Helminths Classification: Metazoa

• Metazoa refers to Helminths of medical importance.

Helminths Classification

• Nematodes (roundworms) and Platyhelminthes (flatworms) are the two major groups.
• Platyhelminthes include Trematodes (flukes) and Cestodes (tapeworms).
• These can affect the tissue or GI tract
• Tissue worms:
  • Onchocerca
  • Brugia
  • Wuchereria
  • Dracuncula
  • Loa loa
  • Trichinella
• GI Worms:
  • Nematodes: -Toxocara, Ascaris, Strongyloides, Trichuris, Enterobius, Hookworms
  • Cestodes -Trichinella, Taenia saginata, Taenia solium, Echinococcus, Coenurosis, Cysticercosos, Diphylloboth-rium latum, Hymenolepis
  • Trematodes: -Schistosoma, Paragonimus, Fasciola, Clonorchis, Opisthorchis, Fasciola, Heterophyes

Intestinal Helminths

• Intestinal helminths are multicellular parasitic organisms causing significant morbidity and mortality worldwide.
• Like enteric protozoa, they significantly cause diarrheal diseases and extraintestinal manifestations like Loeffler syndrome, sepsis, cholangiocarcinoma, and neurocysticercosis.
• Nematodes (roundworms), cestodes (tapeworms), and trematodes (flukes) are the most significant intestinal helminths.
• Some helminths have simple life cycles involving only the human host, while others require one or more hosts.
• Humans can be definitive or intermediate hosts, and in zoonotic parasites, they are often dead-end hosts.
• Some parasites (e.g., Enterobius vermicularis, Hymenolepis nana) are infectious shortly after being shed.
• Some parasites can be passed directly from person to person.
• Others require an incubation stage in the environment (Ascaris lumbricoides, Trichuris trichiura, hookworms, Strongyloides stercoralis) or another host (most cestodes and trematodes) before becoming infectious.
• Understanding helminth life cycles is essential for understanding associated pathology and identifying infection.
• Most intestinal helminths are diagnosed through identifying eggs or larvae in stool, sputum, or urine.
• Size and morphologic features of eggs and larvae are important for identifying the causative agent.
• Important external features include wall thickness, operculum, opercular shoulders, spines, abopercular knob, external mamillations, and polar plugs.
• The degree of egg development (e.g., embryonated vs. unembryonated) and presence of internal hooklets are also important differentiating features.
• Serologic and molecular testing are also useful for detecting some intestinal helminths.

Nematodes

• Commonly known as roundworms.
• They are non-segmented, tapered, elongated, cylindrical organisms with separate sexes and a full digestive tract.
• Adult forms range in size from a few millimeters to over 30 cm.
• They have recognizable external features for identification.
• Some move freely in the bowel lumen (e.g., E. vermicularis, A. lumbricoides).
• Others attach to or embed within the intestinal wall (T. trichiura, hookworms, S. stercoralis, Trichinella spp.).
• The degree of symptoms correlates with the extent of infection.
• Patients with high worm burdens are more likely to experience symptoms.
• Hosts are often infected with multiple genera of intestinal nematodes.
• Nematodes are the most common helminths to cause infections worldwide.
• All nematodes, except E. vermicularis, undergo an incubation and maturation stage in the soil before becoming infectious to humans.
• Geohelminths are also known as soil-transmitted helminths (STHs).
• The life cycle of geohelminths relies on fecal contamination of soil, with resultant human exposure to eggs or larvae in the contaminated soil.
• Soil-transmitted helminthiases predominate in regions with poor sanitation and lack of proper waste treatment facilities.
• They are classified as neglected tropical diseases by the WHO.
• Infections are uncommon in developed countries, but prevalent in low- and middle-income countries (LMICs).
• Most intestinal nematodes are identified through microscopic examination of stool specimens.
• Molecular methods have been described, but their use is limited primarily to specialized research and reference centers due to high cost and complexity.

Enterobius vermicularis

• Pinworm infection
• Commonly known as pinworm.
• Has a global distribution with reported prevalence rates ranging from 0.5% to 54.9% in recent studies.
• It is the most reported helminth infection.
• Prevalence is highest in school-age children.
• High infection rates are largely attributable to its ability to pass directly from person to person without environmental incubation.
• It is primarily a parasite of children.
• It is also commonly transmitted to adults in institutional (e.g., daycare) and family settings.
• Adult worms live primarily in the human cecum, and may also be found in the appendix and neighboring regions of the large intestine.
• After mating, the gravid adult female migrates at night to the anus, where she deposits 10,000 or more eggs onto the perianal skin.
• Eggs become infective within 4 to 6 hours and can then infect other hosts.
• Autoinfection may also occur.
• Enterobiasis may be asymptomatic.
• The most common symptom is nighttime perianal itching (nocturnal pruritus ani).
• Heavy infections may cause loss of sleep and irritability.
• The presence of adults in the appendix has also been associated with appendicitis.
• Less commonly, adult females can migrate outside the intestinal tract and enter the female genital tract, triggering a localized granulomatous inflammatory response in the vagina, uterus, fallopian tubes, and/or peritoneum.
• Rarely, adults and eggs have been reported in other extraintestinal sites.
• Enterobiasis can be treated with albendazole, mebendazole, ivermectin, or pyrantel pamoate.
• These drugs are administered in one dose initially, followed by a second dose 2 weeks later to eliminate potential reinfection.
• Members of the household and close contacts are also commonly treated.
• Diagnosis is usually made by detecting the eggs, or less commonly, adult females, from the perianal skin using the cellulose tape method ("Scotch tape" or "Sellotape" test).
• Specimens should be obtained early in the morning, before the patient bathes or defecates.

Trichuris trichiura

• Whipworm Infection
• Soil-transmitted helminth.
• Found primarily in tropical and subtropical regions where sanitation and hygiene conditions are poor.
• Trichuriasis is a global infection.
• Ranked in recent surveys as the second most common intestinal nematode.
• It causes an estimated 464.6 million annual cases and 570,000 DALYS.
• An estimated 800 million individuals are infected worldwide.
• The life cycle is very similar to that of E. vermicularis, with the important exception that eggs are not infective when shed.
• After being passed in the stool, eggs undergo embryonation in the soil, becoming infective within 15 to 30 days.
• Humans become infected when ingesting mature eggs in food or on hands contaminated with soil containing T. trichiura eggs.
• The eggs hatch in the small intestine, and the adults take up a stationary position in the host's cecum and colon by embedding their slender anterior ends into the intestinal mucosa.
• Adults live for approximately 1 year, and the female worm begins to produce eggs approximately 60 to 70 days after infection.
• Each female sheds between 3000 and 20,000 eggs in the feces each day.
• Trichuriasis is mostly asymptomatic, but heavy infections (>300 worms) are associated with abdominal pain and diarrhea, iron deficiency anemia, growth retardation, and in severe cases, "trichuris dysentery" syndrome, characterized by severe, frequent, bloody, mucoid diarrhea, tenesmus, and potential rectal prolapse.
• Treatment is with albendazole, mebendazole, or ivermectin.

Ascaris lumbricoides

• Ascariasis
• The largest nematode to inhabit the human intestinal tract
• Most common helminth infection worldwide.
• Ascaris suum, a species recovered primarily from pigs, is morphologically and genetically indistinguishable from A. lumbricoides and hence usually considered the same species.
• A soil-transmitted helminth, as they must undergo maturation in warm, moist soil to develop and become infective.
• The prevalence is highest in tropical and subtropical regions with poor sanitation.
• WHO estimates ranked ascariasis as the most common cause of food-borne infections.
• The life cycle is like that of Trichuris trichiura, but with the important exception that larvae must undergo a migration stage through the lungs before maturing into adults.
• The lung migration stage is also a part of the hookworm and Strongyloides stercoralis life cycles.
• It is important to be aware of this stage of infection since it is associated with a self-limited respiratory syndrome, and larvae can be identified in sputum during this time.
• Adults reside and mate in the small intestine.
• A gravid female can lay up to 200,000 eggs per day.
• These are shed in the stool
• This is the diagnostic stage of infection.
• Ascariasis is usually asymptomatic, with the infected host unknowingly shedding unembryonated eggs in their stools.
• During the lung migration stage of infection, patients may experience a self-limited phase of infection termed Loeffler syndrome.
• It is associated with nonproductive cough, chest pain, fever, pneumonitis, and peripheral eosinophilia.
• This syndrome is most commonly seen in previously exposed individuals.
• When present, symptoms associated with the presence of adult worms include abdominal discomfort, nausea, and loss of appetite.
• In heavy infections, particularly in children, life-threatening small-bowel obstruction can occur.
• Since the adult worms are not anchored to the intestinal mucosa, they move freely in the intestinal lumen.
• They occasionally migrate into the biliary tree, pancreatic duct, or out of the nose or mouth.

Hookworms

• Ancylostomiasis, Necator Americanus Infection, Cutaneous Larva Migrans
• The two species of hookworm, Necator americanus and Ancylostoma duodenale, are responsible for an estimated 438.9 million infections worldwide.
• This makes it the second most common human helminth infection after ascariasis.
• Like ascariasis and trichuriasis, these soil-transmitted nematodes are more prevalent in tropical and subtropical countries with poor sanitation.
• Larvae, rather than eggs, are the infective form of the parasite.
• They live in the soil and can penetrate intact human skin.
• Because larvae are less resistant to environmental factors than eggs, they can only survive in regions with suitable moisture, shade, and warmth.
• Both species are found in the Americas, Africa, and Asia, although N. americanus predominates in the Americas, giving it the moniker New World Hookworm.
• Only A. duodenale is found in northern Africa, the Middle East, and southern Europe, and has therefore been called Old World Hookworm.
• Rarely, the zoonotic hookworm, A. ceylanicum, can cause similar intestinal disease; typically found in Southeast Asia.
• The life cycle of A. duodenale and N. americanum is very similar to the life cycle of A. lumbricoides, with the important exception that humans become infected when larvae in the soil penetrate intact skin rather than through ingestion of eggs.
• Once in the body, the larvae migrate to the lungs, where they penetrate pulmonary alveoli and ascent the bronchial tree to the oropharynx.
• They are then swallowed and reach the small intestine, where they mature into adults.
• Adult female and male worms attach to the intestinal wall using specialized mouth parts and feed on the blood of the host.
• A. duodenale has toothlike structures, while N. americanus has cutting plates.
• Worms may live for 1 to 2 years or more, and females produce as many as 20,000 eggs per day.
• The eggs are shed in the stool into the environment, where they hatch in warm and humid soil into rhabditiform (L1) larvae that will mature after 1 to 2 weeks into the infective (L3) filariform larvae.
• Light intestinal infections are generally asymptomatic.
• However, hosts may exhibit symptoms related to the life cycle of the hookworms: a self-limited pruritic rash called ground itch may develop at the point of entry of the larvae, while Loeffler syndrome may occur as the filariform larvae migrate through the lungs.
• The most common manifestation of intestinal infection is iron-deficiency anemia due to blood loss at the site of worm attachment.
• Infection with A. duodenale may cause a greater degree of anemia than infection with N. americanus, since each adult A. duodenale can result in 0.15 to 0.25 mL of blood loss each day.
• Heavy infections may also be associated with metabolic abnormalities, growth stunting, and developmental delays in children.
• Anemia can be particularly severe in infants with heavy infection and result in potentially fatal cardiac insufficiency.
• Effective treatment includes iron replacement therapy and antiparasitic agents such as albendazole, mebendazole, or pyrantel pamoate.
• Cutaneous larva migrans is characterized by an intensely pruritic rash at the site of larva entry, commonly taking the form of an erythematous serpiginous track.
• Infection is self-limited and will usually resolve without treatment in 4 to 8 weeks.
• However, topical or oral antihelminthic therapy with thiabendazole, albendazole, mebendazole, or ivermectin will shorten the course of disease.

Cestodes

• Tapeworms
• Segmented flatworms (platyhelminths) with three distinct anatomic sections: the scolex (head), neck, and body (strobila).
• Tapeworms attach to the intestinal mucosa using their scolex, which may contain suckers, hooklets, or grooves (bothria), depending on the infecting species.
• The neck is the mitotically active segment of the worm where new independent units called proglottids are formed.
• Each proglottid contains male and female reproductive units that will produce several hundred to thousands of eggs.
• Most common cestodes to infect the human intestinal tract: Taenia spp., Hymenolepis spp., Dipylidium caninum, and Diphyllobothrium spp.

Taenia saginata and Taenia solium

• Are among the most common tapeworm infections reported worldwide.
• Taeniasis is the name of the infection caused by adult worms of T. saginata, T. solium, and T. asiatica.
• During this stage of infection, the adult is attached to the wall of the small intestine, and proglottids and eggs are shed in the feces.
• T. saginata, commonly known as the beef tapeworm, has a global prevalence estimate of 60 million infected individuals.
• Higher prevalence rates have been reported in Asia, Latin America, the Middle East, and Eastern Africa.
• T. solium is considered the more important of the two tapeworms because of its potential for causing neurocysticercosis.
• It is the leading cause of acquired epilepsy worldwide.
• Taenia solium is present worldwide.
• Its higher prevalence of human infections in poorer communities where undercooked pork is ingested, such as Latin America, Eastern Europe, China, India, and Pakistan.
• Humans are the definitive hosts of T. saginata and T. solium and become infected following ingestion of infective larvae (cysticerci) in contaminated beef or pork meat, respectively.
• Following ingestion, the ingested cysticerci mature into adult worms in the small intestine and attach to the mucosal lining using their specialized scoleces.
• Each worm produces several thousand proglottids, which will eventually detach from the main body and be shed in the host feces.
• Eggs may contaminate the environment (e.g., grass) and are then ingested by grazing cattle (T. saginata) or pigs (T. solium), the intermediate hosts.

Diphyllobothrium Species

• (Diphyllobothriasis)
• Humans serve as the definitive host along with other mammals and birds.
• Crustaceans and fish serve as intermediate hosts.
• Diphyllobothrium spp. are the longest human tapeworms, measuring greater than 10-15 meters in length and consisting of over 3000 proglottids.
• They are commonly known as the "broad fish tapeworm" since its proglottids are wider than they are long.
• Diphyllobothriasis has a worldwide distribution, with an estimate of 20 million infected individuals.

Filariasis (Nematodes)

• Filarial worms are common vector-borne parasites of vertebrate animals.
• The adults are long, slender worms measuring up to 20 cm in length and inhabit a variety of tissues in the host, including:
  • the lymphatics (lymphatic filariasis),
  • blood vessels (dirofilariasis),
  • subcutaneous tissues (onchocerciasis, loaiasis), and
  • peritoneal and pleural cavities (mansonellosis).
• The adults produce microfilariae (larvae), which can be found in the blood or the skin, depending on the infecting species.
• The microfilariae are then taken up with the blood meal of a suitable arthropod vector and continue their development into an infective stage that can be inoculated into a new host.
• Some microfilariae are released from the adult female during the day (diurnal periodicity) or night (nocturnal periodicity), whereas others have no specific cycle.
• The diagnosis of filariasis is usually made by identification of characteristic microfilariae in blood or skin specimens.
• Less commonly, identification is made by removal of the adults.
• The blood microfilariae can be seen on conventional thick and thin films, but the use of concentration methods such as the Knott's concentration and Nucleopore membrane filtration methods improve the sensitivity of detection.
• The adults reside in the lymphatics and release microfilariae into the blood, typically at night.
• Microfilariae are then taken up by the nocturnal biting mosquito vectors and undergo further development in the mosquito before being passed on to another host.

Wuchereria bancrofti and Brugia Species

• (Lymphatic Filariasis)
• Lymphatic filariasis is caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori.
• W. bancrofti is the most common filarial worm to infect humans, being responsible for approximately 90% of cases.
• Wucheria bancrofti is distributed throughout much of the tropics and subtropics, including parts of Africa, India, Southeast Asia, Latin America, the West Indies, and the South Pacific Islands.
• The agents of lymphatic filariasis, Wuchereria bancrofti and Brugia spp., exhibit a nocturnal periodicity and therefore, blood is ideally obtained between 10 PM and 2 AM.
• Lymphatic filariasis is a leading cause of global disability worldwide and is classified by the WHO as a neglected tropical disease.
• The WHO estimates that 120 million individuals are infected with lymphatic filariasis worldwide, with nearly 15 million individuals, mostly women, having symptomatic lymphedema or elephantiasis of a lower extremity, and nearly 25 million men having genital hydrocele or elephantiasis.
• Worldwide elimination strategies using mass drug administration (MDA) with albendazole, ivermectin, or diethylcarbamazine in conjunction with vector control strategies have shown significant success in reducing the burden of lymphatic filariasis worldwide.
• Culex spp. mosquitoes are the primary vectors for W. bancrofti.
• Anopheles and Aedes mosquitoes are also responsible for transmission in some areas.
• Brugia spp. are transmitted by Mansonia spp. and, less commonly, Anopheles spp. mosquitoes.

Loa Loa

• Loiasis
• Commonly known as the African eye worm.
• It migrates through the subcutaneous tissues as an adult and releases microfilariae into the blood.
• It has only been definitively reported from patients in Africa.
• Ongoing subcutaneous migration of the adult produces transient associated inflammatory reactions called Calabar swellings, which are accompanied by a high eosinophilia.
• The adult can occasionally be detected during subconjunctival migration, during which it can be removed for definitive identification.
• Infection is transmitted to humans through the bite of an infected deer fly (genus Chrysops), which inoculates L3 larvae into the bite wound.
• The migrating adults release microfilariae into the blood during the day (diurnal periodicity), which corresponds with the biting activity of the Chrysops vector.

Onchocerciasis

• River blindness
• A chronic parasitic infection involving the skin and eye.
• Leading cause of blindness in endemic areas.
• Infections are found primarily in tropical sub-Saharan Africa, with fewer cases in Latin America and Yemen.
• WHO estimates that 120 million individuals are at risk for infection and has classified onchocerciasis as one of the 14 NTDs.
• Humans acquire infection through the bite of an infected blackfly (genus Simulium) when L3 larvae enter the bite wound.
• These flies are found primarily in remote rural areas and breed in fast-flowing streams and rivers, hence, the name "river blindness."
• After inoculation by the blackfly vector, the L3 larvae develop into male and female adults that live in a subcutaneous fibrous nodule called an onchocercoma.

Trichinella Species

• (Trichinellosis, Trichinosis)
• Caused by several species in the genus Trichinella.
• A zoonotic infection, infecting a wide variety of mammals, birds, reptiles, and other animals in sylvatic and domestic cycles.
• Trichinella spiralis is the classical agent implicated in human disease and is found throughout the world.
• Other known species that cause human trichinellosis are T. pseudospiralis (worldwide), T. nativa (Arctic), T. nelsoni (Africa), T. britovi (Europe and Western Asia), and T. papuae (Papua New Guinea and Thailand).
• Trichinella spp. have been found in wild and domestic animals in 66 countries.
• Human cases have been reported from 55 countries, and are most common in regions where raw or undercooked meat is commonly consumed.
• Older estimates suggest that 10 million individuals are infected worldwide.
• A wide variety of animals, including humans, can serve as the definitive and potential intermediate host to Trichinella spp.
• Hosts acquire infection through ingestion of undercooked meat containing viable Trichinella larvae, resulting in a short-lived reproductive phase by the adult worms in the small intestine.
• The adult female releases larvae into the intestinal mucosa, which then enter the circulation and migrate to striated muscles throughout the body.

Paragonimus Species

• Paragonimiasis, Lung Fluke Infection
• Greater than 10 species of flukes in the genus Paragonimus have been reported to cause human paragonimiasis.
• P. westermani, the oriental lung fluke, is the most common cause.
• Paragonimus spp. have been found throughout Africa, the Americas, and Southeast Asia.
• Paragonimiasis is a food-borne trematodiasis, which is one of the NTDs recognized by the WHO.
• Humans acquire infection primarily through ingestion of undercooked crustaceans, including crabs and crayfish.
• Examples of potentially infectious foods include pickled, salted, dried, marinated, raw, or partially cooked crustaceans.
• Paragonimus spp. are a common cause of human and animal infections.

Schistosoma Species

• Schistosomiasis, Blood Fluke Infection
• Human schistosomiasis, also known as bilharziasis, is caused by several species in the genus Schistosoma.
• The main causes of human disease are S. mansoni, S. japonicum, and S. haematobium, while S. mekongi and S. intercalatum are responsible for a smaller number of cases in localized geographic regions.
• Schistosomiasis is arguably one of the most important parasitic infections in the world.
• It is found throughout regions of the tropics and subtropics worldwide.
• S. mansoni has the greatest geographic distribution, being found in parts of Africa, the Middle East, South America, and the Caribbean, while S. haematobium is found only in parts of Africa and the Middle East, and S. japonicum in the Far East.
• Infection occurs when free-swimming cercariae penetrate the skin.
• This commonly occurs while the host is bathing or swimming in contaminated water, or using contaminated water for household chores.
• Once entering the body, the cercariae lose their tails to become schistosomulae, and undertake a migratory path through several tissues, including the liver, where they mature into adults.
• Occasionally, humans can become transiently infected with bird or other mammal schistosomes, causing a self-limited cutaneous infection called cercarial dermatitis ("swimmer's itch" or "Clam-digger's disease").
• The cercariae may penetrate human skin but cannot mature into adults and eventually die.
• Human activities have, at times, resulted in the increase of suitable habitat for the snail intermediate host resulting in a spread of disease.
• Cercarial dermatitis due to nonhuman schistosomes can occur in both fresh and brackish water.
• Finally, human schistosomes have a significantly different life cycle than the other trematodes. Rather than ingestion of contaminated food, Schistosoma spp. infect their host through direct skin penetration.
• They thus present more like hookworm and strongyloidiasis in this regard.