Pathogenesis of parasitic infections Flashcards
What is the life cycle of leishmaniasis?
- Caused by the sandfly
- Sandfly bite transmits promastigote
- Promastigote invades immune cells e.g. macrophages
- Forms nest of amastigotes inside the macrophages
- Cells eventually burst releasing amastigotes, causing infection to other cells
What is the source of transmission of leishmaniasis in urban environments?
• In urban environments, the source of transmission is domestic dogs
What does bite of a sandfly cause the formation of and what happens gradually after?
• The bite causes a papule to form on the skin
§Gradually the papule spreads and the centre becomes necrotic
What are the 3 steps involved in the pathogenesis of cutaneous leishmaniasis?
- Acute lesions
- Latency
- Relapse
What is tissue damage due to in acute lesions phase?
○ Tissue damage caused by inflammatory response to presence of parasites in macrophages
What is parasite killed by in the acute lesions phase?
○ Parasite killing by Th1 pro-inflammatory responses and macrophage killing
What happens in the latency phase of cutaneous leishmaniasis?
○ Parasites in their lesions but do not become activated again
○ Parasites remain present long term
○ Regulatory immune response characterised by balance of Th1 and anti-inflammatory responses
What may trigger relapse of cutaneous leishmaniasis?
○ Alteration in immune response (i.e. change in Th1 vs. immune regulation secondary to HIV, malnutrition) may trigger relapse
What are the 3 main species of schistosomiasis?
- Schistosoma mansoni
- S. haematobium
- S. japnicum
What does the schistosoma mansoni affect?
Affects hepatic and intestinal system
What does the s.haematobium affect?
Affects urinary tract
What does the S.japnicum affect?
Affects hepatic and intestinal system
How do people become exposed to the infective state of schistosomiasis?
• People become exposed to the infective stage in contaminated water
What is the life cycle of schistosomiasis?
- Parasites migrate through the body forming adults in the mesenteric system depending on which species it is
- Female and adult mate; female releases eggs which are pushed through the mucosal epithelium and excreted through faeces or urine, which contaminates the water
What is cercarial dermatitis?
• Allergic reaction to presence of cercarie – the parasites of schistosomiasis
What does cercarial dermatitis require?
Requires pre-sensitisation
What is the key feature of the immune response in schistosomiasis?
KEY FEATURE OF IMMUNE RESPONSE IS GRANULOMA FORMATION
What is the immune response in schistosomiasis an example of?
This is an example of Th2 delayed type hypersensitivity
What happens to egg in granulomas?
Eggs become organised in granulomas
What response is key in schistosomiasis?
The response to the egg is key in schistosomiasis
What happens in the immune response to schistosomiasis and what can this cause?
Repeated episodes of inflammation = damage to the tissue = repair = fibrosis and organ damage – can cause hepatosplenomegaly
What infection results in hepato-intestinal schistosomiasis?
Infections with S.mansoni and S. japonicum
What is the pathology caused by in hepato-intestinal schistosomiasis?
Pathology caused by immune response to eggs
Where are the adults parasites in hepato-intestinal schistosomiasis and what does this lead to?
Because the adults are in the mesenteric system, the female releases eggs which go through capillary, into intestine and are pushed by the immune response through the intestinal wall, through the mucosa and then excreted
Where do the adult parasites live in urinary disease?
In urinary disease, the adults live in the vessels around the bladder
Where are the parasite eggs release in urinary schistosomiasis and where do they go?
Release eggs into these vessels which are pushed the bladder mucosa and then excreted into urine
What can be present in urine in urinary schistosomiasis?
Can get haematuria – blood in urine
Why can urinary schistosomiasis result in bladder cancer?
As there is damage to the bladder wall, it can result in bladder cancer
What parasite causes onchocerciasis and what is this disease?
Caused by the onchocerca volvulus
Is a major blinding disease
What is the onchocerca volvulus transmitted by?
Transmitted by blackflies
What is the life cycle of the onchocerca volvulus?
- Blackfly bites you and transmits infectious larvae
- Larvae migrates under skin ande develops into adults
- Male and female mate, females release eggs which are taken up by blackfly and transmitted
What is the pathology of Onchocerciasis?
Repeated episodes of inflammation to presence of microfilariae leads to permanent damage and scarring in skin and eyes
Why is there no immune response when larvae is in the dermis?
- Larvae in dermis of skin but no immune response
- Larvae is downregulating the body’s immune response
What happens once the down-regulatoin caused by larvae is switched off?
Once switched off, get strong allergic type response due to a lot of eosinophils
What are the clinical diseases caused due to Onchocerciasis?
- Onchocercal nodules
- Skin disease
- Eye disease
What are the skin diseases due to onchocerciasis?
- Acute papular onchodermatitis
- Chronic onchodermatitis
- Sowda
What are the eye diseases due to onchocerciasis?(anterior segment)
Anterior segment – area around iris
- Punctate keratitis
- Invade cornea - Acute iridocyclitis
- Sclerosing keratitis
- Repeated exposure leads to opacification of cornea
- Eventual complete occlusion = blindness
What are the eye diseases due to onchocerciasis?(Posterior segment)
- Optic neuritis/atrophy
- Chorioretinopathy – retinal pigment epithelium dies, complete damage of the retina = blindness
What are the immunopathogenesis of onchocerciasis in acute disease?
- We can get rapid allergic reactions where microfilariae die in the skin
- Strong Th2 response
- Production of IL4 (to make igE) and IL5 (to recruit and activate eosinophils)
What are the immunopathogens of onchocerciasis in chronic diseease?
- Immune response starts to shut down
- Host immune response starts to become regulated
- Modified Th2 response – production of IL10, Treg cells and IgG4 antibodies
What do ticks do?
Sticks mouth into skin and releases cement which keeps it stuck
What do ticks feed off?
Feeds off the blood
What are ticks important vectors of?
Ticks are important vectors of different infections
What are the 2 types of ticks?
- Hard ticks
2. Soft ticks
What can hard ticks transmit?
Transmits many infections including: viral haemorrhagic fevers, tick paralysis etc
What do soft ticks fo?
Mechanical injury by bite
How do soft ticks cause tick paralysis?
Progressive flaccidity due to failure of ACh liberation in the neuromuscular junction
What does the soft ticks toxin produce?
Tick’s toxins produce a block in motor nerve fibres
What do head lice do?
Suck blood from the scalp and lay eggs on the hair
What do body lice do?
Suck blood from body and lay eggs on clothing
What is lousiness related to?
Lousiness related to sanitation
What are pthirus pubus confined to and what do the bites cause?
Confined to human pubic region
-Bites cause irritation and typical rash
What is the appearance of pthiridae?
- Broad, flat lice that appear crab-like
- Mid and hind legs stout with very large claws
- Abdominal segments have distinct lateral lobes
What is the life cycle of a botfly?
- Lays eggs on mosquitoes
- When a mosquito lands on an animal, the change in temperature causes the egg to migrate to the skin
What are drugs used to control parasite infectons?
- Tinidazole
- Metonidazole
- Benzniadazole
What is the advantage of tinidazole?
advantage of shorter dosage regimens: 1g once a day for three days
What are the drawbacks of metonidazole?
More adverse reactions
What disease it benzniadazole a treatment for?
Treatment for Chagas disease
What does benzniadazole cause?
Causes adverse reactions so many people cannot complete course of treatment
What are behavioural ways to control parasite infections?
- Education – avoid exposure to certain infections
- Hand washing and hygiene behaviours
What are environmental interventions to control parasite infections?
- Spraying of residual insecticides for household vectors
- Mosquito nets for malaria
- Improved housing i.e. for Chagas disease
- Sewage disposal and potable water
- Drainage of swamps
What is given to high risk groups to control STH infections?
Single dose of albendazole is given to high risk groups such as school children up to every 4 months to control STH infections
What is given to endemic communities to control onchocerciasis?
Single ivermectin is given to endemic communities (mass drug administration) every 6 or 12 months to control onchocerciasis
What is given to endemic communities to control schistosomiasis?
Single dose of praziquantel is given to endemic communities (mass drug administration) every 6-12 months to control schistosomiasis
