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ن م ح ر ل ه ا ل ل م ا س ب م ی ح ر ل ا

بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

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Page 1: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

الله بسمالرحیم الرحمن

Page 2: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

parasitologyparasitology

• Medical Parasites:

• - Protozoa 1- Platyhelminthes

• - Helminthes: 2- Nemathelminthes

• - Arthropoda 3- Nematomorpha

• 4- Acanthocephala• 5- Annelida

Page 3: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Classification of Helminthes Classification of Helminthes According to transmission methodsAccording to transmission methods

• 1- Soil transmitted Helminthes : Ascaris, Hook worms

• 2- Snail t. H. : Trematoda ( Schistosoma,….)

• 3- Arthropods t. H. : Fillaria, Dracanculus medinensis

• 4- Food and Meat t. H. : Taenia saginata, Taenia solium

• 5- Direct t. H. ( contagious H.): Enterobius vermicularis,…

Page 4: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Platyhelminthes:Platyhelminthes:

- Eucestoda- Eucestoda

1- Cestoda( Tape-worms): 1- Cestoda( Tape-worms):

2- Trematoda2- Trematoda - Cestodaria- Cestodaria

Eucestoda: Eucestoda: ( Human Parasites);( Human Parasites);

Order: Order: - Cyclophyllidea: - Cyclophyllidea: Taenia spp. , EchinococcusTaenia spp. , Echinococcus

- Pseudophyllidea: - Pseudophyllidea: Diphyllobothrium latumDiphyllobothrium latum

-…………………-………………… -…………………-…………………

Page 5: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Human pathogen CestodsHuman pathogen Cestods

• A- Ault forms of Cestoda( Definitive host): Taenia spp.

• B- Larva stage of Cestoda( intermediate host): E. granulosus

• General characters of Cestoda: 1- an anterior attachment organ( scolex);

- sucker( bothria, bothridia) - rostellum

Cestode body : 2- neck region

3- a chain of segments( strobila): - Immature proglottids - Mature p.

- Gravid p.

Page 6: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Different Tracts of CestodaDifferent Tracts of Cestoda

• Digestive system; tegument play role of absorption tract

• Reproduction system : • all tapeworms of man are hermaphroditic*male and female organs are found in mature proglottids.

Page 7: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Diphyllobothrium latumDiphyllobothrium latum

Causal Agents:The cestode Diphyllobothrium latum (the fish or broad tapeworm), the largest human tapeworm. 

Several other Diphyllobothrium species have been reported to infect humans, but less frequently; they include D. pacificum, D. cordatum, D. ursi, ….

Page 8: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Section of an adult Section of an adult D. latumD. latum containing many containing many

proglottids proglottids

Scolex of D. latum

Page 9: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Proglottids of Proglottids of DD. . latumlatum

Page 10: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Geographic DistributionGeographic Distribution

• :Diphyllobothriasis occurs in the Northern Hemisphere (Europe, newly independent states of the former Soviet Union [NIS], North America, Asia) and in Uganda and Chile. 

• Freshwater fish infected with Diphyllobothrium sp. larva may be transported to and consumed in geographic areas where active transmission does not occur, resulting in human diphyllobothriasis.  For example, cases of D. latum infection associated with consumption of imported fish have been reported in Brazil.

Page 11: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Diphyllobothriosis

Page 12: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Clinical FeaturesClinical Features

Diphyllobothriasis can be a long-lasting infection (decades). 

Most infections are asymptomatic.  Manifestations may include abdominal discomfort,

diarrhea, vomiting, and weight loss.  Vitamin B12 deficiency with pernicious anemia may

occur.  Massive infections may result in intestinal obstruction. 

Migration of proglottids can cause cholecystitis or cholangitis.

Page 13: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Laboratory DiagnosisLaboratory Diagnosis

• Microscopic identification of eggs in the stool is the basis of specific diagnosis. 

•   Examination of proglottids passed in the stool is also of diagnostic value.

Page 14: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Diagnostic findingsDiagnostic findingsMicroscopyMicroscopy

Page 15: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

                                          

        

                                          

        C D

Page 16: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

CarmineCarmine--stained proglottids of stained proglottids of D. D. latumlatum, showing the rosette-shaped , showing the rosette-shaped

ovaries ovaries

                                          

        

                                          

        G H

Page 17: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-
Page 18: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Taenia saginataTaenia saginata( beef tapeworm)( beef tapeworm)

• Geographical distribution- infection is cosmopolitan

- Location in host: - ileum of small intestine

- Morphology:- Scolex is pear-shaped with 4 prominent round sucker without rostellum

- Size of worm is very long( usually about 5 meters, sometimes exceeding 20 meters)

- Posses 1000-2000 proglottids.

- Mature proglottid measures about 12mm wide and 10mm long.

Page 19: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

T. Saginata adult wormT. Saginata adult worm

                                     

    

                                        

    K L

Page 20: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Taenia saginataTaenia saginata (Scolex and segments) (Scolex and segments)

Page 21: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Taenia soliumTaenia solium( pork tapeworm)( pork tapeworm)

• Geographical distribution- infection is cosmopolitan in countries where pork is eaten raw or

undercooked.

- Location in host: - The scolex is embedded in the mucosa of the jejunum with the rest of the

tape extending through the ileum.

- Morphology:- Scolex is soliel-shaped with 4 large suckers and a conspicuous rostellum

with 2 rows of alternating large and small hooks(25-30 hooks). - Size of worm is long( 2-10 meters in length), with usually around 1000

proglottids. - Mature proglottids are roughly square (12 x 10 mm ).

Page 22: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Scoleces of Scoleces of Taenia saginataTaenia saginata and and Taenia soliumTaenia solium

                             

 

                             

 

                             

 

I J

Page 23: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Gravid proglottids of Gravid proglottids of Taenia saginataTaenia saginata (Figures (Figures DD and and

EE) and ) and Taenia soliumTaenia solium (Figures (Figures FF and and GG))

                                         

    

                          

    D E

D E

F G

Page 24: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Life cycle of TaeniaLife cycle of Taenia

Page 25: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Life cycle of T. soliumLife cycle of T. solium

Page 26: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-
Page 27: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Clinical ManifestationClinical Manifestationdue to adult wormdue to adult worm

• Often the first and only sign of infection:• - Presence of active proglottids in the feces• - feeling of them crawling out through the anus.

• there may be umbilical pain, nausea, weakness, loss of weight, alteration of appetite and headache (possibly caused by toxic products or are allergic reaction) .

• Generalized allergic manifestations, such as urticaria with pruritis ani or widespread pruritis, result.

Page 28: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

PathogenesisPathogenesis

• Physical action of the scolex on the mucosa

• Inflamation of the mucosa in the ileum sometimes occurs.

• Intestinal obstruction, perforation or appendicitis have been reported.

Page 29: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

CysticercosisCysticercosis( infection with the C. cellulosae( infection with the C. cellulosae))

• Cerebral Cysticercosis:*epilepsiform attacks, headache, visual and aural symptoms and ...

*Muscular Cysticercosis

Ocular Cysticercosis

Subcutaneous Cysticercosis

Page 30: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Cysticercus bovisCysticercus bovis

Page 31: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

cysticercus

Subcutaneous cysticercosis

Page 32: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

• Cerebral cysticercosis Muscular cysticercosis

Page 33: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Subcutaneous nodulesSubcutaneous nodules

Page 34: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Laboratory diagnosiosLaboratory diagnosios

• Microscopic identification :

• Detect of eggs and proglottids in feces is diagnostic for taeniasis,( but is not possible during the first 3 months following infection, prior to development of adult tapeworms).

• Microscopic identification of gravid proglottids (or, more rarely, examination of the scolex) allows species determination.

Page 35: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

MicroscopyMicroscopy FindingsFindings

A, B: Taeniid eggs.  The eggs of Taenia saginata and Taenia solium are indistinguishable morphologically. The eggs are rounded, diameter 31 to 43 µm, with a thick radially striated brown shell.  Inside each shell is an embryonated oncosphere with 6 hooks. 

A B

Page 36: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

TreatmentTreatment

• Niclosamide ( Yomesan); are given in a single dose,2 g for adults, 1.5 g for children weighing over 34 kg and 1 g for those weighing 11-34 kg .

• Praziquntel administered in a single dose of 10 mg/kg body weight.

Page 37: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Prevention and controlPrevention and control

• Meat inspection ( include the heart, shoulder muscle, tungue and …)

• Freezing meat at -15ºС for 3 days 0r by heating thoroughly 56ºС.

• Treatment of patients.

Page 38: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Hymenolepis nanaHymenolepis nana (the dwarf tapeworm) (the dwarf tapeworm)

• Geographical distribution

• Location in host: • the adults are found in the lumen of the upper three-quarters of the ileum.• Morphology:• It is a very short tapeworm, measuring 15-40 mm and has approximately

200 proglottids.• Scolex :• retractible rostellum with a single row of 20-30 small hooks and 4 suckers.

• Neck is long and slender.

• Mature proglottids are broader than long with a single common genital pore on one side of strobila.

Page 39: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

H. nana( adult worm)H. nana( adult worm)

Page 40: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Life cycle of Hymenolepis

Page 41: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Mature proglottids, Cysticercoid and eggMature proglottids, Cysticercoid and egg of of H. nanaH. nana

Page 42: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Clinical Manifestations and Clinical Manifestations and PathogenesisPathogenesis

•Hymenolepis nana infections are most often asymptomatic.

•   Heavy infections with H. nana( more than 2000 worms) can cause weakness, loss of appetite, vomiting, headaches, anorexia, abdominal pain, and diarrhea.

• Eosinophilia of up to 15% occurs in about 7% of infected persons.

• Necrosis of the mucosa has been found in rats but has not been proved to occur in man.

Page 43: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-
Page 44: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-
Page 45: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Hymenolepis diminutaHymenolepis diminuta life cycle life cycle

Page 46: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Laboratory DiagnosisLaboratory DiagnosisEggs of Eggs of Hymenolepis nanaHymenolepis nana

                         

    A B

Page 47: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Eggs of Eggs of Hymenolepis diminutaHymenolepis diminuta

                                     

        

                                     

        A B

Page 48: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

TreatmentTreatment

Praziquantel* is the drug of choice( given in a single oral dose of 25 mg/kg body weight).

Niclosamide must be given daily for 5 days

Page 49: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-
Page 50: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

• Dipylidium caninum (the double-pored dog tapeworm) mainly infects dogs and cats, but is occasionally found in humans.

Page 51: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-
Page 52: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-
Page 53: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Adult tapeworm of Adult tapeworm of Dipylidium caninumDipylidium caninum

adults measure 10-70 cm long adults measure 10-70 cm long

Page 54: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Life Life CycleCycle

Page 55: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Dipylidium CaninumDipylidium Caninum

Page 56: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

TrichodectesTrichodectes

Intermediate host of Dipylidium caninumIntermediate host of Dipylidium caninum

Page 57: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Geographic DistributionGeographic Distribution

Worldwide.  Human infections have been reported in Europe, the Philippines, China, Japan, Argentina, and the United States.

Page 58: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Clinical FeaturesClinical Features

Most infections with Dipylidium caninum are asymptomatic.  Pets may exhibit behavior to relieve anal pruritis (such as

scraping anal region across grass or carpeting).  Mild gastrointestinal disturbances, and the passage of

proglottids. 

These can be found in the perianal region, in the feces, on diapers, and occasionally on floor covering and furniture. 

The proglottids are motile when freshly passed and may be mistaken for maggots or fly larvae.

Page 59: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

Laboratory DiagnosisLaboratory Diagnosis

• The diagnosis is made by demonstrating the typical proglottids or egg packets in the stool or the environment.

• Diagnostic findings:

• Microscopy

• Macroscopy

Page 60: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

CC:: D. caninumD. caninum proglottid under a dissecting proglottid under a dissecting microscope cleared with lactophenol.microscope cleared with lactophenol.D:D: D. caninumD. caninum proglottid partially cleared with proglottid partially cleared with

lactophenol, showing eggs and egg packetslactophenol, showing eggs and egg packets..

                                                                                           

C D

Page 61: بسم الله الرحمن الرحیم. parasitology Medical Parasites : - Protozoa 1- Platyhelminthes - Helminthes: 2- Nemathelminthes - Arthropoda 3- Nematomorpha 4-

MicroscopyMicroscopyEggsEggsAA:: D. caninumD. caninum egg packet, containing 8 visible eggs egg packet, containing 8 visible eggsB:B: D. caninumD. caninum eggs clumped together eggs clumped together

                                     

        

                                     

        A B

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TreatmentTreatment

• Treatment for both animals and humans is simple and very effective.

•   Praziquantel is given either orally or by injection (pets only). 

• The medication causes the tapeworm to dissolve within the intestines.  Since the worm is usually digested before it passes, it may not be visible in the dog's stool.  These drugs are generally well tolerated.