A life without worms

Sanya, Richard E.; Nkurunungi, Gyaviira; Andia-Biraro, Irene; Mpairwe, Harriet; Elliott, Alison M.

doi:10.1093/trstmh/trx010

Cited by 12 publications

(12 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Induction of immunomodulatory mechanisms has been used to explain epidemiological data reporting an inverse association between exposure to helminth infections and human chronic inflammatory diseases, including allergic conditions (19, 59). However, a putative causal relationship between helminth infection and reduction of allergic diseases is mainly supported by data from experimental animal models, while evidence from human studies are still controversial and suggest that aspects such as helminth species, chronicity and site of infection, and parasite burden should be taken into consideration (45, 60, 61). Here, we conducted a cross-sectional study in a schistosomiasis endemic area where most infected individuals harbor a small number of parasites, with the aim of evaluating whether low parasite burden could affect the modulation of allergic reactivity against common household allergens.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Allergic Reactivity in Humans Is Dependent on Schistosoma mansoni Parasite Burden, Low Levels of IL-33 or TNF-α and High Levels of IL-10 in Serum

et al. 2019

View full text Add to dashboard Cite

Helminth infections and allergies are characterized by a predominant type-2 immune response. In schistosomiasis, the Th-2 response is usually accompanied by induction of immunoregulatory mechanisms that contribute to worm survival and less severe schistosomiasis. Although helminth-induced immunomodulatory mechanisms seem to affect atopy, epidemiological studies on the relationship between helminths and allergy have been inconsistent, and data suggest that the modulatory effects may be influenced by helminth species, chronicity of infection, and parasite burden. Here we performed a cross-sectional study to investigate the effects of Schistosoma mansoni parasite burden and immune response on allergic reactivity of individuals living in a schistosomiasis endemic area in Brazil. Fecal samples from the participants were collected for extensive parasitological examinations by spontaneous sedimentation, Kato-Katz, Helmintex and Saline Gradient tests and molecular detection of S. mansoni by qPCR. Additionally, the concentrations of cytokines and chemokines, total IgE and IgE-reactivity to common house dust allergens were quantified from serum samples. IgE reactivity to dust allergens was detected in 47 individuals (23.8%), and 140 individuals (54.4%) were diagnosed with S. mansoni infection. Most of the infected population (108 individuals) presented very low parasite burden (≤12 eggs/g of feces). The frequency and intensity (p ≤ 0.03) of allergic reactivity were lower in S. mansoni-infected compared with non-infected individuals. Multivariable logistic regression models adjusted by age revealed that allergic reactivity was positively associated with low IL-10 response (OR, 4.55, 95% CI, 0.56–7.36) and high concentration of the inflammatory mediators IL-33 (OR, 2.70, 95% CI, 1.02–7.15) or TNF-α (OR, 6.88, 95% CI, 0.32–143.39) in serum, and inversely associated with S. mansoni infection (OR, 0.38, 95% CI, 0.16–0.87). Most importantly, the logistic regression demonstrated that the modulatory effects of Schistosoma infection depend on parasite burden, with individuals infected with ≤12 eggs/g of feces showing allergic IgE-reactivity similar to non-infected individuals Altogether, our data show that immunomodulation of allergic reactivity depends on S. mansoni burden, low type-2 inflammatory response, and high level of IL-10.

show abstract

Section: Discussionmentioning

confidence: 99%

Modulation of Allergic Reactivity in Humans Is Dependent on Schistosoma mansoni Parasite Burden, Low Levels of IL-33 or TNF-α and High Levels of IL-10 in Serum

et al. 2019

View full text Add to dashboard Cite

show abstract

“…If this holds for human malaria parasites, it suggests that co-infections that cause anaemia (e.g. helminth infections, [ 80 ]) could select for less virulent malaria genotypes. Further, anaemic patients may require additional transmission-reducing measures because they may be more infectious than their counterparts [ 44 , 72 ].…”

Section: Discussionmentioning

confidence: 99%

Phenotypic plasticity in reproductive effort: malaria parasites respond to resource availability

Birget¹,

Repton²,

O’Donnell³

et al. 2017

Proc. R. Soc. B.

View full text Add to dashboard Cite

The trade-off between survival and reproduction is fundamental in the life history of all sexually reproducing organisms. This includes malaria parasites, which rely on asexually replicating stages for within-host survival and on sexually reproducing stages (gametocytes) for between-host transmission. The proportion of asexual stages that form gametocytes (reproductive effort) varies during infections-i.e. is phenotypically plastic-in response to changes in a number of within-host factors, including anaemia. However, how the density and age structure of red blood cell (RBC) resources shape plasticity in reproductive effort and impacts upon parasite fitness is controversial. Here, we examine how and why the rodent malaria parasite Plasmodium chabaudi alters its reproductive effort in response to experimental perturbations of the density and age structure of RBCs. We show that all four of the genotypes studied increase reproductive effort when the proportion of RBCs that are immature is elevated during host anaemia, and that the responses of the genotypes differ. We propose that anaemia (counterintuitively) generates a resource-rich environment in which parasites can afford to allocate more energy to reproduction (i.e. transmission) and that anaemia also exposes genetic variation to selection. From an applied perspective, adaptive plasticity in parasite reproductive effort could explain the maintenance of genetic variation for virulence and why anaemia is often observed as a risk factor for transmission in human infections.

show abstract

“…In animal models, helminths generally impair priming and accelerate waning of vaccine responses, although effects vary with helminth species, vaccine type and the timing of infection and immunisation. 22 Most observational studies in humans also suggest suppressed or biased responses during helminth infection, especially during systemic infections, such as schistosomiasis and the filariases. There is modest evidence that treating geohelminths in humans improves responses to BCG 23 24 or oral cholera vaccine 25 and we found that schistosomiasis treatment improved the measles-booster response in preschool children.…”

Section: Introductionmentioning

confidence: 99%

Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

et al. 2021

Self Cite

View full text Add to dashboard Cite

IntroductionSeveral licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.Methods and analysisWe have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9–17 years) from rural Schistosoma mansoni-endemic Ugandan islands. Vaccines to be studied comprise BCG on day ‘zero’; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with S. mansoni at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on S. mansoni infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.Ethics and disseminationEthics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.Trial registration numberISRCTN60517191.

show abstract

A life without worms

Cited by 12 publications

References 113 publications

Modulation of Allergic Reactivity in Humans Is Dependent on Schistosoma mansoni Parasite Burden, Low Levels of IL-33 or TNF-α and High Levels of IL-10 in Serum

Modulation of Allergic Reactivity in Humans Is Dependent on Schistosoma mansoni Parasite Burden, Low Levels of IL-33 or TNF-α and High Levels of IL-10 in Serum

Phenotypic plasticity in reproductive effort: malaria parasites respond to resource availability

Effect of intensive treatment for schistosomiasis on immune responses to vaccines among rural Ugandan island adolescents: randomised controlled trial protocol A for the ‘POPulation differences in VACcine responses’ (POPVAC) programme

Contact Info

Product

Resources

About