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Author(s): Vernon Carruthers, Ph.D., Cary Engleberg, M.D., D.T.M.&H., 2009 License: Unless otherwise noted, this material is made available under the terms of the Creative Commons Attribution 3.0 License: http://creativecommons.org/licenses/by/3.0/

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Helmintic Infections

M1 Infectious Diseases Sequence Vernon Carruthers

Cary Engleberg

Spring 2009

Infection vs. disease

• successful parasites live in, but do not kill their hosts

• protozoa multiply within hosts expression of disease depends on host

factors • helminths do not multiply within hosts

severity of disease depends on parasite burden and immunologic response to parasites

3

Helminth forms

Egg

Cyst

Larva

Adults 4

C. Engleberg/V. Carruthers

Helminth modes of entry

• Ingestion (eggs or cysts) • Arthropod bites (larvae) • Penetration of intact skin or

mucous membranes (larvae)

5

Spread and tropisms

• Some parasites must migrate to certain locations within the host in order to complete their life cycle

• Non-human parasites, in humans, often fail to migrate properly and become “dead-end infections”

6

7

Cary Engleberg

Mechanisms for evading the host response

• antigenic variation - trypanosomes, malaria, giardia

•  intracellular infection - malaria, toxoplasma • encystation* - Toxoplasma, cestodes • camouflage - schistosomes • cleavage of ABs or C’ components - amoebae,

leishmania • suppression/redirection of the cellular immune

response - malaria, leishmania, schistosomes

* “cyst” has multiple meanings 8

Tissue damage and host response

• direct destruction of tissue • hypersensitivity reactions • eosinophila

– occurs with helminths, not protozoa – results from tissue migration

9

Classification of helminths

Nematodes (roundworms)

Platyhelminthes (flatworms)

Trematodes (“flukes”)

Cestodes (“tapeworms”)

10 C. Engleberg/V. Carruthers

Helmintic diseases • Intestinal

– Others – Strongyloides

• Invasive – Trichinosis – Filaria – Schistosomiasis

– Cysticercosis – Echinococcus

(autoinfection cycle)

(muscle pain, uncooked carnivores) (worms in lymphatics or under skin)

(liver or urinary tract granulomas and fibrosis)

(cysts in brain, seizures) (massive cysts in liver or lung)

roundworms

flukes

tapeworms

11

Intestinal nematodes

Larvae pass through lungs

Larvae penetrate through intact skin

strongyloides hookworm

Eggs ingested

Trichiuris (whipworm) Enterobius (pinworm)

Larvae enter bloodstream

ascaris

Adult worms in the the intestine

Eggs

Larvae hatch from eggs


Strongyloides life cycle Adult worms in the the intestine

Eggs

1st stage larvae hatch from eggs

Larvae penetrate through intact skin

Larvae enter bloodstream

Larvae pass through lungs

Larvae molt twice to form filariform larvae (infectious)

Autoinfection


14

Source Undetermined

Strongyloides - clinical features

• uncomplicated – GI upset

• autoinfection • hyperinfection

– rash – bronchspasm, chest X-ray infiltrates – diarrhea – profound eosinophilia – recurrent Gram-negative bacteremia

15

Trichinosis

16

Trichinella spiralis - life cycle

• “cycle of carnivorism” among hogs and rats • humans ingest encysted larvae in infected,

undercooked pork • larvae exist in stomach and burrow into small

intestinal mucosa • adult males and female reemerge and produce

larvae which penetrate intestine and circulate in bloodstream

• larvae enter skeletal muscle cells and encyst

17

18

Source Undetermined Source Undetermined

Trichinosis cases, by source of infection, U.S.,1981

Pork products sausage 93 other 44 unspecified 9

Non-pork products hamburger 18 bear 10 other wild animals 7

Unknown 7 188 19

Clinical features of trichinosis

• Most common sxs: – muscle pain and tenderness – fever +/- chills – edema (often periorbital)

• >10% eosinophilia (often ~50%) • elevated creatine phosphokinase (CPK) • +/- chronic neurologic/myocardial sxs • self-limited (2% mortality)

20

Treatment of trichinosis

• antihelmintic (albendazole) to kill any intestinal adults

• steroids to relieve inflammatory reactions

• antipyretics

21

Filaria

22

Life cycles of two types of filaria

Arthropod vector

Adult worm pairs

Larvae (microfilariae)

Lymph- mosquitoes peripheral circulate dwelling lymphatics in bloodstream (e.g, Wuchereria bancroftii )

Skin- biting flies skin nodules migrate through dwelling or migratory dermis

23

Microfiliaria found in the blood of lymph dwelling species

24

Armed Forces Institute of Pathology

Long-term consequences of persistent lymph-dwelling filarial infection: Blockage of lymph drainage with chronic lymphedema (elephantiasis)

25 Source Undetermined

Life cycles of two types of filaria

Arthropod vector

Adult worm pairs

Larvae (microfilariae)

Skin- biting flies skin nodules migrate through dwelling or migratory dermis (e.g., Onchocerca volvulus & Loa loa )

Lymph- mosquitoes peripheral circulate dwelling lymphatics in bloodstream (e.g, Wuchereria bancroftii )

27

Black fly: vector of Onchocerciasis

28

Source Undetermined

Snip site

O. volvulus microfilaria (a skin-dwelling species) in skin snip

Depigmentation due to chronic microfilarial production, degradation, and allergic host responses in the skin

29 Cary Engleberg

Source Undetermined

30

Cary Engleberg

O. volvulus skin nodule removed and sectioned, showing cross-sections of male and female

adult worms (source of microfiliariae) 31

Source Undetermined

Onchocerciasis (”River blindness”) 32

Source Undetermined

Role of endosymbiont Wohlbachia sp. in filiaria infection

• Rickettsia-like organisms required for fecundity and viability of filaria

• Wohlbachia-free worms produce less inflammation in tissue (? LPS)

• Implications for rx: – ivermectin kills microfilaria only – tetracycline may destroy adult worms

33

Schistosomiasis

34

Geographic distribution of schistosomiasis

S. mansoni

S. hematobium

S. japonicum 35

Cary Engleberg

Schistosomiasis - life cycle

S.m. S.h. S.j.

Eggs Cercaria

36 Cary Engleberg (All other images)

(snail) Pearson Scott Foresman, wikimedia commons

S. mansoni S. haematobium S. japonicum

37

Source Undetermined Source Undetermined Source Undetermined

38

Source Undetermined

Events following cercarial penetration 1.  Larva migrate to lungs and develop as “schistosomulae” (this may trigger a self-limited febrile illness).

2.  Male and female schistomulae migrate to the abdominal venules: I.  Superior mesenteric (S. japonicum) II.  Inferior mesenteric (S. mansoni) III.  Bladder plexus (S. hematobium)

3.  Males and females pair off and egg production begins

4.  Eggs migrate out of the body through visceral organs or become trapped and die in tissues.

39

Immune response to schistosoma infection


41

Source Undetermined

42

Source Undetermined

43

Source Undetermined

44

Source Undetermined

45

Source Undetermined

“pipestem” fibrosis 46

Source Undetermined

47

Source Undetermined

Schistosomiasis - pathogenesis

• egg granuloma (type IV reaction)--> fibrosis • morbidity ~ worm (egg) burden • concomitant immunity to schistosomula • adult worms: invisible to the immune

system (survive for years)

48

Schistosomiasis- clinical features

• Cercarial dermatitis • Intestinal schistosomiasis (granulomas -->

polyps, protein loss, malabsorption, strictures) • Hepatosplenic schistosomiasis (portal

hypertension --> ascites, varices, splenomegaly, normal hepatic function)

• Urinary schistosomiasis (hematuria, chronic infection, obstruction)

• Other (cardiopulmonary, CNS, etc.)

49

Drug treatment of schistosomiasis

• Praziquantel increases permeability of adult parasite to Ca++.

• Tetanospasm --> death

50

Cestode infections

51

Tapeworms

• Definitive hosts: harbor adult worms • Intermediate hosts: harbor tissue cysts

(containing worm heads) • Humans acquire infection two ways:

– ingestion of eggs from feces (to acquire tissue cysts)

– ingestion of tissue cysts in undercooked meat (to acquire a tapeworm)

= Intermediate host = Definitive host

52

Taeniasis

Tapeworm Cysticercosis

poor hygiene

poor sanitation

ingestion of undercooked pork

53 Cary Engleberg (All other images) (pig) Martin von Nathusius, wikimedia commons

54

Source Undetermined

56

Source Undetermined

57

Source Undetermined

Cysticerci Hydatid Cyst


Isolated cysticerci Hydatid cyst

59

Source Undetermined Source Undetermined

60

Source Undetermined

Duane Newton

Echinococcosis

Cystic Hydatid Disease

contact with dogs

ingestion of entrails

ingestion of eggs in pastures

61 Cary Engleberg (All other images) (sheep) wikimedia commons (dog) Abujoy, wikimedia commons

62 Cary Engleberg

Treatment of cysticercosis and echinococcosis

• Antihelminthic therapy (e.g., albendazole, praziquantel)

• (Echinococcus only) – Surgical removal – Irrigation-evacuation of cysts

63

Comparison of pork tapeworm and Echinococcus life cycles

Definitive hosts (adult tapeworms)

Intermediate hosts (tissue cysts)

Dead-end hosts

Dog

Sheep

Human

Pig

Human

Human


Cary Engleberg and Vernon Carruthers Slide 8: Cary Engleberg Slide 11: Cary Engleberg and Vernon Carruthers Slide 13: Cary Engleberg and Vernon Carruthers Slide 14: Cary Engleberg and Vernon Carruthers Slide 15: Source Undetermined Slide 19: Sources Undetermined Slide 25: Armed Forces Institute of Pathology, http://www.afip.org/index.html Slide 26: Source Undetermined Slide 27: Source Undetermined Slide 29: Source Undetermined Slide 30: Cary Engleberg (left) Sources Undetermined (right) Slide 31: Cary Engleberg Slide 32: Source Undetermined Slide 33: Source Undetermined Slide 36: Cary Engleberg Slide 37: (snail) Pearson Scott Foresman, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Snail_(PSF).png; Cary Engleberg All other images) Slide 38: Sources Undetermined Slide 39: Source Undetermined Slide 41: Source Undetermined Slide 42: Source Undetermined Slide 43: Source Undetermined Slide 44: Source Undetermined Slide 45: Source Undetermined Slide 46: Source Undetermined Slide 47: Source Undetermined Slide 48: Source Undetermined Slide 54: (pig) Martin von Nathusius, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Cochon.svg; Cary Engleberg (All other images) Slide 55: Source Undetermined Slide 56: Source Undetermined Slide 57: Source Undetermined Slide 58: Source Undetermined Slide 59: Cary Engleberg and Vernon Carruthers Slide 60: Sources Undetermined Slide 61: Duane Newton, University fo Michigan Slide 62: (dog) Abujoy, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Dog_silhouette.svg, CC:BY-SA,

http://creativecommons.org/licenses/by-sa/2.5/deed.en ; (sheep) Wikimedia Commons, http://commons.wikimedia.org/wiki/File:LA2-Blitz-Ostfriesisches_Milchschaf.png ; Cary Engleberg (All other images)

Slide 63: Cary Engleberg Slide 65: Cary Engleberg and Vernon Carruthers

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