Transcript 043009.Engleberg-Carruthers.Helminths

Author(s): Vernon Carruthers, Ph.D., Cary Engleberg, M.D., D.T.M.&H., 2009
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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
Larva
Egg
Cyst
Adults
C. Engleberg/V. Carruthers
4
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
Cary Engleberg
7
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”)
C. Engleberg/V. Carruthers
10
Helmintic diseases
• Intestinal
–Others
–Strongyloides
roundworms
flukes
• Invasive
(autoinfection cycle)
–Trichinosis (muscle pain, uncooked carnivores)
–Filaria (worms in lymphatics or under skin)
–Schistosomiasis (liver or urinary tract
granulomas and fibrosis)
tapeworms
–Cysticercosis (cysts in brain, seizures)
–Echinococcus (massive cysts in liver or lung)
11
Intestinal nematodes
Adult worms in the
the intestine
Larvae pass
through lungs
Trichiuris (whipworm)
Enterobius (pinworm)
Larvae enter
bloodstream
Eggs
Eggs ingested
ascaris
Larvae penetrate
through intact skin
C. Engleberg/V. Carruthers
strongyloides
hookworm
Larvae hatch
from eggs
12
Strongyloides life cycle
Adult worms in the
the intestine
Larvae pass
through lungs
Larvae enter
bloodstream
Autoinfection
Larvae penetrate
through intact skin
C. Engleberg/V. Carruthers
Larvae molt
twice to form
filariform larvae
(infectious)
Eggs
1st stage
larvae hatch
from eggs
13
Source Undetermined
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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
Source Undetermined
Source Undetermined
18
Trichinosis cases, by source of
infection, U.S.,1981
Pork products
sausage
other
unspecified
93
44
9
Non-pork products
hamburger
bear
other wild animals
Unknown
18
10
7
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
Lymphdwelling
Arthropod
vector
Adult
worm pairs
Larvae
(microfilariae)
mosquitoes
peripheral
lymphatics
circulate
in bloodstream
biting flies
skin nodules
or migratory
migrate through
dermis
(e.g, Wuchereria
bancroftii )
Skindwelling
23
Microfiliaria found in the blood of
lymph dwelling species
Armed Forces Institute of Pathology
24
Long-term
consequences of
persistent lymphdwelling filarial
infection:
Blockage of lymph
drainage with
chronic lymphedema
(elephantiasis)
Source Undetermined
25
Source Undetermined
26
Life cycles of two types of
filaria
Lymphdwelling
Arthropod
vector
Adult
worm pairs
Larvae
(microfilariae)
mosquitoes
peripheral
lymphatics
circulate
in bloodstream
biting flies
skin nodules
or migratory
migrate through
dermis
(e.g, Wuchereria
bancroftii )
Skindwelling
(e.g., Onchocerca
volvulus &
Loa loa )
27
Source Undetermined
Black fly: vector of Onchocerciasis
28
O. volvulus microfilaria (a skindwelling species) in skin snip
Snip site
Source Undetermined
Depigmentation due to chronic
microfilarial production, degradation,
and allergic host responses in the skin
Cary Engleberg
29
Cary Engleberg
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Source Undetermined
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
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
Eggs
Cercaria
S.m. S.h. S.j.
(snail) Pearson Scott Foresman, wikimedia commons
Cary Engleberg (All other images)
36
Source Undetermined
S. mansoni
Source Undetermined
S. haematobium
Source Undetermined
S. japonicum
37
Source Undetermined
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Events following cercarial penetration
1. Larva migrate to lungs and develop as
“schistosomulae” (this may trigger a selflimited 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
Source Undetermined
40
Source Undetermined
41
Source Undetermined
42
Source Undetermined
43
Source Undetermined
44
Source Undetermined
45
Source Undetermined
“pipestem” fibrosis
46
Source Undetermined
47
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) = Intermediate host
–ingestion of tissue cysts in undercooked
meat (to acquire a tapeworm) = Definitive host
52
Taeniasis
poor
sanitation
ingestion of
undercooked pork
poor
hygiene
Tapeworm
(pig) Martin von Nathusius, wikimedia commons
Cary Engleberg (All other images)
Cysticercosis
53
Source Undetermined
54
Source Undetermined
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Source Undetermined
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Source Undetermined
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Cysticerci
C. Engleberg/V. Carruthers
Hydatid Cyst
58
Isolated cysticerci
Hydatid cyst
Source Undetermined
Source Undetermined
59
Source Undetermined
Duane Newton
60
Echinococcosis
ingestion of
eggs in
pastures
ingestion of
entrails
contact
with
dogs
(dog) Abujoy, wikimedia commons
(sheep) wikimedia commons
Cary Engleberg (All other images)
Cystic Hydatid Disease
61
Cary Engleberg
62
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)
Dog
Human
Dead-end
hosts
Human
Human
Intermediate
hosts
(tissue cysts)
C. Engleberg/V. Carruthers
Sheep
Pig
64
Additional Source Information
for more information see: http://open.umich.edu/wiki/CitationPolicy
Slide 5: Cary Engleberg and Vernon Carruthers
Slide 8: Cary Engleberg
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Slide 25: Armed Forces Institute of Pathology, http://www.afip.org/index.html
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Slide 30: Cary Engleberg (left) Sources Undetermined (right)
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Slide 37: (snail) Pearson Scott Foresman, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Snail_(PSF).png; Cary Engleberg All other images)
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Slide 54: (pig) Martin von Nathusius, Wikimedia Commons, http://commons.wikimedia.org/wiki/File:Cochon.svg; Cary Engleberg (All other images)
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Slide 59: Cary Engleberg and Vernon Carruthers
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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/bysa/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