Pathogenesis of Parasitic Infections Flashcards
Which parasite causes schistosomiasis?
Helminths
What are the 3 main species of Schistosomiasis?
- Schistosoma mansoni
- S. haematobium
- S. japonicum
Outline where and what effect S. japonicum has
- Asia
- Hepatic & intestinal system
Outline effects of S. haeatobium
- Sub-saharan Africa
- Urinary tract
Where and what does S. mansoni effect?
- Latin America, Sub-saharan Africa
- Hepatic & intestinal system
Outline the life cycle of schistosomiasis
- Exposed to infective stage in contaminated water
- Cercariae migrate through body
- Adults form in mesenteric system
- Eggs lain and pushed through mucosal epithelium
- Excreted in faeces/urine
What is Cercarial Dermatitis?
Schistosomiasis exposure to cercariae from animal or bird schistosomes
Requires pre-sensitization - allergic type reaction
Describe the immune response to schistosomiasis
key feature of immune response is granuloma formation of eggs
Th2 delayed type hypersensitivity
What does repeated exposure of schistosomiasis cause?
Repeated insults and tissue repair leads to fibrosis and organ damage
What causes Hepato-intestinal schistosomiasis?
Infections with S.mansoni and S. japonicum
Pathology caused by immune response to eggs
How does S.mansoni and S.japonicum effect the hepatic and intestinal space?
When infected, adults present in mesenteric vessels
Females release 1000’s of eggs - travel through intestine to capillaries and pushed into intestinal wall through mucosa due to immune response and excreted
What does chronic schistosomiasis (mansoni + japonicum) exposure cause?
Chronic exposure leads to inflammation repair and fibrosis
Typical pipe stem fibrosis seen in advanced schistosoma liver disease ⇒ secondary hepato-splenomegaly
How does urinary schistosomiasis occur?
Adults live in vessels surrounding bladder and release eggs there
Eggs pushed through bladder mucosa and excreted in urine
How is urinary schistosomiasis diagnosed?
urine tests show haematuria to diagnose schistosomiasis
> Very common in adolescence in endemic areas
What causes haematuria in urinary schistosomiasis?
Damage due to inflammation caused by the eggs in bladder wall commonly leads to secondary development of cancer
What is onchocerciasis?
Major binding disease
Caused by worm infection; filarial parasite (onchocerca volvulus)
Transmitted by backflies
What is the vector of onchocerciasis?
Simulium
Where is onchocerciasis (river blindness) common?
Present in equatorial regions of Africa and Central and South America
Outline the life cycle of onchocerciasis
- Blackfly bite transmits infectious larvae
- Larvae migrates under the skin
- Develops into adults and mate to release 1000s of eggs (microfilariae)
- Microfilariae taken up by blackfly
How does onchocerciasis lead to blindness?
Repeated episodes of inflammation to presence of microfilariae leads to permanent damage and scarring in skin and eyes
Outline the different forms of Onchocerciasis clinical disease
- Onchocercal nodules
- skine disease
- Eye disease
Describe the skin disease of onchocerciasis
- Acute papular onchodermatitis
- Chronic onchodermatitis
- Sowda
Outline the 2 types of eye disease associated with onchocerciasis
Anterior segment
- Punctate keratitis
- Acute iridocyclitis
- Sclerosing keratitis
Posterior segment
- Optic neuritis/atrophy
- Chropretinopathy
Describe what acute papular onchodermatitis looks like
Looks like an acute papular rash but looking closely at skin shows microfilariae surrounded by inflammatory response; characterised by eosinophils
How does the immune system respond to acute papular ochodermatitis?
Myocelles activated; immediate hypersensitive immune response recruits eosinophils ⇒ delayed response to kill and destroy microfilariae
How does chronic onchodermatitis occur?
Chronic onchodermatitis occurs with repeated inflammation causing skin elastin and collagen damage
=> leads to aged appearance
What causes punctate keratitis?
Microfilariae can infect the cornea of the eye -> punctate keratitis
What are the clouded patches in the eye seen in punctate keratitis?
Fluffy patterns visible in cornea shows where microfilariae are being destroyed by the immune response
What is sclerosing keratitis?
Repeated episodes of inflammation over long periods of time causes opacification of cornea due to chronic inflammation ⇒ leads to eventual blindness
What is chorioretinopathy?
complete damage of retina
Describe the presentation of chorioretinopathy
Small white spots present very early on in eye - where microfilariae have been destroyed by inflammatory response
How does chrioretinopathy lead to blindness?
Chronic inflammation causes damage to retinal pigment epithelium which causes overlying neuronal cells to also die
Choroid (structure under retina) now visible as retina and macula is destroyed ⇒ blindness
What is optic atrophy?
Microfilariae enter optic nerve - typical of onchocerciasis
What are the effects of inflammation in optic atrophy
Sheathing of retinal vessels caused by inflammation
Pale optic disc seen in optic atrophy - post inflammatory optic atrophy causes blindness in onchocerciasis
Describe the acute response to onchocerciasis
In acute responses there are rapid allergic reactions where microfilariae die in skin:
Myocelles activated which recruit other immune cells; eosinophils causing eosinophilic abscesses
Which inflammatory cells are active in an acute response to onchocerciasis?
strong Th2 and allergic response (IL-4; IgE, IL-5; recruits & activates eosinophils)
What happens in a chronic response to onchocerciasis?
In chronic episodes of inflammation, the immune response begins to shut down; host immune cell is regulated
Which inflammatory immune cells are responsible for chronic response to onchocerciasis?
modified Th2 response (IL-10, T reg cells and IgG4
Why do chronic onchocerciasis patients not produce an apparent immune response?
Someone with chronic infection produces no apparent immune response due to microfilariae presence in skin
What is the significance of ticks?
Ticks act as important vectors for infections
How do ticks spread infection?
Mechanical injury by bite; Stick mouth parts into the skin and forms a cement which keeps it in to feed off blood
What is tick paralysis?
The progressive flaccidity due to a failure of acetylcholine liberation in neuromuscular junction
Ticks toxin produces a block in the motor nerve fibres
What diseases are caused by Hard-bodied ticks?
Hard-bodied ticks (ixodidae) carriers of rickettsial, spirochetal, viral, bacterial and protozoan diseases: - tick typhus - Viral encephalitis - Viral fevers - Viral hemorrhagic fevers - Tularemia - Tick paralysis - Human babesiosis
What diseases are caused by soft-bodied ticks?
Soft-bodied ticks (omithodorus)
vectors of endemic relapsing fever (caused by borrelia duttoni) and Q-fever
What is the effect of head lice?
Suck blood from scalp and lay eggs on hair
Common and easily spread by close contact, sharing of combs, brushes, hats, etc.
What is the mechanism of action of body lice?
Suck blood from body and lay eggs on clothing
How common are body lice?
Uncommon and spread by bodily contact, sharing clothes and bedding
Which diseases do body lice spread?
Vector diseases (epidemic typhus, trench fever, relapsing fever)
What increases risk of ectoparasite infection?
Lousiness related to sanitation
- Crowded conditions
- Long periods without bathing or changing clothes
What are pthirus?
Pthirus (crab lice, pubic lice)
- sucking lice
Describe the structure of pthirus
Broad, flat lice; appear crab like
Stout mid and hind legs, large claws
Abdominal segments with distinct lateral lobes
Where do pthirus infect?
Single species (pthirus pubus), confined to human pubic region
- Bites cause irritation & typical rash
- Spread by close body contact (sexual intercourse)
- No diseases
Outline the lifecycle of botflies
- Botfly mid flight lays eggs on a mosquito
- Mosquito bites animal and egg hatches due to temp change
- Larvae enters skin
Where are myiasis causing botflies commonly found?
Common in central and latin america
More common in tropical areas of countries - coastal and amazon areas as well as the highlands
How do botflies cause infection?
Botfly sticks head out of lesion, and has spines that stick to surrounding tissue making it difficult to remove
What drugs are used to control protozoa infections?
- Tinidazole
- Metronidazole
- Notazoxanide
- Benznidazole
- Heavy metals (meglumine antimoniate)
What drugs are administered for helminth infections?
- Albendazole / Mebendazole
- Praziquantel
- Ivermectin
- Diethylcarbamazine
- Pyrantel
What drugs are available for ectoparasite infections?
- Ivermectin
- Benzyl/malathion lotions
Compare and contrast protozoa medications
Tinidazole has advantage of shorter dose regimens (e.g. 1g)
Metronidazole has longer course of dose and isn’t well tolerated
Benznidazole used to treat Chagas disease however has very nasty adverse effects; peripheral neuropathy and dermatitis - many patients don’t complete the course
How can behaviours effect control of parasitic infections?
Education
Hand washing and hygiene behaviours
What environmental interventions can prevent spread of parasitic infections?
Spraying residual insecticides (household vectors) Mosquito nets (malaria) Improved housing Sewage disposal and potable water Swamp drainage
How should treatments be administered in endemic areas of parasite infections?
For many parasite infections in an endemic settings, treatments must be given periodically over long periods of time because re-infections are rapid, and treatments kill larvae rather than adult stages
