Pathogenesis of Parasitic Infections Flashcards
What are the different kinds of leishmaniasis?
Visceral leishmaniasis
- Asia: Leishmania donovani
- Middle East/Africa/Asia: L. infantum variants
- Latin America: L. chagasi
Cutaneous leishmaniasis
- Old World: Mediterranean/Middle East: L. Infantum/L. major/L. tropica
- New world: Central and South America: L. braziliensis/amazonensis/mexicana
Describe leishamaniasis’ life cycle.
The disease is caused by the sand-fly. A sand-fly will bite you, and transfer you a promastigote; those invade immune cells such as macrophages.
Inside the macrophage, it forms nests of amastigotes. The cells then burst, releasing lots of the pathogen to infect other cells.
Describe the different clinical forms of cutaneous leishmaniasis.
Leishmania tropica:
A few weeks after being bitten, you’d get a papule on you body. Gradually, the papule would spread and become a lesion. The centre then becomes necrotic, and you get an ulcer formation.
Leishmania recidivans:
Some lesions can reactivate months or years later.
Sporotrichoid leishmania:
Some lesions can go along the lymphatic vessels.
Diffuse cutaneous leishmaniasis:
Some people are unable to generate an adequate response and so they get packed full of parasites.
Mucocutaneous leishmaniasis:
Some individuals get infected when they are younger, get a scar and years later, a portion of them will get a stuffy nose. It then becomes more marked and you start seeing these lesions around the area – the parasite can reactivate. It becomes a very destructive lesion.
Describe the pathogenesis of cutaneous leishmaniasis.
ACUTE LESIONS:
- Tissue damage caused by inflammatory response to presence of parasites in macrophages
- Parasite killing by Th1 pro-inflammatory responses and macrophage killing.
LATENCY:
- Parasites remain present long-term. Regulatory immune response characterized by balance of Th1 and anti-inflammatory responses
RELAPSE (RARE):
- Alteration in immune response (i.e change in Th1 vs. immune regulation secondary to HIV, malnutrtition) may trigger relapse
- Mucocutaneous disease associated with strong but inadequate inflammatory response to parasites that have metastasized to mucosa
- Diffuse cutaneous leishmaniasis associated with uncontrolled parasite replication.
- Recividans – recurrence of lesions at old ulcer site.
What are the three main species of schistosomiasis?
- Schistosoma mansoni: affects the hepatic and intestinal system
- S. haematobium: affects the urinary tract
- S. japonicum: affects the hepatic and intestinal system, just found in Asia
As a recap, describe the schistosomiasis life cycle.
Water is contaminated with human faeces and the eggs are in the water
It develops into an intermediate stage called the miracidium, which infects the snail (amplifier).
They asexually reproduce in the snail, and release thousands of cercarie and this infects humans when they walk in contaminated water.
They develop into adults in the human (mesenteric system), undergo sexual reproduction and produce many eggs, which are then released into the environment again, continuing the life cycle.
What is cercarial dermatitis?
It presents as a nasty allergic reaction when people who have becomes sensitised are exposed to cercarie in the water source.
What is the key feature of the immune response to schistosomiasis?
The key feature of the immune response to schistosomiasis is the response to granuloma formation.
The eggs become organised into granulomas.
In schistosomiasis, you get these repeated episodes of inflammation, and then you get damage to the tissues, repair and fibrosis, which causes damage related to the disease.
This is a classical example of Th2-delayed hypersensitivity.
How would you get hepato-intestinal schistosomiasis?
It occurs in infections with S.mansoni and S.japonicum. Again, the pathology is caused by the immune resposne to the egg.
Since the adults are in the mesenteric vessels, the female gives birth to many eggs and these go into the intestines, through the capillaries and are pushed by the immune response through the intestinal wall and through the mucosa and are excreted.
Describe urinary schistosomiasis.
The adults live in the vessels around the bladder and they release eggs into these vessels – these are pushed through the mucosa in the bladder and pushed into the urine.
A symptom of urinary schistosomiasis is haematuria.
As a result of its prevalance in endemic areas, peeing blood has become so common that it is seen as a right of passage.
Because of inflammation to the bladder wall, you get damage to the bladder wall, which can lead to cancer development.
Describe onchocerciasis.
It is a major blinding disease. It used to be a major cause of blindness in West Africa, but now there are effective control programme.
It is caused by the filarial parasite (Onchocerca volvulus), and it transmitted by blackflies (simulium).
It is distributed in equatorial regions of Africa, and Central and South America.
Describe how you would get onchocerciasis from a blackfly.
A blackfly will bite you and transmit its larvae into you. The larvae migrates under the skin and develops into an adult (male and female).
After mating, the female releases thousands or larvae called microfilariae – these are taken up by the blackfly.
Describe the pathology of onchocerciasis.
Repeated episodes of inflammation to presence of microfilariae leads to permanent damage and scarring in skin and eyes.
For an adult in an endemic area, you will be able to see the larvae in the dermis of the skin, but there won’t be an immune response. The parasite is actively down-regulating the host immune response.
It can switch off its downregulation if given treatment.
Describe the clinical presentations of onchocerciasis.
Onchocercal nodules (the males migrate from nodule to nodule, fertilising females).
Skin disease (can be acute or chronic):
- acute papular onchodermatitis
- chronic onchodermatitis (sowda)
Eye disease:
Anterior segment
- Punctate keratitis – death of small groups of cells on surface of cornea
- Acute iridocyclitis – inflammation of the anterior chamber of the eye
- Sclerosing keratitis – inflammation of the cornea
Posterior segment
- Optic neuritis/atrophy – atrophy of the optic nerve
- Chorioretinopathy – fluid accumulates in the retina, causing serous detachment and vision loss
Describe acute papular onchodermatitis.
It looks like an acute papular rash, but if you look under the skin, you’ll see microfilariae surrounded by an inflammatory response, characterised by a lot of eosinophils.