Cited by 82Parasites and Host InteractionsAsthma and respiratory diseasesAllergic Rhinitis and Sensitization

The DOI matches its Crossref record; 109 of the 109 references it cites were found in a registry or an index; 1 of the 124 sources its claims cite were checked for support.

Global issues in allergy and immunology: Parasitic infections and allergy

Open access
Cruz, Alvaro A., Cooper, Philip J., Figueiredo, Camila A., Alcantara-Neves, Neuza M., Rodrigues, Laura C., Barreto, Mauricio L.·2017·Journal of Allergy and Clinical Immunology

Abstract

Allergic diseases are on the increase globally in parallel with a decrease in parasitic infection. The inverse association between parasitic infections and allergy at an ecological level suggests a causal association. Studies in human subjects have generated a large knowledge base on the complexity of the interrelationship between parasitic infection and allergy. There is evidence for causal links, but the data from animal models are the most compelling: despite the strong type 2 immune responses they induce, helminth infections can suppress allergy through regulatory pathways. Conversely, many helminths can cause allergic-type inflammation, including symptoms of "classical" allergic disease. From an evolutionary perspective, subjects with an effective immune response against helminths can be more susceptible to allergy. This narrative review aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy. Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases, but thus far, clinical trials in human subjects have not demonstrated unequivocal clinical benefits. Nevertheless, there is sufficiently strong evidence to support continued investigation of the potential benefits of helminth-derived therapies for the prevention or treatment of allergic and other inflammatory diseases.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review synthesizes evidence on parasitic infections and allergy, concluding that helminths can suppress allergy through regulatory pathways but that human clinical trials of helminth therapy have not shown unequivocal benefit. It highlights strong animal-model evidence alongside inconsistent human epidemiologic and interventional data.

Key findings

  • Worldwide, an estimated 1.5 billion people are infected with a soil-transmitted helminth, and *Schistosoma* species are estimated to infect 230 million persons; in one rural Brazilian village, helminth prevalence was 83.5%, compared with less than 20% among children in nearby Salvador.
  • Meta-analyses found that *Ascaris lumbricoides* was associated with increased asthma risk, whereas hookworm infection was associated with reduced risk; current STH infections were protective against atopy, consistent for all 3 of the most common STH infections and also schistosomiasis.
  • Four prospective studies were identified; maternal and childhood hookworm and childhood *Trichuris trichiura* were associated with reduced eczema at 5 years, and *T trichiura* infections during the first 5 years of life were associated with reduced SPT reactivity in later childhood.
  • Clinical trials of live helminths have been disappointing: *Trichuris suis* showed no efficacy for allergic rhinitis, *Necator americanus* showed no clinical benefit in celiac disease, and a small randomized trial in asthma showed no significant benefit of hookworm infection on clinical symptoms, bronchial responsiveness, or SPT reactivity.

Methods

  • Narrative review; the paper states it aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy, without a systematic search or meta-analysis.
  • Evidence synthesized includes human epidemiologic studies, meta-analyses, prospective birth cohorts, randomized anthelmintic trials, animal models, and preclinical/clinical studies of helminth-derived molecules.
  • Main analysis is qualitative synthesis, with tables and figures summarizing associations between helminths, atopy, and asthma and candidate immunomodulatory molecules.

Limitations

  • The paper states that evidence from human studies has been equivocal, that there is still very limited evidence that STH infections protect against allergic symptoms, that early-life exposures are insufficiently studied, and that the role of human genetic determinants of IL33/ST2 in helminth infection is poorly understood.
  • The paper states that clinical trials in human subjects have been disappointing, possibly because they attempted to modify preexisting disease while most animal models studied prevention, because of high placebo response rates, because patients continued immunosuppressive medications, and because of safety and ethical concerns with large infectious doses and long-term infections.
  • Evident from the text: as a narrative review, it does not use a systematic search strategy or formal risk-of-bias assessment, and many cited human associations are cross-sectional, limiting causal inference.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jaci.2017.09.005

Cites

109 of 109 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

FIG 1 Typical features of a rural household in a village in the municipality of Conde, Brazil, in which the prevalence of helminth infections was 83.5% (picture taken in 2005). 5
FIG 1 Typical features of a rural household in a village in the municipality of Conde, Brazil, in which the prevalence of helminth infections was 83.5% (picture taken in 2005). 5CC-BY · From the PDF
FIG 2 Typical urban underserved neighborhood of Salvador, Brazil, in which the prevalence of helminth infection among children was less than 20%. 6 Figure Attribution: original image by user sergio_65_ita (Sussuarana [Salvador] -DSC03080 [CC BY 2.0; http://creativecommons.org/licenses/by/2.0]), via Wikimedia Commons.
FIG 2 Typical urban underserved neighborhood of Salvador, Brazil, in which the prevalence of helminth infection among children was less than 20%. 6 Figure Attribution: original image by user sergio_65_ita (Sussuarana [Salvador] -DSC03080 [CC BY 2.0; http://creativecommons.org/licenses/by/2.0]), via Wikimedia Commons.CC-BY · From the PDF
FIG 3 Schematic representation summarizing findings from epidemiologic studies on the relationships between helminth parasites, atopy, and asthma.
FIG 3 Schematic representation summarizing findings from epidemiologic studies on the relationships between helminth parasites, atopy, and asthma.CC-BY · From the PDF
FIG 4 Helminths suppress autoimmunity and allergy through type 2 or regulatory immune response. Immunomodulatory molecules (IMs) of parasites activate innate immune cells that promote either TH2 or Treg cell responses. IMs that induce TGFb and IL-10 production by dendritic cells or macrophages (Mø) prime IL-10-or TGFb -producing Treg cells to suppress TH2, TH1, or TH17 responses. A separate set of helminth-derived IMs activate type 2 innate cells, including basophils, M2 macrophages, and ILC2s, and induce innate IL-4 production, which drives differentiation of TH2 cells. TH2 cells and type 2 innate immune cells can suppress TH1 and TH17 responses. Modified from Finlay et al. 47
FIG 4 Helminths suppress autoimmunity and allergy through type 2 or regulatory immune response. Immunomodulatory molecules (IMs) of parasites activate innate immune cells that promote either TH2 or Treg cell responses. IMs that induce TGFb and IL-10 production by dendritic cells or macrophages (Mø) prime IL-10-or TGFb -producing Treg cells to suppress TH2, TH1, or TH17 responses. A separate set of helminth-derived IMs activate type 2 innate cells, including basophils, M2 macrophages, and ILC2s, and induce innate IL-4 production, which drives differentiation of TH2 cells. TH2 cells and type 2 innate immune cells can suppress TH1 and TH17 responses. Modified from Finlay et al. 47CC-BY · From the PDF
FIG 5 Pathway analysis using PANTHER, version 11, 49 for the top SNPs associated in GWASs for asthma to date. EGF , Epidermal growth factor; FGF , fibroblast growth factor; JAK/STAT , Janus kinase/signal transducer and activator of transcription; PDGF , platelet-derived growth factor.
FIG 5 Pathway analysis using PANTHER, version 11, 49 for the top SNPs associated in GWASs for asthma to date. EGF , Epidermal growth factor; FGF , fibroblast growth factor; JAK/STAT , Janus kinase/signal transducer and activator of transcription; PDGF , platelet-derived growth factor.CC-BY · From the PDF

Verification

Claims the paper makes

63 Own interpretation · 52 Check pending · 41 No full text of the sources · 13 Not checked yet · 5 No basis given · 1 Supported · 1 Own result

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Show all 125 claims

  • It may state two separate claims as one. 40
  • Probably not a substantial claim. 13
51 of 51
  • The authors state this as an assumption.

    IgE plays a central role in protective immunity against helminth parasites.

    “Because of the presumed central role of IgE in protective immunity against helminth parasites”
  • The paper relies on this without support.

    Findings from animal models of helminth infection and allergy are informative for human allergic disease.

    “the data from animal models are the most compelling”
    “Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases”
  • The paper relies on this without support.

    The key effects of protective environmental exposures occur during early life, during which there is a limited window of opportunity for such exposures to mediate their effects.

    “It has been suggested that the key effects of protective environmental exposures occur during early life, during which there might be a limited window of opportunity for such exposures to mediate their effects.9”
  • The authors state this as an assumption.

    The immune system can be modulated with amelioration or remission of the inflammatory disease.

    “The premise is that the immune system can be modulated with amelioration or remission of the inflammatory disease.”
  • The paper relies on this without support.

    Experimental animal models have demonstrated helminth parasites reduce allergic reactivity.

    “Experimental animal models have demonstrated helminth parasites reduce allergic reactivity, but”
  • The paper relies on this without support.

    Most studies have been designed to prevent the development of allergic reactivity rather than treat established disease.

    “most studies have been designed to prevent the development of allergic reactivity rather than treat established disease.”
  • The paper relies on this without support.

    Recombinant proteins can reproduce the biological effects observed in infection with live worms.

    “Recombinant proteins can reproduce the biological effects observed in infection with live worms.”
  • The paper relies on this without support.

    Molecule-based helminth treatment offers the advantage of delivery directly to the site of pathology.

    “Furthermore, molecule-based helminth treatment offers the advantage of delivery directly to the site of pathology.”
  • The paper relies on this without support.

    No safety issues have been reported after administration of T. suis ova thus far, even to immunosuppressed patients.

    “No safety issues have been reported after administration of T suis ova thus far, even to immunosuppressed patients, but in general, there are safety and ethical concerns with treating human subjects with large infectious doses and maintaining infections for a period of years that might be required to induce clinically relevant immunomodulatory effects.”
  • The paper relies on this without support.

    The effects of helminth infections in humans are related to parasite burden and duration of infection.

    “The effects of helminth infections in humans are related to parasite burden and duration of infection.”
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Metadata

Authors
Cruz, A. A., Cooper, P. J., Figueiredo, C. A., Alcantara-Neves, N. M., Rodrigues, L. C., & Barreto, M. L.
Affiliations
  • St George's, University of London (GB)
  • Universidade Federal da Bahia (BR)
  • London School of Hygiene & Tropical Medicine (GB)
Venue
Journal of Allergy and Clinical Immunology
Publisher
Elsevier BV
Published
2017-11
Volume
140
Issue
5
Pages
1217-1228
ISSN
0091-6749 (ISSN-L)
OpenAlex
W2765928288
Cited by
82
References
109
Citations by year
2026: 6 · 2025: 6 · 2024: 6 · 2023: 12 · 2022: 7 · 2021: 10 · 2020: 11 · 2019: 12 · 2018: 12
FWCI
1.39
Type
journal article
Language
en
Open access
Locations
  • Journal of Allergy and Clinical Immunology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • St George's Online Research Archive (St George's University of London) (acceptedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • Americanae (AECID Library) (submittedVersion, other-oa)
  • Arca - Repositório Institucional da Fiocruz (submittedVersion, other-oa)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
Keywords
helminthiasis, allergy, allergic diseases, Th2 immune response, regulatory immune response, allergic inflammation, chronic inflammatory diseases, animal models of allergy
MeSH terms
Allergens, Allergy and Immunology, Animals, Antigens, Helminth, Clinical Trials as Topic, Disease Models, Animal, Helminthiasis, Helminths, Humans, Hypersensitivity, Parasitic Diseases, Immunomodulation, Therapy with Helminths

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