Pathogenesis of Parasitic Infections Flashcards
Leishmaniasis - what is it?
a protozoa
2 types of this disease: visceral and cutaneous
Leishmaniasis: life cycle
-fairly simple life cycle
- sand fly bites you and transmits a promastigote
- promastigote invades immune cells, e.g. neutrophils and macrophages
- inside the macrophage it forms nests of amastigotes
- the cells eventually burst and release amistogotes, which can infect other cells or be taken up by a sand fly at another blood meal and transmitted to someone else
what is the vector of leishmaniasis?
Sand-flies
they are very common in tropical regions and tend to affect poorer households - housing not up to standard
they love feeding on chickens as a source of blood, and they are small enough to get through mosquito nets.
what type of infection is leishmaniasis?
largely a zoonotic infection - the reservoir are rodents and animals like sloths, but humans can become infected, as can domestic dogs
domestic dogs being infected then paves the way for urban transmission
clinical forms of leishmaniasis?
Cutaneous leishmaniasis:
- papule gradually spreads into a lesion - the centre becomes necrotic and you get ulcer formation
- if these people move to a different area, and are exposed to a different strain of Leishmania, they can get it again
Diffuse cutaneous Leishmaniasis:
- some individuals aren’t able to generate an adequate immune response so they get packed full of parasites
- uncontrolled parasite replication
Mucocutaneous leishmaniasis:
- everyone is infected as a child and have a scar
- strong but inadequate inflammatory response to parasites that have metastasized to mucosa
- small % of individuals, years later, start to get a stuffy nose and then it becomes more marked, lesions around the mucosal area
- break down of nasal septum region
Pathogenesis of cutaneous leishmaniasis
Acute lesions
• Presence of parasites in macrophages cause tissue damage due to the Th1 pro inflammatory responses, which kill both the parasite and macrophage
Latency
• Parasites remain present long-term, there is a regulatory immune response characterized by balance of Th1 and anti-inflammatory responses (tnf beta, IL10)
Relapse (rare)
• Alteration in immune response (change in Th1, HIV, malnutrition) may trigger relapse
does leishmaniasis go away?
never goes away
-the leishmania parasites can linger, and may reactivate at other sites in the body due to situations, eg. malnutrition or stress
Recividans?
recurrence of lesions at old ulcer site
Helminths - what important infections do they cause?
schistosomiasis
onchocerciasis
Schistosomiasis (worm infections): geography
3 main species:
- Schistosoma mansono – affects hepatic and intestinal system
- S. Haematobium – affects urinary tract
- S. japonicum – affects hepatic and intestinal system, found in Asia
Schistosomiasis: Life cycle
people become exposed to the infective stage in contaminated water – they get infected with cercarae.
cercarae migrate through the body forming adults in the mesenteric system (manosono and japonicum in the intestinal mesenteric system, haemabotium in the vessels around the bladder)
the female and male mate, female releases lots of eggs which are pushed through the mucosal epithelium and leave via the faeces, which enter the water system and infect snails
Cercarial dermatitis?
allergic reaction to the presence of cercariae in the water source
- Exposure to cercariae from animal or bird schistosomes
- Requires pre-sensitization
- Allergic-type reaction
key feature of the immune response is granuloma formation
-eggs become organised in granulomas, and repeated insults and tissue repair leads to fibrosis and organ damage
Hepato-intestinal schistomiasis
- Infections with S.mansoni and S. japonicum
- Pathology caused by immune response to eggs
- adults are in the mesenteric vessels
- the female releases thousands of eggs which go into the intestines through the capillaries, and are pushed by the immune response through the intestinal wall through the mucosa, and are then excreted
-chronic inflammation over a long period of time will cause fibrosis, splenamegaly and hepatomegaly
Urinary schistomiasis
- adults live in the vessels around the bladder and release eggs into those vessels which are pushed through the mucosa of the bladder and excreted into the urine
- in endemic areas, what is quite common at puberty is haematuria – peeing blood
- because of inflammation in the bladder wall related to the eggs, you get damage to the bladder walls which can lead to the development of cancer
Helminths: onchocerciasis?
river blindness - major blinding disease
- caused by a filarial parasite called Onchocerca volvulus
- transmitted by blackflies
- female worm is long, coiled up into tight bundles in fibrous nodules found under the skin
complex life cycle:
- black fly bites you and transmitter infectious larvae
- the larvae migrate under the skin and develop into adults
- male and female adults mate and the female release thousands on larvae called microfilariae, and are taken up by the black fly and can be transmitted
Onchocerciasis - pathology
skin disease can be acute or chronic
- pathology caused by the host inflammatory response to the larvae (microfilarae). They are in the skin but can invade into the eyes
- Repeated inflammation episodes due to microfilariae leads to permanent damage and scarring in skin and eyes - blindness (they first affect the anterior part of the eye, the area around the iris, and then attack the posterior part of the eye, affecting the retina and optic nerve)
- the parasite is actively downregulating the host immune response, but you can switch off this downregulation through treatment
Onchocerciasis- clinical disease
(skin diseases are Acute papular onchodermatitis and Chronic onchodermatitis)
Puncatate keratitis (anterior)
- they can invade the cornea
- little fluffy pacities in the cornea – this is where the microfilaria are being killed by immune cells
Sclerosing keratitis (anterior) -due to chronic cornea inflammation over a long period of time you get opacification of the cornea, eventually leading to blindness
Chorioretinopathy (posterior)
- chronic inflammation damages retina
- damage to retinal pigment epithelium causes retina to die, which means you can see the choroid and leads to blindness
Optic Atrophy (posterior)
- larvae get into the optic nerve, sheathing of the retinal nerves due to inflammation
- blindness
Immunopathogenesis of onchocerciasis
we have acute and chronic responses.
acute:
- rapid allergic responses
- microfilaria dying in the skin
- activation of mast cells which recruit other immune cells, eosinophils
- eosinophil abcesses
chronic:
- the host immune response regulated and shut down
- production of IL10, T regulatory cells and antibodies such as IgG4 – all regulate the immune system
- the parasite wants to shut down the immune system, but the host also needs to downregulate the immune response in order to survive – tricky.
Ectoparasites – ticks
-a tick sticks its mouth parts into the skin and forms a cement which keeps it in the skin – difficult to get it out
2 types of ticks:
hard ticks have a dorsal plate, abdomen increases massively during a blood meal. the hard stick can transmit a large number of infections
hard ticks can cause tick typhus, tick paralysis
soft ticks can cause Q fever and relapsing fever
ticks toxin produces a block in the motor nerve fibres
Sucking Lice - types:
head lice and body lice
head lice suck from scalp and lay eggs on hair, spread by close contact
body lice suck from body and lay eggs on clothing, spread by clothes sharing, vector of diseases e.g.. trench fever and relapsing fever
crowded conditions, long periods without changing clothes is not good
ectoparasites - types
ticks
sucking lice
botfly
Ectoparasites – the Botfly
- doesn’t directly transmit the infection, mid-flight it grabs a mosquito and lays it egg on a mosquito
- mosquito bites an animal and the egg hatches and the larvae migrae into the skin – very common in cattle, bumps where you have larvae and flies living inside
Control of parasite infections – drugs
ectoparasites - not as many treatment options
tinidazole has the advantage of shorter dose regiments
metronizadole has more adverse reactions and longer dose regiments
benznidazole – severe side effects, most people cannot finish treatment course
Control of parasite infections - not drugs
Behaviours
• Education
• Hand washing and hygiene behaviours
Environmental interventions • Spraying of residual insecticides for household vectors • Mosquito nets for malaria • Improved housing • Sewage disposal and potable water • Drainage of swamps
Poverty reduction
• Micro-financing, etc
For many parasite infections in an endemic setting, treatment must be given periodically over long periods of time - why?
because re-infections are rapid or because the treatment kills larval rather than adult stages
