Another infodumping lecture! Yay!
Classification
The two main phylums of helminths (worms) are nematodes (round worms) and platyhelminthes (flat worms). Platyhelminthes can be subdivided into two main classes: cestodes (which includes tapeworms) and trematodes (which includes flukes and Schistosoma).
Transmission
Helminths can be transmitted by direct transmission, ingestion or by vectors (e.g. mosquitoes). The most common helminths to be transmitted directly are gastrointestinal nematodes, while the most common to be transmitted by ingestion are tapeworms and some nematodes. Vector-borne helminths have a limited geographical range compared to the other two types of transmission.
Nematodes
Nematodes (round worms) come in all shapes and sizes, from under 1mm to over 1m in length. They are dioecious (have male and female forms). Nematodes can be roughly divided into gastrointestinal nematodes, or tissue/blood nematodes. Gastrointestinal nematodes are some of the commonest worm infections and are predicted to infect roughly 50% of the world's population. They can be ingested, or larvae can burrow into the skin.
Caenorhabditis elegans is one of the most important nematodes in medicine and medical research. It is known to survive space. It is also transparent and emits blue fluorescence upon death, which makes it useful for research. Other nematodes include Trichuris trichura ("whipworm"), Enterobius vermicularis ("pinworm"), Trichinella spiralis (a tissue/blood nematode that is the only intracellular helminth), Guinea Worm (a tissue/blood nematode that is predicted to be the next disease to be eradicated) and Toxocara canis (a tissue/blood nematode that often affects the eye).
In this post, we'll focus on a couple of gastrointestinal nematodes (Ascaris lumbricoides and hookworms) as well as a tissue worm (filarial worms). Let's get started!
Ascaris lumbricoides
Ascaris lumbricoides is a fairly large worm (15-50cm long) that can lay around 200 000 eggs per day. Infection by Ascaris is often asymptomatic, but can lead to abdominal pain, bowel obstruction, ulcers, bloody sputum and faeces, fever and cough. If the larvae migrate through the lungs, they can cause Loffler's syndrome, which is basically eosinophilia in the lungs. Children infected with Ascaris may also experience growth retardation.
Ascaris can be diagnosed by identifying the eggs in the faeces. In severe cases, adult worms can be seen protruding from the anus. The infection can be treated with anti-helminthic agents such as mebendazole, nitazoxanide and ivermectin.
Hookworms
The main species of hookworms are Ancylostoma duadenale and Necator americanus. Infection is usually asymptomatic, but since hookworms feed on blood, they can cause anaemia. Hookworms can also cause growth retardation in children, and if infection occurs during pregnancy, children may be born with a low birth weight. Diagnosis is by identification of eggs in faeces, and treatment is with mebendazole or albendazole.
Filarial Worms
Filarial worms can cause three types of filariasis, all of which are spread via vectors such as mosquitoes. In lymphatic filariasis, the worms live in the lymphatic system and cause chronic disease, which may lead to elephantiasis (swelling of the legs). Subcutaneous filariasis, where worms stay in the subcutaneous layer of the skin, may lead to "river blindness." Finally, serous cavity filariasis has relatively mild symptoms.
Filarial worms can enter our blood when mosquitoes bite us. Once in the human body, adults can produce sheathed microfilariae that can enter lymph and blood. At night, these microfilariae enter the peripheral blood, where they can be taken up by the next mosquito to bite us. Once in the mosquito, microfilariae shed their sheaths and move to the mosquito's thoracic cavity to form larvae, which grow and move back to the head. The worms can then enter the blood of the mosquito's next victim.
Lymphatic filariasis can be diagnosed by looking for microfilaria in a finger prick test. As microfilaria move towards the peripheral blood during the night, the timing of the test is important. Subcutaneous filariasis can be diagnosed via a skin snip. All kinds of filariasis can be diagnosed with antigen tests.
Treatment for filarial worms mainly targets microfilaria. Albendazole combined with ivermectin kills microfilaria, as does diethylcarbamazine. A new treatment for filariasis uses the antibiotic doxycycline to kill off Wolbachia, which is a bacteria that is needed for the worms to survive.
Platyhelminthes- Cestodes
Cestodes (tapeworms) are haemaphrodites (each worm has male and female reproductive organs). Their bodies are composed of segments and their heads have a structure called a scolex (suckers and hooks), which helps them to attach to the gut. They can cause intestinal infections (which are mainly asymptomatic, with some exceptions) or tissue infections (which tend to be pathological).
Intestinal tapeworms
Intestinal tapeworms, which include Taenia solium and Taenia saginata, can be acquired by eating undercooked meat. Cattle and pigs acquire intestinal tapeworms by ingesting contaminated vegetation and then form cysts in their muscles. Humans can then acquire the infection by eating undercooked meat of infected animals. Once inside humans, these worms can attach to the gut via the scolex and grow up to around 3m long. If humans directly ingest the eggs of Taenia solium (not Taenia saginata), they can develop cysticercosis (cysts). These cysts usually form in subcutaneous tissue, muscle or brain.
Intestinal tapeworms can be diagnosed by identifying eggs in stool sample. The eggs are identical between T. solium and T. saginata, so proglottids (one of the segments or joints) need to be visualised with India ink, or adult worms need to be found, in order to differentiate the species. PCR of ribosomal genes can also be done. Cysticercosis can also be diagnosed with X-rays, CT or biopsy.
Treatment of intestinal tapeworms can be done with praziquantel, niclosamide or albendazole. Some care needs to be taken as dying larvae can elicit a major immune response. Corticosteroids may be given at the same time as anti-helminthic therapy in order to prevent this major immune response.
Tissue tapeworms
Tissue tapeworms include Echinococcus species, such as Echinococcus granulosus and Echinococcus multilocularis. They are acquired by ingesting ova in contaminated food or by direct contact with certain animals, such as dogs. In contrast to intestinal tapeworms, these worms tend to be quite small (~2-7mm). They can form "bladder-like" cysts in Hydatid disease, or they can form new "daughter cysts." The "daughter cysts" of E. granulosus are membrane-bound and are a bit more like a benign tumour, whereas the daughter cysts of E. multilocularis tend to spread more like a metastatic tumour.
Cysts caused by tissue tapeworms can be detected via X-ray or MRI, and diagnosis can be confirmed with biopsy or PCR. Treatment begins with surgery to remove the cysts (if possible), followed by long-term (>2 years) benzimidazoles (class of drugs including albendazole and mebendazole). In non-responsive cases, intravenous amphotericin B may also be used.
Platyhelminthes- Trematodes
The trematodes include tissue flukes and schistosomes. Tissue flukes are haemaphrodites, whereas schistosomes are dioecious. They are obligate parasites (i.e. need to live in a host cell in order to reproduce) and can live for a long time.
Schistosomes
Schistosomes cause schistosomiasis, also known as Bilharzia. Adult schistosomes are asymptomatic, but eggs can cause tissue damage, which over time can lead to chronic organ damage and cancer. Schistosomes are spread by snails: miracidia (trematode larvae) can penetrate snail tissue. Once inside snails, schistosomes form sporocysts, and eventually are released into the water as cercariae (which I *think* is the larval form? Too many unexplained words). Cercariae can penetrate human skin. Once inside humans, they lose their tails and migrate to the liver, where they mature.
Diagnosis of schistosomes is done through identification of eggs, serology tests and biopsy. Treatment is done via praziquantel. As with intestinal tapeworms, dying worms can elicit an immune response, so steroids are also necessary.
Flukes
Flukes include Fasciola, Clonorchis and Opisthorchis, which live in the liver, and Paragonimus, which lives in the lung. The life cycle of flukes is similar to that of schistosomes, aside from the fact that they don't mate (they are haemaphrodites). Flukes are often acquired by eating seafood.
Diagnosis of flukes is done via identifying eggs in the faeces or bile. There is a risk of false positives, however, as no eggs are laid in the first few months. A serology test for antibodies (ELISA) can also be done, as can PCR on faecal material. Treatments include triclabendazole (a benzimidazole) and praziquantel.
Anti-Helminthic Drugs
I'm just going to cross my fingers and hope that we don't need to know everything on this slide. Anyway, apparently we will be getting a lecture on antiparasitic agents in two weeks' time, so stay tuned, I guess!
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