worm.

CLINICAL FEATURES

Often the infection is asymptomatic except noticing whitish segments in faeces or experience of segments actively moving out of the anus. Vague abdominal symptoms such as pain, nausea, weight loss and anorexia may be present. In some the symptoms are relieved by ingestion of food.

DIAGNOSIS

The diagnosis is made by the detection of eggs or proglottids in the stool. Eggs may also be present in the perianal area.

1. The gravid segments passed in the faeces could be injected with Indian ink to show the lateral uterine branches of the uterus. In Taenia saginata there are more than 13 primary branches of the uterus(compare with Taenia solium).

2. If the scolex is passed following treatment, the absence of hooks distinguishes it from the Taenia solium.
   

3. If the gravid segments are ruptured eggs may be found in faeces (taenid egg).

EPIDEMIOLOGY

This is common infection where beef consumption is high. Infection often occurs when cattle are young. Faeces containing eggs pollute pastures. The role of birds transmitting eggs from sewage to pastures is also possible.

PREVENTION AND CONTROL

Meat infection is the important public health measure. Cycticerci in muscle are usually killed when frozen at minus 10ºC for 10 days or heating thoroughly above 56ºC is also effective.

TREATMENT

A single dose of praziquantel (10 mg/kg) is highly effective. Niclosamide can also be given. The dose is 2gm for adults and lower doses for the children. The tablets are chewed and washed down with a little water.