Helminths
Helminths are parasitic worms, causing neglected tropical disease. The study of these diseases receives <1% of global
research funding. Very common in developing countries, causing heavy burden in low/middle income regions. They
are large, multicellular organisms with parts of their lifecycle in and out of humans; adults cannot multiply in
humans. They cause 26 million DALYs worldwide, 4 main contributors including soil-transmitted helminths
(intestinal), Schistosomiasis (vasculature), Lymphatic filariasis (lymphatics) and Onchocerciasis (skin). They are a
burden to human and livestock health, as well as worldwide economy.
Schistosomiasis
Its also known as bilharzia and impacts 230+ million people worldwide with >200,000 deaths a year (WHO, 2014). It
is caused by trematode (blood fluke) parasites. It can establish a chronic infection that lasts years, with >20 million
suffering severe morbidity. Schistosoma has a freshwater snail intermediate host. They generally live within the
hepatoportal vein. Most severe clinical symptoms caused by eggs:
Hepatosplenomegaly
Liver fibrosis, kidney failure, obstruction of urinary tract, abdominal pain
Bladder/Colon cancer
Rash
Cough
Genitourinary disease – linked to increased rates of HIV transmission.
Common mouse models are S. mansoni and S. japonicum.
Mouse model for S. haematobium egg-related pathology (urogenital schistosomiasis) has also been developed.
Lymphatic filariasis
A disease caused by a chronic mosquito-borne parasitic infection, with 90% of cases caused by Wuchereria bancrofti
which establishes a chronic infection in humans of 5-7 years. Its intermediate host is the mosquito, and adults live in
the lymphatics producing microfilariae that migrate into lymphatic and blood circulation. This impairs the lymphatics
resulting in swelling and “elephantiasis”. Murine models include: Brugia malayi and Litosomoides sigmodontis
Onchocerciasis (River blindness)
Disease caused by the parasitic worm Onchocerca volvulus with the blackfly as the intermediate host. It inhabits
subcutaneous tissues.
Symptoms: Visual impairment, blindness (2nd infectious cause of blindness worldwide) & skin diseases (itch, rash)
because of the immune response.
Soil-transmitted Helminths: Account for major burden of parasitic disease worldwide. ~1.5 billion
people (>20%) of the world is infected with a STH (WHO, 2020). Cause 5.2 million DALYs. Control is based on regular deworming
with drugs.
Main species: Roundworm (Ascaris lumbricoides). Whipworm (Trichuris trichiura). Hookworms (Necator americanus and
Ancylostoma duodenale).
Roundworm:
Ascaris lumbricoides tend to affect children aged 5-15. Adult worms can live 1-2 years in the small infection and are
15-85cm long. ~3.2k deaths in 2017, and cause heavy infection resulting in abdominal pain and intestinal
obstruction. The migratory phase is associated with liver and lung pathology. No rodent model of Ascaris that
reflects whole life cycle. However, mouse models with Ascarius suum do provide insights on early
infection/migration.
Whipworm
Trichuris Trichiura affects children aged 5-15. The adult worms are large (4 cm long) and can live for 1 year in the
large intestine. Infection is often asymptomatic but heavy infection can cause gastrointestinal problems e.g.
abdominal pain, diarrhea and rectal prolapse, particularly in young children. It can also cause colitis and Trichuris
dysentery syndrome (TDS), as well as anaemia. This is because eggs hatch in the small intestine and adults live in the
caecum and the ascending colon.
It may influence cognitive function, school performance and school attendance (Simeon et al. 1995; Gardner et al. 1996),
although the impact of deworming on these parameters is controversial (Welch et al. 2017).
, Well established pre-clinical models include: Trichuris muris (mouse) and Trichuris suis (pig)
Hookworm
Ancylostoma duodenale and Necator americanus affects children and adults. Most adult worms live for 1-2 years
but can survive longer. The larva penetrates the skin which can cause “ground itch”. The adults attach to the
intestinal wall (distal jejunum) and secrete anti-coagulants to stop blood clotting whilst they feed. This can lead to
anaemia and protein deficiency. The loss of iron/protein impairs growth and mental development of children and
anaemia in mothers can lead to reduced birthweight and infant survival (Christian et al. 2004).
Models
1. Pre-clinical model organisms include dogs (A. ceylanicum and A. caninum) and hamsters (A. ceylanicum and
N. americanus infections). However, both develop natural resistance to infection (unlike human disease).
2. Common rodent model 1: Nippostrongylus brasiliensis: Causes goblet hyperplasia in gut and long-term lung
emphysema. Nb-infected mothers (infected before they are pregnant) can transfer protective immunity
against Nb infection to offspring.
3. Common rodent model 2: Heligmosomoides polygyrus bakeri: Natural infection of wild wood mice.
Establishes a chronic infection, causing goblet hyperplasia in gut. Can cause mortality if host is immune
compromised. Modifies the host and secretes proteins, glycoproteins (ES products) & small RNAs in
exosomes.
Nutrition
Heavy infection = stunted growth in children, depends on drug and helminth as well as the intensity of infection or
phase of infection.
- Found that the mice with the highest weight loss had a much larger number of worms in the lungs.
- Weight loss could depend on where the worm is in the body during its lifecycle.
Ascariasis infection = vitamin A deficiency and poor lactose digestion.
Hookworms infection = iron deficiency and protein malnutrition (hypoproteinaemia).
Mix = Iron, zinc, and Vitamin A deficiency in preschool-age children.
They also alter short chain fatty acids metabolism, polyunsaturated fatty acid metabolism and macrophage
metabolism. Macrophage = krebs cycle
Key questions
How does a hookworm enter the human body and where do the adults reside?
A larva enters through the skin and travels to bloodstream. Larvae exit blood circulation in the lungs and are
coughed up and swallowed so that they travel to the gut. This is where they mature into adults and attach
themselves to the distal jejunum.
The eggs live in the soil where it is moist, warm, and shaded. The filariform larva can then penetrate a foot’s skin.
How does a whipworm enter the human body?
The eggs are ingested, hatch in the small intestine where they mature and then reside in the cecum.
Which parasite causes River blindness and what is the intermediate host?
Onchocerca volvulus
Inter mediate host = blackfly
Mention some consequences caused by Roundworm, Hookworm and Whipworm.
Roundworm = abdominal pain and intestinal obstruction.
Whipworm = colitis and Trichuris dysentery syndrome (TDS), anaemia.
Hookworm = ground itch, anaemia, and protein deficiency.
In what ways do helminths influence the host?
They also alter short chain fatty acids metabolism, polyunsaturated fatty acid metabolism and macrophage
metabolism.
Stunted growth in children
Helminths are parasitic worms, causing neglected tropical disease. The study of these diseases receives <1% of global
research funding. Very common in developing countries, causing heavy burden in low/middle income regions. They
are large, multicellular organisms with parts of their lifecycle in and out of humans; adults cannot multiply in
humans. They cause 26 million DALYs worldwide, 4 main contributors including soil-transmitted helminths
(intestinal), Schistosomiasis (vasculature), Lymphatic filariasis (lymphatics) and Onchocerciasis (skin). They are a
burden to human and livestock health, as well as worldwide economy.
Schistosomiasis
Its also known as bilharzia and impacts 230+ million people worldwide with >200,000 deaths a year (WHO, 2014). It
is caused by trematode (blood fluke) parasites. It can establish a chronic infection that lasts years, with >20 million
suffering severe morbidity. Schistosoma has a freshwater snail intermediate host. They generally live within the
hepatoportal vein. Most severe clinical symptoms caused by eggs:
Hepatosplenomegaly
Liver fibrosis, kidney failure, obstruction of urinary tract, abdominal pain
Bladder/Colon cancer
Rash
Cough
Genitourinary disease – linked to increased rates of HIV transmission.
Common mouse models are S. mansoni and S. japonicum.
Mouse model for S. haematobium egg-related pathology (urogenital schistosomiasis) has also been developed.
Lymphatic filariasis
A disease caused by a chronic mosquito-borne parasitic infection, with 90% of cases caused by Wuchereria bancrofti
which establishes a chronic infection in humans of 5-7 years. Its intermediate host is the mosquito, and adults live in
the lymphatics producing microfilariae that migrate into lymphatic and blood circulation. This impairs the lymphatics
resulting in swelling and “elephantiasis”. Murine models include: Brugia malayi and Litosomoides sigmodontis
Onchocerciasis (River blindness)
Disease caused by the parasitic worm Onchocerca volvulus with the blackfly as the intermediate host. It inhabits
subcutaneous tissues.
Symptoms: Visual impairment, blindness (2nd infectious cause of blindness worldwide) & skin diseases (itch, rash)
because of the immune response.
Soil-transmitted Helminths: Account for major burden of parasitic disease worldwide. ~1.5 billion
people (>20%) of the world is infected with a STH (WHO, 2020). Cause 5.2 million DALYs. Control is based on regular deworming
with drugs.
Main species: Roundworm (Ascaris lumbricoides). Whipworm (Trichuris trichiura). Hookworms (Necator americanus and
Ancylostoma duodenale).
Roundworm:
Ascaris lumbricoides tend to affect children aged 5-15. Adult worms can live 1-2 years in the small infection and are
15-85cm long. ~3.2k deaths in 2017, and cause heavy infection resulting in abdominal pain and intestinal
obstruction. The migratory phase is associated with liver and lung pathology. No rodent model of Ascaris that
reflects whole life cycle. However, mouse models with Ascarius suum do provide insights on early
infection/migration.
Whipworm
Trichuris Trichiura affects children aged 5-15. The adult worms are large (4 cm long) and can live for 1 year in the
large intestine. Infection is often asymptomatic but heavy infection can cause gastrointestinal problems e.g.
abdominal pain, diarrhea and rectal prolapse, particularly in young children. It can also cause colitis and Trichuris
dysentery syndrome (TDS), as well as anaemia. This is because eggs hatch in the small intestine and adults live in the
caecum and the ascending colon.
It may influence cognitive function, school performance and school attendance (Simeon et al. 1995; Gardner et al. 1996),
although the impact of deworming on these parameters is controversial (Welch et al. 2017).
, Well established pre-clinical models include: Trichuris muris (mouse) and Trichuris suis (pig)
Hookworm
Ancylostoma duodenale and Necator americanus affects children and adults. Most adult worms live for 1-2 years
but can survive longer. The larva penetrates the skin which can cause “ground itch”. The adults attach to the
intestinal wall (distal jejunum) and secrete anti-coagulants to stop blood clotting whilst they feed. This can lead to
anaemia and protein deficiency. The loss of iron/protein impairs growth and mental development of children and
anaemia in mothers can lead to reduced birthweight and infant survival (Christian et al. 2004).
Models
1. Pre-clinical model organisms include dogs (A. ceylanicum and A. caninum) and hamsters (A. ceylanicum and
N. americanus infections). However, both develop natural resistance to infection (unlike human disease).
2. Common rodent model 1: Nippostrongylus brasiliensis: Causes goblet hyperplasia in gut and long-term lung
emphysema. Nb-infected mothers (infected before they are pregnant) can transfer protective immunity
against Nb infection to offspring.
3. Common rodent model 2: Heligmosomoides polygyrus bakeri: Natural infection of wild wood mice.
Establishes a chronic infection, causing goblet hyperplasia in gut. Can cause mortality if host is immune
compromised. Modifies the host and secretes proteins, glycoproteins (ES products) & small RNAs in
exosomes.
Nutrition
Heavy infection = stunted growth in children, depends on drug and helminth as well as the intensity of infection or
phase of infection.
- Found that the mice with the highest weight loss had a much larger number of worms in the lungs.
- Weight loss could depend on where the worm is in the body during its lifecycle.
Ascariasis infection = vitamin A deficiency and poor lactose digestion.
Hookworms infection = iron deficiency and protein malnutrition (hypoproteinaemia).
Mix = Iron, zinc, and Vitamin A deficiency in preschool-age children.
They also alter short chain fatty acids metabolism, polyunsaturated fatty acid metabolism and macrophage
metabolism. Macrophage = krebs cycle
Key questions
How does a hookworm enter the human body and where do the adults reside?
A larva enters through the skin and travels to bloodstream. Larvae exit blood circulation in the lungs and are
coughed up and swallowed so that they travel to the gut. This is where they mature into adults and attach
themselves to the distal jejunum.
The eggs live in the soil where it is moist, warm, and shaded. The filariform larva can then penetrate a foot’s skin.
How does a whipworm enter the human body?
The eggs are ingested, hatch in the small intestine where they mature and then reside in the cecum.
Which parasite causes River blindness and what is the intermediate host?
Onchocerca volvulus
Inter mediate host = blackfly
Mention some consequences caused by Roundworm, Hookworm and Whipworm.
Roundworm = abdominal pain and intestinal obstruction.
Whipworm = colitis and Trichuris dysentery syndrome (TDS), anaemia.
Hookworm = ground itch, anaemia, and protein deficiency.
In what ways do helminths influence the host?
They also alter short chain fatty acids metabolism, polyunsaturated fatty acid metabolism and macrophage
metabolism.
Stunted growth in children
