Nemotodes

• Nematodes

  Parasitic worms that are successful parasites of humans, animals and plants
• Nematodes

  • Have a stylised body plan - 'a tube within a tube' with an alimentary canal extending from mouth to anus
  • Exhibit a high degree of preadaptation which contributes to their success
  • Have highly adapted biochemistry and physiology to survive wide range of conditions, utilize wide range of food sources, and withstand environmental insults and host immune responses
• Nematodes do not undergo asexual reproduction (parthenogenesis is rare)
• Nematodes have a life cycle with 4 larval stages and 4 moults
• World Health Organisation definition of health

  The state of complete physical, mental and social well-being and not merely the absence of disease or infirmity
• Estimated global prevalence and associated morbidity of soil-transmitted helminths
• 20% of world's population harbour at least one species of gastrointestinal nematode
• Polyparasitism is common - many people harbour many different species of parasites
• Population dynamics of nematode parasites

  • Most do not multiply within an individual host, so number of adult worms is due to number of infection events - degree of exposure
  • Infections are overdispersed, with a small number of hosts harbouring a large number of worms
• The most heavily infected hosts are at greatest risk of morbidity and are the major source of infective stages
• There may be an underlying physiological defect to explain the overdispersed distribution of nematode infections
• Ascariasis


  A disease caused by infection with Ascaris lumbricoides
• The vertebrate intestine is a major ancestral site for parasitic helminths, suggesting mammals have developed mechanisms to tolerate this infectious disease
• Reasons for high prevalence of soil-transmitted helminth infections

  • Widespread distribution of nematodes
  • Resilience of eggs to harsh environmental conditions
  • High number of eggs produced per parasite
  • Poor socioeconomic conditions
  • Lack of education
• Ascaris lumbricoides has a worldwide distribution, with highest prevalence in tropical and subtropical regions with inadequate sanitation
• Pathology of ascariasis

  • Associated with ingestion and migration of larvae
  • Associated with adult parasites in the intestine
  • Due to "wandering" adults outside of the intestine
• Pathology associated with ingestion and migration of Ascaris larvae


  • Severe haemorrhagic pneumonia that can lead to life-threatening respiratory failure. Due larvae migrating through the lungs
  • Smaller scale haemorrhages leading to breathing difficulties, pneumonia, fever
  • As many parasite proteins are highly allergenic and cause eosinophilia which causes Allergic hypersensitivity reactions such as asthma
• Pathology associated with adult Ascaris worms in the intestine

  • Generalised digestive disorders
  • Malnutrition in hosts, especially children
  • Intestinal obstruction requiring surgical removal
• Pathology associated with "wandering" adult Ascaris worms

  • Blockage of bile duct causing jaundice and interference in fat metabolism
  • Perforation of appendix or intestinal wall causing peritonitis
  • Emergence through nose or vomiting, or entry into trachea causing suffocation
• Ascariasis diagnosis methods

  • Coprological - detection of eggs in faeces
  • Serological - detection of antibodies or antigens
  • Molecular - PCR detection of parasite DNA
  • Image-based diagnostics
• 85% of obstructions occur in children aged 1-5 years
• Clinical and laboratory examinations

  • Coprological - detection of eggs in faeces
  • Serological - detection of antibodies or antigens – but presently no point-of-care test available for STHs
  • Molecular - PCR detection of parasite DNA from eggs passed in faeces, multiplex PCR can detect multiple parasite species in single reaction, qPCR enables quantification of infection intensity
  • Image-based diagnostics
• Filariasis


  A disease caused by infection with Wuchereria bancrofti
• Groups of filarial nematodes that infect humans

  • Lymphatic filariasis - worms occupy the lymphatic system (e.g. Wuchereria bancrofti - responsible for 90% of cases)
  • Subcutaneous filariasis - worms occupy subcutaneous layer of skin (e.g. Loa loa and Onchocerca volvulus - river blindness)
  • Serous cavity filariasis - worms occupy peritoneal, pleural or pericardial cavity (e.g. Mansonella perstans & Dirofilaria immitis - dog heartworm)
• Filarial worms are transmitted by mosquitoes and black flies
• Currently, 856 million people in 52 countries live in areas that require preventive chemotherapy to stop the spread of lymphatic filariasis infection
• An important difference with Plasmodium transmission is that W. bancrofti larvae are deposited from the mouthparts onto the skin of the host. They then migrate through microcuts in the dermis or the tract created by the proboscis into the bloodstream of the new human host.
• Clinical presentations of lymphatic filariasis

  • Although the parasite damages the lymph system, most infected people are asymptomatic
  • Lymphoedema - improper functioning of lymph system - results in swelling caused by fluid collection - mostly affects legs but also arms, breasts and genitalia - ~25 million men affected by hydrocele (swelling in the scrotum)
  • Swelling and decreased lymph system function also make it difficult to fight infection - bacterial infections cause hardening and thickening of skin – called elephantiasis
  • Filarial infections also cause tropical pulmonary eosinophilia syndrome - symptoms include cough, shortness of breath and wheezing
• Consequences of lymphatic filariasis

  • Social stigma and sub-optimal mental health
  • Loss of income-earning opportunities
  • Increased medical expenses for patients (and their carers)
  • Socioeconomic burdens of isolation and poverty are immense
  • Body deformities caused by lymphatic elephantiasis
• Morbidity management for lymphatic filariasis


  • Surgery can alleviate most cases of hydrocele
  • Clinical severity and disease progression can be reduced with simple hygiene measures, skin care, exercises and elevation of affected limbs
  • People with lymphoedema must have access to continuing care throughout their lives, both to manage the disease and prevent progression to more advanced stages
• No prophylactic treatment (2024 CDC)
• Measures to avoid mosquito bites

  • Sleep under a mosquito net, or in air-conditioned room
  • Wear long sleeves and trousers
  • Use mosquito repellent on exposed skin
• Another approach involves annual mass drug treatment of entire communities and control of mosquitoes – reduces microfilariae in the blood of infected people and diminishes transmission (basis of Global Programme to Eliminate Lymphatic Filariasis – more on this later)
• Mebendazole


  For Ascaris treatment
• WHO recommendations for periodic administration of anti-helminthic drugs


  • Treatment is given once a year when prevalence of STH infections is >20%
  • Treatment is given twice a year when prevalence is >50%
• Measures to prevent re-infection of soil transmitted helminthiases

  • Health and hygiene education to encourage 'healthy' behaviour
  • Improved sanitation to reduce soil contamination with infective eggs
• WHO global target - eliminate morbidity due to soil transmitted helminthiases in children by 2030
• Ivermectin


  Paralyses body wall and pharyngeal muscle in nematodes but has no effect on mammals as it cannot cross the blood-brain barrier into the CNS
• Ivermectin mechanism of action

  1. Binds with high affinity to glutamate-gated chloride channels in invertebrate nerve and muscle cells

  2. Binding causes increased permeability of cell membrane to chloride ions and hyperpolarization of nerve or muscle cell

  3. Hyperpolarization results in paralysis and death - either directly or by causing the worms to starve
• William C. Campbell and Satoshi Ōmura – Nobel Prize for Physiology or Medicine 2015