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.
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
Formation of nurse cells
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.
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
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 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.
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
What drives severe inflammatory disease with Wolbachia pipientis?
Wolbachia and wBmPAL released by dying microfilaria drives severe inflammatory disease
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
