Rodent Models for the Study of Soil-Transmitted Helminths: A Proteomics Approach

Soil-transmitted helminths (STH) affect hundreds of millions worldwide and are some of the most important neglected tropical diseases in terms of morbidity. Due to the difficulty in studying STH human infections, rodent models have become increasingly used, mainly because of their similarities in life cycle. Ascaris suum and Trichuris muris have been proven appropriate and low maintenance models for the study of ascariasis and trichuriasis. In the case of hookworms, despite most of the murine models do not fully reproduce the life cycle of Necator americanus, their proteomic similarity makes them highly suitable for the development of novel vaccine candidates and for the study of hookworm biological features. Furthermore, these models have been helpful in elucidating some basic aspects of our immune system, and are currently being used by numerous researchers to develop novel molecules with immunomodulatory proteins. Herein we review the similarities in the proteomic composition between Nippostrongylus brasiliensis, Heligmosomoides polygyrus bakeri and Trichuris muris and their respective human counterpart with a focus on the vaccine candidates and immunomodulatory proteins being currently studied.

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Research Note. Occurrence of gastrointestinal helminths in commensal rodents from Tabasco, Mexico

Helminthologia ◽

10.1515/helm-2017-0014 ◽

2017 ◽

Vol 54 (2) ◽

pp. 170-173 ◽

Cited By ~ 2

Author(s):

N. Cigarroa-Toledo ◽

Y. De Los Santos-Martinez ◽

C. V. Zaragoza-Vera ◽

M. M. Garcia-Rodriguez ◽

C. M. Baak-Baak ◽

...

Keyword(s):

Rattus Rattus ◽

Hymenolepis Diminuta ◽

Nippostrongylus Brasiliensis ◽

Gastrointestinal Helminths ◽

Trichuris Muris ◽

Heligmosomoides Polygyrus ◽

Syphacia Muris ◽

Commensal Rodents ◽

Syphacia Obvelata ◽

Moniliformis Moniliformis

Summary The aim of this study was to determine the prevalence and species composition of helminths in commensal rodents captured inside private residences in the city of Villahermosa in Tabasco, Mexico. Trapping was performed at each house for three consecutive nights from October to December 2015. Fifty commensal rodents were captured: 23 Rattus norvegicus, 16 Mus musculus and 11 Rattus rattus. Rodents were transported alive to the laboratory and held in cages until they defecated. Feces were analyzed for helminth eggs using the Sheather’s flotation technique. The overall prevalence of helminths in rodents was 60 %: R. norvegicus was more likely to be parasitized (87.0 %) than R. rattus (63.6 %) and M. musculus (18.8 %). Eggs from at least 13 species of helminths were identified: Hymenolepis diminuta, Rodentolepis nana, Moniliformis moniliformis, Heligmosomoides polygyrus, Heterakis spumosa, Mastophorus muris, Nippostrongylus brasiliensis, Strongyloides ratti, Syphacia obvelata, Syphacia muris, Toxocara sp., Trichosomoides crassicauda, and Trichuris muris. This is the first study to report the presence of H. polygyrus, S. ratti and T. crassicauda in commensal rodents in Mexico. In conclusion, our results suggest that helminths commonly infect commensal rodents in Villahermosa and therefore rodents present a health risk to inhabitants in this region.

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Structural Requirements for Dihydrobenzoxazepinone Anthelmintics: Actions against Medically Important and Model Parasites: Trichuris muris, Brugia malayi, Heligmosomoides polygyrus, and Schistosoma mansoni

ACS Infectious Diseases ◽

10.1021/acsinfecdis.1c00025 ◽

2021 ◽

Author(s):

Frederick A. Partridge ◽

Carole J.R. Bataille ◽

Ruth Forman ◽

Amy E. Marriott ◽

Josephine Forde-Thomas ◽

...

Keyword(s):

Schistosoma Mansoni ◽

Brugia Malayi ◽

Trichuris Muris ◽

Heligmosomoides Polygyrus ◽

Structural Requirements

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Modelling the impact of COVID-19-related control programme interruptions on progress towards the WHO 2030 target for soil-transmitted helminths

Transactions of the Royal Society of Tropical Medicine and Hygiene ◽

10.1093/trstmh/traa156 ◽

2020 ◽

Cited By ~ 1

Author(s):

Veronica Malizia ◽

Federica Giardina ◽

Carolin Vegvari ◽

Sumali Bajaj ◽

Kevin McRae-McKee ◽

...

Keyword(s):

Neglected Tropical Diseases ◽

Control Programme ◽

Mitigation Strategy ◽

Mitigation Strategies ◽

Preventive Chemotherapy ◽

Soil Transmitted Helminths ◽

Individual Based Models ◽

Control Programmes ◽

Catch Up ◽

The Impact

Abstract Background On 1 April 2020, the WHO recommended an interruption of all activities for the control of neglected tropical diseases, including soil-transmitted helminths (STH), in response to the COVID-19 pandemic. This paper investigates the impact of this disruption on the progress towards the WHO 2030 target for STH. Methods We used two stochastic individual-based models to simulate the impact of missing one or more preventive chemotherapy (PC) rounds in different endemicity settings. We also investigated the extent to which this impact can be lessened by mitigation strategies, such as semiannual or community-wide PC. Results Both models show that without a mitigation strategy, control programmes will catch up by 2030, assuming that coverage is maintained. The catch-up time can be up to 4.5 y after the start of the interruption. Mitigation strategies may reduce this time by up to 2 y and increase the probability of achieving the 2030 target. Conclusions Although a PC interruption will only temporarily impact the progress towards the WHO 2030 target, programmes are encouraged to restart as soon as possible to minimise the impact on morbidity. The implementation of suitable mitigation strategies can turn the interruption into an opportunity to accelerate progress towards reaching the target.

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Exposure of Heligmosomoides polygyrus and Trichuris muris to albendazole, albendazole sulfoxide, mebendazole and oxantel pamoate in vitro and in vivo to elucidate the pathway of drug entry into these gastrointestinal nematodes

International Journal for Parasitology Drugs and Drug Resistance ◽

10.1016/j.ijpddr.2017.03.005 ◽

2017 ◽

Vol 7 (2) ◽

pp. 159-173 ◽

Cited By ~ 9

Author(s):

Noemi Cowan ◽

Charles Meier ◽

Anna Neodo ◽

Jennifer Keiser

Keyword(s):

Gastrointestinal Nematodes ◽

Trichuris Muris ◽

Heligmosomoides Polygyrus ◽

Albendazole Sulfoxide ◽

Oxantel Pamoate ◽

Drug Entry

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daf-7-related TGF-β homologues from Trichostrongyloid nematodes show contrasting life-cycle expression patterns

Parasitology ◽

10.1017/s0031182009990321 ◽

2009 ◽

Vol 137 (1) ◽

pp. 159-171 ◽

Cited By ~ 42

Author(s):

H. J. McSORLEY ◽

J. R. GRAINGER ◽

Y. HARCUS ◽

J. MURRAY ◽

A. J. NISBET ◽

...

Keyword(s):

Amino Acids ◽

Life Cycle ◽

Gene Family ◽

Transforming Growth Factor ◽

Signal Sequence ◽

Expression Patterns ◽

Transforming Growth Factor Β ◽

Laboratory Model ◽

Parasitic Nematodes ◽

Nippostrongylus Brasiliensis

SUMMARYThe transforming growth factor-β (TGF-β) gene family regulates critical processes in animal development, and plays a crucial role in regulating the mammalian immune response. We aimed to identify TGF-β homologues from 2 laboratory model nematodes (Heligmosomoides polygyrus and Nippostrongylus brasiliensis) and 2 major parasites of ruminant livestock (Haemonchus contortus and Teladorsagia circumcincta). Parasite cDNA was used as a template for gene-specific PCR and RACE. Homologues of the TGH-2 subfamily were isolated, and found to differ in length (301, 152, 349 and 305 amino acids respectively), with variably truncated N-terminal pre-proteins. All contained conserved C-terminal active domains (>85% identical over 115 amino acids) containing 9 cysteine residues, as in C. elegans DAF-7, Brugia malayi TGH-2 and mammalian TGF-β. Surprisingly, only the H. contortus homologue retained a conventional signal sequence, absent from shorter proteins of other species. RT-PCR assays of transcription showed that in H. contortus and N. brasiliensis expression was maximal in the infective larval stage, and very low in adult worms. In contrast, in H. polygyrus and T. circumcincta, tgh-2 transcription is higher in adults than infective larvae. The molecular evolution of this gene family in parasitic nematodes has diversified the pre-protein and life-cycle expression patterns of TGF-β homologues while conserving the structure of the active domain.

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Intestinal epithelial cell secretion of RELM-β protects against gastrointestinal worm infection

Journal of Experimental Medicine ◽

10.1084/jem.20091268 ◽

2009 ◽

Vol 206 (13) ◽

pp. 2947-2957 ◽

Cited By ~ 173

Author(s):

De'Broski R. Herbert ◽

Jun-Qi Yang ◽

Simon P. Hogan ◽

Kathryn Groschwitz ◽

Marat Khodoun ◽

...

Keyword(s):

Epithelial Cells ◽

Trichinella Spiralis ◽

Intestinal Lumen ◽

Th2 Cells ◽

Nippostrongylus Brasiliensis ◽

Intestinal Epithelial ◽

Cell Secretion ◽

Heligmosomoides Polygyrus ◽

Parasitic Helminths

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) β. RELM-β is essential for normal spontaneous expulsion and IL-4–induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-β is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-β–driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.

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Host–parasite interactions in rodent nematode infections

Journal of Helminthology ◽

10.1079/joh2003172 ◽

2003 ◽

Vol 77 (2) ◽

pp. 125-131 ◽

Cited By ~ 11

Author(s):

Y.R. Mahida

Keyword(s):

Neutralizing Antibodies ◽

Host Response ◽

Trichinella Spiralis ◽

Host Responses ◽

Nippostrongylus Brasiliensis ◽

Trichuris Muris ◽

Epithelial Phenotype ◽

Worm Expulsion ◽

Genetically Manipulated ◽

Host Parasite

AbstractIn rodents,Trichinella spiralisandNippostrongylus brasiliensisinfect the small intestine andTrichuris murisresides in the colon. The intestinal host response in these animals is characterized by changes in mucosal architecture and inflammation and is associated with worm expulsion. The requirement of T cell-mediated host response in worm expulsion has been demonstrated over many years. Subsequent studies have shown that Th2-type, but not Th1-type, responses mediate resistance to the nematodes. Investigations using neutralizing antibodies and genetically manipulated mice have characterized the contribution of individual Th2-type cytokines in not only worm expulsion, but also specific cellular changes that occur in the mucosa, such as alterations in epithelial phenotype and smooth muscle. There is also increasing appreciation of the contribution of non-bone marrow-derived cells in innate and adaptive host responses in these models.

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Some Observations on the Transmission of Bacteria by Infective Larvae of Nippostrongylus brasiliensis

Journal of Helminthology ◽

10.1017/s0022149x00024184 ◽

1955 ◽

Vol 29 (1-2) ◽

pp. 27-32 ◽

Cited By ~ 3

Author(s):

H. M. Gharib

Keyword(s):

Life Cycle ◽

Definitive Host ◽

Infected Host ◽

Nippostrongylus Brasiliensis ◽

Infective Stage ◽

Natural Conditions ◽

Larval Stages ◽

Infective Larvae ◽

External Development

It is well known that the first two larval stages in the life cycle of nematodes belonging to the superfamily Strongloidea, have a freeliving existence. During this time, the larva which hatches from the egg feeds actively, undergoes two moults and grows considerably before reaching the infective stage, when it is ready to invade a definitive host. Under natural conditions this external development takes place in the faeces, which have been deposited by the infected host on ground likely to be contaminated with various bacteria.

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Vaccines against malaria

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2011.0091 ◽

2011 ◽

Vol 366 (1579) ◽

pp. 2806-2814 ◽

Cited By ~ 125

Author(s):

Adrian V. S. Hill

Keyword(s):

Life Cycle ◽

Malaria Vaccine ◽

Vaccine Development ◽

Viral Vector ◽

Cost Effective ◽

Life Cycle Stage ◽

Phase Iii ◽

Small Scale ◽

Vaccine Candidates ◽

Adjuvant Vaccine

There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.

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