Diphyllobothrium/Diphyllobothriasis

Diphyllobothriasis represents an intestinal parasitic infection caused by the cestode Diphyllobothrium (also known as “fish tapeworm” or “broad tapeworm”). Diphyllobothriasis is acquired by ingestion of late larvae in undercooked or raw fish. The clinical presentation of diphyllobothriasis varies from asymptomatic, nonspecific symptoms to intestinal obstruction, and/or vitamin B12 deficiency. Identification of eggs or proglottids in the stool can provide the diagnosis. Management includes anthelmintic therapy and, if needed, vitamin B12 supplementation.

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General Characteristics and Epidemiology

General features of Diphyllobothrium

Diphyllobothriasis is caused by a parasitic infection from the cestode (tapeworm) Diphyllobothrium

  • The largest human parasite (length up to 10 meters)
  • Adult morphology:
    • Scolex
      • No hooks 
      • Paired slit-like attachment grooves (bothria)
    • Neck
    • Strobila with up to 3,000–4,000 proglottids
      • Segmented
      • Contains sets of reproductive organs
  • Eggs:
    • Ellipsoidal or oval
    • Operculum (lid-like structure) at 1 end
    • Mature in water within 3 weeks
  • Feeds through absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption

Clinically relevant species

  • D. latum (most common)
  • D. nihonkaiense
  • D. dendriticum
  • D. pacificus

Epidemiology

  • Approximately 20 million people are infected worldwide.
  • Traditionally found in areas where raw fish consumption is common:
    • Northern Europe
    • North America
    • Japan
    • South America (rare)
  • No reported age or sexual predilection
  • No racial predilection

Pathogenesis

Hosts

Definitive hosts:

  • Humans
  • Mammals
  • Birds

Intermediate hosts:

  • Freshwater fish (most common) 
  • Marine fish
  • Crustaceans

Transmission

Diphyllobothriasis is transmitted through the consumption of raw or undercooked fish.

Life cycle

  • Immature eggs are passed in the feces of a definitive host.
  • Eggs mature → oncospheres → develop into coracidia → ingested by crustaceans (1st intermediate host)
  • Develop into procercoid larvae
  • Crustacean ingested by fish (2nd intermediate host) → procercoid larvae develop into plerocercoid larvae (infectious stage) 
  • 2nd intermediate host can be eaten by larger predators → plerocercoid larvae migrate to musculature
  • Humans (definitive host) consume infected raw or undercooked fish → develop into adult worms in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine → produce eggs
  • Immature eggs are passed in the feces → cycle continues
Life cycle of diphyllobothriasis

The life cycle of the Diphyllobothrium species (causal agent of diphyllobothriasis)

Image: “Diphyllobothrium” by CDC. License: Public Domain

Clinical Presentation

General signs and symptoms

  • Most patients are asymptomatic.
  • Passage of proglottids in the stool can occur.
  • Nonspecific symptoms:
    • Fatigue
    • Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Dizziness
    • Weight loss

Complications

The following may be caused by heavy infections or aberrant migration of the tapeworms:

  • Vitamin B12 deficiency → D. latum has a high affinity for vitamin B12
    • Anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview 
    • Paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Respiratory Alkalosis
    • Weakness
    • Hyporeflexia
    • Ataxia
    • Encephalopathy
  • Bowel obstruction → occurs if worms become entangled
  • Biliary disease → migration of proglottids 
    • Cholecystitis Cholecystitis Cholecystitis is the inflammation of the gallbladder (GB) usually caused by the obstruction of the cystic duct (acute cholecystitis). Mechanical irritation by gallstones can also produce chronic GB inflammation. Cholecystitis is one of the most common complications of cholelithiasis but inflammation without gallstones can occur in a minority of patients. Cholecystitis 
    • Cholangitis

Diagnosis and Management

Diagnosis

  • Microscopic examination of the stool can reveal operculated eggs or proglottids.
  • Laboratory testing is largely nonspecific, but may reveal: 
    • Eosinophilia
    • Megaloblastic anemia Megaloblastic anemia Megaloblastic anemia is a subset of macrocytic anemias that arises because of impaired nucleic acid synthesis in erythroid precursors. This impairment leads to ineffective RBC production and intramedullary hemolysis that is characterized by large cells with arrested nuclear maturation. The most common causes are vitamin B12 and folic acid deficiencies. Megaloblastic Anemia
    • ↓ Vitamin B12 

Management

  • Anthelmintic therapy:
    • Praziquantel (preferred)
    • Niclosamide
  • Correction of vitamin B12 deficiency

Prevention

  • Cook fish properly.
  • If eating sashimi or sushi, freeze fish to kill the tapeworm larvae.
  • Water sanitation measures

Comparison of Tapeworm Species

Table: Characteristics and diseases of different tapeworm species
Organism Diphyllobothrium latum Taenia Taenia Taenia belong to the Cestoda class of helminths. Humans are infected with these tapeworms by eating undercooked beef (T. saginata) or pork (T. solium and T. asiatica). Taeniasis is often asymptomatic, but the ingestion of larvae can cause abdominal discomfort, nausea, and constipation or diarrhea. Taenia/Taeniasis saginata Echinococcus Echinococcus Echinococcosis is a parasitic disease caused by Echinococcus tapeworms. Infection most often occurs from the ingestion of Echinococcus eggs in food or water contaminated with dog feces. Signs and symptoms are caused by hydatid cyst development in visceral organs and depend on the species. Echinococcus/Echinococcosis granulosus
Characteristics
  • Approximately 10 meters long
  • No hooks
  • Bothria present
  • > 3,000 proglottids
  • < 5 meters long
  • No hooks
  • No neck
  • Approximately 1,000 proglottids
  • 2–7 mm long
  • Hooks present
  • 3–6 proglottids
Transmission Eating raw, infected fish Eating raw, infected beef Fecal to oral (ingestion of contaminated food or water)
Disease Diphyllobothriasis Taeniasis Taeniasis Taenia belong to the Cestoda class of helminths. Humans are infected with these tapeworms by eating undercooked beef (T. saginata) or pork (T. solium and T. asiatica). Taeniasis is often asymptomatic, but the ingestion of larvae can cause abdominal discomfort, nausea, and constipation or diarrhea. Taenia/Taeniasis Cystic echinococcosis Echinococcosis Echinococcosis is a parasitic disease caused by Echinococcus tapeworms. Infection most often occurs from the ingestion of Echinococcus eggs in food or water contaminated with dog feces. Signs and symptoms are caused by hydatid cyst development in visceral organs and depend on the species. Echinococcus/Echinococcosis
Clinical
  • Abdominal discomfort
  • Weight loss
  • Vitamin B12 deficiency
  • Bowel obstruction
  • Usually asymptomatic
  • Mild GI symptoms
Depends on location and size of hydatid cysts
Diagnosis Eggs or proglottids in stool Eggs or proglottids in stool
  • Imaging
  • Serology
Management
  • Praziquantel
  • Niclosamide
  • Praziquantel
  • Niclosamide
  • Albendazole
  • Percutaneous drainage
  • Surgical excision
Prevention
  • Freeze fish.
  • Thoroughly cook fish.
  • Water sanitation measures
Cook beef thoroughly.
  • Personal hygiene
  • Avoid contact with stray dogs.
  • Avoid potentially contaminated food.
  • Improve water sanitation.

Differential Diagnosis

  • Ascariasis Ascariasis Ascariasis is most often caused by A. lumbricoides. If symptomatic, characteristics typically follow 2 phases, which correlate with the migration of the parasite through the body. The early phase may include cough, dyspnea, and wheezing. The late phase typically includes abdominal discomfort, bloating, nausea, and intermittent diarrhea. Ascaris/Ascariasis: an infection caused by the parasitic roundworm Ascaris Ascaris Ascaris is a genus of parasitic nematodes. The infection, ascariasis, is most often caused by A. lumbricoides. Transmission occurs primarily via ingestion of water or food contaminated with Ascaris eggs. Most patients with ascariasis are asymptomatic. Ascaris/Ascariasis lumbricoides. Transmission occurs from the ingestion of water or food contaminated with Ascaris Ascaris Ascaris is a genus of parasitic nematodes. The infection, ascariasis, is most often caused by A. lumbricoides. Transmission occurs primarily via ingestion of water or food contaminated with Ascaris eggs. Most patients with ascariasis are asymptomatic. Ascaris/Ascariasis eggs. Patients may be asymptomatic or experience cough and hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis. A large worm burden can cause intestinal obstruction and impair growth in children. Examination of the stool may show the presence of worms or eggs.  Management is with anthelmintic therapy.
  • Pernicious anemia: causes vitamin B12 deficiency and megaloblastic anemia due to a deficiency of intrinsic factor, which is required for vitamin B12 absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption. Patients may have fatigue, cognitive decline, neuropathy, ataxia, and glossitis. Low vitamin B12 levels, anti-intrinsic factor antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins, and the Schilling test can be used for diagnosis. Management includes vitamin B12 replacement.
  • Small intestinal bacterial overgrowth: Aerobic and anaerobic microbes normally present in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix grow excessively in the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine. Approximately 90% of cases are due to motility disorders and chronic pancreatitis Chronic pancreatitis Chronic pancreatitis is due to persistent inflammation, fibrosis, and irreversible cell damage to the pancreas, resulting in a loss of endocrine and exocrine gland function. The most common etiologies are alcohol abuse and pancreatic duct obstruction. Patients often present with recurrent epigastric abdominal pain, nausea, and features of malabsorption syndrome (diarrhea, steatorrhea, and weight loss). Chronic Pancreatitis. Presentation includes bloating, flatulence, watery diarrhea, and abdominal discomfort; vitamin B12 deficiency can occur. The diagnosis can be made with breath testing. The mainstay of treatment is antibiotics and the correction of nutritional deficiencies.
  • Inflammatory bowel disease (IBD): characterized by chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the GI tract due to a cell-mediated immune response to GI mucosa. Crohn’s disease and ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn's disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis are inflammatory bowel diseases. Symptoms include diarrhea, abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, weight loss, and extraintestinal manifestations. Diagnosis includes imaging, endoscopy, and biopsy. Management involves steroids, aminosalicylates, immunomodulators, and biologic agents.

References

  1. Hochberg NS, Hamer DH. Anisakidosis: Perils of the deep. Clin Infect Dis 2010;51:806–12.
  2. Scholz T, Garcia HH, Kuchta R, Wicht B. Update on the human broad tapeworm (genus diphyllobothrium), including clinical relevance. Clin Microbiol Rev. 2009 Jan. 22 (1):146–60. http://reference.medscape.com/medline/abstract/19136438
  3. Vindigni SM, Hahn H, Zhang Q. Intermittent obstructive symptoms in a patient with diphyllobothriasis. Gastrointest Endosc. 2017 Dec. 86 (6):1185–1186. http://reference.medscape.com/medline/abstract/28602516
  4. Maithel S, Duong AK, Zhang J, Nguyen DL. An unusual cause of vitamin B12 and iron deficiency. Cleve Clin J Med. 2015 Jul. 82 (7):406–8. http://reference.medscape.com/medline/abstract/26185938
  5. Kuchta R, Serrano-Martínez ME, Scholz T. Pacific Broad Tapeworm Adenocephalus pacificus as a Causative Agent of Globally Reemerging Diphyllobothriosis. Emerg Infect Dis. 2015 Oct. 21 (10):1697–703. http://reference.medscape.com/medline/abstract/26402440
  6. Arizono N, Yamada M, Nakamura-Uchiyama F, Ohnishi K. Diphyllobothriasis associated with eating raw Pacific salmon. Emerg Infect Dis. 2009 Jun. 15 (6):866–70. http://reference.medscape.com/medline/abstract/19523283
  7. Haburchak, D.R. (2019). Diphyllobothriasis. In Chandrasekar, P.H. (Ed.), Medscape. Retrieved April 19, 2021, from https://emedicine.medscape.com/article/216089-overview
  8. Leder, K., and Weller, P.F. (2019). Tapeworm infections. In Baron, E.L. (Ed.), UpToDate. Retrieved April 19, 2021, from https://www.uptodate.com/contents/tapeworm-infections
  9. Durrani, M.I., Basit, H., and Blazar, E. (2021). Diphyllobothrium latum. [online] StatPearls. Retrieved April 19, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK540971/
  10. Pearson, R.D. (2020). Diphyllobothriasis (fish tapeworm infection). [online] MSD Manual Professional Version. Retrieved April 20, 2021, from https://www.msdmanuals.com/professional/infectious-diseases/cestodes-tapeworms/diphyllobothriasis-fish-tapeworm-infection
  11. Centers for Disease Control and Prevention (2019). Diphyllobothriasis. Retrieved April 19, 2021, from https://www.cdc.gov/dpdx/diphyllobothriasis/index.html

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