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Recently in the news Introduc)on to Parasi)c Worms (Helminths) 1 Introduc)on to Helminth Parasites Parasite Diseases Plasmodium No. people infected malaria Soil transmitted helminths: Roundworm (Ascaris) Pneumonitis, intestinal obstruction Whipworm (Trichuris) Bloody diarrhoea, rectal prolapse Hookworm (Ancylostoma and Necator) Coughing, wheezing, abdominal pain and anaemia Deaths/yr 273 million 1.12 million >2 billion 200,000 Schistosoma Renal tract and intestinal disease 200 million 15,000 Filariae Lymphatic filariasis and elephantiasis 120 million Not fatal but 40 million disfigured or incapacitated Trypanosoma cruzi Chagas disease (cardiovascular) 13 million 14,000 African trypanosomes African sleeping sickness <100,000 <10,000 Leishamania Cutaneous, mucocutaneous and visceral leishmaniasis 12 million; 2 million new cases/yr 50,000 Introduc)on to Helminth Parasites Sub kingdom Metazoa Phylum Class Nematodes Ascaris (roundworm) Trichuris (whipworm) Ancylostoma (hookworm) Necator (hookworm) Enterobius (pinworm or threadworm) Strongyloides C. elegans Probably >1 mill species 25000 species described Round worms; appear round in cross section, they have body cavities, a straight alimentary canal and an anus Platyhelminthes Flat worms; dorsoventrally flattened, no body cavity and, if present, the alimentary canal is blind ending Genus – examples Cestodes Taenia (tapeworm) Adult tapeworms are found in the intestine of their host They have a head (scolex) with sucking organs, a segmented body but no alimentary canal Each body segment is hermaphrodite Trematodes Non-segmented, usually leafshaped, with two suckers but no distinct head They have an alimentary canal and are usually hermaphrodite and leaf shaped Schistosomes are the exception. They are threadlike, and have separate sexes Fasciola (liver fluke) Schistosoma (not leaf shaped!) 2 Structure of nematodes (C. elegans) 100 µm Nematodes Ascaris • Formally they are bilaterally symmetrical, vermiform. • They have a thick complex cuCcle underlain by longitudinal muscles (but no circular muscles) • A pseudocoelom (blastocoelom), and a single cell-‐layered gut running from the anterior mouth to a sub-‐terminal anus. The pharynx is strongly muscular, with a triangular cross secCon, and sucks in liquid / micro-‐parCculate food. There is no circulatory system, and the excretory system is very basic (neither flame cells nor nephridia, but unique structures called reneIe cells.) • • • • 3 Nematodes • • Cuticle Arguably the defining feature of the nematode body is its thick cuticle. All nematodes have a thick collagen body wall retaining a high internal hydrostatic pressure, up to half an atmosphere - they are almost impossible to squash under normal circumstances. The design of the body wall is unique to the phylum. It has up to 9 layers (typically 4), these fibres run in different directions, very much like a high-pressure tyre. The fibres are inelastic, so preventing changes in body volume while permitting lateral undulations. This high internal pressure defines many aspects of the nematode’s life. Thickness of cuticle: ~80 µm Nematodes Feeding • The gut is a tube lined by a single cell layer, with no muscles, but microvilli. Its transit Cme is very short, around 3 minutes, with the animals defecaCng conCnuously as fast as is compaCble with their hydrostaCc pressure. It is thought that this is too fast for much enzymaCc/digesCve acCon, and that they simply absorb useful nutrients without engaging in digesCon per se. 4 Nematodes • The fundamental design is pre-‐adapted to endo-‐parasiCsm. • 1:The thick body wall is an excellent protecCon against chemical or immune aIack, allowing them to survive gut acids or anCbody aIack. (AnCbodies certainly do bind to nematode cuCcle, but can’t puncture it.) • 2: The vast numbers of resistant eggs allow dispersal in Cme and space, maximizing the chance of infecCng a new host. • 3: The microphagous habit pre-‐adapts to a gut content / body fluid diet. • 4: The body design works well at small body size, which is advantageous for most parasiCc lifestyles (although some worms are up to 9 m in length). Nematode reproducCon • Most Nematodes produce eggs in prodigious quanCCes (oviparous). A typical gut parasite releases 15,000 eggs per day. One such prolific producer the human hookworm Ancylostoma duodenale may shed eggs at this rate for all of its life of 5 -‐ 15 years. • Onchocerca does not produce eggs (viviparous). The first stage in its life cycle are live young called microfilariae. However, they are also produced in vast quanCCes. 50 µm Taenia solium egg 50 µm Trichuris egg 5 Life cycle of nematodes (C. elegans) • normally male and female worms (dioecious/diözisch) • occasionally hermaphrodites (e.g. C. elegans) • 4 larval stages (L1-‐L4) • adult worm about 1 cm in length Introduc)on to Helminth Parasites -‐ Nematodes Trichuris (whipworm [Peitschenwurm]) • A soil transmitted helminth • prevalent in warm, humid conditions • Can cause diarrhoea, rectal prolapse and anaemia in heavily-infected people Ancylostoma and Necator (hookworms [Hakenwurm]) • A major cause of anaemia in the tropics Strongyloides [Zwergfadenwurm] • inhabits the small bowel • infection more severe in immuno-suppressed people (e.g. HIV/AIDS, malnutrition) Enterobius (pinworm or threadworm [Madenwurm]) • prevalent in cold and temperate climates but rare in the tropics • found mainly in children – this is one YOU are likely to have had in your own childhood 6 Enterobius vermicularis (pinworm, Madenwurm)Life Cycle Nematodes • Ancylostoma duodenale – Hookworm (Hakenwurm) 7 Ancylostoma duodenale – Life Cycle (L3) (L1-L2) (L4) Introduc)on to Helminthe Parasites -‐ Hookworms Life cycle Adult worms live in the intestine and excrete eggs in the faeces In the absence of latrines, eggs contaminate soil and develop in warm, damp conditions (Grubenwurm) eggs hatch and infective filariform larvae develop in about one week and remain infective in soil for up to 3 weeks filariform larvae penetrate the skin when a person walks barefoot in the soil Larvae migrate from the skin to the lungs via the lymphatic and blood systems Larvae penetrate the capillary wall to enter the alveoli Larvae are propelled up the respiratory tree to the epiglottis where they are swallowed Develops to adult stage in upper intestine; adult worms are fully mature after about 5 weeks Infection load can be up to 1000 worms (average 50-100) Eggs are excreted in the faeces 8 Introduc)on to Helminthe Parasites -‐ Hookworms Pathology Hookworms move several times a day to different attachment sites in the upper intestinal mucosa to ingest blood They secrete an anticoagulant which causes the old attachment sites to continue to bleed Heavy hookworm infection results in chronic haemorrhage from the duodenal and jejunal mucosa The combination of constant blood loss due to hookworm infection and poor iron intake in the diet results in iron deficiency anaemia In a child, the continued daily loss of 10ml of blood can lead to severe anaemia 1000 worms can consume up to 500 ml blood per day Introduc)on to Helminthe Parasites -‐ Hookworm Symptoms and signs Minor Often itchy papules are found at the site where the larva penetrated the skin There may be cough and wheezing as the larva migrates through the lungs Major Hookworm anaemia • Tiredness, aches and pains (stomach) • Breathlessness • Oedema Cardiac complications Diagnosis Microscopic examination of faecal smears to demonstrate significant numbers of hook worm eggs Measure Hb, serum ferritin, iron Exclude other causes of anaemia 9 Introduc)on to Helminthe Parasites -‐ Hookworm Treatment Mebendazole (cheap) – 100mg, twice daily for 3 days Mebendazole is contraindicated in pregnancy – use Bephenium hydroxynaphthoate “alcopar” Mebendazole (a benzamidine) destroys microtubules For anaemia: ferrous sulphate 200-400 mg three times a day for 3 months (adult regimen) Prevention and control Health education and improve sanitation facilities – install pit latrines Encourage use of protective footwear Mass drug treatment of communities Iron supplementation in areas of low iron intake Introduc)on to Helminthe Parasites -‐ Hookworms Epidemiology >1200m infections each year of which 100m are symptomatic It is due to 2 parasites both of which occur worldwide: • Necator americanus - predominant species in subSaharan Africa, south Asia and the Pacific • Ancylostoma duodenale –predominant in S. Europe, N. Africa, western Asia, northern China, Japan and the west coast of America 10 Introduc)on to Helminthe Parasites -‐ Nematodes Ascaris (roundworm [Spulwurm]) • Found world-wide in conditions of poor hygiene, transmitted by the faecal- oral route • Adult worms lives in the small intestine • Causes eosinophilia Filarial Worms including: Onchocerca volvulus – Transmitted by the simulium black fly (Kriebelmücke), this microfilarial parasite can cause visual impairment, blindness and severe itching of the skin in those infected Wuchereria bancrofti – The major causative agent of lymphatic filariasis Brugia malayi – Another microfilarial parasite that causes lymphatic filariasis Ascaris –Life Cycle • • • • • • • • • • • Eggs are ingested L3 larvae hatches in intestines Penetrate gut wall into blood Migrate to liver Mold into L4 larvae Transport via vena cava to heart and lung Penetrate alveolae Passiv transport up airways Swallowing, transport to small intestine Develop into adult worms Eggs are excreted 11 Nematodes • Ascaris – Heavy InfestaCon Introduc)on to Helminthe Parasites -‐ Nematodes Toxocara canis & cati (Hunde/Katzen-Spulwurm) • • • A world-wide infection of dogs and cats Human infection occurs when embryonated eggs are ingested from dog or cat faeces (eggs can be infectious for up to 2 years) sandpits It is common in children and can cause visceral larva migrans (VLM) • Dead larvae cause inflammations and granulomas • If eyes are infected, blindness can occur • • Human is a paratenic host (parasites survives but doesn’t undergo further development) Deworm your cats and dogs regularly! 12 Toxocara canis Introduc)on to Helminth Parasites -‐ Filarial Worms Some species cause Elephan)asis 13 Introduc)on to Helminthe Parasites -‐ Filarial Worms Symptoms and signs – 3 stages 1. Asymptomatic stage There is internal damage to the lymphatics and kidneys 2. Acute stage – Filarial lymphangitis (inflammation) Characterised by bouts of fever heat, redness, pain, swelling and tenderness of the lymph nodes and ducts 3. Chronic stage Usually results in elephantiasis as a result of chronic lymphoedema (=lymphatic obstruction) There is a massive overgrowth of tissue resulting in severe deformities The legs are often affected and result in inability to walk The scrotum is often affected in men and the breasts and vulva in women Introduc)on to Helminthe Parasites -‐ Filarial Worms MoldL4 larvae Up to 108 filaria in heavy infections 14 Nematodes • Simulium (Blackfly[Kriebelmücke]) – Vector for Onchocerca volvulus • Feeds on blood and tissue • Takes up subcutaneous microfilaria Nematodes • Onchocerca Microfilaria Length: ~300 µm Nodule (Onchocercoma) with adult worms Length: 25 (males)-50 cm (females) 15 Nematodes • Onchocerca nodule Nematodes • Onchocerca volvulus – The cause of River Blindness 16 Filarial worms – Wuchereria bancroci/Brugia malayi • Transmitted by mosquitos • Reside in blood & lypmphatic system • Periodicity of appearnace of microfilaria in the blood • Peak between 10 pm and 2 am • Night-feeding mosquitoes are main vectors • During daytime microfilaria are mainly in pulmonary arteries (high O2) • Change in sleep pattern reverses periodicity from nocturnal to diurnal • Cause of lymphatic filariasis (Elephantiasis) • No known animal reservoir hosts Introduc)on to Helminthe Parasites -‐ Filarial Worms Diagnosis Microscopic examination of Giemsa stained thick blood films for the presence of microfilariae W. bancrofti shows marked nocturnal periodicity, so it’s best to collect blood samples between 10pm and 1 am Serology Treatment Diethylcarbamazine (DEC) rapidly kills microfilariae and will kill adult worms if given in full dosage over 3 weeks Release of antigens from dying microfilaria causes allergic-type reactions – add an antihistamine and aspirin to treatment regimen Other treatment options are • ivermectin • combination of DEC and albendazole 17 Introduc)on to Helminthe Parasites -‐ Filarial Worms Prevention and control Rapid diagnosis and treatment of infected individuals Mass drug administration to at risk communities Vector control: eliminate mosquito breeding sites through improved sanitation and environmental management Personal protection against mosquito bites by insecticides, bed nets and repellents 18