Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Whipworm and roundworm infections

Nature Reviews Disease Primers volume 6, Article number: 44 (2020) Cite this article

Subjects

Abstract

Trichuriasis and ascariasis are neglected tropical diseases caused by the gastrointestinal dwelling nematodes Trichuris trichiura (a whipworm) and Ascaris lumbricoides (a roundworm), respectively. Both parasites are staggeringly prevalent, particularly in tropical and subtropical areas, and are associated with substantial morbidity. Infection is initiated by ingestion of infective eggs, which hatch in the intestine. Thereafter, T. trichiura larvae moult within intestinal epithelial cells, with adult worms embedded in a partially intracellular niche in the large intestine, whereas A. lumbricoides larvae penetrate the gut mucosa and migrate through the liver and lungs before returning to the lumen of the small intestine, where adult worms dwell. Both species elicit type 2 anti-parasite immunity. Diagnosis is typically based on clinical presentation (gastrointestinal symptoms and inflammation) and the detection of eggs or parasite DNA in the faeces. Prevention and treatment strategies rely on periodic mass drug administration (generally with albendazole or mebendazole) to at-risk populations and improvements in water, sanitation and hygiene. The effectiveness of drug treatment is very high for A. lumbricoides infections, whereas cure rates for T. trichiura infections are low. Novel anthelminthic drugs are needed, together with vaccine development and tools for diagnosis and assessment of parasite control in the field.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Soil-transmitted helminth infections.
Fig. 2: Prevalence of Trichuris trichiura and Ascaris lumbricoides infections in 2010.
Fig. 3: Life cycles of Trichuris trichiura and Ascaris lumbricoides.
Fig. 4: The anti-parasite effector mechanisms induced by the protective immune response.
Fig. 5: Clinical complications of trichuriasis and ascariasis.
Fig. 6: Outlook for the development of novel drugs for soil-transmitted helminth infections.

Similar content being viewed by others

References

  1. Araujo, A., Reinhard, K. J., Ferreira, L. F. & Gardner, S. L. Parasites as probes for prehistoric human migrations? Trends Parasitol. 24, 112–115 (2008).

    Article  PubMed  Google Scholar 

  2. Hawash, M. B. et al. Whipworms in humans and pigs: origins and demography. Parasit. Vectors 9, 37 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Ledger, M. et al. Parasite infection at the early farming community of Çatalhöyük. Antiquity 93, 573–587 (2019).

    Article  Google Scholar 

  4. Soe, M. J., Kapel, C. M. & Nejsum, P. Ascaris from humans and pigs appear to be reproductively isolated species. PLoS Negl. Trop. Dis. 10, e0004855 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Mitchell, P. D. The origins of human parasites: exploring the evidence for endoparasitism throughout human evolution. Int. J. Paleopathol. 3, 191–198 (2013).

    Article  PubMed  Google Scholar 

  6. Pullan, R. L., Smith, J. L., Jasrasaria, R. & Brooker, S. J. Global numbers of infection and disease burden of soil transmitted helminth infections in 2010. Parasites Vectors 7, 37 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Hotez, P. J. et al. The global burden of disease study 2010: interpretation and implications for the neglected tropical diseases. PLoS Negl. Trop. Dis. 8, e2865 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  8. World Health Organization. Preventive chemotherapy to control soil-transmitted helminths in at-risk population groups: guideline (WHO, 2017).

  9. Hotez, P. J. Global deworming: moving past albendazole and mebendazole. Lancet Infect. Dis. 17, 1101–1102 (2017).

    Article  PubMed  Google Scholar 

  10. GBD 2015 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1603–1658 (2016).

    Article  Google Scholar 

  11. World Health Organization. Eliminating soil-transmitted helminthiases as a public health problem in children: progress report 2001–2010 and strategic plan 2011–2020 (WHO, 2012).

  12. Yakob, L. et al. Slaving and release in co-infection control. Parasites Vectors 6, 157 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Pullan, R. & Brooker, S. The health impact of polyparasitism in humans: are we under-estimating the burden of parasitic diseases? Parasitology 135, 783–794 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Brooker, S., Clements, A. C. & Bundy, D. A. Global epidemiology, ecology and control of soil-transmitted helminth infections. Adv. Parasitol. 62, 221–261 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Owada, K. et al. Spatial distribution and populations at risk of A. lumbricoides and T. trichiura co-infections and infection intensity classes: an ecological study. Parasites Vectors 11, 535 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Global Health Data Exchange. GBD results tool. GHDx http://ghdx.healthdata.org/gbd-results-tool (2020).

  17. Beer, R. J. The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig. Res. Vet. Sci. 20, 47–54 (1976).

    Article  CAS  PubMed  Google Scholar 

  18. Bundy, D. A. & Cooper, E. S. Trichuris and trichuriasis in humans. Adv. Parasitol. 28, 107–173 (1989).

    Article  CAS  PubMed  Google Scholar 

  19. Summers, R. W., Elliott, D. E., Urban, J. F. Jr., Thompson, R. A. & Weinstock, J. V. Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial. Gastroenterology 128, 825–832 (2005).

    Article  PubMed  Google Scholar 

  20. Williams, A. R. et al. Immune responses and parasitological observations induced during probiotic treatment with medicinal Trichuris suis ova in a healthy volunteer. Immunol. Lett. 188, 32–37 (2017).

    Article  CAS  PubMed  Google Scholar 

  21. Ghai, R. R. et al. Hidden population structure and cross-species transmission of whipworms (Trichuris sp.) in humans and non-human primates in Uganda. PLoS Negl. Trop. Dis. 8, e3256 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bundy, D. A., Cooper, E. S., Thompson, D. E., Didier, J. M. & Simmons, I. Epidemiology and population dynamics of Ascaris lumbricoides and Trichuris trichiura infection in the same community. Trans. R. Soc. Tropical Med. Hyg. 81, 987–993 (1987).

    Article  CAS  Google Scholar 

  23. Bundy, D. A., Cooper, E. S., Thompson, D. E., Anderson, R. M. & Didier, J. M. Age-related prevalence and intensity of Trichuris trichiura infection in a St. Lucian community. Trans. R. Soc. Tropical Med. Hyg. 81, 85–94 (1987).

    Article  CAS  Google Scholar 

  24. de Silva, N. R. et al. Soil-transmitted helminth infections: updating the global picture. Trends Parasitol. 19, 547–551 (2003).

    Article  PubMed  Google Scholar 

  25. Schulz, J. D., Moser, W., Hurlimann, E. & Keiser, J. Preventive chemotherapy in the fight against soil-transmitted helminthiasis: achievements and limitations. Trends Parasitol. 34, 590–602 (2018).

    Article  CAS  PubMed  Google Scholar 

  26. Elliott, D. E. in Sleisenger and Fordtran’s Gastrintestinal and Liver Disease: Pathophysiology/Diagnosis/Management (eds Friedman, L. S., Feldman, M., Brandt, L. J.) 2435–2457 (Elsevier, Philadelphia, 2006).

  27. Wright, J. E., Werkman, M., Dunn, J. C. & Anderson, R. M. Current epidemiological evidence for predisposition to high or low intensity human helminth infection: a systematic review. Parasites Vectors 11, 65 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bundy, D. A. et al. Predisposition to Trichuris trichiura infection in humans. Epidemiol. Infect. 98, 65–71 (1987).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ellis, M. K. et al. Familial aggregation of human susceptibility to co- and multiple helminth infections in a population from the Poyang Lake region, China. Int. J. Parasitol. 37, 1153–1161 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Williams-Blangero, S. et al. Two quantitative trait loci influence whipworm (Trichuris trichiura) infection in a Nepalese population. J. Infect. Dis. 197, 1198–1203 (2008). This study identified two quantitative trait loci that influence egg counts for Trichuris trichiura infection, one on chromosome 9 and one on chromosome 12.

    Article  PubMed  Google Scholar 

  31. Costa, R. D. et al. Effect of polymorphisms on TGFB1 on allergic asthma and helminth infection in an African admixed population. Ann. Allergy Asthma Immunol. 118, 483–488.e1 (2017).

    Article  CAS  PubMed  Google Scholar 

  32. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 386, 743–800 (2015).

    Article  PubMed Central  Google Scholar 

  33. Avery, R. H., Wall, L. A., Verhoeve, V. I., Gipson, K. S. & Malone, J. B. Molecular confirmation of Ascaris suum: further investigation into the zoonotic origin of infection in an 8-year-old boy with Loeffler syndrome. Vector Borne Zoonotic Dis. 18, 638–640 (2018).

    Article  PubMed  Google Scholar 

  34. Sadaow, L. et al. Molecular identification of Ascaris lumbricoides and Ascaris suum recovered from humans and pigs in Thailand, Lao PDR, and Myanmar. Parasitol. Res. 117, 2427–2436 (2018).

    Article  PubMed  Google Scholar 

  35. Monteiro, K. J. L. et al. Genetic diversity of Ascaris spp. infecting humans and pigs in distinct Brazilian regions, as revealed by mitochondrial DNA. PLoS One 14, e0218867 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Betson, M., Nejsum, P., Bendall, R. P., Deb, R. M. & Stothard, J. R. Molecular epidemiology of ascariasis: a global perspective on the transmission dynamics of Ascaris in people and pigs. J. Infect. Dis. 210, 932–941 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nejsum, P., Betson, M., Bendall, R. P., Thamsborg, S. M. & Stothard, J. R. Assessing the zoonotic potential of Ascaris suum and Trichuris suis: looking to the future from an analysis of the past. J. Helminthol. 86, 148–155 (2012).

    Article  CAS  PubMed  Google Scholar 

  38. Benjamin-Chung, J. et al. The interaction of deworming, improved sanitation, and household flooring with soil-transmitted helminth infection in rural Bangladesh. PLoS Negl. Trop. Dis. 9, e0004256 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kightlinger, L. K., Seed, J. R. & Kightlinger, M. B. Ascaris lumbricoides intensity in relation to environmental, socioeconomic, and behavioral determinants of exposure to infection in children from southeast Madagascar. J. Parasitol. 84, 480–484 (1998).

    Article  CAS  PubMed  Google Scholar 

  40. Croll, N. A. & Ghadirian, E. Wormy persons: contributions to the nature and patterns of overdispersion with Ascaris lumbricoides, Ancylosotma duodenale, Necator americanus and Trichuris trichiura. Tropical Geographical Med. 33, 241–248 (1981).

    CAS  Google Scholar 

  41. Holland, C. V. et al. Intestinal helminthiases in relation to the socioeconomic environment of Panamanian children. Soc. Sci. Med. 26, 209–213 (1988).

    Article  CAS  PubMed  Google Scholar 

  42. Haswell-Elkins, M., Elkins, D. & Anderson, R. M. The influence of individual, social group and household factors on the distribution of Ascaris lumbricoides within a community and implications for control strategies. Parasitology 98, 125–134 (1989).

    Article  PubMed  Google Scholar 

  43. Holland, C. V. et al. The epidemiology of Ascaris lumbricoides and other soil-transmitted helminths in primary school children from Ile-Ife, Nigeria. Parasitology 99, 275–285 (1989).

    Article  PubMed  Google Scholar 

  44. Nogueira, D. S. et al. Multiple exposures to Ascaris suum induce tissue injury and mixed Th2/Th17 immune response in mice. PLoS Negl. Trop. Dis. 10, e0004382 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Chan, L., Bundy, D. A. & Kan, S. P. Genetic relatedness as a determinant of predisposition to Ascaris lumbricoides and Trichuris trichiura infection. Parasitology 108, 77–80 (1994).

    Article  PubMed  Google Scholar 

  46. Williams-Blangero, S. et al. Genetic analysis of susceptibility to infection with Ascaris lumbricoides. Am. J. Tropical Med. Hyg. 60, 921–926 (1999).

    Article  CAS  Google Scholar 

  47. Williams-Blangero, S. et al. Genes on chromosomes 1 and 13 have significant effects on Ascaris infection. Proc. Natl Acad. Sci. USA 99, 5533–5538 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Peisong, G. et al. An asthma-associated genetic variant of STAT6 predicts low burden of Ascaris worm infestation. Genes. Immun. 5, 58–62 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Williams-Blangero, S. et al. Localization of multiple quantitative trait loci influencing susceptibility to infection with Ascaris lumbricoides. J. Infect. Dis. 197, 66–71 (2008).

    Article  PubMed  Google Scholar 

  50. Acevedo, N. et al. Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes. Clin. Exp. Immunol. 157, 282–290 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dold, C. & Holland, C. V. Investigating the underlying mechanism of resistance to Ascaris infection. Microbes Infect. 13, 624–631 (2011).

    Article  CAS  PubMed  Google Scholar 

  52. O’Sullivan, J. D. B. et al. X-ray micro-computed tomography (muCT): an emerging opportunity in parasite imaging. Parasitology 145, 848–854 (2018).

    Article  PubMed  Google Scholar 

  53. Starborg, T. et al. Experimental steering of electron microscopy studies using prior X-ray computed tomography. Ultramicroscopy 201, 58–67 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hayes, K. S. et al. Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris. Science 328, 1391–1394 (2010). The study demonstrated a crucial relationship between intestinal bacteria and Trichuris muris in the mouse, with successful establishment of infection dependent on the microbiota.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cliffe, L. J. & Grencis, R. K. The Trichuris muris system: a paradigm of resistance and susceptibility to intestinal nematode infection. Adv. Parasitol. 57, 255–307 (2004).

    Article  PubMed  Google Scholar 

  56. Hurst, R. J. & Else, K. J. Trichuris muris research revisited: a journey through time. Parasitology 140, 1325–1339 (2013).

    Article  PubMed  Google Scholar 

  57. Pike, E. H. Egg output of Trichuris muris (Schrank, 1788). J. Parasitol. 55, 1046–1049 (1969).

    Article  Google Scholar 

  58. Eichenberger, R. M. et al. Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication. J. Extracell. Vesicles 7, 1428004 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  59. Bancroft, A. J. et al. The major secreted protein of the whipworm parasite tethers to matrix and inhibits interleukin-13 function. Nat. Commun. 10, 2344 (2019).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  60. Leroux, L. P. et al. Analysis of the Trichuris suis excretory/secretory proteins as a function of life cycle stage and their immunomodulatory properties. Sci. Rep. 8, 15921 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. Faulkner, H. et al. Age- and infection intensity-dependent cytokine and antibody production in human trichuriasis: the importance of IgE. J. Infect. Dis. 185, 665–672 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. de Ruiter, K. et al. Helminth infections drive heterogeneity in human type 2 and regulatory cells. Sci. Transl Med. 12, eaaw3703 (2020).

    Article  PubMed  Google Scholar 

  63. Turner, J. D. et al. Th2 cytokines are associated with reduced worm burdens in a human intestinal helminth infection. J. Infect. Dis. 188, 1768–1775 (2003). The authors report that an increase in type 2 immunity-associated cytokines correlates with an age-dependent reduction in Ascaris lumbricoides infection intensity.

    Article  CAS  PubMed  Google Scholar 

  64. Dige, A. et al. Mucosal and systemic immune modulation by Trichuris trichiura in a self-infected individual. Parasite Immunol. 39, e12394 (2017).

    Article  CAS  Google Scholar 

  65. Broadhurst, M. J. et al. IL-22+ CD4+ T cells are associated with therapeutic Trichuris trichiura infection in an ulcerative colitis patient. Sci. Transl Med. 2, 60ra88 (2010). This study showed that Trichuris trichiura infection may decrease the symptoms of colitis by promoting type 2 immunity dependent goblet cell hyperplasia and mucus production.

    Article  CAS  PubMed  Google Scholar 

  66. Kringel, H., Iburg, T., Dawson, H., Aasted, B. & Roepstorff, A. A time course study of immunological responses in Trichuris suis infected pigs demonstrates induction of a local type 2 response associated with worm burden. Int. J. Parasitol. 36, 915–924 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Else, K. J., Finkelman, F. D., Maliszewski, C. R. & Grencis, R. K. Cytokine-mediated regulation of chronic intestinal helminth infection. J. Exp. Med. 179, 347–351 (1994).

    Article  CAS  PubMed  Google Scholar 

  68. Grencis, R. K. Immunity to helminths: resistance, regulation, and susceptibility to gastrointestinal nematodes. Annu. Rev. Immunol. 33, 201–225 (2015).

    Article  CAS  PubMed  Google Scholar 

  69. Hadidi, S. et al. Myeloid cell-specific expression of Ship1 regulates IL-12 production and immunity to helminth infection. Mucosal Immunol. 5, 535–543 (2012).

    Article  CAS  PubMed  Google Scholar 

  70. Artis, D. New weapons in the war on worms: identification of putative mechanisms of immune-mediated expulsion of gastrointestinal nematodes. Int. J. Parasitol. 36, 723–733 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Klementowicz, J. E., Travis, M. A. & Grencis, R. K. Trichuris muris: a model of gastrointestinal parasite infection. Semin. Immunopathol. 34, 815–828 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Sorobetea, D., Svensson-Frej, M. & Grencis, R. Immunity to gastrointestinal nematode infections. Mucosal Immunol. 11, 304–315 (2018).

    Article  CAS  PubMed  Google Scholar 

  73. Blackwell, N. M. & Else, K. J. B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris. Infect. Immun. 69, 3860–3868 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Perrigoue, J. G. et al. MHC class II-dependent basophil-CD4+ T cell interactions promote T(H)2 cytokine-dependent immunity. Nat. Immunol. 10, 697–705 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Huang, X., Zeng, L. R., Chen, F. S., Zhu, J. P. & Zhu, M. H. Trichuris suis ova therapy in inflammatory bowel disease: a meta-analysis. Medicine 97, e12087 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Bager, P. Use of Trichuris suis ova (TSO) therapy for the treatment of allergy. Arb. Paul Ehrlich Inst. Bundesinstitut Impfstoffe Biomed. Arzneim. Langen Hess. 97, 128–129 (2013).

    PubMed  Google Scholar 

  77. Schölmerich, J. et al. A randomised, double-blind, placebo-controlled trial of Trichuris suis ova in active Crohn’s disease. J. Crohns Colitis 11, 390–399 (2017).

    PubMed  Google Scholar 

  78. Sobotkova, K. et al. Helminth therapy – from the parasite perspective. Trends Parasitol. 35, 501–515 (2019).

    Article  PubMed  Google Scholar 

  79. Bager, P. et al. Trichuris suis ova therapy for allergic rhinitis: a randomized, double-blind, placebo-controlled clinical trial. J. Allergy Clin. Immunol. 125, 123–130.e1–3 (2010).

    Article  PubMed  Google Scholar 

  80. Hasnain, S. Z. et al. Muc5ac: a critical component mediating the rejection of enteric nematodes. J. Exp. Med. 208, 893–900 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hasnain, S. Z. et al. Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection. Gastroenterology 138, 1763–1771 (2010). This study provided evidence of a functional role for mucins in type 2 controlled anti-nematode immunity using the mouse model of human trichuriasis.

    Article  CAS  PubMed  Google Scholar 

  82. Foth, B. J. et al. Whipworm genome and dual-species transcriptome analyses provide molecular insights into an intimate host-parasite interaction. Nat. Genet. 46, 693–700 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Khan, W. I. et al. Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections. Infect. Immun. 71, 2430–2438 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Cliffe, L. J. et al. Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science 308, 1463–1465 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Jarrett, E. E. & Miller, H. R. Production and activities of IgE in helminth infection. Prog. Allergy 31, 178–233 (1982).

    CAS  PubMed  Google Scholar 

  86. Else, K. J. & Grencis, R. K. Antibody-independent effector mechanisms in resistance to the intestinal nematode parasite Trichuris muris. Infect. Immun. 64, 2950–2954 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Constant, S., Schweitzer, N., West, J., Ranney, P. & Bottomly, K. B lymphocytes can be competent antigen-presenting cells for priming CD4+ T cells to protein antigens in vivo. J. Immunol. 155, 3734–3741 (1995).

    CAS  PubMed  Google Scholar 

  88. Lund, F. E., Garvy, B. A., Randall, T. D. & Harris, D. P. Regulatory roles for cytokine-producing B cells in infection and autoimmune disease. Curr. Dir. Autoimmun. 8, 25–54 (2005).

    Article  CAS  PubMed  Google Scholar 

  89. Wojciechowski, W. et al. Cytokine-producing effector B cells regulate type 2 immunity to H. polygyrus. Immunity 30, 421–433 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Schopf, L. R., Hoffmann, K. F., Cheever, A. W., Urban, J. F. Jr. & Wynn, T. A. IL-10 is critical for host resistance and survival during gastrointestinal helminth infection. J. Immunol. 168, 2383–2392 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Duque-Correa, M. A. et al. Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection. PLoS Pathog. 15, e1007265 (2019).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  92. Houlden, A. et al. Chronic Trichuris muris infection in c57bl/6 mice causes significant changes in host microbiota and metabolome: effects reversed by pathogen clearance. PLoS One 10, e0125945 (2015).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  93. Holm, J. B. et al. Chronic Trichuris muris infection decreases diversity of the intestinal microbiota and concomitantly increases the abundance of lactobacilli. PLoS One 10, e0125495 (2015).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  94. Li, R. W. et al. Alterations in the porcine colon microbiota induced by the gastrointestinal nematode Trichuris suis. Infect. Immun. 80, 2150–2157 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Wu, S. et al. Worm burden-dependent disruption of the porcine colon microbiota by Trichuris suis infection. PLoS One 7, e35470 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Lee, S. C. et al. Helminth colonization is associated with increased diversity of the gut microbiota. PLoS Negl. Trop. Dis. 8, e2880 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Cooper, P. et al. Patent human infections with the whipworm, Trichuris trichiura, are not associated with alterations in the faecal microbiota. PLoS One 8, e76573 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. White, E. C. et al. Manipulation of host and parasite microbiotas: survival strategies during chronic nematode infection. Sci. Adv. 4, eaap7399 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  99. Stephenson, L. S. & Holland, C. The Impact of Helminth Infections on Human Nutrition: schistosomes and soil-transmitted helminths 93 (Taylor and Francis, 1987).

  100. Wong, M. S. & Bundy, D. A. Quantitative assessment of contamination of soil by the eggs of Ascaris lumbricoides and Trichuris trichiura. Trans. R. Soc. Tropical Med. Hyg. 84, 567–570 (1990).

    Article  CAS  Google Scholar 

  101. Douvres, F. W. & Urban, J. F. Jr. Factors contributing to the in vitro development of Ascaris suum from second-stage larvae to mature adults. J. Parasitol. 69, 549–558 (1983).

    Article  CAS  PubMed  Google Scholar 

  102. Fagerholm, H. P., Nansen, P., Roepstorff, A., Frandsen, F. & Eriksen, L. Differentiation of cuticular structures during the growth of the third-stage larva of Ascaris suum (Nematoda, Ascaridoidea) after emerging from the egg. J. Parasitol. 86, 421–427 (2000).

    Article  CAS  PubMed  Google Scholar 

  103. Pilitt, P. A., Lichtenfels, J. R., Tromba, F. G. & Madden, P. A. Differentiation of late fourth and early fifth stages of Ascaris suum Goeze, 1782 (Nematoda: Ascaridoidea) in swine. Proc. Helminthol. Soc. 48, 1–7 (1981).

    Google Scholar 

  104. Anderson, R. M. in The Population Dynamics of Infectious Diseases: Theory and Applications (ed. Anderson, R. M.) 67–108 (Springer, 1982).

  105. Pawlowski, Z. S. & Arfaa, F. in Tropical and Geographical Medicine (eds Warren, K. S. & Mahmoud, A. A. F. 347–358 (McGraw-Hill, 1984).

  106. Read, A. F. & Skorping, A. The evolution of tissue migration by parasitic nematode larvae. Parasitology 111, 359–371 (1995).

    Article  PubMed  Google Scholar 

  107. Javid, G. et al. Ascaris-induced liver abscess. World J. Surg. 23, 1191–1194 (1999).

    Article  CAS  PubMed  Google Scholar 

  108. Ribeiro, J. D. F. G. Eosinophilic lung diseases. Paediatr. Respir. Rev. 3, 278–284 (2002). This review highlights eosinophilic lung diseases, with an emphasis on lung pathology due to parasitic infections including Ascaris lumbricoides infection.

    Article  PubMed  Google Scholar 

  109. Hagel, I. et al. Ascaris reinfection of slum children: relation with the IgE response. Clin. Exp. Immunol. 94, 80–83 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Palmer, D. R., Hall, A., Haque, R. & Anwar, K. S. Antibody isotype responses to antigens of Ascaris lumbricoides in a case-control study of persistently heavily infected Bangladeshi children. Parasitology 111, 385–393 (1995).

    Article  PubMed  Google Scholar 

  111. McSharry, C., Xia, Y., Holland, C. V. & Kennedy, M. W. Natural immunity to Ascaris lumbricoides associated with immunoglobulin E antibody to ABA-1 allergen and inflammation indicators in children. Infect. Immun. 67, 484–489 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. King, E. M. et al. Immuno-epidemiology of Ascaris lumbricoides infection in a high transmission community: antibody responses and their impact on current and future infection intensity. Parasite Immunol. 27, 89–96 (2005).

    Article  CAS  PubMed  Google Scholar 

  113. Cooper, P. J. et al. Human infection with Ascaris lumbricoides is associated with a polarized cytokine response. J. Infect. Dis. 182, 1207–1213 (2000).

    Article  CAS  PubMed  Google Scholar 

  114. Jackson, J. A. et al. T helper cell type 2 responsiveness predicts future susceptibility to gastrointestinal nematodes in humans. J. Infect. Dis. 190, 1804–1811 (2004).

    Article  CAS  PubMed  Google Scholar 

  115. Cooper, P. J. et al. Repeated treatments with albendazole enhance Th2 responses to Ascaris lumbricoides, but not to aeroallergens, in children from rural communities in the tropics. J. Infect. Dis. 198, 1237–1242 (2008). This paper presents data indicating that repeated doses of albendazole over the course of 1 year are associated with enhanced production of Ascaris lumbricoides-specific type 2 immunity cytokines in humans.

    Article  CAS  PubMed  Google Scholar 

  116. Holland, C. V., Behnke, J.M. and Dold, C. in Ascaris: the Neglected Parasite (ed. Holland, C. V.) 107–125 (Elsevier, 2013).

  117. Lewis, R., Behnke, J. M., Stafford, P. & Holland, C. V. Dose-dependent impact of larval Ascaris suum on host body weight in the mouse model. J. Helminthol. 83, 1–5 (2009).

    Article  CAS  PubMed  Google Scholar 

  118. Deslyper, G., Holland, C. V., Colgan, T. J. & Carolan, J. C. The liver proteome in a mouse model for Ascaris suum resistance and susceptibility: evidence for an altered innate immune response. Parasites Vectors 12, 402 (2019).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  119. Lewis, R., Behnke, J. M., Stafford, P. & Holland, C. V. The development of a mouse model to explore resistance and susceptibility to early Ascaris suum infection. Parasitology 132, 289–300 (2006).

    Article  CAS  PubMed  Google Scholar 

  120. Dold, C., Cassidy, J. P., Stafford, P., Behnke, J. M. & Holland, C. V. Genetic influence on the kinetics and associated pathology of the early stage (intestinal-hepatic) migration of Ascaris suum in mice. Parasitology 137, 173–185 (2010).

    Article  CAS  PubMed  Google Scholar 

  121. Deslyper, G., Colgan, T. J., Cooper, A. J., Holland, C. V. & Carolan, J. C. A proteomic investigation of hepatic resistance to Ascaris in a murine model. PLoS Negl. Trop. Dis. 10, e0004837 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  122. Gazzinelli-Guimaraes, P. H. et al. Parasitological and immunological aspects of early Ascaris spp. infection in mice. Int. J. Parasitol. 43, 697–706 (2013).

    Article  CAS  PubMed  Google Scholar 

  123. Weatherhead, J. E. et al. Ascaris larval infection and lung invasion directly induce severe allergic airway disease in mice. Infect. Immun. 86, e00533-18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Gazzinelli-Guimaraes, P. H. et al. Allergen presensitization drives an eosinophil-dependent arrest in lung-specific helminth development. J. Clin. Invest’. 130, 3686–3701 (2019).

    Article  Google Scholar 

  125. Guo, L. et al. Innate immunological function of TH2 cells in vivo. Nat. Immunol. 16, 1051–1059 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Dowling, D. J. et al. Ascaris lumbricoides pseudocoelomic body fluid induces a partially activated dendritic cell phenotype with Th2 promoting ability in vivo. Int. J. Parasitol. 41, 255–261 (2011).

    Article  CAS  PubMed  Google Scholar 

  127. Favoretto, B. C. et al. High molecular weight components containing N-linked oligosaccharides of Ascaris suum extract inhibit the dendritic cells activation through DC-SIGN and MR. Mol. Immunol. 87, 33–46 (2017).

    Article  CAS  PubMed  Google Scholar 

  128. Almeida, S., Nejsum, P. & Williams, A. R. Modulation of human macrophage activity by Ascaris antigens is dependent on macrophage polarization state. Immunobiology 223, 405–412 (2018).

    Article  CAS  PubMed  Google Scholar 

  129. Titz, T. O. et al. Ascaris suum infection modulates inflammation: implication of CD4(+) CD25(high) Foxp3(+) T cells and IL-10. Parasite Immunol. 39, e12453 (2017).

    Article  CAS  Google Scholar 

  130. Nascimento, W. C. et al. Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis. Parasitol. Res. 113, 3309–3317 (2014).

    Article  PubMed  Google Scholar 

  131. Paterson, J. C., Garside, P., Kennedy, M. W. & Lawrence, C. E. Modulation of a heterologous immune response by the products of Ascaris suum. Infect. Immun. 70, 6058–6067 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Gazzinelli-Guimaraes, P. H. et al. Concomitant helminth infection downmodulates the Vaccinia virus-specific immune response and potentiates virus-associated pathology. Int. J. Parasitol. 47, 1–10 (2017).

    Article  PubMed  Google Scholar 

  133. Suzuki, M. et al. Presensitization to Ascaris antigens promotes induction of mite-specific IgE upon mite antigen inhalation in mice. Allergol. Int. 65, 44–51 (2016).

    Article  CAS  PubMed  Google Scholar 

  134. Jungersen, G., Fagerholm, H. P., Nansen, P. & Eriksen, L. Development of patent Ascaris suum infections in pigs following intravenous administration of larvae hatched in vitro. Parasitology 119, 503–508 (1999).

    Article  PubMed  Google Scholar 

  135. Masure, D. et al. The intestinal expulsion of the roundworm Ascaris suum is associated with eosinophils, intra-epithelial T cells and decreased intestinal transit time. PLoS Negl. Trop. Dis. 7, e2588 (2013).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  136. Schwartz, B. A. J. Ascaris larvae as a cause of liver and lung lesions in swine. J. Parasitol. 19, 17–24 (1932).

    Article  Google Scholar 

  137. Copeman, D. B. & Gaafar, S. M. Sequential development of hepatic lesions of ascaridosis in colostrum-deprived pigs. Aust. Vet. J. 48, 263–268 (1972).

    Article  CAS  PubMed  Google Scholar 

  138. Perez, J., Garcia, P. M., Mozos, E., Bautista, M. J. & Carrasco, L. Immunohistochemical characterization of hepatic lesions associated with migrating larvae of Ascaris suum in pigs. J. Comp. Pathol. 124, 200–206 (2001).

    Article  CAS  PubMed  Google Scholar 

  139. Masure, D. et al. A role for eosinophils in the intestinal immunity against infective Ascaris suum larvae. PLoS Negl. Trop. Dis. 7, e2138 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Ashraf, M., Urban, J. F. Jr., Lee, T. D. & Lee, C. M. Characterization of isolated porcine intestinal mucosal mast cells following infection with Ascaris suum. Vet. Parasitol. 29, 143–158 (1988).

    Article  CAS  PubMed  Google Scholar 

  141. Uston, P. I., Urban, J. F. Jr., Ashraf, M., Lee, C. M. & Ampy, F. R. L3L4ES antigen and secretagogues induce histamine release from porcine peripheral blood basophils after Ascaris suum infection. Parasitol. Res. 100, 603–611 (2007).

    Article  CAS  PubMed  Google Scholar 

  142. Urban, J. F. Jr., Alizadeh, H. & Romanowski, R. D. Ascaris suum: development of intestinal immunity to infective second-stage larvae in swine. Exp. Parasitol. 66, 66–77 (1988).

    Article  PubMed  Google Scholar 

  143. Wang, Y. et al. Ascaris suum infection was associated with a worm-independent reduction in microbial diversity and altered metabolic potential in the porcine gut microbiome. Int. J. Parasitol. 49, 247–256 (2019).

    Article  PubMed  Google Scholar 

  144. McCraw, B. M. & Greenway, J. A. Ascaris suum infection in calves. 3. Pathology. Can. J. Comp. Med. 34, 247–255 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Fallis, A. M. Ascaris lumbricoides infection in guinea pigs with special reference to eosinophilia and resistance. Can. J. Res. 26, 307–327 (1948).

    Article  CAS  PubMed  Google Scholar 

  146. Arean, V. M. & Crandall, C. A. The effect of immunization on the fate of injected second stage Ascaris lumbricoides larvae in the rabbit. Am. J. Tropical Med. Hyg. 11, 369–379 (1962).

    Article  CAS  Google Scholar 

  147. Cho, S. et al. Migration behaviour and pathogenesis of five ascarid nematode species in the Mongolian gerbil Meriones unguiculatus. J. Helminthol. 81, 43–47 (2007).

    Article  CAS  PubMed  Google Scholar 

  148. Weiszer, I., Patterson, R. & Pruzansky, J. J. Ascaris hypersensitivity in the rhesus monkey: I. A model for the study of immediate type hypersensitity in the primate. J. Allergy 41, 14–22 (1968).

    Article  CAS  PubMed  Google Scholar 

  149. Pritchard, D. I. et al. Laboratory infection of primates with Ascaris suum to provide a model of allergic bronchoconstriction. Clin. Exp. Immunol. 54, 469–476 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Patterson, R., Harris, K. E. & Pruzansky, J. J. Induction of IgE-mediated cutaneous, cellular, and airway reactivity in rhesus monkeys by Ascaris suum infection. J. Lab. Clin. Med. 101, 864–872 (1983).

    CAS  PubMed  Google Scholar 

  151. Layrisse, M., Aparcedo, L., Martinez-Torres, C. & Roche, M. Blood loss due to infection with Trichuris trichiura. Am. J. Trop. Med. Hyg. 16, 613–619 (1967).

    Article  CAS  PubMed  Google Scholar 

  152. Ramdath, D. D., Simeon, D. T., Wong, M. S. & Grantham-McGregor, S. M. Iron status of schoolchildren with varying intensities of Trichuris trichiura infection. Parasitology 110, 347–351 (1995).

    Article  PubMed  Google Scholar 

  153. Robertson, L. J., Crompton, D. W., Sanjur, D. & Nesheim, M. C. Haemoglobin concentrations and concomitant infections of hookworm and Trichuris trichiura in Panamanian primary schoolchildren. Trans. R. Soc. Trop. Med. Hyg. 86, 654–656 (1992).

    Article  CAS  Google Scholar 

  154. Gyorkos, T. W., Gilbert, N. L., Larocque, R. & Casapia, M. Trichuris and hookworm infections associated with anaemia during pregnancy. Trop. Med. Int. Health 16, 531–537 (2011).

    Article  PubMed  Google Scholar 

  155. Cooper, E. S. & Bundy, D. A. Trichuris is not trivial. Parasitol. Today 4, 301–306 (1988).

    Article  CAS  PubMed  Google Scholar 

  156. Wolfe, M. S. Oxyuris, Trichostrongylus and Trichuris. Clin. Gastroenterol. 7, 201–217 (1978).

    CAS  PubMed  Google Scholar 

  157. Khuroo, M. S., Khuroo, M. S. & Khuroo, N. S. Trichuris dysentery syndrome: a common cause of chronic iron deficiency anemia in adults in an endemic area (with videos). Gastrointest. Endoscopy 71, 200–204 (2010).

    Article  Google Scholar 

  158. Stephenson, L. S., Holland, C. V. & Cooper, E. S. The public health significance of Trichuris trichiura. Parasitology 121, S73–S95 (2000).

    Article  PubMed  Google Scholar 

  159. Kaminsky RG, C. R., & Flores, C. A. Growth retardation and severe anemia in children with Trichuris dysenteric syndrome. Asian Pac. J. Trop. Biomed. 5, 591–597 (2015).

    Article  Google Scholar 

  160. Al-Mekhlafi, M. H. et al. Anaemia and iron deficiency anaemia among aboriginal schoolchildren in rural Peninsular Malaysia: an update on a continuing problem. Trans. R. Soc. Tropical Med. Hyg. 102, 1046–1052 (2008).

    Article  Google Scholar 

  161. Sarkar, M., Mahesh, D. M. & Madabhavi, I. Digital clubbing. Lung India 29, 354–362 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  162. Cooper, E. S., Bundy, D. A. & Henry, F. J. Chronic dysentery, stunting, and whipworm infestation. Lancet 2, 280–281 (1986).

    Article  CAS  PubMed  Google Scholar 

  163. MacDonald, T. T. et al. Immunoepidemiology of intestinal helminthic infections. 3. Mucosal macrophages and cytokine production in the colon of children with Trichuris trichiura dysentery. Trans. R. Soc. Tropical Med. Hyg. 88, 265–268 (1994).

    Article  CAS  Google Scholar 

  164. Ok, K. S. et al. Trichuris trichiura infection diagnosed by colonoscopy: case reports and review of literature. Korean J. Parasitol. 47, 275–280 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Jha, A. K., Goenka, M. K. & Suchismita, A. Clinical correlates of trichuriasis diagnosed at colonoscopy. Indian. J. Gastroenterol. 36, 420–423 (2017).

    Article  PubMed  Google Scholar 

  166. Martin, I. et al. Dynamic changes in human-gut microbiome in relation to a placebo-controlled anthelminthic trial in Indonesia. PLoS Negl. Trop. Dis. 12, e0006620 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  167. Gilman, R. H. et al. The adverse consequences of heavy Trichuris infection. Trans. R. Soc. Tropical Med. Hyg. 77, 432–438 (1983).

    Article  CAS  Google Scholar 

  168. Shin, J. L., Gardiner, G. W., Deitel, W. & Kandel, G. Does whipworm increase the pathogenicity of Campylobacter jejuni? A clinical correlate of an experimental observation. Can. J. Gastroenterol. 18, 175–177 (2004).

    Article  PubMed  Google Scholar 

  169. Jensen, L. A., Marlin, J. W., Dyck, D. D. & Laubach, H. E. Prevalence of multi-gastrointestinal infections with helminth, protozoan and Campylobacter spp. in Guatemalan children. J. Infect. Dev. Ctries. 3, 229–234 (2009).

    PubMed  Google Scholar 

  170. Mansfield, L. S. et al. Enhancement of disease and pathology by synergy of Trichuris suis and Campylobacter jejuni in the colon of immunologically naive swine. Am. J. Tropical Med. Hyg. 68, 70–80 (2003).

    Article  Google Scholar 

  171. Croll, N. A., Anderson, R. M., Gyorkos, T. W. & Ghadirian, E. The population biology and control of Ascaris lumbricoides in a rural community in Iran. Trans. R. Soc. Tropical Med. Hyg. 76, 187–197 (1982).

    Article  CAS  Google Scholar 

  172. Thein, H., Than, S., Htay Htay, A., Myint, L. & Thein Maung, M. Epidemiology and transmission dynamics of Ascaris lumbricoides in Okpo village, rural Burma. Trans. R. Soc. Tropical Med. Hyg. 78, 497–504 (1984).

    Article  Google Scholar 

  173. Löffler, W. Transient lung infiltrations with blood eosinophilia. Int. Arch. Allergy Appl. Immunol. 8, 54–59 (1956).

    Article  PubMed  Google Scholar 

  174. Khuroo, N. S., Khuroo, M. S. & Khuroo, M. S. Gastric ascariasis presenting as unique dyspeptic symptoms in an endemic area. Am. J. Gastroenterol. 105, 1675–1677 (2010).

    Article  PubMed  Google Scholar 

  175. Das, A. K. Hepatic and biliary ascariasis. J. Glob. Infect. Dis. 6, 65–72 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  176. Khuroo, M. S. Ascariasis. Gastroenterol. Clin. North. Am. 25, 553–577 (1996).

    Article  CAS  PubMed  Google Scholar 

  177. Efem, S. E. Ascaris lumbricoides and intestinal perforation. Br. J. Surg. 74, 643–644 (1987).

    Article  CAS  PubMed  Google Scholar 

  178. Paul, M. The movements of the adult Ascaris lumbricoides. Br. J. Surg. 59, 437–442 (1972).

    Article  CAS  PubMed  Google Scholar 

  179. Villamizar, E., Mendez, M., Bonilla, E., Varon, H. & de Onatra, S. Ascaris lumbricoides infestation as a cause of intestinal obstruction in children: experience with 87 cases. J. Pediatric Surg. 31, 201–204 (1996).

    Article  CAS  Google Scholar 

  180. Nokes, C. & Bundy, D. A. Does helminth infection affect mental processing and educational achievement? Parasitol. Today 10, 14–18 (1994). This article reviews the evidence linking helminth infections with impaired cognitive function and the difficulties associated with such studies.

    Article  CAS  PubMed  Google Scholar 

  181. Symons, L. E. Anorexia: occurrence, pathophysiology, and possible causes in parasitic infections. Adv. Parasitol. 24, 103–133 (1985).

    Article  CAS  PubMed  Google Scholar 

  182. Stephenson, L. S. The contribution of Ascaris limbricoides to malnutrition in children. Parasitology 81, 221–233 (1980).

    Article  CAS  PubMed  Google Scholar 

  183. Katz, N., Chaves, A. & Pellegrino, J. A simple device for quantitative stool thick-smear technique in Schistosomiasis mansoni. Rev. Inst. Med. Trop. Sao Paulo 14, 397–400 (1972).

    CAS  PubMed  Google Scholar 

  184. World Health Organization. Prevention and control of schistosomiasis and soil-transmitted helminthiasis: report of a WHO expert committee (WHO, 2002).

  185. Nikolay, B., Brooker, S. J. & Pullan, R. L. Sensitivity of diagnostic tests for human soil-transmitted helminth infections: a meta-analysis in the absence of a true gold standard. Int. J. Parasitol. 44, 765–774 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  186. Bogoch, I. I. et al. Mobile phone microscopy for the diagnosis of soil-transmitted helminth infections: a proof-of-concept study. Am. J. Tropical Med. Hyg. 88, 626–629 (2013). This paper explores the use of mobile phone microscopy as a novel method for point-of-care diagnosis of soil-transmitted helminth infections.

    Article  Google Scholar 

  187. Moser, W. et al. Diagnostic comparison between FECPAKG2 and the Kato-Katz method for analyzing soil-transmitted helminth eggs in stool. PLoS Neglected Tropical Dis. 12, e0006562 (2018).

    Article  CAS  Google Scholar 

  188. Arndt, M. B. et al. Impact of helminth diagnostic test performance on estimation of risk factors and outcomes in HIV-positive adults. PLoS One 8, e81915 (2013).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  189. Easton, A. V. et al. Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming. Parasites Vectors 9, 38 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  190. Liu, J. et al. A laboratory-developed TaqMan Array Card for simultaneous detection of 19 enteropathogens. J. Clin. Microbiol. 51, 472–480 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Mationg, M. L. S. et al. Status of soil-transmitted helminth infections in schoolchildren in Laguna Province, the Philippines: determined by parasitological and molecular diagnostic techniques. PLoS Negl. Trop. Dis. 11, e0006022 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  192. O’Connell, E. M. & Nutman, T. B. Molecular diagnostics for soil-transmitted helminths. Am. J. Tropical Med. Hyg. 95, 508–513 (2016).

    Article  CAS  Google Scholar 

  193. Phuphisut, O. et al. Triplex polymerase chain reaction assay for detection of major soil-transmitted helminths, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, in fecal samples. Southeast. Asian J. Tropical Med. Public. Health 45, 267–275 (2014).

    CAS  Google Scholar 

  194. Llewellyn, S. et al. Application of a multiplex quantitative PCR to assess prevalence and intensity of intestinal parasite infections in a controlled clinical trial. PLoS Negl. Trop. Dis. 10, e0004380 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  195. Cunningham, L. J. et al. Developing a real-time PCR assay based on multiplex high-resolution melt-curve analysis: a pilot study in detection and discrimination of soil-transmitted helminth and schistosome species. Parasitology 145, 1733–1738 (2018).

    Article  PubMed  CAS  Google Scholar 

  196. Mejia, R. et al. A novel, multi-parallel, real-time polymerase chain reaction approach for eight gastrointestinal parasites provides improved diagnostic capabilities to resource-limited at-risk populations. Am. J. Tropical Med. Hyg. 88, 1041–1047 (2013).

    Article  CAS  Google Scholar 

  197. Pilotte, N. et al. Improved PCR-based detection of soil transmitted helminth infections using a next-generation sequencing approach to assay design. PLoS Negl. Trop. Dis. 10, e0004578 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  198. Rashwan, N., Diawara, A., Scott, M. E. & Prichard, R. K. Isothermal diagnostic assays for the detection of soil-transmitted helminths based on the SmartAmp2 method. Parasites Vectors 10, 496 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  199. Schrader, C., Schielke, A., Ellerbroek, L. & Johne, R. PCR inhibitors-occurrence, properties and removal. J. Appl. Microbiol. 113, 1014–1026 (2012).

    Article  CAS  PubMed  Google Scholar 

  200. World Health Organization. Prevention and control of intestinal parasitic infections: report of a WHO expert committee (WHO, 1987).

  201. Marocco, C., Bangert, M., Joseph, S. A., Fitzpatrick, C. & Montresor, A. Preventive chemotherapy in one year reduces by over 80% the number of individuals with soil-transmitted helminthiases causing morbidity: results from meta-analysis. Trans. R. Soc. Tropical Med. Hyg. 111, 12–17 (2017).

    Google Scholar 

  202. Bah, Y. M. et al. Soil-transmitted helminth infection in school age children in Sierra Leone after a decade of preventive chemotherapy interventions. Infect. Dis. Poverty 8, 41 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  203. Shumbej, T. et al. Impact of annual preventive mass chemotherapy for soil-transmitted helminths among primary school children in an endemic area of Gurage zone: a prospective cross-sectional study. Res. Rep. Tropical Med. 10, 109–118 (2019).

    Google Scholar 

  204. Bartram, J. & Cairncross, S. Hygiene, sanitation, and water: forgotten foundations of health. PLoS Med. 7, e1000367 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  205. Fewtrell, L. et al. Water, sanitation, and hygiene interventions to reduce diarrhoea in less developed countries: a systematic review and meta-analysis. Lancet. Infect. Dis. 5, 42–52 (2005). This article provides a systematic review and meta-analysis summarizing the importance of water, sanitation and hygiene (WASH) interventions in the control of soil transmitted helminth infections.

    Article  PubMed  Google Scholar 

  206. Cairncross, S. et al. Water, sanitation and hygiene for the prevention of diarrhoea. Int. J. Epidemiol. 39 (Suppl 1), i193–i205 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  207. Strunz, E. C. et al. Water, sanitation, hygiene, and soil-transmitted helminth infection: a systematic review and meta-analysis. PLoS Med. 11, e1001620 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  208. Vaz Nery, S. et al. The role of water, sanitation and hygiene interventions in reducing soil-transmitted helminths: interpreting the evidence and identifying next steps. Parasites Vectors 12, 273 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  209. Freeman, M. C. et al. Challenges and opportunities for control and elimination of soil-transmitted helminth infection beyond 2020. PLoS Negl Trop Dis 13, e0007201 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  210. World Health Organization. 2030 targets for soil-transmitted helminthiases control programmes (WHO, 2020).

  211. Turner, K. J., Fisher, E. H. & McWilliam, A. S. Homology between roundworm (Ascaris) and hookworm (N. americanus) antigens detected by human IgE antibodies. Australian J. Exp. Biol. Med. Sci. 58, 249–257 (1980).

    Article  CAS  Google Scholar 

  212. Correa-Oliveira, R. et al. Human antibody responses against schistosomal antigens. I. Antibodies from patients with Ancylostoma, Ascaris lumbricoides or Schistosoma mansoni infections react with schistosome antigens. Am. J. Tropical Med. Hyg. 38, 348–355 (1988).

    Article  CAS  Google Scholar 

  213. Betschart, B., Marti, S. & Glaser, M. Antibodies against the cuticlin of Ascaris suum cross-react with epicuticular structures of filarial parasites. Acta Tropica 47, 331–338 (1990).

    Article  CAS  PubMed  Google Scholar 

  214. Cuellar, C., Fenoy, S. & Guillen, J. L. Cross-reactions of sera from Toxascaris leonina and Ascaris suum infected mice with Toxocara canis, Toxascaris leonina and Ascaris suum antigens. Int. J. Parasitol. 25, 731–739 (1995).

    Article  CAS  PubMed  Google Scholar 

  215. Santos, A. B. et al. Cross-reactive IgE antibody responses to tropomyosins from Ascaris lumbricoides and cockroach. J. Allergy Clin. Immunol. 121, 1040–1046.e1 (2008).

    Article  CAS  PubMed  Google Scholar 

  216. Caraballo, L. & Acevedo, N. Allergy in the tropics: the impact of cross-reactivity between mites and Ascaris. Front. Biosci. 3, 51–64 (2011).

    Article  Google Scholar 

  217. Elsemore, D. A. et al. Enzyme-linked immunosorbent assay for coproantigen detection of Trichuris vulpis in dogs. J. Veterinary Diagn. Invest. 26, 404–411 (2014).

    Article  CAS  Google Scholar 

  218. Martinez-Perez, J. M., Vandekerckhove, E., Vlaminck, J., Geldhof, P. & Martinez-Valladares, M. Serological detection of Ascaris suum at fattening pig farms is linked with performance and management indices. Veterinary Parasitol. 248, 33–38 (2017).

    Article  CAS  Google Scholar 

  219. Geng, J., Elsemore, D. A., Oudin, N. & Ketzis, J. K. Diagnosis of feline whipworm infection using a coproantigen ELISA and the prevalence in feral cats in southern Florida. Veterinary Parasitol. Regional Stud. Rep. 14, 181–186 (2018).

    Google Scholar 

  220. Lassen, B. et al. Anti-Ascaris suum IgG antibodies in fattening pigs with different respiratory conditions. Veterinary Parasitol. 265, 85–90 (2019).

    Article  CAS  Google Scholar 

  221. Yoshida, A., Kikuchi, T., Nakagaki, S. & Maruyama, H. Optimal ELISA antigen for the diagnosis of Ascaris suum infection in humans. Parasitology Res. 115, 4701–4705 (2016).

    Article  Google Scholar 

  222. Lopes, C. A. et al. Anti-Ascaris suum immunoglobulin Y as a novel biotechnological tool for the diagnosis of human ascariasis. J. Helminthol. 94, e71 (2019).

    Article  CAS  PubMed  Google Scholar 

  223. Gazzinelli-Guimaraes, A. C. et al. IgG induced by vaccination with Ascaris suum extracts is protective against infection. Front. Immunol. 9, 2535 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  224. Robinson, K., Bellaby, T. & Wakelin, D. Efficacy of oral vaccination against the murine intestinal parasite Trichuris muris is dependent upon host genetics. Infect. Immun. 63, 1762–1766 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Dixon, H., Little, M. C. & Else, K. J. Characterisation of the protective immune response following subcutaneous vaccination of susceptible mice against Trichuris muris. Int. J. Parasitol. 40, 683–693 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Zhan, B. et al. Advancing a multivalent ‘Pan-anthelmintic’ vaccine against soil-transmitted nematode infections. Expert. Rev. Vaccines 13, 321–331 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  227. World Health Organization. Preventive chemotherapy in human helminthiasis. Coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers (WHO, 2006).

  228. Olliaro, P. et al. Potential drug development candidates for human soil-transmitted helminthiases. PLoS Negl. Trop. Dis. 5, e1138 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Palmeirim, M. S., Ame, S. M., Ali, S. M., Hattendorf, J. & Keiser, J. Efficacy and safety of a single dose versus a multiple dose regimen of mebendazole against hookworm infections in children: a randomised, double-blind trial. EClinicalMedicine 1, 7–13 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  230. World Health Organization. WHO model list of essential medicines (WHO, 2017).

  231. Moser, W., Schindler, C. & Keiser, J. in Highlighting Operational and Implementation Research for Control of Helminthiasis (ed. Keiser, J.) 91–115 (Academic Press, 2019).

  232. Palmeirim, M. S. et al. Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: a systematic review, meta-analysis and individual patient data analysis. PLoS Negl. Trop. Dis. 12, e0006458 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  233. Patel, C. et al. Efficacy and safety of ivermectin and albendazole co-administration in school-aged children and adults infected with Trichuris trichiura: study protocol for a multi-country randomized controlled double-blind trial. BMC Infect. Dis. 19, 262 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  234. Opoku, N. O. et al. Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trial. Lancet 392, 1207–1216 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Keller, L. et al. Efficacy and safety of ascending dosages of moxidectin and moxidectin-albendazole against Trichuris trichiura in adolescents: a randomized controlled trial. Clin. Infect. Dis. 70, 1193–1201 (2020).

    CAS  PubMed  Google Scholar 

  236. Wimmersberger, D. et al. Efficacy and safety of ivermectin against Trichuris trichiura in preschool- and school-aged children: a randomized controlled dose-finding trial. Clin. Infect. Dis. 67, 1247–1255 (2018).

    Article  CAS  PubMed  Google Scholar 

  237. Kopp, S. & Keiser, J. in Kucers’ the Use of Antibiotics: a Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs, 7th edn (ed. Grayson, M. L. et al.) 3381–3384 (CRC Press, 2017).

  238. Moser, W. et al. Efficacy and tolerability of triple drug therapy with albendazole, pyrantel pamoate, and oxantel pamoate compared with albendazole plus oxantel pamoate, pyrantel pamoate plus oxantel pamoate, and mebendazole plus pyrantel pamoate and oxantel pamoate against hookworm infections in school-aged children in Laos: a randomised, single-blind trial. Lancet. Infect. Dis. 18, 729–737 (2018).

    Article  CAS  PubMed  Google Scholar 

  239. Krucken, J. et al. Anthelmintic cyclcooctadepsipeptides: complex in structure and mode of action. Trends Parasitol. 28, 385–394 (2012).

    Article  PubMed  CAS  Google Scholar 

  240. Karpstein, T. et al. Evaluation of emodepside in laboratory models of human intestinal nematode and schistosome infections. Parasites Vectors 12, 226 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  241. Matamoros, G. et al. High endemicity of soil-transmitted helminths in a population frequently exposed to albendazole but no evidence of antiparasitic resistance. Trop. Med. Infect. Dis. 4, 73 (2019).

    Article  PubMed Central  Google Scholar 

  242. Moser, W., Schindler, C. & Keiser, J. Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis. BMJ 358, j4307 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  243. Khuroo, M. S., Rather, A. A., Khuroo, N. S. & Khuroo, M. S. Hepatobiliary and pancreatic ascariasis. World J. Gastroenterol. 22, 7507–7517 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  244. Alhamid, A. et al. Successful elimination of gallbladder ascariasis by conservative therapy, followed by cholecystectomy due to developing cholecystitis. Case Rep. Gastrointest. Med. 2018, 5831257 (2018).

    PubMed  PubMed Central  Google Scholar 

  245. Gupta, S. et al. Ascaris lumbricoides: an unusual aetiology of gastric perforation. J. Surg. Case Rep. 2012, rjs008 (2012).

    PubMed  PubMed Central  Google Scholar 

  246. Campbell, S. J. et al. Complexities and perplexities: a critical appraisal of the evidence for soil-transmitted helminth infection-related morbidity. PLoS Negl. Trop. Dis. 10, e0004566 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  247. Taylor-Robinson, D. C., Maayan, N., Donegan, S., Chaplin, M. & Garner, P. Public health deworming programmes for soil-transmitted helminths in children living in endemic areas. Cochrane Database Syst. Rev. 9, CD000371 (2019).

    PubMed  Google Scholar 

  248. Welch, V. A. et al. Mass deworming to improve developmental health and wellbeing of children in low-income and middle-income countries: a systematic review and network meta-analysis. Lancet. Glob. Health 5, e40–e50 (2017).

    Article  PubMed  Google Scholar 

  249. Taylor-Robinson, D. C., Maayan, N., Soares-Weiser, K., Donegan, S. & Garner, P. Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance. Cochrane Database of Syst. Rev. 7, CD000371 (2015).

    Google Scholar 

  250. Pabalan, N. et al. Soil-transmitted helminth infection, loss of education and cognitive impairment in school-aged children: a systematic review and meta-analysis. PLoS Negl. Trop. Dis. 12, e0005523 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  251. Yap, P., Utzinger, J., Hattendorf, J. & Steinmann, P. Influence of nutrition on infection and re-infection with soil-transmitted helminths: a systematic review. Parasites Vectors 7, 229 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  252. Cooper, E. S., Duff, E. M., Howell, S. & Bundy, D. A. ‘Catch-up’ growth velocities after treatment for Trichuris dysentery syndrome. Trans. R. Soc. Tropical Med. Hyg. 89, 653 (1995).

    Article  CAS  Google Scholar 

  253. Cooper, E. S., Bundy, D. A., MacDonald, T. T. & Golden, M. H. Growth suppression in the Trichuris dysentery syndrome. Eur. J. Clin. Nutr. 44, 285–291 (1990).

    CAS  PubMed  Google Scholar 

  254. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1789–1858 (2018).

    Article  Google Scholar 

  255. The World Bank. Decline of global extreme poverty continues but has slowed: World Bank. The World Bank https://www.worldbank.org/en/news/press-release/2018/09/19/decline-of-global-extreme-poverty-continues-but-has-slowed-world-bank (2018).

  256. Brooker, S. Estimating the global distribution and disease burden of intestinal nematode infections: adding up the numbers–a review. Int. J. Parasitol. 40, 1137–1144 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  257. Gardner, J. M., Grantham-McGregor, S. & Baddeley, A. Trichuris trichiura infection and cognitive function in Jamaican school children. Ann. Tropical Med. Parasitol. 90, 55–63 (1996).

    Article  CAS  Google Scholar 

  258. Simeon, D. T., Grantham-McGregor, S. M., Callender, J. E. & Wong, M. S. Treatment of Trichuris trichiura infections improves growth, spelling scores and school attendance in some children. J. Nutr. 125, 1875–1883 (1995).

    Article  CAS  PubMed  Google Scholar 

  259. Ahmed, A. et al. Soil-transmitted helminthiasis: a critical but neglected factor influencing school participation of Aboriginal children in rural Malaysia. Parasitology 139, 802–808 (2012).

    Article  PubMed  Google Scholar 

  260. Callender, J., Grantham-McGregor, S., Walker, S. & Cooper, E. Developmental levels and nutritional status of children with the Trichuris dysentery syndrome. Trans. R. Soc. Tropical Med. Hyg. 87, 528–529 (1993).

    Article  CAS  Google Scholar 

  261. Stephenson, L. S., Latham, M. C., Adams, E. J., Kinoti, S. N. & Pertet, A. Physical fitness, growth and appetite of Kenyan school boys with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved four months after a single dose of albendazole. J. Nutr. 123, 1036–1046 (1993).

    Article  CAS  PubMed  Google Scholar 

  262. Lenk, E. J., Redekop, W. K., Luyendijk, M., Rijnsburger, A. J. & Severens, J. L. Productivity loss related to neglected tropical diseases eligible for preventive chemotherapy: a systematic literature review. PLoS Negl. Trop. Dis. 10, e0004397 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  263. GBD 2017 DALYs and HALE Collaborators. Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1859–1922 (2018).

    Article  PubMed Central  Google Scholar 

  264. Gyorkos, T. W. et al. The right to deworming: the case for girls and women of reproductive age. PLoS Negl. Trop. Dis. 12, e0006740 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  265. Galgamuwa, L. S., Iddawela, D. & Dharmaratne, S. D. Prevalence and intensity of Ascaris lumbricoides infections in relation to undernutrition among children in a tea plantation community, Sri Lanka: a cross-sectional study. BMC Pediatrics 18, 13 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  266. Drake, L. J., Jukes, M. C. H., Sternberg, R. J. & Bundy, D. A. P. Geohelminth infections (ascariasis, trichuriasis and hookworm): cognitive and developmental impacts. Semin. Pediatric Infect. Dis. 11, 245–251 (2000).

    Article  Google Scholar 

  267. Dickson, R., Awasthi, S., Williamson, P., Demellweek, C. & Garner, P. Effects of treatment for intestinal helminth infection on growth and cognitive performance in children: systematic review of randomised trials. BMJ 320, 1697–1701 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  268. O’Lorcain, P. & Holland, C. V. The public health importance of Ascaris lumbricoides. Parasitology 121, S51–S71 (2000).

    Article  PubMed  Google Scholar 

  269. de Silva, N. R., Guyatt, H. L. & Bundy, D. A. Morbidity and mortality due to Ascaris-induced intestinal obstruction. Trans. R. Soc. Tropical Med. Hyg. 91, 31–36 (1997).

    Article  Google Scholar 

  270. Roy, K., Kundra, P. & Ravishankar, M. Unusual foreign body airway obstruction after laryngeal mask airway insertion. Anesthesia Analgesia 101, 294–295 (2005).

    Article  PubMed  Google Scholar 

  271. Husain, S. J., Zubairi, A. B., Sultan, N., Beg, M. A. & Mehraj, V. Recurrent episodes of upper airway blockage associated with Ascaris lumbricoides causing cardiopulmonary arrest in a young patient. BMJ Case Rep. 2009, bcr0120091415 (2009).

    Google Scholar 

  272. Prakash, S., Sitalakshmi, N., Singh, J., Dayal, M. & Gogia, A. R. Ascaris: an unusual cause of airway obstruction during general anesthesia with ProSeal laryngeal mask airway. J. Anaesthesiol. Clin. Pharmacol. 30, 298–300 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  273. Endara, P. et al. Effect of urban vs. rural residence on the association between atopy and wheeze in Latin America: findings from a case-control analysis. Clin. Exp. Allergy 45, 438–447 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  274. Caraballo, L., Acevedo, N. & Zakzuk, J. Ascariasis as a model to study the helminth/allergy relationships. Parasite Immunol. 41, e12595 (2019).

    Article  PubMed  Google Scholar 

  275. Dunn, J. C. et al. A cross-sectional survey of soil-transmitted helminthiases in two Myanmar villages receiving mass drug administration: epidemiology of infection with a focus on adults. Parasites Vectors 10, 374 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  276. Asbjornsdottir, K. H. et al. Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: the DeWorm3 cluster randomized trial protocol. PLoS Negl. Trop. Dis. 12, e0006166 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  277. Anderson, R. M., Turner, H. C., Truscott, J. E., Hollingsworth, T. D. & Brooker, S. J. Should the goal for the treatment of soil transmitted helminth (STH) infections be changed from morbidity control in children to community-wide transmission elimination? PLoS Negl. Trop. Dis. 9, e0003897 (2015).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  278. Pullan, R. L. et al. Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial. Lancet 393, 2039–2050 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  279. Becker, S. L. et al. Toward the 2020 goal of soil-transmitted helminthiasis control and elimination. PLoS Negl. Trop. Dis. 12, e0006606 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  280. Hollingsworth, T. D., Truscott, J.E. & Anderson, R.M. in Ascaris: the Neglected Parasite (ed. Holland, C.) 231-262 (Elsevier, 2013).

  281. Jex, A. R. et al. Ascaris suum draft genome. Nature 479, 529–533 (2011).

    Article  CAS  PubMed  Google Scholar 

  282. Coghlan, A. et al. Comparative genomics of the major parasitic worms. Nat. Genet. 51, 163–174 (2019).

    Article  CAS  Google Scholar 

  283. Kaminsky, R. et al. A new class of anthelmintics effective against drug-resistant nematodes. Nature 452, 176–180 (2008).

    Article  CAS  PubMed  Google Scholar 

  284. Partridge, F. A. et al. An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes. Int. J. Parasitol. Drugs Drug. Resistance 8, 8–21 (2018).

    Article  Google Scholar 

  285. Yemini, E., Jucikas, T., Grundy, L. J., Brown, A. E. & Schafer, W. R. A database of Caenorhabditis elegans behavioral phenotypes. Nat. Methods 10, 877–879 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  286. Partridge, F. A. et al. Dihydrobenz[e][1,4]oxazepin-2(3H)-ones, a new anthelmintic chemotype immobilising whipworm and reducing infectivity in vivo. PLoS Negl. Trop. Dis. 11, e0005359 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  287. Partridge, F. A. et al. 2,4-Diaminothieno[3,2-d]pyrimidines, a new class of anthelmintic with activity against adult and egg stages of whipworm. PLoS Negl. Trop. Dis. 12, e0006487 (2018). This paper reports the discovery of a novel anthelminthic compound with activity against both adult Trichuris spp. parasites and the parasitic egg stage and discusses the potential for environmental control to break the parasite life cycle.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  288. Mejer, H. & Roepstorff, A. in Proc. 23rd International Conference of the World Association for the Advancement of Veterinary Parasitology 113 (International Conference of the World Association for the Advancement of Veterinary Parasitology, 2011).

  289. Tilney, L. G., Connelly, P. S., Guild, G. M., Vranich, K. A. & Artis, D. Adaptation of a nematode parasite to living within the mammalian epithelium. J. Exp. Zool. Part. A, Comp. Exp. Biol. 303, 927–945 (2005).

    Article  Google Scholar 

  290. Lee, T. D. & Wright, K. A. The morphology of the attachment and probable feeding site of the nematode Trichuris muris (Schrank, 1788) Hall, 1916. Can. J. Zool. 56, 1889–1905 (1978).

    Article  CAS  PubMed  Google Scholar 

  291. Glover, M., Colombo, S. A. P., Thornton, D. J. & Grencis, R. K. Trickle infection and immunity to Trichuris muris. PLoS Pathog. 15, e1007926 (2019).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  292. Abolins, S. et al. The comparative immunology of wild and laboratory mice, Mus musculus domesticus. Nat. Commun. 8, 14811 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  293. Leung, J. M. et al. Rapid environmental effects on gut nematode susceptibility in rewilded mice. PLoS Biol. 16, e2004108 (2018).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  294. Vercruysse, J. et al. Is anthelmintic resistance a concern for the control of human soil-transmitted helminths? Int. J. Parasitol. Drugs Drug Resistance 1, 14–27 (2011).

    Article  CAS  Google Scholar 

  295. Diawara, A. et al. Association between response to albendazole treatment and β-tubulin genotype frequencies in soil-transmitted helminths. PLoS Negl. Trop. Dis. 7, e2247 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  296. Ronéus, O. Studies on the aetiology and pathogenesis of white spots in the liver of pigs. Acta Veterinaria Scandinavica 7 (Suppl 16), 1–112 (1966).

    Google Scholar 

  297. Urban, J. F. Jr. & Tromba, F. G. An ultraviolet-attenuated egg vaccine for swine ascariasis: parameters affecting the development of protective immunity. Am. J. Veterinary Res. 45, 2104–2108 (1984).

    Google Scholar 

  298. Tsuji, N. et al. Intranasal immunization with recombinant Ascaris suum 14-kilodalton antigen coupled with cholera toxin B subunit induces protective immunity to A. suum infection in mice. Infect. Immun. 69, 7285–7292 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  299. Wei, J. et al. Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response. PLoS Negl. Trop. Dis. 11, e0005769 (2017).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  300. Versteeg, L. et al. Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection. PLoS Negl. Trop. Dis. 14, e0008057 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  301. Briggs, N. et al. Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm. PLoS Pathog. 14, e1007273 (2018). The authors identify the Trichuris muris whey acidic protein as a promising human vaccine candidate.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  302. Zawawi, A. et al. In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection. PLoS Pathog. 16, e1008243 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  303. Khurana, S. & Sethi, S. Laboratory diagnosis of soil transmitted helminthiasis. Tropical Parasitol. 7, 86–91 (2017).

    Google Scholar 

  304. Lamberton, P. H. & Jourdan, P. M. Human ascariasis: diagnostics update. Curr. Tropical Med. Rep. 2, 189–200 (2015).

    Article  Google Scholar 

  305. Knopp, S. et al. A single FLOTAC is more sensitive than triplicate Kato-Katz for the diagnosis of low-intensity soil-transmitted helminth infections. Trans. R. Soc. Tropical Med. Hyg. 103, 347–354 (2009).

    Article  Google Scholar 

  306. Cools, P. et al. Diagnostic performance of a single and duplicate Kato-Katz, Mini-FLOTAC, FECPAKG2 and qPCR for the detection and quantification of soil-transmitted helminths in three endemic countries. PLoS Negl. Trop. Dis. 13, e0007446 (2019).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  307. Levecke, B. et al. A comparison of the sensitivity and fecal egg counts of the McMaster egg counting and Kato-Katz thick smear methods for soil-transmitted helminths. PLoS Negl. Trop. Dis. 5, e1201 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  308. Shiraho, E. A. et al. Development of a loop mediated isothermal amplification for diagnosis of Ascaris lumbricoides in fecal samples. J. Parasitol. Res. 2016, 7376207 (2016).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  309. Holt, D. C. et al. Soil-transmitted helminths in children in a remote aboriginal community in the Northern Territory: hookworm is rare but Strongyloides stercoralis and Trichuris trichiura persist. Trop. Med. Infect. Dis. 2, 51 (2017).

    Article  PubMed Central  Google Scholar 

  310. Briolat, E. Worming it out. MRC http://www.bpod.mrc.ac.uk/archive/2016/9/13 (2018).

  311. Arnold, M., Alves, J. & Plessis, J. in ABC of Pediatric Surgical Imaging (eds Andronikou, S., Alexander, A., Kilborn, T., Millar, A. J. W. & Daneman, A.) (Springer, 2010).

  312. Yetim, I. et al. Rare cause of intestinal obstruction, Ascaris lumbricoides infestation: two case reports. Cases J. 2, 7970 (2018).

    Article  Google Scholar 

  313. O’Sullivan, J. D. B., Cruickshank, S. M., Starborg, T., Withers, P. J. & Else, K. J. Characterisation of cuticular inflation development and composition in Trichuris muris using correlative X-ray computed tomography and electron microscopy. Sci. Rep. 10, 5846 (2020).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  314. Mayer, J. U. et al. Different populations of CD11b(+) dendritic cells drive Th2 responses in the small intestine and colon. Nat. Commun. 8, 15820 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  315. Luda, K. M. et al. IRF8 transcription-factor-dependent classical dendritic cells are essential for intestinal t cell homeostasis. Immunity 44, 860–874 (2016).

    Article  CAS  PubMed  Google Scholar 

  316. Gold, M. J., Antignano, F., Hughes, M. R., Zaph, C. & McNagny, K. M. Dendritic-cell expression of Ship1 regulates Th2 immunity to helminth infection in mice. Eur. J. Immunol. 46, 122–130 (2016).

    Article  CAS  PubMed  Google Scholar 

  317. Owyang, A. M. et al. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J. Exp. Med. 203, 843–849 (2006).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  318. Taylor, B. C. et al. TSLP regulates intestinal immunity and inflammation in mouse models of helminth infection and colitis. J. Exp. Med. 206, 655–667 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  319. Hopwood, T. W. et al. The circadian regulator BMAL1 programmes responses to parasitic worm infection via a dendritic cell clock. Sci. Rep. 8, 3782 (2018). The authors provide evidence for an increased susceptibility of mice to Trichuris muris infection if the infection is given at night rather than day; they also show that this time of day dependency of the outcome of infection involves a molecular clock within the dendritic cells.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank R. Forman, J. O’Sullivan and H. Smith (Lydia Becker Institute for Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK) for providing images and design of Fig. 3 and Fig. 6. The authors also thank J. O’Sullivan for design of Fig. 4. The authors acknowledge the Engineering and Physical Science Research Council (EPSRC) for funding the Henry Moseley X-ray Imaging Facility through grants (EP/F007906/1, EP/F001452/1, EP/I02249X, EP/F028431/1 and EP/M022498/1 and platform grant EP/M010619/1) within the Henry Royce Institute.

Author information

Authors and Affiliations

  1. Lydia Becker Institute for Immunology and Inflammation, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

    Kathryn J. Else & Richard K. Grencis

  2. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland

    Jennifer Keiser

  3. University of Basel, Basel, Switzerland

    Jennifer Keiser

  4. Department of Zoology, School of Natural Sciences, Trinity College Dublin, Dublin, Ireland

    Celia V. Holland

  5. Centre for Respiratory Biology, UCL Respiratory, Rayne Building, University College London, London, UK

    David B. Sattelle

  6. Department of Parasitology, Institute of Biological Sciences (ICB), Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Ricardo T. Fujiwara & Lilian L. Bueno

  7. Department of Zoology, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria

    Samuel O. Asaolu & Oluyomi A. Sowemimo

  8. Institute of Infection and Immunity, St George’s University of London, London, UK

    Philip J. Cooper

  9. Facultad de Ciencias Medicas, de la Salud y la Vida, Universidad Internacional del Ecuador, Quito, Ecuador

    Philip J. Cooper

Authors
  1. Kathryn J. Else
    View author publications

    Search author on:PubMed Google Scholar

  2. Jennifer Keiser
    View author publications

    Search author on:PubMed Google Scholar

  3. Celia V. Holland
    View author publications

    Search author on:PubMed Google Scholar

  4. Richard K. Grencis
    View author publications

    Search author on:PubMed Google Scholar

  5. David B. Sattelle
    View author publications

    Search author on:PubMed Google Scholar

  6. Ricardo T. Fujiwara
    View author publications

    Search author on:PubMed Google Scholar

  7. Lilian L. Bueno
    View author publications

    Search author on:PubMed Google Scholar

  8. Samuel O. Asaolu
    View author publications

    Search author on:PubMed Google Scholar

  9. Oluyomi A. Sowemimo
    View author publications

    Search author on:PubMed Google Scholar

  10. Philip J. Cooper
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Introduction (K.J.E. and C.V.H.); Epidemiology (P.J.C., L.L.B., S.O.A. and O.A.S.); Mechanisms/pathophysiology (K.J.E., R.K.G., C.V.H., R.T.F. and L.L.B.); Diagnosis, screening and prevention (P.J.C., L.L.B., S.O.A., O.A.S. and R.T.F.); Management (J.K., S.O.A. and O.A.S.); Quality of Life (P.J.C., S.O.A. and O.A.S.); Outlook (D.B.S. and C.V.H.); Overview of Primer (K.J.E.).

Corresponding author

Correspondence to Kathryn J. Else.

Ethics declarations

Competing interests

All authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Disease Primers thanks A. Clements, A. Loukas, J. Urban and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Else, K.J., Keiser, J., Holland, C.V. et al. Whipworm and roundworm infections. Nat Rev Dis Primers 6, 44 (2020). https://doi.org/10.1038/s41572-020-0171-3

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-020-0171-3

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing