Nematodes Flashcards
What type of worms are Nematodes?
Tell me some general facts about them
Nematodes- round worms
- Intestinal round worm infections constitute the larges group of helminthic disease
- Tissue living filarial worms cause devastating disease e.g., River blindness
Tell me about the structure of nematodes
- Size-Adults vary from ~1mm to >Placentonema gigantissima (means basically giant worm of the placenta) (~10m)
- Typically- dioecious (XX and XO) with sexual dimorphism cf C elegans (these are a great model to study for nematodes and anti-nematode)
(Males spicules to hold vulva open bursa in some males hold to female)
Tell me about the shedding of the nematodes and when this occurs?
Tell me how growth occurs
All show growth with shedding of a complex cuticle
– shedding occurs 4 times, sometimes 5 (as the egg could be viewed as one of the shedding stages)
- L1 to L4 to adult (L5)- only adult have formed gonads which are matured (microfilaria- differ, have a microfilarial stage…?)
- L5 is the sexually mature stage
- In adults any growth is by cellular hypertrophy (increase and growth of muscle cells) rather than hyperplasia (increase in the number of cells in an organ or tissue)
Tell me more about the nematodes structure
- Have usually a uniform cylindrical shape, with lips (0 to 6) opening onto a buccal cavity
- C elegans hermaphrodite (XX) and XO male, other species use XX female and XY male
- hardened structure in the wall that guides the protrusion of the spicule at copulation.[spicules open and dilate the vagina of the female and the gubernaculum is a plate which controls the spicules motion- useful for telling males and females and species apart;
- Pre L1 (prelarval- or embryo form)- in blood vessel dwellers known as a microfilaria – but this can be debated as some texts also call L1 microfilaria
- Nitrogenous breakdown products – lost as ammonia through cuticle, while more significant for excretory pore – ion balance
Nematodes usually lack holdfasts (cf cestodes and trematodes)
But instead, what do they have?
How does this work?
Nematodes- usually lack holdfasts (cf Cestodes and Trematodes)
But some have “teeth”- sit around pharynx so also suck through this
The GI tract is full and patent at both end- strong pumping oesophagus which changes between species and over life span of organism
Tell me about the muscular oesophagus in the nematodes
Muscular oesophagus – changes in shape between groups and in developmental stages -all have associated glands
Beyond the oesophagus valve the gut is a simple epithelial tube until the cloaca
Shape of oesophagus used to identify species and stage
Hermaphroditic here – and sincytial hypodermis
Full of fluid and acts as a skeleton of organism as helps to keep its structure
Excretory duct and channel which is important for ionic balance as opposed to nitrogenous balance
What are the different forms of the nematodes, describe their appearance and when this form is taken?
The exact arrangement of muscle fibres alters between species
The cuticle is under high pressure
Over 100 collagen forms- in cuticle- far more than mammals
Cells below basement membrane which produce that membrane (this is a mirror in humans as they have the other way round)
30 collagen tubes?
Tell me about the Pseudocoelom
Between the somatic muscles and the GI tract
Non compressible fluid – i.e., a hydrostatic skeleton
No circulatory system – but haemolymph acts to transport solutes
Some forms have a defined excretory system but most loss of nitrogenous waste is via diffusion over cuticle
Is under pressure and if damaged will burst
Tell me about the nervous system of the nematode
Formed predominantly from a nerve ring about the oesophagus / pharynx
C elegans 20 neurons innervate the pharynx and organise a ring shape structure, 282 somatic neurons
Dorsal/ Ventral and smaller lateral nerves innervating glands, rectum/ cloaca/ muscles (former) receive input from touch and chemoreceptive cilia, papillae, and bristles
Classes causing human disease
What is the life cycle of the Rhabditodea?
What is the timing of the cycle based on?
What are some signals?
Timing based upon C elegans - Egg dauer stage- diapause
Signals such as temperature, food supply, and levels of a dauer-inducing pheromone, a population density cue,
- Egg (L1) and L3 hardiness
- Inutero development –> hatching occurs in around 10-11 hours
- Then can stay in resting state where it can survive for several weeks
- Usual cycle is L2–> L3
- L4–> L5 in host
- Then mature as L5 sexually then reproduce
What does the Rhabditodea (Rhabditina) Class contain?
Rhabditoidea (C elegans and others- free living or parasitic)
Strongyloides (mostly parasitic worms)
This class contains the widest selection of nematodes- many are free living non parasites
some are obligate parasites and some facultative parasites
C elegans is a member of the group
Heterorhabditis … obligate parasites of insects, used as biological control agent
What does the nematode carry and what does this cause?
The nematode carries a toxic bacterium Photorhabdus luminensces which kills the grub
- Causes a colour change
- Causes fluorescence- prevents eating by predators
- Causes chemical releases
What is Strongyloidea?
Superfamily of worms mainly GI worms of herbivores (generally 2 sexes and oviparous)
Give an example of a Strongyloidea
Eg Haemochonchus contortus (sheep- v high losses, if infected it will kill sheep)
However, Human Hookworms* are part of this family
- Ancylostoma duodenale*
- Necator americanus*
*Don’t need to know these two names but it would be good if we did
Whats the life cycle of the Strongyloidea?
Blood sucking GI worms
Tell me about the stages of the Rhabditodea and what this means
L1 and. L2, the feeding non-infective rhabditoform stage, feed on soil microbes L3 the filariform stage is the non-feeding infective form of the larvae.
The filariformL3 larvae highly motile non feeding, and migrates up through soil.
Tell me about how the Rhabditodea infects their host?
Infect host through skin penetration (rare ingested) usually from soil with faecal contamination.
Larvae enters the vascular system (Blood Vessels and lymphatics)
carried to the lungs (see later)
and coughed or passed in cilia up the trachea
are swallowed and attach to the small intestine
where the larvae L3- mature to adult worms L5 (~ 1cm long- but can have infections of 1000s and each removed ~0.3ml blood per day)
- Necator infection, >5 years
- Ancylostoma ~ 6 months.
Long term infection. Don’t need to know exact times just that its long term
(However, L3 may encyst during body migration- give longer infection)
They mate inside the host, females laying up to 30,000 eggs per day, in warm conditions eggs develop in ~10 days to L3
Infection is usually asymptomatic with hookworm disease but what can it cause?
- Allergic reaction at the sire of parasitic penetration
- Migratory phase cough/ pneumonia
- Diarrhoea and GI colic
What can a high infection with hookworm disease lead to?
However high infection levels may cause chronic disease iron deficiency, anaemia, and protein malnutrition in children causes growth retardation and cognitive impairment.
Tell me about Translactation and Transplacental infection with hookworm disease
Skin-invasive larvae may migrate around the body via the circulation, to become dormant inside muscle fibres.
They may reactivate and re-enter the circulation (very common during pregnancy presumably by sudden hormonal changes), pass into the mammary glands and through its mother’s milk (cf canine infection). Explains heavy, hookworm infections very young children. (May also show transplacental infection – also observed in other species
Human ileum with hookworm infection
What is the life cycle for
Rhabditodea
Strongyloides stercoralis- human threadworm- a more complex facultative cycle
Strongyloid’s- have a complex life cycle choosing between free-living and parasitic heterogonic
The parasitic cycle is homogenic (pathogenic eggs formed),
The free-living cycle is heterogenic (male and female).
This allows reproduction in the absence of a host.
L1 rhabditiform larvae in faeces can either moult twice and become infective filariform larvae (L3), ormoult four times, become free-living adult males and females, mate, and produce eggs in the soil. These develop to infective filariform L3 larvae or can repeat a non-parasitic cycle.
Filariform L3 penetrate the skin to initiate the parasitic cycle (locate their hosts via chemicals in the skin and CO2). They pass into blood vessels carried to the lungs, where they enter the alveoli. Coughed up and swallowed they mature in SI mucosa to adult female worms, parthenogenically producing eggs…
The Rhabditodea also participate in autoinfection, tell me about this
Some eggs laid within the mucosa develop to L3 in the GI tract and penetrate either the intestinal mucosa or perianal skin. They then migrate to the lungs as before.
This can cause persistent infections cycling in the host for many years after having left an endemic area
Hence a female strongyloid can produce eggs which are one sex or both sexes
This can vary over her lifetime and is independent of the mothers (worm) age
External factors in differentiation of larvae/eggs
Warm soil temperatures and moisture- favours heterogenic development (likelihood large numbers of worms present to can find mate)
Internal factors in differentiation of larvae/eggs
Higher immune response in host result in heterogenic development
?? Higher fitness
(Immunosuppressed animals biased to homogenic females)
?? Lower pressure
Tell me about Strongyloidiasis- i.e., the disease
100M infected
Frequently asymptomatic
Migration stage- Skin rashes symptoms, respiratory signs (occasionally may migrate to other organs eg CNS)
Mature- colic diarrhoea and weight loss.
males 0.9mm in length, females to 2.5 mm
If an individual is immunosuppressed what could they get if infected with Strongyloids?
If immunosuppressed- hyper infection syndrome, disseminated (CNS)- due to autoinfection this may occur many years after initial infection due to steroids, or drug treatments (cf organ transplants) superimposed upon autoinfection
immune response may limit infection but not clear it always… but because autoinfection may result in low levels maintenance of parasite
Classes causing human disease
Tell me about Trichinellida (also called Trichocephalida or Trichurida) and what they often need to complete their life cycle
They are all vertebrates’ or parasites in their adult stage and often need the death followed by the rotting or ingestion of flesh of the primary host to complete their life cycle (rare)
What is the Trichinellida oesophagus formed from?
Glandular cells stichicytes which form a stichosome.
What are the important members of the Trichinellida ?
- Trichinella spiralis
- Capillaria
- Trichuris
Tell me about the eggs of Trichinellida
The eggs generally bipolar /biopercular plugs – however some are viviparous
Tell me about Trichinella spiralis
Small 1-3mm long worm dependent on gender
Same individual is definitive (primary) host and intermediate (secondary)
Huge number of hosts –carnivore/ omnivore (including man)- (but called “the pork worm”)
10,000 newly infected in China/ year
~1,000,000 people infected world-wide
Yugoslavian war showed still common in Europe
What is the life cycle of Trichinellida?
Adults INSIDE fused (syncytial) cells in the SI epithelium, mate and females produce live L1 larvae (~ 2000 in total).
These (0.1mm long) have stylets and penetrate membrane exiting the cell and enter the circulation, via lymphatics.
L1 transferred to muscle and invade cells. This results in the formation of a nurse cell from the muscle cell (see below).
This encapsulates the L1 as a small cystic structure
They grow as L2 here to reach ~1mm long, coiling up within the cell, - remain here viable for life of host
On ingestion of flesh (muscle mainly), L2 released from the nurse cell (stomach pH and proteolytic action) and migrate to the intestine, undergo 3 moults to L5 where they burrow into the intestinal mucosa, mature, and reproduce.
Will stay in L2 form for as long as it takes, sometimes they will die in this form
In regard to Trichinellida what is a Nurse cell?
Nurse cells- first description of parasite as “hard sand in muscle”
Driven by infection with L1
A multicellular parasite that lives within a single muscle cell, which it modifies according to its own requirements.
What happens within the first five days of nurse cell formation?
The first five days of Nurse cell formation -loss of normal structures and contractile functions.
- Actin and myosin filaments disappear.
- Muscle mitochondria become vacuolated (becoming larger) and reduced or lost
After the nurse cells form, the cell then shows a defined differentiation, tell me the changes in the cell seen here
Nuclei increased in size and altered mRNA transcriptome occurs (driven by paracrine products from larvae)
Outer “sarcoplasmic” membrane becomes highly convoluted and double membrane surrounds the larvae
Up-regulation of angiogenic cytokines, (esp -vascular endothelial growth factor (VEGF))- neovascularisation, TGFbeta, CTGF Increased synthesis of collagen type 1 and IV - capsule formation
Glycogen formation is retained or increased by the nurse cell
What is the resulting formation of the Trichinellida after the nurse cells develop?
Results in the formation of a protective niche, high blood flow, reduced nutritive competition (from nurse cell), allows anaerobic metabolism (NB – other stages of this nematode are aerobic), a degree of immunological protection (TGFb)-survives here the lifespan of the host!
Formation of nurse cells
For Trichinellida tell me the following…
How do the larvae travel?
What does the migration of worms result in and what can this cause?
How can infection be prevented?
The larvae travel by capillaries most organs retina, myocardium, or lymph nodes; (only larvae that migrate to skeletal muscle cells survive)
The migration of worms - traumatic damage and immunological reactions.
The resulting inflammation can cause symptoms sweating, facial oedema fever, muscular pain, difficulty breathing, heart damage, CNS disease
Prevention – Cooking of raw meat, limiting killing with salting, curing micro-waving
Outlawing -Feeding pigs uncooked meat products
Where does the pathogen
Trichinellida
Trichuris trichiura
Infect people?
Whip worm- estimated ~ 1,000,000,000 people infected worldwide
Mainly Asia (lesser Africa, South America)
Very extended oesophagus
What is the life cycle of Trichuris Trichiura?
Simple lifecycle
L1- L3/4 mature within
villus on the wall of the SI
The female produces
~10,000 single-celled eggs per day- survives ~1yr
Generally, causes mild GI
problems- Head buried into wall of intestine
Heavier infestations, (children), can present gastrointestinal problems colic, diarrhoea, tenesmus
Growth retardation, weight loss, nutritional deficiencies, and anaemia
Single cell egg formed
*Classes causing human disease
What is the life cycle of
Spirurina-Oxyuridomorpha
Enterobius vermicularis – pin or threadworm (Oxyurias vermicularis)
Lifecycle, from egg to adult, occurs in GI tract over ~4-8 weeks
Ingested Eggs, hatch in duodenum, larvae migrate through the small intestine with classical L1-L4 stages., Adult (L5) mate in the ileum (i.e., lower SI)
The gravid female remains in large intestine attached to mucosa and produces and matures eggs over 2-4 weeks- a gravid female pinworm holds ~15,000 eggs.
Adult 2-13mm long
The female pinworms migrate through the colon emerge from the anus, deposit eggs on skin or dies and then disintegrating, (rupture due to the host scratching the worm)
Eggs are reasonably hardy (>4 weeks and can survive freezing)
Eggs are sticky when laid and remain on perianal skin till moved to fingernails, hands, or clothing. Often part of dust in houses-, the eggs can enter the mouth and nose through inhalation and be swallowed.
What is the most common helminth infection in the west?
Pinworm
Tell me about Pinworm infection
Prevalence rates in children 50% in England~ 12% kids infected every year
Most cases are asymptomatic- anal, perianal pruritus
Reinfection is common-Autoinfection (i.e., infection from the original host to itself), very common – so repeated treatment is needed
- Finger sucking
- Nail biting
Close contact spreads (ie often infecting people within a household)
Common in both poor and affluent communities.
Whats the simple life cycle of Spiruromorpha ?
All produce live L1-
All have an arthropod intermediate
Produce some of the most devastating diseases
Life cycle of
Spirurina-Spiruromorpha
Dracunculus medinensis-Guinea worm-
Copepod – small (here freshwater crustacians -1-2mm e.g., daphnia ~
Infection from drinking water contaminated by water fleas (copepods) that host the Dracunculus medinensis larvae (L3). Hence infections related to limitation of clean water.
After ingestion, the copepods are digested releasing L3 larvae, which then penetrate the host intestine and then enter the abdominal cavity – Here they mature to adult (L5) and mate.
The male guinea worm 12–29 mm dies, while the female grows further (to 100cm- over 6-12 months)
The fertilized females migrate in the subcutaneous tissues over long bones and emerges often over joints causing blisters on the skin. (Often foot).
The blister is very painful leading the host to immerse the limb in water the female releases hundreds of thousands of L1 guinea worm larvae, contaminating the water.
The female worm may release larvae over a month
Larvae are eaten by copepods, L1- in~ two weeks and remain encysted in tissue for the lifespan of the second host ~4mths
Whats a disease caused by Dracunculus
Tell me about this disease
What symptoms does it cause?
Pain “fiery serpent” or “dragon disease”- Dracunculus
Female worms often cause allergic reactions during blister formation and migration
- Fever, nausea, GI problems dizziness, and oedema
- skin ulcers form and remain until worm is removed- infections
Death of adult worms can result in massive tissue damage due to inflammatory response to released antigens
Is Dracunculiasis an eradicable disease ?
Yes
Is Dracunculiasis easy to diagnose?
Yes and its umambiguous
How long does the Dracunculiasis worm survive?
roughly 12 months (cf other nematode infections of this clade)
What is the intermediate host of D. medinensis and where is it restricted to?
Intermediate host of D. medinensis (Cyclops spp.) is restricted to stagnant water bodies;(cf flying mosquitos)
What are some control interventions to prevent the spread of disease for Dracunculiasis?
Control interventions are simple to implement, cost effective; -
- Water treatment
- Water filtering when drinking
- Prevent infected people contacting open water
- Treatment of patient, potential patients
Does the D. medinensis disease have limited graphical distribution?
The disease has limited geographical distribution and transmission is seasonal (rainy season) the Carter Centre / WHO / UNICEF
Many water sources dry each year, copepods survive as eggs (uninfected) – but these not infected so annual cycle maintained by worms in primary hosts
Number of human cases of Guinea worm disease worldwide since 1986
Guinea-worm cases in dogs
1030 + cases in dogs
Emerg Infect Dis 2016 Aug;22(8):1428-30Possible Role of Fish and Frogs as Paratenic Hosts of Dracunculus medinensis, Chad
Mark L Eberhard, Michael J Yabsley, Hubert Zirimwabagabo, Henry Bishop, Christopher A Cleveland, John C Maerz, Robert Bringolf, Ernesto Ruiz-Tiben
What is Filariasis?
Parasitic disease caused by an infection with nematode spread by blood-feeding black flies and mosquitoes
Tell me about the adult worm of Spirurina-Spiruromorpha
They stay in one tissue, release L1 forms of microfilariae into the host blood stream
These are taken up with a blood meal by the arthropod vector, where they develop into infective larvae
The insects need to take two meals for infection and transmission
How many known filarial nematodes use humans as their definitive hosts?
Why does disease differ?
8
Disease differs and can be caused by adult or filaria, dependent on the species
What is Lymphatic filariasis caused by?
Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi and Brugia timori (elephantiasis)
What is Subcutaneous filariasis caused by?
Subcutaneous filariasis is caused by Loa loa (the eye worm), Mansonella streptocerca, and Onchocerca volvulus. Adults’ worms present in the subcutaneous layers (dermis/ fat layers),
What is Serous cavity filariasis cased by?
Serous cavity filariasis is caused by Mansonella perstans and Mansonella ozzardi adults found the cavity of the abdomen
What is the life cycle for
Spirurina-Spiruromorpha
Onchocerca volvulus
O. volvulus - a (Simulium) female black fly bites and ingests microfilariae form of the parasite in vessels of the dermis of the host.
The microfilariae penetrate the gut and migrates to thoracic flight muscles of the fly. After maturing to L2, (~3weeks) the second larval phase, it migrates to the proboscis and found in the saliva.
Saliva containing stage L3 O. volvulus larvae passes into the blood of the host at biting. L3s migrate to the subcutaneous tissue, form nodules and mature to L5/ adult worms over ~six months.
On maturation, the adult males migrate through subcutaneous tissue looking for females
Adult females produce ~3,000 microfilariae per day. The normal female worm lifespan is up to 15 years.
The eggs mature internally to form stage one microfilariae, released from the female’s body one at a time and remain in the subcutaneous tissue.
What do the adult worm of Onchocerca volvulus induce?
Limited immune response (generally a type 2 response)
If the adult worms of Onchocerca volvulus are in nodules, what are they protected from?
The immune response
Microfilarae of Onchocerca volvulus can drive what and what does it trigger and what response does it have?
However, Microfilarae can drive violent inflammation, especially when dying as release Wolbachia (see later), This has toll-like-receptor triggering antigens (TLR2 and TLR4), driving strong innate immune responses– severe inflammation.
As in skin- Can cause intense itching, swelling and inflammation (which can result in suicide)
Should antifilarials be used to treat disease by Onchocerca volvulus?
No, it may make the disease worse because the microfilaraw die
Why does Onchocerca volvulus lead to Onchocerciasis, (river blindness- Robles’disease) ?
Onchocerciasis, (river blindness- Robles’disease) as microfilaria can enter conjunctiva, cornea and retina and optic nerve.
Main effect is on the cornea which can show chronic inflammation like skin and in time scarring
The skin is itchy, with severe rashes permanently damaging areas of skin
What is the treatment for river blindness?
- Infected (diagnosis)
- Secondary host- treat water sources with insect larvaecides- as simulium larval stage in water
- Both have limitations
What are the problems with river blindness?
- Long term disease
- Pathology seen late
- Fast flowing water- rapid transfer
- Flying vector- rapid transfer
- Long lived parasite and fecund
- Treatments reduce Mf production
- Don’t kill adult (do Mf)
- Difficult to kill secondary host
- Treatment itself causes pathology
- Resistance
Name a therapeutic in use for onchocerciasis
Ivermectin
How does Ivermectin work against onchocerciasis?
Ivermectin paralyses and kills microfilariae, relieving intense skin itching and halting the progression towards blindness (may have short term worsening of symptoms)
It also prevents adult worms from producing more microfilariae for a few months following treatment, so reduces transmission.
Second host spraying - usually not cost effective and much damage to other insects
Tell me about Ivermectins/ Avermectin, what is its mechanism of action?
Wide-spectrum anti-parasiticide
Arthropods and Nematodes
Agonist Glutamate gated Cl- channel (non-competitive to glutamate)
Cl- influx causes hyperpolarisation and paralysis at level of nervous and muscle cells
Why is ivermectin toxic to mammals?
Mammals, these receptors only present in brain and avermectins don’t cross the BBB
in part is due to the efflux transporter P-glycoprotein
genetic defects in MDR1 (P-glycoprotein) gene result in ivermectin toxicity eg Collie dogs
some drugs e.g. statins, glucocorticoids can effect P glucoprotein function or expression and increase likelihood of ivermectin toxicity
Where is
Spirurina-Spiruromorpha
Wolbachia pipientis
Found?
Found in all filarial worms except Loa Loa-
Elephantiasis / lymphatic filariasis Wuchereria bancrofti and Brugia malayi,
River Blindness/ onchocerciasis Onchocerca volvulus
Serous cavity filariasis Mansonella perstans
Heart-worm Dirofilaria immitis- seen in dogs
Also Pleomorphic (0.2 to 4µm long) bacteria
Pleomorphic is a term to describe cells that are all different to each other in size
Where does Wolbachia reside ?
Wolbachia reside in specific intracellular vacuoles (one bacteria within one vacuole except when multiplying)- show a specific cell tropism in syncytial hypodermal cord cells (under the cuticle) ovarian tissues, oogonia, oocytes and developing embryos within the uterus
How are Wolbachia transmitted from mother to offspring?
Tell me about this
Wolbachia are vertically transmitted from mother to offspring
Levels of infection alter over the life cycle
Numbers vary considerably during filarial development
Wolbachia numbers are at their lowest (~ 70–100) in microfilariae (Mf) and the insect-borne stages (L2 and L3).
After transmission to the mammalian host a dramatic increase occurs 4–14x 106 in female worms.
??Needed for oogenesis and/or embryogenesis
Higher levels of Wolbachia infection may confer what?
Selective advantages in development of fecundity
Where does Wolbachia pipientis exist?
only exists Intracelluarly
What has Wolbachia pipientis lost genes for? but what is it still able to do?
Has lost genes needed for making complete bacterial peptidoglycan wall- but still make some molecules of the wall including
Wolbachia peptidoglycan-associated lipoprotein (wBmPAL) stimulates both innate and adaptive inflammatory responses associated with filarial disease
What drives severe inflammatory disease with Wolbachia pipientis?
Wolbachia and wBmPAL released by dying microfilaria drives severe inflammatory disease
Antibiotic elimination of the bacteria Wolbachia pipientis leads to what?
Antibiotic elimination of the bacteria leads to apoptosis specific form cells adult germline cells, somatic cells of the embryos, microfilariae and L4 (NB not seen in all somatic cells especially in adult)
Genome of filarial nematodes shows loss of what?
Shows loss of the ability to produce haem, riboflavin and adenine nucleotides de novo and requires Wolbachia (these produces not generally obtained from parasitised host- nematodes dont have suitable transporters in gut/ hypodermal cells
In some filarial species, Wolbachia may also have what role?
An ATP generating role
(NB –a true symbiotic relationship as coenzyme A, biotin, ubiquinone, folate, lipoic acid and pyridoxal phosphate etc can’t be formed by the bacteria and obtained from the nematode)
What are the treatments for filarial nematodes based on?
Killing wolbachia
Tell me some treatments for filarial nematodes
Doxycycline (licenced tetracycline antibiotic) used to treat filariae-infected individuals’ permanent sterilization of female worms and slow death of adults loss of microfilariae no severe inflammatory reactions as Wolbachia main cause of inflammation dies in nematode cells and undergoes degradation in nematode endosomes without releasing wBmPAL
What is Nodding syndrome linked to?
Incidence and geography of O.Volvulus
Tell me about Nodding syndrome, what do patients with this syndrome have?
What type of disease is nodding syndrome thought to be and why is this the case?
Patients with nodding syndrome have autoantibodies to leiomodin-1 that are neurotoxic Leiomodin-1 is expressed in regions of the brain affected in nodding disease.
Leiomodin-1 antibodies cross-react with O. volvulus proteins, linking the parasite to the autoantibody.
Thus, nodding syndrome may be an autoimmune disease initiated by a parasitic infection
Tell me about the carbohydrate larval antigen and what nematode species it is present on
Present on the exposed surface of L3 larvae of strongyloid nematodes
Leads to rapid immune rejection
antibodies against CarLA –> Rapid immune rejection of incoming Trichostrongylus calubriforms larvae in sheep
Antigenic variation within CarLA is a likely mechanism of immune evasion of strongyloid nematodes
