6/7 - Parasitic Infections: Examples

Question 1

what causes Chagas disease?

Answer 1

Trypanosoma cruzi protozoa

Question 2

describe the life cycle of Trypanosoma cruzi

Answer 2

triatome bug takes a blood meal, defecates in human skin

metacyclic trypomastigotes from faeces enter the blood through the bite wound or mucosal membranes - infect cells and transform into amastigotes inside cells, which multiple by binary fusion

intracellular amastigotes transform into trypomastigotes, burst out the cell into blood and invade other tissues

another triatomine bug takes a blood meal from the infected host, and ingests the trypomastigotes

inside the bug’ midgut, the trypomastigotes transform into epimastigotes , which multiply and differentiate into infective metacyclic trypomastigotes in the bug’s hindgut

once bug defecates on a new host’s skin - metacyclic trypomastigotes are released and the cycle continues

Question 3

what are the three phases of Chagas infection?

Answer 3

acute
chronic ‘indeterminate’ phase
chronic ‘determinate’ phase

Question 4

describe the features (detection)/ symptoms and pathogenesis of the acute phase for Chagas infection

Answer 4

features:
1-2 week incubation period, can last a few months
trypanosome detectable in blood

symptoms:
- generally mild or asymptomatic
- nodule or localised swelling
- fever, malaise, anorexia
- rarer symptoms emerge in the young or immunosuppressed = e.g. myocarditis, meningoencephalitis, hepatosplenomegaly, fatality

pathogenesis:
- parasite forms nests if amastigotes in different muscles, stimulates innate immune response to release antibodies and Th1 producing pro-inflammatory cytokines (TNF-alpha, IFN-gamma)
- help control infection by promoting parasite killing but inflammation can cause tissue damage
(tissue damage caused by strong inflammatory response of Th1 cells + antibody release)

Question 5

describe the features/ symptoms and pathogenesis of the chronic indeterminate phase for Chagas infection

Answer 5

features:
- lifelong infection
- parasite DNA is detectable, trypanosomes aren’t, seropositive for T. cruzi antibodies

symptoms:
- no ECG or X-ray changes yet

pathogenesis:
- immune response shifts to a more regulatory state - production of regulatory cytokines (IL-10/17) to control inflammation and prevent tissue damage
- parasite still persists

Question 6

describe the features/ symptoms and pathogenesis of the chronic determinate phase for Chagas infection

Answer 6

• long-term infection, can last decades, seropositive for T. cruzi antibodies

symptoms:
- cardiac complications
= arrhythmias, bradycardia, conduction abnormalities - detectable on ECGs
= heart failure, sudden cardiac arrest
= cardiomyopathy, fibrosis
- digestive complications
= megaoesophagus, rectum and sigmoid colon affected
- megacolon
= severe constipation, hardened stool mass, twisted sigmoid colon, ulceration and perforation
- ECG and X-ray abnormalities

pathogenesis:
- immune system continues mounting a response to T. cruzi’s persistent presence, causes chronic inflammation driven by Th1 cytokines, CD8+ T cells and autoimmune mechanisms = leads to progressive tissue damage especially in the heart
- degree of cardiomyopathy depends on balance of cytokines present = moderate cardiomyopathy means more anti-inflammatory cytokines, more severe cardiomyopathy means more pro-inflammatory Th1 cytokines

Question 7

pathogenesis of the chronic determinate phase for T. cruzi

Answer 7

immune system continues mounting a response to T. cruzi’s persistent presence, causes chronic inflammation driven by Th1 cytokines, CD8+ T cells and autoimmune mechanisms

leads to progressive tissue damage especially to the heart

degree of cardiomyopathy depends on balance of cytokines present = moderate cardiomyopathy means more anti-inflammatory cytokines, more severe cardiomyopathy means more pro-inflammatory Th1 cytokines

Question 8

what are the two types of leishmania?

Answer 8

visceral leishmania
cutaneous leishmania - typical, atypical, mucocutaneous, diffuse

Question 9

what protozoa tend to cause visceral leishmania?

Answer 9

different causative agents across different geographical locations

Leishmania donovani for Asia
Leishmania infantum variants for Middle East & Africa

Question 10

what protozoa tend to cause cutaneous leishmania?

Answer 10

different causative agents across different geographical locations

Leishmania infantum/ major or tropica for the Old Word (Middle East)

Lieshmania braziliensis, amazonensis for the New World (Central/ South America)

Question 11

what is the vector for Leishmania?

Answer 11

sandflies

• different species in New vs Old World
• sandfly vectors vary by geographic region and species of Leishmania

Question 12

what are the reservoirs for Leishmania protozoa?

Answer 12

domestic animals - e.g. dogs
sylvatic reservoirs - wild animals like sloths

Question 13

what is the life cycle of Leishmania protozoa?

Answer 13

sandfly bites individual and takes up blood meal - injects promastigotes into blood which are phagocytosed by macrophages

inside macrophages, promastigotes transform into amastigotes, which multiply and infect the macrophage

another sandfly feeds off infected person - ingests the macrophages containing amastigotes during a blood meal

amastigotes in sandfly’s midgut transform into promastigotes - migrate to proboscis to be transmitted to another host

Question 14

what are the different clinical forms of cutaneous leishmania (CL)?

Answer 14

typical
atypical
mucocutaneous
diffuse

Question 15

describe typical CL - symptoms, response?

Answer 15

symptoms:
- ulcerative skin lesions art site of sandfly bite = iniitally appear as papules, progress to nodules and then ulcerate

response:
- spontaneous healing over several months/ years, with scarring

Question 16

describe atypical CL - symptoms, response?

Answer 16

variants of the typical CL form presenting with different clinical features

symptoms:
- papular, nodular or verrucous lesions with less ulceration

response:
- can resolve spontaneously or persist chronically

Question 17

describe mucocutaneous CL

Answer 17

severe CL form affecting skin and mucous membranes

ulcerative lesions extend from initial cutaneous site to invade oral, nasal and pharyngeal mucosa

destructive lesions lead to disfigurement or impaired function of invaded sites

Question 18

describe diffuse CL

Answer 18

rare and severe form

symptoms:
- widespread, non-ulcerative nodular lesions
- resemble leprosy

response:
- often associated with an impaired immune response, lesions are resistant to treatment

Question 19

describe the pathogenesis stages of CL

Answer 19

1. acute lesions = presence of parasite in macrophages triggers an inflammatory response
   - pro-inflammatory Th1 responses and macrophage activation contribute to parasite killing & tissue damage
2. latency = parasite persist in the skin during a latency period
   - immune response returns to a regulatory state - balanced by Th1 pro-inflammatory and other anti-inflammatory mechanisms to control the parasite and tissue damage
3. relapse = certain trigger that affect the pro- anti-inflammatory response can affect the controlled immune response, cause lesions to re-occur
4. mucocutaneous disease = parasites that metastasis from skin to mucosal tissues and cause a strong but insufficient immune response - leads to mucocutaneous CL
5. diffuse disease = uncontrolled parasite infection causing widespread, non-ulcerative lesions, immune response is ineffective
6. recidivans = recurrence of lesions at old ulcer sites indicate parasite’s persistence and immune dysregulation

Question 20

what are the (immune) cellular responses to CL?

Answer 20

infected macrophages activated to clear the parasites and combat tissue damage

Th1 cells are important for parasite control - produce pro-inflammatory cytokines to mediate parasite killing, contribute to tissue damage/ inflammation

dysregulated immune responses can lead to chronicity or relapse

Question 21

what type of parasite infection is schistosomiasis?

Answer 21

helminth

Question 22

what causes schistosomiasis?

Answer 22

parasitic flatworm/ Trematodes of the genus Schistosoma

Question 23

where is schistosomiasis common?

Answer 23

in tropical/ subtropical regions

areas with inadequate sanitisation and access to clean water

Question 24

what are the three main species of Schistosoma responsible for human infection? where do they each preferentially migrate to?

Answer 24

S. mansoni - liver
S. haematobium - bladder/ urinary tract
S. japonicum - liver

Question 25

describe the life-cycle of the Schistosoma parasite

Answer 25

Schistosoma parasite/ worm develops and multiplies in freshwater snails (intermediate host) - free-swimming larvae are released into water

humans become infected upon contact with contaminated freshwater

larvae penetrate the skin and transform into schistosomula - enter the blood - travel to the liver, mature into adult worms in the mesenteric arteries

adult worms migrate to preferred sites - e.g. intestines, bladder - depending on the species

Question 26

how does hepato-intestinal schistosomiasis occur? - cause? pathology?

Answer 26

cause: mainly by S. mansoni and S. japonicum infections as they tend to migrate to the liver and intestine as their preferred sites

pathology: liver damage, fibrosis, cirrhosis, portal hypertension, and other liver dysfunction
- occurs due to immune response mounted against eggs deposited in the hepatic portal system

Question 27

cercarial dermatitis in schistosomiasis - cause? pathology?

Answer 27

cause: following pre-sensitisation, exposure to Schistosoma larvae which penetrate the skin during contaminated freshwater contact

pathology: an allergic-type reaction characterised by granuloma formation
- can contribute to fibrosis and eventual organ damage with repeat exposure

Question 28

urinary schistosomiasis - cause? pathology?

Answer 28

cause: mainly S. haematobium - migrates to bladder preferentially
= presence of eggs in the urinary tract triggers inflammation and tissue damage

pathology: haematuria, other bladder pathologies like fibrosis, bladder wall thickening
- leads to complications =urinary tract obstruction, increased UTI susceptibility

Question 29

describe the immune response associated with granuloma formation in schistosomiasis - mechanism?

Answer 29

eggs deposited in tissues like the liver, bladder and intestines, are detected by the immune system as foreign

Th2 cells activated to produce IL-4, 5, 13, 10

IL-4 and 13 promote macrophages differentiation and activation, IL-5 stimulates eosinophil activation for granuloma response, IL-10 helps regulate and control the inflammatory response

granulomas form around the parasite eggs - isolate and contain the eggs within an area with macrophages

Question 30

why can granuloma formation in schistosomiasis become counterproductive?

Answer 30

initially protective as it forms around the parasite eggs, keeps them isolated

however the chronic inflammatory response can lead to tissue damage and specific organ damage - e.g. liver/ bladder fibrosis

Question 31

what type of disease is onchocerciasis?

Answer 31

helminth - filarial parasite

Question 32

what is onchocerciasis? causative pathogen? where is it most common?

Answer 32

major blinding disease – also known as river blindness

caused by filarial parasite Onchocerca volvulus

most common in sub-Saharan Africa, also in Latin America and Yemen

Question 33

transmission of onchocerciasis? - vector? transmission route?

Answer 33

transmitted by Simulium blackflies - breed in fast-flowing rivers

female blackflies transmit onchocerciasis/ Onchocerca volvulus by taking blood meals

Question 34

describe the life cycle of Onchocerca volvulus

Answer 34

infected larvae are transmitted to humans through an infected blackfly bite

larvae enter subcutaneous tissue and develop into adult worms over 6-12 months

adult worms form nodules under the skin = live in them for up to 15 years

female worms release microfilariae – migrate to the skin and eyes

blackflies ingest microfilariae when they bite an infected person

microfilariae develop into infective larvae within the blackfly over 10-12 days

infected larvae transmitted to another human host when the infected blackfly bites again… cycle repeats

Question 35

different pathologies/ effects of onchocerciasis?

Answer 35

mainly driven by body’s repeat inflammatory response to the presence of microfilariae – leads to permanent damage and scarring, esp. in the skin and eyes

microfilarie in skin

onchocercal (subcutaneous) nodules

skin disease (various forms of dermatitis) - sowda, chronic onchodermatitis

eye disease - affecting anterior or posterior segments, can lead to permanent blindness
- anterior segment = e.g. punctuate keratitis, sclerosing keratitis
- posterior segment = optic neuritis/ atrophy, chorioretinopathy

Question 36

onchocerciasis - immunopathology of acute/ initial infection?

Answer 36

parasite enters human host through bite of an infected Simulium blackfly - initial exposure, immune system responds to presence of microfilariae and adult worms

innate immune system responds with macrophages, neutrophils and eosinophils to target the larvae - predominantly Th2-type immune response with IL-4, 5, 13 production

acute inflammation induced by presence of microfilariae in skin & eyes, leads to dermatitis and acute eye inflammation

eosinophils and other immune cells try and kill larvae – results in localised tissue damage and inflammation

Question 36

onchocerciasis - immunopathology of chronic infection?

Answer 36

regulatory T cells and anti-infl. cytokines (e.g. IL-10, IL-17) are upregulated to modulate the immune response, prevent excessive tissue damage

adult worms live within host for many years - secrete immunomodulatory molecules to evade host immune system and establish a chronic infection

chronic inflammation with chronic dermatitis form persistent microfilariae, onchocercal nodules with granulomatous inflammatory response, ocular lesions affecting vision

Question 37

hard ticks - features?

Answer 37

hard shell-like plate called a scutum on their dorsal surface

generally larger, more rigid body structure

go through three main life cycle stages – larva, nymph, adult

attach to host for several days whilst feeding

Question 38

soft ticks - features?

Answer 38

lack a scum, more leathery, flexible body

tend to be smaller

go through multiple nymphal stages – feed for shorter periods but more frequently

Question 39

hard ticks - associated diseases?

Answer 39

tick typhus
viral encephalitis, viral (haemorrhagic) fevers
tick paralysis
human babesiosis

Question 40

soft ticks - associated diseases?

Answer 40

Q fever
relapsing fever

Question 41

Lyme disease - describe? causative ectoparasite?

Answer 41

caused by Borrelia burgdorferi - transmitted through the bite of infected Ixodes ectoparasite/ticks

early symptoms = bull’s eye rash, fever and fatigue

later symptoms = arthritis, neurological and cardiac issues

Question 42

pathology of ticks?

Answer 42

mechanical injury by tick bite causing irritation and redness

tick paralysis from neurotoxins produced by some tick species, interfere with host nerve function

ticks are vectors for various diseases

some ticks produce toxins that can cause localised/ more systemic allergic reactions

Question 43

botfly - life cycle?

Answer 43

adult botflies capture and use another insect – e.g. a mosquito, tick – to deliver their eggs to the host

when the carrier insect lands on a human/ warm-blooded animal (e.g. cow) – botfly eggs hatch, and larvae burrow into the skin

Question 44

botfly - symptoms?

Answer 44

localised skin lesions - itchy, red, may ooze fluid

crawling/ wriggling sensation beneath skin from larvae

inflammation, swelling, warm to the touch

Question 45

myiasis?

Answer 45

infestation of fly larvae in the body – can present various symptoms depending on the infected area

may include visible larvae under the skin, discomfort and localised infection

bleeding or spots in the eyes – ocular myiasis = can evolve into orbital cavitary myiasis
- swelling, pain and bleeding in the eye as larvae infest the eye are