Pathogenesis of Parasitic Infections

Question 1

Leishmaniasis - what is it?

Answer 1

a protozoa

2 types of this disease: visceral and cutaneous

Question 2

Leishmaniasis: life cycle

Answer 2

-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

Question 3

what is the vector of leishmaniasis?

Answer 3

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.

Question 4

what type of infection is leishmaniasis?

Answer 4

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

Question 5

clinical forms of the disease?

Answer 5

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 to leishmanial so they get packed full of parasites
• associated with uncontrolled parasite replication

Mucocutaneous leishmaniasis:

• everyone is infected as a child and have a scar
• associated with 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

Question 6

Pathogenesis of cutaneous leishmaniasis

Answer 6

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, malnutrition) may trigger relapse

Question 7

does leishmania go away?

Answer 7

leishmania never goes away

-the parasites can linger, and may reactivate at other sites in the body due to situations, eg. malnutrition or stress

Question 8

Recividans?

Answer 8

recurrence of lesions at old ulcer site

Question 9

Helminths - what important infections do they cause?

Answer 9

schistosomiasis

onchocerciasis

Question 10

Schistosomiasis (worm infections): geography

Answer 10

3 main species:

1. Schistosoma mansono – affects hepatic and intestinal system
2. S. Haematobium – affects urinary tract
3. S. japonicum – affects hepatic and intestinal system, found in Asia

Question 11

Schistosomiasis: Life cycle

Answer 11

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

Question 12

Cercarial dermatitis?

Answer 12

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

Question 13

Hepato-intestinal schistomiasis

Answer 13

• 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

Question 14

Urinary schistomiasis

Answer 14

• 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

Question 15

Helminths: onchocerciasis?

Answer 15

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

Question 16

Onchocerciasis - pathology

Answer 16

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

Question 17

Onchocerciasis- clinical disease

Answer 17

(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

Question 18

Immunopathogenesis of onchocerciasis

Answer 18

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.

Question 19

Ectoparasites – ticks

Answer 19

-a tick sticks its mouth parts into the skin and forms a cement which keeps it in the skin – difficult to get it out

Question 20

2 types of ticks:

Answer 20

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

Question 21

Sucking Lice - types:

Answer 21

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

Question 22

ectoparasites - types

Answer 22

ticks
sucking lice
botfly

Question 23

Ectoparasites – the Botfly

Answer 23

• 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

Question 24

Control of parasite infections – drugs

Answer 24

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

Question 25

Control of parasite infections - not drugs

Answer 25

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

Question 26

For many parasite infections in an endemic setting, treatment must be given periodically over long periods of time - why?

Answer 26

because re-infections are rapid or because the treatment kills larval rather than adult stages