29 Helminths Flashcards
where is a parasite
live on or in a host organism and benefit by deriving nutrients at the other’s expense
where is an endoparasite
live within their host
what is a helminth
parasitic organisms with worm-like anatomy
examples of nematoda - nematodes
roundworms
hookworms
filaria
examples of where trematoda - flukes infect
liver, blood, lung and intestinal
examples of cestoda
tapeworms
which are platyhelminths (flatworms)
trematoda
cestoda
which helminth causes high mortality
schistosomiasis worst
what causes disease burden
Disease burden is not just about deaths – also the rate of infection
- incidence of infection is very high for some helminth infections
- e.g. ascariasis kills 60,000 but infected 900 million
what is morbidity
incidence of ill health within a population
what can cause great burden but not death
Chronic infections in particular can create a great burden through non-fatal ill-health
Lymphatic filariasis - blocking of the lymph nodes, inflammation
what is DALY stand for
DALY = YLL + YLD
Disability-adjusted life years
what is DALY
Number of productive years ‘lost’ due to disability or premature death (morbidity and mortality) expressed in the same unit
what is DALY dependent on
Years of Lost Life (due to premature mortality)
Years Lost to Disability (due to injury or illness)
YLD = I x DW x L
Incidence in population
Disability Weight of specific condition
Average Length of time (years) until remission or death
what is one DALY equivalent to
one year of healthy life lost
what is helminths burden names
Neglected Tropical Diseases
where do helminths diseases effect
Helminths burden is in low socio-economic countries
what increases helminths infections
Increased sanitation removes a lot of these diseases
Warm climates required for a number of them either because
why can helminths infect better in warmer climates
- a vector is required for them e.g. a flying insect /snail in water – required for lifecycle
- hookworm require warm climate for larvae stage
what are nematoda
Round worms
what have nematoda got
Have a proper mouth and anus – proper absorptive gut
Reproductive organs
do nematoda have genders
dioecious (separate males and females) – they generally mate in the host
what do nematoda have on outside of cuticle
on their outside they have a tough cuticle: moults with growth; tough outer layer; environmental resistance in free-living relatives; glycoprotein/glycolipid coverage; interface with the immune system
what is the phylogeny of nematodes based on
18S sequences
what are there within the nematode phylogeny clades
Within clades there are many free-living lineages Multiple lineages show parasitism with: - Invertebrates - Plants - Vertebrates
what is the most common drug used in against nematodes
albendazole
what is the most common human infecting nematode
pinworm
what are the modes of transmission for common nematode parasites of humans
Those that infect us are mostly intestinal; many are transmitted by direct routes: ingestion or skin penetration, exit host faecally
Filaria nematodes transmitted by biting insects, not intestinal – direct through the bite
how is ascaris spread
transmitted by SOIL ingestion
how does ascaris infect
ingestion of eggs
what is ascaris
soil transmitted nematode
example of roundworms
what is necator
soil transmitted nematode
example of hookworm
how is necator transmitted
transmitted by skin penetration from SOIL
how does necator infect
larvae skin penetration
where is part of the development for soil transmitted helminths
in the soil
why do soil transmitted helminths require warm climate
Eggs more resilient than larvae (even more so the hookworm as the larvae are more effected than the eggs)
what causes the burden of disease
Burden of disease greatest in conditions of poverty, largely due to:
- poor sanitation
- warm climate
what does the soil transmitted helminths result in
- stunting (nutritional burden as nematodes ‘steal’)
- anaemia (particulary from hookworm)
- diminished school performance (many years of lost schooling attributable to soil-transmitted helminths)
what is Ascaris lumbricoides
giant round worm
how is Ascaris lumbricoides transmitted
through eggs ingestion
what are the Ascaris lumbricoides hosts
humans
what DALY does Ascaris lumbricoides cause
high mortality but higher incidence = high DALY
how long can ascaris eggs persist in soil
eggs in soil infections after 2 weeks can persist for years
how many eggs can females lay in ascaris lifecycle
Each adult female in host can lay 200,00 eggs a day
how can humans get contaminated with ascaris
Humans contaminated through environment (hands feet in soil) lead to eating the helminths (in at the mouth and out at the anus)
what is the route that ascaris infect
‘direct route’ parasite; eggs ingested by human hosts
what are the intermediate hosts
non
what does ascaris do inside the host
When in the body it does a lap of the body
- larvae escape from intestine into bloodstream
- migrate (via liver and heart) to lungs
- leave bloodstream to escape into alveoli (grow here)
- migrate up trachea (coughed up)
- Swallowed back to intestine for maturation, mating and egg laying
why are encounters with the human immune system are complex
due to multiple:
- growth stages (larvae, adults, eggs)
- locations in the body
how does larvae in ascaris lifecycle lead to pathology
Larvae: immune-mediated pathology e.g. eosinophilia, pneumonitis
how does adult ascaris lead to pathology
- malnutrition
- small bowel obstruction
wandering Ascaris: biliary tract obstruction, pancreatitis, liver abscess
what is the host for Necator americanus
humans
how is Necator americanus transmitted
skin penetration by larvae
what is Necator americanus
hookworm
what do hookworms require in their lifecycle
- filariform larvae need warm wet conditions
- hookworms gain access to host by burrowing into skin
where do adults live in hookworm lifecycle
small intestine
what do the adult hookworms do in the intestine
attach to intestine wall and take blood
30-200μL blood per day per hookworm
what do hookworms cause
Intestinal blood loss + iron deficiency anaemia
what interactions do hookworms have with host immune system
- Transient (larvae) systemic
- Prolonged (adults) intestine
what changes with hookworm infection as we age
Human burden of soil-transmitted nematodes with age
Even older people previously exposed to intestinal nematodes often do not mount a protective immune response – chronic and repeat infections common
how are filarial nematodes transmitted
biting insects
what can mosquitoes transmit
wucheria
what is Wuchereria bancrofti
filarial roundworm
what does the Wuchereria bancrofti infect
lymph system
what is Wuchereria bancrofti vector
mosquito
what is the Wuchereria route
caused by mosquito – straight into bloodstream
what is the Onchocerca route
transmitted by blackfly – scratches at skin till blood comes out and starts to drink – within the skin
how can onchocerca route cause blindness
if happens near eye = blindness
what are platyhelminths
flat worms
largely free-living group
what are neodermata
entirely parasite lineage
where are human parasites
Eucestoda [Cestoda class] – common name tapeworms
Digenea [Trematoda class] – common name flukes
what are trematoda like
Have mouth anus and intestine – not a proper absorptive intestine
Often hermaphroditic
what is tegument
protective, but also highly dynamic – secretion, absorption of nutrients, glycocalyx, turnover
what is the glycocalyx
Sugar coating – glycocalyx, don’t need to malt the same way nematodes do
what are the 3 main blood fluke species infecting humans
Schistosoma mansoni
haemotobium
japonicum
what do Schistosoma mansoni, haemotobium, japonicum cause
get a red rash where the snail enters the skin
what is the host of Schistosoma mansoni, haemotobium, japonicum
snails
how is Schistosoma mansoni excreted
excreted faecally
how is haemotobium excreted
in urine
how is japonicum secreted
faecally
what do cercariae do
penetrate skin of humans who contact contaminated water
what do larvae do in lifecycles of Schistosoma mansoni, haemotobium & japonicum
mature, mate in circulatory system (dioecious) & move to bowl or bladder venules
where do the eggs go in the lifecycles of Schistosoma mansoni, haemotobium & japonicum
eggs move across the epithelium into the lumen of intestines or urinary bladder
what is the problem with japonicum
zoonosis disease = more troublesome
can humans get immunity to Schistosoma mansoni, haemotobium & japonicum
Humans can induce protective immunity to Schistosoma over time
what are Th2 important for
clearance of helminth infections, characterised by IgE, IgA & eosinophils
what is Treg important for
for resolving anti-Helminth inflammatory response
what do immature Th0 do
cells can differentiate into number of different T helper cell types
what are Th1 and Th17 used for
Th1 and Th17 can be treated as a combined pro-inflammatory force
what do Treg cells do
- Self-stimulation - TGF-β
- Suppress activity of other Th types
- Produce anti-inflammatory IL-10
what do Th1 and Th2 release
release cytokines that reinforce response direction (IFN-γ, IL-4) – “self-stimulating”
=> response can be polarised towards (Th1 or Th17) or Th2
what does the presence of helminths cause
elicits a strong Th2 response in host (IL-4 as marker)
what is Th2 beneficial to
Th2 is beneficial to the host and parasite
why is Th2 beneficial to host
- lower Th1, less inflammation
- required for clearance
why is Th2 beneficial to parasite
- less cytotoxicity to kill them off
why have we evolved to prevent Th1 response
prevent Th1 response as this would be more harmful than chronic illness being caused
why is Th2 response referred to as quick and dirty
Th2-mediated tissue-repair allows tissue regeneration without excessive inflammatory tissue damage, BUT there is often scarring
what do Th2 cells make
IL-4
IL-5
what can IL-5 activate
eosinophils
what can IL-4 activate
B cells, switch to producing IgE
what does IgE bind to
a helminth antigen it recognises can bid to IgE receptor on eosinophils/mast cells
can signal downstream from these motifs
when are eosinophils activated
Eosinophils effector cells are induced during helminth infections
Eosinophils activated by IL-5 in helminth infections
how can eosinophils kill helminths
Signals from the eosinophil FceRI-IgE-helminth antigen trigger potential pathogen killing mechanisms
what are the mechanisms that eosinophils do to kill helminths - schistosoma
attack a Schistosoma larva in the presence of infected patient serum in vitro
what are the mechanisms that eosinophils do to kill helminths
vasodilation, neutrophil & eosinophil recruitment and activation of more eosinophils
IgE bound to helminth antigen
how can IgE binding to helminth lead to helminth kills
- Granules (enzymatic and nonenzymatic cationic proteins)
- Oxygen radical release (damaging to pathogens)
what does the lack of schistosomiasis mean
For Schistosomiasis patients lack of reinfection DOES correlate with high peripheral blood eosinophils
what makes IL-10
Treg
what is the effect of modified Th2
generally reduce response to Tregs
- makelots IgG4
effect of balanced Th1/Th2
- more IgE
- still some IgG4
effect of uncontrolled Th1
- little IgG4
- more but not lots IgE
what is the effect of modified TH2 response cytokines
HIGH IL-4, HIGH IL-10 and LOW IL-5 compared to balanced or TH1-dominant states
effect on B cells in modified TH2 response cytokines
B cells make IgG4 (protects from over inflammation, doesn’t activate complement – no immune response)
how is inflammation reduced in modified TH2 response cytokines
absence of high levels of IgG, Treg are making IL-10, the IL-10 inhibits the IgE and allows IgG4 to dominate = reduce eosinophil activation and increases IgG4, reduces inflammation
how do helminths actively modulate adaptive immune response
secrete a range of substances that modulate immune system
- cytokine mimics (e.g. TGF-β-mimics)
- non-protein signatures (e.g. host-like glycans & phospho-lipids) – hiding!
- protease inhibitors
how do protease inhibitors modulate adaptive immune response
cystatins block inflammatory signalling cascades
what do helminths secrete that modulate immune effectors
- proteases and anti-oxidant enzymes
- protease inhibitors
what do protease and anti-oxidant enzymes do
block Eosinophil recruitment and killing
what do protease inhibitors do
serpins block neutrophil secreted proteases
what are the disadvantages of immunoregulation by helminths
require a strong Th1 response for:
- fight bacterial, viral and protozoal infections – which can be downregulated by helminth infection
- fight tumours, reduced anti-tumour immunity
- vaccines usually require Th1 mediated response, and high IgG levels = reduced efficacy
what are the benefits of immunoregulation by helminths
Anti-inflammatory activity for
- asthma
- autoimmune diseases
- inflammatory bowl disease
what will helminths possibly be used for in the future
Helminth-derived products may be the anti-inflammatories of the future
what are Schistosoma eggs like
highly immunogenic
what does SEA stand for
Schistosoma egg antigen
what does SEA do
recruits immune cells (Th2-mediated) = Granuloma
where does the granuloma form
Body ‘pushes’ granuloma across intestine or bladder wall to expel
