Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Serena Cavallero
 -- 1635 2022-04-19 12:26:38 |
2 format correct
Conner Chen
 Meta information modification 1635 2022-04-20 02:45:17 |

Video Upload Options

Do you have a full video?
Send video materials Upload full video

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Cavallero, S.; Bellini, I.; , .; D'amelio, S. Anisakiasis. Encyclopedia. Available online: https://encyclopedia.pub/entry/21941 (accessed on 21 July 2024).
Cavallero S, Bellini I,  , D'amelio S. Anisakiasis. Encyclopedia. Available at: https://encyclopedia.pub/entry/21941. Accessed July 21, 2024.
Cavallero, Serena, Ilaria Bellini,  , Stefano D'amelio. "Anisakiasis" Encyclopedia, https://encyclopedia.pub/entry/21941 (accessed July 21, 2024).
Cavallero, S., Bellini, I., , ., & D'amelio, S. (2022, April 19). Anisakiasis. In Encyclopedia. https://encyclopedia.pub/entry/21941
Cavallero, Serena, et al. "Anisakiasis." Encyclopedia. Web. 19 April, 2022.
Anisakiasis
Edit
This entry is adapted from the peer-reviewed paper 10.3390/pathogens11030285

Anisakiasis is a zoonosis caused by the ingestion of raw or undercooked seafood infected with third-stage larvae (L3) of the marine nematode Anisakis. Based on L3 localization in human accidental hosts, gastric, intestinal or ectopic (extra-gastrointestinal) anisakiasis can occur, in association with mild to severe symptoms of gastrointestinal and/or allergic nature.

anisakiasis immune response anisakis zoonosis fish-borne

1. Introduction

Fish-borne parasitic helminthiasis caused by trematodes, cestodes and nematodes has recently emerged as a major food safety concern, which causes economic impact and significant public health concern. In fact, fishery and aquaculture sectors are growing in global production and consumption [1], and the growing popularity of eating raw or undercooked fish, such as sushi, sashimi, carpaccio or fish tartare, has led to a consequent increase in risk of human exposure to the infective stages of fish-borne helminths [2]. Among these, Anisakis spp. (Nematoda: Anisakidae) is the etiological agent of the gastrointestinal zoonotic disease known as anisakiasis. The genus Anisakis includes nine species distributed worldwide, and two of them are mainly associated with human infections [3]: Anisakis simplex sensu stricto, occurring in the subarctic and temperate waters of the northern hemisphere, and Anisakis pegreffii, distributed in the Mediterranean Sea and widespread in the Austral region.
Anisakis spp. are gastrointestinal ascaridoid nematodes that infect the digestive system of marine vertebrates. They have a complex life cycle in which developmental stages are transmitted along different levels of the trophic web. Definitive hosts are marine mammals, which release eggs with feces and, after larval molting from stage 1 to stage 3 (L1, L2, L3), they are ingested by crustacean hosts. Then, the infective stage L3 reaches other suitable hosts (paratenic hosts), such as fishes and squids, based on the prey–predator relationship [4]. Humans become accidental hosts after the ingestion of raw or undercooked marine products containing L3 larvae.
The first case of anisakiasis was diagnosed in the Netherlands in the 1960s [5], and, to date, more than 20,000 cases have been reported, of which 90% were in Japan (2000/3000 every year), most likely due to the traditional, local dietary habits. In Europe, estimates range from 20 to 500 cases/year [6][7] according to hospital discharge records and published case reports, and a quantitative risk assessment indicated a risk of anisakiasis in between 7700 and 8320 cases annually in Spain [8]. Considering the intrinsic limitations of currently available diagnostic tools, the heterogeneity of symptoms and the paucity of epidemiological data, the global prevalence of anisakiasis is likely to be severely underestimated [4]. Moreover, Anisakis is the only fish parasite able to trigger an allergic reaction in humans by sensitization occurring via infection by live larvae [2]. Allergic reactions may arise even with cooked fish, given the thermostability of some Anisakis allergens [9].

2. Anisakiasis

Different anisakid nematodes may cause anisakidosis, most frequently species belonging to the Anisakis and Pseudoterranova genera or, very rarely, to the genus Contracaecum. Hereafter, the term anisakiasis will be used to refer to the disease, as most of the evidences reported here were based on Anisakis spp.
Although larval nematodes cannot reach the adult stage in humans, L3 is able to perforate the gastrointestinal tract, causing severe pathological consequences. Acute or moderate, non-specific clinical manifestations are commonly reported. In addition, the onset of serious allergic reactions, such as asthma, hives or urticaria, dermatitis and anaphylactic shock, can be observed [10]. The disease can be classified as acute and moderate by the entity of symptoms and into gastric anisakiasis (GA) and intestinal anisakiasis (IA) or extra-gastrointestinal anisakiasis (ectopic), depending on larval localization. Other forms of anisakiasis are recognized, such as the gastro-allergic anisakiasis (GAA) caused by an IgE-mediated allergic reaction and an asymptomatic form observed in seropositive cases [11]. In some cases, larvae were found in the gastroesophageal junction [12] and in the ileocecal region [13].
In acute forms of GA, early symptoms appear 4–6 h after the ingestion of infected food, causing nausea, vomiting and epigastric pain. Moderate forms of GA are characterized by appetite loss, epigastralgia and the occurrence of gastric pseudotumors. On the contrary, acute signs appear later in IA (around 7 days after eating infected seafood), with abdominal pain, nausea, vomiting, fever, diarrhea, fecal occult blood, leukocytosis and, rarely, eosinophilia [14]. Several rare, extra-gastrointestinal localizations were documented in the abdominal cavity [15], mesenteries and omentum [16] and liver [17], among many other locations. GAA is the most common clinical form, showing the abovementioned gastric symptoms and signs combined with allergic reactions [10]. Chronic gastrointestinal forms are associated with appetite loss, epigastralgia and possible granuloma formation [18]. Due to the heterogeneity of symptoms, the diagnosis of anisakiasis is complicated. Three diagnostic approaches are commonly used: endoscopic examination, X-ray examinations and hematochemical assay with particular attention to specific and total IgE antibodies [19]. Additional imaging techniques, such as CT or RMN, may be of diagnostic support. A good medical anamnesis is essential before carrying out invasive clinical tests. An endoscopic diagnostic approach may be also curative, in the case of larval removal, and a colonoscopy diagnostic approach should be considered as well. The anthelmintic drugs used are albendazole and ivermectin, about which, however, there are conflicting opinions regarding their real efficacy in vivo [20]. The effectiveness of alternative drugs, such as gastric acid secretion inhibitors and gastric mucosal protectants, are under evaluation in Wistar rats model [21]. Regarding this, EFSA expressed its opinion in 2010, stating that, having not identified specific and targeted pharmacological treatments for the effective killing of the parasite in vivo, the most effective treatment remains prevention, as the eradication of such nematodes in natural settings is not desirable [2].

3. Features of Immune Response to Helminthiasis and Anisakiasis

The gastrointestinal helminths of public health concern usually use humans as natural, final hosts, while the natural life cycle of anisakids includes several aquatic organisms, and humans are accidental hosts not accounted for in the natural evolution processes, such as co-evolution and/or co-adaptation, that have occurred over time between hosts and parasites [22]. Despite that, only one L3 is sufficient to cause clinical outcomes in humans. A few hours after ingestion, the L3 reaches the gastrointestinal tract. Through a combination of mechanical tissue disruption and release of secrete/excrete (E/S) factors, such as soluble, potent proteolytic enzymes able to degrade the extracellular matrix [23], together with the extracellular vesicles, including exosomes, the L3 starts to invade the mucosa and submucosa of the gastrointestinal tract. Audicana et al. [24] described this mechanism in a time-dependent manner, accounting for a progressive process that leads to ulcerous, erosive and granulomatous lesions [24][25]. Helminths, such as Anisakis, are macro pathogens, a condition that prevents them from being quickly captured by phagocytic cells. Therefore, immunomodulating messengers released by immune cells and the parasite itself play a pivotal role in host–parasite interactions, contributing to the onset of an inflammatory microenvironment able to induce a specific Th2 response [26][27]. The epithelial barrier, macrophages (MØ) and dendritic cells (DCs) represent the first line of the human innate immune response. A further pivotal element of the innate immune response is the receptors and, among them, toll-like receptors (TLRs) are the most investigated in several helminthic infections [28]. In particular, DCs identify Schistosoma mansoni lipid antigens containing phosphatidyl serine through TLR2, while glycoprotein ES-62 of filarial nematodes is recognized through TLR4 [29]. Despite their relevance, information about TLRs in anisakiasis is still poor and not clear. Usually, the activation of TLRs leads to downstream intracellular signaling. The MAPK pathway is one of the main signaling cascades associated with TLRs stimulation, and it is composed of the extracellular, signal-related kinases 1 and 2 (ERK 1/2), p38 MAPK and c-jun NH2-terminal kinase (JNK). ERK 1/2 usually induces Th2 activation during infections due to extracellular pathogens [30], while P38 and JNK are mostly involved in the Th1 responses commonly reported for intracellular pathogens [31]. Once activated, these molecules induce gene expression, DC maturation and cytokine production via the phosphorylation of transcription factors, such as activating protein 1 (AP-1) and nuclear factor-κB (NF-κB) [32]. The cytokine and chemokine milieu derived from the innate immune cells activation results in the release of specific, pro-inflammatory products, such as thymic stromal lymphopoietin (TSLP), eotaxin and interleukins, such as IL-25, IL-4, IL-5, IL-13, IL-9 and IL-33 [27], that contribute to DC activation and type 2 response initiation. It was demonstrated that mice deficient in IL-25 are susceptible to infection with the rodent whipworm Trichuris muris, and mice with a dysregulation in TSLP production are unable to induce Th2-driven worm expulsion [33]. The tissue damage and the release of inflammatory products allow the recruitment of competent cells, such as neutrophils, eosinophils and basophils, among several others, in the site of damage. Actually, one of the main signatures of local lesions produced by Anisakis larvae is the presence of an appreciable eosinophilic infiltration in the tissues surrounding the parasite [24]. At this point, mature DCs migrate to lymph nodes, priming T naïve cells and giving arise to a Th2 clonal proliferation. The triggering of the Th2 response induced by intestinal nematodes leads to a stereotyped signal cascade of effector mechanisms, including immunoglobulin E isotype-switched B-cell responses, increased permeability, epithelial cell turnover, smooth muscle contractility, mucus production, eosinophilia and mastocytosis, with consequent parasite expulsion [34]. To avoid this, helminths have devised different strategies to manipulate the host immune system. The alarmin release inhibitor E/S product HpARI released by murine intestinal nematode Heligmosomoides polygyrus suppresses the IL-33 ablating Th2 response [35][36]. Again, asu-miR-5361-5p, a miRNA observed in adult pig roundworm Ascaris suum exosome content, downregulates CD80, a receptor involved in the induction of T-cell proliferation and cytokine production [37]. The suppression of the host immune response and tolerance can lead to a parasite persistence and chronic inflammation. During chronic anisakiasis, the persistent stimulus of the L3 amplifies the inflammatory state and continuously attracts eosinophils, as well as neutrophils, lymphocytes, monocytes and fibroblasts, recruited to deposit connective tissue to form a granuloma [25]. The main role of granuloma is to protect the host from pathogens and/or persistent irritants and, after larval death, Anisakis remains are broken down, in time, becoming unrecognizable. This phenomenon contributes to complication of the diagnosis; thus, Anisakis-induced granulomas have been misdiagnosed for tumors in the past but gradually disappear in infected patients, leading to the term “vanishing tumors”.

References

  1. FAO. The State of World Fisheries and Aquaculture—Opportunities and Challenges; Food and Agriculture Organisation of the United Nations: Rome, Italy, 2014.
  2. Panel EFSA. On biological hazards (BIOHAZ) scientific opinion on risk assessment of parasites in fishery products. EFSA J. 2010, 8, 1543.
  3. Jeon, C.H.; Kim, J.H. Pathogenic potential of two sibling species, Anisakis simplex (s.s.) and Anisakis pegreffii (Nematoda: Anisakidae): In vitro and in vivo studies. Biomed. Res. Int. 2015, 2015, 983656.
  4. Anderson, R.C. Nematodes Parasites of Vertebrates: Their Development and Transmission, 2nd ed.; CABI Publishing: Wallingford, UK, 2000.
  5. Van Thiel, F.; Kuipers, F.C.; Roskam, R.T. A nematode parasitic to herring, causing acute abdominal syndromes in man. Trop. Geogr. Med. 1960, 12, 97–113.
  6. Cavallero, S.; Martini, A.; Migliara, G.; De Vito, C.; Iavicoli, S.; D’Amelio, S. Anisakiasis in Italy: Analysis of hospital discharge records in the years 2005–2015. PLoS ONE 2018, 13, e0208772.
  7. Guardone, L.; Armani, A.; Nucera, D.; Costanzo, F.; Mattiucci, S.; Bruschi, F. Human anisakiasis in Italy: A retrospective epidemiological study over two decades. Parasite 2018, 25, 41.
  8. Bao, M.; Pierce, G.J.; Pascual, S.; González-Muñoz, M.; Mattiucci, S.; Mladineo, I.; Cipriani, P.; Bušelić, I.; Strachan, N.J. Assessing the risk of an emerging zoonosis of worldwide concern: Anisakiasis. Sci. Rep. 2017, 7, 43699.
  9. Rodriguez-Mahillo, A.I.; Gonzalez-Muñoz, M.; Gomez-Aguado, F.; Rodriguez-Perez, R.; Corcuera, M.T.; Caballero, M.L.; Moneo, I. Cloning and characterisation of the Anisakis simplex allergen Ani s 4 as a cysteine-protease inhibitor. Int. J. Parasitol. 2007, 37, 907–917.
  10. Daschner, A.; Alonso-Gómez, A.; Cabañas, R.; Suarez-de-Parga, J.M.; López-Serrano, M.C. Gastroallergic anisakiasis: Borderline between food allergy and parasitic disease-clinical and allergologic evaluation of 20 patients with confirmed acute parasitism by Anisakis simplex. J. Allergy Clin. Immunol. 2000, 105 Pt 1, 176–181.
  11. Moneo, I.; Carballeda-Sangiao, N.; González-Muñoz, M. New Perspectives on the Diagnosis of Allergy to Anisakis spp. Curr. Allergy Asthma Rep. 2017, 17, 27.
  12. Muguruma, N.; Okamura, S.; Okahisa, T.; Shibata, H.; Ito, S.; Terauchi, A. Anisakis larva involving the esophageal mucosa. GIE 1999, 49, 653–654.
  13. Woon-Mok, S.; Jung-Mi, K.; Byoung-Kuk, N. Molecular analysis of Anisakis Type I larvae in marine fish from three different sea areas in Korea. Korean J. Parasitol. 2014, 52, 383–389.
  14. Cong, W.; Elsheikha, H.M. Biology, Epidemiology, Clinical Features, Diagnosis, and Treatment of Selected Fish-borne Parasitic Zoonoses. Yale J. Biol. Med. 2021, 94, 297–309.
  15. Nogami, Y.; Fujii-Nishimura, Y.; Bann, K.; Suzuki, A.; Susumu, N.; Hibi, T.; Murakami, K.; Yamada, T.; Sugiyama, H.; Morishima, Y.; et al. Anisakiasis mimics cancer recurrence: Two cases of extragastrointestinal anisakiasis suspected to be recurrence of gynecological cancer on PET-CT and molecular biological investigation. BCM Med. Imaging 2016, 26, 16–31.
  16. Pampiglione, S.; Rivasi, F.; Criscuolo, M.; De Benedittis, A.; Gentile, A.; Russo, S.; Testini, M.; Villan, M. Human anisakiasis in Italy: A report of eleven new cases. Pathol. Res. Pract. 2002, 198, 429–434.
  17. Yamamoto, T.; Miyazaki, T.; Kurashima, Y.; Ohata, K.; Okawa, M.; Tanaka, S.; Uenishi, T.; Miyaji, K.; Fukumoto, N. Solitary hepatic eosinophilic granuloma accompanied by eosinophilia without parasitosis: Report of a case. Int. Surg. 2015, 100, 1011–1017.
  18. D’Amelio, S.; Brandonisio, O.; Bruschi, F.; Genchi, C.; Pozio, E. Anisakidosi. In Parassitologia Medica e Diagnostica Parassitologica; Casa Editrice Ambrosiana: Milano, Italy, 2013; pp. 237–239.
  19. Valle, J.; Lopera, E.; Sánchez, M.E.; Lerma, R.; Ruiz, J.L. Spontaneous splenic rupture and Anisakis appendicitis presenting as abdominal pain: A case report. J. Med. Case Rep. 2012, 6, 114.
  20. Pacios, E.; Arias-Diaz, J.; Zuloaga, J.; Gonzalez-Armengol, J.; Villarroel, P.; Balibrea, J.L. Albendazole for the Treatment of Anisakiasis Ileus. Clin. Infect. Dis. 2013, 41, 1825–1826.
  21. Gómez-Mateos, M.; Arrebola, F.; Navarro, M.C.; Romero, M.C.; González, J.M.; Valero, A. Acute Anisakiasis: Pharmacological Evaluation of Various Drugs in an Animal Model. Dig. Dis. Sci. 2021, 66, 105–113.
  22. Trumbić, Ž.; Hrabar, J.; Palevich, N.; Carbone, V.; Mladineo, I. Molecular and evolutionary basis for survival, its failure, and virulence factors of the zoonotic nematode Anisakis pegreffii. Genomics 2021, 113, 2891–2905.
  23. D’Amelio, S.; Lombardo, F.; Pizzarelli, A.; Bellini, I.; Cavallero, S. Advances in omic studies drive discoveries in the biology of Anisakid Nematodes. Genes 2020, 11, 801.
  24. Audicana, M.T.; Kennedy, M.W. Anisakis simplex: From obscure infectious worm to inducer of immune hypersensitivity. Clin. Microbiol. Rev. 2008, 21, 360–379.
  25. Nieuwenhuizen, N.E. Anisakis—Immunology of a foodborne parasitosis. Parasite Immunol. 2016, 38, 548–557.
  26. Inclan-Rico, J.M.; Siracusa, M.C. First Responders: Innate Immunity to Helminths. Trends Parasitol. 2018, 34, 861–880.
  27. Maizels, R.M.; Smits, H.H.; McSorley, H.J. Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules. Immunity 2018, 49, 801–818.
  28. Rajasekaran, S.; Anuradha, R.; Bethunaickan, R. TLR specific immune responses against helminth infections. J. Parasitol. Res. 2017, 2017, 6865789.
  29. Motran, C.C.; Silvane, L.; Chiapello, L.S.; Theumer, M.G.; Ambrosio, L.F.; Volpini, X.; Celias, D.P.; Cervi, L. Helminth infections: Recognition and modulation of the immune response by innate immune cells. Front. Immunol. 2018, 9, 664.
  30. Tripathi, P.; Sahoo, N.; Ullah, U.; Kallionpää, H.; Suneja, A.; Lahesmaa, R.; Rao, K.V. A novel mechanism for ERK-dependent regulation of IL4 transcription during human Th2-cell differentiation. Immunol. Cell Biol. 2012, 90, 676–687.
  31. Su, H.; Zhang, Z.; Liu, Z.; Peng, B.; Kong, C.; Wang, H.; Zhang, Z.; Xu, Y. Mycobacterium tuberculosis PPE60 antigen drives Th1/Th17 responses via Toll-like receptor 2-dependent maturation of dendritic cells. J. Biol. Chem. 2018, 293, 10287–10302.
  32. Zakeri, A.; Hansen, E.P.; Andersen, S.D.; Williams, A.R.; Nejsum, P. Immunomodulation by helminths: Intracellular pathways and extracellular vesicles. Front. Immunol. 2018, 9, 2349.
  33. Owyang, A.M.; Zaph, C.; Wilson, E.H.; Guild, K.J.; McClanahan, T.; Miller, H.R.P.; Cua, D.J.; Goldschmidt, M.; Hunter, C.A.; Kastelein, R.A.; et al. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J. Exp. Med. 2006, 203, 843–849.
  34. Jackson, J.A.; Friberg, I.M.; Little, S.; Bradley, J.E. Review series on helminths, immune modulation and the hygiene hypothesis: Immunity against helminths and immunological phenomena in modern human populations: Coevolutionary legacies? Immunology 2009, 126, 18–27.
  35. McSorley, H.J.; Blair, N.F.; Smith, K.A.; McKenzie, A.N.; Maizels, R.M. Blockade of IL-33 release and suppression of type 2 innate lymphoid cell responses by helminth secreted products in airway allergy. Mucosal Immunol. 2014, 7, 1068–1078.
  36. Osbourn, M.; Soares, D.C.; Vacca, F.; Cohen, E.S.; Scott, I.C.; Gregory, W.F.; Smyth, D.J.; Toivakka, M.; Kemter, A.M.; Le Bihan, T.; et al. HpARI protein secreted by a helminth parasite suppresses interleukin-33. Immunity 2017, 47, 739–751.
  37. Hansen, E.P.; Fromm, B.; Andersen, S.D.; Marcilla, A.; Andersen, K.L.; Borup, A.; Williams, A.R.; Jex, A.R.; Gasser, R.B.; Young, N.D.; et al. Exploration of extracellular vesicles from Ascaris suum provides evidence of parasite-host cross talk. J. Extracell. Vesicles 2019, 8, 1578116.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Infectious Diseases
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Serena Cavallero
,
Ilaria Bellini
,
,
Stefano D'Amelio
View Times: 583
Entry Collection: Gastrointestinal Disease
Revisions: 2 times (View History)
Update Date: 20 Apr 2022
Table of Contents
    1000/1000
    Hot Most Recent
    Video Production Service
    Feedback