Week 2 - The Helminths

Question 1

What does the word ‘helminth’ mean?

Answer 1

‘Helminth’ is a general term meaning worm, prefixes are used to determine the type of worm.

Question 2

What type of worm are platy-helminths?

Answer 2

Platy-helminths are flat worms.

Question 3

What type of worm are nemat-helminths?

Answer 3

Nemat-helminths are round worms.

Question 4

How many major groups of parasitic helminths are there?

Answer 4

There are three major assemblages of parasitic helminths:

Nematodes, Cestodes and Trematodes

Question 5

What characteristics do all helminths share?

Answer 5

All helminths are multicellular eukaryotic invertebrates with tube-like or flattened bodies and exhibit bilateral symmetry.

Question 6

Do flatworms have body cavities?

Answer 6

No, the flatworms are a coelomate, they do not have body cavities.

Question 7

Do the roundworms have body cavities?

Answer 7

Yes, the roundworms (nematodes) are pseudocoelomate, that is they have body cavities which are not enclosed by mesoderm.

Question 8

Describe the nematodes anatomy.

Answer 8

Nematodes (roundworms) have long thin unsegmented tube-like bodies with anterior mouths and longitudinal digestive tracts. They have a fluid-filled internal body cavity (pseudocoelum), which acts as a hydrostatic skeleton providing rigidity.

They have a tough outer layer (cuticle), that offers environmental resistance in free-living relatives. The nematodes use longitudinal muscles to provide a sideways thrashing motion.

Question 9

How do nematodes typically mate?

Answer 9

Nematodes are ‘dioecious’, they generally mate in the host. Adult worms form separate sexes with well developed reproductive systems.

Question 10

Do nematodes have any free-living lineages?

Answer 10

Yes, there are many free living nematode lineages. These lineages show parasitism with vertebrate, invertebrate and plant hosts.

Question 11

Nematodes are primarily parasites of which body area?

Answer 11

Nematodes are primarily intestinal parasites.

Question 12

What is the typical transmission method for nematodes?

Answer 12

Most nematodes are transmitted via DIRECT routes - Ingestion or Skin Penetration.

Question 13

Describe the disease ‘Filariasis’.

Answer 13

Filariasis is a parasitic disease caused by a nematode infection. It is spread by black flies and mosquitos when they take a blood meal. A symptom is elephantiasis, rashes, arthritis and abdominal pain may also be present.

Question 14

How many filarial nematodes use humans as their definitive hosts?

Answer 14

Eight known filarial nematodes.

Question 15

How are the filarial nematodes that use humans as their definitive hosts grouped?

Answer 15

They are divided according to the niche within the body they occupy into 3 groups.

Lymphatic filariasis
Subcutaneous filariasis
Serious cavity filariasis

Question 16

How do Soil-Transmitted Helminths (STH) reach a human host?

Answer 16

STH infect via eggs which are ingested from contaminated soil (Ascaris, Trichuris) or via skin penetration (hookworm).

Question 17

Name some soil-transmitted helminths.

Answer 17

Ascaris, Trichuris (whipworm), hookworm and pinworm.

Question 18

What climate do STH require?

Answer 18

Soil-transmitted helminths typically require warm and wet climates.

Question 19

Why are STH a greater burden in poorer countries?

Answer 19

Poor sanitation conditions and poverty increase the burden caused by STH. This leads to stunted growth, anaemia and reduced school performance due to years of lost education due to infection.

Question 20

Provide details of ‘Trichuris trichiura’.

Answer 20

Trichuris trichiura
A nematode parasite also known as ‘whipworm’. It is transmitted through egg ingestions and present in human hosts.

The worms are ~4cm and infect 470M and kill 10000 a year. Whipworm causes trichuriasis, a neglected tropical disease, that infects the human large intestine

Question 21

Describe the disease Trichuriasis

Answer 21

Trichuriasis is also known as whipworm infection. It an infection by the parasitic worm Trichuris trichiura. A few worms cause no symptoms, however a large infection by many worms results in abdominal pain, tiredness and diarrhoea, sometimes containing blood. Low RBC levels may occur due to blood loss.

Question 22

Describe the lifecycle of Trichuris.

Answer 22

Trichuris is a direct route parasite. The eggs are ingested and hatch in the human small intestine. Here they exploit the microflora and this stimulates hatching. The infective larvae penetrate the villi and continue to develop in the S intestine.

The young worms move to the cecum and penetrate the mucosa, they then develop into adult worms in the large intestine. It takes approx. 3 months to go from ingestion of eggs to mature worms.

Worms can live up to 5 years, during this time females can lay up to 20,000 eggs a day.

Question 23

How are people typically infected by Trichuris?

Answer 23

Trichuris infection typically occurs through the ingestions of eggs and is more common in warmer areas. Whipworm eggs are passed in the feces of infected persons, and if an infected person defecates outside, eggs are deposited onto the soil where they can mature into an infective stage.

Ingestion of these eggs can occur through eating unwashed vegetables or not cleaning contaminated hands.

Question 24

Provide details of ‘Ascaris lumbricoides’.

Answer 24

Ascaris lumbricoides
Causes the disease Ascariasis. It is a nematode also known as ‘giant roundworm’. It exists in human hosts and can grow to >50cm. 900M are infected and 60,000 die each year.

Question 25

Describe the lifecycle of 'Ascaris'.

Answer 25

1. Embryo within shell passes in feces. 2. The Egg develops into a first-stage juvenile. 3. Two jolts occur and the Egg then contains a third-stage juvenile. 4. The J3 egg is then ingested on raw fruit or vegetable. 5. Egg hatches in the small intestine and the juvenile penetrates the intestinal wall and enters venues of hepatic portal system. 6. The juveniles undergo further development during migration. 7. J4 emerges into the alveoli and migrates in bronchioles to trachea and then up the trachea. They are then swallowed down the oesophagus. 8. The worms reach the small intestine again and develop into adults. 9. The fertilised and unfertilised eggs pass out in feces.

Question 26

What symptoms does Ascariasis cause?

Answer 26

Larvae - eosinophilia and pneumonitas. Adults - malnutrition, small bowel obstruction, wandering ascaris (biliary tract obstruction), liver abscess.

Question 27

How many eggs can a female Ascaris lay a day?

Answer 27

200,000 eggs a day.

Question 28

Provide details about the parasite 'Necator americanus'.

Answer 28

``` Necator americanus Causes the disease Necatoriasis. Is a nematode. Known as 'New World Hookworm' Human hosts, penetrates through skin. 1cm long. Infects 660million, 125,000 deaths ```

Question 29

How do Hookworms gain access to the host?

Answer 29

They burrow directly through the skin.

Question 30

Where do hookworms occupy?

Answer 30

The adults live in the small intestine. They attach to the intestinal wall and take blood.

Question 31

How much blood do hookworms take a day?

Answer 31

30-200microlitres per day, per hookworm. | This can lead to intestinal blood loss and therefore iron deficiency anaemia.

Question 32

Describe the lifecycle of the Hookworm.

Answer 32

1. The embryonated egg is passed in feces. 2. The first-stage juvenile (rhabditiform) hatches. 3. Two jolts ensue and the infective third-stage juvenile (filariform) enters developmental arrest until it reaches a new host. 4. Filariform juveniles 'quest' on blades of grass and penetrate the skin of humans. 5. Juveniles migrate through the circulatory system to the lungs. 6. Juveniles break out of the circulatory system into alveoli where they molt to the fourth stage. 7. Juveniles then migrate to small intestine via the trachea where they are swallowed. 8. Fourth stage juveniles molt to adults in the small intestine, mate, and produce eggs.

Question 33

What proportion of the World's population are infected with Hookworms?

Answer 33

~10% of the World's population are infected. | This results in significant levels of anemia and protein malnutrition.

Question 34

Do hookworm burdens decrease in adult years?

Answer 34

No, worm burdens do not decline in adult years.

Question 35

What are filarial nematodes?

Answer 35

Infections with parasitic filarial worms cause filariasis. Filarial nematodes congregate in the heart or beneath the skin. There are 8 human host filarial nematodes.

Question 36

Provide details about 'Wuchereria bancrofti'.

Answer 36

``` W. bancrofti Causes lymphatic filariasis. Is a nematode, also known as 'filarial roundworm'. Transmitted via a mosquito host. Infects 120 million, kills 300. ```

Question 37

Describe the lifecycle of W. bancrofti.

Answer 37

1. Mosquito ingests microfilariae when biting human. 2. Microfilariae (live young) pass through mosquito gut into hemocoel and develop into filariform juveniles. 3. The infected mosquito transmits filariform juveniles which enter through the wound puncture. 4. Juveniles migrate via lymphatics to regional lymph nodes. 5. The adult worms develop to sexual maturity in afferent lymphatic vessels. 6. Adult worms mate and female gives birth to sheathed microfilariae. 7. Microfilariae migrate to bloodstream.

Question 38

Describe 'Onchocerca olvulus'.

Answer 38

'O. olvulus' is a filarial nematode. Adults exist in subcutaneous nodules and the disease - Onchocerciasis is transmitted by blackflies. Unsheathed microfilariae are found in the skin.

Question 39

What is Neodermata?

Answer 39

Neodermata is an entirely parasitic lineage of the platyhelminths.

Question 40

What two subclasses of platyhelminths contain human parasites?

Answer 40

Digenea (Trematoda) | Eucestoda (Cestoda)

Question 41

Describe the morphology of Trematodes.

Answer 41

Trematodes have a ventral sucker and a simple digestive system. The intestine is a simple sac. They possess tegument which is a hardened cuticle that offers protection but is highly dynamic. Eggs are present in a coiled uterus, testes are also present. Often hermaphroditic.

Question 42

Describe the trematodes tegument.

Answer 42

Tegument is a living complex tissue. It is protective but highly dynamic. It can absorb nutrients and secrete glycocalyx.

Question 43

Describe the morphology of the Cestoda.

Answer 43

Cestoda are tapeworms. They possess long flat ribbon like bodies with a single attachment structure - scolex. They have numerous segments (proglottids). They do not have a gut and all nutrients are taken up through the tegument. They are acoelomate, meaning they do not have a body cavity. The segments can move slowly due to longitudinal and transverse muscle contractions. Tapeworms are hermaphroditic and each segment contains both male and female organs.

Question 44

What are trematodes also known as?

Answer 44

Flukes

Question 45

What are cestodes also known as?

Answer 45

Tapeworms

Question 46

Describe the generalised lifecycle of flukes.

Answer 46

1. Eggs are passed into the environment in feces or urine. 2. In water, eggs hatch into free-swimming miracidia (larvae). 3. Miracidia penetrate freshwater snail. 4. Miracidia reproduce asexually in snail, forming cercariae. 5. Swimming cercariae escape from the snail host. 5a. Cercariae of blood flukes penetrate human skin. 5b. Cercariae of lung and of some intestinal and liver flukes settle on plants and become metacercariae. 5c. Cercariae of lung and of some intestinal liver flukes penetrate molluscs, fish or crustaceans and become encysted metacercariae in muscle. 6. Metacercariae on plants or in undercooked fish are ingested by humans. 7. Adults develop in definitive host.

Question 47

What do all flukes require for larval development?

Answer 47

All require mollusc for larval development.

Question 48

What is the basic pattern of a trematode's life cycle?

Answer 48

Egg → Miracidium → Sporocyst → Redia → Cercaria → Metacercaria → Adult

Question 49

What are sporocysts?

Answer 49

Sporocysts are formed from the metamorphosis of a miracidium near the penetration site. Ciliated epithelial cells are lost and new tegument is formed with its microvilli. A sporocyst has no mouth or digestive system. It absorbs nutrients from its host tissue. The structure serves only to nurture the developing embryos.

Question 50

What is a Miracidium, how does it function?

Answer 50

A typical miracidium is a tiny, ciliated organism. It has a retractable apical papilla at the anterior end. This has five pairs of duct openings from glands and two pairs of sensory nerve endings. Free-swimming miracidia are very active. They must find a suitable mollusc host rapidly as they can only survive free living for a few hours. When they contact the appropriate mollusc, the miracidium attaches to it with its apical papilla, this actively contracts and extends. The miracidium embeds itself deeper and deeper and cytolysis the snail tissue. As penetration proceeds the ciliated epithelium is lost, this takes 30 minutes.

Question 51

What are Redia, and what is their function?

Answer 51

Rediae burst their way out of the sporocyst or leave through a terminal birth port and migrate to the gonad or pancreas of their mollusc host. They crawl within their host and have a functional but basic digestive system (mouth, pharynx and short unbranched gut). They pump food into their gut through the use of their pharyngeal muscles. They can also prey on sporocysts. Embryos in rediae develop either into daughter rediae or the next stage cercariae. These emerge through a birth pore near the pharynx. The rediae must reach a certain population density before they can start producing cercariae.

Question 52

What are cercariae?

Answer 52

Cercariae represent a juvenile stage of the vertebrate inhabiting adult. Most have a mouth near the anterior end, surrounded by an oral sucker, a pre pharynx, muscular pharynx and a forked intestine. Mature cercariae emerge from the mollusc and seek a new host

Question 53

What are Metacercariae?

Answer 53

Metacercariae are usually encysted and are found in or on an intermediate host. A cercariae's first step is to cast off its tail. This allows cyst formation. There are three cyst developmental groups which are correlated with longevity of the metacercariae.

Question 54

Describe the life cycle of the Lung fluke, 'Paragonimus westermani'.

Answer 54

1. Unembryonated eggs are deposited in feces into water. 2. The miracidia hatch from the eggs and penetrate the snail. 3. The miricidia develop through sporocysts, to rediae to cercariae. 4. The cercariae invade the crustacean and encyst into metacercariae. 5. Humans ingest inadequately cooked or pickled crustaceans containing the metacercariae. 6. The metacercariae excyst in the duodenum. 7. The adults in cystic cavities in lungs lay eggs which are excreted in sputum. Eggs may also be swallowed and passed with the stool.

Question 55

What are the three common species of Schistosoma?

Answer 55

S. mansoni, S. haemotobium, S. japonicum.

Question 56

What is the common name of Schistosoma?

Answer 56

Blood fluke.

Question 57

What class does Schistosoma belong to?

Answer 57

Trematoda.

Question 58

How many people does Schistosoma affect yearly?

Answer 58

600 million infected | 250,000 deaths

Question 59

What are the hosts of Schistosome?

Answer 59

Snails and humans.

Question 60

What are the life cycles of Schistosoma species?

Answer 60

1. Eggs hatch from the Schistosoma species and release miracidia. 2. The miracidia penetrate the snail tissue. 3. Sporocysts in snail are formed. 4. Cercariae are released by the snail into water and are free-swimming. 5. The cercariae penetrate the human skin. 6. The cercariae lose their tails during penetration and become schistosomulae. 7. The schistosomulae enter the circulation. 8. They migrate to portal blood in liver and mature into adults. 9. 'S. japonicum' and 'S. mansoni' migrate to the mesenteric venules of the bowel/rectume and lay eggs that circulate to the liver and shed in stools. 'S. haematobium' migrate to the venous plexus of the bladder. 10. Eggs are then excreted into water.

Question 61

What specialisations do Cestodes possess?

Answer 61

They have no digestive system - all nutrients are absorbed through the cuticle. They have a segmented body (strobila) - mature segments (proglottids) are released which transmits eggs to feces.

Question 62

Describe 'Taenia saginata'.

Answer 62

``` Taenia saginata Causes the disease Taeniasis Belongs to the class Cestoda Also known as the 'Beef tapeworm' Present in Cattle and Human hosts. Can be >20m ```

Question 63

What is the common name of 'Taenia saginata'?

Answer 63

Beef tapeworm

Question 64

What is the generalised Cestode lifecycle?

Answer 64

1. Eggs and egg-filled proglottids are passed into the environment in feces. 2. Intermediate (secondary) hosts ingest eggs on contaminated hosts. 3. Eggs hatch into larvae that penetrate the intestinal wall and migrate to other tissues. 4. Larva develops into a cysticercus in muscle. 5. Human, the definitive (primary) host, ingests cysticercus in undercooked contaminated meat. 6. Cystericus excysts to become a scolex that attaches to intestinal wall and matures. 7. Adult worm forms new proglottids.

Question 65

What is the common name of 'Taenia solium'?

Answer 65

Pork tapeworm

Question 66

Describe the characteristics of Taenia.

Answer 66

Taenia saginate - Beef tapeworm Taenia solium - Pork tapeworm Adults attach to the intestinal epithelium. Most individuals shed strobila without having obvious pathology. - nutritional burden - intestinal blockage if tapeworm is large

Question 67

What is the common name of 'Echinococcus granulosus'?

Answer 67

Canine tapeworm

Question 68

What disease can 'Echinococcus granulises' cause?

Answer 68

It can cause hydatid disease. Humans are accidentally intermediate hosts - food/water contaminated with dog feces. Zoonosis: larvae create cysts in tissue as in intermediate host.

Question 69

What is the role of 'T helper cells'?

Answer 69

Helper T cells (TH) that express the CD4 marker (CD4þ T cells), and mainly ‘helps’ or ‘induces’ immune responses, divided into two main subsets (TH1 and TH2). They release cytokines (immune signalling peptides).

Question 70

What are the major types of T helper cells?

Answer 70

Th0 can differentiate into different subtypes based on cytokines and interaction with dendritic cells. Major types: Th1, Th2, Th17 and Treg.

Question 71

How do Th1 and Th2 interact?

Answer 71

Th1 and Th2 inhibit each other. Cytokines are released that reinforce the response direction, either towards the humoral (B cells and AB) response or a cell-mediated response (Cytotoxic TCs, NKCs, Macrophages for phagocytosis).

Question 72

Th1 is responsible for which type of immunity?

Answer 72

Th1 : Cellular immunity (cell-mediated) - | Cytotoxic TCs, NKCs, Macrophages for phagocytosis

Question 73

Th2 is responsible for which type of immunity?

Answer 73

Th2: Humoral immunity (B cells and AB)

Question 74

What is the role of Treg cells?

Answer 74

Treg cells suppress the activity of other Th types. - they are induced by TGF-β - they produce anti-inflammatory IL-10

Question 75

What are the system-wide effects of helminth infection?

Answer 75

Initial strong response Increasing exposure to antigens leads to hyporesponsiveness, first to parasite antigens, then to other antigens. The response is restored by killing helminths of blocking TGF-β/IL-10.

Question 76

How can Helminths create Th2 polarisation?

Answer 76

The presence of helminths elicits a strong Th2 response in the host. Th2 is beneficial to the host as lower Th1 results in less inflammation. Th2 is beneficial to the parasite as there is reduced cytotoxicity.

Question 77

How do Helminths modulate immune response?

Answer 77

Helminths can actively modulate the immune response through the secretion of substances. - cytokine mimics (e.g. TGF-β-mimics) - non-protein signatures (e.g. host like glycans) - protease inhibitors (cystatins/serpins) : block inflammatory signalling cascades - anti-oxidants : block cytotoxic killing

Question 78

How do Schistosoma spp. use the immune response for transmission?

Answer 78

Schistosoma adults live in blood vessels around the intestine and bladder. The eggs are highly immunogenic, containing the antigen SEA which recruits immune cells (Th2). This results in Granuloma formation which is detrimental, but prevents constant inflammatory signal from damaging the surrounding tissue. The body pushes the granuloma across the intestine wall to expel.

Question 79

What are the knock on effects of Immunomodulation by helminths?

Answer 79

Immunosuppression and Th2 polarisation leads to... - greater susceptibility to microbes, this requires Th1 response - reduced efficacy of vaccines: helminth burden is a serious issue for the success of vaccine trials intro NTDs. Pre-treatment with an anti-helminthic may be required.

Question 80

What is the 'hygiene hypothesis'?

Answer 80

Declining family size, improved household amenities and higher standard of personal cleanliness have reduced the opportunities for cross-infection in young families. This may have resulted in more widespread clinical expression of atopic disease. This means there is a failure to microbially modulate the default Th2 responses in childhood.

Question 81

What is the 'old friends' hypothesis?

Answer 81

It states that conventional childhood infections are mostly 'crowd infections' that kill or immunise and thus cannot persist in isolated hunter-gatherer groups. Crowd infections started to appear after the neolithic agricultural revolution, when human populations increased in size and proximity. Microbes coevolved with human immune systems. Humans became so dependent on them that their immune systems cannot develop or function properly without them. In a 'normal' situation therefore, the IS developed in the presence of a heavy burden of malaria and other microbes (Th1 response). Also burden of helminths (anti-inflammatory response - TGF-β-mimics, IL-10 induction; Th2). The immune system is therefore set at an inappropriate level in developed countries as there is low incidence of infectious disease and worm infection. However there is high incidence of allergic disease.

Question 82

How can Helminths be used in a therapeutic way?

Answer 82

The helminths and our Immune System developed together. The parasites suppressed our immune response, now they are gone our immune system has become too sensitive. Identifying the component of the parasite (perhaps a protein) that is responsible for suppressing the immune response may allow for the development of a drug. This may allow for the effects of allergies to be reduced, or stop their occurrence altogether.