Pathogenesis of Parasitic Infections

Question 1

What are Helminths- schistosomiasis?

Answer 1

Helminths- schistosomiasis:
Worm.
Schistosoma mansoni- hepatic/intestinal system. (latin America and sub-Saharan africa).
S. haematobium- hepatic/intestinal system (Africa)
S. japonicum- urinary tract (Asia- zoonotic- cattle and buffalo).

Question 2

Describe the life cycle of schistosomiasis?

Answer 2

Exposed to infective stage in water.

Infected with cercariae.

Migrates in body and become male and female adults in mesenteric system (intestinal or bladder mesentery).

Female releases many eggs released in faeces.

When sensitised, exposure to cercariae in water causes cercarial dermatitis. Allergic reaction.

Question 3

What is Onchocerciasis?

Answer 3

River blindness (was common to west Africa).

Filarial parasite (onchocerca volvulus) transmitted by blackflies.

Worm- 50cm long found in fibrous nodules.

Controlled in Latin America.

Females 30cm and males 1-2cm.

Question 4

Describe the life cycle and pathology of Onchocerciasis

Answer 4

Bite from blackfly (simulium) transmits infectious larvae.

Migrates under skin and become male female adults.

Mate. Eggs released (called microfilariae) and taken up by blackfly.

Pathology:

Caused by host inflammatory response to larvae in skin and eyes (blindness).

Parasite actively downregulated host immune response.

Treatment increases immune response causing allergic response- eosinophils form abscess killing microfilariae, causing rash.

Skin disease- subcutaneous nodules containing females- males migrate between nodules, fertilising females (not large problem except at joint)- can be acute or chronic. Acute popular onchodermatitis- popular rash. Over time, chronic onchodermatitis- damage to elastin and collagen in skin- looks like aged skin.

Eye disease- anterior chamber- iris inflammation.

Posterior segment- damage to retina and optic nerve- optic neuritis (Sheathing of retinal vessels due to inflammation. Pale optic disc typical of optic atrophy) and chorioretinopathy (initially- white spots in eye where microfilariae have been killed. Chronic, damage to retinal pigment epithelium and overlying neural cells- so can see choroid due to loss of macular).

Can invade cornea. Punctate keratitis. Repeated infection lead to sclerosing keratitis and occlusion of cornea.

Question 5

What is the immune response to Onchocerciasis?

Answer 5

Immune response:
Acute- rapid allergic reaction- mast cell, eosinophils and abscesses. Strong Th2 response- production of IL-4 (IgE) and Il-5 (recruit and activate eosinophils).
Chronic- regulating immune response. Modified Th2 response- IL-10, T-regulated cells (immune regulation) and IgG4. No apparent response to presence of microfilariae in skin.
Parasite switches on host regulatory response to survive and host reduced inflammation to also survive.

Question 6

What are ticks?

How do they attach to the skin?

What are the two types of ticks?

What can they cause when they are removed?

What diseases do they cause?

Answer 6

Sticks mouth part into skin and releases cement to keeps in skin.

Hard ticks- big dorsal plate. Filled with blood and becomes very large. Typhus, encephalitis, haemorrhagic fevers, tick paralysis and human babesiosis.

Soft ticks- q fever and relapsing fever.

Mechanical injury at site of bite.

Muscular paralysis- rapid recovery once removed.

Lyme disease (bacterial infection)- risk when hiking.

Different larvae forms. Small ones similar to jigger mites.

Question 7

What are botflies?

Answer 7

• Dermatobia hominis.
• Mid-flight grabs mosquito and lays egg.
• Mosquito lands on body and egg hatches due to change in temperature.
• Larvae migrates into skin- myiasis.
• Common in cattle.
• Rows of spines on skin make it difficult to extract- sticks to tissue.
• Body within and head sticks out to breathe.
• Will fall out eventually by itself but wriggles around, making it uncomfortable.
• Can cut it out or ivermectin treatment, which kills it and you can squeeze it out like papule.
• Other forms- cavitary myiasis by cochliomyia hominovorax. Risk to alcoholics, elderly and indigenous people. Untreated in eye can lead to blindness and death.

Question 8

How are parasites controlled?

Answer 8

• Protozoa- Tinidazole (shorter dose regiment) or Metronidazole (more adverse reactions/not well tolerated and longer duration). Nitazoxanide. Benznidazole- Chagas disease (bad side-effects- severe peripheral neuropathy and dermatitis, and not well tolerated). Leishmania still treated with heavy metals- meglumine antimoniate- over 100 years old.
• Helminth- benzimidazole (albendazole/mebendazole)- single dose usually. Praziquantel- trematodes (lung and liver flukes- schistosoma). Ivermetin- filarial disease- onchocerciasis. Diethylcarbamazine (older drug).
• Ectoparasite- Ivermectin (single dose for botfly, scabies, lice- not widely used) and benzyl/malathion lotions (repeated and not very effective- used in shapoos for lice, etc).
• Education- prevent exposure, hygiene behaviours, environmental intervention (spraying with insecticides and using bed nets, improved housing), adequate sewage disposal and portable water, drainage of swamps, poverty reduction (microfinancing), etc.
• Treatments must be periodic over long duration due to high risk of reinfection or treatment kills larvae but not adults.
• E.g. helminth treated with albendazole once a year or more.
• Ivermectin kills onchocerciasis larvae but not adult- treatment of whole community every 6 months for 15 years until all adults are gone- can eliminate local parasite infections.
• Single dose of praziquantel to endemic communities every 6 months for schistosomiasis.